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Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons., Competing Interests: Declaration of interests J.R.E. serves on the scientific advisory board of Zymo Research Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This was a retrospective chart review in Western Australia, Australia.To describe the diagnosis, management, and treatment outcomes of ocular TB in Western Australia (WA).This was a retrospective review of ocular TB cases in WA from 2007 to 2018 with a minimum 2-year follow-up upon completion of anti-TB therapy (ATT).A total of 44 patients were referred to WA TB clinic. Ten were excluded from the analysis of treatment response; 34 met the inclusion criteria, of whom 97.1% were born overseas. No patients had symptomatic extraocular TB. Chest X-ray showed prior pulmonary TB in 11.7% of patients ( n = 4). All patients were treated with three or four ATT drugs. The most common ocular TB manifestation was retinal vasculitis (23.5%). Full resolution of ocular inflammation following ATT occurred in 66.7% ( n = 22), and reduced ocular inflammation requiring only topical steroid treatment was seen in 21.2% ( n = 7). Treatment failure occurred in 12.1% ( n = 4). Side effects were reported in 45.6% of patients, with gastrointestinal symptoms most common (27.2%).Our study is the first Australian study examining the management of ocular TB. Our study highlights the challenges in diagnosing TB ocular disease in a low-endemicity setting and the importance of the collaboration between uveitis and TB subspecialists..

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq) 1 technologies to generate 301,626 methylomes and 176,003 chromatin conformation-methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 cross-modality-annotated subclasses. We identified 2.6 million differentially methylated regions across the genome that represent potential gene regulation elements. Notably, we observed spatial cytosine methylation patterns on both genes and regulatory elements in cell types within and across brain regions. Brain-wide spatial transcriptomics data validated the association of spatial epigenetic diversity with transcription and improved the anatomical mapping of our epigenetic datasets. Furthermore, chromatin conformation diversities occurred in important neuronal genes and were highly associated with DNA methylation and transcription changes. Brain-wide cell-type comparisons enabled the construction of regulatory networks that incorporate transcription factors, regulatory elements and their potential downstream gene targets. Finally, intragenic DNA methylation and chromatin conformation patterns predicted alternative gene isoform expression observed in a whole-brain SMART-seq 2 dataset. Our study establishes a brain-wide, single-cell DNA methylome and 3D multi-omic atlas and provides a valuable resource for comprehending the cellular-spatial and regulatory genome diversity of the mouse brain., (© 2023. The Author(s).)

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. We further developed single-cell methylation barcodes that reliably predict brain cell types using the methylation status of select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell-type-specific gene regulation in adult human brains.

Planets grow in rotating disks of dust and gas around forming stars, some of which can subsequently collide in giant impacts after the gas component is removed from the disk 1-3 . Monitoring programmes with the warm Spitzer mission have recorded substantial and rapid changes in mid-infrared output for several stars, interpreted as variations in the surface area of warm, dusty material ejected by planetary-scale collisions and heated by the central star: for example, NGC 2354-ID8 (refs.  4,5 ), HD 166191 (ref.  6 ) and V488 Persei 7 . Here we report combined observations of the young (about 300 million years old), solar-like star ASASSN-21qj: an infrared brightening consistent with a blackbody temperature of 1,000 Kelvin and a luminosity that is 4 percent that of the star lasting for about 1,000 days, partially overlapping in time with a complex and deep, wavelength-dependent optical eclipse that lasted for about 500 days. The optical eclipse started 2.5 years after the infrared brightening, implying an orbital period of at least that duration. These observations are consistent with a collision between two exoplanets of several to tens of Earth masses at 2-16 astronomical units from the central star. Such an impact produces a hot, highly extended post-impact remnant with sufficient luminosity to explain the infrared observations. Transit of the impact debris, sheared by orbital motion into a long cloud, causes the subsequent complex eclipse of the host star., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years 1 . AU Mic possesses a relatively rare 2 and spatially resolved 3 edge-on debris disk extending from about 35 to 210 astronomical units from the star 4 , and with clumps exhibiting non-Keplerian motion 5-7 . Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic 'activity' on the star 8,9 . Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.

