Hayase, M. | Search bioRxiv

bioRxiv2020

Linker histone H1 determines cell stiffness and differentiation

ABSTRACTThe flexibility or stiffness, one mechanical property of cells, is a promising label-free biomarker for underlying cytoskeletal or nuclear changes associated with various disease processes and changes in cell state. However, the molecular changes responsible for the whole-cell mechanical stiffness remain to be clarified. Recently, it was shown that the deterministic lateral displacement (DLD) microfluidic device, originally developed for size fractionation of some particles, might be applied to distinguish cells according to their stiffness. In this experiment, using the DLD device and various cell lines differentially expressing histone H1, a positively-charged protein localized in the linker region of chromatin, we found linear relationships between histone H1 quantity and cell stiffness. We also found that the histone H1 quantity affected cell size and even cell differentiation.

cell biology↗

bioRxiv2019

Atypical spatial frequency dependence of visual metacognition among schizophrenia patients

Although altered early stages of visual processing have been reported among schizophrenia patients, how such atypical visual processing may affect higher-level cognition remains largely unknown. Here we tested the hypothesis that metacognitive performance may be atypically modulated by spatial frequency (SF) of visual stimuli among individuals with schizophrenia, given their altered magnocellular function. To study the effect of SF on metacognitive performance, we asked patients and controls to perform a visual detection task on gratings with different SFs and report confidence, and analyzed the data using the signal detection theoretic measure meta-d. Control subjects showed better metacognitive performance after yes- (stimulus-presence) than after no- (stimulus-absence) responses ( yes-response advantage) for high SF (HSF) stimuli but not for low SF (LSF) stimuli. The patients, to the contrary, showed a yes-response advantage not only for HSF but also for LSF stimuli, indicating atypical SF dependency of metacognition. An fMRI experiment using the same task revealed that the dorsolateral prefrontal cortex (DLPFC), known to be crucial for metacognition, shows activity mirroring the behavioral results: decoding accuracy of perceptual confidence in DLPFC was significantly higher for HSF than for LSF stimuli in controls, whereas this decoding accuracy was independent of SF in patients. While individuals without schizophrenia may flexibly adapt metacognitive computations across SF ranges, patients may employ a different mechanism that is independent of SF. Because visual stimuli of low SF have been linked to top-down processing in predictive coding, this may reflect atypical functioning in these processes in schizophrenia. HighlightsO_LIVisual metacognition of controls was dependent on spatial frequency. C_LIO_LIVisual metacognition of schizophrenia patients was independent of spatial frequency. C_LIO_LIPatients and controls differently rely on the dorsolateral prefrontal cortex. C_LIO_LISensory inputs may reach metacognitive circuits in an atypical manner among patients. C_LI

neuroscience↗