Simulating My Own or Others Action Plans? – Motor Representations,Not Visual Representations Are Recalled in Motor Memory

Action plans are not generated from scratch for each movement, but features of recently generated plans are recalled for subsequent movements. This study investigated whether the observation of an action is sufficient to trigger plan recall processes. Participant dyads performed an object manipulation task in which one participant transported a plunger from an outer platform to a center platform of different heights (first move). Subsequently, either the same (intra-individual task condition) or the other participant (inter-individual task condition) returned the plunger to the outer platform (return moves). Grasp heights were inversely related to center target height and similar irrespective of direction (first vs. return move) and task condition (intra- vs. inter-individual). Moreover, participants'' return move grasp heights were highly correlated with their own, but not with their partners'' first move grasp heights. Our findings provide evidence that a simulated action plan resembles a plan of how the observer would execute that action (based on a motor representation) rather than a plan of the actually observed action (based on a visual representation).     

Relationship between Intracellular Na+ Concentration and Reduced Na+ Affinity in Na+,K+-ATPase Mutants Causing Neurological Disease

The neurological disorders familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism (RDP) are caused by mutations of Na⁺,K⁺-ATPase α₂ and α₃ isoforms, expressed in glial and neuronal cells, respectively. Although these disorders are distinct, they overlap in phenotypical presentation. Two Na⁺,K⁺-ATPase mutations, extending the C terminus by either 28 residues (“+28” mutation) or an extra tyrosine (“+Y”), are associated with FHM2 and RDP, respectively. We describe here functional consequences of these and other neurological disease mutations as well as an extension of the C terminus only by a single alanine. The dependence of the mutational effects on the specific α isoform in which the mutation is introduced was furthermore studied. At the cellular level we have characterized the C-terminal extension mutants and other mutants, addressing the question to what extent they cause a change of the intracellular Na⁺ and K⁺ concentrations ([Na⁺]_i and [K⁺]_i) in COS cells. C-terminal extension mutants generally showed dramatically reduced Na⁺ affinity without disturbance of K⁺ binding, as did other RDP mutants. No phosphorylation from ATP was observed for the +28 mutation of α₂ despite a high expression level. A significant rise of [Na⁺]_i and reduction of [K⁺]_i was detected in cells expressing mutants with reduced Na⁺ affinity and did not require a concomitant reduction of the maximal catalytic turnover rate or expression level. Moreover, two mutations that increase Na⁺ affinity were found to reduce [Na⁺]_i. It is concluded that the Na⁺ affinity of the Na⁺,K⁺-ATPase is an important determinant of [Na⁺]_i.     

The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations

The Na+,K+-ATPase transforms the energy of ATP to the maintenance of steep electrochemical gradients for sodium and potassium across the plasma membrane. This activity is tissue specific, in particular due to variations in the expressions of the alpha subunit isoforms one through four. Several mutations in alpha2 and 3 have been identified that link the specific function of the Na+,K+-ATPase to the pathophysiology of neurological diseases such as rapid-onset dystonia parkinsonism and familial hemiplegic migraine type 2. We show a mapping of the isoform differences and the disease-related mutations on the recently determined crystal structure of the pig renal Na+,K+-ATPase and a structural comparison to Ca2+-ATPase. Furthermore, we present new experimental data that address the role of a stretch of three conserved arginines near the C-terminus of the alpha subunit (Arg1003-Arg1005).     

Fitting of one ARMA model to multiple trials increases the time resolution of instantaneous coherence

This study presents a least mean squares (LMS) algorithm for the ensemble modeling of a multivariate ARMA process. Generally, an LMS algorithm makes possible the tracking of parameters for nonstationary time series. Our estimation incorporates multiple process observations that improve the accuracy of the parameter estimation. As a consequence, the estimation sequences come close to the true model parameters with a fast adaptation speed. This advantage also holds true of spectral quantities (e.g., the momentary coherence), which are derived from the model parameters. Thus the extension of the ARMA fitting from one to multiple trajectories allows the investigation of nonstationary biological signals with an increased time resolution. The applicability of the algorithm is demonstrated for event-related EEG coherence analysis of the Sternberg task. The changing interaction between posterior association cortex and anterior brain area was shown for verbal and nonverbal stimuli by means of the time-variant theta coherence.     

