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Blanc, F.

Publications and source records attributed to Blanc, F..

9 recordsLinked to original sources

Identifying the immunocompetence markers at weaning to predict long-term vaccine response and persistence in pigs

Vaccination is a key strategy for controlling infectious disease in pigs, but the magnitude and persistence of vaccine-induced immunity vary among individuals. We investigated whether immune and physiological traits measured at weaning could predict long-term antibody (Ab) status and Ab persistence following vaccination against Mycoplasma hyopneumoniae (MH) and Influenza A virus (IAV), and whether predictive markers were shared between vaccines. Two vaccination trials were conducted in a cohort of 381 Large White pigs (MH, n=189; IAV, n=192). Animals were vaccinated at weaning (28 days of age) and received a booster 21 days later. Long-term Ab status was defined at 118 days post-vaccination (dpv) using assay-specific thresholds, while Ab persistence was defined as the decline from the individual peak response at 28 or 35 dpv to 118 dpv. A broad panel of immune and physiological traits measured at weaning was evaluated as candidate predictors. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was used for variable selection, followed by PLS-DA classification models. Cross-validated accuracies ranged from 64.7% to 67.7%, indicating moderate predictive performance. Across vaccines, eight predictors were shared for long-term Ab status and twelve for Ab persistence. Hematocrit, IgG, platelet count, and plateletcrit (PCT) were associated with positive long-term Ab status for both vaccines, whereas mean corpuscular hemoglobin concentration (MCHC) and neutrophil percentage were associated with negative status. For persistence, higher vitamin D, -1 globulin concentration, platelet count, and PCT were consistently associated with persistent responses across vaccines, while MCHC and spectral absorbance traits were associated with non-persistence. These findings indicate that early-life immune and physiological traits measured at weaning are associated with immunocompetence traits that contribute to variation in subsequent long-term vaccine antibody outcomes and responsiveness. The identification of both shared and vaccine- or phenotype-specific predictors suggests that vaccine responsiveness reflects both general features of baseline immunocompetence and context-specific determinants.

immunology↗

An ancestral pronephric contribution reveals the multilineage origin of the teleost gonad and revises the evolution of vertebrate gonadogenesis

Challenging the paradigm that pronephric field contribution to gonadal formation would be an amniote innovation, we demonstrate this trait is ancestral to bony vertebrates. Using cell lineage tracing, single-cell and spatial transcriptomics, and functional validation, we show that the teleost gonad arises from three distinct embryonic tissues, the pronephros, the coelomic epithelium, and the lateral plate mesoderm, in contrast to amniotes. This multi-tissue origin generates an unexpected lineage-based cellular diversity. Further cross-species comparisons over medaka, mouse, chicken and turtle unravel how lineage-specific deviations shape early gonadal development. Specifically, we map these variations amongst the different gene regulatory networks, outlining their physiological implications for specialized gonadal functions. Our results support a model in which heterochronic shifts are coupled to regulatory rewiring of conserved gene networks, driving lineage-specific developmental trajectories through a canalized developmental system drift.

developmental biology↗

Mature plant chloroplasts form reversible gyroid cubic membranes

Across kingdoms, cells fold their membranes into precise shapes closely linked to their functions. In mature land-plant chloroplasts, the photosynthetic membranes have been viewed as strictly lamellar and it is unknown whether they can take on a different structure while remaining functional. Here, we show that mature Arabidopsis thaliana chloroplasts can transform this network into a gyroid-type cubic membrane, which we call the gyrobody. The gyrobody forms reversibly during the night and preserves photosystem II photochemistry. A decrease in stromal side thylakoid surface charge, caused by lower protein phosphorylation, triggers the lamellar-to-gyroid transition which the curvature-inducing lipid MGDG facilitates. This shows that the mature plant thylakoid network is not locked into its lamellar form, revealing unexpected structural flexibility of this system.

