Biology subjects

Gobbo, F.

Publications and source records attributed to Gobbo, F..

12 recordsLinked to original sources

bioRxiv2026

The PSD-95 interactome of hippocampal synapses potentiated in response to an in vivo learning task

Changes in the molecular composition of synapses underlie the functional changes in synaptic strength after learning. These phenomena have been studied either via imaging of individual candidate proteins, or via the global analysis of the synaptic proteome, lumping together all synapses, regardless of their activation or potentiation status. As a step towards the characterization of the proteome of synapses that have undergone potentiation following a learning paradigm, we have designed SynActive-PSD95-FLAG, a genetically encoded probe consisting of a FLAG-tagged PSD-95 endowed with activity-dependent local translation and expression enrichment at potentiating dendritic spines. SynActive-PSD95-FLAG was expressed via Adeno Associated Viral vectors (AAVs) in the hippocampus of mice which were exposed to contextual fear conditioning. Then, PSD95-FLAG immunoprecipitation from hippocampal extracts, followed by mass spectrometry, was used to characterize the changes in the PSD-95 interactome caused by in vivo synaptic potentiation. This revealed extensive rearrangements in the stoichiometry between PSD-95 and its direct and indirect interactors, highlighting proteins involved in peptide translation, including ribosomal components, and vesicle trafficking. Our results, obtained with a selectively expressed proteomic handle, provide new insight into the molecular substrates of hippocampal learning and a novel tool to study the proteome of potentiated synapses.

neuroscience↗

bioRxiv2026

West Nile virus response to mosquito and avian biodiversity in rural environments

ContextThe relationship between biodiversity and zoonotic disease risk is a central topic in community ecology, yet empirical evidence in Europe remains scarce and often contradictory compared to North American studies. Addressing this gap is fundamental to better anticipate zoonotic disease dynamics. ObjectivesWe investigated the transmission dynamics of West Nile virus (WNV) in Veneto (Italy), a major European hotspot. Because this vector-borne pathogen is primarily transmitted by Culex mosquitoes and maintained by several avian hosts, we analysed how multiple facets of both avian and mosquito biodiversity influence its transmission. MethodsUsing Generalized Additive Models (GAMs) trained on longitudinal entomological and ornithological surveillance data, we modelled the probability of WNV presence in mosquito pools as a function of host and vector community structure. To isolate the effects of biodiversity, we explicitly controlled for climatic and landscape covariates. ResultsIn agricultural landscapes, we found that higher avian diversity leads to higher viral presence, driven by the dominance of highly competent synanthropic hosts. Conversely, a dilution effect emerges across the broader regional landscape where areas of higher ecological integrity allow for more complex and functionally diverse avian communities. Furthermore, we identified significant vector-mediated regulation, where high abundances of mammophilic vectors effectively suppress viral prevalence through larval competition. ConclusionsOur findings suggest that the dilution effect is a property of intact ecosystems which can be lost, or even locally reversed, in anthropogenically altered environments. Because such habitat degradation fundamentally alters zoonotic transmission dynamics, landscape planning must prioritize ecological restoration. Ultimately, embedding these practices into One Health strategies represents a proactive approach to mitigating disease emergence.

ecology↗

bioRxiv2026

Tracking kdr Alleles Associated with Pyrethroid Resistance in Aedes albopictus across Italy: A Nationwide Genotypic Dataset by MosqIRIT Network.

This data paper presents a curated, georeferenced dataset of the frequencies of the two main target site mutations (V1016G and F1534C) associated with resistance to pyrethroid insecticides in Aedes albopictus in Italy. Populations were collected in 102 out 107 Italian provinces between 2023 and 2025. Specimens were sampled by members of the Mosquito Insecticide Resistance Italian Network (MosqIRIT) as part of RN2 activities within the INF-ACT project. Genotyping was performed on 3,517 individuals by specific allele-specific PCR assays. Each record includes metadata on sampling site, administrative location, developmental stage, collection method, and mutation-specific genotype frequencies. To support spatial analysis modelling effort, the dataset integrates geographic, eco-climatic, and demographic data. This resource will support mosquito control programs, pyrethroid resistance monitoring and managing, as well as ecological modelling, and is compliant with the FAIR data program.

genetics↗

bioRxiv2025

Distinct spatial distribution of potentiated dendritic spines in encoding- and recall-activated hippocampal neurons

