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PLOS Biology: New Articles

  • A comprehensive atlas of full-length <i>Arabidopsis</i> eccDNA populations identifies their genomic origins and epigenetic regulation

    by Syed Shan-e-Ali Zaidi, Sara Shakir, Hanne De Kort, Devang Mehta, Vu Nguyen, Ruben Gutzat, Hervé Vanderschuren

    Extrachromosomal circular DNA (eccDNA) has been described in several eukaryotic species and has been shown to impact phenomena as diverse as cancer and herbicide tolerance. EccDNA is thought to arise mainly through transposable element (TE) mobilization. Because studies based on short-read sequencing cannot efficiently identify full-length eccDNA forms generated from TEs, we employed the CIDER-Seq pipeline based on long-read sequencing, to obtain full-length eccDNAs from Arabidopsis. The generated eccDNA datasets identified centromeric/pericentromeric regions as hotspots of eccDNAs with several eccDNA molecules originating from Helitron and LTR TEs. To investigate the role of epigenetic marks on TE-derived eccDNA biogenesis, we studied Arabidopsis methylation mutants dcl3, rdr6, ros1, and ddm1. Contrasting the TE-suppression previously reported in the hypermethylated ros1 mutants, we identified activation of TEs in ros1, specifically of LTR/Gypsy TEs. An enrichment of LTR/Copia elements was identified in actively dividing calli and the shoot apical meristem (SAM). Uncharacterized “variable TEs” with high eccDNA and expression were identified in the SAM, including ATCOPIA58. Together, our study reveals the genomic origins of eccDNAs and delineates the link between epigenetic regulation, transposon mobilization, and eccDNA biogenesis.

  • Long-term musical training can protect against age-related upregulation of neural activity in speech-in-noise perception

    by Lei Zhang, Bernhard Ross, Yi Du, Claude Alain

    During cognitive tasks, older adults often show increased frontoparietal neural activity and functional connectivity. Cognitive reserve accrued from positive life choices like long-term musical training can provide additional neural resources to help cope with the effect of aging. However, the relationship between cognitive reserve and upregulated neural activity in older adults remains poorly understood. In this study, we measured brain activity using functional magnetic resonance imaging during a speech-in-noise task and assessed whether cognitive reserve accumulated from long-term musical training bolsters or holds back age-related increase in neural activity. Older musicians exhibited less upregulation of task-induced functional connectivity than older non-musicians in auditory dorsal regions, which predicted better behavioral performance in older musicians. Furthermore, older musicians demonstrated more youth-like spatial patterns of functional connectivity, as compared to older non-musicians. Our findings show that cognitive reserve accrued through long-term music training holds back age-related neural recruitment during speech-in-noise perception and enlighten the intricate interplay between cognitive reserve and age-related upregulated activity during cognitive tasks.

  • Correction: Engineering of a chitin deacetylase to generate tailor-made chitosan polymers

    by Martin Bonin, Antonia L. Irion, Anika Jürß, Sergi Pascual, Stefan Cord-Landwehr, Antoni Planas, Bruno M. Moerschbacher



  • Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation

    by Bowen Xu, Alexander Hull, Olivia N. M. Hill, Naja Kobal, Enric Ureña, Linda Partridge, Nazif Alic

    Attenuating protein synthesis promotes longevity in multiple species. However, numerous studies indicate that aging drives a decrease in protein synthetic capacity. These observations hint at potential, unexplored benefits of stimulating protein synthesis in old age. In this work, we focus on Maf1, a repressor of protein synthesis genes transcribed by RNA Polymerase (Pol) III, such as the 5S rRNA and tRNAs, and its role in aging. We show that the knockdown of Maf1 extends lifespan in Drosophila. Maf1 limits longevity specifically from adult neurons in both female and male fruit flies. In older females, adult neuron-specific knockdown of Maf1 improves neuromuscular function as well as the function of a distal organ, the gut. We find that the extension of female lifespan upon Maf1 knockdown requires Pol III initiation on the 5S rRNA. Indeed, reducing neuronal Maf1 activity rescues the age-related decline in 5S expression and protein synthesis in the brain of female flies. Hence, our findings show that stimulating neuronal protein synthesis can promote healthy aging.

  • A toolkit for mapping cell identities in relation to neighbors reveals conserved patterning of neuromesodermal progenitor populations

    by Matthew French, Rosa P. Migueles, Alexandra Neaverson, Aishani Chakraborty, Tom Pettini, Benjamin Steventon, Erik Clark, J. Kim Dale, Guillaume Blin, Valerie Wilson, Sally Lowell

    Patterning of cell fates is central to embryonic development, tissue homeostasis, and disease. Quantitative analysis of patterning reveals the logic by which cell-cell interactions orchestrate changes in cell fate. However, it is challenging to quantify patterning when graded changes in identity occur over complex 4D trajectories, or where different cell states are intermingled. Furthermore, comparing patterns across multiple individual embryos, tissues, or organoids is difficult because these often vary in shape and size. This problem is further exacerbated when comparing patterning between species. Here we present a toolkit of computational approaches to tackle these problems. These strategies are based on measuring properties of each cell in relation to the properties of its neighbors to quantify patterning, and on using embryonic landmarks in order to compare these patterns between embryos. We perform detailed neighbor-analysis of the caudal lateral epiblast of E8.5 mouse embryos, revealing local patterning in emergence of early mesoderm cells that is sensitive to inhibition of Notch activity. We extend this toolkit to compare mouse and chick embryos, revealing conserved 3D patterning of the caudal-lateral epiblast that scales across an order of magnitude difference in size between these two species. We also examine 3D patterning of gene expression boundaries across the length of Drosophila embryos. We present a flexible approach to examine the reproducibility of patterning between individuals, to measure phenotypic changes in patterning after experimental manipulation, and to compare of patterning across different scales and tissue architectures.