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The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1-3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1-10 ppm)4-9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 µm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 µm in the 5-12-µm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5-25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 µm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1-8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.
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The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy1-4. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality5-9. Here we present the transmission spectrum of WASP-39b obtained using the Single-Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument on the JWST. This spectrum spans 0.6-2.8 µm in wavelength and shows several water-absorption bands, the potassium resonance doublet and signatures of clouds. The precision and broad wavelength coverage of NIRISS/SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favouring a heavy-element enhancement ('metallicity') of about 10-30 times the solar value, a sub-solar carbon-to-oxygen (C/O) ratio and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are also best explained by wavelength-dependent, non-grey clouds with inhomogeneous coverageof the planet's terminator.
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Close-in giant exoplanets with temperatures greater than 2,000 K ('ultra-hot Jupiters') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble Space Telescope (HST) and Spitzer Space Telescope1-3. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis3-12. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS13 instrument on the JWST. The data span 0.85 to 2.85 µm in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at >6σ confidence) and evidence for optical opacity, possibly attributable to H-, TiO and VO (combined significance of 3.8σ). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy-element abundance ('metallicity', [Formula: see text] times solar) and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the substellar point that decreases steeply and symmetrically with longitude towards the terminators.
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Women make less than men in some science, technology, engineering, and math (STEM) fields. While explanations for this gender pay gap vary, they have tended to focus on differences that arise for women and men after they have worked for a period of time. In this study we argue that the gender pay gap begins when women and men with earned degrees enter the workforce. Further, we contend the gender pay gap may arise due to cultural beliefs about the appropriateness of women and men for STEM professions that shape individuals' self-beliefs in the form of self-efficacy. Using a three-wave NSF-funded longitudinal survey of 559 engineering and computer science students that graduated from over two dozen institutions in the United States between 2015 and 2017, we find women earn less than men, net of human capital factors like engineering degree and grade point average, and that the influence of gender on starting salaries is associated with self-efficacy. We find no support for a competing hypothesis that the importance placed on pay explains the pay gap; there is no gender difference in reported importance placed on pay. We also find no support for the idea that women earn less because they place more importance on workplace culture; women do value workplace culture more, but those who hold such values earn more rather than less. Overall, the results suggest that addressing cultural beliefs as manifested in self-beliefs-that is, the confidence gap-commands attention to reduce the gender pay gap.
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Engenharia , Matemática , Ciência , Tecnologia , Cultura , Pesquisa Empírica , Feminino , Humanos , Masculino , Análise de Regressão , Salários e Benefícios , Autoeficácia , Fatores Sexuais , Recursos HumanosRESUMO
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). In mammalian cells, UPR signals generated by several ER-membrane-resident proteins, including the bifunctional protein kinase endoribonuclease IRE1α, control cell survival and the decision to execute apoptosis. Processing of XBP1 mRNA by the RNase domain of IRE1α promotes survival of ER stress, whereas activation of the mitogen-activated protein kinase JNK family by IRE1α late in the ER stress response promotes apoptosis. Here, we show that activation of JNK in the ER stress response precedes activation of XBP1. This activation of JNK is dependent on IRE1α and TRAF2 and coincides with JNK-dependent induction of expression of several antiapoptotic genes, including cIap1 (also known as Birc2), cIap2 (also known as Birc3), Xiap and Birc6 ER-stressed Jnk1(-/-) Jnk2(-/-) (Mapk8(-/-) Mapk9(-/-)) mouse embryonic fibroblasts (MEFs) display more pronounced mitochondrial permeability transition and increased caspase 3/7 activity compared to wild-type MEFs. Caspase 3/7 activity is also elevated in ER-stressed cIap1(-/-) cIap2(-/-) and Xiap(-/-) MEFs. These observations suggest that JNK-dependent transcriptional induction of several inhibitors of apoptosis contributes to inhibiting apoptosis early in the ER stress response.
