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Background Exposure to air pollution is associated with worldwide morbidity and mortality. Diesel exhaust (DE) emissions are important contributors which induce vascular inflammation and metabolic disturbances by unknown mechanisms. We aimed to determine molecular pathways activated by DE in the liver that could be responsible for its cardiometabolic toxicity. Methods Apolipoprotein E knockout (ApoE KO) mice were exposed to DE or filtered air (FA) for two weeks, or DE for two weeks followed by FA for 1 week. Expression microarrays and global metabolomics assessment were performed in the liver. An integrated transcriptomic and metabolomic analytical strategy was employed to dissect critical pathways and identify candidate genes that could dissect DE-induced pathogenesis. HepG2 cells were treated with an organic extract of DE particles (DEP) vs. vehicle control to test candidate genes. Results DE exposure for 2 weeks dysregulated 658 liver genes overrepresented in whole cell metabolic pathways, especially including lipid and carbohydrate metabolism, and the respiratory electron transport pathway. DE exposure significantly dysregulated 118 metabolites, resulting in increased levels of triglycerides and fatty acids due to mitochondrial dysfunction as well as increased levels of glucose and oligosaccharides. Consistently, DEP treatment of HepG2 cells led to increased gluconeogenesis and glycogenolysis indicating the ability of the in-vitro approach to model effects induced by DE in vivo. As an example, while gene network analysis of DE livers identified phosphoenolpyruvate carboxykinase 1 (Pck1) as a key driver gene of DE response, DEP treatment of HepG2 cells resulted in increased mRNA expression of Pck1 and glucose production, the latter replicated in mouse primary hepatocytes. Importantly, Pck1 inhibitor mercaptopicolinic acid suppressed DE-induced glucose production in HepG2 cells indicating that DE-induced elevation of hepatic glucose was due in part to upregulation of Pck1 and increased gluconeogenesis. Conclusions Short-term exposure to DE induced widespread alterations in metabolic pathways in the liver of ApoE KO mice, especially involving carbohydrate and lipid metabolism, together with mitochondrial dysfunction. Pck1 was identified as a key driver gene regulating increased glucose production by activation of the gluconeogenesis pathway.

Inflammatory bowel disease (IBD) is an immunologically complex disorder involving genetic, microbial, and environmental risk factors. Its global burden has continued to rise since industrialization, with epidemiological studies suggesting that ambient particulate matter (PM) in air pollution could be a contributing factor. Prior animal studies have shown that oral PM10 exposure promotes intestinal inflammation in a genetic IBD model and that PM2.5 inhalation exposure can increase intestinal levels of pro-inflammatory cytokines. PM10 and PM2.5 include ultrafine particles (UFP), which have an aerodynamic diameter of <0.10 μm and biophysical and biochemical properties that promote toxicity. UFP inhalation, however, has not been previously studied in the context of murine models of IBD. Here, we demonstrated that ambient PM is toxic to cultured Caco-2 intestinal epithelial cells and examined whether UFP inhalation affected acute colitis induced by dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid. C57BL/6J mice were exposed to filtered air (FA) or various types of ambient PM reaerosolized in the ultrafine size range at ~300 μg/m3, 6 h/day, 3–5 days/week, starting 7–10 days before disease induction. No differences in weight change, clinical disease activity, or histology were observed between the PM and FA-exposed groups. In conclusion, UFP inhalation exposure did not exacerbate intestinal inflammation in acute, chemically-induced colitis models.

The protein forms of transporter associated with antigen processing, subunit 2 (TAP2), differ either by amino acid substitutions (Thr374Ala, Ile379Val, Ile467Val, Thr565Ala, Val577Met, Cys651Arg, and Ala665Thr) or by a truncation (Gln687Stop) of 17 amino acid residues at the C-terminus. Nonsynonymous single nucleotide polymorphisms (N-SNPs) causing these amino acid variations except 577Val were detected in genomic DNA samples from North American Caucasians (n = 76), Brazilians (n = 148), Rwandans (n = 285), and Zambians (n = 117). Exclusive (100%) and nearly exclusive (>95%) linkage disequilibrium was seen with a number of N-SNPs. The average heterozygosity at any given dimorphic site ranged from 7.3% to 44.6%, and at least four N-SNPs showed clear population specificity. N-SNP combinations alone led to the identification of 16 relatively common alleles, which appeared to form at least three lineages. Further analyses of 101 cDNA samples from Brazilians detected nine expressed TAP2 alleles, four of which matched the official assignments. Genetic complexity at the TAP2 locus was further enhanced by two out of five synonymous SNPs (S-SNPs), especially the GGT386GGG (Gly) that had similar heterozygosity rates in Caucasians (28.9%), Rwandans (33.3%), and Zambians (33.3%). Overall, distribution of both synonymous and nonsynonymous SNPs in the various ethnic groups examined here conformed well to the Hardy-Weinberg equilibrium, and between 57.9% and 77.0% of subjects in each ethnic group were heterozygous with two TAP2 alleles predicted to differ by at least one amino acid residue. Such complexity of TAP2 polymorphisms, in the form of SNPs as well as alleles, is likely to complicate the analyses of disease associations and haplotype structures in the HLA class II region.

