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Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is an important cause of drug-resistant epilepsy. A significant subset of individuals diagnosed with MOGHE display somatic mosaicism for loss-of-function variants in SLC35A2, which encodes the UDP-galactose transporter. We developed a mouse model to investigate how disruption of this transporter leads to a malformation of cortical development. We used in utero electroporation and CRISPR/Cas9 to knockout Slc35a2 in a subset of layer 2/3 cortical neuronal progenitors in the developing brains of male and female fetal mice to model mosaic expression. Mosaic Slc35a2 knockout was verified through next-generation sequencing and immunohistochemistry of GFP-labelled transfected cells. Histology of brain tissue in mosaic Slc35a2 knockout mice revealed the presence of upper layer-derived cortical neurons in the white matter. Reconstruction of single filled neurons identified altered dendritic arborisation with Slc35a2 knockout neurons having increased complexity. Whole-cell electrophysiological recordings revealed that Slc35a2 knockout neurons display reduced action potential firing, increased afterhyperpolarisation duration and reduced burst-firing when compared with control neurons. Mosaic Slc35a2 knockout mice also exhibited significantly increased epileptiform spiking and increased locomotor activity. We successfully generated a mouse model of mosaic Slc35a2 deficiency, which recapitulates features of the human phenotype, including impaired neuronal migration. We show that knockout in layer 2/3 cortical neuron progenitors is sufficient to disrupt neuronal excitability, increase epileptiform activity and cause hyperactivity in mosaic mice. Our mouse model provides an opportunity to further investigate the disease mechanisms that contribute to MOGHE and facilitate the development of precision therapies.

In parallel with the multi-messenger revolution, major advances in time-domain astronomy across multiple science disciplines relevant to astrophysics are becoming more urgent to address. Aside from electromagnetic observations of gravitational wave events and explosive counterparts, there are a number of “classical” astrophysical areas that require new thinking for proper exploration in the time domain. How NASA, NSF, ESA, and ESO consider the 2020 USA Decadal Survey within the astronomy community, as well as the worldwide call to support and expand time domain and multi-messenger astrophysics, it is crucial that all areas of astrophysics, including stellar, galactic, Solar System, and exoplanetary science participate in the discussion, and that it not be made into an exclusive preserve of cosmological, high-energy, explosive and transient science. Time domain astronomy is used to explore many aspects of astrophysics–particularly concerning ground- and space-based mission science goals of exploring how the Universe works, understanding how did we get here, and are we alone. Time domain studies are already built into the core operations of many currently operating and future space telescopes (e.g., Roman, PLATO) as well as current and planned large areal ground-based surveys (e.g., Rubin). Time-domain observations designed for one scientific purpose, also lead to great discoveries in many other science areas. The recent advent of user-friendly hardware, software, observational approaches, and online data infrastructure has also helped make time domain observations especially suitable and appealing for citizen science projects. We provide a review of the current state of TDAMM alerts and observational protocols, revealing a wide array of software and applications, much of which is incompatible. Any conversation regarding TDAMM astrophysics should include all aspects of the field, including those aspects seen as classical applications.

Transiting giant exoplanets around M-dwarf stars (GEMS) are rare, owing to the low-mass host stars. However, the all-sky coverage of TESS has enabled the detection of an increasingly large number of them to enable statistical surveys like the Searching for GEMS survey. As part of this endeavor, we describe the observations of six transiting giant planets, which include precise mass measurements for two GEMS (K2-419Ab, TOI-6034b) and statistical validation for four systems, which includes validation and mass upper limits for three of them (TOI-5218b, TOI-5616b, TOI-5634Ab), while the fourth one—TOI-5414b is classified as a “likely planet.” Our observations include radial velocities from the Habitable-zone Planet Finder on the Hobby–Eberly Telescope, and MAROON-X on Gemini-North, along with photometry and high-contrast imaging from multiple ground-based facilities. In addition to TESS photometry, K2-419Ab was also observed and statistically validated as part of the K2 mission in Campaigns 5 and 18, which provide precise orbital and planetary constraints despite the faint host star and long orbital period of ∼20.4 days. With an equilibrium temperature of only 380 K, K2-419Ab is one of the coolest known well-characterized transiting planets. TOI-6034 has a late F-type companion about 40″ away, making it the first GEMS host star to have an earlier main-sequence binary companion. These confirmations add to the existing small sample of confirmed transiting GEMS.

