3؉ also inhibits fibril formation; however, the annular oligomers co-exist in the aggregation pathway. In conclusion, Zn 2؉ , Cu 2؉ , Fe 3؉ , and Al 3؉ adopt distinct folding and aggregation mechanisms to affect A␤, where A␤ destabilization promotes annular protofibril formation. Our study facilitates the understanding of annular A␤ oligomer formation upon metal ion binding. The brain deposition of amyloid plaques composed of A␤2 is the pathological hallmark of AD (1, 2). A␤ is generated from sequential cleavages of amyloid precursor protein by ␤-and ␥-secretases (3, 4). The predominant A␤ isoforms are A␤40 and A␤42, which differ in two residues at the C terminus, where A␤42 is less abundant but more neurotoxic (5-8). A␤ is a natively unfolded protein prone to aggregating into cross-␤-amyloid fibrils through a nucleation-dependent polymerization pathway (9). A␤ aggregation is considered the major culprit in AD, in which the A␤ oligomers, but not fibrils, better correlate with cognitive impairment and synaptic dysfunction (10). A␤ oligomers are referred to various different metastable intermediates found in the aggregation, including low molecular weight oligomers, spherical oligomers, A␤-derived diffusible ligands, globulomers, annular protofibrils, A␤56*, and curvilinear protofibrils (11)(12)(13)(14)(15)(16)(17)(18) (24 -25). These facts indicate that the elevation of the metal ions is relevant to AD pathology.A␤ is able to bind to the metal ions (22, 23). A␤ ion coordination, binding affinity, and induced aggregation have been studied intensively in various conditions; however, the results and mechanisms remain inconclusive. A␤-Cu 2ϩ coordination involves three intramolecular histidines (i.e. His-6, His-13, and His-14) in A␤ (26 -28), with the fourth coordinate being either the amino group of the N terminus (29), an oxygen from Tyr-10 (30), or an oxygen from Glu-3 (29). The A␤-Zn 2ϩ complex is reportedly more complicated. A similar coordination with Cu 2ϩ has been proposed for Zn 2ϩ using the three histidines and the N terminus (31, 32). Both intermolecular A␤-Cu 2ϩ and A␤-Zn 2ϩ coordination have been reported via histidine bridges (28, 30 -33). Fe 3ϩ has also been shown to interact with histidines (37). Dissociation constants for the binding affinity of

Procedures have been developed for increasing coupling efficiency in solid-phase peptide synthesis by microwave irradiation using a kitchen microwave oven.Recently there has been growing interest in applying microwave heating to rapid thermal digestion prior to element and chemical analysis of inorganic and biological samples.1 The rapid heating capability of the microwave oven leads to a considerable saving in dissolution time, which may eventually replace some of the conventional flame and hot-plate heating procotols.2•3 We describe here a novel application of microwave technology to enhance coupling efficiency in solid-phase peptide synthesis. A significant improvement of the coupling efficiency (a rate increase of at least 2-4-fold), especially in side-chain-hindered amino acids, was obtained in the study.

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We aimed to understand the relationships between care recipients' profiles and home- and community-based services (HCBS use patterns. Data were from the 2010 to 2013 Long-Term Care Service Management System in Taiwan ( N = 78,205). We used latent class analysis and multinomial logistic regression analyses. Three HCBS use patterns were found. Care recipients who lived alone, lived in less urbanized areas, and had instrumental activities of daily living disabilities were more likely to be in the home-based personal care group. Those in the home-based personal and medical care group were more likely than others to have a primary caregiver. Care recipients who had poorer abilities at basic activities of daily living and cognitive function, better household income, and lived in a more urbanized area were more likely to be in the non-personal care multiple services group. The findings suggest that policymakers alleviate barriers to accessing various patterns of HCBS should be encouraged.

ObjectivesThe aims of this study were to investigate (1) whether and (2) the extent to which Taiwanese older adults’ leisure time activity (LTA) trajectories mediated the potential association between their sociodemographic factors and their functional disability trajectories.MethodsLongitudinal data from four waves of the Taiwan Longitudinal Study on Aging (TLSA), collected between 1996 and 2007, were used for analysis (N = 3,429). Parallel-process latent growth curve modeling was adopted to evaluate the process by which LTA mediated between sociodemographic factors (age, gender, education, self-rated health, comorbidities, and depression) and the outcome process of functional disabilities.ResultsWhen mediated by baseline level of LTA, five sociodemographic factors—age, gender, education level, self-rated health, and number of comorbidities—had significant and negative mediating effects on baseline or change in functional disability, thus improving disability outcomes. However, four of the sociodemographic factors (age, education level, and number of comorbidities), when mediated through the rate of change in LTA, were found to have significant and positive mediating effects, which increased disability levels. The proportion of effects mediated by the LTA trajectory ranged from 0% to 194%.DiscussionThe large proportion of effects mediated through the LTA process underlines the importance of LTA to public health policy and health programs for older adults. The study’s findings shed light on how to better target populations of older adults to promote an active lifestyle and achieve more successful aging in late life in Asian countries.

Engagement in leisure time activity in later life is associated with a slower speed of progression toward functional disability. Early functional disability may not inhibit leisure time activity participation in later life.

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