Biology subjects

Marinari, E.

Publications and source records attributed to Marinari, E..

3 recordsLinked to original sources

bioRxiv2023

PTPRZ1-targeting RNA CAR-T cells exert antigen-specific and bystander antitumor activity in glioblastoma

The great success of chimeric antigen receptor (CAR)-T cell therapy in B-cell malignancies has prompted its translation to solid tumors. In the case of glioblastoma (GBM), clinical trials have shown modest efficacy, but anti-GBM CAR-T cells are being intensely developed. In this study, we selected PTPRZ1 as an attractive new target for GBM treatment. We isolated six anti-human PTPRZ1 scFv from a human phage display library and produced 2nd generation CAR-T cells in an RNA format. Patient-derived GBM PTPRZ1-knock-in cell lines were used to select the CAR construct (471_28z), which showed high cytotoxicity while consistently displaying high CAR expression. CAR-T cells incorporating 471_28z were able to release IFN-{gamma}, IL-2, TNF-, Granzyme B, IL-17A, IL-6, and soluble FasL, and displayed low tonic signaling. Additionally, they maintained an effector memory phenotype after in vitro killing. Importantly, 471_28z CAR-T cells displayed strong bystander killing against PTPRZ1-negative cell lines after pre-activation by PTPRZ1-positive tumor cells, but did not kill antigen-negative non-tumor cells. In an orthotopic xenograft tumor model using NSG mice, a single dose of anti-PTPRZ1 CAR-T cells significantly delayed tumor growth. Taken together, these results validate the use of PTPRZ1 as a new GBM target and prompt the use of anti-PTPRZ1 CAR-T cells for clinical translation.

immunology↗

bioRxiv2020

Attention-dependent physiological correlates in sleep deprived healthy humans

Distinct cognitive functions are based on specific brain networks, but they are also affected by workload. The workload is a common factor affecting cognitive functioning that, by activating the Central Autonomic Network, modulates heart rate peripheral correlates of cognitive functioning. Based on these premises, we expected that the peripheral patterns associated with different attentional systems would have common (workload-related) and specific (task-dependent) components. To disentangling the components, a profile of peripheral physiological correlates of cognitive functioning was derived by studying healthy volunteers while performing different cognitive tasks during baseline and post-sleep deprivation conditions. Post-sleep deprivation condition was introduced to increase workload during tasks, allowing the investigation of the same participant at different levels of workload in different conditions. We performed, in each condition, physiological recordings of heart pulse, facial temperature and head movements during tasks assessing attentional networks efficiency (ANT - Attentional Network Task; CCT - Continuous Compensatory Tracker). We assessed perceived workload after the execution of these tasks. Physiological correlates of cognitive performance were identified by associating changes of task indices with the corresponding changes in physiological measures from baseline to post-sleep deprivation condition. Correlation analyses were performed after correction for the between-conditions workload changes: indeed, mental and physical demands of perceived workload increased after sleep deprivation. We found that alerting/vigilance has specific physiological correlates as indicated by the negative correlation between changes in ANT-alerting score and changes in amplitude of head movements and the positive one between changes in CCT-visuomotor speed indexing alertness and changes in facial temperature.

neuroscience↗

bioRxiv2017

A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

Many microbial systems are known to actively reshape their proteomes in response to changes in growth conditions induced e.g. by nutritional stress or antibiotics. Part of the re-allocation accounts for the fact that, as the growth rate is limited by targeting specific metabolic activities, cells simply respond by fine-tuning their proteome to invest more resources into the limiting activity (i.e. by synthesizing more proteins devoted to it). However, this is often accompanied by an overall re-organization of metabolism, aimed at improving the growth yield under limitation by re-wiring resource through different pathways. While both effects impact proteome composition, the latter underlies a more complex systemic response to stress. By focusing on E. coli's acetate switch, we use mathematical modeling and a re-analysis of empirical data to show that the transition from a predominantly fermentative to a predominantly respirative metabolism in carbon-limited growth results from the trade-off between maximizing the growth yield and minimizing its costs in terms of required the proteome share. In particular, E. coli's metabolic phenotypes appear to be Pareto-optimal for these objective functions over a broad range of dilutions.

systems biology↗