Biology subjects

Villa, P.

Publications and source records attributed to Villa, P..

9 recordsLinked to original sources

bioRxiv2025

Glucocorticoids Modulate mRNA Translation Fate Through P-Body Dynamics

Processing bodies (P-bodies) are cytoplasmic, membraneless organelles that play a key role in regulating RNA translation. To identify new pathways controlling their formation, we conducted a Food and Drug Administration (FDA)-approved drug screen. We found that glucocorticoids, among the most prescribed medicines, significantly increase P-body numbers across diverse epithelial cell types. This effect was fully reversible after glucocorticoid withdrawal, illustrating the adaptive dynamics of P-bodies. Using genetic invalidation and rescue approaches, we demonstrated that this accumulation requires the Glucocorticoid Receptor alpha isoform. P-body accumulation was associated with the sequestration of P-body-specific-targeted mRNAs, altering their translation yield. Notably, this translational regulation depends on transcript sequence features rather than abundance, with AU-rich mRNA transcripts being sequestered and GC-rich mRNAs preferentially translated under glucocorticoid treatment. Furthermore, we linked the decrease of LSM14B, a negative regulator of P-bodies, under glucocorticoid treatment to P-body reshaping. Our results reveal that, beyond their known transcriptional activity, prolonged exposure to glucocorticoids influences mRNA post-transcription and translation through a nucleotide composition-based mechanism.

cell biology↗

bioRxiv2024

New therapeutic combination to enhance endocytosis of antibodies and nucleic-acid aptamers targeting EGFR in glioblastoma cells

Active targeting is based on the binding of ligands to receptors present on the surface of targeted cells, in order to promote the internalization of the drugs conjugated to the ligands. Several conjugates are already in use or under development for active targeting of tumors, the most widely known being antibody-drug conjugates (ADC). They combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapeutic molecules. Other than antibodies, nucleic-acid aptamers, are promising ligands to deliver conjugated drugs by active targeting in tumor cells. The therapeutic efficacy of conjugates largely depends on their endocytosis and vesicular trafficking. However, so far, no therapeutic approach to enhance endocytosis of conjugates is available. In recent studies, we showed that gefitinib, a tyrosine kinase inhibitor directed against the epidermal growth factor receptor EGFR, induces a massive, non-physiological endocytosis of EGFR, known as gefitinib-mediated endocytosis (GME), in different glioblastoma cell lines. We thus hypothesized that besides promoting endocytosis of EGFR, gefitinib could also promote endocytosis of its ligands. In this study, we proved by quantitative fluorescence bioimaging, that gefitinib is indeed able to strengthen the endocytosis of fluorophore-conjugated EGFR-specific antibodies and aptamers. We also showed that the GME potentiates the toxicity of an antibody-drug conjugate, even at low concentrations. Our results suggest the development of a new therapeutic combination, of ADC and gefitinib, to potentiate the delivery of ADC and likely other conjugates targeting EGFR in glioblastoma, while limiting side effects on non-targeted cells.

cell biology↗

bioRxiv2023

Genetic drift vs natural selection affecting the evolution of spectral and functional traits of two key macrophytes: Phragmites australis and Nuphar lutea

Both genetic and phenotypic intraspecific diversity play a crucial role in the ecological and evolutionary dynamics of organisms. Several studies have compared phenotypic divergence (Pst) and differentiation of neutral loci (Fst) to infer the relative roles of genetic drift and natural selection in population differentiation (Pst - Fst comparison). For the first time, we assessed and compared the genetic variation and differentiation at the leaf trait level in two key macrophytes, Phragmites australis and Nuphar lutea. To this aim, we quantified and described the genetic structure and phenotypic diversity of both species in five lake systems in north-central Italy. We then investigated the relative roles of genetic drift and natural selection on leaf trait differentiation (Pst - Fst), assuming that Fst reflects divergence caused only by genetic drift while Pst also incorporates the effects of selective dynamics on the phenotype. In terms of genetic structure, the results for P. australis were in line with those observed for other Italian and European conspecific populations. Conversely, N. lutea showed a more complex genetic structure than expected at the site level, likely due to the combined effect of genetic isolation and its mixed mating system. Both species exhibited high variability in leaf functional traits within and among sites, highlighting a high degree of phenotypic plasticity. Pst - Fst comparisons showed a general tendency towards directional selection in P. australis and a more complex pattern in N. lutea. Indeed, the drivers of phenotypic differentiation in N. lutea showed a variable mix of stabilizing and directional selection or neutral divergence at most sites. The prevalence of vegetative over generative reproduction leads P. australis populations to be dominated by a few clones that are well adapted to local conditions, including phenotypes that respond plastically to the environment. In contrast, in N. lutea the interaction of a mixed mating system and geographical isolation among distant sites tends to reduce the effect of outbreeding depression and provides the genetic basis for adaptive capacity. The first joint analysis of the genetic structure of these two key macrophytes allowed a better understanding of the relative roles of genetic drift and natural selection in the diversification of phenotypic traits within habitats dominated by P. australis and N. lutea.