The Gemini South telescope is now equipped with a new high-resolution spectrograph called the Gemini High-resolution Optical SpecTrograph (GHOST). This instrument provides high-efficiency, high-resolution spectra covering 347–1060 nm in a single exposure of either one or two targets simultaneously, along with precision radial velocity spectroscopy utilizing an internal calibration source. It can operate at a spectral element resolving power of either 76,000 or 56,000, and can reach a signal-to-noise ratio of ∼5 in a 1 hr exposure on a V ∼ 20.8 mag target in median site seeing and dark skies (per resolution element). GHOST was installed on-site in 2022 June, and we report performance after full integration to queue operations in 2023 November, in addition to scientific results enabled by the integration observing runs. These results demonstrate the ability to observe a wide variety of bright and faint targets with high efficiency and precision. With GHOST, new avenues to explore high-resolution spectroscopy have opened up to the astronomical community. These are described, along with the planned and potential upgrades to the instrument.

We present the discovery of TOI 762 A b and TIC 46432937 b, two giant planets transiting M-dwarf stars. Transits of both systems were first detected from observations by the NASA TESS mission, and the transiting objects are confirmed as planets through high-precision radial velocity observations carried out with Very Large Telescope/ESPRESSO. TOI 762 A b is a warm sub-Saturn with a mass of 0.251 ± 0.042 M _J , a radius of 0.744 ± 0.017 R _J , and an orbital period of 3.4717 days. It transits a mid-M-dwarf star with a mass of 0.442 ± 0.025 M _☉ and a radius of 0.4250 ± 0.0091 R _☉ . The star TOI 762 A has a resolved binary star companion, TOI 762 B, that is separated from TOI 762 A by 3.″2 (∼319 au) and has an estimated mass of 0.227 ± 0.010 M _☉ . The planet TIC 46432937 b is a warm super-Jupiter with a mass of 3.20 ± 0.11 M _J and radius of 1.188 ± 0.030 R _J . The planet’s orbital period is P = 1.4404 days, and it undergoes grazing transits of its early M-dwarf host star, which has a mass of 0.563 ± 0.029 M _☉ and a radius of 0.5299 ± 0.0091 R _☉ . TIC 46432937 b is one of the highest-mass planets found to date transiting an M-dwarf star. TIC 46432937 b is also a promising target for atmospheric observations, having the highest transmission spectroscopy metric or emission spectroscopy metric value of any known warm super-Jupiter (mass greater than 3.0 M _J , equilibrium temperature below 1000 K).

We have discovered a triply eclipsing triple-star system, TIC 290061484, with the shortest known outer period, P _out , of only 24.5 days. This “eclipses” the previous record set by λ Tauri at 33.02 days, which held for 68 yr. The inner binary, with an orbital period of P _in = 1.8 days, produces primary and secondary eclipses and exhibits prominent eclipse timing variations with the same periodicity as the outer orbit. The tertiary star eclipses, and is eclipsed by, the inner binary with pronounced asymmetric profiles. The inclinations of both orbits evolve on observable timescales such that the third-body eclipses exhibit dramatic depth variations in TESS data. A photodynamical model provides a complete solution for all orbital and physical parameters of the triple system, showing that the three stars have masses of 6.85, 6.11, and 7.90 M _⊙ , radii near those corresponding to the main sequence, and T _eff in the range of 21,000–23,700 K. Remarkably, the model shows that the triple is in fact a subsystem of a hierarchical 2+1+1 quadruple with a distant fourth star. The outermost star has a period of ∼3200 days and a mass comparable to the stars in the inner triple. In ∼20 Myr, all three components of the triple subsystem will merge, undergo a Type II supernova explosion, and leave a single remnant neutron star. At the time of writing, TIC 290061484 is the most compact triple system and one of the tighter known compact triples (i.e., P _out / P _in = 13.7).