We present the James Webb Space Telescope (JWST) transmission spectrum of the exoplanet HAT-P-26 b (18.6 M⊕, 6.33 R⊕), based on a single transit observed with the JWST NIRSpec G395H grating. We detect water vapor ( lnB = 4.1), carbon dioxide ( lnB = 85.6), and sulfur dioxide ( lnB = 13.5) with high confidence, along with marginal indications for hydrogen sulfide and carbon monoxide ( lnB< 0.5). The detection of SO2 in a warm super-Neptune-sized exoplanet (RP ∼ 6 R⊕) bridges the gap between previous detections in hot Jupiters and sub-Neptunes, highlighting the role of disequilibrium photochemistry across a broad range of exoplanet atmospheres, including those cooler than 1000 K. Our precise measurements of carbon, oxygen, and sulfur indicate an atmospheric metallicity of ∼10× solar and a subsolar C/O ratio. Retrieved molecular abundances are consistent within 2σ with predictions from self-consistent models including photochemistry. The elevated CO2 abundance and possible H2S signal may also reflect sensitivities to the thermal structure, cloud properties, or additional disequilibrium processes such as vertical mixing. We compare the SO2 abundance in HAT-P-26 b with that of 10 other JWST-observed giant exoplanets, and find a correlation with atmospheric metallicity. The trend is consistent with the prediction from I. J. M. Crossfield, showing a steep rise in SO2 abundance at low metallicities, and a more gradual increase beyond 30× solar. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).

Water has proven to be ubiquitously detected in near-infrared (NIR) transmission spectroscopy observations of hot Jupiter atmospheres, including WASP-17b. However, previous analyses of WASP-17b’s atmosphere based upon Hubble Space Telescope (HST) and Spitzer data could not constrain the water abundance, finding that subsolar, supersolar, and bimodal posterior distributions were all statistically valid. In this work, we observe one transit of the hot Jupiter WASP-17b using JWST’s Near Infrared Imager and Slitless Spectrograph (NIRISS) Single Object Slitless Spectroscopy (SOSS) mode. We analyze our data using three independent data analysis pipelines, finding excellent agreement between results. Our transmission spectrum shows multiple H2O absorption features and a flatter slope towards the optical than seen in previous HST observations. We analyze our spectrum using both PICASO + Virga forward models and free retrievals. POSEIDON retrievals provide a well-constrained supersolar log(H2O) abundance (−2.96 −0.24+0.31 ), breaking the degeneracy from the previous HST + Spitzer analysis. We verify our POSEIDON results with petitRADTRANS retrievals. Additionally, we constrain the abundance of log(H−), −10.19 −0.23+0.30 , finding that our model including H− is preferred over our model without H− to 5.1 σ. Furthermore, we constrain the log(K) abundance (−8.07 −0.52+0.58 ) in WASP-17b’s atmosphere for the first time using space-based observations. Our abundance constraints demonstrate the power of NIRISS SOSS’s increased resolution, precision, and wavelength range to improve upon previous NIR space-based results. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).

