Biology subjects

Clement, P.

Publications and source records attributed to Clement, P..

7 recordsLinked to original sources

bioRxiv2026

Aesthetic Appreciation and Environmental Values: A Cross-Cultural Study of Teachers in 34 Countries

BackgroundThe relationship between aesthetic appreciation and environmental values remains a critical yet under-researched area in environmental psychology. Although the Two-Major Environmental Values (2-MEV) model--encompassing preservation and utilization dimensions--serves as a standard framework for assessing environmental attitudes, the integration of aesthetic perception within this structure has largely remained unexplored. This study investigates the conceptual linkages across a diverse international sample to determine whether aesthetic appreciation functions independently of a traditional environmental value framework. Methods and FindingsWe conducted a large-scale, cross-sectional survey involving 11,800 pre- and in-service teachers across 34 countries. Participants environmental values were evaluated using the 2-MEV scale, while their aesthetic appreciation of nature and the built environment was assessed using Osgoods semantic differential technique. Employing principal component analysis, hierarchical exploratory factor analysis (EFA), analysis of variance (ANOVA), and within-class analysis (WCA), we accounted for cross-national variations and evaluated response consistency. The results demonstrate that aesthetic appreciation comprises two distinct dimensions-- focusing separately on nature and the built environment--that operate independently of traditional preservation and utilization values, showing only weak correlations. Furthermore, while the overarching psychological structure remains consistent globally, our findings reveal significant cross-national variations in respondent scores, particularly concerning utilization-related values. ConclusionsThese findings establish that aesthetic appreciation constitutes a distinct psychological construct separate from conventional environmental value frameworks. The observed cross-cultural variability underscores the necessity of accounting for national and cultural contexts when designing environmental education programs. By leveraging a robust, comprehensive global dataset, this study provides a vital empirical foundation for integrating aesthetic and value-based dimensions into future environmental research and educational policy.

scientific communication and education↗

bioRxiv2026

Longitudinal tumor ecosystem mapping defines glioblastoma treatment trajectories

Glioblastoma remains an invariably recurring and lethal brain tumor shaped by complex interactions between malignant and microenvironmental cells. How these interactions evolve under first-line standard-of-care (SOC) therapy remains unclear. We performed spatial single-cell profiling of 671 paired newly diagnosed and recurrent glioblastoma samples from 96 patients to map tumor-ecosystem evolution and its clinical relevance. We delineated five distinct patient subgroups, each characterized by unique ecosystem trajectories that correlated with clinical outcome. Patients whose tumors transitioned into oligodendrocyte-progenitor-like niches with enhanced vascular integrity, oxygenation and an IL10/CCL/MHCII immunomodulatory environment experienced improved clinical prognosis. In contrast, progression towards hypoxic mesenchymal/astrocyte-like niches dominated by strong LGALS1/SPP1/TGF{beta} immunosuppression predicted poor outcome. Furthermore, a subgroup of early-relapsing patients on SOC therapy that was characterized by a depletion of an antigen-presenting myeloid-cell-rich niche, exhibited diminished responsiveness to second-line lomustine therapy. Overall, mapping evolutions in glioblastoma ecosystems offers a novel framework for prognostic stratification and therapeutic guidance.

cancer biology↗

bioRxiv2025

Mapping Leukocyte Dynamics during Neuroinflammation Identifies Meningeal Monocyte-Derived Macrophages as Drivers of Progressive Disease

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by increasing disability. The cellular and molecular drivers of clinical transition towards progressive disease are poorly understood. Here, we combine single-cell profiling technologies with genetic and pharmacological perturbations across the course of murine CNS inflammation to dissect the role of the local immune landscape in disease progression. We uncover a chronic monocyte-to-phagocyte transition as a hallmark of progressive disease, characterized by the emergence of maladaptive, lipid-associated macrophages (LAMs) marked by lysosomal activation and fibrotic features. Spatial transcriptomics and multiplexed imaging revealed that these LAMs localized to the leptomeninges in close proximity to parenchymal colony-stimulating factor (CSF)-1 producing disease-associated microglia (DAMs) and meningeal granulocyte-macrophage (GM)-CSF-expressing T helper cells that license their differentiation. Interference with this local cytokine network revealed a protective role for resident microglia and implicated monocyte-derived phagocytes as key drivers of progressive neuroinflammation. Notably, LAM-like macrophages could also be identified in the meninges of people with MS, indicating a homology to human disease. By elucidating their ontogeny, spatial niche, and regulatory cytokine milieu, we provide a mechanistic framework for targeting harmful myeloid states while preserving reparative CNS immunity in progressive MS.

