Histone mutations in cancer Espinoza Pereira, Kimberly N; Shan, Jixiu; Licht, Jonathan D ...
Biochemical Society transactions,
10/2023, Volume:
51, Issue:
5
Journal Article
Peer reviewed
Open access
Genes encoding histone proteins are recurrently mutated in tumor samples, and these mutations may impact nucleosome stability, histone post-translational modification, or chromatin dynamics. The ...prevalence of histone mutations across diverse cancer types suggest that normal chromatin structure is a barrier to tumorigenesis. Oncohistone mutations disrupt chromatin structure and gene regulatory mechanisms, resulting in aberrant gene expression and the development of cancer phenotypes. Examples of oncohistones include the histone H3 K27M mutation found in pediatric brain cancers that blocks post-translational modification of the H3 N-terminal tail and the histone H2B E76K mutation found in some solid tumors that disrupts nucleosome stability. Oncohistones may comprise a limited fraction of the total histone pool yet cause global effects on chromatin structure and drive cancer phenotypes. Here, we survey histone mutations in cancer and review their function and role in tumorigenesis.
Abstract
The Near-Infrared Spectrograph (NIRSpec) is one of the four focal plane instruments on the James Webb Space Telescope. In this paper, we summarize the in-orbit performance of NIRSpec, as ...derived from data collected during its commissioning campaign and the first few months of nominal science operations. More specifically, we discuss the performance of some critical hardware components such as the two NIRSpec Hawaii-2RG detectors, wheel mechanisms, and the microshutter array. We also summarize the accuracy of the two target acquisition procedures used to accurately place science targets into the slit apertures, discuss the current status of the spectrophotometric and wavelength calibration of NIRSpec spectra, and provide the “as measured” sensitivity in all NIRSpec science modes. Finally, we point out a few important considerations for the preparation of NIRSpec science programs.
Methane gas hydrates, crystalline inclusion compounds formed from methane and water, are found in marine continental margin and permafrost sediments worldwide. This article reviews the current ...understanding of phenomena involved in gas hydrate formation and the physical properties of hydrate‐bearing sediments. Formation phenomena include pore‐scale habit, solubility, spatial variability, and host sediment aggregate properties. Physical properties include thermal properties, permeability, electrical conductivity and permittivity, small‐strain elastic P and S wave velocities, shear strength, and volume changes resulting from hydrate dissociation. The magnitudes and interdependencies of these properties are critically important for predicting and quantifying macroscale responses of hydrate‐bearing sediments to changes in mechanical, thermal, or chemical boundary conditions. These predictions are vital for mitigating borehole, local, and regional slope stability hazards; optimizing recovery techniques for extracting methane from hydrate‐bearing sediments or sequestering carbon dioxide in gas hydrate; and evaluating the role of gas hydrate in the global carbon cycle.
African swine fever virus (ASFV) causes a virulent, deadly infection in wild and domestic swine and is currently causing a pandemic covering a contiguous geographical area from Central and Eastern ...Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in devastating economic losses to the swine industry. The most advanced vaccine candidates are live attenuated strains developed using a genetically modified virulent parental virus. Recently, we developed a vaccine candidate, ASFV-G-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV pandemic strain Georgia (ASFV-G). ASFV-G-ΔI177L is safe and highly efficacious in challenge studies using parental ASFV-G. Large-scale production of ASFV-G-ΔI177L has been limited because it can replicate efficiently only in primary swine macrophages. Here, we present the development of an ASFV-G-ΔI177L derivative strain, ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine cell line. In challenge studies, ASFV-G-ΔI177L/ΔLVR maintained the same level of attenuation, immunogenic characteristics, and protective efficacy as ASFV-G-ΔI177L. ASFV-G-ΔI177L/ΔLVR is the first rationally designed ASF vaccine candidate that can be used for large-scale commercial vaccine manufacture.
African swine fever is currently causing a pandemic resulting in devastating losses to the swine industry. Experimental ASF vaccines rely on the production of vaccine in primary swine macrophages, which are difficult to use for the production of a vaccine on a commercial level. Here, we report a vaccine for ASFV with a deletion in the left variable region (LVR). This deletion allows for growth in stable cell cultures while maintaining the potency and efficacy of the parental vaccine strain. This discovery will allow for the production of an ASF vaccine on a commercial scale.
Abstract
We report the discovery of HATS-70b, a transiting brown dwarf at the deuterium burning limit. HATS-70b has a mass of
and a radius of
, residing in a close-in orbit with a period of
days. The ...host star is a
A star rotating at
, enabling us to characterize the spectroscopic transit of the brown dwarf via Doppler tomography. We find that HATS-70b, like other massive planets and brown dwarfs previously sampled, orbits in a low projected-obliquity orbit with
. The low obliquities of these systems is surprising given all brown dwarf and massive planets with obliquities measured orbit stars hotter than the Kraft break. This trend is tentatively inconsistent with dynamically chaotic migration for systems with massive companions, though the stronger tidal influence of these companions makes it difficult to draw conclusions on the primordial obliquity distribution of this population. We also introduce a modeling scheme for planets around rapidly rotating stars, accounting for the influence of gravity darkening on the derived stellar and planetary parameters.
