Biology subjects

Bernard, J.

Publications and source records attributed to Bernard, J..

10 recordsLinked to original sources

bioRxiv2026

Molecular characterization of thermo-adapted Novirhabdovirus variants and virulence in vivo in rainbow trout and zebrafish at different temperatures.

Controlling viral diseases in fish is a challenge for the sustainable development of aquaculture and improving the health of fish farms. Infectious hematopoietic necrosis virus (IHNV) is a major pathogen in aquaculture. It infects cold-water fish, but loses its infectivity at temperatures above 20{degrees}C. Since fish are poikilothermic animals, their body temperature fluctuates according to that of their environment. Faced with current climate change, it is crucial to understand how these pathogens will adapt to rising temperatures. Through a strategy simulating the impact of global warming, this virus has been progressively thermo-adapted to 25{degrees}C. The selected variant, IHNV25, replicates at 25{degrees}C while maintaining efficient replication at low temperatures, like its parental strain. Genome sequencing and a reverse genetics approach revealed that only 9 amino acid substitutions, distributed across 4 of the 6 viral genes, were essential for thermo-adaptation. Although IHNV25 was highly attenuated in its natural host, the rainbow trout, at any temperatures, it proved highly virulent when injected in zebrafish larvae at 20{degrees}C and 25{degrees}C, inducing severe symptoms identical to those observed in trout (hemorrhages, oedema, and exophthalmia). At both temperatures, mortality was preceded by a massive viral replication and a delayed and inefficient interferon and inflammatory response. Unlike the parental strain, IHNV25 was also capable of infecting larvae by bath immersion at 25{degrees}C, entering via the caudal fin, thus demonstrating its ability to cross the species barrier. The identification of viral markers of thermo-adaptation will therefore be of great interest for the epidemiological surveillance of field isolates.

microbiology↗

bioRxiv2026

From Growth Faltering to Recovery: Gut Microbial and Body Composition Signatures of Early Childhood Malnutrition Phenotypes

BackgroundChronic malnutrition in early childhood is a multifactorial condition associated with long-term impairments, yet the physiological and gut microbial pathways underlying differential growth trajectories remain poorly understood. ObjectiveWe aimed to characterize phenotypic growth trajectories and identify the associated gut microbial and body composition signatures in infants during the first year of life. MethodsWe analyzed longitudinal data from birth to 12 months in a South African cohort (Soweto, n=45). Individual linear growth trajectories were modeled using the Jenss-Bayley equation, and children were clustered based on model parameters to identify phenotypic subgroups. Body composition (fat-free mass and fat mass) was measured via deuterium dilution at 6 and 12 months, and gut microbiome development was assessed using 16S rRNA gene amplicons at 4, 6, and 12 months. ResultsWe identified distinct phenotypic subgroups including healthy growth, catch-up growth, and growth faltering, that were obscured at the cohort level. These trajectories diverged most dynamically within the first 6 months of life. Integrated analysis revealed that in the growth faltering cluster, height-for-age and fat-free mass z-scores stabilized between 6 and 12 months, whereas fat mass z-scores (FMZ) declined. This trade-off is consistent with a catabolic state where energy reserves are prioritized for lean tissue and bone growth. Furthermore, at 6 months, the growth faltering cluster was enriched with opportunistic pathobionts (e.g., Paraclostridium). In contrast, the catch-up cluster exhibited a transient enrichment of facultative anaerobes (e.g., Enterobacter), supporting a hypothesis that these oxygen-tolerant taxa may help bridge a transitional microbial state in partially oxygenated or inflamed environments to enable physiological recovery. ConclusionsEarly childhood chronic malnutrition phenotypes in South African infants can be defined by distinct microbial and body composition signatures that diverge within six months of life. Integrated interventions should target both host anabolic state and microbiome transitions to support recovery.

microbiology↗

bioRxiv2025

Early life sleep is associated with longevity in Drosophila

Sleep is a universal behavior that is critical for brain function and physiological homeostasis. While growing epidemiological and experimental evidence suggests reduced sleep quality is associated with negative health outcomes, the causal relationship between sleep loss and reduced longevity remains poorly understood. Here, we examine sleep across the lifespan and its relationship to longevity in Drosophila melanogaster. We examined the associations between numerous components of sleep at different life stages to longevity. Early life sleep, but not middle and late-life sleep, was positively associated with longevity. Age-dependent changes in sleep were consistent but accelerated, when flies are housed under stressful conditions including nutrient and temperature stress. Further, pharmacological restoration of sleep in the first 10 days of life, but not at later time points, increases longevity. Together, this work provides a systematic investigation of how different components of sleep impact longevity and suggests early life sleep may be particularly important in promoting sleep across the lifespan.

