Georgoula, K. | Search bioRxiv

bioRxiv2026

PERK retains a predominantly monomeric state under ER stress conditions

The unfolded protein response (UPR) is a central adaptive mechanism that safeguards protein homeostasis in the endoplasmic reticulum (ER). In the heart, UPR signaling contributes to cellular remodeling and survival across a range of pathological contexts, including ischemia, pressure overload, and cardiometabolic stress. Among the three canonical UPR branches, the PKR-like ER kinase (PERK) pathway plays a critical role in modulating translational control and redox balance during stress adaptation. Despite its functional importance, the molecular dynamics of PERK activation and assembly remain incompletely understood. Here, we investigate the oligomerization behavior of PERK in living cells using advanced fluorescence microscopy. We identify a concentration-dependent mechanism of PERK self-association, as well as a distinct population of oligomeric PERK whose assembly state remains stable upon ER stress induction. These findings challenge the traditional view of stress-induced oligomerization as a prerequisite for PERK activation and suggest the existence of non-canonical modes of PERK assembly with potential regulatory significance.

cell biology↗

bioRxiv2021

Mind blanking is associated with a rigid spatio-temporal profile in typical wakefulness

Mind blanking (MB) is a waking state during which we do not report any mental content, challenging the view of a constantly thought-oriented brain. Here, we comprehensively characterize the MBs neurobehavioral profile with the aim to delineate its role during ongoing mentation. Using fMRI experience-sampling, we show that MB is reported less frequently, faster, and with low transitional dynamics among other mental states, pointing to its role as a transient mental relay. Regarding its neural underpinnings, we observe higher global signal amplitude during MB reports, indicating a distinct physiological substrate. Using the time-varying functional connectome MB reports get classified with high accuracy, suggesting that MB has a unique neural composition. Indeed, a pattern of globally positive-phase coherence shows the highest similarity to the connectivity patterns associated with MB reports. We observe that this patterns rigid signal architecture hinders content reportability due to the brains inability to differentiate signals in an informative way. Collectively, we show that MB has a unique neurobehavioural profile, indicating that non-reportable mental events can happen during wakefulness. Our results add to the characterization of spontaneous mentation and pave the way for more mechanistic investigations of MBs phenomenology. Significance StatementThe human mind is generally assumed to be thought-oriented. Mind blanking (MB) challenges this stance because it appears as if we are derived of any particular mental content to report. We here show that, during spontaneous thinking, MB is a mental state that happens by default, it has a unique behavioural profile, and it is of a rigid neural architecture that does not permit the formulation of reportable contents. Our work essentially proposes that non-reportable mental events can happen during wakefulness, and challenges the view of the mind as a constant thought-oriented operator.

neuroscience↗