Exoplanet discoveries have revealed a dramatic diversity of planet sizes across a vast array of orbital architectures. Sub-Neptunes are of particular interest; due to their absence in our own solar system, we rely on demographics of exoplanets to better understand their bulk composition and formation scenarios. Here, we present the discovery and characterization of TOI-1437 b, a sub-Neptune with a 18.84 day orbit around a near-solar analog ( M _⋆ = 1.10 ± 0.10 M _☉ , R _⋆ =1.17 ± 0.12 R _☉ ). The planet was detected using photometric data from the Transiting Exoplanet Survey Satellite (TESS) mission and radial velocity (RV) follow-up observations were carried out as a part of the TESS-Keck Survey using both the HIRES instrument at Keck Observatory and the Levy Spectrograph on the Automated Planet Finder telescope. A combined analysis of these data reveal a planet radius of R _p = 2.24 ± 0.23 R _⊕ and a mass measurement of M _p = 9.6 ± 3.9 M _⊕ ). TOI-1437 b is one of few (∼50) known transiting sub-Neptunes orbiting a solar-mass star that has a RV mass measurement. As the formation pathway of these worlds remains an unanswered question, the precise mass characterization of TOI-1437 b may provide further insight into this class of planet.

The degree of alignment between a star’s spin axis and the orbital plane of its planets (the stellar obliquity) is related to interesting and poorly understood processes that occur during planet formation and evolution. Hot Jupiters orbiting hot stars (≳6250 K) display a wide range of obliquities, while similar planets orbiting cool stars are preferentially aligned. Tidal dissipation is expected to be more rapid in stars with thick convective envelopes, potentially explaining this trend. Evolved stars provide an opportunity to test the damping hypothesis, particularly stars that were hot on the main sequence and have since cooled and developed deep convective envelopes. We present the first systematic study of the obliquities of hot Jupiters orbiting subgiants that recently developed convective envelopes using Rossiter–McLaughlin observations. Our sample includes two newly discovered systems in the Giants Transiting Giants survey (TOI-6029 b, TOI-4379 b). We find that the orbits of hot Jupiters orbiting subgiants that have cooled below ∼6250 K are aligned or nearly aligned with the spin axis of their host stars, indicating rapid tidal realignment after the emergence of a stellar convective envelope. We place an upper limit for the timescale of realignment for hot Jupiters orbiting subgiants at ∼500 Myr. Comparison with a simplified tidal evolution model shows that obliquity damping needs to be ∼4 orders of magnitude more efficient than orbital period decay to damp the obliquity without destroying the planet, which is consistent with recent predictions for tidal dissipation from inertial waves excited by hot Jupiters on misaligned orbits.

