14 research outputs found

    Ready, Steady - Enjoy Your Meal! The Practice of Sports Nutrition at Different Intensity Levels: Extreme Sports/Endurance

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    Nutritional analyses and recommendations for athletes pursuing action sports/extreme sports in the ultra-endurance range and for expeditions into hostile terrains are rare. A study of athletes doing a 24-hour cycling race showed an energy deficit of more than 5000 kcal in spite of an intake of almost 8000 kcal in 24 hours. A combination of sports products, electrolyte products, and normal foods has proved to be a practical solution for energy and nutrient intake. In contrast to organised competitions there are no resupply stations during expeditions. The case example of a desert crossing on foot of several weeks' duration was used to determine energy consumption in advance, under simulated conditions in the laboratory, and serves as a basis for nutrition planning. Analyses before and after expeditions show the differences in body composition and a strongly negative energy and nitrogen balance

    A new moving mesh algorithm for the finite element solution of variational problems

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    SIGLEAvailable from British Library Document Supply Centre-DSC:DXN032408 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    MARCKS affects cell motility and response to BTK inhibitors in CLL

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    Bruton tyrosine kinase (BTK) inhibitors are highly active drugs for the treatment of chronic lymphocytic leukemia (CLL). To understand the response to BTK inhibitors on a molecular level, we performed (phospho)proteomic analyses under ibrutinib treatment. We identified 3466 proteins and 9184 phosphopeptides (representing 2854 proteins) in CLL cells exhibiting a physiological ratio of phosphorylated serines (pS), threonines (pT), and tyrosines (pY) (pS:pT:pY). Expression of 83 proteins differed between unmutated immunoglobulin heavy-chain variable region (IGHV) CLL (UM-CLL) and mutated IGHV CLL (M-CLL). Strikingly, UM-CLL cells showed higher basal phosphorylation levels than M-CLL samples. Effects of ibrutinib on protein phosphorylation levels were stronger in UM-CLL, especially on phosphorylated tyrosines. The differentially regulated phosphopeptides and proteins clustered in pathways regulating cell migration, motility, cytoskeleton composition, and survival. One protein, myristoylated alanine-rich C-kinase substrate (MARCKS), showed striking differences in expression and phosphorylation level in UM-CLL vs M-CLL. MARCKS sequesters phosphatidylinositol-4,5-bisphosphate, thereby affecting central signaling pathways and clustering of the B-cell receptor (BCR). Genetically induced loss of MARCKS significantly increased AKT signaling and migratory capacity. CD40L stimulation increased expression of MARCKS. BCR stimulation induced phosphorylation of MARCKS, which was reduced by BTK inhibitors. In line with our in vitro findings, low MARCKS expression is associated with significantly higher treatment-induced leukocytosis and more pronounced decrease of nodal disease in patients with CLL treated with acalabrutinib
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