Biology subjects

Diop, M.

Publications and source records attributed to Diop, M..

10 recordsLinked to original sources

bioRxiv2026

New whole slide image analysis method for detection and quantification of hepatocellular vacuolization in European flounder (Platichthys flesus) in multipollutant exposure context

A new whole slide image analysis method was developed for hepatocellular vacuolization detection and quantification in European flounder (Platichthys flesus) liver. Histopathological quantification allows a better understanding of how contaminants and biotic factors might influence lesion pathogenesis in a multipollutant exposure context. One of the main findings is the significant difference in the extent of the pathology between the polluted and the control sites,with P. flesus sampled in the Seine estuary presenting a higher proportion of tissue affected by hepatocellular vacuolation (6.88 sd. 3.01%) compared to fish sampled in the Canche estuary (5.46 sd. 2.86%). This result is coherent with the previous qualitative histological assessment done on the same histological samples, it helps validate the method and brings new insight into the pathology intensity level with the level of contamination on each site. The other main finding is the potential synergetic effect of the pollutant mixture on the pathology. The multipollutant analysis showed a positive mixture effect on the proportion of tissue affected by hepatocellular vacuolation in fish from the Seine estuary, while this effect is not observed in fish sampled in the Canche estuary. This study highlights the benefits of developing novel bio-image analysis methods for environmental research. Histopathological diagnostic quantification allows a better understanding of the potential factors inducing and exacerbating the pathology, as well as the potential mixture effect in a context of multipollutant contamination.

pathology↗

bioRxiv2025

Systemic immune dysregulation in hypertensive disorders of pregnancy persists years after delivery

BackgroundHypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are associated with an increased risk of cardiovascular disease (CVD) later in life. Mechanisms that link HDP to CVD, however, remain unclear. MethodsWe used a high-dimensional single-cell mass cytometry approach to profile the distribution and functional responses of maternal immune cells in three separate groups of HDP cases and normotensive controls, sampled antepartum, postpartum, and several years postpartum (midlife). We used multivariable sparse modeling to distinguish HDP cases from controls. ResultsWe accurately distinguished HDP cases from controls at all three study timepoints, with area under the receiver operator characteristic (AUROC) curve values of 0.814 for the antepartum group, 0.757 for the postpartum group, and 0.692 for the midlife group. Distinct immune signatures for each model underscore the dynamic dysregulation of the immune system throughout life. In addition, we identified a persistent immune dysregulation signal among HDP cases at all three timepoints, characterized by increased B cell frequency and decreased pSTAT3 response upon cytokine stimulation in classical monocytes. ConclusionsPersistent immune dysregulation among women with a history of an HDP may contribute to elevated long-term risk of CVD development.

immunology↗

bioRxiv2025

Structure-informed evolutionary analysis of the meiotic recombination machinery

Despite being essential for fertility, many proteins involved in meiotic homologous recombination have diverged rapidly. The evolutionary forces driving this divergence remain mostly unknown, in part because of challenges in accounting for the interplay of sequence changes with constraints imposed by proteins structures and physiological roles. Here, we explore strategies to more sensitively detect signatures of positive or relaxed selection by integrating evolutionary analyses with structural and functional information, using meiotic recombination proteins in four taxa--primates, rodents, birds and budding yeasts. By mapping selection rate estimates onto predicted protein structures, we characterized protein regions likely to have experienced positive selection. We further identified subtle sequence variation within protein domains that are well conserved generally because of structural constraints. To detect sequence variation masked by these constraints, we analyzed selection at structurally matched residues, comparing homologs across different lineages as well as between meiosis-specific and generalist paralogs. These approaches identified lineage- and paralog-restricted enrichment of non-synonymous substitutions that may indicate loss of functional constraints and/or adaptive innovation. Finally, we used cross-species complementation experiments in Saccharomyces cerevisiae to show that sequence variation in the pro-crossover factor MSH4 modulates recombination proficiency. We suggest that evolutionary plasticity per se is a key conserved characteristic of the meiotic recombination machinery. More generally, our approach provides a mechanistic framework to analyze protein evolution.

evolutionary biology↗

bioRxiv2025

Single-cell-level digital twins for preterm birth prevention strategies

Digital twin models can accelerate therapeutic development by enabling low-risk testing of candidate interventions. In preterm labor (PTL), a major pregnancy complication where clinical trials face unique ethical and financial barriers, digital twins are especially valuable for evaluating new therapies targeting immune dysfunctions driving PTL. Yet, current models lack single-cell resolution, limiting detection of cell-type-specific mechanisms, off-target effects, and the design of personalized interventions. We present Simulated Immunome Modeling of Clinical Outcomes (SIMCO), a single-cell-level digital twin framework that models immunomodulatory treatment effects on the timing of labor using immunome-wide, single-cell simulations. SIMCOs digital twins are trained and validated on a newly generated mass cytometry atlas of the pregnant immunome exposed to nine candidate drugs preselected for PTL prevention. Applying SIMCO to an independent cohort of pregnant individuals, we simulate treatment effects on gestational length, screening for candidate drugs that delay labor timing and providing system-level mechanistic insight for each drug candidate. Tetrahydrofolate, maprotiline, and the combination of aspirin and lansoprazole emerged as top candidates for PTL prevention, delaying labor onset primarily through enhanced mTOR signaling in innate immune cells and attenuated JAK/STAT signaling in naive CD4 T cells. The codebase is available at https://github.com/ofondeur/SIMCO/.