The TRAPPIST-1 system offers one of the best opportunities to characterize temperate terrestrial planets beyond our own solar system. Within the TRAPPIST-1 system, planet e stands out as highly likely to sustain surface liquid water if it possesses an atmosphere. Recently, we reported the first JWST/NIRSpec PRISM transmission spectra of TRAPPIST-1 e, revealing significant stellar contamination, which varied between the four visits. Here, we assess the range of planetary atmospheres consistent with our transmission spectrum. We explore a wide range of atmospheric scenarios via a hierarchy of forward modeling and retrievals. We do not obtain strong evidence for or against an atmosphere. Our results weakly disfavor CO2-rich atmospheres for pressures corresponding to the surface of Venus and Mars and the cloud tops of Venus at 2σ. We exclude H2-rich atmospheres containing CO2 and CH4 in agreement with past work but find that higher mean molecular weight, N2-rich atmospheres with trace CO2 and CH4 are permitted by the data. Both a bare rock and N2-rich atmospheric scenario provide adequate fits to the data but do not fully explain all features, which may be due to either uncorrected stellar contamination or atmospheric signals. Ongoing JWST observations of TRAPPIST-1 e, exploiting consecutive transits with TRAPPIST-1 b, will offer stronger constraints via a more effective stellar contamination correction. The present work is part of the JWST Telescope Scientist Team Guaranteed Time Observations, which is performing a Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).

We present the first emission spectrum of the hot Jupiter WASP-17 b using one eclipse observation from the JWST Near Infrared Imager and Slitless Spectrograph (NIRISS) Single Object Slitless Spectroscopy (SOSS) mode. Covering a wavelength range of 0.6–2.8 μm, our retrieval analysis reveals a strong detection of H2O in WASP-17 b’s dayside atmosphere (6.4σ). Our retrievals consistently favor a supersolar dayside H2O abundance and a noninverted temperature–pressure profile over a large pressure range. Additionally, our examination of the brightness temperature reveals excess emission below 1 μm, suggesting the possibility of a high internal temperature (600–700 K) and/or contributions from reflected light. We highlight that JWST emission spectroscopy retrieval results can be sensitive to whether negative eclipse depths are allowed at optical wavelengths during light-curve fitting. Our findings deepen our understanding of WASP-17 b’s atmospheric composition while also highlighting the sensitivity of our results to pressure–temperature profile parameterizations. This work is part of a series of studies by our JWST Telescope Scientist Team (TST), in which we will use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).

TRAPPIST-1 e is one of the very few rocky exoplanets that is both amenable to atmospheric characterization and resides in the habitable zone of its star—located at a distance from its star such that it might, with the right atmosphere, sustain liquid water on its surface. Here, we present a set of four JWST/NIRSpec PRISM transmission spectra of TRAPPIST-1 e obtained in mid-to-late 2023. Our transmission spectra exhibit similar levels of stellar contamination as observed in prior works for other planets in the TRAPPIST-1 system but over a wider wavelength range, showcasing the challenge of characterizing the TRAPPIST-1 planets even at relatively long wavelengths (3–5 μm). While we show that current stellar modeling frameworks are unable to explain the stellar contamination features in our spectra, we demonstrate that we can marginalize over those features instead using Gaussian processes, which enables us to perform novel exoplanet atmospheric inferences with our transmission spectra. In particular, we are able to rule out cloudy, primary H2-dominated (≳80% by volume) atmospheres at better than a 3σ level. Constraints on possible secondary atmospheres on TRAPPIST-1 e are presented in a companion paper. Our work showcases how JWST is breaking ground in the precision needed to constrain the atmospheric composition of habitable-zone rocky exoplanets.

Youth screen media activity is a growing concern, though few studies include objective usage data. Through the longitudinal, U.S.-based Adolescent Brain Cognitive Development (ABCD) Study, youth (m age  = 14; n = 1415) self-reported their typical smartphone use and passively recorded three weeks of smartphone use via the ABCD-specific Effortless Assessment Research System (EARS) application. Here we describe and validate passively-sensed smartphone keyboard and app use measures, provide code to harmonize measures across operating systems, and describe trends in adolescent smartphone use. Keyboard and app-use measures were reliable and positively correlated with one another ( r  = 0.33) and with self-reported use ( r s = 0.21–0.35). Participants recorded a mean of 5 h of daily smartphone use, which is two more hours than they self-reported. Further, females logged more smartphone use than males. Smartphone use was recorded at all hours, peaking on average from 8 to 10 PM and lowest from 3 to 5 AM. Social media and texting apps comprised nearly half of all use. Data are openly available to approved investigators ( https://nda.nih.gov/abcd/ ). Information herein can inform use of the ABCD dataset to longitudinally study health and neurodevelopmental correlates of adolescent smartphone use.