Pyroglutamate-modified amyloid-␤ (pE-A␤) is a highly neurotoxic amyloid-␤ (A␤) isoform and is enriched in the brains of individuals with Alzheimer disease compared with healthy aged controls. Pyroglutamate formation increases the rate of A␤ oligomerization and alters the interactions of A␤ with Cu 2؉ and lipids; however, a link between these properties and the toxicity of pE-A␤ peptides has not been established. We report here that A␤3pE-42 has an enhanced capacity to cause lipid peroxidation in primary cortical mouse neurons compared with the fulllength isoform (A␤(1-42)). In contrast, A␤(1-42) caused a significant elevation in cytosolic reactive oxygen species, whereas A␤3pE-42 did not. We also report that A␤3pE-42 preferentially associates with neuronal membranes and triggers Ca 2؉ influx that can be partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. A␤3pE-42 further caused a loss of plasma membrane integrity and remained bound to neurons at significantly higher levels than A␤(1-42) over extended incubations. Pyroglutamate formation was additionally found to increase the relative efficiency of A␤-dityrosine oligomer formation mediated by copper-redox cycling.A␤ 3 peptides are found in every human brain; however, the concentration and composition of A␤ peptide isoforms are distinctly different in healthy individuals and people with AD (1-3). Amino-truncated A␤ peptides are abundant in the AD brain (4, 5) and increase in prevalence with disease progression (6). The process of A␤ amino-truncation can occur via the actions of aminopeptidases on full-length A␤ peptides (7, 8), via altered cleavage of amyloid precursor protein in the generation of A␤ (9 -11), and potentially by A␤-copper-redox cycling reactions (12). As a consequence, aminotruncation can expose glutamate residues (positions 3 and 11 of A␤) to cyclization by the action of glutaminyl cyclase (QC), forming the highly amyloidogenic pyroglutamate-A␤ (pE-A␤) peptides A␤3pE-40, A␤3pE-42, A␤11pE-40, and A␤11pE-42 (7, 13).Pyroglutamate formation significantly increases the hydrophobicity of A␤, causing the peptide to aggregate more rapidly and form oligomers at lower concentration thresholds (5, 14, 15). pE-A␤ peptides also demonstrate increased ␤-sheet (aggregate structure) stability (16, 17), differences in fibril ultrastructure (18,19), and altered interactions with copper ions (20, 21) and synthetic lipid membranes (22, 23). Notably, trace quantities of A␤3pE-42 have been observed to dramatically enhance the aggregation and neurotoxicity of A␤(1-42) (24), prompting descriptions of pE-A␤ as "prionlike." Still, it remains unclear as to the cytotoxic potency of pE-A␤ peptides compared with their full-length A␤ counterparts. Some studies have demonstrated pE-A␤ peptides to have enhanced toxicity (24 -26), although others have reported no difference in toxicity between the isoforms (27-30). Methodological differences may account somewhat for variability in the relative toxicities reported (Table 1), yet molecular mechanisms to explain...

Cyclopropyl malonoyl peroxide (1), which can be prepared in a single step from the commercially available diacid, is an effective reagent for the dihydroxylation of alkenes. Reaction of 1 with an alkene in the presence of 1 equiv of water at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (40-93%). With 1,2-disubstituted alkenes, the reaction proceeds with syn selectivity (3:1 to >50:1). A mechanism consistent with the experimental findings that is supported by oxygen-labeling studies is proposed.

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This article first makes a case for the need to establish evaluation reporting standards, support for which is rooted in the growing demand for professionalization, in the growing metaevaluation literature, and in growing efforts to develop reporting standards for inquiry efforts. Then, a case is made for a particular set of such standards introduced in this article—the CHecklist for Evaluation-Specific Standards (CHESS). In doing so, this article outlines the process used and presents the resulting checklist and associated standards, which are defined as the minimum, evaluation-specific elements that must be reported to make judgments about the quality of the evaluation. This article also describes a few of the categories to offer illustrative information to help readers better understand and consider the usefulness of the proposed checklist. A discussion of CHESS, including challenges and next steps, is also included.

Photoinduced charge carrier behavior is critical in determining photoelectrocatalytic activity. In this study, a unique layer‐doped metal‐free polymeric carbon nitride (C3N4) photoanode is fabricated by using one‐pot thermal vapor deposition. With this method, a photoanode consisting of a phosphorus‐doped top layer, boron‐doped middle layer, and pristine C3N4 bottom layer, was formed as a result of the difference in thermal polymerization kinetics associated with the boron‐containing H3BO3–melamine complex and the phosphorus‐containing H3PO4–dicyandiamide complex. This layer‐doping fabrication strategy effectively contributes to the formation of dual junctions that optimizing charge carrier behavior. The ternary‐layer C3N4 photoanode exhibits significantly enhanced photoelectrochemical water oxidation activity compared to pristine C3N4, with a record photocurrent density of 150±10 μA cm−2 at 1.23 V vs. RHE. This layer‐doping strategy provides an effective means for design and fabrication of photoelectrodes for solar water oxidation.

Leaf is a free-standing photocatalytic system that can effectively harvest solar energy and convert CO2 and H2O into carbohydrates in a continuous manner without the need of regeneration or tedious...

Histidine functional block copolymers are thermally self‐assembled into polymer micelles with poly‐N‐isopropylacrylamide in the core and the histidine functionality in the corona. The thermally induced self‐assemblies are reversible until treated with Cu2+ ions at 50 °C. Upon treatment with 0.5 equivalents of Cu2+ relative to the histidine moieties, metal‐ion coordination locks the self‐assemblies. The self‐assembly behavior of histidine functional block copolymers is explored at different values of pH using DLS and 1H NMR. Metal‐ion coordination locking of the histidine functional micelles is also explored at different pH values, with stable micelles forming at pH 9, observed by DLS and imaged by atomic force microscopy. The thermal self‐assembly of glycine functional block copolymers at pH 5, 7, and 9 is similar to the histidine functional materials; however, the self‐assemblies do not become stable after the addition of Cu2+, indicating that the imidazole plays a crucial role in metal‐ion coordination that locks the micelles. The reversibility of the histidine‐copper complex locking mechanism is demonstrated by the addition of acid to protonate the imidazole and destabilize the polymer self‐assemblies. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1964–1973

House's classic Evaluating with Validity proposes three dimensions—truth, justice, and beauty—for evaluation validity. A challenge to achieving validity is balancing the priorities between these three dimensions when they conflict. This chapter examines the concept of validity and the values inherent in each of these dimensions and any choices between them. Our analysis of these inherent values and any prioritization between truth, justice, and beauty aims to help the evaluator confront the kinds of dilemmas faced when one's commitment to values, evaluation theories, or methodology comes up against conflicting realities for a particular evaluation. Striking an appropriate balance can be particularly challenging in contexts involving diverse cultures or even homogenous cultures of which the evaluator is not a part. We use two case examples to explore the issues in real‐life contexts.