Oskar Bordeaux
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Biometrics
No full textMediation analysis aims to decipher the underlying causal mechanisms between an exposure, an outcome, and intermediate variables called mediators. Initially developed for fixed-time mediator and outcome, it has been extended to the framework of longitudinal data by discretizing the assessment times of mediator and outcome. Yet, processes in play in longitudinal studies are usually defined in continuous time and measured at irregular and subject-specific visits. This is the case in dementia research when cerebral and cognitive changes measured at planned visits in cohorts are of interest. We thus propose a methodology to estimate the causal mechanisms between a time-fixed exposure (), a mediator process (), and an outcome process () both measured repeatedly over time in the presence of a time-dependent confounding process (). We consider 2 types of causal estimands, the natural effects and path-specific effects. We provide identifiability assumptions, and we employ a multivariate mixed model based on differential equations for their estimation. The performances of the method are assessed in simulations, and the method is illustrated in 2 real-world examples motivated by the 3C cerebral aging study to assess (1) the effect of educational level on functional dependency through depressive symptomatology and cognitive functioning and (2) the effect of a genetic factor on cognitive functioning potentially mediated by vascular brain lesions and confounded by neurodegeneration
iScience
Get PDFAdeno-associated virus (AAVs) with a self-complementary genome (sc) comprising a gene of interest are used in gene therapy. Their efficiency is limited but the molecular factors contributing to this restriction are poorly understood. We utilized scAAV2 containing a fluorescent protein-binding anchor sequence on its genome allowing visualization of released genomes by time-lapse microscopy. Pairing this technique with capsid staining, we showed that scAAV2 genome release was initiated by a partial genome exposure, triggered by elevated calcium levels while the capsids interacted with proteins of the nuclear pore. Genome release occurred subsequently requiring Rad52 decamerization in the vicinity of the host chromatin. A fraction of the released genomes was degraded by Mre11, an essential factor for chromatin stability, and cellular DNA double-strand breaks. These steps were key-factors limiting transduction, suggesting that temporary modulation of DNA damage-response-proteins is a promising way to increase scAAV efficiency in therapy
Mating before host colonization: a common trait in outbreeding Scolytinae, potentially linked to invasiveness
No full textLittle is known about the influence of mating strategies that could potentially facilitate the colonization of new hosts in outbreeding species of the weevil subfamily Scolytinae. Individuals typically emerge from their host tree, disperse, and then mate with unrelated conspecifics in a new host where the females establish maternal galleries. Yet, in several species commonly classified as outbreeding, females have been found already mated before host colonization. Precolonization mating provides female with a sperm supply before they find a new host and allows them to establish a maternal gallery on their own. We compared the proportion of females mated before host colonization across 18 European and four American outbreeding Scolytinae species using a phylogenetically controlled analysis. To this end, we determined whether females caught in the spring had sperm in their spermathecae. We found that a proportion of females (range: 16-100%) mated before host colonization in all 22 species. Moreover, this trait was biased, although not significantly, toward invasiveness. Species known to have established outside their native range (Scolytinae with an Invasion History -SIH) displayed a higher proportion of females mated before host colonization than did species restricted to their native range (non-SIH). In Hylurgus ligniperda (Fabricius), a Palearctic species currently present across the globe, the proportions of females mated before host colonization reach 90% in the species' native range and up to 99% in its nonnative range (Argentina and New Zealand). Overall, these results show that precolonization mating is widespread among the Scolytinae. This trait could enhance the invasive capacities of outbreeding species by allowing females to establish a maternal gallery independently of any male during colonization, thus facilitating the establishment and spread of species introduced in new geographical areas.</div
L'association entre le nématode du pin invasif et un insecte local menace les forêts françaises
