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Magnetars are neutron stars with extremely strong magnetic fields (1013 to 1015 gauss)1,2, which episodically emit X-ray bursts approximately 100 milliseconds long and with energies of 1040 to 1041 erg. Occasionally, they also produce extremely bright and energetic giant flares, which begin with a short (roughly 0.2 seconds), intense flash, followed by fainter, longer-lasting emission that is modulated by the spin period of the magnetar3,4 (typically 2 to 12 seconds). Over the past 40 years, only three such flares have been observed in our local group of galaxies3-6, and in all cases the extreme intensity of the flares caused the detectors to saturate. It has been proposed that extragalactic giant flares are probably a subset7-11 of short γ-ray bursts, given that the sensitivity of current instrumentation prevents us from detecting the pulsating tail, whereas the initial bright flash is readily observable out to distances of around 10 to 20 million parsecs. Here we report X-ray and γ-ray observations of the γ-ray burst GRB 200415A, which has a rapid onset, very fast time variability, flat spectra and substantial sub-millisecond spectral evolution. These attributes match well with those expected for a giant flare from an extragalactic magnetar12, given that GRB 200415A is directionally associated13 with the galaxy NGC 253 (roughly 3.5 million parsecs away). The detection of three-megaelectronvolt photons provides evidence for the relativistic motion of the emitting plasma. Radiation from such rapidly moving gas around a rotating magnetar may have generated the rapid spectral evolution that we observe.Autism spectrum disorder (ASD) is an early-onset developmental disorder characterized by deficits in communication and social interaction and restrictive or repetitive behaviours1,2. Bexotegrast cell line Family studies demonstrate that ASD has a substantial genetic basis with contributions both from inherited and de novo variants3,4. It has been estimated that de novo mutations may contribute to 30% of all simplex cases, in which only a single child is affected per family5. Tandem repeats (TRs), defined here as sequences of 1 to 20 base pairs in size repeated consecutively, comprise one of the major sources of de novo mutations in humans6. TR expansions are implicated in dozens of neurological and psychiatric disorders7. Yet, de novo TR mutations have not been characterized on a genome-wide scale, and their contribution to ASD remains unexplored. Here we develop new bioinformatics methods for identifying and prioritizing de novo TR mutations from sequencing data and perform a genome-wide characterization of de novo TR mutations in ASD-affected probands and unaffected siblings. We infer specific mutation events and their precise changes in repeat number, and primarily focus on more prevalent stepwise copy number changes rather than large expansions. Our results demonstrate a significant genome-wide excess of TR mutations in ASD probands. Mutations in probands tend to be larger, enriched in fetal brain regulatory regions, and are predicted to be more evolutionarily deleterious. Overall, our results highlight the importance of considering repeat variants in future studies of de novo mutations.Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.The ability to associate memorized objects with their location in space gradually declines during normal aging and can drastically be affected by neurodegenerative diseases. This study investigates object-location paired-associates learning (PAL) in the grey mouse lemur (Microcebus murinus), a nonhuman primate model of brain aging. Touchscreen-based testing of 6 young adults (1-5 years) and 6 old adults (> 7 years) in the procedural rodent dPAL-task revealed significant age-related performance decline, evident in group differences in the percentage of correct decision during learning and the number of sessions needed to reach a predefined criterion. Response pattern analyses suggest decreased susceptibility to relative stimulus-position biases in young animals, facilitating PAL. Additional data from a subset of "overtrained" individuals (n = 7) and challenge sessions using a modified protocol (sPAL) further suggest that learning criteria routinely used in animal studies on PAL can underestimate the endpoint at which a stable performance is reached and that more conservative criteria are needed to improve construct validity of the task. To conclude, this is the first report of an age effect on dPAL and corroborates the role of mouse lemurs as valuable natural nonhuman primate models in aging research.The community of cells lining our airways plays a collaborative role in the preservation of immune homeostasis in the lung and provides protection from the pathogens and pollutants in the air we breathe. In addition to its structural attributes that provide effective mucociliary clearance of the lower airspace, the airway epithelium is an immunologically active barrier surface that senses changes in the airway environment and interacts with resident and recruited immune cells. Single-cell RNA-sequencing is illuminating the cellular heterogeneity that exists in the airway wall and has identified novel cell populations with unique molecular signatures, trajectories of differentiation and diverse functions in health and disease. In this Review, we discuss how our view of the airway epithelial landscape has evolved with the advent of transcriptomic approaches to cellular phenotyping, with a focus on epithelial interactions with the local neuronal and immune systems.

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