Biology subjects

Marin, P.

Publications and source records attributed to Marin, P..

10 recordsLinked to original sources

bioRxiv2025

A reciprocal interplay between 5-HT2A and mGlu5 receptors underlies neuroplasticity

The serotonin (5-HT)2A receptor is the primary target of numerous psychoactive drugs including serotonergic psychedelics, and mediates psychedelics-induced neuroplasticity, but the signaling mechanisms involved remain poorly characterized. Using quantitative phosphoproteomics, we show that the administration of the hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) to mice promotes the phosphorylation of synaptic proteins belonging to a strongly interconnected protein network and comprising the metabotropic glutamate (mGlu)5 receptor and the scaffolding protein Shank3. Functional studies revealed that hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists promote synaptic targeting of mGlu5 receptor and its association with Shank3. Furthermore, they gate neuroplasticity in cortical neurons through a mechanism requiring mGlu5 receptor, protein kinase C and Shank3. Conversely, neuroplasticity elicited by mGlu5 receptor activation depends on 5-HT2A receptor. Collectively, these findings demonstrate that neuroplasticity-promoting properties of psychedelics depend on a functional, reciprocal interplay between 5-HT2A and mGlu5 receptors involving the synaptic scaffolding protein Shank3.

neuroscience↗

bioRxiv2025

Plant Growth Promoting fungal endophyte Colletotrichum tofieldiae Ct0861 reduces mycotoxigenic Aspergillus fungi in maize grains

1.BackgroundMaize (Zea mays L.) is a globally critical crop that faces numerous challenges, including contamination by mycotoxigenic fungi such as Aspergillus spp., which threaten food safety and marketability. This study evaluates the potential of the fungal endophyte Colletotrichum tofieldiae strain Ct0861 as a bioinoculant to enhance maize productivity and investigates its impact on the maize-associated bacterial and fungal microbiomes. ResultsField trials showed that Ct0861 treatment enhances biomass and yield compared to controls, irrespective of the application method assayed (seed or spray application). Comprehensive microbiome profiling across soil, rhizosphere, roots, leaves, and grains revealed that Ct0861 inoculation induced subtle, compartment-specific effects on microbial diversity and composition, with similar effects for the two application methods used. Fungal alpha-diversity in grains was significantly reduced, while beta-diversity analyses showed localized shifts, particularly in soil and grain-associated microbial communities. Despite these changes, the core microbiome assemblages remained stable, indicating minimal alteration to the broader microbiome structure. Remarkably, Ct0861 significantly reduced the prevalence of Aspergillus spp. in maize grains, as confirmed by controlled infection assays. This reduction resulted in lower aflatoxin levels, demonstrating the biocontrol potential of Ct0861. ConclusionThese findings underscore Ct0861s dual benefits in enhancing crop yield and safety reducing fungal mycotoxin contamination. Further studies are necessary to elucidate the underlying mechanisms and expand its application across diverse agroecosystems.

microbiology↗

bioRxiv2024

Physical interaction with Ephrin B1 promotes CXCR4 intracellular localization and oncogenic potential

Chemokine receptor 4 (CXCR4) is a member of the chemokine receptor exclusively activated by the chemokine CXCL12. While CXCR4 regulates numerous physiological processes associated with cell migration and embryogenesis, its overexpression has been involved in various cancer types. Studies suggest that intracellular CXCR4 expression rather than CXCR4-operated signaling underlies its pro-tumorigenic functions. Given the role of GPCR interacting proteins in their trafficking and subcellular localization, we characterized the CXCR4 interactome using an affinity purification coupled to mass spectrometry (AP-MS) strategy. The most abundant protein identified in the CXCR4 interactome is Ephrin B1, a member of the Ephrin protein family that shares several functions with CXCR4, such as the regulation of cell migration and proliferation. Further studies showed that interaction between CXCR4 and Ephrin B1 is direct and enhanced by treating cell with CXCL12. They also indicated that Ephrin B1 prevents CXCR4 N-glycosylation, decreases CXCR4 cell surface expression and consistently inhibits CXCL12-induced CXCR4 coupling to Gi1-3 and the recruitment of {beta}-arrestins 1 and 2. Conversely, Ephrin B1 signals to Erk1,2 through CXCR4 activation and mediates the decrease in Death Receptor 5 expression elicited by intracellular CXCR4. Collectively, these findings identify Ephrin B1 as a key mediator of CXCR4 tumorigenic signaling.