Hot Jupiters were many of the first exoplanets discovered in the 1990s, but in the decades since their discovery the mysteries surrounding their origins have remained. Here we present nine new hot Jupiters (TOI-1855 b, TOI-2107 b, TOI-2368 b, TOI-3321 b, TOI-3894 b, TOI-3919 b, TOI-4153 b, TOI-5232 b, and TOI-5301 b) discovered by NASA’s TESS mission and confirmed using ground-based imaging and spectroscopy. These discoveries are the first in a series of papers named the Migration and Evolution of giant ExoPlanets survey and are part of an ongoing effort to build a complete sample of hot Jupiters orbiting FGK stars, with a limiting Gaia G -band magnitude of 12.5. This effort aims to use homogeneous detection and analysis techniques to generate a set of precisely measured stellar and planetary properties that is ripe for statistical analysis. The nine planets presented in this work occupy a range of masses (0.55 M _J < M _P < 3.88 M _J ) and sizes (0.967 R _J < R _P < 1.438 R _J ) and orbit stars that have an effective temperature in the range of 5360 K < T _eff < 6860 K with Gaia G -band magnitudes ranging from 11.1 to 12.7. Two of the planets in our sample have detectable orbital eccentricity: TOI-3919 b ( $e={0.259}_{-0.036}^{+0.033}$ ) and TOI-5301 b ( $e={0.33}_{-0.10}^{+0.11}$ ). These eccentric planets join a growing sample of eccentric hot Jupiters that are consistent with high-eccentricity tidal migration, one of the three most prominent theories explaining hot Jupiter formation and evolution.

We follow our first paper with an analysis of the ensemble of the extensive preexplosion ground- and space-based infrared observations of the red supergiant (RSG) progenitor candidate for the nearby core-collapse supernova SN 2023ixf in Messier 101, together with optical data prior to the explosion obtained with the Hubble Space Telescope (HST). We have confirmed the association of the progenitor candidate with the supernova (SN), as well as constrained the metallicity at the SN site, based on SN observations with instruments at Gemini-North. The internal host extinction to the SN has also been confirmed from a high-resolution Keck spectrum. We fit the observed spectral energy distribution (SED) for the star, accounting for its intrinsic variability, with dust radiative-transfer modeling, which assumes a silicate-rich dust shell ahead of the underlying stellar photosphere. The star is heavily dust obscured, likely the dustiest progenitor candidate yet encountered. We found median estimates of the star’s effective temperature and luminosity of 2770 K and 9.0 × 10 ^4 L _⊙ , with 68% credible intervals of 2340–3150 K and (7.5–10.9) × 10 ^4 L _⊙ , respectively. The candidate may have a Galactic RSG analog, IRC −10414, with a strikingly similar SED and luminosity. Via comparison with single-star evolutionary models we have constrained the initial mass of the progenitor candidate from 12 M _⊙ to as high as 14 M _⊙ . We have had available to us an extraordinary view of the SN 2023ixf progenitor candidate, which should be further followed up in future years with HST and the James Webb Space Telescope.

Sub-Neptunes with radii of 2–3 R _⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of ${R}_{{\rm{p}}}={2.740}_{-0.079}^{+0.082}\,{R}_{\oplus }$ , ${2.769}_{-0.068}^{+0.073}\,{R}_{\oplus }$ , 2.120 ± 0.067 R _⊕ , and ${2.830}_{-0.066}^{+0.068}\,{R}_{\oplus }$ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2 σ upper limits on the masses of

We report the discovery of the transiting planet GJ 238 b, with a radius of 0.566 ± 0.014 R _⊕ (1.064 ± 0.026 times the radius of Mars) and an orbital period of 1.74 days. The transit signal was detected by the TESS mission and designated TOI-486.01. The star’s position close to the southern ecliptic pole allows for almost continuous observations by TESS when it is observing the southern sky. The host star is an M2.5 dwarf with V = 11.57 ± 0.02 mag, K = 7.030 ± 0.023 mag, a distance of 15.2156 ± 0.0030 pc, a mass of ${0.4193}_{-0.0098}^{+0.0095}$ M _☉ , a radius of ${0.4314}_{-0.0071}^{+0.0075}$ R _☉ , and an effective temperature of 3485 ± 140 K. We validate the planet candidate by ruling out or rendering highly unlikely each of the false positive scenarios, based on archival data and ground-based follow-up observations. Validation was facilitated by the host star’s small size and high proper motion of 892.633 ± 0.025 mas yr ^–1 .

