Biology subjects

Marks, M.

Publications and source records attributed to Marks, M..

14 recordsLinked to original sources

bioRxiv2026

A community benchmark enables high-resolution, cross-lab quantification of mouse social behavior

Social behavior is a sensitive readout of brain state, but quantifying rodent social behavior at scale has relied on siloed, lab-specific tools. We assembled Days of our Mice (DooM), a benchmark of manually annotated video and pose tracking spanning 15 laboratories and 33 social and solitary behaviors, and hosted a community behavior classification challenge. We built on challenge solutions to develop the High-Dimensional Rodent Annotator (HiDRA), a behavior classification tool that generalizes to labs unseen during training and learns cross-lab movement features. Applied without retraining to experimental data, HiDRA resolves line-specific and state-dependent behavioral fingerprints with strong generalizability and reproducibility, establishing high-resolution, shareable social phenotyping as a scalable readout of brain and internal state. We release the DooM dataset and HiDRA classifiers as open resources.

neuroscience↗

bioRxiv2026

Hypoxia Disrupts Multiple Processes Supporting Spatial Navigation

Hypoxia impairs cognitive function, yet its effects on navigation and intrinsic brain activity remain poorly understood. This study investigated whether a continuous exposure to hypoxia (CH) or an intermittent exposure to hypoxia (IH) differentially influence navigation performance and resting-state electroencephalography (EEG) in healthy young adults. Seventy-two participants completed sham (FiO2 = .209) and hypoxia (FiO2 = .13) sessions during either a one hour of CH or IH intervention. Navigation was assessed using the Spatial Performance Assessment for Cognitive Evaluation (SPACE), while resting-state EEG was recorded before and after the intervention in a subset of participants (n = 40). EEG spectra were parameterised into periodic (alpha and beta power and central frequency) and aperiodic (exponent and offset) components. Aligned rank transform (ART) analyses of variance examined effects of hypoxia and intervention group, while linear regression determined whether reductions in peripheral oxygen saturation (SpO2) predicted changes in navigation or EEG. Hypoxia impaired multiple components of navigation, increasing path integration distance error and egocentric pointing angle error irrespective of intervention group, while mapping accuracy was preferentially impaired following IH and perspective taking performance following CH. Hypoxia also reduced alpha and beta power, beta central frequency, and aperiodic exponent, while aperiodic offset and alpha central frequency remained stable. The reduction in aperiodic exponent was primarily evident following IH, suggesting that the temporal pattern of oxygen delivery may influence specific neurophysiological responses. Contrary to our hypothesis, SpO2 reduction did not predict individual differences in navigation performance or EEG activity. These findings demonstrate that brief, moderate hypoxic exposure can disrupt allocentric and egocentric components of spatial navigation while selectively altering periodic and aperiodic features of intrinsic brain activity.

neuroscience↗

bioRxiv2023

Distributed representations of innate behaviors in the hypothalamus do not predict specialized functional centers

Artificial activation of anatomically localized, genetically defined hypothalamic neuron populations is known to trigger distinct innate behaviors, suggesting a hypothalamic nucleus-centered organization of behavior control. To assess whether the encoding of behavior is similarly anatomically confined, we performed simultaneous neuron recordings across twenty hypothalamic regions in freely moving animals. Here we show that distinct but anatomically distributed neuron ensembles encode the social and fear behavior classes, primarily through mixed selectivity. While behavior class-encoding ensembles were spatially distributed, individual ensembles exhibited strong localization bias. Encoding models identified that behavior actions, but not motion-related variables, explained a large fraction of hypothalamic neuron activity variance. These results identify unexpected complexity in the hypothalamic encoding of instincts and provide a foundation for understanding the role of distributed neural representations in the expression of behaviors driven by hardwired circuits.