ecology↗

bioRxiv2023

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils

Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity co-morbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELM critically protects females against high fat diet-induced obesity. Compared to male mice, RELM levels were elevated in both control and high fat dietfed females and correlated with adipose macrophages and eosinophils. RELM-deficient females gained more weight and had pro-inflammatory macrophage accumulation and eosinophil loss, while both RELM treatment and eosinophil transfer rescued this phenotype. Single cell RNA-sequencing of the adipose stromal vascular fraction was performed and identified sex and RELM-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELM-deficient animals. Collectively, these studies implicate a RELM-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

immunology↗

bioRxiv2022

Assessing the haplotype and spectro-functional traits interactions to explore the intraspecific diversity of common reed in Central Italy

As reflectance measured via remote sensing is connected to plant light use and morpho-structural features, it can be used to derive spectral proxies of functional traits, or spectro-functional traits. Focusing on disentangling intraspecific trait variability in nature, we evaluated the links between haplotype and spectro-functional traits in Phragmites australis populations. Haplotypes sequencing and multi-seasonal satellite data were used to evaluate the temporal dynamics of spectro-functional traits for reed stands sampled from seven wetlands in Central Italy, investigating meteo-climatic drivers, the differences across ecological statuses, sites, and haplotypes, and quantifying intraspecific variability due to haplotype or phenotypic plasticity. Five haplotypes were identified, including an unedited one, which explained a substantial portion of intraspecific variability in canopy traits, differing for aquatic and terrestrial stands. We found that meteo-climatic factors impact on aquatic reeds traits (not over terrestrial ones) and a dualism between most and less common haplotypes, pointing to different evolutionary strategies. Dynamics in reed canopy traits were linked to ecological status, site and haplotype, with signs of haplotype-variable effects of dieback on aquatic stands. Evaluating the spectro-functional variability over reed haplotypes may provide a straightforward approach for monitoring the genotype-phenotype relations across scales and assessing their ecological drivers.

ecology↗

bioRxiv2020

Leaf reflectance can surrogate foliar economics better than physiological traits across macrophyte species

Macrophytes are key players in aquatic ecosystems diversity, but knowledge on variability of their functional traits, among and within species, is still limited. Remote sensing is a high-throughput, feasible option for characterizing plant traits at different scales, provided that reliable spectroscopy models are calibrated with congruous empirical data. We sampled leaves from six floating and emergent macrophyte species common in temperate areas, covering different phenological stages, seasons, and environmental conditions, and measured leaf reflectance (400-2500 nm) and leaf traits (dealing with photophysiology, pigments and structure). We explored optimal spectral bands combinations and established non-parametric reflectance-based models for selected traits, eventually showing how airborne hyperspectral data can capture spatial-temporal macrophyte variability. Our key finding is that structural - leaf dry matter content, leaf mass per area - and biochemical - chlorophyll-a content and chlorophylls to carotenoids ratio - traits can be surrogated by leaf reflectance with relative error under 20% across macrophyte species, while performance of reflectance-based models for photophysiological traits depends on species. This finding shows the link between leaf reflectance and leaf economics (structure and biochemistry) for aquatic plants, thus supporting the use of remote sensing for enhancing the level of detail of macrophyte functional diversity analysis, to intra-site and intra-species scales.

ecology↗

bioRxiv2019

Impact of upstream landslide on perialpine lake ecosystem: an assessment using multi-temporal satellite data