immunology↗

bioRxiv2025

How fast can PPRV spread? Analyzing the results of an experimental PPRV infection of goats equipped with Ultra-WideBand sensors

Peste des Petits Ruminants (PPR) is a highly contagious disease affecting goats and sheep. The speed and extent of its spread depend on contact patterns and the viruss intrinsic characteristics. To estimate propagation speed and the role of inter-individual patterns, we analyzed the results of a series of 12 experimental infections conducted in five different sessions, involving six or seven goats in a secured stable. In each experiment, one animal was inoculated with the PPR strain and placed in contact with the other naive animals. All the animals were equipped with Ultra-WideBand sensors to collect inter-individual distance data. The duration of this phase varied from 1 to 48 hours across the experiments. Afterwards, the animals were isolated and monitored for three to five weeks. Temperature, symptoms, nasal and ocular discharges, and blood samples were routinely collected to detect the presence of the virus. Using Bayesian statistical analysis, data on inter-individual distances, and health status were analyzed to estimate R0, the incubation period, and PPRV transmissibility. The latter was used to estimate the exposure period, i.e., the minimum amount of time for a naive animal to become infected. Of the 70 naive animals exposed to the virus, 18 were infected. R0 was estimated to be around 4.3 or 8.6, depending on the infectious period value. The incubation period was estimated to be around 16.3 days (95% CI: 12.6-23.3 days). The exposure time varies greatly depending on the density, ranging from nearly two days at low density to around four hours at high density. Large gatherings of animals, such as at livestock markets, could greatly facilitate the spread of PPRV. Furthermore, the long incubation period coupled with livestock mobility could favor the virus geographical dissemination on a large scale. Author summaryPPR is an infectious disease that is transmitted directly and affects goats and sheep. Since its discovery in the Ivory Coast in 1942, the PPR virus has spread worldwide, reaching China in 2010 and Europe in 2018. Despite the fact that PPR poses a huge threat to the lives of small ruminants and the livelihoods of smallholders, more research is needed into its epidemic potential and transmission speed. Here, we used a combined approach of experimental infections and contact tracing with UWB devices to estimate the probability of transmission of a specific PPRV strain, and to determine the minimum exposure time required for an animal to become infected. Our results indicate that reducing the average distance between animals by a factor of four could reduce exposure time tenfold, indicating a much higher risk for high-density herds compared to roaming ones. Coupled with new estimates of R0 and incubation time inferred from data analysis, our work sheds light on the danger posed by PPR. These informations are valuable to veterinarians and policymakers, to better assess the risk of introduction, spread, and impact of PPR, to implement timely and effective interventions.

animal behavior and cognition↗

bioRxiv2025

A Transcriptomics-Based Computational Drug Repositioning Pipeline Identifies Simvastatin And Primaquine As Novel Therapeutics For Endometriosis Pain

Endometriosis has limited treatment options, prompting the search for novel therapeutics. We previously used a transcriptomics-based computational drug repositioning pipeline to analyze public bulk transcriptomic data of eutopic endometrium from cases and controls and identified several drug candidates. Fenoprofen, our top in silico candidate, was validated in a rat model of endometriosis-associated pain. Building on this, we evaluated herein two additional candidates, simvastatin (a cholesterol-lowering drug) and primaquine (an antimalarial), based on strong endometrial gene expression reversal scores and favorable safety profiles. Using the rat model, we conducted behavioral testing, bulk RNA sequencing, and differential expression analysis to assess their therapeutic potential. We also assessed endometriosis diagnosis among patients prescribed simvastatin in electronic medical records (EMR) across six University of California (UC) healthcare institutions. In vivo validation using a rat model of endometriosis demonstrated that both simvastatin and primaquine significantly reduced vaginal hyperalgesia, a surrogate marker of endometriosis-related pain. RNA-seq of uteri and lesions confirmed reversal of disease-associated gene expression signatures following treatment. Analysis of UC-wide EMR data found lower relative risk of endometriosis among those prescribed simvastatin compared to a matched control group. Overall, simvastatin and primaquine attenuated pain-associated behaviors and reversed endometriosis-related gene expression changes in an animal model. Moreover, simvastatin prescription was associated with a lower relative risk of endometriosis in our retrospective multi-center cohort study. These findings highlight their potential as repurposed therapeutics for endometriosis and support the effectiveness of computational drug repositioning in identifying new treatment strategies. One Sentence SummarySimvastatin and primaquine reduced endometriosis pain and reversed gene signatures, with simvastatin also linked to lower disease risk.

