The mechanism by which oxidative stress induces inflammation and vice versa is unclear but is of great importance, being apparently linked to many chronic inflammatory diseases. We show here that ...inflammatory stimuli induce release of oxidized peroxiredoxin-2 (PRDX2), a ubiquitous redox-active intracellular enzyme. Once released, the extracellular PRDX2 acts as a redox-dependent inflammatory mediator, triggering macrophages to produce and release TNF-α. The oxidative coupling of glutathione (GSH) to PRDX2 cysteine residues (i.e., protein glutathionylation) occurs before or during PRDX2 release, a process central to the regulation of immunity. We identified PRDX2 among the glutathionylated proteins released in vitro by LPS-stimulated macrophages using mass spectrometry proteomic methods. Consistent with being part of an inflammatory cascade, we find that PRDX2 then induces TNF-α release. Unlike classical inflammatory cytokines, PRDX2 release does not reflect LPS-mediated induction of mRNA or protein synthesis; instead, PRDX2 is constitutively present in macrophages, mainly in the reduced form, and is released in the oxidized form on LPS stimulation. Release of PRDX2 is also observed in human embryonic kidney cells treated with TNF-α. Importantly, the PRDX2 substrate thioredoxin (TRX) is also released along with PRDX2, enabling an oxidative cascade that can alter the –SH status of surface proteins and thereby facilitate activation via cytokine and Toll-like receptors. Thus, our findings suggest a model in which the release of PRDX2 and TRX from macrophages can modify the redox status of cell surface receptors and enable induction of inflammatory responses. This pathway warrants further exploration as a potential novel therapeutic target for chronic inflammatory diseases.
We present the 2012 Hubble Ultra Deep Field campaign (UDF12), a large 128 orbit Cycle 19 Hubble Space Telescope program aimed at extending previous Wide Field Camera 3 (WFC3)/IR observations of the ...UDF by quadrupling the exposure time in the F105W filter, imaging in an additional F140W filter, and extending the F160W exposure time by 50%, as well as adding an extremely deep parallel field with the Advanced Camera for Surveys (ACS) in the F814W filter with a total exposure time of 128 orbits. In this paper we present the observational overview of the project and describe the procedures used in reducing the data as well as the final products that were produced. We release the full, combined mosaics comprising a single, unified set of mosaics of the UDF, providing the deepest near-infrared blank-field view of the universe currently achievable, reaching magnitudes as deep as AB ~ 30 mag in the near-infrared, and yielding a legacy dataset on this field.
Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.
The goal ...of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.
Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders.
In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 P < .001; St. George’s Respiratory Questionnaire, 1.67 P < .001; Medical Outcomes Study Short Form 36 Physical Function, –0.89 P < .001), exercise performance (6-min walk distance, –45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).
Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.
Motivated by the current controversy over the redshift distribution and physical properties of luminous (sub-)mm sources, we have undertaken a new study of the brightest sample of unlensed (sub-)mm ...sources with pre-Atacama Large Millimeter/submillimeter Array (ALMA) interferometric follow-up in the Cosmological Evolution Survey field. Exploiting the very latest multifrequency supporting data, we find that this sample displays a redshift distribution indistinguishable from that of the lensed sources uncovered with the South Pole Telescope, with z
median ≃ 3.5. We also find that, over the redshift range z ≃ 2–6, the median stellar mass of the most luminous (sub-) mm sources is M
* ≃ 3 × 1011 M⊙, yielding a typical specific star formation rate sSFR ≃ 3 Gyr− 1. Consistent with recent ALMA and the Submillimeter Array studies, we confirm that source blending is not a serious issue in the study of luminous (sub-) mm sources uncovered by ground-based, single-dish surveys; only ≃10–15 per cent of bright (S
850 ≃ 5–10 mJy) (sub-) mm sources arise from significant (i.e. >20 per cent) blends, and so our conclusions are largely unaffected by whether we adopt the original single-dish mm/sub-mm flux densities/positions or the interferometric data. Our results suggest that apparent disagreements over the redshift distribution of (sub-)mm sources are a result of ‘down-sizing’ in dust-enshrouded star formation, consistent with existing knowledge of the star formation histories of massive galaxies. They also indicate that extreme star-forming galaxies at high redshift are, on average, subject to the same star formation rate-limiting processes as less luminous objects, and lie on the ‘main sequence’ of star-forming galaxies at z > 3.
