Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe