Biology subjects

Rose, L.

Publications and source records attributed to Rose, L..

13 recordsLinked to original sources

bioRxiv2026

Lack of Consensus for Manual Mouse Sleep Scoring Limits Implementation of Automatic Deep Learning Models

Scientists have for decades attempted to automate the manual sleep staging problem not only for human polysomnography data but also for rodent data. No model has, however, succeeded in fully replacing the manual procedure across clinics and laboratories. We hypothesize that this is due to the models limited ability to generalize to data from unseen laboratories. Our findings show that despite the high performance of four state-of-the-art models reported in initial publications, the published models struggle to generalize to other laboratories. We further show a significant improvement in model performance across labs by re-training them on a diverse dataset from five different sites. To assess the contribution of variability in manual scoring, ten experts from five laboratories all labelled the same nine mouse sleep recordings. The result revealed substantial scoring variability, particularly for rapid eye movement (REM) sleep, both within and between labs. In conclusion our study demonstrates that key challenges in the generalizability of state-of-the-art sleep scoring models are signal variability and label noise. Our study highlights the need for a standardized set of mouse sleep scoring guidelines to enable consistency and collaboration across the field. Until such a consensus is reached, we present four sufficiently robust models trained on diverse datasets that can serve as standardized tools across labs.

neuroscience↗

bioRxiv2025

Interlocus gene conversion causes mosaic divergence in tandem paralogues - simulating HMA4 evolution in Arabidopsis halleri

Following gene duplication, the evolutionary trajectories of gene copies can be shaped by various processes including mutation, selection, recombination and interlocus gene conversion (IGC). To explore their dynamics and consequences, we developed a mathematical model that simulates the early evolution of recently duplicated, tandemly arrayed gene families with positive selection on the new gene copy. We compared the results of our model to sequence variation of the three tandemly arrayed HEAVY METAL ATPase 4 (HMA4) gene copies of Arabidopsis halleri, which are known to undergo IGC. However, rate and efficacy of IGC vary within genes, resulting in a mosaic pattern of divergence. Informed by empirical data, our model captures the impact of IGC and unequal crossing-over on the diversity within each gene copy and the divergence among them. By tailoring the model to the HMA4 gene copies, we demonstrate the models flexibility and its potential to provide insights into the evolutionary dynamics driving the evolution of tandemly arrayed paralogues. This study enhances our understanding of the balance between homogenization and divergence of gene family evolution.

evolutionary biology↗

bioRxiv2025

Unlocking the Forgotten Dimension of Biodiversity: A Scalable Genetic Diversity Index for Multi-Species Analysis

Geographic patterns of community-level genetic diversity provide key information about evolutionary processes and are increasingly relevant for conservation planning under rapid environmental change. Yet, continental-scale, multi-taxon assessments of genetic diversity remain rare, largely due to difficulties in integrating heterogeneous datasets across species and markers. Here, we develop a scalable framework to quantify and map nucleotide diversity ({pi}) across co-occurring taxa using georeferenced sequence data. We compiled and harmonized genetic metadata for European vascular plants and calculated site-level{pi} for individual species. By spatially aggregating values across taxa, we derived the Genetic Diversity Index (GDI), designed to capture shared geographic structure in intraspecific variation while minimizing species-specific noise. We evaluated robustness using simulations and rarefaction procedures to assess sensitivity to sampling intensity and taxonomic composition. Using [~]630,000 sequences from 1,860 species, GDI identified consistent hotspots of genetic diversity in the Anatolian Peninsula, Southern Iberia, and the Eastern Alps. These regions coincide with areas widely recognized as long-term refugia and biogeographic transition zones. GDI showed weak relationships with species richness and phylogenetic diversity, indicating that it captures a distinct dimension of biodiversity linked to demographic persistence and evolutionary history. In addition, GDI increased significantly with late-Quaternary climate stability, supporting the expectation that regions experiencing reduced climatic fluctuation tend to retain higher levels of genetic variation. Our results demonstrate that publicly available sequence data can be synthesized into reproducible, large-scale estimates of community-level diversity. The GDI provides a practical tool for integrating genetic information into biodiversity assessments and for identifying regions where evolutionary potential may be concentrated. This framework opens new opportunities for incorporating genomic resources into conservation prioritization and macroecological research.

genetics↗

bioRxiv2025

Live Cell Extrusion in Cervical Cancer - A Novel Mechanism for Cancer Progression

Extrusion during development or of transformed cells in normal epithelia has been described as a process of elimination. However, the role of extrusion in transformed epithelia is still unclear. Here, we report that in a primary tumor-derived cervical cancer cell line, SiHa, overcrowding results in the extrusion of a subset of cells. We find that the mechanism of extrusion in SiHa cells is similar to those that drive live cell extrusion in normal epithelia, suggesting the utility of this model. We propose that the subset that is extruded during overcrowding is resistant to anoikis and acquires promigratory features. We find that this population also exhibits an increase in TGF-{beta} signaling, which we show is a promigratory factor in cervical cancer cells and is a potential driver for the migratory potential observed in the extruded population. Our study shows that extrusion in cervical cancers in response to overcrowding underlies promigratory behavior of sub-populations in cervical cancer cell lines.

cancer biology↗

bioRxiv2025

When does additional information improve accuracy of RNA secondary structure prediction?