Experimental advancements in neuroscience have identified cellular engrams -- ensembles of neurons whose activation is necessary and sufficient for memory retrieval. Synaptic plasticity, including long-term potentiation, is key to memory encoding and recall, but the relationship between learning-induced dendritic spine potentiation and neuron-wide activation remains unclear. Here, we employ a post-synaptic translation-dependent potentiation reporter (SA-PSD{Delta}Venus) and a neuronal activation reporter (ESARE-dTurquoise) to determine their spatiotemporal correlation in the mouse hippocampal CA1 following contextual fear conditioning (CFC). Potentiated spines were enriched in activated neurons, with distribution varying across CA1 layers at different phases of memory: potentiated spines were more frequent in activated neurons in stratum oriens and stratum lacunosum moleculare after CFC (encoding), while recall-activated neurons showed a larger number of potentiated spines in the stratum radiatum. These findings demonstrate that the relative weight and spatial distribution of potentiated synaptic inputs to hippocampal CA1 pyramidal neurons changes between the encoding and retrieval phases of memory.

neuroscience↗

bioRxiv2025

Hippocampal reactivation of planned trajectories is required for effective goal choice in an allocentric memory task

Hippocampal activity provides a representation of the world around us, as well as our position within that world. However, it is not known if and to what extent the chosen navigational reference frame can influence hippocampal representations during memory-based tasks, including those focused on future activity. Here, we develop and employ two naturalistic, carefully controlled variants of the everyday memory task to model the use of egocentric and allocentric coordinates in the same arena. By recording hippocampal neural activity through miniature microscopes in male rats performing each of the two tasks, we uncover differences in the representation of space, and in the features of memory-based action planning. By also deploying optogenetic inactivation during navigational decision making, we find that hippocampal representations observed during the planning phase are necessary for solving the allocentric, but not the egocentric version of the task. Overall, our findings reveal a functional link between non-local hippocampal representations and allocentric navigation.

neuroscience↗

bioRxiv2024

Opposing roles of physiological and pathological amyloid-β on synapses in live human brain slice cultures

In Alzheimers disease, it is theorised that amyloid beta (A{beta}) and tau pathology contribute to synapse loss. However, there is limited information on how endogenous levels of tau and A{beta} protein relate to patient characteristics, or how manipulating physiological levels of A{beta} impacts synapses, in living adult, human brain. Here, we employed live human brain slice cultures as a translational tool to assess endogenous tau and A{beta} release, pathology, and response to experimental manipulation. We found that the levels of A{beta}1-40 and tau detected in the culture medium depend on donor age, and brain region, respectively. Pharmacologically raising physiological A{beta} concentration enhanced levels of synaptic transcripts. Treatment of slices with A{beta}-containing Alzheimers disease brain extract resulted in postsynaptic A{beta} uptake and loss of presynaptic puncta. These data indicate that physiological and pathological A{beta} can have opposing effects on synapses in living human brain tissue.

neuroscience↗

bioRxiv2023

GATA1-defective immune-megakaryocytes as possible drivers of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disorder with limited therapeutic options. Insufficient understanding of driver mutations and poor fidelity of currently available animal models has limited the development of effective therapies. Since GATA1 deficient megakaryocytes sustain myelofibrosis, we hypothesized that they may also induce fibrosis in lungs. We discovered that lungs from IPF patients and Gata1lowmice contain numerous GATA1negative immune-poised megakaryocytes that, in mice, have defective RNA-seq profiling and increased TGF-{beta}1, CXCL1 and P-selectin content. With age, Gata1low mice develop fibrosis in lungs. Development of lung fibrosis in this model is prevented by P-selectin deletion and rescued by P-selectin, TGF-{beta}1 or CXCL1 inhibition. Mechanistically, P-selectin inhibition decreases TGF-{beta}1 and CXCL1 content and increases GATA1positive megakaryocytes while TGF-{beta}1 or CXCL1 inhibition decreased CXCL1 only. In conclusion, Gata1low mice are a novel genetic-driven model for IPF and provide a link between abnormal immune-megakaryocytes and lung fibrosis.

immunology↗

bioRxiv2022

Arbuscular mycorrhizae reduce stress-induced plasticity of plant functional traits. A meta-analysis study

We aimed at exploring the plant functional traits whose stress-induced plasticity is altered by the presence of AM fungi, considering the direction of their changes. We also sought for a coordinated variation of plant biomass and functional traits, during plant adaptation to environmental stressors, and the role of AM status on the variation. We performed a meta-analysis across 114 articles spanning 110 plant species or cultivars. We quantified the size effect of AM symbiosis on the stress-induced plasticity of several reported and calculated functional traits, and using linear mixed model analysis (LMM). Correlation between traits plasticity and total biomass variation were also performed through LMM. The literature search and further selection yielded seven functional traits, extracted from 114 laboratory studies, including 888 observations and 110 plant species/cultivars. Evidence for significant effects of predictor variables (type of stress, AM symbiosis and/or their interaction) on plasticity were found for three of these functional traits: leaf-area ratio (LAR), root mass fraction (RMF) and root-shoot (R:S) ratio. Our results provided evidence to accept the hypothesis that AM fungal inoculation may reduce the phenotypic plasticity of important plant functional traits leaf area ratio (LAR), root mass fraction (RMF) and root-shoot (R:S) ratio, by decreasing its magnitude. We also found a weak correlation between traits plasticity and total biomass variation. Although our literature search and data collection were intensive and our results robust, the scope of our conclusions is limited by the agronomical bias of plant species targeted by the meta-analysis. Further knowledge on non-cultivable plant species and better understanding of the mechanisms ruling resources allocation in plants would allow more generalized conclusions.

