Cu(II) ions are implicated in the pathogenesis of Alzheimer disease by influencing the aggregation of the amyloid-β (Aβ) peptide. Elucidating the underlying Cu(II)-induced Aβ aggregation is paramount for understanding the role of Cu(II) in the pathology of Alzheimer disease. The aim of this study was to characterize the qualitative and quantitative influence of Cu(II) on the extracellular aggregation mechanism and aggregate morphology of Aβ(1-40) using spectroscopic, microelectrophoretic, mass spectrometric, and ultrastructural techniques. We found that the Cu(II):Aβ ratio in solution has a major influence on (i) the aggregation kinetics/mechanism of Aβ, because three different kinetic scenarios were observed depending on the Cu(II):Aβ ratio, (ii) the metal:peptide stoichiometry in the aggregates, which increased to 1.4 at supra-equimolar Cu(II):Aβ ratio; and (iii) the morphology of the aggregates, which shifted from fibrillar to non-fibrillar at increasing Cu(II):Aβ ratios. We observed dynamic morphological changes of the aggregates, and that the formation of spherical aggregates appeared to be a common morphological end point independent on the Cu(II) concentration. Experiments with Aβ(1-42) were compatible with the conclusions for Aβ(1-40) even though the low solubility of Aβ(1-42) precluded examination under the same conditions as for the Aβ(1-40). Experiments with Aβ(1-16) and Aβ(1-28) showed that other parts than the Cu(II)-binding His residues were important for Cu(II)-induced Aβ aggregation. Based on this study we propose three mechanistic models for the Cu(II)-induced aggregation of Aβ(1-40) depending on the Cu(II):Aβ ratio, and identify key reaction steps that may be feasible targets for preventing Cu(II)-associated aggregation or toxicity in Alzheimer disease.

Laboratory work has been a common element of science courses at university level for around two centuries, but its practice has been criticised by scholars in the field and related stakeholders. Mainly on a rationale of financial justification and educational efficacy, more evidence for learning has been called for. The aims of this systematic review were to characterise learning in the laboratory and substantiate learning outcomes associated with laboratory instructions in university chemistry. Analysis of 355 empirical studies revealed that students develop five clusters of laboratory‐related competences pertaining to experimental competences , disciplinary learning , higher‐order thinking and epistemic learning , transversal competences as well as affective domain . These competences were specified into related constructs measured in the studies. Synthesis of published studies led to a substantiated view on multidimensional learning in the laboratory and its implications for research, practice and theory are suggested. Representations of research areas that deserve appraisals and further investigations are also proposed. The video abstract for this article is available at https://video.ku.dk/secret/76185334/73665cb966315601404b793ffc234a77 . Context and implications: Rationale for this study: To provide comprehensive evidence for learning outcomes associated with laboratory work. Why the new findings matter: Our research synthesis substantiates a multidimensional view of laboratory learning. There is a large scope for empirical and theoretical development in this complex setting. Implications for researchers and practitioners: Future research should be directed towards a more comprehensive and rigorous inquiry into student learning that considers a more holistic view. Focus on higher‐order competences is needed. Practice wise, laboratory curricula should better accommodate students' learning progression throughout their higher education. Assessment and feedback practices should be revisited.

A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly adminis

Human urine samples were analysed by a reversed-phase chromatographic system and an ion-pair chromatographic system. The chromatographic system was connected to the ICP-MS either by a microconcentric nebulizer (MCN) in combination with a cyclonic spraychamber or by a modified direct injection nebulizer (MDIN). The sensitivity of the latter was better than the sensitivity of the MCN, which on the other hand was more robust for the analysis of samples with high concentrations of dissolved solids. Urine sample composition did not seem to change when urine was exposed to evaporation under nitrogen at ambient temperature and methanol extraction. A pre-concentration factor of 10 was achieved with this procedure. On occasions when a pre-concentration factor of 100 was obtained by lyophilsation and methanol extraction, at least 10 selenium compounds were separated in the urine sample. Urine samples were collected from two healthy volunteers who had been supplied with 1000 µg and 2000 µg of selenium, respectively, in the form of selenized yeast. When samples were spiked with 8 different standards, only two standards co-eluted with compounds in urine in both chromatographic systems: the major urinary metabolite Se-methyl-N-acetylgalactosamine and Se-methyl-N-acetylglucosamine. The presence of Se-methyl-N-acetylglucosamine in urine was verified by co-migration with the standard in capillary electrophoresis after fractionation by preparative reversed-phase chromatography. Se-methyl-N-acetylglucosamine is only a minor metabolite as its concentration was less than 2% of the concentration of Se-methyl-N-acetylgalactosamine. The presence of this metabolite in urine has, to our knowledge, not been suggested before. Trimethylselenonium, selenomethionine, Se-methylselenocysteine, Se-methylselenomethionine and selenocystamine were not detected in these samples.

A demountable direct injection high efficiency nebulizer operating at low sample uptake rates was developed and used for coupling of capillary electrophoresis (CE) with inductively coupled plasma mass spectrometry (ICP-MS). When the nebulizer was used for continuous sample introduction, detection limits of 20 and 1 ng L⁻¹ were obtained for ⁸²Se and ¹⁰³Rh, respectively, at sample uptake rates of 10–30 μL min⁻¹, based on three times the standard deviation of blank solution (3σ_b, n = 10). The nebulizer was used as part of the interface for coupling of CE with ICP-MS and applied for speciation of aqueous selenium standards. The interface was operated in the self-aspirating mode with a sheath liquid uptake of 10 μL min⁻¹. The CE-ICP-MS system resulted in baseline separation of selenate, selenite, selenocystine and selenomethionine within a total analysis time of 5.4 min. Detection limits were in the sub µg Se L⁻¹ range, corresponding to absolute detection limits in the range 25–125 fg selenium. Repeatability (n = 6) expressed as relative standard deviations with respect to migration times, peak heights and peak areas were better than 1.6, 6.7 and 6.0%, respectively.