Plant Biology↗

Host genetics and pre-vaccination blood transcriptome as determinants of vaccine-induced immunity to Influenza A virus in swine

Influenza A virus (IAV) is a major respiratory pathogen in pigs, causing diseases that have significant economic and potential public health consequences. Vaccine effectiveness varies among animals, impacting long-term herd protection due to individual variabilities in antibody levels and persistence over time. Our aim was to identify the genetic factors and pre-vaccination blood transcriptomic profiles that influence immune response levels to the IAV vaccine. A total of 187 piglets were vaccinated at weaning (28 days of age, 0 days post-vaccination, dpv) and boosted three weeks later, and humoral responses were assessed until slaughter (21, 28, 35, and 118 dpv) by measuring serum IAV-specific IgG and hemagglutination inhibition (HAI) titers. The results revealed varying antibody responses and persistence. Genome-wide association studies identified two loci on chromosomes SSC5 and SSC8 associated with a persistence of HAI titers until slaughter. Pre-vaccination blood transcriptomic analyses showed that early and post-boost antibody responses (21, 28 and 35 dpv) and long-term persistence (118 dpv) were associated with distinct baseline immune programs, with extracellular matrix and myeloid-related signatures predicting strong early and peak responses, whereas interferon-related signatures were linked to reduced long-term antibody persistence. Our results highlight the importance of considering the role of immune competence and genetics in vaccine responses in pigs and suggest candidate biomarkers to improve vaccination strategies within breeding programs.

genomics↗

Porcine Intestinal Organoids as Models of Regional Gut and Animal Identities: a Transcriptomic Approach

BackgroundOrganoids offer controlled epithelial systems for functional follow-up of candidate genes and variants in farm animals, but their usefulness for genotype-to-phenotype research depends on whether they retain intestinal regional identity and animal-specific molecular signatures. We profiled 32 RNA-seq libraries from matched tissues and organoids derived from duodenum, jejunum, ileum and colon of four slaughter-age Large White pigs. ResultsOrganoids were transcriptionally distinct from native tissues but remained within the intestinal transcriptional space and retained regional structure, particularly when epithelial cell signature genes were considered. Most expressed genes were shared between tissues and organoids (81.2% of all detected genes and 81.8% of epithelial cell signature genes). Innate immune genes were also largely detected in organoids (79.6% shared), but with a lower regional organisation. Projection of ileal organoids onto an in vivo developmental reference positioned them closer to foetal or newborn samples than to slaughter-age ileum tissue, consistent with a comparatively immature transcriptional state. Differential expression and enrichment analyses showed attenuation of gene-level segment differences in organoids but partial preservation of regional markers and Gene Ontology terms linked to intestinal development and regionalisation, absorption, metabolism, epithelial signalling, mucosal immune responses and transport. Animal-associated differences were retained for selected epithelial signatures, notably the glycosylation-related genes FUT2 and B4GALNT2. FUT2 expression was strongly reduced in one animal and associated with linked intronic variants, whereas B4GALNT2 separated two pairs of animals and segregated with candidate variants affecting protein expression or transcript processing. ConclusionsAdult porcine intestinal organoids retain a substantial epithelial component of regional identity and preserve selected animal-specific regulatory signatures, while showing reduced immune spatial patterning and immature transcriptional features. Standardised organoid biobanks from genotyped and phenotyped pigs may support functional follow-up of candidate genes, variants and pathways when intestinal epithelial mechanisms are implicated.

genomics↗

Network Signatures of Disease Progression and Core Symptoms in Dementia with Lewy Bodies Distinct from Alzheimer's Disease

BackgroundResting-state fMRI studies in dementia with Lewy bodies (DLB) and Alzheimers disease (AD) have described connectivity alterations in large-scale brain networks. However, little is known about functional changes across disease stages, particularly in DLB. ObjectiveTo investigate functional connectivity of key brain networks in DLB patients at different stages, compare them to AD and healthy controls (HC) and examine associations with core clinical symptoms. MethodsNinety DLB patients, comprising 63 with mild cognitive impairment (MCI-DLB) and 27 with dementia (d-DLB), along with 25 AD patients (11 MCI-AD and 14 d-AD) and 34 HC underwent clinical, neuropsychological and resting-state fMRI assessment. ROI-to-ROI analyses were performed using the CONN toolbox, (pFDR<0.05). ResultsThe DLB group showed reduced functional connectivity within the salience network (SN) compared with HC, but did not differ from AD. While MCI-DLB patients showed no significant differences, d-DLB patients showed reduced SN and frontoparietal network (FPN) connectivity compared to HC and AD. SN connectivity was associated with severity of fluctuations and FPN connectivity with REM sleep behavior disorder and cognitive decline in DLB. In contrast, in the AD group, decreased default mode network (DMN) connectivity was associated with lower MMSE scores. ConclusionSN and FPN connectivity impairments relate to disease progression and core clinical features in DLB, whereas DMN connectivity is linked to cognitive decline in AD. These distinct patterns highlight divergent paths of network dysfunction in the two diseases, offering insight into their underlying mechanisms and clinical expression.

