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ABSTRACT:We hypothesized that maternal creatine supplementation from mid-pregnancy would protect the diaphragm of the newborn spiny mouse from the effects of intrapartum hypoxia. Pregnant mice were fed a control or 5% creatine-supplemented diet from mid-gestation. On the day before term, intrapartum hypoxia was induced by isolating the pregnant uterus in a saline bath for 7.5-8 min before releasing and resuscitating the fetuses. Surviving pups were placed with a cross-foster dam, and diaphragm tissue was collected at 24 h postnatal age. Hypoxia caused a significant decrease in the cross-sectional area (ϳ19%) and contractile function (26.6% decrease in maximum Ca 2ϩ -activated force) of diaphragm fibers. The mRNA levels of the muscle mass-regulating genes MuRF1 and myostatin were significantly increased (2-fold). Maternal creatine significantly attenuated hypoxia-induced fiber atrophy, contractile dysfunction, and changes in mRNA levels. This study demonstrates that creatine loading before birth significantly protects the diaphragm from hypoxiainduced damage at birth. (Pediatr Res 68: 393-398, 2010)

Small cardiac myofibrillar preparations were obtained from the right ventricle of normal (129/ReJ) and dystrophic (129/ReJ dy/dy) mice and were chemically skinned in a relaxing solution by exposure to Triton X-100 (3% v/v). (2) The isometric force produced in these skinned cardiac preparations at different sarcomere lengths was measured in solutions of different [Ca2+] and ionic strength. The effect of the negative inotropic drug 2,3-butanedione monoxime (BDM), which is known to act at the myofibrillar level was also investigated. (3) The murine cardiac preparation from normal animals was found to develop 50% maximal force at a pCa (= -log10[Ca2+]) of 5.59 +/- 0.08 and 5.94 +/- 0.03 (mean +/- SD) under physiological (ionic equivalents concentration, I = 154 mM; pH 7.10; [Mg2+] 1 mM) and low ionic strength (I = 94 mM; pH 7.10; [Mg2+] 1 mM) conditions respectively. The isometric force curves were significantly shallower at low ionic strength (Hill coefficient, 1.8 +/- 0.1) than at physiological ionic strength (Hill coefficient, 2.6 +/- 0.3) and the sarcomere length effect on the force-pCa relation was markedly reduced at lower ionic strength. (4) Increasing BDM concentrations in solutions up to 100 mM reduced the maximum Ca2+-activated force of cardiac preparations from normal mice to less than 6% of the control values in a dose dependent fashion. BDM also rendered the cardiac preparations less sensitive to Ca2+ by a factor of up to 1.5 in a process which showed saturation at BDM concentrations higher than 15 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

The properties of bi-directional sliding of F-actin prepared from rabbit skeletal muscle moving along clam thick filaments have been characterized in the presence of agents known to modify unloaded shortening velocity in muscle to determine if the sliding characteristics of actin are similar in the two directions of movement. Actin filaments moved at a fast velocity towards the central bare zone (11.1 +/- 0.2 microns s-1) and at a slower velocity away from the bare zone (3.9 +/- 0.3 microns s-1). Movement of filaments at the slow sliding velocity is thought to be sustained by a change in orientation of the myosin head. The Michaelis Menten constant (Km values) of approximately 0.3 mM in the presence of MgATP concentrations of 0.01-2.0 mM at an ionic strength of 43.5 mM were reduced to approximately 0.1 mM at low ionic strength (18.5 mM) although the Km values at the fast and slow sliding velocities at each ionic strength were similar. In the presence of constant concentrations of MgATP, increasing the MgADP concentrations from 0.5 to 2mM, decreased the bi-directional sliding velocity of actin. The data were well fitted with an equation described by Michaelis Menten kinetics yielding mean absolute Km and Ki values of 0.41 +/- 0.01 and 0.44 +/- 0.05 mM for the fast velocity and 0.29 +/- 0.07 and 0.45 +/- 0.02 mM for the slow velocity of sliding, respectively. The Km and Ki values were not significantly different from each other at either the fast or slow sliding velocities. The actin filament sliding velocity appeared to be controlled through the thick filament as actin was devoid of regulatory proteins and the presence of Ca2+ modified the MgATP dependent movement of actin. The pCa value for half maximal sliding velocity was 7.0 for both fast and slow velocities. The Km and Ki values and the Ca2+ sensitivity of the actin movement at the fast and slow sliding velocity are similar suggesting that no major biochemical changes have occurred in the myosin head as a result of a change in orientation.

Digital credentials (or badges) allow evidence of achievement to be more detailed than is possible through grades, and can be shared more broadly than is possible through the academic transcript. Here, we illustrate the potential use of digital credentials in higher education through sharing an approach that utilised digital credentials to recognise the achievement of students who demonstrate outstanding achievement of specific graduate attributes. More specifically, we explore the potential use of digital credentials to contribute to the development of citizen scholars through engaging students at the course (degree) level, promoting experiential learning and facilitating public sharing. The credentialing strategy described was designed to enhance employability, and the standards and criteria associated with the award were developed in collaboration with industry partners to give students the opportunity to differentiate themselves in the graduate job market. However, student applications, perceptions of the application process and feedback from industry partners who assessed the submissions suggest that an unintended, but positive, outcome of the credentialing strategy was promotion of students’ personal identity and broader social engagement. We suggest that digital credentials at course level could be a useful tool to engage students with graduate attributes, foster graduate identity and develop graduates who are active and engaged citizens.