OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand

Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1''s role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.     

Human cortical traveling waves: dynamical properties and correlations with responses

The spatiotemporal behavior of human EEG oscillations is investigated. Traveling waves in the alpha and theta ranges are found to be common in both prestimulus and poststimulus EEG activity. The dynamical properties of these waves, including their speeds, directions, and durations, are systematically characterized for the first time, and the results show that there are significant changes of prestimulus spontaneous waves in the presence of an external stimulus. Furthermore, the functional relevance of these waves is examined by studying how they are correlated with reaction times on a single trial basis; prestimulus alpha waves traveling in the frontal-to-occipital direction are found to be most correlated to reaction speeds. These findings suggest that propagating waves of brain oscillations might be involved in mediating long-range interactions between widely distributed parts of human cortex.     

Joint moment work during the stance-to-swing transition in hemiparetic subjects

Following stroke many individuals are left with neurological and functional deficits, including hemiparesis, which impair their ability to walk. Our previous work reported that propulsion of the paretic leg during pre-swing is impaired and may limit gait speed and knee flexion during swing. To elucidate the mechanism of this impairment, we assessed the mechanical work produced by the hip, knee, and ankle moments during pre-swing of the paretic limb in a group of stroke subjects and compared it with the work produced by non-disabled controls walking at similar speeds. Kinematic and kinetic gait data were collected from 23 hemiparetic and 10 control subjects. The hemiparetic subjects walked at their self-selected speeds. The controls walked at their self-selected and two or three slower speeds. Even when compared to controls walking at slow speeds, ankle plantarflexor work during pre-swing was greatly reduced (-0.136+/-0.062J/kg) in the hemiparetic subjects. Differences in hip (+0.006+/-0.020J/kg) and knee (+0.040+/-0.026J/kg) moment work partially offset the reduction in ankle work, but net joint moment work was still significantly reduced (-0.088+/-0.056J/kg). The reduction in work accounts for the low energy of the paretic limb at the stance-to-swing transition previously reported. Future investigation is needed to determine if targeted training of the plantarflexors in the paretic limb improves swing-phase function and locomotor performance in hemiparetic individuals.     

Development of ionic currents of zebrafish slow and fast skeletal muscle fibers

Voltage-gated Na+ and K+ channels play key roles in the excitability of skeletal muscle fibers. In this study we investigated the steady-state and kinetic properties of voltage-gated Na+ and K+ currents of slow and fast skeletal muscle fibers in zebrafish ranging in age from 1 day postfertilization (dpf) to 4-6 dpf. The inner white (fast) fibers possess an A-type inactivating K+ current that increases in peak current density and accelerates its rise and decay times during development. As the muscle matured, the V50s of activation and inactivation of the A-type current became more depolarized, and then hyperpolarized again in older animals. The activation kinetics of the delayed outward K+ current in red (slow) fibers accelerated within the first week of development. The tail currents of the outward K+ currents were too small to allow an accurate determination of the V50s of activation. Red fibers did not show any evidence of inward Na+ currents; however, white fibers expressed Na+ currents that increased their peak current density, accelerated their inactivation kinetics, and hyperpolarized their V50 of inactivation during development. The action potentials of white fibers exhibited significant changes in the threshold voltage and the half width. These findings indicate that there are significant differences in the ionic current profiles between the red and white fibers and that a number of changes occur in the steady-state and kinetic properties of Na+ and K+ currents of developing zebrafish skeletal muscle fibers, with the most dramatic changes occurring around the end of the first day following egg fertilization.     

Abundance and distribution of sturgeon feeding pits in a Washington estuary

Sturgeon diet and feeding habitats are notoriously difficult to document. We mapped the locations of feeding pits in Willapa Bay, Washington, to characterize estuarine habitats used by sub-adult and adult sturgeon for infaunal feeding. Monthly summer surveys of intertidal plots revealed that feeding pit density was highest in July and August, when sturgeon occupy Willapa Bay. The ephemeral nature of feeding pits and high daily densities (> 1000 pits/ha) indicated intensive sturgeon feeding over unvegetated littoral mud flats during high tide. Feeding pit density was lowest in subtidal areas, over sand (grain sizes primarily >63 μ), and at sites with dense stands of non-indigenous seagrass, Zostera japonica. Sub-adult and adult sturgeon apparently used these habitats significantly less than would be predicted based on their availability. Feeding pit formation was negatively correlated with Z. japonica shoot dry weight and positively correlated with the abundance of thalassinid shrimp burrows. Experimental removal of Z. japonica resulted in increased sturgeon feeding, but experimental removal of burrowing shrimp did not significantly affect feeding pit formation. Aquaculture activities that harden substrate and proliferation of invasive seagrass both appear to produce estuarine substrates that are unsuitable for benthic feeding by sturgeon.     

Opponent activities of Shh and BMP signaling during floor plate induction in vivo.

We performed in vivo experiments in chick embryos that examined whether application of an exogenous source of Shh protein mimics the ability of the notochord to induce ectopic floor plate cells in the neural tube. Shh cannot act alone to induce a floor plate. However, coapplication of Shh and chordin, a BMP antagonist normally coexpressed with Shh in the notochord, results in a marked switch from dorsal to ventral cell fate, including a dramatic and widespread induction of floor plate cells. These data provide in vivo evidence that notochord-derived BMP antagonists may normally generate a permissive environment for the Shh-mediated induction of floor plate. Further experiments performed to address the source of BMPs that are inhibited by the action of chordin suggest that they derive specifically from the surface ectoderm and dorsal-most neuroepithelium. These data indicate that, at neural groove stages, dorsally derived BMPs affect ventral-most regions of the neural plate, suggesting a novel long-range action of BMPs. Together, these studies suggest that the balance of dorsally derived signals and notochord-derived signals determines the extent of floor plate cell induction.