Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient regeneration of skeletal muscle along with transient expression of dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon of reexpression of functional dystroglycan in regenerating muscle fibers in a mild form of human muscular dystrophy caused by disruption of posttranslational dystroglycan processing. Thus, maintenance of regenerative capacity by satellite cells expressing dystroglycan is likely responsible for mild disease progression in mice and possibly humans. Therefore, inadequate repair of skeletal muscle by satellite cells represents an important mechanism affecting the pathogenesis of muscular dystrophy.

[1] We perform a series of 3-D Direct Numerical Simulations (DNS) to assess the vertical heat transport through thermohaline staircases in the Arctic Ocean. The diagnostics of DNS, performed for the first time in the realistic parameter range, result in vertical fluxes exceeding those of extant "four-thirds flux laws" by as much as a factor of 2 and suggest that the 4/3 exponent may require downward revision. Through a series of equivalent 2-D DNS, we show that they are consistent with their more resource-intensive 3-D counterparts for sufficiently large density ratio (R r ) but underestimate heat transport for low R r . Finally, we examine the role of boundary conditions in controlling the vertical heat transport. Rigid boundaries-a necessary ingredient in laboratoryderived flux-laws-are shown to reduce the estimates of heat fluxes relative to the corresponding periodic boundary conditions.

Three-dimensional dynamics of thermohaline staircases are investigated using a series of basin-scale staircase-resolving numerical simulations. The computational domain and forcing fields are chosen to reflect the size and structure of the North Atlantic subtropical thermocline. Salt-finger transport is parameterized using the flux-gradient formulation based on a suite of recent direct numerical simulations. Analysis of the spontaneous generation of thermohaline staircases suggests that thermohaline layering is a product of the gamma instability, associated with the variation of the flux ratio g with the density ratio R r . After their formation, numerical staircases undergo a series of merging events, which systematically increase the size of layers. Ultimately, the system evolves into a steady equilibrium state with pronounced layers 20-50 m thick. The size of the region occupied by thermohaline staircases is controlled by the competition between turbulent mixing and double diffusion. Assuming, in accordance with observations, that staircases form when the density ratio is less than the critical value of R cr ' 1:7, the authors arrive at an indirect estimate of the characteristic turbulent diffusivity in the subtropical thermocline.

Voltage-gated calcium channels mediate excitationcontraction coupling in the skeletal muscle. Their molecular composition, similar to neuronal channels, includes the pore-forming ␣ 1 and auxiliary ␣ 2 ␦, ␤, and ␥ subunits. The ␥ subunits are the least characterized, and their subunit interactions are unclear. The physiological importance of the neuronal ␥ is emphasized by epileptic stargazer mice that lack ␥ 2 . In this study, we examined the molecular basis of interaction between skeletal ␥ 1 and the calcium channel. Our data show that the ␣ 1 1.1, ␤ 1a , and ␣ 2 ␦ subunits are still associated in ␥ 1 null mice. Reexpression of ␥ 1 and ␥ 2 showed that ␥ 1 , but not ␥ 2 , incorporates into ␥ 1 null channels. By using chimeric constructs, we demonstrate that the first half of the ␥ 1 subunit, including the first two transmembrane domains, is important for subunit interaction. Interestingly, this chimera also restores calcium conductance in ␥ 1 null myotubes, indicating that the domain mediates both subunit interaction and current modulation. To determine the subunit of the channel that interacts with ␥ 1 , we examined the channel in muscular dysgenesis mice. Cosedimentation experiments showed that ␥ 1 and ␣ 2 ␦ are not associated. Moreover, ␣ 1 1.1 and ␥ 1 subunits form a complex in transiently transfected cells, indicating direct interaction between the ␥ 1 and ␣ 1 1.1 subunits. Our data demonstrate that the first half of ␥ 1 subunit is required for association with the channel through ␣ 1 1.1. Because subunit interactions are conserved, these studies have broad implications for ␥ heterogeneity, function and subunit association with voltage-gated calcium channels.The L-type voltage-gated calcium channels of the skeletal muscle serve both as a voltage-gated calcium channel and as a voltage sensor for excitation-contraction (EC) 1 coupling (1, 2). These channels serve to couple depolarization to intracellular calcium release via the ryanodine receptor. The sites of EC coupling in the skeletal muscle are the triads, which are highly organized junctions comprising the t-tubules and the underlying sarcoplasmic reticulum (3). The voltage-gated calcium channels are localized predominantly in the t-tubules in close association with the ryanodine receptor in the sarcoplasmic reticulum (4, 5).At the molecular level, the calcium channel is composed of the pore-forming ␣ 1 1.1 subunit and auxiliary ␣ 2 ␦, ␤ 1 , and ␥ 1 subunits (6). This four-subunit composition of the channels is similar to that of the neuronal voltage-gated channels (7, 8). The auxiliary ␣ 2 ␦ and ␤ subunits enhance membrane trafficking of the ␣ 1 1.1 subunit and modulate the voltage-dependent kinetics of the channel (9). In addition to the role of the ␤ 1 subunit in the trafficking of the channel, it also has a crucial role in EC coupling as emphasized by the absence of EC coupling and early lethality in mice that lack the skeletal ␤ 1 subunit (10). The subunit interactions of the ␣ 2 ␦ and ␤ subunits have been relatively well defined.The ␥ 1 subunit is ...