The Transiting Exoplanet Survey Satellite (TESS) has discovered hundreds of new worlds, with TESS planet candidates now outnumbering the total number of confirmed planets from Kepler. Owing to differences in survey design, TESS continues to provide planets that are better suited for subsequent follow-up studies, including mass measurement through radial velocity (RV) observations, compared to Kepler targets. In this work, we present the TESS-Keck Survey’s (TKS) Mass Catalog: a uniform analysis of all TKS RV survey data that has resulted in mass constraints for 126 planets and candidate signals. This includes 58 mass measurements that have reached ≥5 σ precision. We confirm or validate 32 new planets from the TESS mission either by significant mass measurement (15) or statistical validation (17), and we find no evidence of likely false positives among our entire sample. This work also serves as a data release for all previously unpublished TKS survey data, including 9,204 RV measurements and associated activity indicators over our three-year survey. We took the opportunity to assess the performance of our survey and found that we achieved many of our goals, including measuring the mass of 38 small (

We explore the possibility of detecting very faint, very close-in stellar companions using large aperture ground-based telescopes and the technique of optical speckle imaging. We examine the state of high-angular-resolution speckle imaging and contrast levels being achieved using current speckle cameras on the Gemini 8 m telescope. We then explore the use of the modern image reconstruction technique—multiframe blind deconvolution (MFBD)—applied to speckle imaging from the Gemini 8 m telescope. We show that MFBD allows us to measure the flux ratio of the imaged stars to high accuracy and the reconstructed images yield higher precision astrometry. Both of these advances provide a large refinement in the derived astrophysical parameters compared with current Fourier techniques. MFBD image reconstructions reach contrast levels of ∼5 × 10 ^−3 , near the diffraction limit, to ∼10 ^−4 about 1.″0 away. At these deep contrast levels with angular limits starting near the 8 m diffraction limit (∼20 mas), most stellar companions to a solar-like stars can be imaged in the optical to near-IR bandpass (320–1000 nm). “To Xanadu we go...” —adapted from S. T. Coleridge.

We report on the discovery and validation of a transiting long-period mini-Neptune orbiting a bright ( V = 9.0 mag) G dwarf (TOI 4633; R = 1.05 R _⊙ , M = 1.10 M _⊙ ). The planet was identified in data from the Transiting Exoplanet Survey Satellite by citizen scientists taking part in the Planet Hunters TESS project. Modelling of the transit events yields an orbital period of 271.9445 ± 0.0040 days and radius of 3.2 ± 0.20 R _⊕ . The Earth-like orbital period and an incident flux of ${1.56}_{-0.16}^{+0.20}$ F _⊕ places it in the optimistic habitable zone around the star. Doppler spectroscopy of the system allowed us to place an upper mass limit on the transiting planet and revealed a non-transiting planet candidate in the system with a period of 34.15 ± 0.15 days. Furthermore, the combination of archival data dating back to 1905 with new high angular resolution imaging revealed a stellar companion orbiting the primary star with an orbital period of around 230 yr and an eccentricity of about 0.9. The long period of the transiting planet, combined with the high eccentricity and close approach of the companion star makes this a valuable system for testing the formation and stability of planets in binary systems.

JWST has ushered in an era of unprecedented ability to characterize exoplanetary atmospheres. While there are over 5000 confirmed planets, more than 4000 Transiting Exoplanet Survey Satellite (TESS) planet candidates are still unconfirmed and many of the best planets for atmospheric characterization may remain to be identified. We present a sample of TESS planets and planet candidates that we identify as “best-in-class” for transmission and emission spectroscopy with JWST. These targets are sorted into bins across equilibrium temperature T _eq and planetary radius R _p and are ranked by a transmission and an emission spectroscopy metric (TSM and ESM, respectively) within each bin. We perform cuts for expected signal size and stellar brightness to remove suboptimal targets for JWST. Of the 194 targets in the resulting sample, 103 are unconfirmed TESS planet candidates, also known as TESS Objects of Interest (TOIs). We perform vetting and statistical validation analyses on these 103 targets to determine which are likely planets and which are likely false positives, incorporating ground-based follow-up from the TESS Follow-up Observation Program to aid the vetting and validation process. We statistically validate 18 TOIs, marginally validate 31 TOIs to varying levels of confidence, deem 29 TOIs likely false positives, and leave the dispositions for four TOIs as inconclusive. Twenty-one of the 103 TOIs were confirmed independently over the course of our analysis. We intend for this work to serve as a community resource and motivate formal confirmation and mass measurements of each validated planet. We encourage more detailed analysis of individual targets by the community.

