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Garrido, C.

Publications and source records attributed to Garrido, C..

2 recordsLinked to original sources

Characterizing the dynamical complexity underlying meditation

Over the past 2,500 years, contemplative traditions have explored the nature of the mind using meditation. More recently, neuroimaging research on meditation has revealed differences in brain function and structure in meditators. Nevertheless, the underlying neural mechanisms are still unclear. In order to understand how meditation shapes global activity through the brain, we investigated the spatiotemporal dynamics across the whole-brain functional network using the Intrinsic Ignition Framework. Recent neuroimaging studies have demonstrated that different states of consciousness differ in their underlying dynamical complexity, i.e., how the broadness of communication is elicited and distributed through the brain over time and space. In this work, controls and experienced meditators were scanned using functional magnetic resonance imaging (fMRI) during resting-state and meditation (focused attention on breathing). Our results evidenced that the dynamical complexity underlying meditation shows less complexity than during resting-state in the meditator group but not in the control group. Furthermore, we report that during resting-state, the brain activity of experienced meditators showed higher metastability (i.e., a wider dynamical regime over time) than the one observed in the control group. Overall, these results indicate that the meditation state operates in a different dynamical regime than the resting-state.

neuroscience

CBP/EP300-dependent acetylation and stabilization of HSF2 are compromised in the rare disorder, Rubinstein-Taybi syndrome

Cells respond to protein-damaging insults by activating heat shock factors (HSFs), key transcription factors of proteostasis. Abnormal HSF protein levels occur in cancer and neurodegenerative disorders, highlighting the importance of the tight control of HSF expression. HSF2 is a short-lived protein, but it is abundant in the prenatal brain cortex and required for brain development. Here, we reveal that HSF2 is acetylated and co-localized with the lysine-acetyl transferases CBP and EP300 in human brain organoids. Using unbiased, biochemical, cell-imaging, and in silico approaches, we show that CBP/EP300 acetylates HSF2 at specific lysine residues, which promotes HSF2 stabilization, whereas the lysine deacetylase HDAC1 catalyzes its proteasomal degradation. The CBP KIX domain and KlX-recognizing motifs in HSF2 are critical for its interaction with acetylating enzymes. The functional importance of acetylated HSF2 is evidenced in Rubinstein-Taybi syndrome (RSTS), characterized by mutated CBP or EP300. We show that RSTS patient cells exhibit decreased HSF2 levels and impaired heat shock response. The dysregulated HSF pathway in RSTS opens new avenues for understanding the molecular basis of this multifaceted pathology.

developmental biology