The dynamic upper limit of human lifespan, bioRxiv, 2017-04-06

AbstractWe respond to claims by Dong et al. that human lifespan is limited below 125 years. Using the log-linear increase in mortality rates with age to predict the upper limits of human survival we find, in contrast to Dong et al., that the limit to human lifespan is historically flexible and increasing. This discrepancy can be explained by Dong et al.’s use of data with variable sample sizes, age-biased rounding errors, and log(0) instead of log(1) values in linear regressions. Addressing these issues eliminates the proposed 125-year upper limit to human lifespan.

Sex differences in the adult human brain Evidence from 5,216 UK Biobank participants, bioRxiv, 2017-04-05

AbstractSex differences in the human brain are of interest, for example because of sex differences in the observed prevalence of psychiatric disorders and in some psychological traits. We report the largest single-sample study of structural and functional sex differences in the human brain (2,750 female, 2,466 male participants; 44-77 years). Males had higher volumes, surface areas, and white matter fractional anisotropy; females had thicker cortices and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume or height. There was generally greater male variance across structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

The 100 € lab A 3-D printable open source platform for fluorescence microscopy, optogenetics and accurate temperature control during behaviour of zebrafish, Drosophila and C. elegans, bioRxiv, 2017-04-01

An Integrative Framework for Detecting Structural Variations in Cancer Genomes, bioRxiv, 2017-03-29

AbstractStructural variants can contribute to oncogenesis through a variety of mechanisms, yet, despite their importance, the identification of structural variants in cancer genomes remains challenging. Here, we present an integrative framework for comprehensively identifying structural variation in cancer genomes. For the first time, we apply next-generation optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole genome sequencing to systematically detect SVs in a variety of cancer cells.Using this approach, we identify and characterize structural variants in up to 29 commonly used normal and cancer cell lines. We find that each method has unique strengths in identifying different classes of structural variants and at different scales, suggesting that integrative approaches are likely the only way to comprehensively identify structural variants in the genome. Studying the impact of the structural variants in cancer cell lines, we identify widespread structural variation events affecting the functions of non-coding sequences in the genome, including the deletion of distal regulatory sequences, alteration of DNA replication timing, and the creation of novel 3D chromatin structural domains.These results underscore the importance of comprehensive structural variant identification and indicate that non-coding structural variation may be an underappreciated mutational process in cancer genomes.

Beyond differences in means robust graphical methods to compare two groups in neuroscience, bioRxiv, 2017-03-28

AbstractIf many changes are necessary to improve the quality of neuroscience research, one relatively simple step could have great pay-offs to promote the adoption of detailed graphical methods, combined with robust inferential statistics. Here we illustrate how such methods can lead to a much more detailed understanding of group differences than bar graphs and t-tests on means. To complement the neuroscientist’s toolbox, we present two powerful tools that can help us understand how groups of observations differ the shift function and the difference asymmetry function. These tools can be combined with detailed visualisations to provide complementary perspectives about the data. We provide implementations in R and Matlab of the graphical tools, and all the examples in the article can be reproduced using R scripts.

Regulation of Life Span by The Gut Microbiota in The Short-Lived African Turquoise Killifish, bioRxiv, 2017-03-28

ABSTRACTGut bacteria occupy the interface between the organism and the external environment, contributing to homeostasis and disease. Yet, the causal role of the gut microbiota during host aging is largely unexplored. Here, using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, we show that the gut microbiota plays a key role in modulating vertebrate life span. Recolonizing the gut of middle-age individuals with bacteria from young donors resulted in life span extension and delayed behavioral decline. This intervention prevented the decrease in microbial diversity associated with host aging and maintained a young-like gut bacterial community, characterized by overrepresentation of the key genera Exiguobacterium, Planococcus, Propionigenium and Psychrobacter. Our findings demonstrate that the natural microbial gut community of young individuals can causally induce long-lasting beneficial systemic effects that lead to life span extension in a vertebrate model.