We report on contemporaneous optical observations at ≈10 ms timescales from the fast radio burst (FRB) 20180916B of two repeat bursts (FRB 20201023 and FRB 20220908) taken with the ‘Alopeke camera on the Gemini-North telescope. These repeats have radio fluences of 2.8 and 3.5 Jy ms, respectively, approximately in the lower 50th percentile for fluence from this repeating burst. The ‘Alopeke data reveal no significant optical detections at the FRB position and we place 3 σ upper limits to the optical fluences of

Multiplanet systems exhibit a diversity of architectures that diverge from the solar system and contribute to the topic of exoplanet demographics. Radial velocity (RV) surveys form a crucial component of exoplanet surveys, as their long observational baselines allow for searches for more distant planetary orbits. This work provides a significantly revised architecture for the multiplanet system HD 134606 using both HARPS and UCLES RVs. We confirm the presence of previously reported planets b, c, and d with periods of ${12.0897}_{-0.0018}^{+0.0019}$ , ${58.947}_{-0.054}^{+0.056}$ , and ${958.7}_{-5.9}^{+6.3}$ days and masses of ${9.14}_{-0.63}^{+0.65}$ , 11.0 ± 1, and 44.5 ± 2.9 Earth masses, respectively, with the planet d orbit significantly revised to over double that originally reported. We report two newly detected super-Earths, e and f, with periods of ${4.31943}_{-0.00068}^{+0.00075}$ and ${26.9}_{-0.017}^{+0.019}$ days and masses of ${2.31}_{-0.35}^{+0.36}$ and ${5.52}_{-0.73}^{+0.74}$ Earth masses, respectively. In addition, we identify a linear trend in the RV time series, and the cause of this acceleration is deemed to be a newly detected massive companion with a very long orbital period. HD 134606 now displays four low-mass planets in a compact region near the star, one gas giant further out in the habitable zone, an additional companion in the outer regime, and a low-mass M dwarf stellar companion at large separation, making it an intriguing target for system formation/evolution studies. The location of planet d in the habitable zone proves to be an exciting candidate for future space-based direct imaging missions, whereas continued RV observations of this system are recommended for understanding the nature of the massive, long-period companion.

Pre-main-sequence disk accretion is pivotal for determining the final stellar properties and the early conditions for close-in planets. We aim to establish the impact of internal (stellar mass) and external (radiation field) parameters on the disk evolution in the Lagoon Nebula massive star-forming region. We employ simultaneous u , g , r , i , H α time-series photometry, archival infrared data, and high-precision K2 light curves to derive the stellar, disk, and accretion properties for 1012 Lagoon Nebula members. We estimate that of all young stars in the Lagoon Nebula, 34%–37% have inner disks traceable down to ∼12 μ m, while 38%–41% are actively accreting. We detect disks ∼1.5 times more frequently around G, K, and M stars than around higher-mass stars, which appear to deplete their inner disks on shorter timescales. We find tentative evidence for a faster disk evolution in the central regions of the Lagoon Nebula, where the bulk of the O/B population is located. Conversely, disks appear to last longer at the nebula outskirts, where the measured fraction of disk-bearing stars tends to exceed that of accreting and disk-free stars. The derived mass accretion rates show a nonuniform dependence on stellar mass between ∼0.2 and 5 M _⊙ . In addition, the typical accretion rates appear to differ across the Lagoon Nebula extension, with values twice lower in the core region than at its periphery. Finally, we detect tentative radial density gradients in the surface accretion shocks, leading to lags in the appearance of light curve brightness features as a function of wavelength that can amount to ∼7%–30% of the rotation period.

