Physics of Life Reviews最新文献

The current discussion on the neural correlates of the contents of consciousness (NCCc) focuses mainly on the post-stimulus period of task-related activity. This neglects the substantial impact of the spontaneous or ongoing activity of the brain as manifest in pre-stimulus activity. Does the interaction of pre- and post-stimulus activity shape the contents of consciousness? Addressing this gap in our knowledge, we review and converge two recent lines of findings, that is, pre-stimulus alpha power and pre- and post-stimulus alpha trial-to-trial variability (TTV). The data show that pre-stimulus alpha power modulates post-stimulus activity including specifically the subjective features of conscious contents like confidence and vividness. At the same time, alpha pre-stimulus variability shapes post-stimulus TTV reduction including the associated contents of consciousness. We propose that non-additive rather than merely additive interaction of the internal pre-stimulus activity with the external stimulus in the alpha band is key for contents to become conscious. This is mediated by mechanisms on different levels including neurophysiological, neurocomputational, neurodynamic, neuropsychological and neurophenomenal levels. Overall, considering the interplay of pre-stimulus intrinsic and post-stimulus extrinsic activity across wider timescales, not just evoked responses in the post-stimulus period, is critical for identifying neural correlates of consciousness. This is well in line with both processing and especially the Temporo-spatial theory of consciousness (TTC).

In primary or idiopathic osteoarthritis (OA), it is unclear which factors trigger the shift of articular chondrocyte activity from pro-anabolic to pro-catabolic. In fact, there is a controversy about the aetiology of primary OA, either mechanical or inflammatory. Chondrocytes are mechanosensitive cells, that integrate mechanical stimuli into cellular responses in a process known as mechanotransduction. Mechanotransduction occurs thanks to the activation of mechanosensors, a set of specialized proteins that convert physical cues into intracellular signalling cascades. Moderate levels of mechanical loads maintain normal tissue function and have anti-inflammatory effects. In contrast, mechanical over- or under-loading might lead to cartilage destruction and increased expression of pro-inflammatory cytokines. Simultaneously, mechanotransduction processes can regulate and be regulated by pro- and anti-inflammatory soluble mediators, both local (cells of the same joint, i.e., the chondrocytes themselves, infiltrating macrophages, fibroblasts or osteoclasts) and systemic (from other tissues, e.g., adipokines). Thus, the complex process of mechanotransduction might be altered in OA, so that cartilage-preserving chondrocytes adopt a different sensitivity to mechanical signals, and mechanic stimuli positively transduced in the healthy cartilage may become deleterious under OA conditions. This review aims to provide an overview of how the biochemical exposome of chondrocytes can alter important mechanotransduction processes in these cells. Four principal mechanosensors, i.e., integrins, Ca²⁺ channels, primary cilium and Wnt signalling (canonical and non-canonical) were targeted. For each of these mechanosensors, a brief summary of the response to mechanical loads under healthy or OA conditions is followed by a concise overview of published works that focus on the further regulation of the mechanotransduction pathways by biochemical factors. In conclusion, this paper discusses and explores how biological mediators influence the differential behaviour of chondrocytes under mechanical loads in healthy and primary OA.