Biology subjects

Denis, C.

Publications and source records attributed to Denis, C..

8 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

Sex-dependent involvement of lateral septum astrocytes in social fear: Role of oxytocin receptor signaling

Astrocytes are now widely recognized as important modulators of synaptic plasticity and socio-emotional behaviors. Recent studies highlight their involvement in anxiety- and depressive-like behaviors, particularly via oxytocin (OXT) signaling. While the specific contributions of astrocytes remain largely unexplored, the role of OXT receptor (OXTR) signaling in the lateral septum (LS) in regulating social fear expression has been well characterized. Here, we studied the differential contribution of astrocytic OXTR signaling using a social fear conditioning (SFC+) paradigm. We found the highest abundance of astrocytes, and especially of OXTR-expressing (OXTR+) astrocytes, within the caudal LC (LSc) compared to the rostral LS in both male and female mice. Interestingly, female mice displayed a significantly higher number of astrocytes and OXTR+ astrocytes in the LSc in comparison to males. However, social fear acquisition resulted in dynamic changes in LSc astrocytic morphology and calcium activity in male mice. Furthermore, we showed that pre-SFC acquisition pharmacology-induced loss of local astrocytic function facilitated the extinction of social fear in males. In support, astrocyte-specific OXTR knockdown in the LSc also facilitated social fear extinction in both males and females. Taken together, our study identifies OXTR-signaling in LSc astrocytes as a crucial component in the mechanisms underlying the regulation of social fear in a sex-dependent manner.

neuroscience↗

bioRxiv2024

Oxytocin Gαi signaling-induced amygdala astrocytes processes retraction shapes behavioral stress response

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin- dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology- dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.

neuroscience↗

bioRxiv2021

Distinct signatures of loss of consciousness during Focal Impaired Awareness (FIA) versus Focal to Bilateral Tonic-Clonic (FBTC) seizures

Loss of consciousness (LOC) is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany LOC during focal impaired awareness (FIA) seizures, the mechanisms of LOC during focal to bilateral tonic-clonic (FBTC) seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between FIA and FBTC seizures may also help to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of LOC and intracranial EEG (iEEG) activity during 129 FIA and 50 FBTC from 41 patients. We characterized iEEG changes both in the seizure onset zone (SOZ) and in areas remote from SOZ with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of iEEG sleep-like activities: slow-wave activity (SWA; 1-4 Hz) and beta/delta ratio (B/D; a validated marker of cortical activation) during FIA vs. FBTC. Second, we quantified differences between FBTC and FIA for a marker validated to detect ictal cross-frequency coupling: phase-locked high-gamma (PLHG; high gamma phased locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index (i.e. the number of channels crossing an energy ratio threshold for high vs. low frequency power). Third, we assessed changes in iEEG activity preceding and accompanying behavioral generalization onset and their correlation with electromyogram (EMG) channels. In addition, we analyzed human cortical multi-unit activity recorded with Utah arrays during three FBTC. Compared to FIA, FBTC seizures were characterized by deeper LOC and by stronger increases in SWA in parieto-occipital cortex. FBTC also displayed more widespread increases in cortical activation (B/D), ictal cross-frequency coupling (PLHG) and ictal recruitment (epileptogenicity index). Even before generalization, FBTC displayed deeper LOC; this early LOC was accompanied by a paradoxical increase in B/D in fronto-parietal cortex. Behavioral generalization coincided with complete loss of responsiveness and a subsequent increase in high-gamma in the whole brain, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of FBTC revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the SOZ. Unlike during FIA, LOC during FBTC is characterized by a paradoxical increase in cortical activation and neuronal firing. These findings suggest differences in the mechanisms of ictal LOC between FIA and FBTC and may account for the more negative prognostic consequences of FBTC.

