Bridging spatial and temporal scales of developmental gene regulation

International audienceThe development of multicellular organisms relies on the precise coordination of molecular events across multiple spatial and temporal scales. Understanding how information flows from molecular interactions to cellular processes and tissue organization during development is crucial for explaining the remarkable reproducibility of complex organisms. This review explores how chromatin-encoded information is transduced from localized transcriptional events to global gene expression patterns, highlighting the challenge of bridging these scales. We discuss recent experimental findings and theoretical frameworks, emphasizing polymer physics as a tool for describing the relationship between chromatin structure and dynamics across scales. By integrating these perspectives, we aim to clarify how gene regulation is coordinated across levels of biological organization and suggest strategies for future experimental approaches

Seroprevalence and preventive practices of dengue and chikungunya among school children in Bangkok: Gaps in prevention and vaccination strategies

Abstract Background Dengue and chikungunya, both transmitted by Aedes mosquitoes, continue to pose significant public health concerns in Thailand, particularly during the rainy season. Despite ongoing vector control efforts, the incidence of infection remains high, with an increasing trend observed in chikungunya. This underscores the need for additional control measures, including vaccination, to reduce disease burden and morbidity. This study aims to assess the seroprevalence of dengue and chikungunya infections among children aged 10-15 years in Bangkok and to evaluate the knowledge, attitudes, and practices (KAP) related to mosquito-borne disease prevention. Methodology A cross-sectional descriptive study was conducted across 12 schools in Bangkok. Children aged 10 to 15 years were included. Seroprevalence was determined using rapid diagnostic tests (Abbott DENGUE IgG/IgM and Citest Chikungunya IgG/IgM) based on the immunochromatography technique, using fingertip blood samples. Parents completed KAP questionnaires, including factors influencing vaccination decisions. Principal findings From June to August 2024, 937 participants were enrolled, with a mean (SD) age of 11 (1.6) years; 67% were aged 10–12 years, and 33% were aged 13–15 years. The seroprevalence of dengue was 28.1% (95% CI 25.2-31.0), while that of chikungunya was 6.3% (95% CI 4.7-7.9). KAP assessments revealed a high level of awareness regarding symptoms and transmission; however, notable deficiencies in preventive behaviors were identified. Only 14.8% of respondents reported consistent use of mosquito repellent, and 17.5% routinely inspected and removed mosquito larvae from their homes. Conclusion The substantial seroprevalence of dengue and the emerging trend of chikungunya among children in Bangkok highlights the urgent need to enhance community education and strengthen vector control interventions. Expanding dengue vaccination coverage and raising awareness about chikungunya prevention, including consideration for future vaccine implementation, are essential to mitigating future outbreaks and reducing the disease burden. Author summary Mosquito-borne diseases, including dengue and chikungunya, are significant health problems in Southeast Asia. In our study, we evaluate the seroprevalence of these diseases using rapid blood tests in a school-based setting among children in Bangkok. The seroprevalence data highlight the risk of exposure, particularly among children, and can guide preventive practices, including vaccination. Despite the widespread recognition of these diseases, preventive practices remain limited. Therefore, implementing effective preventive measures and vaccination strategies could significantly reduce the severity of infections and improve public health outcomes

Feeding state-dependent neuropeptidergic modulation of reciprocally interconnected inhibitory neurons biases sensorimotor decisions in Drosophila

International audienceAn animal’s feeding state changes its behavioral priorities and thus influences even nonfeeding-related decisions. How the feeding state information is transmitted to nonfeeding-related circuits and what circuit mechanisms are involved in biasing nonfeeding-related decisions remain open questions. By combining calcium imaging, neuronal manipulations, behavioral analysis and computational modeling, we determined that the competition between different aversive responses to mechanical cues is biased by changes in the feeding state. We found that this effect is achieved by the differential modulation of two different types of reciprocally connected inhibitory neurons promoting opposing actions. This modulation results in a more frequent active type of response and, less frequently, a protective type of response if larvae are fed sugar than when they are fed a balanced diet. Information about the internal state is conveyed to inhibitory neurons through homologs of the vertebrate neuropeptide Y, which is known to be involved in regulating feeding behavior

Poliovirus surveillance in Mayotte, Indian Ocean, reveals encephalomyocarditis virus type 1 and a wide diversity of non-polio enteroviruses

