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Dose- and genotype-dependent cardiac arrhythmia and sudden death in rats following microdystrophin gene therapy
No full textInternational audienceRecombinant adeno-associated virus (rAAV) vectors encoding microdystrophin (MD) are a promising treatment for Duchenne muscular dystrophy (DMD). GNT0004, an rAAV2/8 vector expressing MD1, is currently being tested in patients with DMD. Here, we explored supra-optimal intravenous doses of GNT0004 (2.1 × 1014 and 4.2 × 1014 vg/kg, up to 14 times the therapeutic dose) in wild-type (WT) and DMDmdx rats. In all cohorts, robust MD1 protein expression was observed. In DMD animals, creatine kinase levels were normalized, and skeletal muscle and heart histology and functions were improved. However, unexpected sudden deaths occurred at the highest dose. In WT animals, deaths were observed at both doses and were associated with increased arrhythmic events, which may promote structural and functional heart issues. Immunohistological analysis suggested that overexpression of MD1 may disrupt the dystrophin-associated protein complex, increasing the risk of arrhythmias and sudden death. In DMDmdx rats, the 2.1 × 1014 vg/kg dose was well tolerated, but some deaths occurred at 4.2 × 1014 vg/kg, for which a causal link to GNT0004 cannot be excluded. At this dose, increased arrhythmic risk and cardiac pathological remodeling were observed. These observations highlight the potential risk of MD overexpression in the heart and suggest a need for careful monitoring of patients with DMD treated with gene therapy
Brain size reduction in dogs was already established at least by the Late Neolithic of western Europe, 5,000 years ago
No full textThe timing and causes of brain size reduction in domestic dogs remain uncertain. Using endocast's volume as a proxy for brain size, this study provides a first insight into long-term brain size evolution in the wolf-dog lineage. We compared endocranial volumes of 185 modern and 22 prehistoric wolves and dogs ranging from Western Europe to Australia, and spanning the Pleniglacial (35 Ky BP) to the Late Neolithic (5 Ky BP). Our results reveal that Pleistocene so called "protodogs" show no brain size reduction compared to coeval Pleistocene wolves. Instead, we observed a slightly larger relative endocranial volume in the 35,000-year-old 'protodog' from Goyet, which could suggest increased behavioural flexibility in the presence of humans. This hypothesis needs to be tested further. In contrast, Late Neolithic dogs show a drastic 46% brain size reduction with an endocranial volumes comparable to modern small terrier and toy breeds. The anxious and wary temperaments of these Late Neolithic dogs, induced by the brain tissue reorganization associated with such a size reduction, could have served an alerting purpose, among the many other potential roles dogs could have played within this Late Neolithic socio-ecosystems
Ticks and associated pathogens recovered from dogs and cats during a longitudinal collection study at veterinary practices in France
No full textInternational audienceAbstract Background Documented changes in spatial and seasonal tick distribution highlight the importance of continuous surveillance. This paper documents results of a year-round sampling campaign in France, including identification of ticks and associated pathogens recovered from dogs and cats, as part of the European project “Protect Our Future Too.” Methods Ticks were collected from dogs and cats presented to 35 veterinary practices from 27 administrative French departments between April 2021 and July 2022. DNA extracted from each tick sample was amplified by polymerase chain reaction (PCR) for simultaneous detection of 18 types of protozoan or bacterial microorganisms. Results Among 777 collected ticks, 6 species were morphologically identified in descending prevalence order as: Ixodes ricinus (58.3%), Dermacentor reticulatus (24.2%, mainly on dogs), I. hexagonus (7.2%, mainly on cats), Rhipicephalus sanguineus sensu lato (3.6%, mainly on dogs), I. canisuga (one tick collected from a cat), and Haemaphysalis punctata (one tick from a dog). Geographical distribution varied by tick species: I. ricinus and D. reticulatus were more frequent in northeast France, whereas R. sanguineus (s.l.) was predominant in southeast France. Ticks were collected throughout the study period but peaked in spring and early summer for I. ricinus and late winter and spring for D. reticulatus . The ticks R. sanguineus (s.l.) were collected only during summer. In total, 71.0% of the ticks were positive for DNA of at least one microorganism. Anaplasma bacteria were most frequent (up to 75.3% in I. ricinus ) followed by Rickettsia (up to 49.5% in D. reticulatus ). Piroplasm DNA ( Babesia / Theileria / Cytauxzoon spp.) was found in 6.4% of I . ricinus , 5.3% of D. reticulatus , and 3.6% of both I. hexagonus and R. sanguineus (s.l). Borrelia burgdorferi sensu lato DNA was detected in 10.2% of I. ricinus . Mycoplasma haemominutum/haematoparvum DNA was detected in 21.8% of D. reticulatus , whereas M. turicensis DNA was detected in 14.3% of I. hexagonus. Conclusions Results of this study show that ticks are a year-round risk for dogs and cats in France, and tick-borne pathogens are present as mono- or coinfections at high frequencies. Tick control recommendations for veterinarians and dog and cat owners should incorporate these risks. Graphical abstrac