neuroscience↗

bioRxiv2021

Haploinsufficiency of the mouse Tshz3 gene leads to kidney dysfunction

Renal tract defects and autism spectrum disorder (ASD) deficits represent the phenotypic core of the 19q12 deletion syndrome caused by the loss of one copy of the TSHZ3 gene. While a proportion of Tshz3 heterozygous (Tshz3+/lacZ) mice display ureteral defects, no kidney defects have been reported in these mice. The purpose of this study was to characterize the expression of Tshz3 in adult kidney as well as the renal physiological consequences of embryonic haploinsufficiency of Tshz3 by analyzing the morphology and function of Tshz3 heterozygous adult kidney. Here, we described Tshz3 expression in the smooth muscle and stromal cells lining the renal pelvis, the papilla and glomerular endothelial cells (GEnCs) of the adult kidney. Histological analysis showed that Tshz3+/lacZ adult kidney had an average of 29% fewer glomeruli than wild type kidney. Transmission electron microscopy (TEM) of Tshz3+/lacZ glomeruli revealed ultrastructural defects. Compared to wild type, Tshz3+/lacZ mice showed no difference in their urine parameters but lower blood urea, phosphates, magnesium and potassium at 2 months of age. At the molecular level, transcriptome analysis identified differentially expressed genes related to inflammatory processes in Tshz3+/lacZ compare to wild type (WT; control) adult kidneys. Lastly, analysis of the urinary peptidome revealed 33 peptides associated with Tshz3+/lacZ adult mice. These results provide the first evidence that in the mouse Tshz3 haploinsufficiency leads to cellular, molecular and functional abnormalities in the adult mouse kidney.

genetics↗

bioRxiv2021

Naturalized Dolichogenidea gelechiidivoris Marsh (Hymenoptera: Braconidae) complement the resident parasitoid complex of Tuta absoluta (Meyrick) (Lepidopera:Gelechiidae) in Spain

Our study aimed to assess the contribution of natural parasitism due to Necremnus tutae Ribes & Bernardo (Hymenoptera: Eulophidae) to the biological control of Tuta absoluta (Meyrick) (Lepidopera:Gelechiidae) in commercial plots where an IPM program based on the use of predatory mirid bugs was implemented. During the samplings, the presence of another parasitoid was detected and, therefore, a second part of our study intended to identify this species and to evaluate the importance of its natural populations in the biological control of the pest. Leaflets with T. absoluta galleries were collected during 2017-2020 from commercial tomato plots in the horticultural production area of Catalonia (Northeast Spain), including greenhouses, open fields, and roof covered tunnels that lack side walls. In the laboratory, T. absoluta larvae were classified as ectoparasitized, alive, or dead. Reared parasitoids from ectoparasitized larvae were mostly morphologically identified as Necremnus sp. with parasitism rates that peaked in summer months with values between 9 and 15%. Some of these ectoparasitized larvae also yielded another parasitoid identified as Dolichogenidea gelechiidivoris Marsh (Hymenoptera: Braconidae) by both morphological and molecular-DNA barcoding methods. In 2020, parasitism rates due to D. gelechiidivoris that increased with season up to 22%. Our work reports for the first time in Europe the presence of the neotropical species D. gelechiidivoris adding this biocontrol agent to the resident parasitoid complex of T. absoluta in Spain.

ecology↗

bioRxiv2021

Analysis of viromes and microbiomes from pig fecal samples reveals that phages and prophages are not vectors of antibiotic resistance genes

Understanding the transmission of antibiotic resistance genes (ARGs) is critical for human health. For this, it is necessary to identify which type of mobile genetic elements is able to spread them from animal reservoirs into human pathogens. Previous research suggests that in pig feces, ARGs may be encoded by bacteriophages. However, convincing proof for phage-encoded ARGs in pig viromes is still lacking, because of bacterial DNA contaminating issues. We collected 14 pig fecal samples and performed deep sequencing on both highly purified viral fractions and total microbiota, in order to investigate phage and prophage-encoded ARGs. We show that ARGs are absent from the genomes of active, virion-forming phages (below 0.02% of viral contigs from viromes), but present in three prophages, representing 0.02% of the viral contigs identified in the microbial dataset. However, the corresponding phages were not detected in the viromes, and their genetic maps suggest they might be defective. Furthermore, our dataset allows for the first time a comprehensive view of the interplay between prophages and viral particles.

microbiology↗

bioRxiv2017

Quiescence unveils a novel mutational force in fission yeast

One Sentence SummaryThe quiescence-driven mutational landscape reveals a novel evolutionary force.\n\nAbstractDuring cell division, the spontaneous mutation rate is expressed as the probability of mutations per generation, whereas during quiescence it will be expressed per unit of time. In this study, we report that during quiescence, the unicellular haploid fission yeast accumulates mutations as a linear function of time. We determined that 3 days of quiescence generate a number of invalidating mutations equivalent to that of one round of DNA replication. The novel mutational landscape of quiescence is characterized by insertion/deletion accumulating as fast as single nucleotide variants, and elevated amounts of deletions. When we extended the study to 3 months of quiescence, we confirmed the replication-independent mutational spectrum at the whole-genome level of a clonally aged population and uncovered phenotypic variations that subject the cells to natural selection. Thus, our results support the idea that genomes continuously evolve under two alternating phases that will impact on their size and composition.

genomics↗