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Biology subjects

Zanardi, F.

Publications and source records attributed to Zanardi, F..

4 recordsLinked to original sources

AGE READINGS AND ASSESSMENT IN COASTAL BATOID ELASMOBRANCHS FROM SMALL-SCALE SIZE-SELECTIVE FISHERY: THE IMPORTANCE OF DATA COMPARABILITY IN MULTISPECIFIC ASSEMBLAGES.

Age readings and assessment of vertebral growth increments were obtained in four batoid elasmobranch species, namely Dasyatis pastinaca, Raja asterias, Torpedo marmorata, and Torpedo torpedo. Samples were obtained opportunistically from the bycatch of a size-selective fishery, such as local small-scale trammel net fishing, in the coastal waters of the Central Tyrrhenian Sea during 2019-21. We analysed the vertebrae by a simple and rapid method preventing staining phase and histological preparation to elucidate band pairs in all species studied. Consistency of age estimates was checked by controlling for agreement on band pair counts between and within observers, and by estimating the relationships between vertebral diameter and height, and body size of the animal. Based on these data, we developed a statistical routine to obtain multiple estimates of age and growth parameters for incomplete samples due to size-selective fishing. The acceptable agreement between and within readers and the increase in vertebral size with body size demonstrated the consistency of the method. Based on the results of Von Bertalanffy and Gompertz growth models, body size was a better predictor of age than vertebral size, and Gompertz models were a better estimator of age and growth parameters than Von Bertalanffy models. The estimated parameters (k and t0, kg and cg) matched the data available for the species studied in the Mediterranean Sea. In fact, D. pastinaca, T. torpedo and R. asterias showed the lowest (k = 0.05-0.12), intermediate (k = 0.112-0.19) and highest (k = 0.18-0.23) growth rate, respectively. Overall, the method proved effective both in delineating band pairs in vertebrae of different species by making use of only minimal optical equipment and a single reagent, and in reliably estimating the age and growth parameters of problematic samples due to size-selective fishing. The replicability of the method will help to collect comparable demographic data in similar samples from other areas of the Mediterranean, as well as in assemblages of different species from other places.

zoology↗

Dual role of brain endothelial Gpr126 in blood-brain barrier development and ischemic stroke

The blood-brain barrier (BBB) acquires unique properties for regulation of the neuronal function during development. The genesis of the BBB coupled with angiogenesis is orchestrated by the Wnt/{beta}-catenin signaling pathway. Aside from the importance of Wnt/{beta}-catenin signaling, the molecular mechanisms that regulate these processes are poorly understood. Here, we identify the brain endothelial adhesion G-protein-coupled receptor Gpr126 as a novel target gene of Wnt/{beta}-catenin signaling that is required for postnatal BBB development, and its expression is detrimental for ischemic stroke in adults. We show that Gpr126 expression is high in mouse brain endothelium during BBB formation, but decreases in the adult. Inactivation of Gpr126 in postnatal endothelial cells results in vessel enlargement and impairs acquisition of the BBB characteristics, such as increased neurovascular permeability, and reduced basement membrane protein deposition and pericyte coverage. Mechanistically, Gpr126 is required during developmental angiogenesis to promote endothelial cell migration, acting via an interaction between Lrp1 and 3{beta}1-integrin, which couples vessel morphogenesis to BBB formation. Interestingly, in adult mice with an established BBB, the lack of Gpr126 expression in acute ischemic stroke is protective and coupled with reduced microglia activation, which contributes to an improved neurological outcome. These data identify Gpr126 as a promising therapeutic target to treat ischemic stroke.

cell biology↗

Decellularized Normal and Tumor Scaffolds for Cancer Organoid Cultures as a Model of Colorectal Peritoneal Metastases

Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. SignificanceEvidence of the value of ex vivo 3D models obtained by combining patient-derived extracellular matrices depleted of cellular components and organoids to mimic the metastatic niche, to be used as a tool to develop new therapeutic strategies in a biologically relevant context, to personalize treatments and increase their efficacy.

cancer biology↗

Intra-tumor heterogeneity of Diffuse Large B-cell Lymphoma involves the induction of diversified stroma-tumor interfaces

Intra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-intrinsic mesenchymal determinants impact on the diversification of aggressive lymphomas is still unknown. In this study we adopted the established A20 line-based model of Diffuse Large B-cell Lymphoma (DLBCL), to investigate the intra-tumor heterogeneity associated with the infiltration of different tissue microenvironments and the specific mesenchymal modifications that characterize stromal adaptation to lymphoma seeding. Combining in situ quantitative immunophenotypical analyses and RNA sequencing, we found that the tissue microenvironment casts a relevant influence over A20 transcriptional landscape also impacting on Myc and DNA damage response programs. Extending the investigation to mice deficient for the matricellular protein Sparc, a stromal determinant endowed with a strong prognostic significance in human DLBCL, we demonstrated a different immune imprint on A20 cells related to stromal Sparc proficiency. The study provides the first evidence of human DLBCL intra-lesional heterogeneity arising from diversified mesenchymal contextures and impacting on MYC expression, advancing the challenge for resolving intra-tumor heterogeneity probing stromal/immune interfaces. KEY POINTSO_LIDiversified stromal adaptations of infiltrated tissues shape DLBCL intra-tumor heterogeneity regulating transcriptional/phenotypic features C_LIO_LIStromal Sparc, which endorses prognostic significance in DLBCL, tunes the immune pressure exerted on lymphoma cells by the microenvironment C_LI

cancer biology↗