Monitoring freshwater and wetland systems and their response to stressors of natural or anthropogenic origin is critical for ecosystem conservation. A multi-temporal set of 87 images acquired by Sentinel-2 satellites over three years (2016-2018) provided quantitative information for assessing the temporal evolution of key ecosystem variables in the perialpine Lake Mezzola (northern Italy), which was suffered from the impacts of a massive landslide that took place upstream of the lake basin in summer 2017. Sentinel-2 derived products revealed an increase in lake turbidity triggered by the landslide that amounted to twice the average values scored in the years preceding and following the event. Hotspots of turbidity within the lake were in particular highlighted. Moreover both submerged and riparian vegetation showed harmful impacts due to sediment deposition. A partial loss of submerged macrophyte cover was found, with delayed growth and a possible community shift in favor of species adapted to inorganic substrates. Satellite-derived seasonal dynamics showed that exceptional sediment load can overwrite climatic factors in controlling phenology of riparian reed beds, resulting in two consecutive years with shorter than normal growing season, and roughly 20% drop in productivity according to spectral proxies: compared to 2016, senescence came earlier by around 20 days on average in 2017 season, and green-up was delayed by up to 50 days (20 days, on average) in 2018, following the landslide. The approach presented could be easily implemented for continuous monitoring of similar ecosystems subject to external pressures with periods of high sediment loads.

ecology↗

bioRxiv2018

Aspects of invasiveness of Ludwigia and Nelumbo in shallow temperate fluvial lakes

The relationship between invasive plant functional traits and their invasiveness is still the subject of scientific investigation, and the backgrounds of transition from non-native to invasive species in ecosystems are therefore poorly understood. Furthermore, our current knowledge on species invasiveness is heavily biased toward terrestrial species; we know much less about the influence of allochthonous plant traits on their invasiveness in aquatic ecosystems. We studied physiological and ecological traits of two introduced and three native macrophyte species in the Mantua lakes system (northern Italy). We compared their photophysiology, pigment content, leaf reflectance, and phenology in order to assess how the invasive Nelumbo nucifera and Ludwigia hexapetala perform compared to native species, Nuphar lutea, Nymphaea alba, and Trapa natans. We found L. hexapetala to have higher photosynthetic efficiency and able to tolerate higher light intensities than N. nucifera and the native species especially at extreme weather conditions (prolonged exposure to high light and higher temperatures). Chlorophyll a and b, and carotenoid contents of both allochthonous species was substantially higher than that of the native plants suggesting adaptive response to the ecosystem of Mantua lakes system. Higher variability of recorded data in invasive species also was observed. These observations suggest advanced photosynthetic efficiency of the invasive species, especially L. hexapetala, resulting in faster growth rates and higher productivity. This was supported by the evaluation of seasonal dynamics mapped from satellite remote sensing data. This study provides empirical evidence for the relationship between specific plant physiological traits and invasiveness of aquatic plant species, highlighting the importance of trait studies in predicting ecosystem-level impacts of invasive plant species.

ecology↗

bioRxiv2018

Assessing macrophyte seasonal dynamics using dense time series of medium resolution satellite data

Thanks to the improved spatial and temporal resolution of new generation Earth Observation missions, such as Landsat 8 and Sentinel-2, the potential of remote sensing techniques in mapping land surface phenology of terrestrial biomes can now be tested in inland water systems.\n\nWe assessed the capabilities of dense time series of medium resolution satellite data to deliver quantitative information about macrophyte phenology metrics, focusing on three temperate European shallow lakes with connected wetlands, located in Italy, France and Romania.\n\nLeaf area index (LAI) maps for floating and emergent macrophyte growth forms were derived from semi-empirical regression modelling based on the best performing spectral index, with an error level around 0.11 m2 m-2. Phenology metrics were computed from LAI time series using TIMESAT code and used to analyse macrophyte seasonal dynamics in terms of spatial patterns and species-dependent variability. Peculiar patterns of autochthonous and allochthonous species seasonality across the three study areas were related to the environmental characteristics of each area in terms of ecological and hydrological conditions.\n\nIn addition, the influence of satellite dataset characteristics - i.e. cloud cover thresholding, temporal resolution and missing acquisitions - on phenology timing metrics retrieval was assessed. Results have shown that with full resolution (5-day revisit) time series, cloud cover can bias phenology timing metrics by less than 2 days, and that reducing temporal resolution to 15 days (similar to Landsat revisit) still allows for mapping the start and peak of macrophyte growth with an error level around 2-3 days.

ecology↗