We have constructed a mass-selected sample of M
* > 1011 M⊙ galaxies at 1 < z < 3 in the CANDELS UKIDSS UDS and COSMOS fields and have decomposed these systems into their separate bulge and disc ...components according to their H
160-band morphologies. By extending this analysis to multiple bands, we have been able to conduct individual bulge and disc component SED fitting which has provided us with stellar-mass and star formation rate estimates for the separate bulge and disc components. Having utilized the new decomposed stellar-mass estimates, we confirm that the bulge components display a stronger size evolution than the discs. The median sizes of the bulge components is 3.09 ± 0.20 times smaller than similarly massive local galaxies over the full 1 < z < 3 redshift range; for the discs, the corresponding factor is 1.77 ± 0.10. Moreover, by splitting our sample into the passive and star-forming bulge and disc sub-populations and examining their sizes as a fraction of their present-day counter-parts, we find that the star-forming and passive bulges are equally compact, star-forming discs are larger, while the passive discs have intermediate sizes. This trend is not evident when classifying galaxy morphology on the basis of single-Sérsic fits and adopting the overall star formation rates. Finally, by evolving the star formation histories of the passive discs back to the redshifts when the passive discs were last active, we show that the passive and star-forming discs have consistent sizes at the relevant epoch. These trends need to be reproduced by any mechanisms which attempt to explain the morphological evolution of galaxies.
ABSTRACT
We study the rest-frame ultraviolet (UV) continuum slopes (β) of galaxies at redshifts 8 < z < 16 (〈z〉 = 10), using a combination of JWST ERO and ERS NIRCam imaging and ground-based ...near-infrared imaging of the COSMOS field. The combination of JWST and ground-based imaging provides a wide baseline in both redshift and absolute UV magnitude (−22.6 < MUV < −17.9), sufficient to allow a meaningful comparison to previous results at lower redshift. Using a power-law fitting technique, we find that our full sample (median MUV = −19.3 ± 1.3) returns an inverse-variance weighted mean value of 〈β〉 = −2.10 ± 0.05, with a corresponding median value of β = −2.29 ± 0.09. These values imply that the UV colours of galaxies at z > 8 are, on average, no bluer than the bluest galaxies in the local universe (e.g. NGC 1705; β = −2.46). We find evidence for a β − MUV relation, such that brighter UV galaxies display redder UV slopes ($\rm {d}\beta / \rm {d} M_{\rm UV} = -0.17 \pm 0.05$). Comparing to results at lower redshift, we find that the slope of our β − MUV relation is consistent with the slope observed at z ≃ 5 and that, at a given MUV, our 8 < z < 16 galaxies are bluer than their z ≃ 5 counterparts, with an inverse-variance weighted mean offset of 〈Δβ〉 = −0.38 ± 0.09. We do not find strong evidence that any objects in our sample display ultra-blue UV continuum slopes (i.e. β ≲ −3) that would require their UV emission to be dominated by ultra-young, dust-free stellar populations with high Lyman-continuum escape fractions. Comparing our results to the predictions of theoretical galaxy formation models, we find that the galaxies in our sample are consistent with the young, metal-poor, and moderately dust-reddened galaxies expected at z > 8.
To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD ...exacerbation frequency and quantitative CT measures of emphysema and airway disease.
This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.
In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).
Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.
ABSTRACT We present an analysis of the ultraviolet (UV) continuum slopes (β) for a sample of 172 galaxy candidates at 8 < zphot < 16 selected from a combination of JWST NIRCam imaging and ...COSMOS/UltraVISTA ground-based near-infrared imaging. Focusing primarily on a new sample of 121 galaxies at 〈z〉 ≃ 11 selected from ≃ 320 arcmin2 of public JWST imaging data across 15 independent data sets, we investigate the evolution of β in the galaxy population at z ≥ 9. We find a significant trend between β and redshift, with the inverse-variance weighted mean UV slope evolving from 〈β〉 = −2.17 ± 0.06 at z = 9.5 to 〈β〉 = −2.59 ± 0.06 at z = 11.5. Based on a comparison with stellar population models including nebular continuum emission, we find that at z > 10.5 the average UV continuum slope is consistent with the intrinsic blue limit of dust-free stellar populations (βint ≃ −2.6). These results suggest that the moderately dust-reddened galaxy population at z < 10 was essentially unattenuated at z ≃ 11. The extremely blue galaxies being uncovered at z > 10 place important constraints on dust attenuation in galaxies in the early Universe, and imply that the already observed galaxy population is likely supplying an ionizing photon budget capable of maintaining ionized intergalactic medium fractions of ≳ 5 per cent at z ≃ 11.
Global financial donors have invested billions of dollars in "Sustainable Forest Management" to conserve forests and the ecosystem services they provide. A major contributing mechanism, community ...forest management (CFM), aims to provide global environmental benefits (reduce deforestation, maintain biodiversity), while also improving local human welfare (alleviate poverty). We have systematically reviewed available evidence of CFM effectiveness and consider the implications of our findings for future investment in CFM programs. There is evidence of CFM being associated with greater tree density and basal area but not with other indicators of global environmental benefits. We found no data on local human welfare amenable to meta-analysis. Poor study design, variable reporting of study methodology or context, and lack of common indicators make evidence synthesis difficult. Given the policy interest in and the planned donor expenditure on CFM, evaluation must be improved so that informed decisions can be made about appropriate investment in this approach.
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