The Strategic Control of Multiple Routes in Imitation of Actions.

The aim of this study was to bring to the surface the strategic use of imitative processes in the context of a 2-route model: (a) direct imitation, used in reproducing new, meaningless actions, and (b) imitation based on stored semantic knowledge of familiar meaningful actions. Three experiments were carried out with healthy participants who reproduced meaningful and meaningless actions within an established time limit. The study investigated 3 factors that could potentially affect the selection of processes used for imitation: (a) the composition of the experimental list (blocked or mixed presentation), (b) the presence-absence of instructions (Experiments 1 and 2), and (c) the relative proportions of the stimuli (Experiment 3). Overall, the results suggest that each of these factors influences the selection of imitative strategies in healthy individuals with temporarily reduced capacities, as happens in the case of brain-damaged patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pathogenic Mutations Shift the Equilibria of α‐Synuclein Single Molecules towards Structured Conformers

α‐synuclein (α‐Syn) is an abundant brain protein whose mutations have been linked to early‐onset Parkinson's disease (PD). We recently demonstrated, by means of a single‐molecule force spectroscopy (SMFS) methodology, that the conformational equilibrium of monomeric wild‐type (WT) α‐Syn shifts toward β‐containing structures in several unrelated conditions linked to PD pathogenicity. Herein, we follow the same methodology previously employed for WT α‐Syn to characterize the conformational heterogeneity of pathological α‐Syn mutants A30P, A53T, and E46K. Contrary to the bulk ensemble‐averaged spectroscopies so far employed to this end by different authors, our single‐molecule methodology monitored marked differences in the conformational behaviors of the mutants with respect to the WT sequence. We found that all the mutants have a much higher propensity than the WT to adopt a monomeric compact conformation that is compatible with the acquiring of β structure. Mutants A30P and A53T show a similar conformational equilibrium that is significantly different from that of E46K. Another class of conformations, stabilized by mechanically weak interactions (MWI), shows a higher variety in the mutants than in the WT protein. In the A30P mutant these interactions are relatively stronger, and therefore the corresponding conformations are possibly more structured. The more structured and globular conformations of the mutants can explain their higher propensity to aggregate with respect to the WT.     

System reliability-based design optimization and risk-based optimization: a benchmark example considering progressive collapse

System Reliability-Based Design Optimization (RBDO) considers a single system failure probability constraint. The formulation allows different failure modes to compete with each other. Very few methods and benchmark examples involving optimal design considering system behaviour with progressive failure can be found in the literature. In this article, the conventional System RBDO formulation is compared with a risk-based formulation. A benchmark example involving progressive failure of hyper-static truss is addressed. It is demonstrated that typical System RBDO formulations always lead to isostatic structures, since the formulation does not offer any incentive for the permanence of hyper-static members. In the risk-based formulation, failure costs are differentiated with respect to primary member failure, in hyper-static structures (existence of warning before eventual collapse), and failure of isostatic members (no warning). In this formulation, optimal designs also include hyper-static structures. Results presented herein are relevant in the modern context of robust design considering progressive collapse.     

Heteronuclear NMR studies of the combined Src homology domains 2 and 3 of pp60 c-Src: effects of phosphopeptide binding

The results of heteronuclear NMR studies on the combined Src homology domains 2 and 3 (SH3-SH2) of pp60 c-Src are presented. Resonance assignments were obtained using heteronuclear triple-resonance experiments in conjunction with 15N-separated nuclear Overhauser effect spectroscopy (NOESY) data. A modified three-dimensional 13CO-15N-1H spectral correlation experiment [(HACA)CO(CA)-NH] with improved sensitivity is presented that provided additional sequential information and resolved several ambiguities. Chemical shifts and sequential- and medium-range NOE cross peaks indicate that the structures of both the SH3 and SH2 portions of the polypeptide are very similar to those of the isolated SH3 and SH2 domains. Binding of a high-affinity phosphopeptide, EPQpYEEIPIYL, induces large chemical shift changes at several locations in the SH2 domain. Comparison with known results for peptide binding to SH2 domains shows that the residues displaying the largest effects are all involved in peptide binding or undergo significant conformational changes upon binding. However, subtle changes of both 1H and 15N chemical shifts are observed for residues within the SH3 domain and the connecting linker region, indicating possible cross-domain communication.     

