In view of ever-changing conditions both in the external world and in intrinsic brain states, maintaining the robustness of computations poses a challenge, adequate solutions to which we are only beginning to understand. At the level of cell-intrinsic properties, biophysical models of neurons permit one to identify relevant physiological substrates that can serve as regulators of neuronal excitability and to test how feedback loops can stabilize crucial variables such as long-term calcium levels and firing rates. Mathematical theory has also revealed a rich set of complementary computational properties arising from distinct cellular dynamics and even shaping processing at the network level. Here, we provide an overview over recently explored homeostatic mechanisms derived from biophysical models and hypothesize how multiple dynamical characteristics of cells, including their intrinsic neuronal excitability classes, can be stably controlled.
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http://dx.doi.org/10.1016/j.conb.2021.07.011 | DOI Listing |
RNA Biol
December 2025
Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
We show that a small biotin-binding RNA aptamer that folds into a pseudoknot structure acts as a substrate for bacterial RNase P RNA (RPR) with and without the RNase P C5 protein. Cleavage in the single-stranded region in loop 1 was shown to depend on the presence of a RCCA-motif at the 3' end of the substrate. The nucleobase and the 2'hydroxyl at the position immediately 5' of the cleavage site contribute to both cleavage efficiency and site selection, where C at this position induces significant cleavage at an alternative site, one base upstream of the main cleavage site.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Department of Nephrology, Pu'er People's Hospital, Pu'er, Yunnan, China.
Background: Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of RF. β-catenin is a key component of the Wnt signaling pathway, which has been fully proven to promote EMT.
View Article and Find Full Text PDFBiophys Rev
December 2024
Cancer Research UK Scotland Institute, Garscube Estate, Switchback Rd, Glasgow, G61 1BD UK.
Pancreatic adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and one of the leading causes of cancer-related death worldwide, with an extremely poor prognosis after diagnosis. High mortality from PDAC arises partly due to late diagnosis resulting from a lack of early-stage biomarkers and due to chemotherapeutic drug resistance, which arises from a highly fibrotic stromal response known as desmoplasia. Desmoplasia alters tissue mechanics, which triggers changes in cell mechanosensing and leads to dysregulated transcriptional activity and disease phenotypes.
View Article and Find Full Text PDFThe process by which neocortical neurons and circuits amplify their response to an unexpected change in stimulus, often referred to as deviance detection (DD), has long been thought to be the product of specialized cell types and/or routing between mesoscopic brain areas. Here, we explore a different theory, whereby DD emerges from local network-level interactions within a neocortical column. We propose that deviance-driven neural dynamics can emerge through interactions between ensembles of neurons that have a fundamental inhibitory motif: competitive inhibition between reciprocally connected ensembles under modulation from feed-forward selective (dis)inhibition.
View Article and Find Full Text PDFIntegrins are a large family of heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1, also known as the fibronectin receptor, is a key mediator of angiogenesis and its dysregulation is associated with tumor proliferation, progression, and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful in large part due to efficacy and off-target effects.
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