Allosteric properties of the GTP activated and CTP inhibited uracil phosphoribosyltransferase from the thermoacidophilic archaeon Sulfolobus solfataricus

The upp gene, encoding uracil phosphoribosyltransferase (UPRTase) from the thermoacidophilic archaeon Sulfolobus solfataricus, was cloned and expressed in Escherichia coli. The enzyme was purified to homogeneity. It behaved as a tetramer in solution and showed optimal activity at pH 5.5 when assayed at 60 degrees C. Enzyme activity was strongly stimulated by GTP and inhibited by CTP. GTP caused an approximately 20-fold increase in the turnover number kcat and raised the Km values for 5-phosphoribosyl-1-diphosphate (PRPP) and uracil by two- and >10-fold, respectively. The inhibition by CTP was complex as it depended on the presence of the reaction product UMP. Neither CTP nor UMP were strong inhibitors of the enzyme, but when present in combination their inhibition was extremely powerful. Ligand binding analyses showed that GTP and PRPP bind cooperatively to the enzyme and that the inhibitors CTP and UMP can be bound simultaneously (KD equal to 2 and 0.5 microm, respectively). The binding of each of the inhibitors was incompatible with binding of PRPP or GTP. The data indicate that UPRTase undergoes a transition from a weakly active or inactive T-state, favored by binding of UMP and CTP, to an active R-state, favored by binding of GTP and PRPP.     

Regulation of microRNAs miR-30a and miR-143 in cerebral vasculature after experimental subarachnoid hemorrhage in rats

Background

microRNAs (miRNAs) are important regulators of translation and have been implicated in the pathogenesis of a number of cardiovascular diseases, including stroke, and suggested as possible prognostic biomarkers. Our aim was to identify miRNAs that are differentially regulated in cerebral arteries after subarachnoid hemorrhage (SAH), using a rat injection model of SAH and a qPCR-based screen of 728 rat miRNAs. Additionally, serum was analyzed for a possible spill-over to the circulation of regulated miRNAs from the vessel walls.

Results

We identified 482 different miRNAs expressed in cerebral arteries post-SAH. Two miRNAs, miR-30a and miR-143, were significantly upregulated in cerebral arteries after SAH when compared to sham-operated animals. However, none of these exhibited significantly altered serum levels after SAH versus post-sham surgery. The most robust upregulation was seen for miR-143, which has several predicted targets and is a strong regulator of vascular morphology. We hypothesize that miR-30a and miR-143 may play a role in the vascular wall changes seen after SAH.

Conclusions

We report that miR-30a and miR-143 in the cerebral arteries show significant changes over time after SAH, but do not differ from sham-operated rats at 24 h post-SAH. Although this finding suggests interesting novel possible mechanisms involved in post-SAH cerebrovascular changes, the lack of regulation of these miRNAs in serum excludes their use as blood-borne biomarkers for cerebrovascular changes following SAH.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1341-7) contains supplementary material, which is available to authorized users.     

Crystal structure of the TLDc domain of oxidation resistance protein 2 from zebrafish

The oxidation resistance proteins (OXR) help to protect eukaryotes from reactive oxygen species. The sole C‐terminal domain of the OXR, named TLDc is sufficient to perform this function. However, the mechanism by which oxidation resistance occurs is poorly understood. We present here the crystal structure of the TLDc domain of the oxidation resistance protein 2 from zebrafish. The structure was determined by X‐ray crystallography to atomic resolution (0.97Å) and adopts an overall globular shape. Two antiparallel β‐sheets form a central β‐sandwich, surrounded by two helices and two one‐turn helices. The fold shares low structural similarity to known structures. Proteins 2012. © 2012 Wiley Periodicals, Inc.