The large number of exoplanets discovered with the Transiting Exoplanet Survey Satellite (TESS) means that any observational biases from TESS could influence the derived stellar multiplicity statistics of exoplanet host stars. To investigate this problem, we obtained speckle interferometry of 207 control stars whose properties in the TESS Input Catalog (TIC) closely match those of an exoplanetary host star in the TESS Object of Interest (TOI) catalog, with the objective of measuring the fraction of these stars that have companions within ∼1.″2. Our main result is the identification of a bias in the creation of the control sample that prevents the selection of binaries with 0.″1 ≲ ρ ≲ 1.″2 and Δmag ≲3. This bias is the result of large astrometric residuals that cause binaries with these parameters to fail the quality checks used to create the TIC, which in turn causes them to have incomplete stellar parameters (and uncertainties) in the TIC. Any stellar multiplicity study that relies exclusively upon TIC stellar parameters to identify its targets will struggle to select unresolved binaries in this parameter space. Left uncorrected, this selection bias disproportionately excludes high-mass-ratio binaries, causing the mass-ratio distribution of the companions to deviate significantly from the uniform distribution expected of FGK-type field binaries. After accounting for this bias, the companion rate of the FGK control stars is consistent with the canonical 46% ± 2% rate from Raghavan et al., and the mass-ratio distribution agrees with that of binary TOI host stars. There is marginal evidence that the control-star companions have smaller projected orbital separations than TOI host stars from previous studies.

We recently reported that cranberry proanthocyanidins (C-PACs) inhibit esophageal adenocarcinoma (EAC) by 83% through reversing reflux-induced bacterial, inflammatory and immune-implicated proteins and genes as well as reducing esophageal bile acids, which drive EAC progression. This study investigated whether C-PACs’ mitigation of bile reflux-induced transporter dysregulation mechanistically contributes to EAC prevention. RNA was isolated from water-, C-PAC- and reflux-exposed rat esophagi with and without C-PAC treatment. Differential gene expression was determined by means of RNA sequencing and RT-PCR, followed by protein assessments. The literature, coupled with the publicly available Gene Expression Omnibus dataset GSE26886, was used to assess transporter expression levels in normal and EAC patient biopsies for translational relevance. Significant changes in ATP-binding cassette (ABC) transporters implicated in therapeutic resistance in humans (i.e., Abcb1, Abcb4, Abcc1, Abcc3, Abcc4, Abcc6 and Abcc10) and the transport of drugs, xenobiotics, lipids, and bile were altered in the reflux model with C-PACs’ mitigating changes. Additionally, C-PACs restored reflux-induced changes in solute carrier (SLC), aquaporin, proton and cation transporters (i.e., Slc2a1, Slc7a11, Slc9a1, Slco2a1 and Atp6v0c). This research supports the suggestion that transporters merit investigation not only for their roles in metabolism and therapeutic resistance, but as targets for cancer prevention and targeting preventive agents in combination with chemotherapeutics.

