Amyloid fibrils are associated with more than 20 diseases, including Alzheimer's disease and type II diabetes. Insulin is a 51-residue polypeptide hormone, with its two polypeptide chains linked by one intrachain and two interchain disulfide bonds, and has long been known to self-assemble in vitro into amyloid fibrils. We demonstrate here that bovine insulin forms flexible filaments in the presence of a reducing agent, Tris (2-carboxyethyl) phosphine. The insulin filaments, possibly formed due to partial reduction of S-S bonds in insulin molecules, differ from intact insulin fibrils in terms of their secondary structure. The insulin filaments were determined to have an antiparallel beta-sheet structure, whereas the insulin fibrils have a parallel beta-sheet structure. Of importance, the cell toxicity of the insulin filaments was remarkably lower than that of the insulin fibrils. This finding supports the idea that cell toxicity of amyloids correlates with their morphology. The remarkably low toxicity of the filamentous structure should shed new light on possible pharmacological approaches to the various diseases caused by amyloid fibrils.

Background Although naming deficits are well documented in aphasia, on-line measures of naming processes have been little investigated. The use of on-line measures may offer further insight into the nature of aphasic naming deficits that would otherwise be difficult to interpret when using off-line measures. Aims The temporal activation of semantic and phonological processes was tracked in older normal control and aphasic individuals using a picture–word interference paradigm. The purpose of the study was to examine how word interference results can augment and/or corroborate standard language testing in the aphasic group, as well as to examine temporal patterns of activation in the aphasic group when compared to a normal control group. Methods & Procedures A total of 20 older normal individuals and 11 aphasic individuals participated. Detailed measures of each aphasic individual's language and naming skills were obtained. A visual picture–word interference paradigm was used in which the words bore either a semantic, phonological, or no relationship to 25 pictures. These competitor words were presented at stimulus onset asynchronies of −300 ms, +300 ms, and 0 ms. Outcomes & Results Analyses of naming RTs in both groups revealed significant early semantic interference effects, mid-semantic interference effects, and mid-phonological facilitation effects. A matched control-aphasic group comparison revealed no differences in the temporal activation of effects during the course of naming. Partial support for this RT pattern was found in the aphasic naming error pattern. The aphasic group also demonstrated greater SIEs and PFEs compared to the matched control group, which indicated disruptions of the phonological processing stage. Analyses of behavioural performances of the aphasic group corroborated this finding. Conclusions The aphasic naming RTs results were unexpected given the results from the priming literature, which has supported the idea of slowed or reduced patterns of activation in aphasic individuals. However, analyses of naming RTs also confirmed the behavioural finding of a disruption surrounding phonological processes; thus, the analyses of naming latencies offers another potential means of pinpointing breakdowns of lexical access in individuals with aphasia.

Purpose-The purpose of this study was to examine children's knowledge of semantic relations.Method-In Experiment 1, the 6-year-olds, 8-year-olds, and adults participated in an object decision task. Participants in the primed group made object decisions in response to primes that were related taxonomically, thematically, or perceptually to the target objects. Those in the unprimed group made decisions about the same stimuli without the benefit of primes. In Experiment 2, the children in the primed group explained the taxonomic and thematic relations between the prime-target pairs used in Experiment 1.Results-In Experiment 1, the strength of semantic relations did not vary with type or age, as taxonomic priming was as strong as thematic priming and the degree of priming did not reliably differentiate the 3 age groups. Differential priming effects between taxonomic and perceptual conditions, the former hastening and the latter slowing responses, suggested that the relation binding object concepts into taxonomies was not reducible to common physical features. In Experiment 2, the 6-year-olds had more difficulty describing taxonomic than thematic relations, whereas the 8-yearolds described both with ease.Conclusions-Contrary to the shift hypothesis, taxonomic and thematic relations-structure concepts in children as young as 6 and into adulthood. In accord with the performance hypothesis, 6-year-olds' representations of taxonomic relations are fragile and vulnerable to high task demands.

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Gold nanoparticles conjugated to nucleic acids are widely used for biomedical targeting and sensing applications; however, little is known about the conjugation chemistry covering the impact of steric dimension and strand orientation of single-stranded oligonucleotides (ssO) on the conjugation process and binding efficiencies. In this context, we present an extensive investigation concerning the attachment of thiolated ssO to the surface of laser-generated gold nanoparticles, altering both strand length and binding orientation by the insertion of different spacer types at either the 3' or 5' ssO terminus. A significant reduction of conjugation efficiency of about 30-50% is determined for spacer-prolonged bionanoconjugates due to coiling effects of the flexible ssO strand on the particle surface which increases deflection angle of oligonucleotides and limits the number of biomolecules attached to the nanoparticles.