biochemistry↗

bioRxiv2024

Maize associated bacterial and fungal microbiomes show contrasting conformation patterns that are resilient to water availability

Plant-associated microorganisms can help crops to alleviate water stress and increase the resilience of agricultural ecosystems to climate change. However, we still lack knowledge on the dynamics of bacterial and fungal microbial kingdoms within the soil and plant microbiomes and the response of these communities to different conditions such us, for example, water restrictions. This information is essential for the development of microbiome-based solutions to improve crop resilience to stressors associated to climate change. In this work, we explored: i) the conformation of the bacterial and fungal assemblages of different soil and plant compartments (bulk soil, rhizosphere, roots, leaves and grains) along the crop cycle of maize in an open field trial; and ii) the effect of water restriction on the maize microbiome comparing optimal irrigation with a 30% reduction of water supply. Our results show that microbial communities are highly structured along soil and plant compartments, with contrasting patterns for bacteria and fungi that were intensified towards the end of the plant cycle. Root showed the most differentiated bacterial assemblage while fungi conformed a very distinct community in the leaf, suggesting a relevant contribution of aerial fungal propagules to the microbiome of this plant organ. Despite the reductions in plant growth and yield, the microbiome of limited-watered plants did not show severe alterations. Still, significant impacts were observed within compartments, being fungi more responsive to limited watering than bacteria. Network analysis suggest that bacteria and fungi may play different roles in the shifts observed under water stress.

microbiology↗

bioRxiv2023

CITE-seq reveals inhibition of NF-kB pathway in B cells from vitamin D-treated multiple sclerosis patients

Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS) and has been associated with disease activity and progression. Vitamin D treatment has emerged as potentially protective, despite conflicting results from randomized controlled trials. Here, we used single-cell RNA-sequencing (scRNA-seq) combined with barcoded antibodies targeting surface markers (CITE-seq) to uncover candidate genes and pathways regulated in PBMC subpopulations from MS patients receiving high-dose vitamin D (n=5) or placebo (n=5). Best candidates were combined with genes involved in immune function and vitamin D metabolism for validation in a new cohort (n=8 in each group) by high-throughput quantitative polymerase chain reaction (HT-qPCR) in FACS-sorted naive CD4, Th1, Th17, Treg, naive CD8, memory and naive B cells, and MAIT cells. CITE-seq revealed no significant changes in the proportions of these subpopulations in response to vitamin D treatment. Out of the 92 candidate genes identified by CITE-seq, we validated differential expression of five genes (UXT, SNRPN, SUB1, GNLY and KLF6) using HT-qPCR. Furthermore, CITE-seq uncovered vitamin D-induced regulation of several pathways in naive and memory B cells, including MAPK, TLR and interleukin pathways, that may contribute to counteract Epstein-Barr virus (EBV)-induced resistance to apoptosis, notably through inhibition of the NF-{kappa}B pathway. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/559400v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1ad28c1org.highwire.dtl.DTLVardef@14ed135org.highwire.dtl.DTLVardef@188fea1org.highwire.dtl.DTLVardef@105353c_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2023

Syndecan-1 as specific cerebrospinal fluid biomarker of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease often characterized by remission and relapse periods occurring at irregular intervals after an initial attack (clinically isolated syndrome) and followed by a gradual progression of disability. Clinical symptoms, magnetic resonance imaging and abnormalities in cerebrospinal fluid (CSF) immunoglobulin profile allow diagnosis with a good sensitivity. However, current biomarkers lack specificity or have poor individual prognostic value. To identify novel candidate biomarkers of MS, we analysed 1) the CSF proteome from symptomatic controls and patients with clinically isolated syndrome or remitting-relapsing multiple sclerosis (n=40), and 2) changes in oligodendrocyte secretome upon proinflammatory or pro-apoptotic treatment. Proteins exhibiting differences in abundance in both studies were combined with previously described MS biomarkers to build a list of 87 proteins that were quantified by parallel reaction monitoring (PRM) in CSF samples from a new cohort comprising symptomatic controls and MS patients at different disease stages (n=60). The eleven proteins that passed this qualification step were subjected to a new PRM assay from a larger cohort (n=158) comprising patients with MS at different disease stages or with other inflammatory or non-inflammatory neurological disorders. Collectively, these studies identified a biomarker signature of MS that might improve MS diagnosis and prognosis. These include the oligodendrocyte precursor cell proteoglycan Syndecan-1, which was more efficient than previously described biomarkers to discriminate MS from other inflammatory and non-inflammatory neurological disorders.

