Inhibition of hIAPP Amyloid Aggregation and Pancreatic β‐Cell Toxicity by OH‐Terminated PAMAM Dendrimer

Human islet amyloid polypeptide (hIAPP, or amylin) forms amyloid deposits in the islets of Langerhans, a phenomenon that is associated with type‐2 diabetes impacting millions of people worldwide. Accordingly, strategies against hIAPP aggregation are essential for the prevention and eventual treatment of the disease. Here, it is shown that generation‐3 OH‐terminated poly(amidoamine) dendrimer, a polymeric nanoparticle, can effectively halt the aggregation of hIAPP and shut down hIAPP toxicity in pancreatic MIN6 and NIT‐1 cells as well as in mouse islets. This finding is supported by high‐throughput dynamic light scattering experiment and thioflavin T assay, where the rapid evolution of hIAPP nucleation and elongation processes is halted by the addition of the dendrimer up to 8 h. Discrete molecular dynamics simulations further reveal that hIAPP residues bound strongly with the dendrimer near the c‐terminal portion of the peptide, where the amyloidogenic sequence (residues 22–29) locates. Furthermore, simulations of hIAPP dimerization reveal that binding with the dendrimer significantly reduces formation of interpeptide contacts and hydrogen bonds, thereby prohibiting peptide self‐association and amyloidosis. This study points to a promising nanomedicinal strategy for combating type‐2 diabetes and may have broader implications for targeting neurological disorders whose distinct hallmark is also amyloid fibrillation.     

Do problematic and non-problematic video game players differ in extraversion,trait empathy,social capital and prosocial tendencies?

The increasing popularity of online and multiplayer games has meant that for many, social interaction and cooperation are vital components of the gaming experience. Previous research has suggested that not only has this made gaming more attractive to socially oriented people but also that it may be socially beneficial in terms of social capital and prosocial behaviors. However, for problematic video game players (those showing signs of compulsive or detrimental video game use), this may not be the case, and a number of theories hold deficiencies in socializing in real life as central to the development of this issue. In the present study, an online questionnaire completed by 416 participants assessed problematic video game use, extraversion, trait empathy, online and offline social capital and prosocial tendencies. Contrary to hypotheses, non-problematic, problematic and non-gamers did not differ in empathy, extraversion or prosocial tendencies. Problematic video game play was, however, associated with significantly higher online social capital and lower offline social capital whereas non-problematic players demonstrated only higher online capital than non-players. This highlights the importance of social support but suggests personality is not an influential factor.     

Emotional selection in memes: The case of urban legends.

This article explores how much memes like urban legends succeed on the basis of informational selection (i.e., truth or a moral lesson) and emotional selection (i.e., the ability to evoke emotions like anger, fear, or disgust). The article focuses on disgust because its elicitors have been precisely described. In Study 1, with controls for informational factors like truth, people were more willing to pass along stories that elicited stronger disgust. Study 2 randomly sampled legends and created versions that varied in disgust; people preferred to pass along versions that produced the highest level of disgust. Study 3 coded legends for specific story motifs that produce disgust (e.g., ingestion of a contaminated substance) and found that legends that contained more disgust motifs were distributed more widely on urban legend Web sites. The conclusion discusses implications of emotional selection for the social marketplace of ideas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sharing the floodplain: Mediated modeling for environmental management

Complex ecosystems, such as the Upper Mississippi River (UMR), present major management challenges. Such systems often provide a range of ecosystem services that are differentially valued by stakeholders representing distinct interests (e.g., agriculture, conservation, navigation) or institutions (e.g., federal and state agencies). When no single entity has the knowledge or authority to resolve conflicts over shared resource use, stakeholders may struggle to jointly understand the scope of the problem and to reach reasonable compromises. This paper explores mediated modeling as a group consensus building process for understanding relationships between ecological, economic and cultural well-being in the UMR floodplain. We describe a workshop structure used to engage UMR stakeholders that may be extended to resource use conflicts in other complex ecosystems. We provide recommendations for improving on these participatory methods in structuring future efforts. In conclusion, we suggest that tools which facilitate collaborative learning, such as mediated modeling, need to be incorporated at an institutional level as a vital element of integrated ecosystem management.     

Effect of dopants on alumina grain boundary sliding: implications for creep inhibition

We investigate by means of periodic density functional theory the mechanism of grain boundary sliding along the α-alumina Σ11 tilt grain boundary. We identify minimum and maximum energy structures along a preferential sliding pathway for the pure grain boundary, as well as for grain boundaries doped with a series of early transition metals, as well as barium, gadolinium, and neodymium. We predict that the segregation of those dopants results in a considerable increase in the grain boundary sliding barrier. Grain boundary sliding occurs by a series of bond breaking and forming across the grain boundary. Our results suggest that the presence of large cations inhibits the regeneration of bonds during sliding, which results in a decrease in total number of bonds across the grain boundary interface, thereby raising the barrier to sliding. Trends in predicted grain boundary sliding energies are in good agreement with recently measured creep activation energies in polycrystalline alumina, lending further credence to the notion that grain boundary sliding plays a dominant role in alumina creep.     

Embedded cluster Δ-XANES modeling of adsorption processes on Pt

Full multiple scattering models of X-ray absorption near edge spectra of Pt Janin clusters, with atop and bridge bound oxygen, were systematically improved by increasing the number of cluster atoms contributing X-ray photoelectrons from unity (limited-absorber model), to all six Janin cluster Pt atoms, and finally embedding the Janin cluster into a larger Pt reservoir with photoelectron contributions from all atoms. The simulated XANES of the adsorbate modified clusters were subtractively normalized to their respective clean clusters to yield Δ-XANES signatures. The sequential analysis of previously published limited-absorber model, and the isolated and embedded all atoms models provide insights concerning the relative contribution of surface vs. subsurface atoms to adsorbate induced ligand effects and charge compensation provided by the bulk lattice. Limitations to the application of Δ-XANES signatures to interpretation of Δ-XANES data obtained from an air-breathing fuel cell are discussed.     

A longitudinal study of children's depressive symptoms, self-perceptions, and cognitive distortions about the self.

This longitudinal study examined how depressive symptoms relate to children's self-perceptions and to estimates of children's cognitive distortions about the self in a nonclinical sample of children who were followed from 4th grade (n=248) through 6th grade (n=227). Report card grades measured children's academic competence, and teachers' ratings of children's level of peer acceptance at school indicated social acceptance. Self-reported depressive symptoms predicted a change in children's negative views of the self. Moreover, the self-perceptions of children who exhibited more symptoms of depression appeared to reflect an underestimation of their actual competence. Children's negative self-perceptions and underestimations about the self were not associated with a subsequent change in depressive symptoms. The implications of the findings for cognitive theories of depression and future research with this population are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)