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Chest, Heart and Stroke Scotland

By lx.iriss.org.uk
Published On :: Friday, November 27, 2015 - 14:16

Chest, Heart and Stroke Scotland aims to improve the quality of life for people in Scotland affected by chest, heart and stroke illness, through medical research, influencing public policy, advice and information and support in the community.

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FRET and optical trapping reveal mechanisms of actin activation of the power stroke and phosphate release in myosin V [Enzymology]

By www.jbc.org
Published On :: 2020-12-18T00:06:18-08:00

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

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Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure [Molecular Bases of Disease]

By www.jbc.org
Published On :: 2020-12-25T00:06:31-08:00

Infiltration of peripheral immune cells after blood-brain barrier dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx, a network of membrane-bound glycoproteins and proteoglycans that covers the lumen of endothelial cells, functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans, a component of the endothelial glycocalyx, were studied in the context of ischemic stroke using a photochemically induced thrombosis mouse model. Decreased levels of heparan sulfate and chondroitin sulfate and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine + glycosaminoglycan oligosaccharides as compared with N-acetylcysteine administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by immortalized endothelial cells and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein (ACR) exposure. We identified the ACR-modified amino acid residues of proHPSE using nano LC–MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), Lys107, and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part is attributed to the activation of proHPSE. Because proHPSE, but not HPSE, localizes outside cells by binding with heparan sulfate proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.

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A Mouse Brain-based Multi-omics Integrative Approach Reveals Potential Blood Biomarkers for Ischemic Stroke

By www.mcponline.org
Published On :: 2020-12-01

Alba Simats
Dec 1, 2020; 19:1921-1935
Research

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A Mouse Brain-based Multi-omics Integrative Approach Reveals Potential Blood Biomarkers for Ischemic Stroke [Research]

By www.mcponline.org
Published On :: 2020-12-01T00:05:33-08:00

Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures in the hyper-acute phase of ischemic stroke is still a primary interest for translational research on stroke diagnosis, prognosis, and treatment. Data integration from high-throughput -omics techniques has become crucial to unraveling key interactions among different molecular elements in complex biological contexts, such as ischemic stroke. Thus, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics data sets obtained from mouse brains at 2 h after cerebral ischemia. By modeling net-like correlation structures, we identified an integrated network of genes and proteins that are differentially expressed at a very early stage after stroke. We validated 10 of these deregulated elements in acute stroke, and changes in their expression pattern over time after cerebral ischemia were described. Of these, CLDN20, GADD45G, RGS2, BAG5, and CTNND2 were next evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples, which were obtained from stroke patients and patients presenting stroke-mimicking conditions. Our findings indicate that CTNND2 levels in blood might potentially be useful for distinguishing ischemic strokes from stroke-mimicking conditions in the hyper-acute phase of the disease. Furthermore, circulating GADD45G content within the first 6 h after stroke could also play a key role in predicting poor outcomes in stroke patients. For the first time, we have used an integrative biostatistical approach to elucidate key molecules in the initial stages of stroke pathophysiology and highlight new notable molecules that might be further considered as blood biomarkers of ischemic stroke.

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Patients taking dabigatran to prevent stroke should avoid simvastatin and lovastatin, study suggests

By www.bmj.com
Published On :: Tuesday, November 22, 2016 - 06:31

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Moderate alcohol intake is linked to lower risk of ischaemic stroke, study finds

By www.bmj.com
Published On :: Thursday, November 24, 2016 - 06:31

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RCP warns over shortage of stroke physicians

By www.bmj.com
Published On :: Tuesday, November 29, 2016 - 06:30

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Lying flat after stroke achieves similar outcomes to sitting up, trial finds

By www.bmj.com
Published On :: Friday, June 23, 2017 - 05:33

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Endovascular treatment for acute ischaemic stroke in routine clinical practice: prospective, observational cohort study (MR CLEAN Registry)

By www.bmj.com
Published On :: Friday, March 9, 2018 - 14:16

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Thrombectomy can be considered up to 24 hours after onset of stroke, says NICE

By www.bmj.com
Published On :: Friday, November 23, 2018 - 15:56

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NICE recommends implantable monitor to identify atrial fibrillation after stroke

By www.bmj.com
Published On :: Tuesday, January 14, 2020 - 00:30

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Stroke: “striking reductions” are seen in number of people with symptoms seeking help

By www.bmj.com
Published On :: Monday, April 6, 2020 - 11:10

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Stroke: Take test for genetic variant to ensure clopidogrel works for prevention, says NICE

By www.bmj.com
Published On :: Friday, May 19, 2023 - 08:36

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Stroke: New NHS campaign urges people to call 999 as soon as symptoms show

By www.bmj.com
Published On :: Monday, November 4, 2024 - 15:26

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BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices

By www.hpcwire.com
Published On :: Fri, 08 Nov 2024 14:26:21 +0000

Nov. 8, 2024 — Barcelona Supercomputing Center‘s Innostroke project aims to transform the prevention and monitoring of stroke, one of the leading causes of death and disability worldwide, through artificial […]

The post BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices appeared first on HPCwire.

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Ali Stroker Makes History, and More From the Tony Awards

By www.smithsonianmag.com
Published On :: Mon, 10 Jun 2019 17:54:14 +0000

The actress becomes the first wheelchair user ever to take home the coveted prize at the 73rd annual award show

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