neuroscience↗

bioRxiv2023

A Foundation Model for Cell Segmentation

Cells are a fundamental unit of biological organization, and identifying them in imaging data - cell segmentation - is a critical task for various cellular imaging experiments. While deep learning methods have led to substantial progress on this problem, most models are specialist models that work well for specific domains but cannot be applied across domains or scale well with large amounts of data. In this work, we present CellSAM, a universal model for cell segmentation that generalizes across diverse cellular imaging data. CellSAM builds on top of the Segment Anything Model (SAM) by developing a prompt engineering approach for mask generation. We train an object detector, CellFinder, to automatically detect cells and prompt SAM to generate segmentations. We show that this approach allows a single model to achieve human-level performance for segmenting images of mammalian cells, yeast, and bacteria collected across various imaging modalities. We show that CellSAM has strong zero-shot performance and can be improved with a few examples via few-shot learning. Additionally, we demonstrate how CellSAM can be applied across diverse bioimage analysis workflows. A deployed version of CellSAM is available at https://cellsam.deepcell.org/.

bioinformatics↗

bioRxiv2023

Simultaneous single-cell calcium imaging of neuronal population activity and brain-wide BOLD fMRI

Blood Oxygen Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows for non-invasive, indirect recordings of neural activity across the whole brain in both humans and animals. However, the relationship between the local neural population activity and the vascular activity is not completely understood. To investigate this relationship, we present a novel MRI compatible single-photon microscope capable of measuring cellular resolution Ca2+ activity of genetically defined neurons during whole-brain BOLD fMRI in awake behaving mice. Using this combined imaging approach, we found a difference in activity patterns between cells which was dependent on their location with respect to the vasculature. Notably, neurons near the vasculature showed pronounced negative activity during contralateral whisker movements at 3 Hz. In a second proof of concept experiment, we demonstrate the potential of recording both local neural activities, like those in the barrel field (SSp-bfd), and BOLD fMRI readings from interlinked brain regions. In sum, the presented technological advancement paves the way for studies examining the interplay between local brain circuits and overarching brain functions. In addition, the new approach enhances our understanding of the vascular BOLD fMRI signal, providing insights into the determinants of local neurovascular functions and the brains organizational framework across various scales.

neuroscience↗

bioRxiv2022

Genetic architecture and evolution of color variation in American black bears

Color variation is a frequent evolutionary substrate for camouflage in small mammals but the underlying genetics and evolutionary forces that drive color variation in natural populations of large mammals are mostly unexplained. The American black bear, Ursus americanus, exhibits a range of colors including the cinnamon morph which has a similar color to the brown bear, U. arctos, and is found at high frequency in the American southwest. Reflectance and chemical melanin measurements showed little distinction between U. arctos and cinnamon U. americanus individuals. We used a genome-wide association for hair color as a quantitative trait in 151 U. americanus individuals and identified a single major locus (P < 10-13). Additional genomic and functional studies identified a missense alteration (R153C) in Tyrosinase-related protein 1 (TYRP1) that impaired protein localization and decreased pigment production. Population genetic analyses and demographic modeling indicated that the R153C variant arose 9.36kya in a southwestern population where it likely provided a selective advantage, spreading both northwards and eastwards by gene flow. A different TYRP1 allele, R114C, contributes to the characteristic brown color of U. arctos, but is not fixed across the range. HIGHLIGHTSO_LIThe cinnamon morph of American black bears and brown bears have different missense mutations in TYRP1 that account for their similar coloration C_LIO_LITYRP1 variants in American black bears and brown bears are loss-of-function alleles associated with impaired protein localization to melanosomes C_LIO_LIIn American black bears, the variant causing the cinnamon morph arose 9,360 years ago in the western lineage where it provides an adaptive advantage, and has spread northwards and eastwards by migration C_LI

evolutionary biology↗

bioRxiv2021

Comparative genomic analysis of skin and soft tissue Streptococcus pyogenes isolates from low- and high-income settings