International audienceBackground: In 2023, Mayotte, a French department in the Mozambique channel, experienced a long drought that led to potable water restrictions. Although the French vaccination schedule makes polio vaccination compulsory for children, the large proportion of migrants on the island coupled with the water crisis raised concerns about the establishment of poliovirus transmission chains. Therefore, a surveillance was implemented to detect polioviruses in sewage sampled in the two main wastewater treatment plants.Methods: Samples collected from September 2023 through January 2024 were processed following the Global Polio Laboratory Network's algorithm.Results: Only two polioviruses were detected, both featuring a low number of nucleotide differences compared with vaccine strains, which suggested excretion by recently vaccinated people rather than circulation. The surveillance revealed viruses of the species Cardiovirus rueckerti in almost one-half of the samples. Furthermore, 305 non-polio enteroviruses were detected, belonging to various virus types of species Enterovirus betacoxsackie (53%), Enterovirus coxsackiepol (44%), and Enterovirus alphacoxsackie (3%).Conclusions: The poliovirus surveillance did not detect any wild or highly mutated poliovirus strains and did not highlight poliovirus circulation. This provided an opportunity to obtain the first overview of the non-polio enteroviruses circulating in Mayotte

Introduction of epigenetic variation contribute to resistance against the human parasite Schistosoma mansoni

International audienceBackgroundWaddington-type kick-start of adaptive evolution is assumed to be possible based on epigenetic variation alone. We tested this hypothesis in the snail Biomphalaria glabrata, vector of Schistosoma mansoni, the causative agent of the human disease schistosomiasis. Epilines and epigenetic recombinant inbred lines (epiRILs) were used to propagate DNA methylation variants over 3 generations.ResultsThe fecundity and susceptibility to infection by S. mansoni were measured. Average parasite prevalence has a higher variance in epiRILs than in controls and decreased from 84 ± 5% in controls to 68 ± 21% in epiRILs. The increase in fertility in epiRILs was 12%, with an average heritability of 0.55. The introduction of 1% epimutant offspring snail into resident susceptible populations was simulated by a model. If genetic assimilation of the resistance occurred in 0.3% of the introduced epimutants, susceptibility would be replaced by resistance after less than one hundred generations.ConclusionsEnvironmental management can therefore be envisaged by introducing epigenetically modified organisms to prevent parasite infections from spreading to the intermediate host and, ultimately, the human population

Features of Invasive Aspergillosis Caused by Aspergillus flavus , France, 2012–2018

International audienceInvasive aspergillosis (IA) caused by Aspergillus flavus remains poorly described. We retrospectively analyzed 54 cases of IA caused by A. flavus reported in France during 2012–2018. Among cases, underlying IA risk factors were malignancy, solid organ transplantation, and diabetes. Most (87%, 47/54) infections were localized, of which 33 were pleuropulmonary and 13 were ear-nose-throat (ENT) infection sites. Malignancy (70% [23/33]) and solid organ transplantation (21% [7/33]) were the main risk factors in localized pulmonary infections, and diabetes mellitus was associated with localized ENT involvement (61.5%, [8/13]). Fungal co-infections were frequent in pulmonary (36%, 12/33) but not ENT IA (0 cases). Antifungal monotherapy was prescribed in 45/50 (90%) cases, mainly voriconazole (67%, 30/45). All-cause 30-day case-fatality rates were 39.2% and 90-day rates were 47.1%, and rates varied according to risk factor, IA site, and fungal co-infections. Clinicians should remain vigilant for A. flavus and consider it in the differential diagnosis for IA

The virulence regulator CovR boosts CRISPR-Cas9 immunity in Group B Streptococcus

International audienceCRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae , a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction

N⁶-methyladenosine primes the malaria parasite for transmission

Posted March 28, 2025 on bioRxiv.International audienceSudden environmental changes are a recurring challenge for unicellular organisms, but a necessity for many to progress through their lifecycle. To transmit from its human host to mosquito vector, malaria parasites differentiate into male and female, semi-quiescent stages that can re-initiate development within seconds after transmission. Here, we identify the RNA modification N 6 methyladenosine (m 6 A) as the mediator of a rapid, sex-specific, and temperature-sensitive mechanism to restructure protein synthesis during transmission. We find that male parasites maintain high levels of translation during their semi-quiescence that are rapidly repressed following mosquito uptake. This translational shutdown is essential for the continuation of male parasite development and depends on the m 6 A-binding protein YTH.2. We further show that m 6 A and YTH.2 are already present prior to transmission, but that their repressive interaction requires a temperature drop accompanying the exit from the human host. Hence, m 6 A appears to prime the parasite transcriptome and subsequently converts an environmental shift into a rapid translational response.</div

