Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells. The expression of Tay is maximal in motoneurons with low levels of activated ERK, suggesting that Tay modulates the activity of Erk in these cells. We also found that loss of tay expression and increased Erk activity specifically in the motoneurons cause a reversible decrease in walking speed. Impaired motoneurons activity may be caused by alterations in the functionality and number of synaptic boutons developing at the neuromuscular junction in tay mutants.
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http://dx.doi.org/10.1111/gbb.12470 | DOI Listing |
Ann Acad Med Singap
November 2024
Department of Dermatology, Singapore General Hospital, Singapore.
J Vasc Access
November 2024
Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore.
Background: A multidisciplinary care model involving the interventional radiologist, vascular surgeon, interventional nephrologist, renal advanced nurse practitioner, and renal coordinators was implemented to improve the care for the patient admitted with dysfunctional hemodialysis access. This study aims to evaluate the effectiveness and sustainability of this multidisciplinary care model.
Method: A dedicated interventional nephrology suite was established to perform endovascular procedures for patients admitted with hemodialysis access dysfunction via the emergency department of the hospital.
N Engl J Med
November 2024
From the Translational and Clinical Research Institute, Faculty of Medical Sciences (V.K.), the Population Health Sciences Institute (H.M., M.D.T.), and the Newcastle Clinical Trials Unit (C.S., M. Bardgett, P.W., M.D.T., J.P.), Newcastle University, and the Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust (V.K., J.A.H., I.U.H.), Newcastle upon Tyne; Northumbria Healthcare NHS Foundation Trust, Cramlington (C.R., D.P.R.); the Faculty of Health Sciences and Wellbeing, School of Medicine, University of Sunderland Medical School, Sunderland (D.P.R.); North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (J. Carter, J.Q.); Chesterfield Royal Hospital, Chesterfield (J. Cooke); South Tees NHS Foundation Trust, Middlesbrough (D.A.); County Darlington and Durham NHS Foundation Trust, Darlington (J. Murphy); Royal Derby Hospital, Derby (D.K.); University Hospital Ayr, Ayr (J. McGowan); Leeds Teaching Hospital NHS Trust, Leeds (M.V.); Torbay and South Devon NHS Foundation Trust, Torquay (D.F.); Manchester University NHS Foundation Trust, Manchester (H.C.); Epsom and St. Helier University Hospitals, Epsom (S.M.); Ninewells Hospital, Dundee (J.I.); Bradford Royal Infirmary, Bradford (S.L.); Blackpool Victoria Hospital, Blackpool (G.G.); United Lincolnshire Hospitals NHS Trust, Lincoln (K.L.); Wrightington Wigan and Leigh Teaching Hospitals NHS Foundation Trust, Wigan (A.S.); North Bristol NHS Trust, Bristol (A.G.D.); University Hospital of Leicester NHS Trust, Leicester (S.H.); Barts Health NHS Trust (M. Belder) and London School of Hygiene and Tropical Medicine (S.J.P.), London; the Centre for Cardiovascular Science, University of Edinburgh, Edinburgh (M.D., D.E.N., K.A.A.F.); Norwich Medical School, University of East Anglia, Norwich (M.F.); and Sheffield Teaching Hospital, Sheffield (R.F.S.) - all in the United Kingdom.
Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear.
Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy.
Chem Sci
July 2024
Department of Chemistry, Chemistry Research Laboratory, University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
Bridged bicycloalkanes such as bicyclo[1.1.1]pentanes (BCPs) and bicyclo[3.
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