Biology subjects

Asciutto, E.

Publications and source records attributed to Asciutto, E..

3 recordsLinked to original sources

bioRxiv2023

Spatio-temporal patterns of whiting (Merlangius merlangus) in the Adriatic Sea under environmental forcing

Understanding how environmental factors affect species distribution is crucial for the conservation and management of marine organisms, especially in the face of global changes. Whiting (Merlangius merlangus) is a demersal temperate fish, considered a relict species in the Adriatic Sea. Despite its significance to commercial fisheries in the region, the specific drivers behind its spatial and temporal patterns have not been thoroughly examined. Here, we fitted a set of Generalized Linear Mixed Effects Models to data collected in the Northern and Central Adriatic from 1999 to 2019 during the Mediterranean International Trawl Survey to investigate the potential influence of depth, seafloor temperature and bottom dissolved oxygen on the annual biomass density and spatial distribution of whiting. Our results showed that depth, and to a lesser degree temperature and oxygen, are important predictors of whiting distribution in spring-summer, with preferences for depths of [~] 45 m, temperature of [~] 15.4 {degrees}C and dissolved oxygen > 5.5 ml L-1. We predicted a persistent core area of distribution in front of the Po River Delta, in the Northern Adriatic Sea, while the density progressively declined towards the Central and Southern Adriatic Sea along the Italian coast. Additionally, the temporal trend exhibited high fluctuations over the years, occurring in cycles of 3 to 4 years. Finally, by comparing the biomass density estimates obtained under optimum conditions with those derived from the actual values for each variable, our analysis revealed that temperature had a pronounced and general impact on biomass density in the northern survey area (prediction revealed a ratio of density reduction of approximatively a half), while oxygen displayed a minor and more localized influence. This work deepens the current knowledge about the ecology of whiting in the Adriatic Sea and provides support for the conservation and management of this species.

ecology↗

bioRxiv2021

Depletion of CD206+ Tumour Macrophages via a Peptide-Targeted Star-Shaped Polyglutamate Inhibits Tumourigenesis and Metastatic Dissemination in Mouse Breast Cancer Models

Although many studies have explored the depletion of tumour-associated macrophages (TAMs) as a therapeutic strategy for solid tumours, currently available compounds suffer from poor efficacy and dose-limiting side effects. Here, we developed a novel TAM-depleting agent ("OximUNO") that specifically targets CD206+ TAMs and demonstrated efficacy in triple negative breast cancer (TNBC) mouse models. OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX). In TNBC models, a fluorescently labelled mUNO-decorated St-PGA homed to CD206+ TAMs within primary lesions and metastases. OximUNO exhibited no acute liver or kidney toxicity in vivo. Treatment with OximUNO reduced the progression of primary tumour lesions and pulmonary metastases, significantly diminished the number of CD206+ TAMs and increased the CD8/FOXP3 expression ratio (demonstrating immunostimulation). Our findings suggest the potential benefit of OximUNO as a TAM-depleting agent for TNBC treatment. Importantly, our studies also represent the first report of a peptide-targeted St-PGA as a targeted therapeutic nanoconjugate.

cancer biology↗

bioRxiv2021

PL1 Peptide Engages Acidic Surfaces on Tumor-Associated Fibronectin and Tenascin Isoforms to Trigger Cellular Uptake.

Tumor extracellular matrix (ECM) is a high-capacity and genetically stable target for the precision delivery of affinity ligand-guided drugs and imaging agents. Recently, we developed a PL1 peptide (sequence: PPRRGLIKLKTS) for systemic targeting of malignant ECM. Here we map the dynamics of PL1 binding to its receptors Fibronectin Extra Domain B (FN-EDB) and Tenascin C C-isoform (TNC-C) by computational modeling and cell-free binding studies on mutated receptor proteins, and study cellular binding and internalization of PL1 nanoparticles in cultured cells. Molecular dynamics simulation and docking analysis suggested that the engagement of PL1 peptide with both receptors is primarily driven by electrostatic interactions. Substituting acidic amino acid residues with neutral amino acids at predicted PL1 binding sites in FN-EDB (D52N-D49N-D12N) and TNC-C (D39N-D45N) resulted in the loss of binding of PL1 nanoparticles. Remarkably, PL1-functionalized nanoparticles (NPs) were not only deposited on the target ECM but bound the cells and initiated a robust cellular uptake via a pathway resembling macropinocytosis. Our studies establish the mode of engagement of the PL1 peptide with its receptors and suggest applications for intracellular delivery of nanoscale payloads. The outcomes of this work can be used for the development of PL1-derived peptides with improved stability, affinity and specificity for precision targeting of the tumor ECM and malignant cells. One Sentence SummaryPL1 peptide is recruited to the acidic surfaces on oncofetal fibronectin EDB and tenascin C-C isoform, triggering cellular uptake of PL1-functionalized nanoparticles.

cancer biology↗