Disease-attenuated pneumococcal biosynthesis gene mutants invade the mucosal epithelium and induce innate immunity

International audienceNasopharyngeal colonisation by Streptococcus pneumoniae is characterised by adherence to epithelial cells, microinvasion and innate immune activation. Previously, we have shown that two biosynthesis gene mutants of S. pneumoniae serotype 6B strain ( ΔproABC and Δfhs with an additional ΔpiaA mutation) can successfully colonise murine and human models without causing disease. Here, we test the hypothesis that epithelial microinvasion and an innate immune response persist despite disease attenuation. We show that although the ΔproABC and Δfhs mutations do not attenuate microinvasion in either experimental human pneumococcal challenge or infection of epithelial cell models, there was less transmigration of Detroit 562 nasopharyngeal epithelial cells by the biosynthesis gene mutants than the WT. Cellular reorganisation by primary human airway epithelial cells varied considerably between strains. Compared to the WT, infection of Detroit 562 epithelial cells by the Δfhs/piaA mutant but not the ΔproABC/piaA mutant was less pro-inflammatory, induced less caspase 8 production, associated increased pneumococcal hydrogen peroxide secretion and reduced pneumolysin activity. Under serum stress, these biosynthesis gene mutations had a broad impact on the expression of pneumococcal virulence genes (e.g. ply , nanA and psaA ), those regulating oxidative stress (e.g. SpxB , lctO and adhE ), and genes involved in purine and carbohydrate metabolism. However, although these may result in disease attenuation, they were not directly linked to effects on microinvasion, cellular reorganisation or the epithelial innate immune response. These findings suggest that the strain differences observed were driven by the differential expression of multiple bacterial virulence and metabolic pathways, rather than any single gene or pathway of genes. These data highlight the complex impact of single gene mutations on bacterial virulence and suggest that the virulence determinants of pneumococcal epithelial colonisation, microinvasion and innate immunity are not necessarily directly linked to disease. Author Summary Streptococcus pneumoniae (the pneumococcus) commonly colonises the back of the human nose, and is a leading cause of pneumonia, meningitis, and sepsis. During colonisation, the pneumococcus adheres to the cells in the nose, invades these cells (so-called microinvasion), and activates them. Colonisation is a pre-requisite for disease, however, since disease is largely a dead end for S. pneumoniae , it remains unclear whether these processes are directly linked to disease progression. We have previously shown that if we introduce gene mutations into S. pneumoniae that affect key metabolic pathways, these bacteria retain their ability to colonize human and animal models without causing disease. We now show that these mutants retain their ability to microinvade epithelial cells, and some may still cause inflammation, but are less able to pass through the epithelial barrier. However, although the attenuation of disease may be explained by the broad-ranging impact of these mutations on pneumococcal virulence, oxidative stress, and metabolism, they are not driven by a single determinant. Our findings suggest that pneumococcal microinvasion and immune activation are not necessarily pre-cursors to disease progression. This supports the idea that S. pneumoniae adapts and evolves to promote colonisation and ultimately transmission rather than cause disease. Graphical Abstract S. pneumoniae colonisation is characterised by mucus association, epithelial adherence, microcolony formation and microinvasion – where the pneumococcus invades the epithelial barrier without causing disease. Although mutations in S. pneumoniae biosynthesis genes ( ΔproABC and Δfhs ) attenuate disease in a murine model, they do not attenuate microinvasion in either experimental human pneumococcal challenge (EHPC) or in vitro in primary and immortalised epithelial cells. Transmigration of the epithelial barrier is attenuated. These mutations show strain-dependent effects on both the epithelial and bacterial responses to infection. Factors such as epithelial cellular reorganisation, inflammation and caspase 8 activity alongside pneumococcal metabolic adaptation, virulence factor expression and response to stress are important components of these processes

IA métissée : quand données et symboles s’enlacent

National audienceL'IA ce n'est pas que les réseaux de neurones. Découvrons une IA métissée, au carrefour des données et des symboles. Après une explication sur l'intérêt de l'IA dans la lutte contre les cancers, je m’attarderai sur ces études qui cherchent à « mélanger » réseaux de neurones et graphes de connaissances, afin d'être performants tout en restant explicables