Biology subjects

White, M. L.

Publications and source records attributed to White, M. L..

6 recordsLinked to original sources

bioRxiv2026

Decay chemicals activate a pH-sensing pathway to initiate a persistent state

Animals use multiple sensory systems to identify signs of danger, including dead conspecifics. Fish can identify decaying conspecifics from chemosensory cues, which prompt a long-lasting avoidance; the neural basis of this persistent chemosensory-driven state is not understood. Here, we describe a persistent alarm state in larval zebrafish, where brief exposure to the polyamine decay product, cadaverine, initiates a minutes-long increase in heart rate and suppression of visually-evoked swimming. Cadaverine activates both olfactory and trigeminal neurons, with persistently-active cells in the forebrain and dorsolateral hindbrain. However, we find that cadaverine's persistent effects on hindbrain activity, heart rate, and locomotor suppression are not mediated by olfaction. Instead, they are mediated through trigeminal chemosensation of the basic pH of concentrated cadaverine in solution. Knockout of TrpA1 channels, which are expressed in trigeminal neurons and associated with chemical nociception across species, prevents the persistent suppression of movement from brief exposure to cadaverine. pH-responsive trigeminal neurons project into the dorsolateral hindbrain to mediate persistent activity and long-lasting locomotor suppression through local inhibition. These results demonstrate that non-olfactory chemosensation mediates persistent behavioral responses to death and decay in zebrafish, illustrating how diverse chemosensory systems detect ethologically-relevant cues to drive adaptive behavior.

neuroscience↗

bioRxiv2025

The First Chromosome-Scale Genome Assembly for Dermacentor reticulatus: A Key Vector of Tick-Borne Pathogens of Public and Veterinary Health Importance in Europe

BackgroundDermacentor reticulatus is a key tick species across Europe and an established vector of multiple pathogens that affect both human and animal health. Despite its significant role in disease transmission, genomic data for this species remain limited. Here, we present the first chromosome-scale genome assembly of D. reticulatus, constructed using Oxford Nanopore long-read sequencing data. MethodsHigh molecular weight DNA was extracted from a female Dermacentor reticulatus collected in Devon, UK, and sequenced using Oxford Nanopore long-read technology. Genome assemblies were generated using both guided and unguided approaches, followed by repeat masking, gene prediction, and functional annotation. Genome completeness was assessed using BUSCO, and comparative, phylogenetic, and functional analyses were performed against other Dermacentor and tick species. ResultsThis chromosome-scale genome assembly revealed a repeat-rich genome, with approximately 61.9% of the total sequence consisting of repetitive elements. Benchmarking universal single-copy ortholog (BUSCO) analysis demonstrated strong genome completeness, with guided assembly (chromosome) achieving a score of 97.1%, closely matching those of related Dermacentor species. For comparison, unguided assembly (scaffold) yielded a BUSCO score of 96.7%. Gene annotation following repeat masking resulted in BUSCO completeness scores of 95.1% (guided) and 95.0% (unguided). Functional characterisation included Pfam domain assignment and Gene Ontology analysis. Additionally, we assembled the mitochondrial genome (15,103 bp), comprising 38 genes, providing further insight into D. reticulatus phylogenetic placement. ConclusionsThis genomic resource establishes a foundation for functional genomics, evolutionary studies and supports future research in vector biology and the control of tick-borne diseases.

genomics↗

bioRxiv2025

α7 nicotinic acetylcholine receptors regulate radial glia fate in the developing human cortex

Prenatal nicotine exposure impairs fetal cortical grey matter volume, but the precise cellular mechanisms remain poorly understood. This study elucidates the role of nicotinic acetylcholine receptors (nAChRs) in progenitor cells and radial glia (RG) during human cortical development. We identify two nAChR subunits--CHRNA7 and the human-specific CHRFAM7A--expressed in SOX2+ progenitors and neurons, with CHRFAM7A particularly enriched along RG endfeet. nAChR activation in organotypic slices and dissociated cultures increases RG proliferation while decreasing neuronal differentiation, whereas nAChR knockdown reduces RG and increases neurons. Single-cell RNA sequencing reveals that nicotine exposure downregulates key genes in excitatory neurons (ENs), with CHRNA7 or CHRFAM7A selectively modulating these changes, suggesting an evolutionary divergence in regulatory pathways. Furthermore, we identify YAP1 as a critical downstream effector of nAChR signaling, and inhibiting YAP1 reverses nicotine-induced phenotypic alterations in oRG cells, highlighting its role in nicotine-induced neurodevelopmental pathophysiology.

neuroscience↗

bioRxiv2022

A cross-species proteomic map of synapse development reveals neoteny during human postsynaptic density maturation

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of >1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about two to three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and the functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.

neuroscience↗

bioRxiv2022

MraZ is a transcriptional inhibitor of cell division in Bacillus subtilis

The bacterial division and cell wall (dcw) cluster is a highly conserved region of the genome which encodes several essential cell division factors including the central divisome protein FtsZ. Understanding the regulation of this region is key to our overall understanding of the division process. mraZ is found at the 5 end of the dcw cluster and previous studies have described MraZ as a sequence-specific DNA binding protein. In this article, we investigate MraZ to elucidate its role in Bacillus subtilis. Through our investigation, we demonstrate that increased levels of MraZ result in lethal filamentation due to repression of its own operon (mraZ-mraW-ftsL-pbpB). We observe rescue of filamentation upon decoupling ftsL expression, but not other genes in the operon, from MraZ control. Furthermore, through timelapse microscopy we were able to identify that overexpression of mraZ, results in de-condensation of the FtsZ ring (Z-ring). This is likely due to depletion of FtsL, and thus, we believe the precise role of FtsL is likely in Z-ring maturation and promotion of subsequent treadmilling. Our data suggests that regulation of the mra operon may be an alternative way for cells to quickly arrest cytokinesis potentially during entry into stationary phase and in the event of DNA replication arrest.

microbiology↗

bioRxiv2021

Data Matrix Normalization and Merging Strategies Minimize Batch-specific Systemic Variation in scRNA-Seq Data

Single-cell RNA sequencing (scRNA-seq) can reveal accurate and sensitive RNA abundance in a single sample, but robust integration of multiple samples remains challenging. Large-scale scRNA-seq data generated by different workflows or laboratories can contain batch-specific systemic variation. Such variation challenges data integration by confounding sample-specific biology with undesirable batch-specific systemic effects. Therefore, there is a need for guidance in selecting computational and experimental approaches to minimize batch-specific impacts on data interpretation and a need to empirically evaluate the sources of systemic variation in a given dataset. To uncover the contributions of experimental variables to systemic variation, we intentionally perturb four potential sources of batch-effect in five human peripheral blood samples. We investigate sequencing replicate, sequencing depth, sample replicate, and the effects of pooling libraries for concurrent sequencing. To quantify the downstream effects of these variables on data interpretation, we introduced a new scoring metric, the Cell Misclassification Statistic (CMS), which identifies losses to cell type fidelity that occur when merging datasets of different batches. CMS reveals an undesirable overcorrection by popular batch-effect correction and data integration methods. We show that optimizing gene expression matrix normalization and merging can reduce the need for batch-effect correction and minimize the risk of overcorrecting true biological differences between samples.

systems biology↗