Biology subjects

Baldari, C.

Publications and source records attributed to Baldari, C..

3 recordsLinked to original sources

bioRxiv2025

Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes

Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytrens disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications.

cell biology↗

bioRxiv2023

Polo-like kinase 1 regulates immune synapse assembly and cytotoxic T cell function by driving microtubule dynamics

Elimination of virally infected or tumoral cells is mediated by cytotoxic T cells (CTL). Upon antigen recognition CTLs assemble a specialized signaling and secretory domain at the interface with their target, the immune synapse (IS). During IS formation CTLs acquire a transient polarity, marked by re-orientation of the centrosome and microtubule cytoskeleton toward the IS, thus directing the transport and delivery of the lytic granules to the target cell. Based on the implication of the kinase Aurora-A in CTL function we hypothesized that its substrate, the mitotic regulator Polo-like kinase 1 (PLK1), may participate in CTL IS assembly. We demonstrate that PLK1 is phosphorylated upon TCR triggering and polarizes to the IS. PLK1 silencing or inhibition results in impaired IS assembly and function, as witnessed by defective synaptic accumulation of TCRs as well as compromised centrosome and lytic granule polarization to the IS, resulting in impaired target cell killing. This function is achieved by coupling early signaling to microtubule dynamics, a function pivotal for CTL-mediated cytotoxicity. These results identify PLK1 as a new player in CTL IS assembly and function. Summary statementThe mitotic kinase Polo-like kinase 1 promotes centrosome polarization to the immune synapse in cytotoxic T cells by coupling TCR signaling to microtubule dynamics

immunology↗

bioRxiv2021

Recurrence quantification analysis of heart rate variability is a COVID-safe alternative to gas analysis in the detection of metabolic thresholds

The first aim of the study was to verify if in individuals with different physical fitness levels the Recurrence Quantification Analysis (RQA) of Heart Rate Variability (HRV) time series could be an alternative to Gas Exchange (GE) analysis in the determination of metabolic thresholds. The second aim was to investigate the validity of the RQA method compared to the GE method in thresholds detection. The two metabolic thresholds were estimated in thirty young individuals during Cardiopulmonary Exercise Testing on a cycle-ergometer and HR, VO2 and Workload were measured by the two different methods (RQA and GE methods). RM ANOVA was used to assess main effects of methods and methods-by-groups interaction effects for HR, VO2 and Workload at the aerobic (AerT) and the anaerobic (AnT) thresholds. Validity of the RQA at both thresholds was assessed for HR, VO2 and Workload by Ordinary Least Products (OLP) regression analysis, Typical Percentage Errors (TE), Intraclass Correlation Coefficients (ICC) and the Bland Altman plots. No methods-by-groups interaction effects were detected for HR, VO2 and Workload at the AerT and the AnT. The OLP regression analysis showed that at both thresholds RQA and GE methods had very strong correlations (r >0.8) in all variables (HR, VO2 and Workload). Slope and intercept values always included the 1 and the 0, respectively. At the AerT the TE ranged from 4.02% to 10.47% (HR and Workload, respectively) and in all variables ICC values were excellent ([≥]0.85). At the AnT the TE ranged from 2.61% to 6.64% (HR and Workload, respectively) and in all variables ICC values were excellent ([≥]0.89). Our results suggest that the RQA of HRV time series is a COVID-safe approach for the determination of metabolic thresholds in individuals with different physical fitness levels, therefore, it can be used as a valid method for threshold detection alternative to gas analysis.

biophysics↗