The Responsibility of Schools for Meeting the Leisure Time Needs of the Community

The purpose of this paper was to determine the extent to which authorities in the fields of recreation and education consider the leisure time needs of the community as a responsibility of schools. The author has also attempted to show what changes must take place in educational patterns if schools are to meet these leisure time needs

Role of cardiac troponin I phosphorylation in cardiac function: From molecule to mouse

Abstract only availableThe regulation of cardiac muscle contraction involves the interplay between a variety of molecules on the thick and thin filaments. One important regulatory molecule is troponin, which consists of three subunits, troponin C (TnC) that binds calcium, troponin T (TnT) that binds tropomyosin, and troponin I (TnI) that binds actin and tends to inhibit contraction. Following muscle excitation, cytoplasmic calcium rises and binds TnC, which causes a conformational change in TnI that reduces its affinity for actin; this, in turn, allows TnT and tropomyosin to shift positions revealing myosin binding sites on actin, leading to muscle contraction. Interestingly, cardiac troponin I (cTnI) has several phosphorylation sites, which are known to modulate this regulatory process. For example, phosphorylation of serines 23 and 24 on cTnI by protein kinase A (PKA) is known to decrease the calcium binding affinity of cardiac TnC and, thus, thought to speed muscle relaxation. On the other hand, phosphorylation of cTnI on serines 43 and 45 and threonine 144 by protein kinase C (PKC) decreases both force production and calcium sensitivity of force and is thought to contribute to depressed ventricular function in failing hearts. In this study we investigated the effects of chronic cTnI phosphorylation on cardiac function from transgenic animals in which either PKA phosphorylation sites (Ser-23/Ser-24) (PP) or both the PKA and PKC phosphorylation sites (Ser-23/Ser-24/Ser-43/Ser-45/T-144) (All-P) were replaced with aspartic acid to mimic phosphorylation. Left ventricular cardiac myocytes from PP transgenic mice exhibited less calcium sensitivity of force while myocytes from All-P transgenic mice exhibited decreased maximal force, decreased calcium sensitivity of force, and decreased power output, implicating a dominate role of PKC phosphorylation sites on myofilament function. Consistent with these single myocyte studies, left ventricular power output also was depressed in All-P mice compared to both WT and PP transgenic ventricles. We next tested the hypothesis that PP transgenic mice would engage in greater voluntary running compared to WT and All-P transgenic animals. In contrast to this idea, WT and All-P mice ran ~3- and ~4-fold more than the PP transgenic mouse, respectively. Overall, these results indicate that PKC phosphorylation of cTnI plays a dominant role in depressing contractility and may contribute to the maladaptive behavior.NIH grant to K.S. McDonal

Regulation of Myofilament Contractile Function in Human Donor and Failing Hearts

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca2+ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was similar between groups (donor: length 148 ± 10 μm, width 21 ± 2 μm, n = 13; HF: length 131 ± 9 μm, width 23 ± 1 μm, n = 16). The maximal Ca2+-activated isometric force was also similar between groups (donor: 47 ± 4 kN⋅m–2; HF: 44 ± 5 kN⋅m–2), which implicates that previously reported force declines in multi-cellular preparations reflect, at least in part, tissue remodeling. Maximal force development rates were also similar between groups (donor: ktr = 0.60 ± 0.05 s–1; HF: ktr = 0.55 ± 0.04 s–1), and both groups exhibited similar Ca2+ activation dependence of ktr values. Human cardiac myocyte preparations exhibited a Ca2+ activation dependence of loaded shortening and power output. The peak power output normalized to isometric force (PNPO) decreased by ∼12% from maximal Ca2+ to half-maximal Ca2+ activations in both groups. Interestingly, the SL dependence of PNPO was diminished in failing myocyte preparations. During sub-maximal Ca2+ activation, a reduction in SL from ∼2.25 to ∼1.95 μm caused a ∼26% decline in PNPO in donor myocytes but only an ∼11% change in failing myocytes. These results suggest that altered length-dependent regulation of myofilament function impairs ventricular performance in failing human hearts

Measurements of the persistent current decay and snapback effect in Tevatron dipole magnets

A systematic study of the persistent current decay and snapback effect in the fields of Tevatron accelerator dipoles was performed at the Fermilab Magnet Test Facility (MTF). The decay and snapback were measured under a range of conditions including variations of the current ramp parameters and magnet operational history. The study has mostly focused on the dynamic behavior of the normal sextupole component. In addition, the paper presents the persistent current effects observed in the other allowed field harmonics as well. The results provide new information about the previously observed ''excess'' decay during the first several seconds of the sextupole decay during injection and the correlation between the snapback amplitude and its duration

Cytoplasmic γ-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers

Tropomodulins, cytoplasmic γ-actin, and small ankyrin 1.5 mechanically stabilize the sarcoplasmic reticulum and maintain myofibril alignment in skeletal muscle fibers

Quench performance of superconducting quadrupole magnets for the new Fermilab low beta insertion

Construction and testing of the components for the new Tevatron D0/B0 low beta insertion has been nearly completed. The devices include superconducting cold iron quadrupoles utilizing a 2-shell, cos2{theta} coil geometry with a 7.6 cm aperture. The maximum design gradient is 1.41 T/cm at an operating current of 4832 A. They have the highest current density with the highest peak field on the winding of any quadrupole yet built. This paper summarizes the quench performance and ramp rate sensitivity of the 2-shell design and relates the performance characteristics to the relevant aspects of design and fabrication. 8 refs., 6 figs., 3 tabs

Skeletal Muscle-Specific Ablation of γcyto-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γcyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γcyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γcyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γcyto-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests γcyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a γcyto-actin-utrophin interaction