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Biology subjects

Paulson, S.

Publications and source records attributed to Paulson, S..

2 recordsLinked to original sources

Biolearn, an open-source library for biomarkers of aging

Aging biomarkers are essential for understanding and quantifying the aging process and developing targeted longevity interventions. However, validation of these tools has been hindered by the lack of standardized approaches for cross-population validation, disparate biomarker designs, and inconsistencies in dataset structures. To address these challenges, we developed Biolearn, an open-source library that provides a unified framework for the curation, harmonization, and systematic evaluation of aging biomarkers. Leveraging Biolearn, we conducted a comprehensive evaluation of various aging biomarkers across multiple datasets. Our systematic approach involved three key steps: (1) harmonizing existing and novel aging biomarkers in standardized formats; (2) unifying public datasets to ensure coherent structuring and formatting; and (3) applying computational methodologies to assess the harmonized biomarkers against the unified datasets. This evaluation yielded valuable insights into the performance, robustness, and generalizability of aging biomarkers across different populations and datasets. The Biolearn python library, which forms the foundation of this systematic evaluation, is freely available at https://Bio-Learn.github.io. Our work establishes a unified framework for the curation and evaluation of aging biomarkers, paving the way for more efficient and effective clinical validation and application in the field of longevity research.

bioinformatics↗

On the origin and evolution of the mosquito male-determining factor Nix

The mosquito family Culicidae is divided into two subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Ae. albopictus, two important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from three highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133-165 MYA. Heterologous expression of one of three divergent Nix ORFs in Ae. aegypti resulted in partial masculinization of genetic females as evidenced by morphology and doublesex splicing. It is not clear whether insufficient transgene expression or sequence divergence or both are responsible for the lack of phenotype for the other two. Phylogenetic analysis suggests Nix is related to femaleless (fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes. Nix from all species has a conserved structure, including three RNA-recognition motifs (RRMs), as does fle. However, Nix has evolved at a much faster rate than fle. The RRM3 of both Nix and fle are related to the single RRM of a widely distributed and conserved splicing factor transformer-2 (tra2). RRM3-based phylogenetic analysis suggests this domain in Nix and fle may have evolved from tra2 in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex-determination and homomorphic sex chromosomes in mosquitoes, and will inform broad applications of mosquito-control strategies based on manipulating sex ratios towards the non-biting males.

evolutionary biology↗