Streptococcus pyogenes is a leading cause of human morbidity and mortality, especially in resource limited settings. The World Health Organisation has recently made a vaccine for S. pyogenes a global health priority to reduce the burden of the post-infection rheumatic heart disease. For a vaccine to be active against all relevant strains in each region, molecular characterisation of circulating S. pyogenes isolates is needed. We performed extensive comparative whole genome analyses of S. pyogenes isolates from skin and soft tissue infections in The Gambia, West Africa, where there is a high burden of such infections. To act as a comparator to this low-income country (LIC) collection of isolates, we performed genome sequencing of isolates from skin infections in Sheffield, UK, as representative high-income country (HIC) isolates. LIC isolates from The Gambia were genetically more diverse (46 emm-types in 107 isolates) compared to HIC isolates from Sheffield (23 emm-types in 142 isolates), with only 7 overlapping emm-types and with diverse genetic backgrounds. Characterisation of other molecular markers indicated some shared features, including a high prevalence of the skin infection-associated emm-pattern D and the variable fibronectin-collagen-T antigen (FCT) types FCT-3 and FCT-4. A previously unidentified FCT (FCT-10) was identified in the LIC isolates, belonging to two different emm-types. A high proportion (79/107; 73.8%) of LIC isolates carried genes for tetracycline resistance, compared to 53/142 (37.3%) HIC isolates. There was also evidence of different circulating prophages, as very few prophage-associated DNases and lower numbers of superantigens were detected in LIC isolates. Our study provides much needed insight into the genetics of circulating isolates in a LIC (The Gambia), and how they differ from those circulating in HICs (Sheffield, UK). Common molecular features may act as bacterial drivers for specific infection types, regardless of the diverse genetic background.

microbiology↗

bioRxiv2020

SIPEC: the deep-learning Swiss knife for behavioral data analysis

The quantification of behaviors of interest from video data is commonly used to study brain function, the effects of pharmacological interventions, and genetic alterations. Existing approaches lack the capability to analyze the behavior of groups of animals in complex environments. We present a novel deep learning architecture for classifying individual and social animal behavior, even in complex environments directly from raw video frames, while requiring no intervention after initial human supervision. Our behavioral classifier is embedded in a pipeline (SIPEC) that performs segmentation, identification, pose-estimation, and classification of complex behavior, outperforming the state of the art. SIPEC successfully recognizes multiple behaviors of freely moving individual mice as well as socially interacting non-human primates in 3D, using data only from simple mono-vision cameras in home-cage setups.

neuroscience↗

bioRxiv2019

An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data

Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition.

neuroscience↗

bioRxiv2019

Programmatic goals and spatial epidemiology influence the merit of targeted versus of population-wide interventions for yaws eradication

Infectious disease eradication programs often pursue spatially targeted interventions, but how well they perform might depend on the underlying spatial epidemiology and the specific goal of the program. We use a stochastic compartmental metapopulation model of yaws transmission to investigate how total targeted treatment (TTT) performs compared to mass drug administration (MDA) in different settings. While TTT can efficiently control the prevalence of active yaws disease, we consistently found that multiple rounds of TTT are required to match the impact of 1 round of MDA on the prevalence of latent yaws infection. When complete eradication of yaws is the goal, MDA can achieve the same result as TTT more quickly and probably at lower cost. We found that the performance of TTT is improved when there is little mixing between subpopulations and when there is spatial heterogeneity in transmissibility, but even in these settings, our model suggests that MDA will still outperform TTT.\n\nSignificance StatementYaws is a neglected tropical disease that causes skin lesions. Eradicating yaws is challenging because people can be infected but not show any signs or symptoms for years. Using simulations, we found that targeting antibiotics to people with active yaws and to their neighbors is a good way to combat active yaws, but treating entire populations is a better way to get rid of all infections, including the hidden ones. Also, targeted treatment works better in populations in which people do not move around much and in which how easily the disease is transmitted varies from place to place. Overall, a targeted treatment strategy uses fewer antibiotics but takes longer than mass treatment to achieve results.

