Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation

Predicting risk for radiographic damage in rheumatoid arthritis:comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Pathophysiology and treatment of rheumatic disease

KELT-11b: A Highly Inflated Sub-Saturn Exoplanet Transiting the V=8 Subgiant HD 93396

We report the discovery of a transiting exoplanet, KELT-11b, orbiting the bright ($V=8.0$) subgiant HD 93396. A global analysis of the system shows that the host star is an evolved subgiant star with $T_{\rm eff} = 5370\pm51$ K, $M_{*} = 1.438_{-0.052}^{+0.061} M_{\odot}$, $R_{*} = 2.72_{-0.17}^{+0.21} R_{\odot}$, log $g_*= 3.727_{-0.046}^{+0.040}$, and [Fe/H]$= 0.180\pm0.075$. The planet is a low-mass gas giant in a $P = 4.736529\pm0.00006$ day orbit, with $M_{P} = 0.195\pm0.018 M_J$, $R_{P}= 1.37_{-0.12}^{+0.15} R_J$, $\rho_{P} = 0.093_{-0.024}^{+0.028}$ g cm$^{-3}$, surface gravity log ${g_{P}} = 2.407_{-0.086}^{+0.080}$, and equilibrium temperature $T_{eq} = 1712_{-46}^{+51}$ K. KELT-11 is the brightest known transiting exoplanet host in the southern hemisphere by more than a magnitude, and is the 6th brightest transit host to date. The planet is one of the most inflated planets known, with an exceptionally large atmospheric scale height (2763 km), and an associated size of the expected atmospheric transmission signal of 5.6%. These attributes make the KELT-11 system a valuable target for follow-up and atmospheric characterization, and it promises to become one of the benchmark systems for the study of inflated exoplanets.Comment: 15 pages, Submitted to AAS Journal

Correction: Mucosal Healing and Fibrosis after Acute or Chronic Inflammation in Wild Type FVB-N Mice and C57BL6 Procollagen α1(I)-Promoter-GFP Reporter Mice

BackgroundInjury and intestinal inflammation trigger wound healing responses that can restore mucosal architecture but if chronic, can promote intestinal fibrosis. Intestinal fibrosis is a major complication of Crohn’s disease. The cellular and molecular basis of mucosal healing and intestinal fibrosis are not well defined and better understanding requires well characterized mouse models.MethodsFVB-N wild type mice and C57BL6 procollagen α1(I)-GFP reporter mice were given one (DSS1) or two (DSS2) cycles of 3% DSS (5 days/cycle) followed by 7 days recovery. Histological scoring of inflammation and fibrosis were performed at DSS1, DSS1+3, DSS1+7, DSS2, DSS2+3, and DSS2+7. Procollagen α1(I)-GFP activation was assessed in DSS and also TNBS models by whole colon GFP imaging and fluorescence microscopy. Colocalization of GFP with α-smooth muscle actin (α-SMA) or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen α1(I) mRNA.ResultsMales were more susceptible to DSS-induced disease and mortality than females. In FVB-N mice one DSS cycle induced transient mucosal inflammation and fibrosis that resolved by 7 days of recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset of FVB-N mice but overall, did not yield more consistent, severe or sustained fibrosis. In C57BL6 mice, procollagen α1(I)-GFP reporter was activated at the end of DSS1 and through DSS+7 with more dramatic and transmural activation at DSS2 through DSS2+7, and in TNBS treated mice. In DSS and TNBS models GFP reporter expression localized to vimentin+ cells and much fewer α-SMA+ cells. GFP mRNA strongly correlated with collagen α1(I) mRNA.ConclusionsOne DSS cycle in FVB-N mice provides a model to study mucosal injury and subsequent mucosal healing. The procollagen α1(I)-GFP transgenic provides a useful model to study activation of a gene encoding a major extracellular matrix protein during acute or chronic experimental intestinal inflammation and fibrosis

KELT-12b: A P ~ 5 day, Highly Inflated Hot Jupiter Transiting A Mildly Evolved Hot Star

We announce the discovery of KELT-12b, a highly inflated Jupiter-mass planet transiting the mildly evolved, V = 10.64 host star TYC 2619-1057-1. We followed up the initial transit signal in the KELT-North survey data with precise ground-based photometry, high-resolution spectroscopy, precise radial velocity measurements, and high-resolution adaptive optics imaging. Our preferred best-fit model indicates that the host star has = 6279 ± 51 K, = 3.89 ± 0.05,[Fe/H] = , = , and = 2.37 ± 0.17 . The planetary companion has = 0.95 ± 0.14 , = , = , and density = g cm −3 , making it one of the most inflated giant planets known. Furthermore, for future follow-up, we report a high-precision time of inferior conjunction in of 2,457,083.660459 ± 0.000894 and period of days. Despite the relatively large separation of ∼0.07 au implied by its ∼5.03-day orbital period, KELT-12b receives significant flux of erg s −1 cm −2 from its host. We compare the radii and insolations of transiting gas giant planets around hot ( K) and cool stars, noting that the observed paucity of known transiting giants around hot stars with low insolation is likely due to selection effects. We underscore the significance of long-term ground-based monitoring of hot stars and space-based targeting of hot stars with the Transiting Exoplanet Survey Satellite to search for inflated gas giants in longer-period orbits