bioinformatics↗

bioRxiv2025

Aging-dependent dysregulation of EXOSC2 is maintained in cancer as a dependency

Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.

cell biology↗

bioRxiv2025

Anticlustering for Sample Allocation To Minimize Batch Effects

High throughput sequencing is a powerful tool for processing large amounts of DNA and RNA samples in batches. Proper experimental design and statistical methods are required to mitigate systematic technical factors due to differences in batches ("batch effects"), as data variation due to these non-biological factors can mask actual biological differences. We propose using anticlustering as an automated method to assign samples to balanced batches. Anticlustering effectively negates differences in (numeric and/or categorical) covariates among batches, and implements user-defined restrictions on the number of batches, the number of samples per batch, and whether to assign certain samples to the same batch ("must-link constraints"). A simulation study shows that anticlustering is better at achieving balance among batches than previous approaches. An application from the UCSF-Stanford Endometriosis Center for Discovery, Innovation, Training and Community Engagement ("ENACT", https://enactcenter.org/) is presented as a real-life example. In the application, multiple samples provided by an individual had to be processed on the same batch, so that comparisons among different samples of the same patient were not diluted by batch effects. The novel Two Phase Must Link (2PML) anticlustering algorithm realized the must-link restrictions while simultaneously obtaining balance among batches regarding disease stage, menstrual cycle phase, case versus control sample, and clinical site. All methods presented here are accessible via the free and open source R package anticlust (https://cran.r-project.org/package=anticlust). An interactive visualization and web-based batch assignment tool are made available in the Rshiny app "anticlust" (https://anticlust.org/).

bioinformatics↗

bioRxiv2019

Feeding behavior of Aedes (Aedimorphus) vexans arabiensis, a Rift valley fever virus vector in the Ferlo pastoral ecosystem of Senegal.

Host-vector contact is a key factor in vectorial capacity assessment and thus the transmission of mosquito-borne viruses such as Rift Valley Fever (RVF), an emerging zoonotic disease of interest in West Africa. The knowledge of the host-feeding patterns of vector species constitutes a key element in the assessment of their epidemiological importance in a given environment. The aim of this work was to identify the blood meal origins of Aedes vexans arabiensis Patton (Diptera: Culicidae), the main vector of RVF virus in the Ferlo pastoral ecosystem of Senegal. Engorged female mosquitoes were collected in Younoufere in the pastoral ecosystem in the Ferlo region during the 2014 rainy season. CDC light CO2-baited traps were set at six sites for two consecutive nights every month from July to November. Domestic animals present around traps were identified and counted for each trapping session. Blood meal sources of engorged mosquitoes were identified using a vertebrate-specific multiplexed primer set based on cytochrome b. Blood meal sources were successfully identified for 319 out of 416 blood-fed females (76.68%), of which 163 (51.1%) were single meals, 146 (45.77%) mixed meals from two different hosts and 10 (3.13%) mixed meals from three different hosts. Aedes vexans arabiensis fed preferentially on mammals especially on horse compared to other hosts (P < 0.001). Proportions of single and mixed meals showed significant temporal (P < 0.001) and spatial variations (P < 0.001) according to hosts availability. Aedes vexans arabiensis shows an opportunistic feeding behavior depending on the host availability. Results were discussed in relation with the Rift valley fever virus transmission and vector involvement as well as its primary hosts.

epidemiology↗

bioRxiv2018

Assessing the response of small RNA populations to allopolyploidy using resynthesized Brassica napus allotetraploids

Allopolyploidy, combining interspecific hybridization with whole genome duplication, has had significant impact on plant evolution. Its evolutionary success is related to the rapid and profound genome reorganizations that allow neo-allopolyploids to form and adapt. Nevertheless, how neo-allopolyploid genomes adapt to regulate their expression remains poorly understood. The hypothesis of a major role for small non-coding RNAs (sRNAs) in mediating the transcriptional response of neo-allopolyploid genomes has progressively emerged. Generally, 21-nt sRNAs mediate post-transcriptional gene silencing (PTGS) by mRNA cleavage whereas 24-nt sRNAs repress transcription (transcriptional gene silencing, TGS) through epigenetic modifications. Here, we characterize the global response of sRNAs to allopolyploidy in Brassica, using three independently resynthesized B. napus allotetraploids surveyed at two different generations in comparison with their diploid progenitors. Our results suggest an immediate but transient response of specific sRNA populations to allopolyploidy. These sRNA populations mainly target non-coding components of the genome but also target the transcriptional regulation of genes involved in response to stresses and in metabolism; this suggests a broad role in adapting to allopolyploidy. We finally identify the early accumulation of both 21- and 24-nt sRNAs involved in regulating the same targets, supporting a PTGS-to-TGS shift at the first stages of the neo-allopolyploid formation. We propose that reorganization of sRNA production is an early response to allopolyploidy in order to control the transcriptional reactivation of various non-coding elements and stress-related genes, thus ensuring genome stability during the first steps of neo-allopolyploid formation.

evolutionary biology↗