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Biology subjects

Bartolini, D.

Publications and source records attributed to Bartolini, D..

3 recordsLinked to original sources

Input-space geometry shapes adaptation dynamics underlying repetition suppression in a neural network model of relatedness priming

A key function of the human brain is its ability to dynamically adapt to novel contexts by integrating prior experience. While neural adaptation is widely observed across cortical systems, the microcircuit-level mechanisms governing its intensity and temporal dynamics remain unclear. To bridge this gap, we develop a recurrent network of adaptive exponential integrate-and-fire neurons governed by a triplet spike-timing-dependent plasticity rule, designed to reproduce neural dynamics recorded via intracranial electrophysiology and single-unit recordings from the medial temporal lobe of neurosurgical patients performing a priming task. Using input organizations inspired by the experimental paradigm, we systematically vary input geometry to investigate its impact on adaptation dynamics. We find that neural adaptation emerges from recurrent dynamics shaped by learned connectivity, with both its magnitude and temporal profile depending on the geometry of the input space. This dependence gives rise, at the simulated single-neuron level, to a continuum of response regimes ranging from sharpening-like to fatiguing-like dynamics. Sharpening-like responses dominate when inputs exhibit high within-meta-category similarity and strong between-meta-category separation, whereas fatiguing-like responses emerge under the opposite regime.

neuroscience↗

Patient-derived glioblastoma cells (GBM) exhibit distinct biomechanical profiles associated with altered activity in the cytoskeleton regulatory pathway

Glioblastoma multiforme (GBM) is the most commonly diagnosed brain cancer in adults, characterized by rapid proliferation and aggressive invasion into the stroma. Advances in our understanding of the molecular subtypes of GBM have provided attractive druggable targets. However, the high degree of heterogeneity both among patients and within individual tumors has proven a significant challenge for the development of effective therapies. We hypothesized that this heterogeneity is also represented in the mechanical phenotypes of GBM, as the physical properties of tumor tissue strongly influence elements of tumor progression including cell cycle regulation, migration, and therapeutic resistance. To assess these phenotypes, we employed optical trap-based active microrheology to determine the viscoelastic properties of patient-derived GBM cells in 3D hydrogels mimicking the brain ECM. We found that each GBM cell line had a distinct rheological profile as a function of treatment status, and cell lines could be further characterized by strong power law dependence describing intracellular viscoelastic behavior. Single-cell phenotyping according to power law dependence was able to identify subpopulations of cells within the treatment-resistant line. Finally, proteomic analysis indicated that altered mechanical profiles were associated with differential cytoskeletal regulation, particularly in actin - and myosin-binding pathways. This work suggests that evaluating mechanical properties may serve as a valuable strategy for the further stratification of these tumors, and encourages the investigation of cytoskeleton regulation as a potential therapeutic target for GBM.

biophysics↗

A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicity

2,2-diselenyldibenzoic acid (DSBA) is a mild thiol peroxidase agent presently in preclinical development. This study reports that the drug has novel seleno-hormetic properties in both murine bone marrow and human liver cells. According with previous in vitro findings, mechanistic aspects of such properties were confirmed to include the activation of Nrf2 transcription factor and an increased expression of downstream stress response genes in the liver and in hematopoietic stem and progenitor cells of the myeloid lineage. These genes include glutathione S-transferase that is reported to represent a major player in the metabolism and pharmacological function of seleno-organic compounds. As a practical application, DSBA administration prevented bone marrow toxicities following acute exposure to sub-lethal doses of ionizing radiation in C57 BL/6 mice.\n\nIn conclusion, this study demonstrates for the first time the pharmacological properties of DSBA in vivo. The findings suggest applications for this selenohormetine in radioprotection and prevention protocols.

cancer biology↗