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  1. Tet1 protects against house dust mite (HDM)-induced lung inflammation in mice and alters the lung methylome and transcriptome. In order to explore the role of Tet1 in individual lung epithelial cell types in HDM-induced inflammation, we established a model of HDM-induced lung inflammation in Tet1 knockout and littermate wild-type mice, then studied EpCAM+ lung epithelial cells using single-cell RNA-seq analysis. We identified eight EpCAM+ lung epithelial cell types, among which AT2 cells were the most abundant. HDM challenge altered the relative abundance of epithelial cell types and resulted in cell type-specific transcriptomic changes. Bulk and cell type-specific analysis also showedmore »that loss of Tet1 led to the altered expression of genes linked to augmented HDM-induced lung inflammation, including alarms, detoxification enzymes, oxidative stress response genes, and tissue repair genes. The transcriptomic regulation was accompanied by alterations in TF activities. Trajectory analysis supports that HDM may enhance the differentiation of AP and BAS cells into AT2 cells, independent of Tet1. Collectively, our data showed that lung epithelial cells had common and unique transcriptomic signatures of allergic lung inflammation. Tet1 deletion altered transcriptomic networks in various lung epithelial cells, which may promote allergen-induced lung inflammation.« less
    Free, publicly-accessible full text available May 1, 2023
  2. Mogilner, Alex (Ed.)
    Neurofilaments are abundant space-filling cytoskeletal polymers in axons that are transported along microtubule tracks. Neurofilament transport is accelerated at nodes of Ranvier, where axons are locally constricted. Strikingly, these constrictions are accompanied by sharp decreases in neurofilament number, no decreases in microtubule number, and increases in the packing density of these polymers, which collectively bring nodal neurofilaments closer to their microtubule tracks. We hypothesize that this leads to an increase in the proportion of time that the filaments spend moving and that this can explain the local acceleration. To test this, we developed a stochastic model of neurofilament transport thatmore »tracks their number, kinetic state, and proximity to nearby microtubules in space and time. The model assumes that the probability of a neurofilament moving is dependent on its distance from the nearest available microtubule track. Taking into account experimentally reported numbers and densities for neurofilaments and microtubules in nodes and internodes, we show that the model is sufficient to explain the local acceleration of neurofilaments within nodes of Ranvier. This suggests that proximity to microtubule tracks may be a key regulator of neurofilament transport in axons, which has implications for the mechanism of neurofilament accumulation in development and disease.« less
  3. ABSTRACT For stars with unresolved companions, motions of the centre of light and that of mass decouple, causing a single-source astrometric model to perform poorly. We show that such stars can be easily detected with the reduced χ2 statistic, or renormalized unit weight error (RUWE), provided as part of Gaia DR2. We convert RUWE into the amplitude of the image centroid wobble, which, if scaled by the source distance, is proportional to the physical separation between companions (for periods up to several years). We test this idea on a sample of known spectroscopic binaries and demonstrate that the amplitude ofmore »the centroid perturbation scales with the binary period and the mass ratio as expected. We apply this technique to the Gaia DR2 data and show how the binary fraction evolves across the Hertzsprung–Russell diagram. The observed incidence of unresolved companions is high for massive young stars and drops steadily with stellar mass, reaching its lowest levels for white dwarfs. We highlight the elevated binary fraction for the nearby blue stragglers and blue horizontal branch stars. We also illustrate how unresolved hierarchical triples inflate the relative velocity signal in wide binaries. Finally, we point out a hint of evidence for the existence of additional companions to the hosts of extrasolar hot Jupiters.« less
  4. Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H 2 S)—a toxicant that impairs mitochondrial function—across evolutionarily independent lineages of a fish ( Poecilia mexicana , Poeciliidae) from H 2 S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H 2 S in sulfidemore »spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H 2 S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H 2 S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H 2 S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and—in some instances—codons are implicated in H 2 S adaptation in lineages that span 40 million years of evolution.« less
  5. Hallibert, Pascal ; Hull, Tony B. ; Kim, Daewook ; Keller, Fanny (Ed.)
    The Cherenkov Telescope Array (CTA) is the next-generation ground-based observatory for very-high-energy gamma rays. One candidate design for CTA's medium-sized telescopes consists of the Schwarzschild-Couder Telescope (SCT), featuring innovative dual-mirror optics. The SCT project has built and is currently operating a 9.7-m prototype SCT (pSCT) at the Fred Lawrence Whipple Observatory (FLWO); such optical design enables the use of a compact camera with state-of-the art silicon photomultiplier detectors. A partially-equipped camera has recently successfully detected the Crab Nebula with a statistical significance of 8.6 standard deviations. A funded upgrade of the pSCT focal plane sensors and electronics is currently ongoing,more »which will bring the total number of channels from 1600 to 11328 and the telescope field of view from about 2.7° to 8° . In this work, we will describe the technical and scientific performance of the pSCT.« less
    Free, publicly-accessible full text available August 24, 2022