STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host ...defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING
mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING
mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING
mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 ...December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
Context.
Proxima Centauri is the closest star to the Sun. This small, low-mass, mid M dwarf is known to host an Earth-mass exoplanet with an orbital period of 11.2 days within the habitable zone, as ...well as a long-period planet candidate with an orbital period of close to 5 yr.
Aims.
We report on the analysis of a large set of observations taken with the ESPRESSO spectrograph at the VLT aimed at a thorough evaluation of the presence of a third low-mass planetary companion, which started emerging during a previous campaign.
Methods.
Radial velocities (RVs) were calculated using both a cross-correlation function (CCF) and a template matching approach. The RV analysis includes a component to model Proxima’s activity using a Gaussian process (GP). We use the CCF’s full width at half maximum to help constrain the GP, and we study other simultaneous observables as activity indicators in order to assess the nature of any potential RV signals.
Results.
We detect a signal at 5.12 ± 0.04 days with a semi-amplitude of 39 ± 7 cm s
−1
. The analysis of subsets of the ESPRESSO data, the activity indicators, and chromatic RVs suggest that this signal is not caused by stellar variability but instead by a planetary companion with a minimum mass of 0.26 ± 0.05
M
⊕
(about twice the mass of Mars) orbiting at 0.029 au from the star. The orbital eccentricity is well constrained and compatible with a circular orbit.
Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral ...route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.
Context. The chemical composition of stars that have orbiting planets provides important clues about the frequency, architecture, and composition of exoplanet systems. Aims. We explore the ...possibility that stars from different galactic populations that have different intrinsic abundance ratios may produce planets with a different overall composition. Methods. We compiled abundances for Fe, O, C, Mg, and Si in a large sample of solar neighbourhood stars that belong to different galactic populations. We then used a simple stoichiometric model to predict the expected iron-to-silicate mass fraction and water mass fraction of the planet building blocks, as well as the summed mass percentage of all heavy elements in the disc. Results. Assuming that overall the chemical composition of the planet building blocks will be reflected in the composition of the formed planets, we show that according to our model, discs around stars from different galactic populations, as well as around stars from different regions in the Galaxy, are expected to form rocky planets with significantly different iron-to-silicate mass fractions. The available water mass fraction also changes significantly from one galactic population to another. Conclusions. The results may be used to set constraints for models of planet formation and chemical composition. Furthermore, the results may have impact on our understanding of the frequency of planets in the Galaxy, as well as on the existence of conditions for habitability.
Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome‐wide association studies (GWAS) on NSCL/P have consistently identified ...association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re‐sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in‐frame deletion, and four loss‐of‐function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co‐segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.
The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Simultaneous breaking of inversion- and time-reversal symmetry in Josephson junction (JJ) leads to a possible violation of the
(
) = -
(-
) equality for the current-phase relation. This is known as ...anomalous Josephson effect and it produces a phase shift
in sinusoidal current-phase relations. In ballistic JJs with non-sinusoidal current phase relation the observed phenomenology is much richer, including the supercurrent diode effect and the magnetochiral anisotropy (MCA) of Josephson inductance. In this work, we present measurements of both effects on arrays of JJs defined on epitaxial Al/InAs heterostructures. We show that the orientation of the current with respect to the lattice affects the MCA, possibly as the result of a finite Dresselhaus component. In addition, we show that the two-fold symmetry of the Josephson inductance reflects in the activation energy for phase slips.
Aerobic conditioning improves exercise capacity and decreases symptoms in patients with asthma. However, its benefits in the context of allergic airway inflammation are poorly understood.
To evaluate ...the effects of two intensities of aerobic exercise on airway inflammation and remodeling in a model of chronic allergic lung inflammation.
Mice were subjected to chronic ovalbumin (OVA) sensitization and to 4 weeks of low (OVA+Low) or moderate (OVA+Mod) exercise training in a treadmill. Airway inflammation and remodeling and expression of helper T-cell type 1 and 2 cytokines were evaluated.
OVA-induced allergic airway inflammation and remodeling were characterized by an increase in collagen (288%), elastic fiber (56%), smooth muscle (380%), and epithelial (402%) contents (P < 0.001) when compared with the control group. OVA+Low and OVA+Mod groups presented a decrease in bronchoalveolar lavage fluid eosinophils (respectively, 84 and 75%; P < 0.01) and airway walls (respectively, 94 and 58%; P < 0.001) when compared with the OVA group. OVA+Low and OVA+Mod groups also presented a reduction in the number of peribronchial inflammatory cells expressing IL-4 (respectively, 85 and 75%; P < 0.01) and IL-5 (respectively, 88 and 89%; P < 0.01) when compared with the OVA group. Aerobic conditioning did not change the expression of either IFN-gamma or IL-2 by inflammatory cells or plasma levels of IgE or IgG1. OVA+Low and OVA+Mod groups presented an increase in the expression of IL-10 (P < 0.001). Low and moderate aerobic conditioning also reduced airway remodeling in OVA-sensitized mice when compared with the OVA group.
We concluded that low and moderate aerobic exercise decreases airway inflammation and remodeling in a murine model of asthma.
We present results from a data challenge posed to the radial velocity (RV) community: namely, to quantify the Bayesian "evidence" for n = {0, 1, 2, 3} planets in a set of synthetically generated RV ...data sets containing a range of planet signals. Participating teams were provided the same likelihood function and set of priors to use in their analysis. They applied a variety of methods to estimate , the marginal likelihood for each n-planet model, including cross-validation, the Laplace approximation, importance sampling, and nested sampling. We found the dispersion in across different methods grew with increasing n-planet models: ∼3 for zero planets, ∼10 for one planet, ∼102-103 for two planets, and >104 for three planets. Most internal estimates of uncertainty in for individual methods significantly underestimated the observed dispersion across all methods. Methods that adopted a Monte Carlo approach by comparing estimates from multiple runs yielded plausible uncertainties. Finally, two classes of numerical algorithms (those based on importance and nested samplers) arrived at similar conclusions regarding the ratio of for n- and (n + 1)-planet models. One analytic method (the Laplace approximation) demonstrated comparable performance. We express both optimism and caution: we demonstrate that it is practical to perform rigorous Bayesian model comparison for models of ≤3 planets, yet robust planet discoveries require researchers to better understand the uncertainty in and its connections to model selection.
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