Biology subjects

Brunet, J.

Publications and source records attributed to Brunet, J..

29 records · Page 2Linked to original sources

bioRxiv2025

On the edge of extinction: Delayed plant genetic response to forest edge dynamics

Understanding genetic responses to forest dynamics is essential for predicting the long-term viability of understory plant populations and for developing effective conservation strategies. This study investigates genetic extinction debt and colonization credit in Circaea lutetiana, a clonal forest understory species, across its European range. Using pooled genotype-by-sequencing data from 40 forest edge and core populations, we examined to what extent population size, latitude and historical changes in forest configuration predict genetic diversity. Our findings reveal that the historical forest configuration profoundly shapes present-day genetic diversity. Long-established forest edge populations exhibit significantly reduced allelic richness (-9%) compared to core populations, indicating the partial pay-off of a genetic extinction debt. In contrast, populations from recently established forest edges maintain comparable allelic richness to core populations, suggesting delayed population genetic responses to land use changes. Finally, populations established in areas that were afforested during the past 250 years exhibit lower genetic diversity than historical forest core populations, indicating a delay in genetic recovery and thus a potential genetic colonization credit. Our results highlight that C. lutetiana populations are not at equilibrium with the current forest configuration, underscoring the role of lagged genetic responses across very long time scales. Connectivity and population size further moderate genetic diversity, with smaller, isolated populations particularly vulnerable to genetic erosion. Given the limited research on delayed evolution in forest understory species, our results improve the understanding of extinction risk dynamics and underscore the need for history-informed restoration efforts.

ecology↗

bioRxiv2024

Vasculature segmentation in 3D hierarchical phase-contrast tomography images of human kidneys

Efficient algorithms are needed to segment vasculature in new three-dimensional (3D) medical imaging datasets at scale for a wide range of research and clinical applications. Manual segmentation of vessels in images is time-consuming and expensive. Computational approaches are more scalable but have limitations in accuracy. We organized a global machine learning competition, engaging 1,401 participants, to help develop new deep learning methods for 3D blood vessel segmentation. This paper presents a detailed analysis of the top-performing solutions using manually curated 3D Hierarchical Phase-Contrast Tomography datasets of the human kidney, focusing on the segmentation accuracy and morphological analysis, thereby establishing a benchmark for future studies in blood vessel segmentation within phase-contrast tomography imaging.

bioinformatics↗

bioRxiv2024

Admixture with cultivated sunflower likely facilitated establishment and spread of wild sunflower (H. annuus) in Argentina

A better understanding of the genetic and ecological factors underlying successful invasions is critical to mitigate the negative impacts of invasive species. Here, we study the invasion history of Helianthus annuus populations from Argentina, with particular emphasis on the role of post-introduction admixture with cultivated sunflower (also H. annuus) and climate adaptation driven by large haploblocks. We conducted genotyping-by-sequencing of samples of wild populations as well as Argentinian cultivars and compared them with wild (including related annual Helianthus species) and cultivated samples from the native range. We also characterized samples for 11 known haploblocks associated with environmental variation in native populations to test whether haploblocks contributed to invasion success. Population genomics analyses supported two independent geographic sources for Argentinian populations, the central United States and Texas, but no significant contribution of related annual Helianthus species. We found pervasive admixture with cultivated sunflower, likely as result of post-introduction hybridization. Genomic scans between invasive populations and their native sources identified multiple genomic regions with evidence of selection in the invaded range. These regions significantly overlapped between the two native-invasive comparisons and showed disproportionally high crop ancestry, suggesting that crop alleles contributed to invasion success. We did not find evidence of climate adaptation mediated by haploblocks, yet outliers of genome scans were enriched in haploblock regions and, for at least two haploblocks, the cultivar haplotype was favored in the invaded range. Our results show that admixture with cultivated sunflower played a major role in the establishment and spread of H. annuus populations in Argentina.

evolutionary biology↗

bioRxiv2023

Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT)

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one control without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac blueprint with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.

pathology↗

bioRxiv2023

A closer look at high-energy X-ray-induced bubble formation during soft tissue imaging