Abnormal cytoskeletal protein expression in cultured skin fibroblasts from type 1 diabetes mellitus patients with nephropathy: A proteomic approach

Diabetic nephropathy (DN) develops in about 40% of insulin-dependent type 1 diabetes mellitus (T1DM) patients, and is associated not only with diabetes duration and metabolic control, but also with a genetic predisposition. Constitutive alterations of cytoskeletal proteins may play a role in the development of DN. We investigated the expression of these proteins in cultured skin fibroblasts, obtained from long-term T1DM patients with and without DN but comparable metabolic control, and from matched healthy subjects, by means of 2-DE electrophoresis and MS-MALDI analyses. In T1DM with DN, compared to the other two groups, quantitative analyses revealed an altered expression of 17 spots (p<0.05-p<0.01), corresponding to 12 unique proteins. In T1DM with DN, beta-actin and three isoforms of tubulin beta-2 chain, tropomodulin-3, and LASP-1 were decreased, whereas two tubulin beta-4 chain isoforms, one alpha actinin-4 isoform, membrane-organizing extension spike protein (MOESIN), FLJ00279 (corresponding to a fragment of myosin heavy chain, non-muscle type A), vinculin, a tropomyosin isoform, and the macrophage capping protein were increased. A shift in caldesmon isoforms was also detected. These results demonstrate an association between DN and the constitutive expression of cytoskeleton proteins in cultured skin fibroblasts from T1DM with DN, which may retain pathophysiologycal implications.     

Solution structure of porcine pancreatic phospholipase A2

The lipolytic enzyme phospholipase A2 (PLA2) is involved in the degradation of high-molecular weight phospholipid aggregates in vivo. The enzyme has very high catalytic activities on aggregated substrates compared with monomeric substrates, a phenomenon called interfacial activation. Crystal structures of PLA2s in the absence and presence of inhibitors are identical, from which it has been concluded that enzymatic conformational changes do not play a role in the mechanism of interfacial activation. The high-resolution NMR structure of porcine pancreatic PLA2 free in solution was determined with heteronuclear multidimensional NMR methodology using doubly labeled 13C, 15N-labeled protein. The solution structure of PLA2 shows important deviations from the crystal structure. In the NMR structure the Ala1 alpha-amino group is disordered and the hydrogen bonding network involving the N-terminus and the active site is incomplete. The disorder observed for the N-terminal region of PLA2 in the solution structure could be related to the low activity of the enzyme towards monomeric substrates. The NMR structure of PLA2 suggests, in contrast to the crystallographic work, that conformational changes do play a role in the interfacial activation of this enzyme.     

Convective Drying Analysis of a Single Wheat Kernel Based on an Irreversible Thermodynamics Model

The application of irreversible thermodynamics offers a formal treatment for drying analysis that allows the evaluation of intra-particle or intra-medium temperature and moisture profiles, and enthalpy, liquid, and vapor fluxes. However, researchers have claimed that its implementation is complex. This work presents a simple methodology for modeling, solving, and validating the drying equations, as applied to wheat kernels, and for obtaining the inherent and usually unavailable transport coefficients. To clarify and simplify the ensuing physical analysis, a spherical shape and isotropy were assumed. Additionally, solutions obtained with both Dirichlet and convective boundary conditions were analyzed and compared against experimental data. The thermal and hydro-stresses depend heavily on internal vapor and liquid fluxes and on the respective drying evaporation fronts, all of which were evaluated and compared.     

Irreversible thermodynamics analysis of ellipsoidal wheat kernel drying,aiming at the evaluation of phenomenological properties

Literature data have revealed that wheat kernel stress–strain relationships, thermal conductivity, and specific heat support the assumption of isotropy. Accepting this premise, we show that drying complexity can be reduced by properly defining the kernel shape and an accurate model. Therefore, we present an irreversible thermodynamics procedure for obtaining transport properties of a wheat kernel. The numerical solution of the associated nonlinear conservation equations was based on the Radial Basis Functions method. Drying behavior of both prolate ellipsoidal and spherical grain kernels is presented and compared. The predicted moisture and temperature profiles correlated favorably with experimental drying profiles, obtained for two temperatures of 47 and 67.5°C.     

The synthesis and characterization of monomeric etherified methylolated melamines using gel permeation chromatography and proton magnetic resonance spectroscopy

A series of monomeric etherified methylolated melamines were prepared and characterized by proton magnetic resonance spectroscopy and gel permeation chromatography. Gel permeation chromatographic analysis permits a rapid and accurate determination of the monomer and polymer content of the products. Proton magnetic resonance spectroscopy permits the qualitative identification of the etherifying alcohols and a quantitative estimation of the alkoxy groups present. The molar ratios of alcohols necessary to produce products having specific alkoxy contents are presented graphically.