neuroscience↗

Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments

The release of inorganic phosphate (Pi) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. However, the molecular mechanisms underlying Pi release from both the core and barbed end of actin filaments remain unclear. Here, we combine cryo-EM with molecular dynamics simulations and in vitro reconstitution to demonstrate how actin releases Pi through a molecular backdoor. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and only opens transiently through concerted backbone movements and rotameric rearrangements of residues close to the nucleotide binding pocket. This mechanism explains why Pi escapes rapidly from the filament end and yet slowly from internal actin subunits. In an actin variant associated with nemaline myopathy, the backdoor is predominantly open in filament-core subunits, resulting in greatly accelerated Pi release after polymerization and filaments with drastically shortened ADP-Pi caps. This demonstrates that the Pi release rate from F-actin is controlled by steric hindrance through the backdoor rather than by the disruption of the ionic bond between Pi and Mg2+ at the nucleotide-binding site. Our results provide the molecular basis for Pi release from actin and exemplify how a single, disease-linked point mutation distorts the nucleotide state distribution and atomic structure of the actin filament.

biochemistry↗

Towards the quantitative characterization of piglets’ robustness to weaning: A modelling approach

Weaning is a critical transition phase in swine production in which piglets must cope with different stressors that may affect their health. During this period, the prophylactic use of antibiotics is still frequent to limit piglet morbidity, which raises both economic and public health concerns such as the appearance of antimicrobial-resistant microbes. With the interest of developing tools for assisting health and management decisions around weaning, it is key to provide robustness indexes that inform on the animals capacity to endure the challenges associated to weaning. This work aimed at developing a modelling approach for facilitating the quantification of piglet resilience to weaning. We monitored 325 Large White pigs weaned at 28 days of age and further housed and fed conventionally during the post-weaning period without antibiotic administration. Body weight and diarrhoea scores were recorded before and after weaning, and blood was sampled at weaning and one week later for collecting haematological data. We constructed a dynamic model based on the Gompertz-Makeham law to describe live weight trajectories during the first 75 days after weaning following the rationale that the animal response is partitioned in two time windows (a perturbation and a recovery window). Model calibration was performed for each animal. Our results show that the transition time between the two time windows, as well as the weight trajectories are characteristic for each individual. The model captured the weight dynamics of animals at different degrees of perturbation, with an average coefficient of determination of 0.99, and a concordance correlation coefficient of 0.99. The utility of the model is that it provides biological parameters that inform on the amplitude and length of perturbation, and the rate of animal recovery. Our rationale is that the dynamics of weight inform on the capability of the animal to cope with the weaning disturbance. Indeed, there were significant correlations between model parameters and individual diarrhoea scores and haematological traits. Overall, the parameters of our model can be useful for constructing weaning robustness indexes by using exclusively the growth curves. We foresee that this modelling approach will provide a step forward in the quantitative characterization of robustness.\n\nImplicationsThe quantitative characterization of animal robustness at weaning is a key step for management strategies to improve health and welfare. This characterization is also instrumental for the further design of selection strategies for productivity and robustness. Within a precision livestock farming optic, this study develops a mathematical modelling approach to describe the body weight of piglets from weaning with the rationale that weight trajectories provide central information to quantify the capability of the animal to cope with the weaning disturbance.

systems biology↗

Livestock genome annotation: transcriptome and chromatin structure profiling in cattle, goat, chicken and pig.

BackgroundFunctional annotation of livestock genomes is a critical step to decipher the genotype-to-phenotype relationship underlying complex traits. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project (http://www.fragencode.org) aimed to profile the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in four livestock species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).\n\nResultsRNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically Associating Domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species.\n\nConclusionsWe report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.

genomics↗