The secondary structure of an RNA sequence plays an important role in determining its function, and accurate prediction of the structure is still a major goal in computational biology. Improvements in the prediction accuracy of the secondary structure can be achieved via auxiliary information. In this paper, we study features based on suboptimal formations competing with the minimum-free energy formation and investigate their role in determining the improvement of accuracy via auxiliary information, which we call directability. Here, we introduce a similarity measure among competing substructures called profiles. Then, we present an n-dimensional representation of the profiles which allows the use of topological data analysis (i.e., persistence landscapes) to obtain different metrics that represent topological features. Then, we built random forest classifiers using these novel features. We show how the similarity feature is more important for classifiers trained on sequences with similar structures while the topological features are more important for classifiers trained on sequences with dissimilar structures. We perform extensive testing on two sets of RNA sequences where we studied the sensitivity of the classification accuracy and their feature importance.

bioinformatics↗

bioRxiv2022

The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis

During cytokinesis, signals from the central spindle stimulate the accumulation of active RhoA-GTPase and thus contractile ring components at the equator, while the astral microtubules inhibit such components at the polar cortex. The DEPDC1 family protein LET-99 is required for furrow ingression in the absence of the central spindle signal, and for timely onset of furrowing even in the presence of the central spindle signal. Here we show that LET-99 works downstream or independently of RhoA-GTP and antagonizes branched F-actin and the Rac protein CED-10 to promote furrow initiation. This interaction with CED-10 is separable from LET-99s function in spindle positioning. We also characterize a new role for LET-99 in regulating cortical stability, where LET-99 acts in parallel with the actomyosin scaffolding protein anillin, but LET-99 does not antagonize CED-10 in this case. We propose that LET-99 acts in a pathway that inhibits the Rac CED-10 to promote the proper balance of branched versus linear F-actin for cytokinesis, and that LET-99 also regulates another factor that contributes to cortical stability.

cell biology↗

bioRxiv2022

Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by PCM1. To study the requirement for centriolar satellites, we generated mice lacking PCM1. Pcm1-/- mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia and cerebellar hypoplasia, as well as variable expressivity of other ciliopathy features including cystic kidneys. Pcm1-/- multiciliated ependymal cells and PCM1-/- retinal pigmented epithelial 1 (RPE1) cells showed reduced ciliogenesis. PCM1-/- RPE1 cells displayed reduced docking of the mother centriole to the ciliary vesicle and removal of CP110 and CEP97 from the distal mother centriole, indicating compromized early ciliogenesis. We show these molecular cascades are maintained in vivo, and we suggest that the cellular threshold to trigger ciliogenesis varies between cell types. We propose that PCM1 and centriolar satellites facilitate efficient trafficking of proteins to and from centrioles, inducing the departure of CP110 and CEP97 to initiate ciliogenesis.

cell biology↗

bioRxiv2021

Escaping the Fate of Sisyphus: Assessing Resistome Hybridization Baits for Antimicrobial Resistance Gene Capture

Finding, characterizing, and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive, and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19,933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3,565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement. Originality-Significance StatementThis work is applicable to a wide range of research. It helps to define conditions under which hybridization capture is useful regarding not only antimicrobial resistance specifically, but also more generally how to assess the ongoing utility of existing bait sets - giving objective criteria for when and by what strategies baits should be updated. We also provide a method for quantifying and comparing antimicrobial resistance genes (ARGs) similar to what is used for RNAseq experiments. This approach improves comparison of ARGs across environments. Thus, the work provides an improved foundation for ARG future studies, while cutting across traditional areas of microbiology and extending beyond.

