Biology subjects

Duffy, K.

Publications and source records attributed to Duffy, K..

7 recordsLinked to original sources

bioRxiv2026

Spontaneous eye behavior is an objective marker of parkinsonian severity

Eye behavior disruption is reported in Parkinson's disease (PD), but its correlation with disease severity has not been well examined. Here, in a nonhuman primate model of PD, we show that spontaneous eye behavior is impaired in parkinsonism and correlates with clinical rating scores and subthalamic beta oscillatory activity. These findings suggest that spontaneous eye behavior could serve as an objective, non-invasive biomarker of parkinsonian severity.

neuroscience↗

bioRxiv2026

First estimates of the population growth rate of the parasitic honey bee mite Tropilaelaps mercedesae in Apis mellifera colonies

A parasitic mite of honey bee brood (Tropilaelaps mercedesae), is spreading through populations of Apis mellifera honey bees in new regions and poses a major threat to honey bee health. Despite its clear threat, the biology of this mite is poorly understood, with gaps on such fundamental issues as how fast its populations can grow. This leaves the beekeeping world underprepared to plan for its arrival and management. In this study, we documented the growth of T. mercedesae populations in untreated A. mellifera colonies in Thailand and South Korea, and did the same for another parasitic mite (Varroa destructor) when possible. We found that the population growth of T. mercedesae was variable but could reach high levels (daily r of 0.010, 0.036, and 0.057), while the population growth of V. destructor (r = 0.021) matched previous estimates. Our results indicate that T. mercedesae populations can grow rapidly but they do not always attain this potential. Based on our results, humidity should be studied as a potential driver of population growth. If future work can reveal key drivers of T. mercedesae population growth, this would help predict infestations and help design management strategies that exploit the pests biological vulnerabilities.

zoology↗

bioRxiv2025

Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia

Clonal memory, a cellular property inherited across at least two divisions, has emerged as a key driver of cell heterogeneity. To uncover its roles in human haematopoiesis, we developed high-resolution ex vivo tools that track both division and fate commitment of individual primary human haematopoietic stem and progenitor cells (HSPCs). We show that human HSPCs display a clonal memory of division, as cells descending from the same ancestor cell divide synchronously over multiple generations. In parallel, HSPCs inherit a clonal memory of fate commitment, independently of lineage identity. Both forms of clonal memory persist over at least two divisions, across different HSPC commitment stages and cell culture conditions. In contrast, malignant haematopoiesis exhibits lower synchronicity, revealing a disruption of clonal memory in leukemic cells. Epigenetic remodelling using a bromodomain inhibitor partially restores the clonal memory in division in leukemic HSPCs, highlighting the plasticity of this trait and its potential for therapeutic modulation. Our findings position clonal memory as a key regulator of human haematopoietic stem cell behaviour. Demonstrating that clonal memory can be modulated opens new avenues for tuning cell heterogeneity in healthy and pathological tissues.

cell biology↗

bioRxiv2024

High phenotypic and genotypic plasticity among strains of the mushroom-forming fungus Schizophyllum commune

Schizophyllum commune is a mushroom-forming fungus notable for its distinctive fruiting bodies with split gills. It is used as a model organism to study mushroom development, lignocellulose degradation and mating type loci. It is a hypervariable species with considerable genetic and phenotypic diversity between the strains. In this study, we systematically phenotyped 16 dikaryotic strains for aspects of mushroom development and 18 monokaryotic strains for lignocellulose degradation. There was considerable heterogeneity among the strains regarding these phenotypes. The majority of the strains developed mushrooms with varying morphologies, although some strains only grew vegetatively under the tested conditions. Growth on various carbon sources showed strain-specific profiles. The genomes of seven monokaryotic strains were sequenced and analyzed together with six previously published genome sequences. Moreover, the related species Schizophyllum fasciatum was sequenced. Although there was considerable genetic variation between the genome assemblies, the genes related to mushroom formation and lignocellulose degradation were well conserved. These sequenced genomes will provide a solid basis for functional genomics analyses of the strains of S. commune.