Improving the scalability of tissue imaging throughput with bright, coherent X-rays requires identifying and mitigating artifacts resulting from the interactions between X-rays and matter. At synchrotron sources, long-term imaging of soft tissues in solution can result in gas bubble formation or cavitation, which dramatically compromises image quality and integrity of the samples. By combining in-line phase-contrast cineradiography with operando gas chromatography, we were able to track the onset and evolution of high-energy X-ray-induced gas bubbles in ethanol-embedded soft tissue samples for tens of minutes (2 to 3 times the typical scan times). We demonstrate quantitatively that vacuum degassing of the sample during preparation can significantly delay bubble formation, offering up to a twofold improvement in dose tolerance, depending on the tissue type. However, once nucleated, bubble growth is faster in degassed than undegassed samples, indicating their distinct metastable states at bubble onset. Gas chromatography analysis shows increased solvent vaporization concurrent with bubble formation, yet the quantities of dissolved gases remain unchanged. Coupling features extracted from the radiographs with computational analysis of bubble characteristics, we uncover dose-controlled kinetics and nucleation site-specific growth. These hallmark signatures provide quantitative constraints on the driving mechanisms of bubble formation and growth. Overall, the observations highlight bubble formation as a critical, yet often overlooked hurdle in upscaling X-ray imaging for biological tissues and soft materials and we offer an empirical foundation for their understanding and imaging protocol optimization. More importantly, our approaches establish a top-down scheme to decipher the complex, multiscale radiation-matter interactions in these applications. Significance statementBetter probing the X-ray radiation dose limit of bubble formation in biological tissue and developing mitigation methods is essential for improving imaging techniques involving X-ray, such as synchrotron X-ray tomography or crystallography. Here, we combined operando gas chromatography with in-line X-ray phase-contrast radiography on human lung and brain tissue to investigate bubble formation under high-energy X-ray irradiation. We demonstrate that vacuum degassing delays bubble nucleation up to a factor two, depending on the tissue type. Gas chromatography analysis showed increased solvent vaporization during bubble formation; however, the quantities of dissolved gases remained unchanged. Moreover, depending on the nucleation site, bubble growth can be geometrically constrained by sample microstructure, which influence its dynamics.

biochemistry↗

bioRxiv2022

Persistence of cultivar alleles in wild carrot (Daucus carota L.) populations in the United States

Cultivated species and their wild relatives often hybridize in the wild and crop-wild hybrids can survive and reproduce in some environments. However, it is unclear whether crop alleles are permanently incorporated into the wild genomes in the long run or whether they are purged by natural selection. This question is key to accurately assessing the risk of escape and spread of cultivar genes into wild populations. Here, we use genomic data and population genomic methods to study hybridization and introgression between cultivated and wild carrots (Daucus carota L.) in the United States. We used single nucleotide polymorphisms (SNPs) obtained via genotyping by sequencing for 450 wild individuals from 29 wild georeferenced populations in seven states and 144 cultivars from the United States, Europe, and Asia. Cultivated and wild carrots formed two well differentiated groups, and evidence of crop-wild admixture was detected in several but not all the wild populations in the United States. Two regions were identified where cultivar alleles were introgressed into wild carrots: California and the Nantucket Island, in Massachusetts. In these areas, we found no support for adaptive (or maladaptive) introgression, instead, most crop alleles seemed to be neutral. Surprisingly, there was no evidence of introgression in some populations with a long-known history of sympatry with the crop, suggesting that post-hybridization barriers might prevent introgression in some areas. Further studies are needed to better delineate the geographic patterns of introgression, but our results support the introgression and persistence of cultivar genes in wild carrot populations.

evolutionary biology↗

bioRxiv2022

Preparation of large biological samples for high-resolution, hierarchical, multi-modal imaging

Imaging the different scales of biological tissue is essential for understanding healthy organ behavior and pathophysiological changes. X-ray micro-tomography using both laboratory ({micro}CT) and synchrotron sources (sCT) is a promising tool to image the 3D morphology at the macro- and micro-scale of large samples, including intact human organs. Preparation of large samples for high resolution imaging techniques remains a challenge due to limitations with current methods, such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe a protocol to prepare, stabilize, and image large soft-tissue samples with X-ray microtomography. We demonstrate the protocol using intact human organs and Hierarchical Phase-Contrast Tomography (HiP-CT) imaging at the European Synchrotron Radiation Facility, but the protocol is equally applicable to a range of biological samples, including complete organisms, for both laboratory and synchrotron source tomography. Our protocol enhances the contrast of the sample, while preventing sample motion during the scan, even in case of different sample orientations. Bubbles trapped during mounting and those formed during scanning (in case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging (MRI), CT, and histological observation. We describe a protocol for sample preparation and mounting which requires 25 to 34 days for a large organ such as an intact human brain or heart. This preparation time varies depending on the composition, size, and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local pixel size of one micron using HiP-CT.

