Biology subjects

Yap, M.

Publications and source records attributed to Yap, M..

5 recordsLinked to original sources

bioRxiv2025

stk32a links sleep homeostasis to suppression of sensory and motor systems

Sleep is regulated by a homeostatic process and associated with an increased arousal threshold, but the genetic and neuronal mechanisms that implement these essential features of sleep remain poorly understood. To address these fundamental questions, we performed a zebrafish genetic screen informed by human genome-wide association studies. We found that mutation of serine/threonine kinase 32a (stk32a) results in increased sleep and impaired sleep homeostasis in both zebrafish and mice, and that stk32a acts downstream of neurotensin signaling and the serotonergic raphe in zebrafish. stk32a mutation reduces phosphorylation of neurofilament proteins, which are co-expressed with stk32a in neurons that regulate motor activity and in lateral line hair cells that detect environmental stimuli, and ablating these cells phenocopies stk32a mutation. Neurotensin signaling inhibits specific sensory and motor populations, and blocks stimulus-evoked responses of neurons that relay sensory information from hair cells to the brain. Our work thus shows that stk32a is an evolutionarily conserved sleep regulator that links neuropeptidergic and neuromodulatory systems to homeostatic sleep drive and changes in arousal threshold, which are implemented through suppression of specific sensory and motor systems.

neuroscience↗

bioRxiv2025

Mechanical properties of the unguitractor apodeme of sunny stick insects, Sungaya aeta (Phasmatodea: Heteropterygidae)

An integral component of musculoskeletal systems are elastic elements mechanically in-series with muscle. Although these in-series elastic elements--e. g. tendons in vertebrates, or apodemes in invertebrates--can neither generate force nor do work, they are thought to bring substantial benefits to musculoskeletal performance; the mechanical properties of tendons, crucial determinants of these benefits, have consequently been subject of a large body of work. In sharp contrast, scarce information exists on the mechanical properties of apodemes. The little data that do exist appear to suggest that apodemes differ so substantially from tendons that their functional significance may differ, too. To increase our understanding of apodeme function, we determined the mechanical properties of the unguitractor apodeme (UTA) of Sungaya aeta stick insects. We devised an experimental protocol that permits tensile testing with slippery and brittle apodemes; we derived and validated a mechanical model that extracts the Youngs modulus from tensile tests with specimen with varying cross-sectional area, without the need for explicit measurement of the stress or strain distribution; and we interpreted the magnitude of the UTA modulus, strength and spring constant through allometric comparison with data on vertebrate tendons. The UTA modulus exceeds that of vertebrate tendons by almost one order of magnitude, but the size-corrected spring constant is nevertheless comparable and if anything smaller, due to systematic differences in apodeme and tendon shape. This many-to-one mapping suggests that apodemes may well convey the same functional benefits as tendons, and should not be prematurely excluded from invertebrate musculoskeletal models.

zoology↗

bioRxiv2024

Behavioural biomechanics: leaf-cutter ant cutting behaviour depends on leaf edge geometry

Leaf-cutter ants cut fresh leaves to grow a symbiotic fungus as crop. During cutting, one mandible is typically anchored onto the leaf lamina while the other slices through it like a knife. When initiating cuts into the leaf edge, however, foragers sometimes deviate from this behaviour, and instead used their mandibles symmetrically, akin to scissors. In-vivo behavioural assays revealed that the preference for either of the two cutting strategies depended on leaf edge geometry, and differed between natural leaf margins that were straight or serrated with notch-like folds: leaf-cutter ants displayed a strong preference for scissor-cutting when leaf edges were straight or had wide notches. This preference, however, reversed in favour of knife-cutting when notches were narrow. To investigate whether this behavioural difference had a mechanical origin, we mimicked knife-cutting in ex-vivo cutting experiments: for wide notches, all but the sharpest mandibles failed to initiate cuts, or only did so at large forces, caused by substantial leaf buckling and bending. This increased force demand would substantially limit the ability of foragers to cut leaves, and so reduce the colonys access to food sources. Scissor-cutting may thus be an adaptation to the mechanical difficulties associated with bending and buckling of thin leaves.

animal behavior and cognition↗

bioRxiv2022

Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology

Trust and transparency are critical for deploying deep learning (DL) models into the clinic. DL application poses generalisation obstacles since training/development datasets often have different data distributions to clinical/production datasets that can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise and three approximate Bayesian DL models used to predict cancer of unknown primary with three independent RNA-seq datasets covering 10,968 samples across 57 primary cancer types. Our results highlight simple and scalable Bayesian DL significantly improves the generalisation of uncertainty estimation (e.g., p-value = 0.0013 for calibration). Moreover, we demonstrate Bayesian DL substantially improves accuracy under data distributional shifts when utilising uncertainty thresholding by designing a prototypical metric that evaluates the expected (accuracy) loss when deploying models from development to production, which we call the Area between Development and Production curve (ADP). In summary, Bayesian DL is a hopeful avenue of research for generalising uncertainty, which improves performance, transparency, and therefore safety of DL models for deployment in real-world.

bioinformatics↗

bioRxiv2020

Microbiome-based environmental monitoring of a dairy processing facility highlights the challenges associated with low microbial-load samples

Food processing environments can harbor microorganisms responsible for food spoilage or foodborne disease. Efficient and accurate identification of microorganisms throughout the food chain can allow the identification of sources of contamination and the timely implementation of control measures. Currently, microbial monitoring of the food chain relies heavily on culture-based techniques. These assays are determined on the microbes expected to be present in the environment, and thus do not cater for unexpected contaminants. Many culture-based assays are also unable to distinguish between undesirable taxa and closely related harmless species. Furthermore, even when multiple culture-based approaches are used in parallel, it is still not possible to comprehensively characterize the entire microbiology of a food-chain sample. High throughput DNA sequencing represents a potential means through which microbial monitoring of the food chain can be enhanced. While sequencing platforms, such as the Illumina MiSeq, NextSeq and NovaSeq, are most typically found in research or commercial sequencing laboratories, newer portable platforms, such as the Oxford Nanopore Technologies (ONT) MinION, offer the potential for rapid analysis of food chain microbiomes. In this study, having initially assessed the ability of rapid MinION-based sequencing to discriminate between different microbes within a simple mock metagenomic mixture of related food spoilage, spore-forming microorganisms. Subsequently, we proceeded to compare the performance of both ONT and Illumina sequencing for environmental monitoring of an active food processing facility. Overall, ONT MinION sequencing provided accurate classification to species level, which was comparable to Illumina-derived outputs. However, while the MinION-based approach provided a means of easy library preparations and portability, the high concentrations of DNA needed to run the rapid sequencing protocols was a limiting factor, requiring the random amplification of template DNA in order to generate sufficient material for analysis.

microbiology↗