microbiology↗

bioRxiv2020

Mutually inclusive mechanisms of drought-induced tree mortality

An extreme summer drought caused unprecedented tree dieback across Central Europe in 2018, highlighting the need for a better mechanistic understanding of drought-induced tree mortality. While numerous physiological risk factors have been identified, the principal mechanisms, hydraulic failure and carbon starvation, are still debated. We studied 9,435 trees from 12 temperate species planted in a diversity experiment in 2013 to assess how hydraulic traits, carbon dynamics, pest infestation, tree height and neighbourhood competition influence individual mortality risk. We observed a reduced mortality risk for trees with wider hydraulic safety margins, while a rising sugar fraction of the non-structural carbohydrate pool and bark beetle infestation were associated with higher risk. Taller trees had a lower mortality risk. The sign and magnitude of neighbourhood effects on mortality risk depended on the species-identity of the involved trees, with most species having beneficial and some having deleterious effects on their neighbours. While severe tissue dehydration causing hydraulic failure precedes drought-induced tree mortality, we show that the probability of this event depends on a series of mutually inclusive processes including pest infestation and starch depletion for osmotic adjustment, and is modulated by the size and species identity of a tree and its neighbours.

ecology↗

bioRxiv2020

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

microbiology↗

bioRxiv2020

What drives the assembly of plant-associated protist microbiomes?

In a field experiment we investigated the influence of the environmental filters soil type and plant species identity on rhizosphere community assembly of Cercozoa, a dominant group of (mostly bacterivorous) soil protists. The experiment was set up with two plant species, lettuce and potato, grown in an experimental plot system with three contrasting soils. Plant species (14%) and rhizosphere origin (vs. bulk soil) with 13%, together explained four times more variation in cercozoan beta diversity than the three soil types (7% explained variation in beta diversity). Our results clearly confirm the existence of plant species-specific protist communities. Network analyses of bacteria-Cercozoa rhizosphere communities identified scale-free small world topologies, indicating mechanisms of self-organization. While the assembly of rhizosphere bacterial communities is bottom-up controlled through the resource supply from root (secondary) metabolites, our results support the hypothesis that the net effect may depend on the strength of top-down control by protist grazers. Since grazing of protists has a strong impact on the composition and functioning of bacteria communities, protists expand the repertoire of plant genes by functional traits, and should be considered as protist microbiomes in analogy to bacterial microbiomes. HighlightMicrobiomes of rhizosphere protists are plant species-specific and tightly co-evolving with their bacterial prey, thereby extending and modifying the functional repertoire of the bacterial-plant symbiosis.

plant biology↗

bioRxiv2020

Fast transport of RNA granules by direct interactions with KIF5A/KLC1 motors prevents axon degeneration

Complex neural circuitry requires stable connections formed by lengthy axons. To maintain these functional circuits, fast transport delivers RNAs to distal axons where they undergo local translation. However, the mechanism that enables long distance transport of non-membrane enclosed organelles such as RNA granules is not known. Here we demonstrate that a complex containing RNA and the RNA-binding protein (RBP) SFPQ interacts directly with a tetrameric kinesin containing the adaptor KLC1 and the motor KIF5A. We show that binding of SFPQ to KIF5A/KLC1 motor complex is required for axon survival and is impacted by KIF5A mutations that cause Charcot-Marie-Tooth (CMT) Disease. Moreover, therapeutic approaches that bypass the need for local translation of SFPQ-bound proteins prevent axon degeneration in CMT models. Collectively, these observations show that non-membrane enclosed organelles can move autonomously and that replacing axonally translated proteins provides a therapeutic approach to axonal degenerative disorders.

cell biology↗

bioRxiv2019

A Highly Conserved Shh Enhancer Coordinates Hypothalamic and Craniofacial Development

Enhancers that are conserved deep in evolutionary time regulate characteristics held in common across taxonomic classes. Here, deletion of the highly conserved Shh enhancer SBE2 (Shh brain enhancer 2) markedly reduced Shh expression within the embryonic brain specifically in the rostral diencephalon; however, no abnormal anatomical phenotype was observed due to compensatory low levels of expression mediated by a second enhancer. In contrast, a further reduction of Shh levels, achieved by crossing the SBE2 deletion with the Shh null allele, disrupted brain and craniofacial tissue; thus, linking SBE2 regulated Shh expression to multiple defects and further enabling the study of the effects of differing levels of Shh on embryogenesis. Development of the hypothalamus, derived from the rostral diencephalon, was disrupted along both the anterior-posterior (AP) and the dorsal-ventral (DV) axes. Expression of DV patterning genes and subsequent neuronal population induction were particularly sensitive to Shh expression levels, demonstrating a novel morphogenic context for Shh. The role of SBE2, which is highlighted by DV gene expression, is to step-up expression of Shh above the minimal activity of the second enhancer, ensuring the necessary levels of Shh in a regional-specific manner. We also show that low Shh levels in the diencephalon disrupted neighbouring craniofacial development, including mediolateral patterning of the bones along the cranial floor and viscerocranium. Thus, SBE2 contributes to hypothalamic morphogenesis and ensures there is coordination with the formation of the adjacent midline cranial bones that subsequently protects the neural tissue.

developmental biology↗