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Grigolini, P.

Publications and source records attributed to Grigolini, P..

4 recordsLinked to original sources

From Single-Cell Emergent Behaviors to Clinical Outcome: PTEN-driven Migratory Efficiency as a Potential New Vulnerability in Glioblastoma

BackgroundGlioblastoma (GB) is a highly aggressive brain tumor with a median survival of approximately 14 months, primarily due to its ability to infiltrate healthy brain tissue both as single cells and in collectives. A deeper understanding of GB cell motility, both individual and collective, is crucial for developing patient-specific therapies. We aimed to characterize migration in patient-derived GB cells using advanced modeling to identify stratification markers and therapeutic vulnerabilities. MethodsWe developed Single-Cell Behavior Live Imaging (ScBLI), an approach integrating live imaging with computational analysis, applied to 30 GB primary cell cultures. Trajectories and morphological features were tracked and analyzed. Diffusion Entropy Analysis (DEA) was applied to classify trajectories based on the Delta Scaling parameter ({delta} scaling). We evaluated functional responses correlating all findings with clinical outcomes and transcriptomic profiles. ResultsWe analyzed 4,279 cell trajectories. Based on {delta} scaling (range 0.28-0.837), we defined three distinct motility groups: Low (L, {delta} scaling [&le;]0.5), Medium (M, 0.5 < {delta} scaling [&le;] 0.7), and High (H, {delta} scaling >0.7). Functional assays demonstrated that Group H cells are more performant in both positive and negative chemotaxis. Clinically, the three groups showed a clear linear progression with patient survival: High {delta} scaling correlated with the shortest survival (poorer prognosis), while Low {delta} correlated with the longest survival, suggesting that structured motility drives invasiveness. Integrative multi-omic analysis, encompassing both exome and transcriptome profiling, demonstrated that these groups are defined by distinct molecular landscapes rather than poor behavioral traits. Moreover, exome data revealed that Group H is significantly enriched in PTEN alterations (75% vs. 8% in Group L), with PTEN gain-of-function (GoF) mutations exclusively restricted to this group (100% vs 0% in Group L). Notably, within our extended cohort (n=51) currently characterized by whole-exome sequencing, we observed that specific PTEN GoF mutations were associated with a significantly shorter survival compared to PTEN wild-type cases (median OS 6.4 vs 16.6 months; p=0.02), which typically harbor the canonical loss of chromosome 10q. A similar clinical trend was observed when comparing directly GoF carriers to patients with truncating (Ter) alterations (median OS 6.4 vs 14.3 months; p=0.09). Conversely, no survival difference was found between truncating (Ter) mutations and wild-type cases. ConclusionOur findings demonstrate for the first time that migratory efficiency, quantified through DEA, represents a powerful predictor of glioblastoma aggressiveness. Tumor cells adopting highly efficient exploration strategies are strongly associated with poor clinical outcomes and are characterized by distinct molecular signatures, notably PTEN gain-of-function alterations. Statement of significanceOur multi-scale computational framework elucidates emergent behavioral phenotypes as pivotal drivers of glioblastoma progression. By demonstrating a correlation between enhanced migratory efficiency, PTEN gain-of-function, and significantly reduced overall survival, we establish a foundational paradigm for deciphering the emergent complexity governing tumor invasiveness.

cancer biology↗

Fractal Structure of Human and Primate Social Networks Optimizes Information Flow

Primate and human social groups exhibit a fractal structure that has a very limited range of preferred layer sizes, with groups of 5, 15, 50 and (in humans) 150 and 500 predominating. This same fractal distribution is also observed in the distribution of species mean group sizes in primates. Here we demonstrate that this preferential numbering arises because of the critical nature of dynamic self-organization within complex social networks. We calculate the size dependence of the scaling properties of complex social network models and argue that this aggregate behaviour exhibits a form of collective intelligence. Direct calculation establishes that the complexity of social networks as measured by their scaling behaviour is non-monotonic, peaking globally around 150 with a secondary peak at 500 and tertiary peaks centred on 15 and 50, thereby providing a theory-based rationale for the fractal layering of primate and human social groups.

animal behavior and cognition↗

Biophotons: low signal/noise ratio reveals crucial events

We study the emission of photons from germinating seeds using an experimental technique designed to detect photons of extremely small intensity when the signal/noise ratio is low. We analyze the dark count signal in the absence of germinating seeds as well as the photon emission during the germination process. The technique of analysis adopted here was originally designed to measure the temporal complexity of astrophysical, sociological and physiological processes. The foundation of this method, called Diffusion Entropy Analysis (DEA), rests on Kolmogorov complexity. The updated version of DEA used in this paper is designed to determine if the signal complexity is generated by either non-ergodic crucial events with a non-stationary correlation function or by the infinite memory of a stationary but non-integrable correlation function or by a mixture of both processes. We find that dark count yields the ordinary scaling, thereby showing that no complexity of either kinds may occur in the absence of any seeds in the chamber. In the presence of seeds in the chamber anomalous scaling emerges, reminiscent of that found in neuro-physiological processes. However, this is a mixture of both processes and with the progress of germination the non-ergodic component tends to vanish and complexity is dominated by the stationary infinite memory. We argue that this may be a sign of quantum coherence that according to some authors is the important ingredient of cognition.

biophysics↗

Complexity Matching and Requisite Variety

Complexity matching emphasizes the condition necessary to efficiently transport information from one complex system to another and the mechanism can be traced back to the 1957 Introduction to Cybernetics by Ross Ashby. Unlike this earlier work we argue that complexity can be expressed in terms of crucial events, which are generated by the processes of spontaneous self-organization. Complex processes, ranging from biological to sociological, must satisfy the homeodynamic condition and host crucial events that have recently been shown to drive the information transport between complex systems. We adopt a phenomenological approach, based on the subordination to periodicity that makes it possible to combine homeodynamics and self-organization induced crucial events. The complexity of crucial events is defined by the waiting-time probability density function (PDF) of the intervals between consecutive crucial events, which have an inverse power law (IPL) PDF{psi} ({tau}) {propto}1/({tau}) with 1 < < 3. We establish the coupling between two temporally complex systems using a phenomenological approach inspired by models of swarm cognition and prove that complexity matching, namely sharing the same IPL index , facilitates the transport of information, generating perfect synchronization, reminiscent of, but distinct from chaos synchronization. This advanced form of complexity matching is expected to contribute a significant progress in understanding and improving the bio-feedback therapies.\n\nAuthor SummaryThis paper is devoted to the control of complex dynamical systems, inspired to real processes of biological and sociological interest. The concept of complexity we adopt focuses on the assumption that the processes of self-organization generate intermittent fluctuations and that the time distance between two consecutive fluctuations is described by a distribution density with an inverse power law structure making the second moment of these time distances diverge. These fluctuations are called crucial events and are responsible for the ergodicity breaking that is widely revealed by the experimental observation of biological dynamics. We argue that the information transport from one to another complex system is ruled by these crucial events and we propose an efficient theoretical prescription leading to qualitative agreement with experimental results, shedding light into the processes of social learning. The theory of this paper is expected to have important medical applications, such as an improvement of the biofeedback techniques, the heart-brain communication and a significant progress on cognition and the contribution of emotions to cognition.

evolutionary biology↗