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Estresse do Retículo Endoplasmático , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Processamento Alternativo/genética , Animais , Apoptose/genética , Morte Celular , Citosol/metabolismo , Embrião de Mamíferos/citologia , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/metabolismo , Ativação Enzimática , Fibroblastos/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 µm to 12 µm with the JWST's Mid-Infrared Instrument. The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet's nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.
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The progression and systemic pathobiology of C. auris in the absence of a microbiota have not been described. Here, we describe the influence of the microbiota during the first 5 days of C. auris infection in germ-free or antibiotic-depleted mice. Depletion of the bacterial microbiota in both germ-free and antibiotic-depleted models results in a modest but important increase in the early stages of C. auris infection. Particularly the heart and lungs, followed by the cecum, uterus, and stomach, of intravenously (i.v.) infected neutropenic mice showed significant fungal organ burden. Understanding disease progression and pathobiology of C. auris in individuals with a depleted microbiota could potentially help in the development of care protocols that incorporate supplementation or restoration of the microbiota before invasive procedures, such as transplantation surgeries.
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Animal colouration is often a trade-off between background matching for camouflage from predators, and conspicuousness for communication with con- or heterospecifics. Stomatopods are marine crustaceans known to use colour signals during courtship and contests, while their overall body colouration may provide camouflage. However, we have little understanding of how stomatopods perceive these signals in their environment or whether overall body coloration does provide camouflage from predators. Neogonodactylus oerstedii assess meral spot colour during contests, and meral spot colour varies depending on local habitat. By calculating quantum catch for N. oerstedii's 12 photoreceptors associated with chromatic vision, we found that variation in meral spot total reflectance does not function to increase signal contrast in the local habitat. Neogonodactylus oerstedii also show between-habitat variation in dorsal body colouration. We used visual models to predict a trichromatic fish predator's perception of these colour variations. Our results suggest that sandy and green stomatopods are camouflaged from a typical fish predator in rubble fields and seagrass beds, respectively. To our knowledge, this is the first study to investigate signal contrast and camouflage in a stomatopod. These results provide new insight into the function and evolution of colouration in a species with a complex visual system.
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Mimetismo Biológico/fisiologia , Decápodes/fisiologia , Pigmentação/fisiologia , Animais , Percepção de Cores/fisiologia , Crustáceos , Decápodes/genética , Evolução Molecular , Olho/anatomia & histologia , Variação Genética , Células Fotorreceptoras/fisiologia , Filogenia , Pigmentos Biológicos/fisiologiaRESUMO
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates a signaling network known as the unfolded protein response (UPR). Here we characterize how ER stress and the UPR inhibit insulin signaling. We find that ER stress inhibits insulin signaling by depleting the cell surface population of the insulin receptor. ER stress inhibits proteolytic maturation of insulin proreceptors by interfering with transport of newly synthesized insulin proreceptors from the ER to the plasma membrane. Activation of AKT, a major target of the insulin signaling pathway, by a cytosolic, membrane-bound chimera between the AP20187-inducible FV2E dimerization domain and the cytosolic protein tyrosine kinase domain of the insulin receptor was not affected by ER stress. Hence, signaling events in the UPR, such as activation of the JNK mitogen-activated protein (MAP) kinases or the pseudokinase TRB3 by the ER stress sensors IRE1α and PERK, do not contribute to inhibition of signal transduction in the insulin signaling pathway. Indeed, pharmacologic inhibition and genetic ablation of JNKs, as well as silencing of expression of TRB3, did not restore insulin sensitivity or rescue processing of newly synthesized insulin receptors in ER-stressed cells. [Media: see text].