neuroscience↗

bioRxiv2025

In silico reconstruction of a salmonid alphavirus virion reveals distinctive structural and molecular features implicated in virulence in vivo

Salmonid alphavirus (SAV) poses a significant disease threat to aquaculture. Recently, new alphaviruses from several fish species have been discovered. However, little is known about their biology and diseases potential. Alphaviruses are considered to have originated from a marine environment; therefore, studying fish alphaviruses can inform on the evolutionary history of the genus. Contrary to many terrestrial alphaviruses, there are currently no experimentally-determined structures for aquatic alphaviruses, severely limiting their study. In this work, we harness the power of structural bioinformatics and AlphaFold to reconstruct an entire SAV virion, thereby revealing an exposed and distinctive -helical feature in its E2 envelope protein. Using an integrative approach, we explore the sequence diversity and evolutionary conservation of this predicted feature and investigate the functional consequences of variations on viral fitness and virulence. This study provides a novel framework paving the way to better understand aquatic alphavirus pathogenicity and host species adaptation.

microbiology↗

bioRxiv2024

A 3D-printed cradle for mouse preclinical MRI with an integrated water heating system

Functional Magnetic Resonance Imaging (fMRI) of small animals is mainly performed under sedation or anesthesia to avoid movement, which is detrimental to image quality. Heating systems to warm the animals usually rely on airflow or heating blankets or pads with circulating water to comply with MR compatibility requirements. However, these solutions are often suboptimal for small animals like mice scanned at ultra-high magnetic fields with long-bore MR scanners. We designed and built an MR cradle with an integrated water chamber, maximizing the contact surface with the mouses body. This large contact surface helps maintain body temperature without overheating the animal, thus reducing the risk of burns and hyperthermia. Our cradle keeps the mouses body temperature stable within the physiological range during an MRI session and fits the bore of a Bruker 17.2T scanner. We share the 3D drawings and all the information needed to replicate the cradle. Our design can be adapted to work on preclinical scanners with similar bore sizes and customized to add stimulation devices.

neuroscience↗

bioRxiv2023

The importance of experimental design for studying the vector competence of Ornithodoros ticks for African swine fever virus: a meta-analysis of published evaluations

African Swine Fever (ASF) is a highly economically devastating viral disease for swine. Soft ticks of the genus Ornithodoros are involved in its epidemiology, as vectors and natural reservoirs of African Swine Fever Virus (ASFV). The vector competence of Ornithodoros ticks for ASFV has been mainly studied by mimicking natural tick-to-pig transmission pathways through experimental infections in the laboratory. By reviewing the original research studies dating back to the 1960s on the vector competence of Ornithodoros for ASFV, we estimated the vector competence of 10 tick species in association with 38 viral strains resulting in 51 tick-virus associations. This assessment emphasized the extensive range of protocol designs employed and their impact on the success of tick infection with ASFV. Our results call for standardised procedures in vector competence experiments to facilitate further investigation and reduce potential experimental bias. In particular, we recommend the use of late nymphs or adult ticks from a laboratory colony to achieve efficient infection rates. In addition, viral inoculation should be carried out by blood meal rather than by injection, and preference should be given to high titre blood. Finally, detection of viral DNA should be performed 2 months after inoculation to distinguish between successful replication and residual virus in the tick.

ecology↗

bioRxiv2020

Enhancing c-MYC degradation via 20S proteasome activation induces in vivo anti-tumor efficacy

