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Biology subjects

Massari, S.

Publications and source records attributed to Massari, S..

2 recordsLinked to original sources

Modeling and Tracking of Heterogeneous Cell Populations via Open Multi-Agent Systems

Understanding cellular dynamics represents a critical challenge in biomedical research. Optical microscopy remains a key technique for observing live-cell behaviors in vitro. This paper introduces an enhanced cell-tracking algorithm designed to address dynamic changes in cell populations, including mitosis, migration, and cell-cell interactions, even within complex co-culture models. The proposed method involves three main steps: 1)modeling the movements and interactions of different cell types in co-culture experiments via tailored open multi-agent systems; 2)identifying parameters via real data for a multi-agent, multi-culture framework; 3) embedding the model within an Extended Kalman Filter, to predict the dynamics of heterogeneous cell populations across video frames. To validate the approach, we used a novel dataset involving the interplay between tumor and normal cells, namely osteosarcoma and mesenchymal stromal cells, respectively. This dataset offers a challenging and clinically relevant framework to track cell proliferation and study how cancer cells evolve and interact with stromal cells within their surroundings. Performance metrics demonstrated the effectiveness of the algorithm over state-of-the-art methodologies, highlighting its ability to track heterogeneous cell types, capture their interactions, and generate the estimated cell lineage tree.

systems biology↗

benzothiazole scaffold as versatile nicotinamide mimic allowing nanomolar inhibition of different PARP enzymes

Here we report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogs and their crystal structures with TNKS2, PARP2, PARP14 and PARP15. Based on the substitution pattern, we were able to identify The 3-amino derivatives 21 (OUL243) and 27 (OUL232), as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14 and PARP15 at nM potencies, with compound 27 being the most potent PARP10 inhibitor described to date with an IC50 of 7.8 nM and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity towards PARP2. The scaffold does not possess inherent cell toxicity and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of the TBT scaffold for future drug development efforts towards selective inhibitors against specific enzymes.

biochemistry↗