We report the discovery of two TESS sub-Neptunes orbiting the early M dwarf TOI-904 (TIC 261257684). Both exoplanets, TOI-904 b and c, were initially observed in TESS Sector 12 with twin sizes of ${2.426}_{-0.157}^{+0.163}$ and ${2.167}_{-0.118}^{+0.130}$ R _⊕ , respectively. Through observations in five additional sectors in the TESS primary mission and the first and second extended missions, the orbital periods of the planets were measured to be 10.887 ± 0.001 and 83.999 ± 0.001 days, respectively. Reconnaissance radial velocity measurements (taken with EULER/CORALIE and SMARTS/CHIRON) and high-resolution speckle imaging with adaptive optics (obtained from SOAR/HRCAM and Gemini South/ZORRO) show no evidence of an eclipsing binary or a nearby companion, which, together with the low false-positive probabilities calculated with the statistical validation software TRICERATOPS, establishes the planetary nature of these candidates. The outer planet, TOI-904 c, is the longest-period M dwarf exoplanet found by TESS, with an estimated equilibrium temperature of 217 K. As the three other validated planets with comparable host stars and orbital periods were observed by Kepler around much dimmer stars ( J _mag > 12), TOI-904 c, orbiting a brighter star ( J _mag = 9.6), is the coldest M dwarf planet easily accessible for atmospheric follow-up. Future mass measurements and transmission spectroscopy of the similar-sized planets in this system could determine whether they are also similar in density and composition, suggesting a common formation pathway, or whether they have distinct origins.

Abstract This concise review summarizes results of the latest clinical trials that support the use of standardized cranberry juice intake as a complementary means of suppressing Helicobacter pylori infections. While not a replacement for antibiotic therapies, this tolerable and accessible dietary approach to help reduce inoculum levels in high‐risk populations could help curb infections and potentially reduce antibiotic use and subsequent stomach cancer prevalence.

The αV integrin is expressed in most cancer cells where it regulates a diverse array of cellular functions essential to the initiation, progression and metastasis of solid tumors. However, little is known about how αV integrin modulates cellular sensitivity to chemotherapeutic agents, particularly the platinum drugs. In this study, we found that down-regulation of αV sensitized human M21 cells to cisplatin (cDDP) through up-regulation of the copper influx transporter CTR1. Cells selected for low αV integrin expression (M21L) were more sensitive to cDDP, accompanied by increase in CTR1 mRNA and CTR1 protein levels, more intracellular cDDP accumulation and cDDP DNA adduct formation. Basal copper (Cu) content, Cu uptake, and Cu cytotoxicity were also increased. Transfection of a luciferase reporter construct containing the hCTR1 promoter sequence revealed an increase of the hCTR1 transcription activity in M21L cells. The basis for the increased hCTR1 transcription was related to an increase in the steady-state level of Sp1, a transcription factor known to drive hCTR1 expression. These results indicate that the αV integrin modulates sensitivity of human cells to the cytotoxic effect of cDDP by regulating expression of the Cu transporter CTR1, and introduce the concept that αV expression is linked to Cu homeostasis.

The αV integrin is expressed in most cancer cells where it regulates a diverse array of cellular functions essential to the initiation, progression and metastasis of solid tumors. However, little is known about how αV integrin modulates cellular sensitivity to chemotherapeutic agents, particularly the platinum drugs. In this study, we found that down-regulation of αV sensitized human M21 cells to cisplatin (cDDP) through up-regulation of the copper influx transporter CTR1. Cells selected for low αV integrin expression (M21L) were more sensitive to cDDP, accompanied by increase in CTR1 mRNA and CTR1 protein levels, more intracellular cDDP accumulation and cDDP DNA adduct formation. Basal copper (Cu) content, Cu uptake, and Cu cytotoxicity were also increased. Transfection of a luciferase reporter construct containing the hCTR1 promoter sequence revealed an increase of the hCTR1 transcription activity in M21L cells. The basis for the increased hCTR1 transcription was related to an increase in the steady-state level of Sp1, a transcription factor known to drive hCTR1 expression. These results indicate that the αV integrin modulates sensitivity of human cells to the cytotoxic effect of cDDP by regulating expression of the Cu transporter CTR1, and introduce the concept that αV expression is linked to Cu homeostasis.

Abstract We sought to determine incidence, etiologies, and yield of genetic testing in infantile onset developmental and epileptic encephalopathies (DEEs) in a population isolate, with an intensive multistage approach. Infants born in Tasmania between 2011 and 2016, with seizure onset