Enhancing proteasome activity is a potential new therapeutic strategy to prevent the accumulation of aberrant high levels of protein that drive the pathogenesis of many diseases. Herein, we examine the use of small molecules to activate the 20S proteasome to reduce aberrant signaling by the undruggable oncoprotein c-MYC, to treat c-MYC driven oncogenesis. Overexpression of c-MYC is found in more than 50% of all human cancer but remains undruggable because of its highly dynamic intrinsically disordered 3-D conformation, which renders traditional therapeutic strategies largely ineffective. We demonstrate herein that small molecule activation of the 20S proteasome targets dysregulated intrinsically disordered proteins (IDPs), including c-MYC, and reduces cancer growth in vitro and in vivo models of multiple myeloma, and is even effective in bortezomib resistant cells and unresponsive patient samples. Genomic analysis of various cancer pathways showed that proteasome activation results in downregulation of many c-MYC target genes. Moreover, proteasome enhancement was well tolerated in mice and dogs. These data support the therapeutic potential of 20S proteasome activation in targeting IDP-driven proteotoxic disorders, including cancer, and demonstrate that this new therapeutic strategy is well tolerated in vivo.

pharmacology and toxicology↗

bioRxiv2020

Multiscale interactions between plant part and a steep environmental gradient determine plant microbial composition in a tropical watershed

Plant microbiomes are shaped by forces working at different spatial scales. Environmental factors determine a pool of potential symbionts while host physiochemical factors influence how those microbes associate with distinct plant tissues. Interactions between these scales, however, are seldom considered. Here we analyze epiphytic microbes from nine Hibiscus tiliaceus trees across a steep environmental gradient within a single Hawaiian watershed. At each location we sampled eight microhabitats: leaves, petioles, axils, stems, roots, and litter from the plant, as well as surrounding air and soil. While the composition of microbial communities is driven primarily by microhabitat, this variable predicted more than twice the compositional variance for bacteria compared to fungi. Fungal community compositional dissimilarity increased more rapidly along the gradient than did bacteria. Additionally, the spatial dynamics of fungal communities differed among plant parts, and these differences influenced the distribution patterns and range size of individual taxa. Within plants, microbes were compositionally nested such that aboveground communities contained a subset of the diversity found belowground. Our findings identify potential differences underlying the mechanisms shaping communities of fungi and bacteria associated with plants, and indicate an interaction between assembly mechanisms working simultaneously on different spatial scales.

microbiology↗

bioRxiv2019

Shaky Scaffolding: Age Differences In Cerebellar Activation Revealed Through Activation Likelihood Estimation Meta-Analysis

Cognitive neuroscience research has provided foundational insights into aging, but has focused primarily on the cerebral cortex. However, the cerebellum is subject to the effects of aging. Given the importance of this structure in the performance of motor and cognitive tasks, cerebellar differences stand to provide critical insights into age differences in behavior. But, our understanding of cerebellar functional activation in aging is limited. Thus, we completed a meta-analysis of neuroimaging studies across task domains. Unlike in the cortex where an increase in bilateral activation is seen during cognitive task performance with advanced age, there is less overlap in cerebellar activation across tasks in older adults relative to young. Conversely, we see an increase in activation overlap in older adults during motor tasks. We propose that this is due to inputs for comparator processing in the context of control theory (cortical and spinal) that may be differentially impacted in aging. These findings advance our understanding of the aging mind and brain.

neuroscience↗

bioRxiv2018

From Synchrony to Asynchrony: Cerebellar-Basal Ganglia Functional Circuits in Young and Older Adults

Resting state functional magnetic resonance imaging (rs-fMRI) has indicated disruptions in functional connectivity in older (OA) relative to young adults (YA). While age differences in cortical networks are well studied, differences in subcortical networks are poorly understood. Both the cerebellum and the basal ganglia are of particular interest given their role in cognitive and motor functions, and work in non-human primates has demonstrated direct reciprocal connections between these regions. Here, our goal was twofold. First, we were interested in delineating connectivity patterns between distinct regions of the cerebellum and basal ganglia, known to have topologically distinct connectivity patterns with cortex. Our second goal was to quantify age-differences in these cerebellar-striatal circuits. We performed a targeted rs-fMRI analysis of the cerebellum and basal ganglia in 33 YA and 31 OA individuals. In the YA, we found significant connectivity both within and between the cerebellum and basal ganglia, in patterns supporting semi-discrete circuits that may differentially subserve motor and cognitive performance. We found a shift in connectivity, from one of synchrony in YA, to asynchrony in OA, resulting in substantial age differences. Connectivity was also associated with behavior. These findings significantly advance our understanding of cerebellar-basal ganglia interactions in the human brain.

neuroscience↗