The aquatic invertebrate Hydra vulgaris releases molecular messages through extracellular vesicles

Recent body of evidence demonstrates that extracellular vesicles (EVs) represent the first language of cell-cell communication emerged during evolution. In aquatic environments, transferring signals between cells by EVs offers protection against degradation, allowing delivering of chemical information in high local concentrations to the target cells. The packaging of multiple signals, including those of hydrophobic nature, ensures target cells to receive the same EV-conveyed messages, and the coordination of a variety of physiological processes across cells of a single organisms, or at the population level, i.e., mediating the population’s response to changing environmental conditions. Here, we purified EVs from the medium of the freshwater invertebrate Hydra vulgaris, and the molecular profiling by proteomic and transcriptomic analyses revealed multiple markers of the exosome EV subtype, from structural proteins to stress induced messages promoting cell survival. Moreover, positive and negative regulators of the Wnt/β-catenin signaling pathway, the major developmental pathway acting in body axial patterning, were identified. Functional analysis on amputated polyps revealed EV ability to modulate both head and foot regeneration, suggesting bioactivity of the EV cargo and opening new perspectives on the mechanisms of developmental signalling. Our results open the path to unravel EV biogenesis and function in all cnidarian species, tracing back the origin of the cell-cell, cross-species or cross-kingdom communication in aquatic ecosystems.Proteomic analyses were performed in the Proteomics Platform of Servicios Científico Técnicos del CIBA (IACS-Universidad de Zaragoza), ProteoRed ISCIII member. RNA-seq analyses were performed by Sequentia Biotech S.L. (Barcelona, Spain). The authors acknowledge Mario Isas, Keck School of Medicine of USC Los Angeles, CA, for the kind gift of anti Hydra annexin B12 antibody. GT thanks the MIUR project SHARID-ARS01-01270 for financial support. MMo acknowledges financial support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No 853468), from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 660228 and from the Spanish Ministry of Science and Innovation through the Ramón y Cajal grant RyC 2019-026860-I.Peer reviewe

An Integrated Multilevel Analysis Profiling Biosafety and Toxicity Induced by Indium- and Cadmium-Based Quantum Dots in Vivo

Indium phosphide quantum dots (QDs) have emerged as a new class of fluorescent nanocrystals for manifold applications, from biophotonics to nanomedicine. Recent efforts in improving the photoluminescence quantum yield, the chemical stability and the biocompatibility turned them into a valid alternative to well established Cd-based nanocrystals. In vitro studies provided first evidence for the lower toxicity of In-based QDs. Nonetheless, an urgent need exists for further assessment of the potential toxic effects in vivo. Here we use the freshwater polyp Hydra vulgaris, a well-established model previously adopted to assess the toxicity of CdSe/CdS nanorods and CdTe QDs. A systematic multilevel analysis was carried out in vivo, ex vivo, and in vitro comparing toxicity end points of CdSe- and InP-based QDs, passivated by ZnSe/ZnS shells and surface functionalized with penicillamine. Final results demonstrate that both the chemical composition of the QD core (InP vs CdSe) and the shell play a crucial role for final outcomes. Remarkably, in absence of in vivo alterations, cell and molecular alterations revealed hidden toxicity aspects, highlighting the biosafety of InP-based nanocrystals and outlining the importance of integrated multilevel analyses for proper QDs risk assessment

FACIN, a Double-Edged Sword of the Emerging Periodontal Pathogen Filifactor alocis: A Metabolic Enzyme Moonlighting as a Complement Inhibitor.

Periodontal disease is one of the most common inflammatory infectious diseases worldwide and it is associated with other syndromes, such as cardiovascular disease or rheumatoid arthritis. Recent advances in sequencing allowed for identification of novel periodontopathogens such as Gram-positive Filifactor alocis, but its virulence mechanisms remain largely unknown. We confirmed that F. alocis is a prevalent species in periodontitis patients, and we also observed strong correlation of this bacterium with clinical parameters, highlighting its role in the pathogenesis of the disease. Further, we found that preincubation of human serum with F. alocis resulted in abolished bactericidal activity and that F. alocis was surviving readily in full blood. We demonstrated that one of the key contributors to F. alocis complement resistance is a unique protein, FACIN (F. alocis complement inhibitor), which binds to C3, resulting in suppression of all complement pathways. Interestingly, FACIN is a nonclassical cell surface protein, a cytosolic enzyme acetylornithine transaminase, for which we now identified a moonlighting function. FACIN binds to C3 alone, but more importantly it also captures activated complement factor 3 within the complex with factor B, thereby locking in the convertase in an inactive state. Because of the indispensable role of alternative pathway convertase in amplifying complement cascades, its inhibition by FACIN results in a very potent downregulation of activated complement factor 3 opsonization on the pathogen surface, accompanied by reduction of downstream C5 cleavage