plant biology↗

bioRxiv2021

CXCL8/CXCR2 signaling mediates bone marrow fibrosis and represents a therapeutic target in myelofibrosis

Pro-inflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution remain yet to be fully elucidated. Previously we identified a critical role for combined constitutive JAK/STAT and aberrant NF-{kappa}B pro-inflammatory signaling in myelofibrosis development. Using single-cell transcriptional and cytokine-secretion studies of primary MF patient cells and two separate murine models of myelofibrosis, we extend this previous work and delineate the role of CXCL8/CXCR2 signaling in MF pathogenesis and bone marrow fibrosis progression. MF patient hematopoietic stem/progenitor cells are enriched in a CXCL8/CXCR2 gene signature and display dose-dependent proliferation and fitness in response to exogenous CXCL8 ligand in vitro. Genetic deletion of Cxcr2 in the hMPLW515L adoptive transfer model abrogates fibrosis and extends overall survival, and pharmacologic inhibition of the CXCR1/2 pathway improves hematologic parameters, attenuates bone marrow fibrosis, and synergizes with JAK inhibitor therapy. Our mechanistic insights provide a rationale for therapeutic targeting of the CXCL8/CXCR2 pathway in MF patients at risk for continued fibrotic progression.

cancer biology↗

bioRxiv2021

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/Beta-catenin activation

Real-time, in vivo imaging provides an essential window into the spatiotemporal cellular and molecular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we captured the earliest cellular events underlying the impact of active Wnt/{beta}-catenin signaling on the organization and differentiation of the mammary epithelium. This enabled us to interrogate how Wnt/{beta}-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that {beta}-catenin stabilization, when targeted to either of the mammary luminal or basal epithelial lineages, invariably leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo, and reveal that in mammary neoplastic development, {beta}-catenin activation dictates a hair-follicle/epidermal differentiation program independently of the targeted cell of origin.

cell biology↗

bioRxiv2018

The structure of the Pro-domain of mouse proNGF in contact with the NGF domain

Nerve Growth Factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation, maintenance, growth and survival of target neurons. Expressed as a proNGF precursor, NGF is then matured by furin-mediated protease cleavage. Increasing evidence suggests that NGF and proNGF have distinct cellular partners which account for different functional roles. While the structure of mature NGF is available, little is known about the structure of the pro-domain within the context of proNGF because the dynamical and structural features of the protein have so far prevented its structure determination. We have exploited a new hybrid strategy based on nuclear magnetic resonance and modelling validated by small angle X-ray scattering to gain novel insights on the pro-domain, both in isolation and in the context of proNGF. We show that the isolated pro-domain is intrinsically unstructured but has a clear tertiary structure propensity and forms transient tertiary intramolecular contacts. It is also able to interact, albeit weakly, with mature NGF and has per se the ability to induce growth cone collapse, indicating functional independence. Based on paramagnetic relaxation enhancement data and advanced molecular modelling, we have then reconstructed the overall properties of the pro-domain in the context of proNGF and showed that it has a compact structure. Our data represent an important step towards the structural and functional characterization of the properties of proNGF and its pro-domain.

biophysics↗

bioRxiv2016

Activity-dependent expression of reporter proteins at dendritic spines for synaptic activity mapping and optogenetic stimulation

Increasing evidence points to the importance of dendritic spines in the formation and allocation of memories, and alterations of spine number and physiology are associated to memory and cognitive disorders. Synaptic connections and pathways constitute the physical substrate that conveys information in the brain, and different combinations of active synaptic connections are believed to be responsible for the encoding of specific memories. In addition, modifications of the activity of such subsets of synapses are believed to be crucial for memory establishment, but a way to directly test this hypothesis, by selectively controlling the activity of potentiated spines, is currently lagging behind. Therefore it would be important to develop methods to tag active synapses for mapping functionally active connections and to selectively stimulate or interfere with active synapses. Here we introduce an approach to express light-sensitive membrane channels at synapses in an activity-dependent way by means of RNA and protein regulatory sequences. This approach is based on the local expression of reporter proteins, including optogenetic probes, at activated synapses and will allow the mapping of previously active synapses and the re-activation of the neuron only at these sites. This will allow extending the investigation of memory processes beyond the current neuron tagging technologies, whose resolution is limited at the cellular scale. Thus, it will be possible to unveil and recall the synaptic engram out of the global set of synapses.

neuroscience↗