Rev. Biol. Trop. 59 (4): 1697-1706. Epub 2011 December 01.”
“Effective management of knee joint disorders demands appropriate rehabilitation programs to restore function while strengthening muscles. Excessive stresses in cartilage/menisci and forces in ligaments should be avoided to not exacerbate
joint condition after an injury or reconstruction. Using a validated 3D nonlinear finite element model, detailed biomechanics of the entire joint in closed-kinetic-chain squat exercises are investigated IWR-1-endo at different flexion angles, weights in hands, femur-tibia orientations and coactivity in hamstrings. Predictions are in agreement with results of earlier studies. Estimation of small forces in cruciate ligaments advocates the use of squat exercises at all joint angles and external loads. In contrast, large contact stresses, especially at the patellofemoral joint, that approach cartilage failure threshold in compression suggest avoiding squatting at greater flexion angles, joint moments and weights in hands. Current results are helpful in comprehensive evaluation and design of effective exercise
therapies and trainings with minimal risk to various components.”
“The G-protein coupled receptor, metabotropic glutamate receptor 5 (mGluR5), is expressed on both cell surface and intracellular membranes in striatal neurons. Using pharmacological tools to differentiate membrane responses, we previously demonstrated that cell surface mGluR5 triggers rapid, transient cytoplasmic Ca2+ rises, resulting in c-Jun N-terminal kinase, Ca2+/calmodulin-dependent NU7441 protein kinase, and cyclic adenosine 3′,5′-monophosphate-responsive element-binding protein (CREB) phosphorylation, whereas stimulation of intracellular mGluR5
induces long, sustained Ca2+ responses leading to the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Elk-1 (Jong, Y. J., Kumar, V., and O’Malley, K. L. (2009) J. Biol. Chem. 284, 35827-35838). Using pharmacological, genetic, and bioinformatics approaches, the current findings show that both receptor populations up-regulate many immediate early genes involved in growth and differentiation. Activation of intracellular mGluR5 also up-regulates genes involved in synaptic plasticity AG-881 supplier including activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mechanistically, intracellular mGluR5-mediated Arc induction is dependent upon extracellular and intracellular Ca2+ and ERK1/2 as well as calmodulin-dependent kinases as known chelators, inhibitors, and a dominant negative Ca2+/calmodulin-dependent protein kinase II construct block Arc increases. Moreover, intracellular mGluR5-induced Arc expression requires the serum response transcription factor (SRF) as wild type but not SRF-deficient neurons show this response.