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Andre, A.

Publications and source records attributed to Andre, A..

6 recordsLinked to original sources

Sarbecovirus-associated gut microbiome instability in a natural bat reservoir

Sarbecoviruses, a subgenus of Betacoronavirus, display both respiratory and gastrointestinal tropism, suggesting potential interactions with host gut microbial communities. However, ecological signatures of infection in wild bats remain poorly understood. We investigated associations between Sarbecovirus infection status, gut microbiome structure, and diet composition in Rhinolophus shameli roosting in northeastern Cambodia. Fecal samples collected across dry and wet seasons (2023-2024) were subject to full-length 16S rRNA gene sequencing and arthropod DNA metabarcoding. Sarbecovirus-positive bats exhibited stable alpha diversity but consistent shifts in gut community composition and increased interindividual variability consistent with the Anna Karenina Principle, suggesting infection-associated destabilization of community assembly rather than diversity erosion. Infection status was associated with enrichment of Shigella and Escherichia species, taxa linked to inflammatory or epithelial stress states in bats. In contrast, dietary composition showed no strong global structuring by infection status and weak coupling with bacterial community structure, suggesting that trophic ecology is unlikely to be the main driver of the infection-associated microbiome signal. Although causal directionality cannot be inferred, our results reveal measurable and consistent microbiome restructuring associated with Sarbecovirus detection in a natural reservoir host and highlight the potential of microbiome profiling for monitoring wildlife disease processes.

ecology↗

Projection-specific Routing of Odor Information in the Olfactory Cortex

Sensory processing in the mammalian cortex relies on extensive feedforward and feedback connections, yet how information is routed along these pathways remains poorly understood. Here, we examined the functional properties of feedback and feedforward neurons in the mouse olfactory (piriform) cortex. We selectively labeled neurons projecting to the olfactory bulb (OB, feedback) or medial prefrontal cortex (mPFC, feedforward) and recorded their activity during passive odor exposure and learning of an odor discrimination task. We found that odor identity and reward associations were encoded by OB-projecting ensembles early during odor exposure, whereas mPFC-projecting neurons encoded this information later, aligned with behavioral responses. Moreover, mPFC-projecting neurons maintained a stable representation of valence across days, while OB-projecting neurons exhibited pronounced plasticity. Together, these findings reveal that odor information is selectively routed through feedforward and feedback pathways and suggest that the functional properties of piriform neurons mirror the computational demands of their downstream targets.

neuroscience↗

tRNASer overexpression induces adaptive mutations in NSCLC tumors

tRNAs are a driving force of genome evolution in Yeast and Bacteria. Their deregulation is frequently observed in tumors with Serine tRNAs being often overexpressed. This has important functional consequences, such as increased metabolism and tumor growth. In yeast, time and chemical stimulus boost alterations in the genome driven by tRNA deregulation. Therefore, we hypothesized that tRNA deregulation may contribute to the increased genome instability observed in tumors. To study the effect of tRNA deregulation in tumors, we overexpressed tRNA-Ser-AGA-2-1 in a NSCLC cell line, H460. This cell line and a Mock (control) were xenografted in nude mice and collected at 3 timepoints: T1-Naive; T2-Treated once with cisplatin/vehicle and; T3) treated twice with cisplatin/vehicle. These tumors were characterized by WES, RNAseq and Mass Spectrometry and the data obtained was integrated. The tumor mutation burden was increased in T3 tRNASerOE tumors, regardless of treatment. Although in T1 Mock and tRNASer tumors have a similar number of variants, in T2&3, tRNASerOE tumors display two times more variants than Mock tumors regardless of treatment. Interestingly, tRNASerOE exclusive variants favor proliferation and therapy resistance, which is in line with the phenotypes observed and supported by RNAseq and proteomics data. In conclusion, tRNASerOE increases the tumor mutation burden and the variants detected favor tumor growth, proving tRNA deregulation is enough to induce adaptive mutations in the genome.

cancer biology↗

Neutrophils degranulate GAG-containing proteoglycofili, which block Shigella growth and degrade virulence factors

