Evaluating Nuclei Concentration in Amyloid Fibrillation Reactions Using Back-Calculation Approach

Background: In spite of our extensive knowledge of the more than 20 proteins associated with different amyloid diseases, we do not know how amyloid toxicity occurs or how to block its action. Recent contradictory reports suggest that the fibrils and/or the oligomer precursors cause toxicity. An estimate of their temporal concentration may broaden understanding of the amyloid aggregation process. Methodology/Principal Findings: Assuming that conversion of folded protein to fibril is initiated by a nucleation event, we back-calculate the distribution of nuclei concentration. The temporal in vitro concentration of nuclei for the model hormone, recombinant human insulin, is estimated to be in the picomolar range. This is a conservative estimate since the back-calculation method is likely to overestimate the nuclei concentration because it does not take into consideration fibril fragmentation, which would lower the amount of nuclei Conclusions: Because of their propensity to form aggregates (non-ordered) and fibrils (ordered), this very low concentration could explain the difficulty in isolating and blocking oligomers or nuclei toxicity and the long onset time for amyloid diseases

Expressions of Multiple Neuronal Dynamics during Sensorimotor Learning in the Motor Cortex of Behaving Monkeys

Previous studies support the notion that sensorimotor learning involves multiple processes. We investigated the neuronal basis of these processes by recording single-unit activity in motor cortex of non-human primates (Macaca fascicularis), during adaptation to force-field perturbations. Perturbed trials (reaching to one direction) were practiced along with unperturbed trials (to other directions). The number of perturbed trials relative to the unperturbed ones was either low or high, in two separate practice schedules. Unsurprisingly, practice under high-rate resulted in faster learning with more pronounced generalization, as compared to the low-rate practice. However, generalization and retention of behavioral and neuronal effects following practice in high-rate were less stable; namely, the faster learning was forgotten faster. We examined two subgroups of cells and showed that, during learning, the changes in firing-rate in one subgroup depended on the number of practiced trials, but not on time. In contrast, changes in the second subgroup depended on time and practice; the changes in firing-rate, following the same number of perturbed trials, were larger under high-rate than low-rate learning. After learning, the neuronal changes gradually decayed. In the first subgroup, the decay pace did not depend on the practice rate, whereas in the second subgroup, the decay pace was greater following high-rate practice. This group shows neuronal representation that mirrors the behavioral performance, evolving faster but also decaying faster at learning under high-rate, as compared to low-rate. The results suggest that the stability of a new learned skill and its neuronal representation are affected by the acquisition schedule.United States-Israel Binational Science FoundationIsrael Science FoundationIda Baruch FundRosetrees Trus

Gas Solid Chromatography Measurements of the Change in the Heat Capacity during Adsorption on Graphitized Thermal Carbon Black

Gas chromatography is widely used to measure the thermodynamic functions of adsorption on the homogeneous surface of graphitized thermal carbon black in the region where Henry\u27s adsorption law is valid. A high-precision instrument with computer data acquisition measures the isosteric heat of adsorption and the change of the heat capacity during adsorption. The method is used to study the adsorption of benzene and n-pentane on different graphitized thermal carbon black samples. The data are directly comparable with the values calculated from statistical thermodynamics on graphite since it is shown that adsorbateadsorbate interactions are negligible and that the behavior of the bulk gas phase is nearly ideal. The results obtained for benzene could be compared with the molar heat capacity of adsorbed benzene measured by calorimetric methods and extrapolated at zero surface coverage. With n-pentane, however, the gas solid chromatographic method is unique, as extrapolation of calorimetric measurements is impossible because of strong adsorbate-adsorbate interactions at relatively low surface coverage

As criações do gênio: Ambivalências da "metafísica da arte" nietzschiana

As criações do gênio apolíneo-dionisíaco estão no centro das preocupações da metafísica de artista, e suscitam a questão acerca do vínculo de Nietzsche com a estética do Romantismo Alemão e de Schopenhauer. Investigamos neste artigo as ambivalências do pensamento nietzschiano no que tange ao conflito entre a arte apolínea da ilusão e a sabedoria dionisíaca, entre o Uno-Primordial e a aparência.<br>The creations of the apollinian-dionysian genius are in the center of the concerns of the artist's metaphysics and raise the question about the relationship of Nietzsche to the aesthetics of German Romanticism and Schopenhauer's. In this article we investigate the ambivalences of the Nietzschean thinking regarding the conflict between the apollinian art of illusion and the Dionysian wisdom, between the Primordial-One and the appearance