Chapter 4 : “Japanese-English Contrasts of Evidentiality and its Applicability to language education”

Orienting attention retrospectively to selective contents in working memory (WM) influences performance. A separate line of research has shown that stimulus strength shapes perceptual representations. There is little research on how stimulus strength during encoding shapes WM performance, and how effects of retrospective orienting might vary with changes in stimulus strength. We explore these questions in three experiments using a continuous-recall WM task. In Experiment 1 we show that benefits of cueing spatial attention retrospectively during WM maintenance (retrocueing) varies according to stimulus contrast during encoding. Retrocueing effects emerge for supraliminal but not sub-threshold stimuli. However, once stimuli are supraliminal, performance is no longer influenced by stimulus contrast. In Experiments 2 and 3 we used a mixture-model approach to examine how different sources of error in WM are affected by contrast and retrocueing. For high-contrast stimuli (Experiment 2), retrocues increased the precision of successfully remembered items. For low-contrast stimuli (Experiment 3), retrocues decreased the probability of mistaking a target with distracters. These results suggest that the processes by which retrospective attentional orienting shape WM performance are dependent on the quality of WM representations, which in turn depends on stimulus strength during encoding

Folding Pathways of Prion and Doppel

The relevance of various residue positions for the stability and the folding characteristics of the prion protein are investigated by using molecular dynamics simulations of models exploiting the topology of the native state. Highly significant correlations are found between the most relevant sites in our analysis and the single point mutations known to be associated with the arousal of the genetic forms of prion disease (caused by the conformational change from the cellular to the scrapie isoform). Considerable insight into the conformational change is provided by comparing the folding process of prion and doppel (a newly discovered protein) sharing very similar native state topology: the folding pathways of the former can be grouped in two main classes according to which tertiary structure contacts are formed first enroute to the native state. For the latter a single class of pathways leads to the native state. Our results are consistent and supportive of the recent experimental findings that doppel lacks the scrapie isoform and that such remarkably different behavior results from differences in the region containing the two $\beta-$strands and the intervening helix.Comment: 16 pages, 2 tables, 5 figure

Methionine 129 variant of human prion protein oligomerizes more rapidly than the valine 129 variant

The human PrP gene (PRNP) has two common alleles that encode either methionine or valine at codon 129. This polymorphism modulates disease susceptibility and phenotype of human transmissible spongiform encyphalopathies, but the molecular mechanism by which these effects are mediated remains unclear. Here, we compared the misfolding pathway that leads to the formation of beta-sheet-rich oligomeric isoforms of the methionine 129 variant of PrP to that of the valine 129 variant. We provide evidence for differences in the folding behavior between the two variants at the early stages of oligomer formation. We show that Met(129) has a higher propensity to form beta-sheet-rich oligomers, whereas Val(129) has a higher tendency to fold into alpha-helical-rich monomers. An equimolar mixture of both variants displayed an intermidate folding behavior. We show that the oligomers of both variants are initially a mixture of alpha- and beta-rich conformers that evolve with time to an increasingly homogeneous beta-rich form. This maturation process, which involves no further change in proteinase K resistance, occurs more rapidly in the Met(129) form than the Val(129) form. Although the involvement of such beta-rich oligomers in prion pathogenesis is speculative, the misfolding behavior could, in part, explain the higher susceptibility of individuals that are methionine homozygote to both sporadic and variant Creutzfeldt-Jakob disease

Intertwining personal and reward relevance: evidence from the drift-diffusion model.

In their seminal paper 'Is our self nothing but reward', Northoff and Hayes (Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) proposed three models of the relationship between self and reward and opened a continuing debate about how these different fields can be linked. To date, none of the proposed models received strong empirical support. The present study tested common and distinct effects of personal relevance and reward values by de-componenting different stages of perceptual decision making using a drift-diffusion approach. We employed a recently developed associative matching paradigm where participants (N = 40) formed mental associations between five geometric shapes and five labels referring personal relevance in the personal task, or five shape-label pairings with different reward values in the reward task and then performed a matching task by indicating whether a displayed shape-label pairing was correct or incorrect. We found that common effects of personal relevance and monetary reward were manifested in the facilitation of behavioural performance for high personal relevance and high reward value as socially important signals. The differential effects between personal and monetary relevance reflected non-decisional time in a perceptual decision process, and task-specific prioritization of stimuli. Our findings support the parallel processing model (Northoff & Hayes, Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) and suggest that self-specific processing occurs in parallel with high reward processing. Limitations and further directions are discussed

Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins

Approximately 15 % of human prion disease is associated with autosomal-dominant pathogenic mutations in the prion protein (PrP) gene. Previous attempts to model these diseases in mice have expressed human PrP mutations in murine PrP, but this may have different structural consequences. Here, we describe transgenic mice expressing human PrP with P102L or E200K mutations and methionine (M) at the polymorphic residue 129. Although no spontaneous disease developed in aged animals, these mice were readily susceptible to prion infection from patients with the homotypic pathogenic mutation. However, while variant Creutzfeldt–Jakob disease (CJD) prions transmitted infection efficiently to both lines of mice, markedly different susceptibilities to classical (sporadic and iatrogenic) CJD prions were observed. Prions from E200K and classical CJD M129 homozygous patients, transmitted disease with equivalent efficiencies and short incubation periods in human PrP 200K, 129M transgenic mice. However, mismatch at residue 129 between inoculum and host dramatically increased the incubation period. In human PrP 102L, 129M transgenic mice, short disease incubation periods were only observed with transmissions of prions from P102L patients, whereas classical CJD prions showed prolonged and variable incubation periods irrespective of the codon 129 genotype. Analysis of disease-related PrP (PrPSc) showed marked alteration in the PrPSc glycoform ratio propagated after transmission of classical CJD prions, consistent with the PrP point mutations directly influencing PrPSc assembly. These data indicate that P102L or E200K mutations of human PrP have differing effects on prion propagation that depend upon prion strain type and can be significantly influenced by mismatch at the polymorphic residue 129

Review: Contribution of transgenic models to understanding human prion disease

J. D. F. Wadsworth, E. A. Asante and J. Collinge (2010) Neuropathology and Applied Neurobiology36, 576–597Contribution of transgenic models to understanding human prion diseas

Behind the Scenes at the DLR National Satellite Data Archive, a Brief History and Outlook of Long Term Data Preservation

The Earth Observation Center (EOC) at the German Aerospace Center (DLR) is the center of competence in Germany, providing expertise in earth observation research and development activities, as well as operational tasks for data reception, processing and archiving. We briefly present the German Satellite Data Archive (D-SDA) with systems and activities that make it possible to accomplish successful Long Term Data Preservation (LTDP) over more than 20 years with nearly exponentially growing data capacity. Tables, facts and figures exhibit the path taken at DLR to successfully establish the infrastructure for long term data preservation for Germany and Europe. Our experience is that that LTDP is manageable but requires following the evolution in technology, new usage scenarios and data policies. DLR is working on the continuous evolution of the flexible DIMS components, infrastructure and management services to serve the processing and archiving centers for the next generation earth observation satellites