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Mengarelli, A.

Publications and source records attributed to Mengarelli, A..

2 recordsLinked to original sources

Embodied Emergence of Temporal Complexity in Finger Tapping: Synaptic and Dopaminergic Control in Cortico-Basal Ganglia Loops

Finger tapping is a crucial clinical window into the brain's motor integrity, particularly in Parkinson's disease (PD). Beyond mere rhythmicity, healthy motor output exhibits long-range correlations (LRCs)--a hallmark of temporal complexity and physiological adaptability. However, how this fractal structure emerges from the interplay between neural circuits and physical body dynamics, and why it collapses under dopamine depletion, remains elusive. Here, we present an embodied computational model integrating the cortico-basal ganglia-thalamocortical (CBGT) loop with a physical finger model under intermittent control. We demonstrate that LRC is not stochastic noise, but emerges from the interaction between physical finger dynamics and intermittent, sensory-driven action selection. Our simulations reveal that while unbiased action selection yields random variability, a sensory-driven striatal bias generates robust LRC, demonstrating that motor complexity can be actively driven by neural "synaptic bias" rather than passive body mechanics. Crucially, simulating PD pathology via dopamine reduction disrupts this bias, leading to a loss of complexity and white-noise transitions that recapitulate a key qualitative feature of the fractal breakdown observed in PD. By bridging neuromodulation, biomechanical execution, and macroscopic behavior, this work provides a mechanistic framework for embodied neural information processing and offers a potential digital-twin platform for objective biomonitoring in neurodegenerative disorders.

neuroscience↗

AATF/Che-1, a new component of paraspeckles, controls R-loops formation and Interferon activation in Multiple Myeloma.

Multiple myeloma (MM) is a hematological neoplasm of plasma cells characterized by abnormal production of immunoglobulins. Che-1/AATF (Che-1) is an RNA binding protein involved in transcription regulation and is highly expressed in this malignancy. Here we experimentally show that Che-1 interacts with paraspeckle components, including the lncRNA NEAT1_2 (NEAT1), which serves as the seed for the maintenance of these structures. Che-1 and NEAT1 localize on R-loops, three-stranded RNA:DNA hybrids structures involved in DNA transcription and repair. Depletion of Che-1 produces a marked accumulation of RNA:DNA hybrids sustaining activation of a systemic inflammatory response. We provide evidence that high levels of Unfolded Protein Response (UPR) in MM cells induces RNA:DNA hybrids and an interferon (IFN) gene signature. We found that MM patients exhibit elevated R-loops levels and paraspeckle genes mRNAs increase linearly to MM progression. Strikingly, patients showing elevated IFN genes signature are associated with a marked poor prognosis. Overall, these findings delineate that elevated R-loops accumulation and inflammatory signaling may contribute to MM progression and that Che-1/NEAT1 plays an essential role in maintaining R-loops homeostasis by preventing excessive inflammatory signaling.

cell biology↗