A warm Neptune's methane reveals core mass and vigorous atmospheric mixing.

Observations of transiting gas giant exoplanets have revealed a pervasive depletion of methane1-4, which has only recently been identified atmospherically5,6. The depletion is thought to be maintained by disequilibrium processes such as photochemistry or mixing from a hotter interior7-9. However, the interiors are largely unconstrained along with the vertical mixing strength and only upper limits on the CH4 depletion have been available. The warm Neptune WASP-107b stands out among exoplanets with an unusually low density, reported low core mass10, and temperatures amenable to CH4, though previous observations have yet to find the molecule2,4. Here we present a JWST-NIRSpec transmission spectrum of WASP-107b that shows features from both SO2 and CH4 along with H2O, CO2, and CO. We detect methane with 4.2σ significance at an abundance of 1.0 ± 0.5 ppm, which is depleted by 3 orders of magnitude relative to equilibrium expectations. Our results are highly constraining for the atmosphere and interior, which indicate the envelope has a super-solar metallicity of 43 ± 8 × solar, a hot interior with an intrinsic temperature of Tint = 460 ± 40 K, and vigorous vertical mixing which depletes CH4 with a diffusion coefficient of Kzz = 1011.6±0.1 cm2 s-1. Photochemistry has a negligible effect on the CH4 abundance but is needed to account for the SO2. We infer a core mass of 11.5 - 3.6 + 3.0 M ⊕ , which is much higher than previous upper limits10, releasing a tension with core-accretion models11.

High atmospheric metal enrichment for a Saturn-mass planet.

Atmospheric metal enrichment (that is, elements heavier than helium, also called 'metallicity') is a key diagnostic of the formation of giant planets1-3. The giant planets of the Solar System show an inverse relationship between mass and both their bulk metallicities and atmospheric metallicities. Extrasolar giant planets also display an inverse relationship between mass and bulk metallicity4. However, there is significant scatter in the relationship and it is not known how atmospheric metallicity correlates with either planet mass or bulk metallicity. Here we show that the Saturn-mass exoplanet HD 149026b (refs. 5-9) has an atmospheric metallicity 59-276 times solar (at 1σ), which is greater than Saturn's atmospheric metallicity of roughly 7.5 times solar10 at more than 4σ confidence. This result is based on modelling CO2 and H2O absorption features in the thermal emission spectrum of the planet measured by the James Webb Space Telescope. HD 149026b is the most metal-rich giant planet known, with an estimated bulk heavy element abundance of 66 ± 2% by mass11,12. We find that the atmospheric metallicities of both HD 149026b and the Solar System giant planets are more correlated with bulk metallicity than planet mass.

Protective role of relaxin in a mouse model of aristolochic acid nephropathy.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a chronic, progressive interstitial nephritis. To date, treatment strategies remain limited. Mounting evidence shows that relaxin (RLX) possesses powerful anti-fibrotic and anti-apoptotic characteristics, therefore, the present study aimed to investigate the possible protective role of RLX in aristolochic acid (AA) induced nephrotoxicity. METHODS: The in vitro cell tests were performed: the embryonic kidney cells 293 were treated with AA-I (40 µg/mL) or with AA-I (40 µg/mL) plus RLX (100 ng/mL) and the cell groups were then tested and the normal 293 cells were set as blank control. In addition, the in vivo animal tests were performed: mice were randomly divided into three groups: a control group injected intraperitoneally with an equal volume of saline every other day for 6 weeks, an AA group injected intraperitoneally with AA-I (5 mg/kg) every other day for 6 weeks, and an AA + RLX group treated with the AA-I for 6 weeks and subsequently received RLX (0.25 mg/kg/day) using an implanted osmotic mini-pump for an additional 2 weeks. 8 weeks post-AA-I, mice were sacrificed for analysis. RESULTS: In the in vivo animal tests, RLX administration prevented increased plasma creatinine and nitrogen levels caused by aristolochic acid as well as alleviated the severity of renal ultrastructural lesions induced by aristolochic acid. Both in the in vitro cell tests and in the in vivo animal tests, Western blotting of the AA-I group showed increased expression of the pro-apoptotic protein genes Bax and the cleaved form of caspase-3, both of which were reversed by RLX. In contrast, the expression of the anti-apoptotic gene Bcl-2 correlated inversely to Bax in RLX treated mice. RLX restored the decreased phosphorylated Akt induced by AA-I. The protein expression of eNOS was also reduced in AA-I treated group compared with control, which was reversed in the presence of RLX. Immunohistochemical staining of the animal tissue revealed that RLX markedly reduced the overexpression of type IV collagen, fibronectin, and alpha-smooth muscle actin in AA-I treated mice. CONCLUSIONS: Our results suggest that RLX alleviates AA-I induced kidney fibrosis by reducing apoptosis and up-regulation the expression of p-Akt.

