Loss of TRP53 (p53) accelerates tumorigenesis and changes the tumor spectrum of SJL/J mice.

Known as the guardian of the genome, transformation-related protein 53 (TRP53) is a well -known tumor suppressor. Here, we describe a novel TRP53 deficient mouse model on a tumor prone background-SJL/J mice. The absence of TRP53 (TRP53 nullizygosity) leads to a shift in the tumor spectrum from a non-Hodgkin\u27s-like disease to thymic lymphomas and testicular teratomas at a very rapid tumor onset averaging ~12 weeks of age. In haplotype studies, comparing tumor prone versus tumor resistant Trp53 null mouse strains, we found that other tumor suppressor, DNA repair and/or immune system genes modulate tumor incidence in TRP53 null strains, suggesting that even a strong tumor suppressor such as TRP53 is modulated by genetic background. Due to their rapid development of tumors, the SJL/J TRP53 null mice generated here can be used as an efficient chemotherapy or immunotherapy screening mouse model

JWST MIRI flight performance: The Medium-Resolution Spectrometer

The Medium-Resolution Spectrometer (MRS) provides one of the four operating modes of the Mid-Infrared Instrument (MIRI) on board the James Webb Space Telescope (JWST). The MRS is an integral field spectrometer, measuring the spatial and spectral distributions of light across the 5-28 $\mu m$ wavelength range with a spectral resolving power between 3700-1300. We present the MRS's optical, spectral, and spectro-photometric performance, as achieved in flight, and we report on the effects that limit the instrument's ultimate sensitivity. The MRS flight performance has been quantified using observations of stars, planetary nebulae, and planets in our Solar System. The precision and accuracy of this calibration was checked against celestial calibrators with well-known flux levels and spectral features. We find that the MRS geometric calibration has a distortion solution accuracy relative to the commanded position of 8 mas at 5 $\mu m$ and 23 mas at 28 $\mu m$. The wavelength calibration is accurate to within 9 km/sec at 5 $\mu m$ and 27 km/sec at 28 $\mu m$. The uncertainty in the absolute spectro-photometric calibration accuracy was estimated at 5.6 +- 0.7 %. The MIRI calibration pipeline is able to suppress the amplitude of spectral fringes to below 1.5 % for both extended and point sources across the entire wavelength range. The MRS point spread function (PSF) is 60 % broader than the diffraction limit along its long axis at 5 $\mu m$ and is 15 % broader at 28 $\mu m$. The MRS flight performance is found to be better than prelaunch expectations. The MRS is one of the most subscribed observing modes of JWST and is yielding many high-profile publications. It is currently humanity's most powerful instrument for measuring the mid-infrared spectra of celestial sources and is expected to continue as such for many years to come.Comment: 16 pages, 21 figure

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems: Best Practices for Data Collection in Cycle 2 and Beyond

We present a set of recommended best practices for JWST data collection for members of the community focussed on the direct imaging and spectroscopy of exoplanetary systems. These findings and recommendations are based on the early analysis of the JWST Early Release Science Program 1386, "High-Contrast Imaging of Exoplanets and Exoplanetary Systems with JWST." Our goal is for this information to be useful for observers in preparation of JWST proposals for Cycle 2 and beyond. In addition to compiling a set of best practices from our ERS program, in a few cases we also draw on the expertise gained within the instrument commissioning programs, as well as include a handful of data processing best practices. We anticipate that this document will be regularly updated and resubmitted to arXiv.org to ensure that we have distributed our knowledge of best-practices for data collection as widely and efficiently as possible.Comment: Not yet submitted for publication. Intended only to be a community resource for JWST Cycle 2 proposal

The JWST Early-Release Science Program for Direct Observations of Exoplanetary Systems Ii: A 1 To 20 Μm Spectrum of the Planetary-Mass Companion Vhs 1256-1257 B