We report the discovery of HATS-71b, a transiting gas giant planet on a day orbit around a mag M3 dwarf star. HATS-71 is the coolest M dwarf star known to host a hot Jupiter. The loss of light during ...transits is 4.7%, more than in any other confirmed transiting planet system. The planet was identified as a candidate by the ground-based HATSouth transit survey. It was confirmed using ground-based photometry, spectroscopy, and imaging, as well as space-based photometry from the NASA Transiting Exoplanet Survey Satellite mission (TIC 234523599). Combining all of these data, and utilizing Gaia DR2, we find that the planet has a radius of and mass of (95% confidence upper limit of ), while the star has a mass of and a radius of .
Abstract
We report the discovery of 10 transiting extrasolar planets by the HATSouth survey. The planets range in mass from the super-Neptune HATS-62b, with
, to the super-Jupiter HATS-66b, with
, ...and in size from the Saturn HATS-69b, with
, to the inflated Jupiter HATS-67b, with
. The planets have orbital periods between
days (HATS-67b) and
days (HATS-61b). The hosts are dwarf stars with masses ranging from
(HATS-69) to
(HATS-64) and have apparent magnitudes between
mag (HATS-68) and
mag (HATS-66). The super-Neptune HATS-62b is the least massive planet discovered to date with a radius larger than Jupiter. Based largely on the
Gaia
DR2 distances and broadband photometry, we identify three systems (HATS-62, HATS-64, and HATS-65) as having possible unresolved binary star companions. We discuss in detail our methods for incorporating the
Gaia
DR2 observations into our modeling of the system parameters and into our blend analysis procedures.
We report the discovery of TOI 837b and its validation as a transiting planet. We characterize the system using data from the NASA Transiting Exoplanet Survey Satellite mission, the ESA Gaia mission, ...ground-based photometry from El Sauce and ASTEP400, and spectroscopy from CHIRON, FEROS, and Veloce. We find that TOI 837 is a T = 9.9 mag G0/F9 dwarf in the southern open cluster IC 2602. The star and planet are therefore million years old. Combining the transit photometry with a prior on the stellar parameters derived from the cluster color-magnitude diagram, we find that the planet has an orbital period of and is slightly smaller than Jupiter ( ). From radial velocity monitoring, we limit to less than 1.20 MJup (3 ). The transits either graze or nearly graze the stellar limb. Grazing transits are a cause for concern, as they are often indicative of astrophysical false-positive scenarios. Our follow-up data show that such scenarios are unlikely. Our combined multicolor photometry, high-resolution imaging, and radial velocities rule out hierarchical eclipsing binary scenarios. Background eclipsing binary scenarios, though limited by speckle imaging, remain a 0.2% possibility. TOI 837b is therefore a validated adolescent exoplanet. The planetary nature of the system can be confirmed or refuted through observations of the stellar obliquity and the planetary mass. Such observations may also improve our understanding of how the physical and orbital properties of exoplanets change in time.
We report six new inflated hot Jupiters (HATS-25b through HATS-30b) discovered using the HATSouth global network of automated telescopes. The planets orbit stars with V magnitudes in the range of ...~12-14 and have masses in the largely populated 0.5MJ-0.7M sub(J) region of parameter space but span a wide variety of radii, from 1.17R sub(J) to 1.75R sub(J). HATS-25b, HATS-28b, HATS-29b, and HATS-30b are typical inflated hot Jupiters (Rp= 1.17-1.26R sub(J)) orbiting G-type stars in short period (P= 3.2-4.6 days) orbits. However, HATS-26b (Rp= 1.75R sub(J), P= 3.3024 days) and HATS-27b (Rp= 1.50R sub(J), P= 4.6370 days) stand out as highly inflated planets orbiting slightly evolved F stars just after and in the turn-off points, respectively, which are among the least dense hot Jupiters, with densities of 0.153 g cm super(-3) and 0.180 g cm super(-3), respectively. All the presented exoplanets but HATS-27b are good targets for future atmospheric characterization studies, while HATS-27b is a prime target for Rossiter-McLaughlin monitoring in order to determine its spin-orbit alignment given the brightness (V= 12.8) and stellar rotational velocity (v sin iapproximate 9.3 km s super(-1)) of the host star. These discoveries significantly increase the number of inflated hot Jupiters known, contributing to our understanding of the mechanism(s) responsible for hot Jupiter inflation.
Abstract
We report the discovery of K2-232 b using photometric data of the Kepler K2 satellite coupled with ground-based spectroscopic observations. K2-232 b has a mass of MP = 0.397 ± 0.037 MJ, a ...radius of RP = 1.00 ± 0.020 RJ, and a moderately low equilibrium temperature of Teq = 1030 ± 15 K due to its relatively large star–planet separation of a = 0.1036 au. K2-232 b orbits its bright (V = 9.9) late F-type host star in an eccentric orbit (e = 0.258 ± 0.025) every 11.2 d, and is one of only four well-characterized warm Jupiters having host stars brighter than V = 10. We estimate a heavy element content of 20 ± 7 M⊕ for K2-232 b, which is consistent with standard models of giant planet formation. The bright host star of K2-232 b makes this system a well-suited target for detailed follow-up observations that will aid in the study of the atmospheres and orbital evolution of giant planets at moderate separations from their host stars.
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