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Estresse do Retículo Endoplasmático/fisiologia , Resistência à Insulina/fisiologia , Precursores de Proteínas/metabolismo , Receptor de Insulina/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos CD/fisiologia , Técnicas de Cultura de Células , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Fibroblastos , Células HEK293 , Humanos , Insulina/metabolismo , Resistência à Insulina/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Fosforilação , Precursores de Proteínas/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Transporte Proteico , Receptor de Insulina/fisiologia , Transdução de Sinais , Resposta a Proteínas não Dobradas/fisiologia , eIF-2 Quinase/metabolismoRESUMO
We present revised stellar properties for 172 K2 target stars that were identified as possible hosts of transiting planets during Campaigns 1-17. Using medium-resolution near-infrared spectra acquired with the NASA Infrared Telescope Facility/SpeX and Palomar/TripleSpec, we found that 86 of our targets were bona fide cool dwarfs, 74 were hotter dwarfs, and 12 were giants. Combining our spectroscopic metallicities with Gaia parallaxes and archival photometry, we derived photometric stellar parameters and compared them to our spectroscopic estimates. Although our spectroscopic and photometric radius and temperature estimates are consistent, our photometric mass estimates are systematically ΔM * = 0.11 Mâ (34%) higher than our spectroscopic mass estimates for the least massive stars (M *,phoi < 0.4 Mâ). Adopting the photometric parameters and comparing our results to parameters reported in the Ecliptic Plane Input Catalog, our revised stellar radii are ΔR * = 0.15Râ (40%) larger and our revised stellar effective temperatures are roughly ΔT eff = 65K cooler. Correctly determining the properties of K2 target stars is essential for characterizing any associated planet candidates, estimating the planet search sensitivity, and calculating planet occurrence rates. Even though Gaia parallaxes have increased the power of photometric surveys, spectroscopic characterization remains essential for determining stellar metallicities and investigating correlations between stellar metallicity and planetary properties.
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AIM: To investigate the effect of high homocysteine (Hcy) levels on apolipoprotein E (apoE) expression and the signaling pathways involved in this gene regulation. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to assess apoE expression in cells treated with various concentrations (50-500 µmol/L) of Hcy. Calcium phosphate-transient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2 (ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcy-mediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKß. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) or nuclear factor of activated T cells (NFAT). Chromatin immunoprecipitation (ChIP) assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 µmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region -100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy (250-750 µmol/L) induced a 2-3 fold decrease in apoE mRNA levels in HEK-293 cells, while apoE gene expression was not significantly affected by treatment with lower concentrations of Hcy (100 µmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apoE promoter activity was counteracted by MAPK/ERK kinase 1/2 (MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChIP experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells. CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apoE expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions.
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Obesity is associated with endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in adipose tissue. In this study we identify physiological triggers of ER stress and of the UPR in adipocytes in vitro. We show that two markers of adipose tissue remodelling in obesity, glucose starvation and hypoxia, cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Both conditions induced molecular markers of the IRE1α and PERK branches of the UPR, such as splicing of XBP1 mRNA and CHOP, as well as transcription of the ER stress responsive gene BiP. Hypoxia also induced an increase in phosphorylation of the PERK substrate eIF2α. By contrast, physiological triggers of ER stress in many other cell types, such as the saturated fatty acid palmitic acid, cholesterol, or several inflammatory cytokines including TNF-α, IL-1ß, and IL-6, do not cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Our data suggest that physiological changes associated with remodelling of adipose tissue in obesity, such as hypoxia and glucose starvation, are more likely physiological ER stressors of adipocytes than the lipid overload or hyperinsulinemia associated with obesity.