epidemiology↗

bioRxiv2019

An Optimized Registration Workflow and Standard Geometric Space for Small Animal Brain Imaging

The reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic workflow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We introduce four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 2-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring workflow robustness, data comparability, and region assignment validity, all of which are indispensable prerequisites for the comparability of scientific results across experiments and centers.

neuroscience↗

bioRxiv2019

High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: a cross-sectional study

BackgroundScabies is a WHO neglected tropical disease common in children in low-and middle-income countries. Excoriation of scabies lesions can lead to secondary pyoderma infection, most commonly by Staphyloccocus aureus and Streptococcus pyogenes (group A streptococcus, GAS), with the latter linked to acute post-streptococcal glomerulonephritis (APSGN) and potentially rheumatic heart disease (RHD). There is a paucity of data on the prevalence of these skin infections and their bacterial aetiology from Africa.\n\nMaterials/methodsA cross-sectional study, conducted over a four-month period that included the dry and rainy season, was conducted to determine the prevalence of common skin infections in Sukuta, a peri-urban settlement in western Gambia, in children <5 years. Swabs from pyoderma lesions were cultured for S. aureus and GAS.\n\nResultsOf 1441 children examined, 15.9% had scabies (95% CI 12.2-20.4), 17.4% had pyoderma (95% CI 10.4-27.7) and 9.7% had fungal infections (95% CI 6.6-14.0). Scabies were significantly associated with pyoderma (aOR 2.74, 95% CI 1.61-4.67). Of 250 pyoderma swabs, 80.8% were culture-positive for S. aureus, and 50.8% for GAS. Participants examined after the first rains were significantly more likely to have pyoderma than those examined before (aRR 2.42, 95% CI 1.38-4.23), whereas no difference in scabies prevalence was seen (aRR 1.08, 95% CI 0.70-1.67). Swab positivity was not affected by the season.\n\nConclusionsHigh prevalence of scabies and pyoderma were observed. Pyoderma increased significantly during rainy season. Given the high prevalence of GAS pyoderma among children, further research on the association with RHD in West Africa is warranted.\n\nSummaryThis cross-sectional study of skin infections in The Gambia revealed prevalence of scabies, pyoderma and fungal infections in children <5 years of 15.9%, 17.4% and 9.7% respectively, with increased bacterial skin infections in the rainy season.

epidemiology↗

bioRxiv2019

Perceptions, attitudes and practices towards scabies in communities on the Bijagos Islands, Guinea-Bissau

IntroductionScabies is highly endemic among impoverished populations and has been recently included in the WHOs list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and health care-seeking behaviours towards scabies in the Bijagos Archipelago of Guinea-Bissau. MethodsData were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis. ResultsThere was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance. ConclusionsThere is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers training and skin NTDs integrated control programmes should address the challenges highlighted in this study. Authors SummaryScabies is a common skin infection in low income settings. We conducted a study in Guinea-Bissau to explore the knowledge, attitudes and practices about scabies. We conducted interviews with healthcare workers, traditional healers and community members and additionally used an oral-administered questionnaire with a larger sample of community residents. Most individuals had knowledge of scabies and were aware that person to person transmission occurred. However personal and environmental hygiene were both incorrectly identified as particularly important in the transmission of scabies. Cost played a major role in determining where individuals sought care and both poverty and disease associated stigma resulted in delays seeking care. There is a need to improve community and health care worker education about scabies and improve affordable access to treatment.

epidemiology↗

bioRxiv2018

Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages

Syphilis is a sexually transmitted infection caused by Treponema pallidum subspecies pallidum and may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. We used direct sequencing of T. pallidum combined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously, incompatible with the notion that SS14-lineage expansion is driven purely by macrolide resistance. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves in Treponema subspecies and provide a warning on broader issues of antimicrobial resistance.

genomics↗