Biology subjects

Brown, K. E.

Publications and source records attributed to Brown, K. E..

6 recordsLinked to original sources

bioRxiv2026

Individual mouse mitotic chromosomes exhibit cell type-specific differences in biomechanical properties

Cyclic episodes of chromosome compaction and de-condensation are features of eukaryotic cell division that aid mitotic segregation and help prevent aneuploidy. While biophysical data on mitotic chromosome structure has been previously obtained, heterogeneity within samples can confound analyses and precludes direct like-for-like comparisons. To circumvent this, we employed advanced flow cytometry to purify specific metaphase chromosomes with biotinylated telomeres from stably engineered mouse cells. We show that ESC-derived metaphase chromosomes 3 and 19 display distinct properties but share a conserved force-dependent mechanical response. In contrast, chromosome equivalents isolated from NSCs and preB cells show markedly different force-dependent responses, reflecting progressive differentiation stages. Covalent crosslinking of ESC-derived chromosomes alters biomechanical properties to mimic equivalents from more differentiated cells. Collectively, these results highlight the need to isolate specific, homogeneous metaphase chromosome samples to accurately decipher their complex behaviours.

biophysics↗

bioRxiv2025

Evolve and resequence provides a granular view of micro-evolution under different mating systems in Mimulus guttatus

We performed 10 generations of experimental evolution in Mimulus guttatus and measured genome-wide change in replicated populations that were compelled to reproduce entirely by self-fertilization, entirely by outcrossing, or by a mixture of the two. We developed a novel testing framework based on ancestral haplotype inference to locate mating system loci. Our results confirm several outstanding theoretical predictions: Selfing populations showed increased homozygosity, widespread hitch-hiking, and higher stochastic changes in allele frequencies compared to outcrossing populations. Despite this variability, approximately 20 genomic regions (QTLs) demonstrated parallel evolution across treatments. We identified candidate genes within QTLs using RNA sequencing data from the ancestral lines. In several instances, we found closely linked candidate genes, suggesting that by inhibiting recombination inbreeding can allow for selection on favorable gene combinations. We observed a general down-regulation of candidate genes in selfing populations, mirroring known transcriptome differences between established selfing and outcrossing sister species. This suggests that gene expression is a significant component of the "selfing syndrome."

evolutionary biology↗

bioRxiv2025

PlantCV v4: Image analysis software for high-throughput plant phenotyping

PlantCV is an open-source Python project aimed at developing tools to address a range of image-based, plant phenotyping questions. PlantCV has been used for more than 10 years to automate trait collection from image data and the newest release, PlantCV version 4, continues to lower the barrier to entry for users without substantial coding experience through extensive example use-case tutorials and simplified installation. In addition to usability, we document added functionality since the release of PlantCV v2, including support for more image types such as fluorescence, thermal, and hyperspectral data. Finally, we describe the development of a new subpackage focused on morphological trait measurements like leaf angle, and demonstrate its utility as compared to more manual methods of data collection. CORE IDEASO_LIPlantCV is an open-source, open-development, Python-based software package that has a new release for improved functionality and usability to make image analysis flexible and easier for researchers without a coding background. C_LIO_LIPlantCV is now capable of handling new data types that are relevant to researchers, such as thermal and hyperspectral, and has built in functionality for extracting information from these image types. C_LIO_LIThe software project aims to lower the barrier to entry into image analysis for researchers by providing numerous, versioned, interactive tutorials that cover most common use cases, particularly in plant science. C_LI

plant biology↗

bioRxiv2023

Natural selection drives emergent genetic homogeneity in a century-scale experiment with barley

Direct observation is central to our understanding of the process of adaptation, but evolution is rarely documented in a large, multicellular organism for more than a few generations. Here, we observe genetic and phenotypic evolution across a century-scale competition experiment, barley composite cross II (CCII). CCII was founded in 1929 with tens of thousands of unique genotypes and has been adapted to local conditions in Davis, CA, USA for 58 generations. We find that natural selection has massively reduced genetic diversity leading to a single clonal lineage constituting most of the population by generation F50. Selection favored alleles originating from similar climates to that of Davis, and targeted genes regulating reproductive development, including some of the most well-characterized barley diversification loci, Vrs1, HvCEN, and Ppd-H1. We chronicle the dynamic evolution of reproductive timing in the population and uncover how parallel molecular pathways are targeted by stabilizing selection to optimize this trait. Our findings point to selection as the predominant force shaping genomic variation in one of the worlds oldest ongoing biological experiments. One-Sentence SummaryWholesale genetic restructuring of an experimental population is a consequence of rapid environmental adaptation.

genetics↗

bioRxiv2023

Bioluminescence imaging of Cyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung

Aryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal and Cyp1a1 expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustained Cyp1a1 expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespoke Cyp1a1-Fluc reporters to longitudinally monitor AHR activity in vivo.

cell biology↗

bioRxiv2020

Influence of fatigue on reaction times and corticospinal excitability during movement preparation

Slower self-selected ballistic movement speeds and reduced corticospinal excitability at rest are associated with post-stroke fatigue (PSF). It is unclear if fatigue-related differences in corticospinal excitability, measured using transcranial magnetic stimulation, prior to a movement will explain slower movement speeds. We hypothesized that the levels of PSF explains the modulation of corticospinal excitability during movement preparation and altered behaviour. In this study, 73 non-depressed, high functioning, chronic, first-time stroke survivors performed a simple warned and unwarned auditory reaction time task. We show a reduced suppression of corticospinal excitability during movement preparation, an increased facilitation immediately prior to movement onset and slower reaction times in those with greater levels of PSF. Reduced suppression and increased facilitation of corticospinal excitability prior to movement onset in high fatigue is an indicator of poor modulation of pre-movement excitability which may in turn reflect poor sensory processing, supporting the sensory attenuation model of fatigue.

neuroscience↗