microbiology↗

bioRxiv2022

A practical extraction and spatial statistical pipeline for large 3D bioimages

ABSTRACT/SUMMARYDespite much being known about the molecular regulation of hematopoiesis, little is understood about how hematopoietic cells are organized within bone marrow (BM) tissue. Recent advances in microscopy have led to the creation of increasingly detailed images of murine hematopoietic tissue. Accurate, efficient, and informative methodologies to extract and analyze the large amount of data generated are, however, still lacking. Indeed, cells are very densely packed in the bone marrow and therefore difficult to efficiently and accurately segment. In addition, currently employed statical analyses of cellular localization are generally unsuitable for the investigation of interactions between more than two cell types. To overcome these limitations, we developed PACESS, a readily applicable method based on neural network classification of hundreds of thousands of cells in thick 3D bone marrow samples, and a combination of statistical techniques to assess the spatial interactions between multiple cell types. To validate this approach, we used it to investigate the spatial organization of T cells, megakaryocytes and leukemic cells. We demonstrate that the presence of large clusters of leukemic cells affects the distribution of both T cells and megakaryocytes, albeit differently, resulting in the generation of previously unrecognized, unique microenvironments adjacent to each other within the same bone marrow cavity. We believe that this approach can contribute to unravel the BM cellular organization. MOTIVATIONThe organization of diverse hematopoietic cells within bone marrow tissue remains unclear. Recently developed tissue clearing methods enable the generation of large, 3D, single cell resolution microscopy images datasets, but the bottleneck in their analysis lies in both the identification and classification of cells, and in statistical analyses to probe their spatial relationships. We present a workflow (PACESS) that takes advantage of a convoluted neural network to identify and classify cells in 2D coupled with an automated method that extrapolates to 3D, followed by a combination of spatial statistics to classify tissue regions based on each cell types density, and logistic regression to test whether the relative abundance of cell types may be explained by reciprocal dependencies. Finally, we provide a combined measurement of the abundance of all cell types in a 3D map, highlighting regional variations found within the tissue. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/521787v3_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@4bcae8org.highwire.dtl.DTLVardef@1f676bcorg.highwire.dtl.DTLVardef@1ed38d3org.highwire.dtl.DTLVardef@12de53b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Dimensionality Reduction of Diffusion MRI Measures for Improved Tractometry of the Human Brain

Various diffusion MRI measures have been proposed for characterising tissue microstructure over the last 15 years. Despite the growing number of experiments using different diffusion measures in assessments of white matter, there has been limited work on: 1) examining their covariance along specific pathways; and on 2) combining these different measures to study tissue microstructure. In this work, we first demonstrate redundancies in the amount of information captured by 10 diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) measures. Using a data-reduction approach, we identified two biologically-interpretable components that capture 80% of the variance in commonly-used DTI and HARDI measures profiled along 22 brain pathways extracted from typically developing children aged 8 - 18 years (n = 36). The first derived component captures properties related to hindrance and restriction in tissue microstructure, while the second component reflects characteristics related to tissue complexity and orientational dispersion. We demonstrate that the components generated by this approach preserve the biological relevance of the original measurements by showing age-related effects across developmentally sensitive pathways. Our results also suggest that HARDI measures are more sensitive at detecting age-related changes in tissue microstructure than DTI measures.

neuroscience↗

bioRxiv2018

Malaria-induced remodelling of the bone marrow microenvironment mediates loss of haematopoietic stem cell function

Severe infections are a major source of stress on haematopoiesis, where consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow niches, which have been shown to be altered during ageing and haematopoietic malignancies. Whether the bone marrow (BM) microenvironment plays a role in mediating the effects of infection on HSCs remains an open question. Here we used an murine model of malaria coupled with intravital microscopy, single cell RNA-Seq, mathematical modelling and transplantation assays to obtain a quantitative understanding of the proliferation dynamics of haematopoietic stem and progenitor cells (HSPCs) during Plasmodium infection. We uncovered that during Plasmodium infection the HSC compartment turns over significantly faster than in steady state, and that a global interferon response and loss of functional HSCs are linked to alterations in BM endothelium function and osteoblasts number. Interventions that targeted osteoblasts uncoupled HSC proliferation and function, thus opening up new avenues for therapeutic interventions that may improve the health of survivors of severe infections.

cell biology↗