No full textDepuis de nombreuses années, le nématode du pin Bursaphelenchus xylophilus, un ver de taille microscopique, est l'auteur de dégâts considérables dans les forêts de pins en Asie et, depuis 1999, en Europe (figure 7.1). Dans sa zone d'origine en Amérique du Nord, où il est largement répandu, cet organisme phytopathogène responsable de la maladie du flétrissement du pin n'affecte apparemment pas l'activité végétale des arbres infestés dans sa gamme d'hôtes d'origine. Ceci est certainement dû à une longue coévolution entre les différents partenaires. En revanche, dans les zones d'introduction, ce nématode est responsable de la mort à grande échelle d'arbres hôtes matures et sans autres facteurs de mortalité au Japon, en Chine, en Corée et aujourd'hui en Europe.C'est en 1999, dans les peuplements de pin maritime au sud de Lisbonne, au Portugal, que le nématode a été détecté pour la première fois en Europe (Mota et al., 1999), la zone infectée atteignant une superficie de plus de 1 Mha en 2006 (Naves et al., 2007) (figure 7.2). Malgré une surveillance accrue et d'importantes mesures d'éradication, un second foyer est détecté dès 2008 à Coimbra, dans le centre du Portugal ( Rodrigues, 2008), puis sur l'île de Madère en 2009 (Fonseca et al., 2012). Tout le territoire est considéré comme zone potentiellement infectée aujourd'hui. En Espagne, ce sont des régions limitrophes qui sont touchées. Des arbres infestés sont régulièrement détectés depuis 2008 en Estrémadure à Castille-et-León (Abelleira et al., 2011) et en Galice depuis 2010 (Robertson et al., 2011).</div
Cureus
No full textThis case report evaluates the efficacy of a personalized, multidisciplinary chronic care management (CCM) program aimed at improving health outcomes for individuals with polychronic conditions within Pakistan's under-resourced healthcare system. Implemented in November 2023, the intervention was designed to help two office employees newly diagnosed with type 2 diabetes and associated comorbidities, such as hypertension and obesity. Over six months, the participants engaged in a structured program that included teleconsultations, personalized care plans, and biweekly follow-ups through a social media application. The 'care team,' comprising doctors, nutritionists, wellness coaches, and care attendants, facilitated these interactions. Specific outcomes included a reduction in hemoglobin A1c (HbA1c) from 15% to 5.4% with a 26.3 kg weight loss for Participant 1 and a 3 kg weight loss with a decrease in HbA1c from 6.5% to 6.1% for Participant 2. This report highlights the potential of comprehensive, integrated, and patient-centered diabetes management to enhance glycemic control and weight management in settings burdened by high disease prevalence and limited healthcare resources
Predictive metabolomic to decipher plant eco-evolutive tendencies
No full textMetabolomics serve as a powerful tool for understanding the biochemical diversity of plants and its relationship with ecological characteristics [1]. Plant metabolic signatures reflect their adaptive strategies, which influence their functional groups, growth forms, and phenological patterns [2]. Recent advancements in machine learning have enhanced the classification and prediction of biological traits derived from complex biochemical datasets [3]. However, the use of metabolomic data for predicting ecological and evolutionary trends in plants remains mostly underexplored. We analyzed the metabolomic profiles of 74 plant species from 38 plant families grown under natural conditions. Different machine learning models were used and enabled us to identify metabolic signatures associated with plant functional groups, growth forms, and phenology with high accuracy, revealing significant correlations between metabolites and botanical traits. Our results demonstrate that metabolomic profiling, along with machine learning, can effectively predict ecological and evolutionary trends in plants. This approach provides a new framework for investigating plant adaptation and ecological strategies.References1. Fiehn O. Metabolomics--the link between genotypes and phenotypes. Plant Mol Biol. 2002 Jan;48(1–2):155–71.2. Petrén H, Anaia RA, Aragam KS, Bräutigam A, Eckert S, Heinen R, et al. Understanding the chemodiversity of plants: Quantification, variation and ecological function. Ecological Monographs. 2024 Nov 1;94(4):e1635.3. Dussarrat T, Prigent S, Latorre C, Bernillon S, Flandin A, Díaz FP, et al. Predictive metabolomics of multiple Atacama plant species unveils a core set of generic metabolites for extreme climate resilience. New Phytologist. 2022;234(5):1614–28
Int.J.Organ.Theory Behav.
No full textPurposeThis study examines whether nurse middle managers’ proactive behavior mediates the relationship between cognitive motivational states (role breadth self-efficacy and positive emotions) and outcomes related to quality of work life (job satisfaction and job stress) and job effectiveness (innovative work behavior and job performance).Design/methodology/approachThe study utilizes two-wave survey data from 152 nurse middle managers. Structural equation modeling was used to test whether proactive behavior mediates the effects of role breadth self-efficacy and positive emotions on both quality of work life and job effectiveness outcomes.FindingsFindings indicate that cognitive motivational states (role breadth self-efficacy and positive emotions) significantly influence proactive behavior. Proactive behavior, in turn, enhances both quality of work life and job effectiveness. Additionally, proactive behavior was found to be the mechanism through which role breadth self-efficacy and positive emotions positively impact innovative work behavior.Practical implicationsThese insights provide valuable guidance for hospital management and HR practitioners on how to foster nurse middle managers’ proactivity, ultimately improving job performance and enhancing the quality of work life within healthcare organizations.Originality/valueThe study identifies proactive behavior as a key mediator in the relationship between cognitive motivational states and both work life quality and job effectiveness, emphasizing its role in driving innovative work behavior among nurse middle managers