For high-contrast imaging systems, the time delay is one of the major limiting factors for the performance of the extreme adaptive optics (AO) sub-system and, in turn, the final contrast. The time delay is due to the finite time needed to measure the incoming disturbance and then apply the correction. By predicting the behavior of the atmospheric disturbance over the time delay we can in principle achieve a better AO performance. Atmospheric turbulence parameters, which determine wavefront phase fluctuations, have time-varying behavior. We present a stochastic model for wind speed and model time-variant atmospheric turbulence effects using varying wind speeds. We test a low-order, data-driven predictor, the linear minimum mean square error predictor, for a near-infrared AO system under varying conditions. Our results show varying wind can have a significant impact on the performance of wavefront prediction, preventing it from reaching optimal performance. The impact depends on the strength of wind fluctuations with the greatest loss in expected performance being for high wind speeds.

We present two complementary algorithms suitable for using focal-plane measurements to control a wavefront corrector with an extremely high-spatial resolution. The algorithms use linear approximations to iteratively minimize the aberrations seen by the focal-plane camera. The first algorithm, Fast & Furious (FF), uses a weak-aberration assumption and pupil symmetries to achieve fast wavefront reconstruction. The second algorithm, an extension to FF, can deal with an arbitrary pupil shape; it uses a Gerchberg-Saxton (GS)-style error reduction to determine the pupil amplitudes. Simulations and experimental results are shown for a spatial-light modulator controlling the wavefront with a resolution of 170×170  pixels. The algorithms increase the Strehl ratio from ∼0.75 to 0.98-0.99, and the intensity of the scattered light is reduced throughout the whole recorded image of 320×320  pixels. The remaining wavefront rms error is estimated to be ∼0.15  rad with FF and ∼0.10  rad with FF-GS.

Objectives: Few studies have examined the long-term effect of age at implantation on outcomes using multiple data points in children with cochlear implants. The goal of this study was to determine whether age at implantation has a significant, lasting impact on speech perception, language, and reading performance for children with prelingual hearing loss., Design: A linear mixed-model framework was used to determine the effect of age at implantation on speech perception, language, and reading abilities in 83 children with prelingual hearing loss who received cochlear implants by the age of 4 years. The children were divided into two groups based on their age at implantation: (1) under 2 years of age and (2) between 2 and 3.9 years of age. Differences in model-specified mean scores between groups were compared at annual intervals from 5 to 13 years of age for speech perception, and 7 to 11 years of age for language and reading., Results: After controlling for communication mode, device configuration, and preoperative pure-tone average, there was no significant effect of age at implantation for receptive language by 8 years of age, expressive language by 10 years of age, reading by 7 years of age. In terms of speech-perception outcomes, significance varied between 7 and 13 years of age, with no significant difference in speech-perception scores between groups at ages 7, 11, and 13 years. Children who used oral communication (OC) demonstrated significantly higher speech-perception scores than children who used total communication (TC). OC users tended to have higher expressive language scores than TC users, although this did not reach significance. There was no significant difference between OC and TC users for receptive language or reading scores., Conclusions: Speech perception, language, and reading performance continue to improve over time for children implanted before 4 years of age. The present results indicate that the effect of age at implantation diminishes with time, particularly for higher-order skills such as language and reading. Some children who receive cochlear implants after the age of 2 years have the capacity to approximate the language and reading skills of their earlier-implanted peers, suggesting that additional factors may moderate the influence of age at implantation on outcomes over time.

We present a method to calibrate a high-resolution wavefront (WF)-correcting device with a single, static camera, located in the focal-plane; no moving of any component is needed. The method is based on a localized diversity and differential optical transfer functions to compute both the phase and amplitude in the pupil plane located upstream of the last imaging optics. An experiment with a spatial light modulator shows that the calibration is sufficient to robustly operate a focal-plane WF sensing algorithm controlling a WF corrector with 40,000 degrees of freedom. We estimate that the locations of identical WF corrector elements are determined with a spatial resolution of 0.3% compared to the pupil diameter.

The objectives of treating asthma are to control symptoms by a minimum of medication, and to prevent severe attacks in the future. However, before these can be achieved the presence of asthma must be recognized, its severity determined, and the individual triggering factors identified. Full assessment is simple and practical: it involves history, measurement of airflow rates and allergy skin tests. Occasionally, if the diagnosis is not certain, trials of treatment and/or histamine (or methacholine) inhalation tests provide confirmation. Treatment involves not only avoidance or protection against triggering factors and trials of medication, but also patient education and modification of behavior to comply with treatment. For this the patient must have ready access to consistent medical advice to ensure and reinforce the correct response to asthmatic symptoms.