The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

Objective Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well‐developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of “brain age” analysis on disability in MS using a large, real‐world dataset. Methods Brain age analysis is predicated on the over‐estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset (>13,000 imaging sessions from >6,000 individual MS patients). Effects of MS, MS disease course, disability, lesion burden, and DMT efficacy were assessed using linear mixed effects models. Results MS was associated with advanced predicted brain age cross‐sectionally and accelerated brain aging longitudinally in all techniques. While MS disease course (relapsing vs. progressive) did contribute to advanced brain age, disability was the primary correlate of advanced brain age. We found that advanced brain age at study enrollment predicted more disability accumulation longitudinally. Lastly, a more youthful appearing brain (predicted brain age less than actual age) was associated with decreased disability. Interpretation Brain age is a technically tractable and clinically relevant biomarker of disease pathology that correlates with and predicts increasing disability in MS. Advanced brain age predicts future disability accumulation.

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SynopsisWith the rise of wearable sensors, advancement in comprehensible artificial intelligence (AI) algorithms, and growing acceptance of AI in medicine, AI has great potential to more reliably diagnose, prognose, and treat mental illnesses. The rapidly rising number of older adults worldwide presents a unique challenge for clinicians due to increased mental health needs in the setting of a dwindling clinical workforce. AI has enabled researchers to better understand mental illnesses by taking advantage of ‘big data.’This symposium will present an overview of novel research leveraging AI (machine learning, natural language processing) to better track, understand, and support mental health and cognitive functioning in older adults.Helmet Karim, PhD will present on prediction of treatment response in late-life major depressive disorder and the implications of those models.Ellen Lee, MD will present on using natural language processing to understand psychosocial functioning in older adults.Ipsit Vahia, MD will present on radio-based sensors to phenotype changes in behavior patterns that may correlate with a range of geropsychiatric symptoms.Andrea Iaboni, MD DPhil FRCPC will present on multimodal wearable and vision-based sensors for the detection and categorization of behavioural symptoms of dementia.The symposium includes three physician-scientists (Iaboni, Lee, Vahia), two women (Iaboni, Lee), and two early career faculty (Lee, Karim – co-chairs). The symposium represents four different institutions across the country (McLean/Harvard, Toronto Rehabilitation Institute/University of Toronto, UC San Diego, University of Pittsburgh) and four very different approaches using AI technology to improve understanding and outcomes in the field of geriatric mental health.The symposium seeks to address the underutilization of AI in psychiatric research, especially in the field of aging research. The increased individual-level heterogeneity associated with aging; complex trajectories of decline in cognitive, mental, and physical health; and lack and slow adoption of older adult-centered technologies present great challenges to advancing the field. However, advances in the field of explainable AI and transdisciplinary development of AI approaches can address the unique challenges of aging research.

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