185 research outputs found

    A Two-Phase Innate Host Response to Alphavirus Infection Identified by mRNP-Tagging In Vivo

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    A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during infection. However, elucidation of this cascade in vivo has been limited by a general inability to distinguish changes occurring in the minority of infected cells from those in surrounding uninfected cells. To circumvent this inherent limitation of traditional gene expression profiling methods, an innovative mRNP-tagging technique was implemented to isolate host mRNA specifically from infected cells in vitro as well as in vivo following Venezuelan equine encephalitis virus (VEE) infection. This technique facilitated a direct characterization of the host defense response specifically within the first cells infected with VEE, while simultaneous total RNA analysis assessed the collective response of both the infected and uninfected cells. The result was a unique, multifaceted profile of the early response to VEE infection in primary dendritic cells, as well as in the draining lymph node, the initially targeted tissue in the mouse model. A dynamic environment of complex interactions was revealed, and suggested a two-step innate response in which activation of a subset of host genes in infected cells subsequently leads to activation of the surrounding uninfected cells. Our findings suggest that the application of viral mRNP-tagging systems, as introduced here, will facilitate a much more detailed understanding of the highly coordinated host response to infectious agents

    Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

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    Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

    TOI-561 b: A Low Density Ultra-Short Period "Rocky" Planet around a Metal-Poor Star

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    TOI-561 is a galactic thick disk star hosting an ultra-short period (0.45 day orbit) planet with a radius of 1.37 R_{\oplus}, making it one of the most metal-poor ([Fe/H] = -0.41) and oldest (\sim10 Gyr) sites where an Earth-sized planet has been found. We present new simultaneous radial velocity measurements (RVs) from Gemini-N/MAROON-X and Keck/HIRES, which we combined with literature RVs to derive a mass of Mb_{b}=2.24 ±\pm 0.20 M_{\oplus}. We also used two new Sectors of TESS photometry to improve the radius determination, finding Rb_{b}=1.37±0.04R1.37 \pm 0.04 R_\oplus, and confirming that TOI-561 b is one of the lowest-density super-Earths measured to date (ρb\rho_b= 4.8 ±\pm 0.5 g/cm3^{3}). This density is consistent with an iron-poor rocky composition reflective of the host star's iron and rock-building element abundances; however, it is also consistent with a low-density planet with a volatile envelope. The equilibrium temperature of the planet (\sim2300 K) suggests that this envelope would likely be composed of high mean molecular weight species, such as water vapor, carbon dioxide, or silicate vapor, and is likely not primordial. We also demonstrate that the composition determination is sensitive to the choice of stellar parameters, and that further measurements are needed to determine if TOI-561 b is a bare rocky planet, a rocky planet with an optically thin atmosphere, or a rare example of a non-primordial envelope on a planet with a radius smaller than 1.5 R_{\oplus}.Comment: Accepted to AJ on 11/28/202

    Investigating the Atmospheric Mass Loss of the Kepler-105 Planets Straddling the Radius Gap

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    An intriguing pattern among exoplanets is the lack of detected planets between approximately 1.51.5 R_\oplus and 2.02.0 R_\oplus. One proposed explanation for this "radius gap" is the photoevaporation of planetary atmospheres, a theory that can be tested by studying individual planetary systems. Kepler-105 is an ideal system for such testing due to the ordering and sizes of its planets. Kepler-105 is a sun-like star that hosts two planets straddling the radius gap in a rare architecture with the larger planet closer to the host star (Rb=2.53±0.07R_b = 2.53\pm0.07 R_\oplus, Pb=5.41P_b = 5.41 days, Rc=1.44±0.04R_c = 1.44\pm0.04 R_\oplus, Pc=7.13P_c = 7.13 days). If photoevaporation sculpted the atmospheres of these planets, then Kepler-105b would need to be much more massive than Kepler-105c to retain its atmosphere, given its closer proximity to the host star. To test this hypothesis, we simultaneously analyzed radial velocities (RVs) and transit timing variations (TTVs) of the Kepler-105 system, measuring disparate masses of Mb=10.8±2.3M_b = 10.8\pm2.3 M_\oplus (ρb=0.97±0.22 \rho_b = 0.97\pm0.22 g cm3^{-3}) and Mc=5.6±1.2M_c = 5.6\pm1.2 M_\oplus (ρc=2.64±0.61\rho_c = 2.64\pm0.61 g cm3^{-3}). Based on these masses, the difference in gas envelope content of the Kepler-105 planets could be entirely due to photoevaporation (in 76\% of scenarios), although other mechanisms like core-powered mass loss could have played a role for some planet albedos.Comment: 14 pages, 3 figures, 2 table

    Giant Outer Transiting Exoplanet Mass (GOT 'EM) Survey. IV. Long-term Doppler Spectroscopy for 11 Stars Thought to Host Cool Giant Exoplanets

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    Discovering and characterizing exoplanets at the outer edge of the transit method's sensitivity has proven challenging owing to geometric biases and the practical difficulties associated with acquiring long observational baselines. Nonetheless, a sample of giant exoplanets on orbits longer than 100 days has been identified by transit hunting missions. We present long-term Doppler spectroscopy for 11 such systems with observation baselines spanning a few years to a decade. We model these radial velocity observations jointly with transit photometry to provide initial characterizations of these objects and the systems in which they exist. Specifically, we make new precise mass measurements for four long-period giant exoplanets (Kepler-111 c, Kepler-553 c, Kepler-849 b, and PH-2 b), we place new upper limits on mass for four others (Kepler-421 b, KOI-1431.01, Kepler-1513 b, and Kepler-952 b), and we show that several "confirmed" planets are in fact not planetary at all. We present these findings to complement similar efforts focused on closer-in short-period giant planets, and with the hope of inspiring future dedicated studies of cool giant exoplanets.Comment: 35 pages, 24 figures, 11 tables. Accepted for publication in ApJ Supplemen

    Overfitting Affects the Reliability of Radial Velocity Mass Estimates of the V1298 Tau Planets

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    Mass, radius, and age measurements of young (<100 Myr) planets have the power to shape our understanding of planet formation. However, young stars tend to be extremely variable in both photometry and radial velocity, which makes constraining these properties challenging. The V1298 Tau system of four ~0.5 Rjup planets transiting a pre-main sequence star presents an important, if stress-inducing, opportunity to directly observe and measure the properties of infant planets. Su\'arez-Mascare\~no et al. (2021) published radial-velocity-derived masses for two of the V1298 Tau planets using a state-of-the-art Gaussian Process regression framework. The planetary densities computed from these masses were surprisingly high, implying extremely rapid contraction after formation in tension with most existing planet formation theories. In an effort to further constrain the masses of the V1298 Tau planets, we obtained 36 RVs using Keck/HIRES, and analyzed them in concert with published RVs and photometry. Through performing a suite of cross validation tests, we found evidence that the preferred model of SM21 suffers from overfitting, defined as the inability to predict unseen data, rendering the masses unreliable. We detail several potential causes of this overfitting, many of which may be important for other RV analyses of other active stars, and recommend that additional time and resources be allocated to understanding and mitigating activity in active young stars such as V1298 Tau.Comment: 26 pages, 12 figures; published in A
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