Thioflavine-T and Congo Red reveal the polymorphism of insulin amyloid fibrils when probed by polarization-resolved fluorescence microscopy.

International audienceAmyloid fibrils are protein misfolding structures that involve a β-sheet structure and are associated with the pathologies of various neurodegenerative diseases. Here we show that Thioflavine-T and Congo Red, two major dyes used to image fibrils by fluorescence assays, can provide deep structural information when probed by means of polarization-resolved fluorescence microscopy. Unlike fluorescence anisotropy or fluorescence detected linear dichroism imaging, this technique allows to retrieve simultaneously both mean orientation and orientation dispersion of the dye, used here as a reporter of the fibril structure. We have observed that insulin amyloid fibrils exhibit a homogeneous behavior over the fibrils' length, confirming their structural uniformity. In addition, these results reveal the existence of various structures among the observed fibrils' population, in spite of a similar aspect when imaged with conventional fluorescence microscopy. This optical nondestructive technique opens perspectives for in vivo structural analyses or high throughput screening

Time perception and the experience of agency in meditation and hypnosis

Mindfulness meditation and hypnosis are related in opposing ways to awareness of intentions. The cold control theory of hypnosis proposes that hypnotic responding involves the experience of involuntariness while performing an actually intentional action. Hypnosis therefore relies upon inaccurate metacognition about intentional actions and experiences. Mindfulness meditation centrally involves awareness of intentions and is associated with improved metacognitive access to intentions. Therefore, mindfulness meditators and highly hypnotizable people may lie at opposite ends of a spectrum with regard to metacognitive access to intention‐related information. Here we review the theoretical background and evidence for differences in the metacognition of intentions in these groups, as revealed by chronometric measures of the awareness of voluntary action: the timing of an intention to move (Libet's “W” judgments) and the compressed perception of time between an intentional action and its outcome (“intentional binding”). We review these measures and critically evaluate their proposed connection to the experience of volition and sense of agency

Spatiotemporal processing of somatosensory stimuli in schizotypy

Unusual interaction behaviors and perceptual aberrations, like those occurring in schizotypy and schizophrenia, may in part originate from impaired remapping of environmental stimuli in the body space. Such remapping is contributed by the integration of tactile and proprioceptive information about current body posture with other exteroceptive spatial information. Surprisingly, no study has investigated whether alterations in such remapping occur in psychosis-prone individuals. Four hundred eleven students were screened with respect to schizotypal traits using the Schizotypal Personality Questionnaire. A subgroup of them, classified as low, moderate, and high schizotypes were to perform a temporal order judgment task of tactile stimuli delivered on their hands, with both uncrossed and crossed arms. Results revealed marked differences in touch remapping in the high schizotypes as compared to low and moderate schizotypes. For the first time here we reveal that the remapping of environmental stimuli in the body space, an essential function to demarcate the boundaries between self and external world, is altered in schizotypy. Results are discussed in relation to recent models of 'self-disorders' as due to perceptual incoherence

What do individuals with schizophrenia need to increase their well-being

The aim of this qualitative study was to deepen the knowledge of how individuals with schizophrenia themselves describe what they need in order to increase their well-being in everyday life. Seven patients were interviewed. An open explorative approach was applied and grounded theory was used for the analysis resulting in five categories illustrating how patients with schizophrenia handle their struggle for a normal life. The patients stressed first the importance of receiving information about the disease: for themselves, for society, and for their families. Taking part in social contacts such as attending meeting places and receiving home visits were identified as important as well as having meaningful employment. They also pointed out the importance of taking part in secure professional relationships. Mainly they expressed the need for continuity in the relationships and the wish to be heard and seen by the professionals. Finally, interviewees addressed the need for support for sustaining independent living through practical housekeeping and financial help. To conclude, the participants in the present study described their need for help as mainly linked to activities in their overall life situation rather than just their psychosis

Molecular Structures of Quiescently Grown and Brain-Derived Polymorphic Fibrils of the Alzheimer Amyloid Aβ9-40 Peptide: A Comparison to Agitated Fibrils

The presence of amyloid deposits consisting primarily of Amyloid-β (Aβ) fibril in the brain is a hallmark of Alzheimer's disease (AD). The morphologies of these fibrils are exquisitely sensitive to environmental conditions. Using molecular dynamics simulations combined with data from previously published solid-state NMR experiments, we propose the first atomically detailed structures of two asymmetric polymorphs of the Aβ9-40 peptide fibril. The first corresponds to synthetic fibrils grown under quiescent conditions and the second to fibrils derived from AD patients' brain-extracts. Our core structure in both fibril structures consists of a layered structure in which three cross-β subunits are arranged in six tightly stacked β-sheet layers with an antiparallel hydrophobic-hydrophobic and an antiparallel polar-polar interface. The synthetic and brain-derived structures differ primarily in the side-chain orientation of one β-strand. The presence of a large and continually exposed hydrophobic surface (buried in the symmetric agitated Aβ fibrils) may account for the higher toxicity of the asymmetric fibrils. Our model explains the effects of external perturbations on the fibril lateral architecture as well as the fibrillogenesis inhibiting action of amphiphilic molecules