TY - JOUR AB - Cells exert forces on each other and their environment, shaping the tissue. The resulting mechanical stresses can be determined experimentally or estimated computationally using stress inference methods. Over the years, mechanical stress inference has become a non-invasive, low-cost computational method for estimating the relative intercellular stresses and intracellular pressures of tissues. This mini-review introduces and compares the static and dynamic modalities of stress inference, considering their advantages and limitations. To date, most software has focused on static inference, which requires only a single microscopy image as input. Although applicable in quasi-equilibrium states, this approach neglects the influence that cell rearrangements might have on the inference. In contrast, dynamic stress inference relies on a time series of microscopy images to estimate stresses and pressures. Here, we discuss both static and dynamic mechanical stress inference in terms of their physical, mathematical, and computational foundations and then outline what we believe are promising avenues for in silico inference of the mechanical states of tissues. AU - Borges, A. AU - Chara, O.* C1 - 72717 C2 - 56710 CY - 1st Flr, 10 Queen Street Place, London, England SP - 2579-2592 TI - Peeking into the future: Inferring mechanics in dynamical tissues. JO - Biochem. Soc. Trans. VL - 52 IS - 6 PB - Portland Press Ltd PY - 2024 SN - 0300-5127 ER - TY - JOUR AB - Enzyme catalysis is omnipresent in the cell. The mechanisms by which highly evolved protein folds enable rapid and specific chemical transformation of substrates belong to the marvels of structural biology. Targeting of enzymes with inhibitors has immediate application in drug discovery, from chemotherapeutics over antibiotics to antivirals. NMR spectroscopy combines multiple assets for the investigation of enzyme function. The non-invasive technique can probe enzyme structure and dynamics and map interactions with substrates, cofactors and inhibitors at the atomic level. With experiments performed at close to native conditions, catalytic transformations can be monitored in real time, giving access to kinetic parameters. The power of NMR in the solid state, in contrast with solution, lies in the absence of fundamental size limitations, which is crucial for enzymes that are either membrane-embedded or assemble into large soluble complexes exceeding hundreds of kilodaltons in molecular weight. Here we review recent progress in solid-state NMR methodology, which has taken big leaps in the past years due to steady improvements in hardware design, notably magic angle spinning, and connect it to parallel biochemical advances that enable isotope labelling of increasingly complex enzymes. We first discuss general concepts and requirements of the method and then highlight the state-of-the-art in sample preparation, structure determination, dynamics and interaction studies. We focus on examples where solid-state NMR has been instrumental in elucidating enzyme mechanism, alone or in integrative studies. AU - Schütz, A.K. C1 - 60966 C2 - 49757 CY - 5th Flr, 90 High Holborn, London Wc1v 6lj, England SP - 131-144 TI - Solid-state NMR approaches to investigate large enzymes in complex with substrates and inhibitors. JO - Biochem. Soc. Trans. VL - 49 IS - 1 PB - Portland Press Ltd PY - 2021 SN - 0300-5127 ER - TY - JOUR AB - The planar cell polarity (PCP) signaling pathway is a potent developmental regulator of directional cell behaviors such as migration, asymmetric division and morphological polarization that are critical for shaping the body axis and the complex three-dimensional architecture of tissues and organs. PCP is considered a noncanonical Wnt pathway due to the involvement of Wnt ligands and Frizzled family receptors in the absence of the beta-catenin driven gene expression observed in the canonical Wnt cascade. At the heart of the PCP mechanism are protein complexes capable of generating molecular asymmetries within cells along a tissue-wide axis that are translated into polarized actin and microtubule cytoskeletal dynamics. PCP has emerged as an important regulator of developmental, homeostatic and disease processes in the respiratory system. It acts along other signaling pathways to create the elaborately branched structure of the lung by controlling the directional protrusive movements of cells during branching morphogenesis. PCP operates in the airway epithelium to establish and maintain the orientation of respiratory cilia along the airway axis for anatomically directed mucociliary clearance. It also regulates the establishment of the pulmonary vasculature. In adult tissues, PCP dysfunction has been linked to a variety of chronic lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary arterial hypertension, stemming chiefly from the breakdown of proper tissue structure and function and aberrant cell migration during regenerative wound healing. A better understanding of these (impaired) PCP mechanisms is needed to fully harness the therapeutic opportunities of targeting PCP in chronic lung diseases. AU - Vladar, E.K.* AU - Königshoff, M. C1 - 58459 C2 - 48451 SP - 231-243 TI - Noncanonical Wnt planar cell polarity signaling in lung development and disease. JO - Biochem. Soc. Trans. VL - 48 IS - 1 PY - 2020 SN - 0300-5127 ER - TY - JOUR AB - Although heat-shock (cell stress) proteins are commonly considered as being intracellular molecular chaperones that undertake a number of cytoprotective and cellular housekeeping functions, there is now a wealth of evidence to indicate that these proteins can be released by cells via active processes. Many molecular chaperones are secreted, or exist as cell surface proteins which can act as powerful signalling agonists and also as receptors for selected ligands. Levels of heat-shock (cell stress) proteins in biological fluids are now being associated with a plethora of clinical conditions, and these proteins therefore have potential utility as biomarkers of disease and/or response to therapeutic intervention. The present article summarizes current knowledge relating to extracellular cell stress proteins as biomarkers of human disease. AU - Pockley, A.G.* AU - Henderson, B.* AU - Multhoff, G. C1 - 42843 C2 - 35419 SP - 1744-1751 TI - Extracellular cell stress proteins as biomarkers of human disease. JO - Biochem. Soc. Trans. VL - 42 IS - 6 PY - 2014 SN - 0300-5127 ER - TY - JOUR AB - Argonaute proteins interact with small RNAs and facilitate small RNA-guided gene-silencing processes. Small RNAs guide Argonaute proteins to distinct target sites on mRNAs where Argonaute proteins interact with members of the GW182 protein family (also known as GW proteins). In subsequent steps, GW182 proteins mediate the downstream steps of gene silencing. The present mini-review summarizes and discusses our current knowledge of the molecular basis of Argonaute-GW182 protein interactions. AU - Pfaff, J. AU - Meister, G.* C1 - 26314 C2 - 32169 SP - 855-860 TI - Argonaute and GW182 proteins: An effective alliance in gene silencing. JO - Biochem. Soc. Trans. VL - 41 IS - 4 PB - Portland Press PY - 2013 SN - 0300-5127 ER - TY - JOUR AB - Pyrite (FeS2) is a major iron- and sulfur-containing mineral phase in the environment. Oxidation of pyrite by aerobic micro-organisms has been well investigated. However, the reactivity of pyrite under anoxic conditions is still an open question. In the present paper, we summarize field and laboratory data on this chemolithotrophic respiration process with nitrate as terminal electron acceptor. Geochemical and stable isotope field data indicate that this process is occurring. Laboratory studies are more ambiguous, but recent positive results provide evidence that anaerobic microbial pyrite oxidation can, in fact, occur with nitrate as electron acceptor. AU - Bosch, J. AU - Meckenstock, R.U. C1 - 11422 C2 - 30659 SP - 1280-1283 TI - Rates and potential mechanism of anaerobic nitrate-dependent microbial pyrite oxidation. JO - Biochem. Soc. Trans. VL - 40 IS - 6 PB - Portland Press Ltd. PY - 2012 SN - 0300-5127 ER -