KELT-8b: A highly inflated transiting hot Jupiter and a new technique for extracting high-precision radial velocities from noisy spectra

We announce the discovery of a highly inflated transiting hot Jupiter discovered by the KELT-North survey. A global analysis including constraints from isochrones indicates that the V = 10.8 host star (HD 343246) is a mildly evolved, G dwarf with $T_{\rm eff} = 5754_{-55}^{+54}$ K, $\log{g} = 4.078_{-0.054}^{+0.049}$, $[Fe/H] = 0.272\pm0.038$, an inferred mass $M_{*}=1.211_{-0.066}^{+0.078}$ M$_{\odot}$, and radius $R_{*}=1.67_{-0.12}^{+0.14}$ R$_{\odot}$. The planetary companion has mass $M_P = 0.867_{-0.061}^{+0.065}$ $M_{J}$, radius $R_P = 1.86_{-0.16}^{+0.18}$ $R_{J}$, surface gravity $\log{g_{P}} = 2.793_{-0.075}^{+0.072}$, and density $\rho_P = 0.167_{-0.038}^{+0.047}$ g cm$^{-3}$. The planet is on a roughly circular orbit with semimajor axis $a = 0.04571_{-0.00084}^{+0.00096}$ AU and eccentricity $e = 0.035_{-0.025}^{+0.050}$. The best-fit linear ephemeris is $T_0 = 2456883.4803 \pm 0.0007$ BJD$_{\rm TDB}$ and $P = 3.24406 \pm 0.00016$ days. This planet is one of the most inflated of all known transiting exoplanets, making it one of the few members of a class of extremely low density, highly-irradiated gas giants. The low stellar $\log{g}$ and large implied radius are supported by stellar density constraints from follow-up light curves, plus an evolutionary and space motion analysis. We also develop a new technique to extract high precision radial velocities from noisy spectra that reduces the observing time needed to confirm transiting planet candidates. This planet boasts deep transits of a bright star, a large inferred atmospheric scale height, and a high equilibrium temperature of $T_{eq}=1675^{+61}_{-55}$ K, assuming zero albedo and perfect heat redistribution, making it one of the best targets for future atmospheric characterization studies.Comment: Submitted to ApJ, feedback is welcom

Stellar Spin-Orbit Misalignment in a Multiplanet System

Stars hosting hot Jupiters are often observed to have high obliquities, whereas stars with multiple co-planar planets have been seen to have low obliquities. This has been interpreted as evidence that hot-Jupiter formation is linked to dynamical disruption, as opposed to planet migration through a protoplanetary disk. We used asteroseismology to measure a large obliquity for Kepler-56, a red giant star hosting two transiting co-planar planets. These observations show that spin-orbit misalignments are not confined to hot-Jupiter systems. Misalignments in a broader class of systems had been predicted as a consequence of torques from wide-orbiting companions, and indeed radial-velocity measurements revealed a third companion in a wide orbit in the Kepler-56 system.Comment: Accepted for publication in Science, published online on October 17 2013; PDF includes main article and supplementary materials (65 pages, 27 figures, 7 tables); v2: small correction to author lis

KELT-18b: Puffy Planet, Hot Host, Probably Perturbed

We report the discovery of KELT-18b, a transiting hot Jupiter in a 2.87-day orbit around the bright ( V = 10.1), hot, F4V star BD+60 1538 (TYC 3865-1173-1). We present follow-up photometry, spectroscopy, and adaptive optics imaging that allow a detailed characterization of the system. Our preferred model fits yield a host stellar temperature of K and a mass of , situating it as one of only a handful of known transiting planets with hosts that are as hot, massive, and bright. The planet has a mass of , a radius of , and a density of , making it one of the most inflated planets known around a hot star. We argue that KELT-18b’s high temperature and low surface gravity, which yield an estimated ∼600 km atmospheric scale height, combined with its hot, bright host, make it an excellent candidate for observations aimed at atmospheric characterization. We also present evidence for a bound stellar companion at a projected separation of ∼1100 au, and speculate that it may have contributed to the strong misalignment we suspect between KELT-18\u27s spin axis and its planet’s orbital axis. The inferior conjunction time is 2457542.524998 ± 0.000416 (BJD TDB ) and the orbital period is 2.8717510 ± 0.0000029 days. We encourage Rossiter–McLaughlin measurements in the near future to confirm the suspected spin–orbit misalignment of this system

A Giant Planet Undergoing Extreme-Ultraviolet Irradiation By Its Hot Massive-Star Host

The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300–10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside2, and is highly inflated–traits that have been linked to high insolation3,4. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star (ref. 6)