Feed First, Ask Questions Later: Alleviating and Understanding Caregiver Food Insecurity in an Urban Children's Hospital.

OBJECTIVES: We estimated the prevalence of caregiver hospital food insecurity (defined as not getting enough to eat during a child's hospitalization), examined associations between food insecurity and barriers to food access, and propose a conceptual framework to inform remedies to this problem. METHODS: We conducted a cross-sectional study of 200 caregivers of hospitalized children in Chicago, Illinois (June through December 2011). A self-administered questionnaire assessed sociodemographic characteristics, barriers to food, and caregiver hospital food insecurity. RESULTS: Caregiver hospital food insecurity was prevalent (32%). Caregivers who were aged 18 to 34 years, Black or African American, unpartnered, and with less education were more likely to experience hospital food insecurity. Not having enough money to buy food at the hospital, lack of reliable transportation, and lack of knowledge of where to get food at the hospital were associated with hospital food insecurity. The proposed conceptual framework posits a bidirectional relationship between food insecurity and health, emphasizing the interdependencies between caregiver food insecurity and patient outcomes. CONCLUSIONS: Strategies are needed to identify and feed caregivers and to eradicate food insecurity in homes of children with serious illness.

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues.

BACKGROUND: During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). METHODS: Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. RESULTS: We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. CONCLUSIONS: Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.

Apurinic/apyrimidinic endonuclease 1 alters estrogen receptor activity and estrogen-responsive gene expression.

Apurinic/apyrimidinic endonuclease 1 or redox factor-1 (Ape1/Ref-1) is a pleiotropic cellular protein involved in DNA repair and, through its redox activity, enhances the binding of a select group of transcription factors to their cognate recognition sequences in DNA. Thus, we were intrigued when we identified Ape1/Ref-1 and a number of DNA repair and oxidative stress proteins in a complex associated with the DNA-bound estrogen receptor alpha (ERalpha). Because Ape1/Ref-1 interacts with a number of transcription factors and influences their activity, we determined whether it might also influence ERalpha activity. We found that endogenously expressed Ape1/Ref-1 and ERalpha from MCF-7 human breast cancer cells interact and that Ape1/Ref-1 enhances the interaction of ERalpha with estrogen-response elements (EREs) in DNA. More importantly, Ape1/Ref-1 alters expression of the endogenous, estrogen-responsive progesterone receptor and pS2 genes in MCF-7 cells and associates with ERE-containing regions of these genes in native chromatin. Interestingly, knocking down Ape1/Ref-1 expression or inhibiting its redox activity with the small molecule inhibitor E3330 enhances estrogen responsiveness of the progesterone receptor and pS2 genes but does not alter the expression of the constitutively active 36B4 gene. Additionally, the reduced form of Ape1/Ref-1 increases and E3330 limits ERalpha-ERE complex formation in vitro and in native chromatin. Our studies demonstrate that Ape1/Ref-1 mediates its gene-specific effects, in part, by associating with endogenous, estrogen-responsive genes and that the redox activity of Ape1/Ref-1 is instrumental in altering estrogen-responsive gene expression.