Inflammatory Pulpal Responses to LPS Repeated Inductions in Rat Molar
No full textInternational audienceObjectives: Repeated lipopolysaccharide (LPS) stimulation is a well-established model of chronic inflammation in conditions such as sepsis, lung disease, and arthritis, where it activates the nuclear factor-κB (NF-κB) pathway. Because deep caries similarly expose dental pulp to bacterial toxins, applying this approach to rat molars could clarify how recurrent LPS challenges drive pulp inflammation. This study evaluated whether one to three inductions of LPS or phosphate-buffered saline (PBS, positive control) induce progressive molecular and histological changes in rat pulp.Methods: Exposed upper first molars received 1-3 inductions of LPS or PBS. Pulp tissue was collected 6, 24, and 48 hours after the final induction for histology and quantitative polymerase chain reaction (qPCR).Results: Gene expression analysis showed significant modulation of inflammatory and remodelling markers (IL6, MMP3, MMP9, CCR7, CXCL1, HO1, and DSPP) with repeated stimulations. Histological alterations were more pronounced after multiple exposures, although no significant differences emerged between LPS- and PBS-treated teeth. The progressive rise in the MMP9/DSPP ratio suggests its potential as an indicator of pulpal tissue degradation.Conclusion: This model offers preliminary knowledge about the sequential molecular and histological responses of rat pulp to repeated bacterial challenges. Although further work is needed to isolate LPS-specific effects and confirm chronic features, these findings help delineate the early dynamics of pulp inflammation
A comprehensive metabolomics approach for enhanced detection of growth promoting practices in livestock
No full textInternational audienc
Contributions to the development and simulations of generic, modular and multiphysics greenhouses dynamic models, evaluated with a whole year study case dataset
No full textAlso known as : A greenhouse dynamic model to assess sustainable solutions Contributions to the development and simulations of generic, modular and multiphysics greenhouses dynamic models, evaluated with a whole year study case datasetInternational audienceNorth-Western Europe heated greenhouses need to address their high fossil energy dependency while they start to face with climate change. In this context, physics-based greenhouses dynamic models can be used for prospective assessments of innovative shapes, equipment, control, etc. A prerequisite for such model-based evaluation is a review of existing implementations, the improvement and development of suitable sub-models in a generic and modular approach that do not require calibration, and the evaluation of a use case global model with a solid experimental dataset. First, this paper details contributions to existing models regarding several aspects: solar gain, boundaries effects, airflows and leakages, heat and mass transfer. The second part is dedicated to the evaluation of an experimental tomato greenhouse global model for an 11-month period. Its assessment is multiphysics: indoor climate, utilities consumptions, yield and Leaf Area Index. The resulting 5 min sampling indoor air climate Root Mean Square Error is 1.3 °C (temperature) and 8.1%RH (relative humidity). The tomato yield Mean Absolute Error is 1.1 kg m-2. Mass balances also quantify the losses and potentials for water and CO2. The global model outputs are compared with literature, and it is demonstrated that assessing the accuracy of models based only on statistical indicators is questionable. This approach is compatible with assessments of prospective solutions, it increases the confidence for scaling results from small to large commercial greenhouses, and it constitutes a base from which simpler and black box models can be derived for other applications such as predictive control
Imaging Diagnosis—Peritoneal Splenosis in a Dog: Computed Tomographic Findings
No full textInternational audienceABSTRACT This report describes a case of peritoneal splenosis in a dog, identified following the discovery of multiple peritoneal nodules on computed tomography (CT) performed for the evaluation of a compressive myelopathy. Histopathologic analysis confirmed the presence of ectopic splenic tissue without evidence of malignancy. In dogs, splenosis results from autotransplantation of splenic tissue within the peritoneal cavity, following splenic injury or surgery. Although most cases are incidental findings, nodule enlargement or rupture may occasionally lead to clinical consequences. This case emphasizes the importance of considering splenosis in the differential diagnosis of peritoneal nodules, particularly when they are not associated with peritoneal effusion and in animals with a history of splenic disease or abdominal trauma
Impact of physical and sensory enrichment on the physiological status and disease resistance of triploid rainbow trout (Oncorhynchus mykiss)
