Learning Redundant Motor Tasks With and Without Overlapping Dimensions: Facilitation and Interference Effects

Prior learning of a motor skill creates motor memories that can facilitate or interfere with learning of new, but related, motor skills. One hypothesis of motor learning posits that for a sensorimotor task with redundant degrees of freedom, the nervous system learns the geometric structure of the task and improves performance by selectively operating within that task space. We tested this hypothesis by examining if transfer of learning between two tasks depends on shared dimensionality between their respective task spaces. Human participants wore a data glove and learned to manipulate a computer cursor by moving their fingers. Separate groups of participants learned two tasks: a prior task that was unique to each group and a criterion task that was common to all groups. We manipulated the mapping between finger motions and cursor positions in the prior task to define task spaces that either shared or did not share the task space dimensions (x-y axes) of the criterion task. We found that if the prior task shared task dimensions with the criterion task, there was an initial facilitation in criterion task performance. However, if the prior task did not share task dimensions with the criterion task, there was prolonged interference in learning the criterion task due to participants finding inefficient task solutions. These results show that the nervous system learns the task space through practice, and that the degree of shared task space dimensionality influences the extent to which prior experience transfers to subsequent learning of related motor skills

The HIV Protease Inhibitor Saquinavir Impairs Lipid Metabolism and Glucose Transport in Cultured Adipocytes

Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 μg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [14C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulin-stimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs

Thiazolidinediones Inhibit Lipoprotein Lipase Activity in Adipocytes

The thiazolidinediones troglitazone and BRL 49653 improve insulin sensitivity in humans and animals with insulin resistance. Adipose tissue lipoprotein lipase is an insulin-sensitive enzyme. We examined the effects of thiazolidinediones on lipoprotein lipase expression in adipocytes. When added to 3T3-F442A, 3T3-L1, and rat adipocytes in culture, troglitazone and BRL 49653 inhibited lipoprotein lipase activity. This inhibition was observed at concentrations as low as 0.1 μM and within 2 h after addition of the drug. Lipoprotein lipase activity was inhibited in differentiated adipocytes as well as the differentiating cells. Despite this decrease in enzyme activity, these drugs increased mRNA levels in undifferentiated 3T3-F442A and 3T3-L1 cells and had no effect on mRNA expression or synthesis of lipoprotein lipase in differentiated cells. Western blot analysis showed that these drugs did not affect the mass of the enzyme protein. Lipoprotein lipase activity in cultured Chinese hamster ovary cells was not inhibited by troglitazone. Glucose transport, biosynthesis of lipids from glucose or the biosynthesis of proteins were unaffected by thiazolidinediones in differentiated cells, whereas glucose transport and lipid biosynthesis were increased when these drugs were added during differentiation. These results show that troglitazone and BRL 49653 have a specific, post-translational inhibitory effect on lipoprotein lipase in adipocytes, yet they promote lipid accumulation and differentiation in preadipocytes

An algorithm for generating quasiperiodic patterns and their approximants

An algorithm for projecting the interior of a hypercube in N-dimensions on to an m-dimensional subspace has been developed and incorporated into a computer program for generating quasiperiodic and periodic patterns in an n-dimensional subspace. Some aspects of the resulting orthorhombic approximants to Penrose tiling patterns are discussed and illustrated

Role of Protein Kinase C in the Translational Regulation of Lipoprotein Lipase in Adipocytes

The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. 100 nM TPA yielded maximal (80%) inhibition of LPL. No stimulation of LPL occurred after short term addition of TPA to cultures. To determine whether TPA treatment of adipocytes decreased LPL synthesis, cells were labeled with [35S]methionine and LPL protein was immunoprecipitated. LPL synthetic rate decreased after 6 h of TPA treatment. Western blot analysis of cell lysates indicated a decrease in LPL mass after TPA treatment. Despite this decrease in LPL synthesis, there was no change in LPL mRNA in the TPA-treated cells. Long term treatment of cells with TPA is known to down-regulate PKC. To assess the involvement of the different PKC isoforms, Western blotting was performed. TPA treatment of 3T3-F442A adipocytes decreased PKC α, β, λ, and ε isoforms, whereas PKC λ, θ, ζ, δ α, and γ remained unchanged or decreased minimally. To directly assess the effect of PKC inhibition, PKC inhibitors (calphostin C and staurosporine) were added to cultures. The PKC inhibitors inhibited LPL activity rapidly (within 60 min). Thus, activation of PKC did not increase LPL, but inhibition of PKC resulted in decreased LPL synthesis by inhibition of translation, indicating a constitutive role of PKC in LPL gene expression

Translational Regulation of Lipoprotein Lipase by Epinephrine Involves a Trans-Acting Binding Protein Interacting with the 3′ Untranslated Region

To better characterize the translational regulation of lipoprotein lipase (LPL) by epinephrine, cytoplasmic extracts were prepared from 3T3-L1 adipocytes, 3T3-F442A adipocytes, and other nonadipocyte cell lines (C2 cells, 3T3 fibroblasts, and Chinese hamster ovary cells). After treatment with epinephrine, cell extracts from the adipocytes inhibited LPL translation in an in vitro translation assay, whereas extracts from the C2 cells and 3T3 fibroblasts did not affect LPL translation. To identify the region on the LPL mRNA that controlled translation, in vitro translation was carried out using constructs containing different LPL sequences. Specific deletion of the first 50 (1601-1650) nucleotides of the 3\u27 untranslated region (UTR) resulted in a loss of translation inhibition. The addition of LPL 3\u27 UTR to a heterologous reporter gene construct resulted in an inhibition of translation. Inhibition of the reporter LPL 3\u27 UTR translation was demonstrated by the addition of epinephrine-treated cell extracts to an in vitro translation assay, as well as by transfection of this construct into 3T3-F442A cells, followed by treatment of the cells with epinephrine. Competition for a trans-acting binding protein was demonstrated by the addition of sense mRNA strands corresponding to the proximal 135 nucleotides of the 3\u27 UTR of LPL. To identify a RNA-binding protein, adipocyte extracts were incubated with 32P- labeled RNA sequences followed by RNase treatment. The epinephrine-treated cell extract protected a fragment of RNA when the RNA included sequences on the proximal 3\u27 UTR of LPL. Cross-linking of this protected fragment and analysis by SDS-polyacrylamide gel electrophoresis revealed a protein that migrated at about 30 kDa. Thus, the addition of epinephrine to 3T3 adipocytes results in an inhibition of translation through the production of a RNA- binding protein that binds to a region on the proximal 3\u27 UTR of the LPL mRNA

Synchnonization, zero-resistance states and rotating Wigner crystal

We show that rotational angles of electrons moving in two dimensions (2D) in a perpendicular magnetic field can be synchronized by an external microwave field which frequency is close to the Larmor frequency. The synchronization eliminates collisions between electrons and thus creates a regime with zero diffusion corresponding to the zero-resistance states observed in experiments with high mobility 2D electron gas (2DEG). For long range Coulomb interactions electrons form a rotating hexagonal Wigner crystal. Possible relevance of this effect for planetary rings is discussed.Comment: 4 pages, 4 fig