Biology subjects

Manfredi, C.

Publications and source records attributed to Manfredi, C..

3 recordsLinked to original sources

bioRxiv2024

Stably-Inverted Apical-Out Human Upper Airway Organoids for SARS-CoV-2 Infection and Therapeutic Testing

While breakthroughs with organoids have emerged as next-generation in vitro tools, standardization for drug discovery remains a challenge. This work introduces human airway organoids with reversed biopolarity (AORBs), cultured and analyzed in a high-throughput, single-organoid-per-well format, enabling milestones towards standardization. AORBs exhibit a spatio-temporally stable apical-out morphology, facilitating high-yield direct intact-organoid virus infection. Single-cell RNA sequencing and immunohistochemistry confirm the physiologically relevant recapitulation of differentiated human airway epithelia. The cellular tropism of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains along with host response differences between Delta, Washington, and Omicron variants, as observed in transcriptomic profiles, also suggest clinical relevance. Dose-response analysis of three well-studied SARS-CoV-2 antiviral compounds (remdesivir, bemnifosbuvir, and nirmatrelvir) demonstrates that AORBs efficiently predict human efficacy, comparable to gold-standard air-liquid interface cultures, but with higher throughput ([~]10-fold) and fewer cells ([~]100-fold). This combination of throughput and relevance allows AORBs to robustly detect false negative results in efficacy, preventing irretrievable loss of promising lead compounds. While this work leverages the SARS-CoV-2 study as a proof-of-concept application, the standardization capacity of AORB holds broader implications in line with regulatory efforts to push alternatives to animal studies.

bioengineering↗

bioRxiv2023

Assessing the overlap between fishing activities and chondrichthyans distribution exposes high-risk areas for bycatch of threatened species

Sharks, rays, and chimaeras (chondrichthyans) play a crucial role in marine ecosystem functioning but are highly vulnerable to fishing. Hence, understanding the spatial overlap between chondrichthyans and fishing effort is essential for effective conservation and management. Here, we propose an integrated approach that combines Vessel Monitoring System data with geostatistical species distribution models to assess the potential impact of fishing on chondrichthyan populations in the western Adriatic Sea. By mapping the overlap between model-based chondrichthyan distribution, species richness, and the proportion of threathened species with bottom trawl fishing activities, we identify areas at high risk for chondrichthyan bycatch. Our findings show that many of these species are at risk across a large part of their distribution within the study area. Notably, there is a substantial spatial overlap between regions where threatened chondrichthyans are found and species-rich areas with locations of intensive bottom trawl fishing in the northern and central offshore regions of the western Adriatic, emphasizing the vulnerability of these species to fishing pressure. Furthermore, differences in overlap between distinct fishing gears highlight the importance of considering specific fishing practices when formulating management strategies. While our work provides novel insights to potential bycatch hotspots, limitations related to data sources, spatial resolution, and the inability to directly quantify fishing impacts should be considered. Nonetheless, our findings contribute to the development of targeted conservation and spatial management measures, offering a general approach to study model-based spatial hotspots aimed at protecting and sustaining chondrichthyan populations in the heavily exploited Adriatic Sea.

ecology↗

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↗