physiology↗

bioRxiv2022

Differential ability of three bee species to move genes via pollen

Since the release of genetically engineered (GE) crops, there has been increased concern about the introduction of GE genes into non-GE fields of a crop and their spread to feral or wild cross-compatible relatives. More recently, attention has been given to the differential impact of distinct pollinators on gene flow, with the goal of developing isolation distances associated with specific managed pollinators. To examine the differential impact of bee species on gene movement, we quantified the relationship between the probability of getting a GE seed in a pod, and the order in which a flower was visited, or the cumulative distance travelled by a bee in a foraging bout. We refer to these relationships as seed curves and compare these seeds curves among three bee species. The experiments used Medicago sativa L. plants carrying three copies of the glyphosate resistance (GR) allele as pollen donors, such that each pollen grain carried the GR allele, and conventional plants as pollen recipients. Different foraging metrics, including the number of GR seeds produced over a foraging bout, were also quantified and contrasted among bee species. Leafcutting bees produced the lowest number of GR genes in a foraging bout, and moved them the shortest distances, bumble bees the longest. Values for honey bees were intermediate. Seed curves correlated with field-based gene flow estimates. Thus, differential seed curves of bee species, reflecting within foraging bout patterns, translated into distinct abilities of bee species to move genes at a landscape level. Differences in seed curves reflected differences in foraging behavior among bee species, and helped explain their differential impact on gene flow and the spread of GE genes in insect-pollinated crops.

plant biology↗

bioRxiv2022

Protein undernutrition reduces the efficacy of praziquantel in a murine model of Schistosoma mansoni infection

BackgroundUndernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a protein-deficient diet on the efficacy of praziquantel. Methodology/principal findingsThirty-day-old mice were fed with a protein-deficient diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins at the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the protein-deficient diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and {gamma}-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1 and CXCL-10/IP-10 induced by S. mansoni infection. Conclusion/significanceThese results demonstrated that a protein-deficient diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel. Authors summaryAlmost 90% of people requiring schistosomiasis preventive chemotherapy in 2018 lived in sub-Saharan Africa. Besides, 205.3 million children under five years suffer and die of undernutrition in low- and middle-income countries. The physiopathology of schistosomiasis mansoni involves liver damage, oxidative stress, and perturbation of the immune response. These disturbances are intensified by undernutrition. Praziquantel is used to treat schistosomiasis, but its efficacy on the comorbidity of S. mansoni infection and undernutrition has not been investigated. We conducted this study to assess the effectiveness of praziquantel on S. mansoni infection in mice fed with a protein-deficient diet. We recorded growth retardation, hepatomegaly, and high worm and egg burdens in mice fed with a protein-deficient diet and treated with PZQ. Moreover, the treatment did not reverse the liver function injury, oxidative stress, high iron level, and low calcium level. The proinflammatory cytokine IL-5 was still high, and the gene expression of some macrophage-associated chemokines was reduced. Therefore, this study demonstrated that in a murine model of a protein-deficient diet, the efficacy of praziquantel on S. mansoni infection was reduced. It also underlines the importance of targeting protein deficiency and malnutrition in populations living in schistosomiasis endemic areas for efficient disease control.

pathology↗

bioRxiv2019

Benchmark of tools for CNV detection from NGS panel data in a genetic diagnostics context

MotivationAlthough germline copy number variants (CNVs) are the genetic cause of multiple hereditary diseases, detecting them from targeted next-generation sequencing data (NGS) remains a challenge. Existing tools perform well for large CNVs but struggle with single and multi-exon alterations. The aim of this work is to evaluate CNV calling tools working on gene panel NGS data with CNVs up to single-exon resolution and their suitability as a screening step before orthogonal confirmation in genetic diagnostics strategies. ResultsFive tools (DECoN, CoNVaDING, panelcn.MOPS, ExomeDepth and CODEX2) were tested against four genetic diagnostics datasets (495 samples, 231 CNVs), using the default and sensitivity-optimized parameters. Most tools were highly sensitive and specific, but the performance was dataset-dependant. In our in-house datasets, DECoN and panelcn.MOPS with optimized parameters showed enough sensitivity to be used as screening methods in genetic diagnostics. AvailabilityBenchmarking-optimization code is freely available at https://github.com/TranslationalBioinformaticsIGTP/CNVbenchmarkeR.

bioinformatics↗

bioRxiv2018

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg=0.57, p=4.6x10-8), breast and ovarian cancer (rg=0.24, p=7x10-5), breast and lung cancer (rg=0.18, p=1.5x10-6) and breast and colorectal cancer (rg=0.15, p=1.1x10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

genomics↗