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a (∼8″, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color-magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256 b with JWST\u27s NIRSpec IFU and MIRI MRS modes for coverage from 1 to 20 μm at resolutions of ∼1000-3700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the JWST spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion

Histone H1 Depletion Impairs Embryonic Stem Cell Differentiation

Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same dataset to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors, and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration, NIRISS AMI can reach contrast levels of $\sim9-10$ mag. These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower mass exoplanets than ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems V: Do Self-Consistent Atmospheric Models Represent JWST Spectra? A Showcase With VHS 1256 b

The unprecedented medium-resolution (R~1500-3500) near- and mid-infrared (1-18um) spectrum provided by JWST for the young (140+/-20Myr) low-mass (12-20MJup) L-T transition (L7) companion VHS1256b gives access to a catalogue of molecular absorptions. In this study, we present a comprehensive analysis of this dataset utilizing a forward modelling approach, applying our Bayesian framework, ForMoSA. We explore five distinct atmospheric models to assess their performance in estimating key atmospheric parameters: Teff, log(g), [M/H], C/O, gamma, fsed, and R. Our findings reveal that each parameter's estimate is significantly influenced by factors such as the wavelength range considered and the model chosen for the fit. This is attributed to systematic errors in the models and their challenges in accurately replicating the complex atmospheric structure of VHS1256b, notably the complexity of its clouds and dust distribution. To propagate the impact of these systematic uncertainties on our atmospheric property estimates, we introduce innovative fitting methodologies based on independent fits performed on different spectral windows. We finally derived a Teff consistent with the spectral type of the target, considering its young age, which is confirmed by our estimate of log(g). Despite the exceptional data quality, attaining robust estimates for chemical abundances [M/H] and C/O, often employed as indicators of formation history, remains challenging. Nevertheless, the pioneering case of JWST's data for VHS1256b has paved the way for future acquisitions of substellar spectra that will be systematically analyzed to directly compare the properties of these objects and correct the systematics in the models.Comment: 32 pages, 16 figures, 6 tables, 2 appendice

The \textit{JWST} Early Release Science Program for Direct Observations of Exoplanetary Systems III: Aperture Masking Interferometric Observations of the star HIP\,65426 at 3.8 μm\boldsymbol{3.8\,\rm{\mu m}}

We present aperture masking interferometry (AMI) observations of the star HIP 65426 at $3.8\,\rm{\mu m}$ as a part of the \textit{JWST} Direct Imaging Early Release Science (ERS) program obtained using the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument. This mode provides access to very small inner working angles (even separations slightly below the Michelson limit of ${}0.5\lambda/D$ for an interferometer), which are inaccessible with the classical inner working angles of the \textit{JWST} coronagraphs. When combined with \textit{JWST}'s unprecedented infrared sensitivity, this mode has the potential to probe a new portion of parameter space across a wide array of astronomical observations. Using this mode, we are able to achieve a contrast of $\Delta m_{F380M}{\sim }7.8$\,mag relative to the host star at a separation of {\sim}0.07\arcsec but detect no additional companions interior to the known companion HIP\,65426\,b. Our observations thus rule out companions more massive than 10{-}12\,\rm{M\textsubscript{Jup}} at separations ${\sim}10{-}20\,\rm{au}$ from HIP\,65426, a region out of reach of ground or space-based coronagraphic imaging. These observations confirm that the AMI mode on \textit{JWST} is sensitive to planetary mass companions orbiting at the water frost line, even for more distant stars at $\sim$100\,pc. This result will allow the planning and successful execution of future observations to probe the inner regions of nearby stellar systems, opening essentially unexplored parameter space.Comment: 15 pages, 9 figures, submitted to ApJ Letter

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a $<$20 M$_\mathrm{Jup}$ widely separated ($\sim$8\arcsec, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color-magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS modes for coverage from 1 $\mu$m to 20 $\mu$m at resolutions of $\sim$1,000 - 3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the \textit{JWST} spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are hosted at this link: https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI