Biology subjects

Duke, E.

Publications and source records attributed to Duke, E..

8 recordsLinked to original sources

bioRxiv2026

A generalized resource-allocation growth law reveals mechanisms of differential responses to intermittent androgen deprivation therapy in prostate cancer

Resource-limited growth frameworks often developed independently. Here, we derived a growth law by assuming a cell balancing internal competing resource demands and generalizing the growth signal through a shape parameter h, the trade-off exponent. In Liebig's single-limiting-resource regime, it recovers Droop's cell quota at h=1 and approaches Prater's growth efficiency as h grows large. h determines how sharply growth declines when allocation departs from optimal, thereby shaping populations evolution. Cyclic environmental stress tests such growth laws. Hence, we built a model from this growth law and applied it to prostate cancer growth in patients undergoing cyclic intermittent androgen deprivation therapy. We showed the model recapitulated longitudinal prostate specific antigen (PSA) and serum androgen measurements from 71 prostate cancer patients using a nonlinear mixed-effects framework (pooled and median individual R^2 {approx} 0.9 for PSA and {approx} 0.8 for serum androgen). h is well-constrained by the data and separates treatment outcomes (success vs. failure, p = 0.003). The results predict that failing cases have cancer that can adapt to a wide range of growth conditions with minimal cost. A simplified model recapitulated PSA dynamics from 32 prostate cancer patients on cyclic adaptive therapy (R^2 {approx} 0.8). Estimates of h for castration resistant cancer in adaptive cohort were similar to failure cases in the intermittent cohort. We found no statistical differences in estimated parameters between the adaptive vs. standard of care arms, suggesting that adaptive schedule may drive the differential outcome. The results support this growth law, providing a foundation for resource-limited growth across biological systems.

ecology↗

bioRxiv2026

iSBEM: An Open-Source Workflow for Automated ROI Targeting in Volume Electron Microscopy

Serial Block Face - Scanning Electron Microscopy (SBF-SEM) is a volume EM method suited to investigate the 3D architecture of tissues and even entire organisms at high resolution. However, imaging large volumes in their entirety is time-consuming and not always necessary. Many research projects have a focused interest in well-defined sub-regions of the samples. The targeting and acquisition of such regions of interest (ROIs) are however currently conducted in a manual way and require heavy involvement of experienced operators. We present a workflow and an original open-source software tool (iSBEM), which allow automated targeting of ROIs in a large tissue sample, based on X-ray microscopy (XRM) maps. After an initial ROI identification and registration of the XRM map with the sample mounted on the SBF-SEM stage, iSBEM takes over the control of the microscope, triggering high resolution acquisitions at defined ROI positions, with minimal user intervention. We demonstrate the approach on two biologically distinct specimens -- malarial oocysts in infected mosquito midgut tissue, and immune cells in human kidney biopsies -- achieving significant improvement in acquisition throughput relative to manual operations, without compromising targeting precision. We also showcase the workflow in a correlative light-Xray-electron microscopy setup, which allowed us to further improve the correct target definition.

cell biology↗

bioRxiv2026

An Advanced Mobile Laboratory to enable field-based microbial ecology and cell biology across scales

Microbial biodiversity is central to ecosystem function, yet mechanistic insights into the cell biology of environmental organisms remain limited. The underlying challenges are twofold: most microbes remain uncultivable, and a persistent gap exists between field sampling and laboratory analyses. Here, we introduce the Advanced Mobile Laboratory (AML), a field-deployable platform that integrates confocal microscopy, image-enabled cell sorting, and cryo-preparation for expansion and electron microscopy. This setup enables immediate, standardized processing and analysis of environmental communities directly at the sampling site. We demonstrate its capability using marine eukaryotic plankton, showing how the AML enables multiscale investigations, from live imaging of natural communities to enabling ultrastructural and single-cell omics analyses, while minimizing sample degradation and enabling on-site experimentation. By bringing high-end sample preparation and analytical capacity into the field, the AML enables studying life in its natural context to mechanistically understand lifes diversity in the environment.

cell biology↗

bioRxiv2025

Critical point drying of brain tissue for X-ray phase contrast imaging

X-ray phase contrast tomography is emerging as a powerful method for imaging large volumes of brain tissue at sub-cellular resolution. However, current sample preparation methods are largely inherited from visible light or electron microscopy workflows and hence are not optimised to exploit the full potential of X-ray contrast mechanisms. Here we propose to replace interstitial material by air to enhance X-ray phase contrast of the ultrastructural features. We used critical point drying (CPD) of heavy metal-stained mouse brain tissue to produce mechanically stable samples with preserved ultrastructure and enhanced refractive index boundaries, a nanofoam-like material that remains compatible with follow-up conventional resin embedding. Using two complementary synchrotron-based setups, a high-throughput microtomography beamline (P14, DESY) and a nanoscale holographic tomography beamline (ID16A, ESRF), we found that CPD samples consistently showed 2-4x stronger phase-shift signal than conventional resin-embedded tissue. The contrast gain remained consistent across samples, imaging conditions, and beamlines. Our results suggest that CPD offers a versatile route for preparing tissue for subcellular and ultrastructural-resolution X-ray imaging. It retains structural detail while improving signal, and is compatible with other processing procedures like femtosecond laser milling or electron microscopy, paving the path for biological tissue imaging beyond the mm3 scale.

neuroscience↗

bioRxiv2025

Synaptic high-frequency jumping synchronises vision to high-speed behaviour

During high-speed behaviour, animals must synchronise perception and action despite rapid environmental and self-generated motion. How neural systems achieve such precision remains unclear. Here we show how the housefly (Musca domestica) maintains visual accuracy during fast motion. Using intracellular and photomechanical recordings during saccade-like stimulation, we traced information flow from photoreceptors to large monopolar cells (LMCs). Visual neurons achieved record-high information sampling ([~]2,500 bits{middle dot}s-1) and synaptic transmission ([~]4,100 bits{middle dot}s-1), far exceeding previous estimates. We identify a previously unknown mechanism - synaptic high-frequency jumping - in which photoreceptor-LMC synapses dynamically shift transmission toward higher frequencies during saccades, extending visual bandwidth to [~]1,000 Hz, effectively eliminating synaptic delays, and quadrupling classical flicker-fusion limits ([~]230 Hz). Behavioural experiments show flies respond synchronously within [~]13-20 ms, even before photoreceptor responses peak. A biophysically realistic model reveals how photomechanical-stochastic-refractory quantal sampling co-adapts with saccadic behaviour: through self-motion, flies efficiently translate image motion into temporally-precise, predictive high-speed vision.

neuroscience↗

bioRxiv2023

High Throughput Tomography (HiTT) on EMBL Beamline P14 on PETRA III

Here we present High-Throughput Tomography (HiTT), a fast and versatile phase-contrast imaging platform for life-science samples on the EMBL beamline P14 at DESY in Hamburg, Germany. We use a high photon flux undulator beamline to perform tomographic phase contrast acquisition in about two minutes which is linked to an automated data processing pipeline that delivers a 3D reconstructed data set less than a minute and a half after the completion of the X-ray scan. Combining this workflow with a sophisticated robotic sample changer enables the streamlined collection and reconstruction of X-ray imaging data from potentially hundreds of samples during a beamtime shift. HiTT permits optimal data collection for many different samples and makes possible the imaging of large sample cohorts thus allowing population studies to be attempted. We demonstrate the successful application of HiTT on various soft tissue samples in both liquid (hydrated and also dehydrated) and paraffin embedded preparations. Furthermore, we demonstrate the feasibility of HiTT to be used as a targeting tool for volume electron microscopy (vEM), as well as using HiTT to study plant morphology. We also show how the high throughput nature of the work has allowed large numbers of "identical" samples to be imaged to enable statistically relevant sample volumes to be studied. SynopsisWe present HiTT - high throughput tomography - a propagation based phase contrast X-ray imaging technique which can visualise 1 mm3 biological samples of various types at high resolution. The 3D reconstructions of the imaged volumes are calculated automatically once data collection is complete. The entire process from pressing start on data collection to viewing the final data takes less than 3 minutes. This speed in combination with the use of the automated sample changer to exchange the samples truly enables high throughput X-ray imaging for the first time.

bioengineering↗

bioRxiv2023

Cancer Prevalence Across Vertebrates

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Statement of SignificanceEvolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.

cancer biology↗

bioRxiv2019

Elimination of HSV-2 infected cells is mediated predominantly by paracrine effects of tissue-resident T cell derived cytokines

The mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in the human genital tract despite low tissue-resident CD8+ T-cell density (TRM) are unknown. We analyzed shedding episodes during chronic HSV-2 infection: viral clearance always occurred within 24 hours of detection even if viral load exceeded 107 HSV DNA copies; surges in granzyme B and interferon-{gamma} occurred within the early hours after reactivation. We next developed a mathematical model of an HSV-2 genital ulcer to integrate mechanistic observations of TRM in situ proliferation, trafficking, cytolytic effects and cytokine alarm signaling from murine studies with viral kinetics, histopathology and lesion size data from humans. A sufficiently high density of HSV-2 specific TRM predicted rapid contact-mediated elimination of infected cells. At lower TRM densities, TRM must initiate a rapidly diffusing, polyfunctional cytokine response in order to eliminate of a majority of infected cells and eradicate briskly spreading HSV-2 infection.\n\nOne Sentence SummaryControl of herpes simplex virus-2 is primarily mediated by rapidly diffusing cytokines secreted by tissue-resident T cells.

immunology↗