neuroscience↗

bioRxiv2023

Identification and Characterisation of Proteins Binding to a G-Quadruplex Origin G-rich Repeated Element in Mammalian Cells

In metazoan cells, replication of genomic DNA initiates from thousands of discrete chromosomal loci known as origins. Proteins such as the Origin Recognition Complex (ORCs) associate with origins, but this does not show clear sequence specificity for DNA binding. Genome-wide origin mapping studies have shown that the region surrounding the replication initiation site contains motifs such as the Origin G-rich Repeated Element (OGRE), proximal to the majority of origins. Here, using an approach coupling DNA affinity purification to quantitative proteomics, we identified proteins that interact specifically with an OGRE. Three of the top-scoring interactors, Dhx36, Pura and Tial1, were selected for further study. We show that Dhx36 and Tial1 localise to the nucleus and their knockdown decreased cells in S-phase resulting in their accumulation in the G1 phase of the cell cycle. Altogether these results indicate that these OGRE-binding factors may play roles in DNA synthesis in mammalian cells.

cell biology↗

bioRxiv2022

Non-cancer stem cell-derived Fibromodulin activates Integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth

Cancer stem cells alone can initiate and maintain tumors, but the function of non-cancer stem cells that form the tumor bulk remains poorly understood. Proteomic analysis showed a higher abundance of the extracellular matrix small leucine-rich proteoglycan Fibromodulin (FMOD) in the conditioned medium of non-cancer stem cells (DGCs; differentiated glioma cells) of glioma compared to that of glioma stem-like cells (GSCs). DGCs silenced for FMOD fail to cooperate with co-implanted GSCs to promote tumor growth. FMOD downregulation neither affects GSC growth and differentiation nor DGC growth and reprogramming in vitro. DGC-secreted FMOD promotes angiogenesis by activating Integrin-dependent Notch signaling in endothelial cells. Furthermore, conditional silencing of FMOD in newly generated DGCs in vivo inhibits the growth of GSC-initiated tumors due to poorly developed vasculature and increases mouse survival. Collectively, these findings demonstrate that DGC-secreted FMOD promotes glioma tumor angiogenesis and growth through paracrine signaling in endothelial cells and identifies a DGC-produced protein as a potential therapeutic target in glioma.

cancer biology↗

bioRxiv2020

Drosophila suzukii oxidative stress response involves Jheh gene cluster but not transposable elements

The study of the mechanisms involved in adaptation remains a timely issue, particularly in the context of global changes. To better understand these mechanisms of rapid adaptation, invasive species are a good model because they are subjected to new and/or different environmental factors. Using different lines of different geographical origin of the invasive pest Drosophila suzukii, we characterized the phenotypic response to oxidative stress. Subsequently, we tested the involvement of the Jheh gene cluster in this response and the possible role of transposable elements. We show that the resistance to oxidative stress of the lines appears to be related to their invasive status and we confirm the role of the Jheh gene cluster in this response. We have not identified any transposable elements in this gene region that could influence the expression of the gene. Summary statementThe responses to oxidative stress of the invasive species, Drosophila suzukii, show variability between genotypes related to their invasion status. The genes of the juvenile hormone epoxide hydrolase cluster are involved in this response.

evolutionary biology↗

bioRxiv2017

Tau hyperphosphorylation on T217 in cerebrospinal fluid is specifically associated to amyloid-β pathology

IntroductionModification of CSF tau phosphorylation in AD remains controversial since total-tau and phospho-tau levels measured by immunoassays are highly correlated.\n\nMethodsStoichiometry of phosphorylation of CSF tau was monitored on five sites by mass spectrometry. We compared 50 participants with AD at mild to moderate stages, others tauopathies and controls then confirmed our results in a cohort of 86 participants cognitively normal or with mild cognitive impairment and stratified according to amyloid-{beta} status.\n\nResultsChanges in tau phosphorylation rates were observed in AD participants but not in other tauopathies. T181 appeared slightly hyperphosphorylated in AD. In comparison, T217 phosphorylation, was considerably modified. We demonstrated T217 hyperphosphorylation occurred systematically in amyloid positive participants even at preclinical stage (AUC 0.999). T217 phosphorylation change specificity overpasses other phosphorylated tau sites investigated in this study, but also CSF total-tau and p-tau levels.\n\nDiscussionCSF T217 hyperphosphorylation defines a specific tauopathy status concomitant with {beta}-amyloidosis.

neuroscience↗