immunology↗

bioRxiv2024

Monocyte-derived cells but not Microglia cause Oxidative Tissue Damage in Neuroinflammation

Multiple sclerosis (MS) is characterized by neuroinflammation, oxidative stress, iron toxicity and mitochondrial dysfunction. Reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs) are widely held to drive tissue damage, yet the specific roles of central nervous system (CNS)- resident versus CNS-invading MPs remain unclear. Here, by combining single-cell profiling with conditional gene targeting, we systematically dissected and interfered with ROS production across CNS MPs in a preclinical model for neuroinflammation. We show that CNS-invading monocyte derived cells (MdCs) exhibit a higher oxidative stress gene signature and produce more ROS compared to CNS-resident microglia. While NADPH oxidase 2 (NOX2), a phagocytic source of ROS, proved redundant, our findings underscore the critical role of mitochondrial ROS (mtROS) in driving oxidative tissue damage. Quenching mtROS through mitocatalase overexpression in MdCs, but not microglia, significantly alleviated neuroinflammation in mice. Thus, our study resolves a longstanding controversy, identifying MdCs as the primary driver of ROS-mediated neuropathology.

immunology↗

bioRxiv2022

Single-cell molecular profiling using ex vivo functional readouts fuels precision oncology in glioblastoma

BackgroundFunctional profiling of freshly isolated glioblastoma cells is being evaluated as a next-generation method for precision oncology. While promising, its success largely depends on the method to evaluate treatment activity which requires sufficient resolution and specificity. MethodsHere, we describe the precision oncology by single-cell profiling using ex vivo readouts of functionality (PROSPERO) assay to evaluate the intrinsic susceptibility of high- grade brain tumor cells to respond to therapy. Different from other assays, PROSPERO extends beyond life/death screening by rapidly evaluating acute molecular drug responses at single-cell resolution. ResultsThe PROSPERO assay was developed by correlating short-term single-cell molecular signatures using CyTOF to long-term cytotoxicity readouts in representative patient- derived glioblastoma cell cultures (n=14) that were exposed to radiotherapy and the small- molecule p53/MDM2 inhibitor AMG232. The predictive model was subsequently projected to evaluate drug activity in freshly resected GBM samples from patients (n=34). Here, PROSPERO revealed an overall limited capacity of tumor cells to respond to therapy, as reflected by the inability to induce key molecular markers upon ex vivo treatment exposure, while retaining proliferative capacity, insights that were validated in PDX models. This approach also allowed the investigation of cellular plasticity, which in PDCLs highlighted therapy-induced proneural-to-mesenchymal transitions, while in patients samples this was more heterogeneous. ConclusionPROSPERO provides a precise way to evaluate therapy efficacy by measuring molecular drug responses using specific biomarker changes in freshly resected brain tumor samples, in addition to providing key functional insights in cellular behavior, which may ultimately complement standard, clinical biomarker evaluations.

cancer biology↗

bioRxiv2020

DNA methylation and survival differences associated with the type of IDH mutation in 1p/19q non-codeleted astrocytomas

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. This high prevalence is important as IDH1R132H is presumed to be relatively poor at producing D-2-hydroxyglutarate (D-2HG) whereas high concentrations of this oncometabolite are required to inhibit TET2 DNA demethylating enzymes. Indeed, patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of site of origin. For 1p/19q non-codeleted glioma patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring non-R132H mutated tumours have better outcome (HR 0.41, 95% CI [0.24, 0.71], p=0.0013). Non-R132H mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p<0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H mutated 1p/19q non-codeleted gliomas have a more favourable prognosis than their IDH1R132H mutated counterpart is clinically relevant and should be taken into account for patient prognostication. Single sentence summaryAstrocytoma patients with tumours harbouring IDH mutations other than p.R132H have increased DNA methylation levels and longer survival

cancer biology↗

bioRxiv2019

ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. The toolbox adheres to previously defined international standards for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts to increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

neuroscience↗