KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation, notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in the human K562 erythro-leukaemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodellers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited at actively transcribed polymerase II promoters, where its depletion resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'

Interferometric Observatories in Earth Orbit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76217/1/AIAA-1728-623.pd

Microbial sharing between pediatric patients and therapy dogs during hospital animal-assisted intervention programs

Microbial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs is unknown. Understanding microbial transmission between patients and therapy dogs can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated for potential microbial sharing between pediatric patients and therapy dogs and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing. Patients, therapy dogs, and the hospital environment were sampled before and after every group therapy session and samples underwent 16S rRNA sequencing to characterize microbial communities. Both patients and dogs experienced changes in the relative abundance and overall diversity of their nasal microbiome, suggesting that the exchange of microorganisms had occurred. Increased contact was associated with greater sharing between patients and therapy dogs, as well as between patients. A topical chlorhexidine-based dog decolonization was associated with decreased microbial sharing between therapy dogs and patients but did not significantly affect sharing between patients. These data suggest that the therapy dog is both a potential source of and a vehicle for the transfer of microorganisms to patients but not necessarily the only source. The relative contribution of other potential sources (e.g., other patients, the hospital environment) should be further explored to determine their relative importance

The immunopeptidome landscape associated with T cell infiltration, inflammation and immune editing in lung cancer.

One key barrier to improving efficacy of personalized cancer immunotherapies that are dependent on the tumor antigenic landscape remains patient stratification. Although patients with CD3 <sup>+</sup> CD8 <sup>+</sup> T cell-inflamed tumors typically show better response to immune checkpoint inhibitors, it is still unknown whether the immunopeptidome repertoire presented in highly inflamed and noninflamed tumors is substantially different. We surveyed 61 tumor regions and adjacent nonmalignant lung tissues from 8 patients with lung cancer and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics, and explored the heterogeneous expression and presentation of tumor (neo)antigens. In the present study, we associated diverse immune cell populations with the immunopeptidome and found a relatively higher frequency of predicted neoantigens located within HLA-I presentation hotspots in CD3 <sup>+</sup> CD8 <sup>+</sup> T cell-excluded tumors. We associated such neoantigens with immune recognition, supporting their involvement in immune editing. This could have implications for the choice of combination therapies tailored to the patient's mutanome and immune microenvironment

OGLE-2005-BLG-153: Microlensing Discovery and Characterization of A Very Low Mass Binary

The mass function and statistics of binaries provide important diagnostics of the star formation process. Despite this importance, the mass function at low masses remains poorly known due to observational difficulties caused by the faintness of the objects. Here we report the microlensing discovery and characterization of a binary lens composed of very low-mass stars just above the hydrogen-burning limit. From the combined measurements of the Einstein radius and microlens parallax, we measure the masses of the binary components of $0.10\pm 0.01\ M_\odot$ and $0.09\pm 0.01\ M_\odot$. This discovery demonstrates that microlensing will provide a method to measure the mass function of all Galactic populations of very low mass binaries that is independent of the biases caused by the luminosity of the population.Comment: 6 pages, 3 figures, 1 tabl

Pharmacological induction of a progenitor state for the efficient expansion of primary human hepatocytes

The liver is an organ with strong regenerative capacity, yet primary hepatocytes have a low amplification potential in vitro, a major limitation for the cell-based therapy of liver disorders and for ex vivo biological screens. Induced pluripotent stem cells (iPSCs) may help to circumvent this obstacle but often harbor genetic and epigenetic abnormalities, limiting their potential. Here, we describe the pharmacological induction of proliferative human hepatic progenitor cells (HPCs) through a cocktail of growth factors and small molecules mimicking the signaling events involved in liver regeneration. Human HPCs from healthy donors and pediatric patients proliferated vigorously while maintaining their genomic stability and could be redifferentiated in vitro into metabolically competent cells that supported the replication of hepatitis B and delta viruses. Redifferentiation efficiency was boosted by three-dimensional culture. Finally, transcriptome analysis showed that HPCs were more closely related to mature hepatocytes than iPSC-derived hepatocyte-like cells were. Conclusion: HPC induction holds promise for a variety of applications such as ex vivo disease modeling, personalized drug testing or metabolic studies, and development of a bioartificial liver

OGLE-2005-BLG-071Lb, the Most Massive M-Dwarf Planetary Companion?

We combine all available information to constrain the nature of OGLE-2005-BLG-071Lb, the second planet discovered by microlensing and the first in a high-magnification event. These include photometric and astrometric measurements from Hubble Space Telescope, as well as constraints from higher order effects extracted from the ground-based light curve, such as microlens parallax, planetary orbital motion and finite-source effects. Our primary analysis leads to the conclusion that the host of Jovian planet OGLE-2005-BLG-071Lb is an M dwarf in the foreground disk with mass M= 0.46 +/- 0.04 Msun, distance D_l = 3.3 +/- 0.4 kpc, and thick-disk kinematics v_LSR ~ 103 km/s. From the best-fit model, the planet has mass M_p = 3.8 +/- 0.4 M_Jup, lies at a projected separation r_perp = 3.6 +/- 0.2 AU from its host and so has an equilibrium temperature of T ~ 55 K, i.e., similar to Neptune. A degenerate model less favored by \Delta\chi^2 = 2.1 (or 2.2, depending on the sign of the impact parameter) gives similar planetary mass M_p = 3.4 +/- 0.4 M_Jup with a smaller projected separation, r_\perp = 2.1 +/- 0.1 AU, and higher equilibrium temperature T ~ 71 K. These results from the primary analysis suggest that OGLE-2005-BLG-071Lb is likely to be the most massive planet yet discovered that is hosted by an M dwarf. However, the formation of such high-mass planetary companions in the outer regions of M-dwarf planetary systems is predicted to be unlikely within the core-accretion scenario. There are a number of caveats to this primary analysis, which assumes (based on real but limited evidence) that the unlensed light coincident with the source is actually due to the lens, that is, the planetary host. However, these caveats could mostly be resolved by a single astrometric measurement a few years after the event.Comment: 51 pages, 12 figures, 3 tables, Published in Ap