No full textInternational audienceEnvironmental enrichment is increasingly recognised as a practical approach to improve the welfare of farmed fish. In rainbow trout (Oncorhynchus mykiss), a species of high economic and scientific relevance, few studies have simultaneously evaluated multiple dimensions of welfare under different enrichment strategies. Here, we investigated the effects of structural and sensory enrichments on growth, physiology, behaviour, neurochemistry, and disease resistance. Female triploid rainbow trout were reared for eight weeks under eight conditions: neutral control, positive stress control (no enrichment with additional handling stress), structural enrichments (rubber hose, rubber wall, floating grass mat, flexible laminaria), and sensory enrichments (continuous gas bubbles, blue light filter). Growth performance, blood markers of stress (cortisol, glucose, lactate), behavioural indicators, enrichment use, and brain monoamine turnover (5-HIAA/5-HT for serotonin; HVA/L-DOPA for dopamine) were assessed at three time points in eight weeks. To evaluate robustness, fish were subsequently challenged with Aeromonas salmonicida subsp. salmonicida. No significant differences in growth were detected across conditions, showed the highest weight gains, raising the hypothesis that they could provide benefits over longer rearing cycles, a question that will require dedicated long-term trials. Behavioural analyses indicated high use of structural enrichments and reduced stress-related behaviours under the blue filter and rubber hose conditions. Stress physiology revealed condition-specific reductions in lactate or cortisol, but no consistent enrichment effect across markers. Neurochemical analyses demonstrated condition-dependent modulation of serotonergic and dopaminergic turnover, with laminaria increasing both systems, blue filter reducing dopaminergic activity, and bubbles strongly decreasing serotonergic turnover. Infection outcomes showed slower disease progression in rubber hose, laminaria, blue filter, and rubber wall conditions, with rubber hose fish exhibiting the slowest mortality kinetics. Overall, our integrative approach highlights that environmental enrichment modulates multiple welfare dimensions in rainbow trout, with laminaria, blue filter, grass mat, and rubber hose emerging as the most promising strategies. These findings support enrichment as a valuable tool to promote fish welfare and resilience, while underlining the need for long-term and context-specific validation before implementation in aquaculture
Plasma and Brain Metabolomics Uncover Modulation of Bile Acid and Pentose Phosphate Pathways by Melissa officinalis in Obese Rat Model
No full textInternational audienceWhile our group previously demonstrated the calming effects of Melissa officinalis extract (MOE) in dogs, the underlying brain-level mechanisms remain unclear. To address this, we investigated these mechanisms in rats using an untargeted metabolomics approach. Twenty-four male Wistar rats were divided into three groups (eight rats per group): control (standard diet, SD), a group fed a high-fat high-sucrose diet (HFHSD), and HFHSD administrated with a hydro-alcoholic standardized MOE (HFHSD MOE) at a dose of 200 mg/kg. Body weight, behavior through elevated plus maze (EPM), and glucose tolerance using the oral glucose tolerance test (OGTT) were monitored. After 12 weeks of supplementation, plasma and brain metabolomes were explored using non-targeted metabolomics. Although the EPM revealed no significant behavioral improvement, the OGTT showed a significant reduction in blood glucose area under the curve (AUC, p < 0.05), suggesting a metabolic effect of MOE. Metabolomic analysis highlighted two key pathways: (1) bile acid biosynthesis in plasma, as previously observed in our dog study, and (2) pentose phosphate metabolism in the brain. These results provide insight into central and peripheral mechanisms influenced by MOE and generate hypotheses on pathways potentially linked to previously reported behavioral effects in dogs, offering targets for nutritional interventions
Tiques et santé. Biologie, maladies, maîtrise du risque
No full textInternational audienceFace aux déséquilibres écologiques et au risque croissant d’épidémies liés au changement global, il est légitime de s’interroger sur le rôle des tiques, connues pour transmettre de nombreux agents pathogènes à l’homme et l’animal. Elles peuvent être à l’origine d’un certain nombre de maladies, comme la maladie de Lyme.Cet ouvrage présente en premier lieu des éléments de base sur la biologie et l’écologie de ces parasites : quels sont leurs habitats, leurs hôtes préférés ? Comment localisent-ils ces hôtes et comment se reproduisent-ils ? Quels agents pathogènes transmettent-ils ? Sommes-nous égaux face au risque de piqûre ? Quelles sont les zones les plus infestées ? Les composantes du risque lié aux tiques et les moyens de connaître et suivre ce risque sont ensuite détaillés. Des stratégies sont proposées, qu’il s’agisse d’actions individuelles (adaptation des comportements, recours éventuel à la vaccination) ou collectives (meilleure gestion des zones de contact entre espaces naturels et zones habitées).Ce livre s’adresse à toute personne pratiquant des activités de plein air, ainsi qu’aux étudiants et enseignants. Il invite, sans alarmisme, à une approche basée sur la vigilance