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OBJECTIVES: To evaluate computed tomography (CT) densitometry as a technique for quantifying contrast enhancement of compressive soft tissues in the canine lumbosacral vertebral canal and to determine whether the degree of contrast enhancement can be used to help predict tissue type or histopathologic characteristics. ANIMALS: 29 large breed dogs with lumbosacral stenosis. PROCEDURE: Contrast-enhanced CT of L5-S3 was performed by use of a previously described protocol. At each disk level, CT densities of a water-filled syringe, epaxial muscles, and 4 vertebral canal locations were measured. Mean tissue enhancement was calculated by vertebral canal location, using water-filled syringe enhancement as a correction factor. Corrected CT enhancement was compared with tissue type, degree of tissue inflammation, and degree of tissue activity. RESULTS: Intravenous contrast administration of contrast medium significantly increased CT densities of water-filled syringes and epaxial muscles. Corrected CT enhancement of vertebral canal soft tissues at stenotic sites was greater than at nonstenotic sites. There was no association between enhancement and tissue type for any vertebral canal location. There was no correlation between enhancement and degree of tissue inflammation. There was a correlation between enhancement and tissue activity in the dorsal vertebral canal only. CONCLUSIONS AND CLINICAL RELEVANCE: A water-filled syringe is a useful calibration tool for CT density measurements. The degree of tissue contrast enhancement, measured by CT densitometry, can be helpful for predicting the location of compressive soft tissues in dogs with lumbosacral stenosis. However, it is of limited value for predicting compressive soft-tissue types or histopathologic characteristics.
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Doenças do Cão/patologia , Estenose Espinal/veterinária , Tomografia Computadorizada por Raios X/veterinária , Animais , Meios de Contraste/química , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Cães , Região Lombossacral , Estudos Prospectivos , Canal Medular/patologia , Canal Medular/cirurgia , Estenose Espinal/diagnóstico , Estenose Espinal/patologia , Estenose Espinal/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
We used whole-body plethysmography to investigate the effect of restraint, ear marking, tail vein and retroorbital blood sampling, and tail clipping on respiration in Balb/c × TCR-HA +/- F1 hybrid mice (F1h). Baseline values of breathing parameters were determined. During the experiment, mice experienced a procedure and then plethysmographic recordings were obtained immediately and at 4, 24, and 48 h afterward. Baseline breathing parameters showed significant differences between sexes. Restraint affected minute volume differently than did handling in male mice and to a lesser extent in female mice. Ear marking significantly changed minute volume compared with handling but not restraint in male mice and in the opposite manner in female mice. Tail vein blood sampling changed minute volume in a significant manner compared with restraint but not compared with handling in both sexes. Retroorbital blood sampling significantly changed minute volume compared with values for both handling and restraint in male mice but only compared with handling in female mice. Tail clipping modified minute volume significantly compared with handling in male mice and compared with restraint in both sexes. Analysis of data showed that routine procedures affect minute volume in mice depending on invasiveness of maneuver and in a sex-biased manner for as long as 24 h after the procedure. Our experiment shows that procedures performed on laboratory mice can change respiratory parameters and can be investigated by plethysmography.
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Camundongos Endogâmicos BALB C/fisiologia , Pletismografia Total/veterinária , Respiração , Manejo de Espécimes/veterinária , Animais , Coleta de Amostras Sanguíneas/efeitos adversos , Coleta de Amostras Sanguíneas/veterinária , DNA/análise , Feminino , Masculino , Camundongos , Camundongos Transgênicos/classificação , Camundongos Transgênicos/genética , Restrição Física/fisiologia , Restrição Física/veterinária , Manejo de Espécimes/efeitos adversos , Cauda/cirurgiaAssuntos
Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/sangue , Feminino , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
There is no consensus regarding the aetiology or treatment of carpal boss. Recurrences or carpometacarpal instability is reported after simple resection. Carpometacarpal arthrodesis has been proposed as a primary treatment and after failure of simple resection. This paper reports the results at a mean follow-up of 17 (range 13-28) months of treatment by wedge-shaped joint resection, corticocancellous radial bone graft and arthrodesis with a shape memory staple of seven of 32 patients who presented with a painful carpal boss. The study group included five women and two men of mean age at operation 29 (range 18-40) years. Fusion was achieved in all cases and all patients were pain free at follow-up. No complications occurred and all the patients were pleased with the aesthetic aspect of the treatment.