FORCE AND MOMENT MEASUREMENTS DURING ALPINE SKIING DEPENDING ON HEIGHT POSITION

INTRODUCTION: When a ski is set on edge a lever arm is produced by the force FS, which is applied through the skier’s leg and boot midline, and the ground reaction force FR, which acts on the ski edge. A moment is necessary to keep the ski in its position (see figure and compare with Lind). It is hypothesized that the magnitude of this moment is mainly determined by the width-height proportion of ski and binding. In order to adjust this moment, the skier has to rotate his knee inwards or angle his hip in the lateral direction (Lind, Howe). The objective of this study was to clarify whether the height of the binding plate has any influence on the generated moment. METHODS: A professional ski racer (A-Kader DSV) descended a giant slalom course (at 25° steepness) nine times consecutively. For every run the equipment was identical (skis: ATOMIC ARC RS, binding: ESS 10.28) except for the adjusted height of the binding plate. Three different height positions were used. System A was comprised without a plate between ski and binding, system B with a plate of 1 cm height and system C with a plate of 2 cm height. Using a previously described measuring boot (Wimmer), the ground reaction forces were determined at four distinct locations underneath the boot soles. The specific set-up of the force sensors (two at every edge of the skis) allowed us to calculate the generated moments by known lever-arms. RESULTS: Out of nine runs, seven runs differed in elapsed time by less than 0.3 sec, and the average duration was 20 sec. For this reason a good comparability can be derived. The three fastest runs were made with the 2 cm binding plate, the three slowest runs without the binding plate. The magnitude of ground reaction force ranged from 2000 to 3500 N. The calculated moment was approx. 40-70 Nm and was independent of height position at all turns. Indeed, the moment variation was more affected by the specific turns of the course than by height position. However, the force readings during turns (and thus the moments) were smoother when a higher plate was used. CONCLUSIONS: Because no moment differences could be assigned to the different height positions, the varying width-height-proportions of the three systems may have resulted in three different edging angles. For system C a smaller edging angle would be necessary than for system B, whereas system A would need the largest edging angle. This might be important for the skier, since a smaller body angle in the lateral direction would be necessary to maintain equilibrium using a binding plate

ADAM10 and ADAM17 promote SARS‐CoV‐2 cell entry and spike protein‐mediated lung cell fusion

The severe‐acute‐respiratory‐syndrome‐coronavirus‐2 (SARS‐CoV‐2) is the causative agent of COVID‐19, but host cell factors contributing to COVID‐19 pathogenesis remain only partly understood. We identify the host metalloprotease ADAM17 as a facilitator of SARS‐CoV‐2 cell entry and the metalloprotease ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID‐19 pathology. ADAM10 and ADAM17, which are broadly expressed in the human lung, cleave the SARS‐CoV‐2 spike protein (S) in vitro, indicating that ADAM10 and ADAM17 contribute to the priming of S, an essential step for viral entry and cell fusion. ADAM protease‐targeted inhibitors severely impair lung cell infection by the SARS‐CoV‐2 variants of concern alpha, beta, delta, and omicron and also reduce SARS‐CoV‐2 infection of primary human lung cells in a TMPRSS2 protease‐independent manner. Our study establishes ADAM10 and ADAM17 as host cell factors for viral entry and syncytia formation and defines both proteases as potential targets for antiviral drug development

NPY Neuron-Specific Y2 Receptors Regulate Adipose Tissue and Trabecular Bone but Not Cortical Bone Homeostasis in Mice

BACKGROUND: Y2 receptor signalling is known to be important in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone physiology. Y2 receptors are located post-synaptically as well as acting as auto receptors on NPY-expressing neurons, and the different roles of these two populations of Y2 receptors in the regulation of energy homeostasis and body composition are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We thus generated two conditional knockout mouse models, Y2(lox/lox) and NPYCre/+;Y2(lox/lox), in which Y2 receptors can be selectively ablated either in the hypothalamus or specifically in hypothalamic NPY-producing neurons of adult mice. Specific deletion of hypothalamic Y2 receptors increases food intake and body weight compared to controls. Importantly, specific ablation of hypothalamic Y2 receptors on NPY-containing neurons results in a significantly greater adiposity in female but not male mice, accompanied by increased hepatic triglyceride levels, decreased expression of liver carnitine palmitoyltransferase (CPT1) and increased expression of muscle phosphorylated acetyl-CoA carboxylase (ACC). While food intake, body weight, femur length, bone mineral content, density and cortical bone volume and thickness are not significantly altered, trabecular bone volume and number were significantly increased by hypothalamic Y2 deletion on NPY-expressing neurons. Interestingly, in situ hybridisation reveals increased NPY and decreased proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of mice with hypothalamus-specific deletion of Y2 receptors in NPY neurons, consistent with a negative feedback mechanism between NPY expression and Y2 receptors on NPY-ergic neurons. CONCLUSIONS/SIGNIFICANCE: Taken together these data demonstrate the anti-obesogenic role of Y2 receptors in the brain, notably on NPY-ergic neurons, possibly via inhibition of NPY neurons and concomitant stimulation of POMC-expressing neurons in the arcuate nucleus of the hypothalamus, reducing lipogenic pathways in liver and/or skeletal muscle in females. These data also reveal as an anti-osteogenic effect of Y2 receptors on hypothalamic NPY-expressing neurons on trabecular but not on cortical bone