Summary paragraphNeutrophil degranulation plays a central role in their ability to kill pathogens but also to stimulate other immune cells1-3. Here we show that neutrophil degranulation, induced in hypoxia or upon Shigella infection in vitro and in vivo, leads to the release of polymers called neutrophil Proteoglycofili (PGF). PGF are mainly composed of granular proteins (myeloperoxidase, elastase, lactoferrin, cathelicidin, albumin) pre-stored in various types of granules, and chondroitin sulfate. PGF individual fibers have a diameter of 43.9 {+/-} 20.3 nm and. They secreted by viable neutrophils and do not contain DNA, as opposed to NETs which contains also granular proteins, chondroitin sulfate in addition to chromatin, released upon neutrophil disintegration and cell death. We demonstrated that PGF block the growth of Shigella and other bacteria and degrade Shigella virulence factors. The degradation of the chondroitin sulfate polymers with testes hyaluronidases destabilizes PGF ultrastructure and abolishes its antimicrobial activity. Our results provide novel insights in the neutrophil degranulation process and open new doors for the investigation of PGF contribution to cytokines concentration gradient formation and adaptive immune cells activation. Further investigations are required to better appreciate the importance of this "sterile blaster" in infectious or inflammatory diseases.

immunology↗

Epithelial-mesenchymal plasticity induced by discontinuous exposure to TGFβ1 promotes tumour growth

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity favouring tumour growth. We developed an EMT model by on/off exposure of epithelial EpH4 cells (E-cells) to TGF{beta}1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia, by using RNA sequencing, Immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays, as well as cell-xenografts in nude mice. Phenotypic reverted-epithelial cells (RE-cells), obtained after MET induction, presented pure epithelial morphology and proliferation rate resembling E-cells. However, RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a unique and heterogeneous mixture of cell-subpopulations, with high self-renewal ability fed by oxidative phosporylation. RE-cells heterogeneity is stably maintained for long periods after TGF{beta}1 removal, both in vitro and in large derived tumours in nude mice. Overall, we show that phenotypic reverted-epithelial cells (RE-cells) do not return to the molecular and functional epithelial state, present mesenchymal features related with aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cells reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour-growth promoting factor in vivo.

cell biology↗

Chronic environmentally relevant levels of Simvastatin induces non-monotonic responses in Zebrafish (Danio rerio)

Simvastatin (SIM), a hypocholesterolaemic compound, is among the most prescribed pharmaceuticals for cardiovascular disease prevention worldwide. Several studies have shown that acute exposure to SIM is able to produce multiple adverse effects in aquatic organisms. However, uncertainties still remain regarding the chronic effects of SIM in aquatic ecosystems. Therefore, the present study aimed to investigate the effects of SIM in the model freshwater teleost zebrafish (Danio rerio) following a chronic exposure (90 days) to environmentally relevant concentrations ranging from 8 ng/L to 1000 ng/L. This study used a multi-parametric approach integrating distinct ecological-relevant endpoints, i.e. survival, growth, reproduction and embryonic development, with biochemical markers (cholesterol and triglycerides). Furthermore, Real Time PCR was used to analyse the transcription levels of key genes involved in the mevalonate pathway (hmgcra, cyp51, and dhcr7). Globally, SIM induced several non-monotonic dose-responses; embryonic development, biochemical and molecular markers, were significantly impacted in the low-intermediate concentrations, 40 ng/L and 200 ng/L, whereas no effects were recorded for the highest tested SIM levels (1000 ng/L). Taken together, these findings expand our understanding of statins effects in teleosts, demonstrating significant impacts at environmentally relevant concentrations. The findings highlight the importance of addressing the effects of chemicals under chronic low-level concentrations.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC=\"FIGDIR/small/289694v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (17K):\norg.highwire.dtl.DTLVardef@1922156org.highwire.dtl.DTLVardef@caad80org.highwire.dtl.DTLVardef@44c058org.highwire.dtl.DTLVardef@1afe60f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISeveral uncertainties exist regarding simvastatin mode of action in non-target organisms\nC_LIO_LIThis work integrates D. rerio multi-level responses after long-term exposure to simvastatin\nC_LIO_LISimvastatin impacted cholesterol/triglycerides levels and transcript levels of genes related to mevalonate pathway.\nC_LIO_LIParental exposure to simvastatin induced offspring embryonic malformations.\nC_LIO_LIEmbryonic abnormalities, biochemical and molecular data did follow a non-monotonic curve.\nC_LI

pharmacology and toxicology↗