Highlights from Faraday Discussion on Nanoalloys: recent developments and future perspectives, London, UK.

In this article, we present a summary of the Faraday Discussion that took place on September 21-23, 2022 in London, UK. The primary goal of this event was to promote and discuss the recent developments in the field of nanoalloys. Here we briefly outline each scientific session as well as other conference events.

Simultaneous Harvesting of Multiple Hot Holes via Visible-Light Excitation of Plasmonic Gold Nanospheres for Selective Oxidative Bond Scission of Olefins to Carbonyls.

Using visible photoexcitation of gold nanospheres we successfully demonstrate the simultaneous harvesting of plasmon-induced multiple hot holes in the complete oxidative scission of the C=C bond in styrene at room temperature to selectively form benzaldehyde and formaldehyde, which is a reaction that requires activation of multiple substrates. Our results reveal that, while extraction of hot holes becomes efficient for interband excitation, harvesting of multiple hot holes from the excited Au nanospheres becomes prevalent only beyond a threshold light intensity. We show that the alkene oxidation proceeded via a sequence of two consecutive elementary steps; namely, a binding step and a cyclic oxometallate transition state as the rate-determining step. This demonstration of plasmon-excitation-mediated harvesting of multiple hot holes without the use of an extra hole transport media opens exciting possibilities, notably for difficult catalytic transformations involving multielectron oxidation processes.

Association of the Protein-Quality-Control Protein Ubiquilin-1 With Alzheimer's Disease Both in vitro and in vivo.

Alzheimer's disease (AD) belongs to a class of diseases characterized by progressive accumulation and aggregation of pathogenic proteins, particularly Aß proteins. Genetic analysis has identified UBQLN1 as an AD candidate gene. Ubiquilin-1 levels reduce with AD progression, suggesting a potential loss-of-function mechanism. The ubiquilin-1 protein is involved in protein quality control (PQC), which plays essential roles in cellular growth and normal cell function. Ubiquilin-1 regulates γ-secretase by increasing endoproteolysis of PS1, a key γ-secretase component. Presently, the effects of ubiquilin-1 on cellular physiology as well as Aß-related events require further investigation. Here, we investigated the effects of ubiquilin-1 on cellular growth and viability in association with APP (amyloid-ß protein precursor), APP processing-related ß-secretase (BACE1, BACE) and γ-secretase using cell and animal-based models. We showed that loss-of-function in Drosophila ubqn suppresses human APP and human BACE phenotypes in wing veins and altered cell number and tissue compartment size in the wing. Additionally, we performed cell-based studies and showed that silencing UBQLN1 reduced cell viability and increased caspase-3 activity. Overexpression of UBQLN1 significantly reduced Aß levels. Furthermore, pharmacological inhibition of γ-secretase increased ubiquilin-1 protein levels, suggesting a mechanism that regulates ubiquilin-1 levels which may associate with reduced Aß reduction by inhibiting γ-secretase. Collectively, our results support not only a loss-of-function mechanism of ubiquilin-1 in association with AD, but also support the significance of targeting ubiquilin-1-mediated PQC as a potential therapeutic strategy for AD.

Laminar Flow on Endothelial Cells Suppresses eNOS O-GlcNAcylation to Promote eNOS Activity.

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ArtontheBrain: Results of a Pilot Project Among Long-Term Care Residents.

For long-term care (LTC) residents, multiple barriers impede access to formal museum-based participa-tory art programming. Capitalizing on available technologies may circumvent common barriers and improve quality of life for those older adults even in the presence of dementia. Targets: A convenience sample of 31 older adults was recruited from the population of residents in one LTC facility. Intervention: ArtontheBrain, a web-based program, engages participants in activities centered on visual artwork, enabling users to learn about artists through activities, such as puzzles, storytelling, and group discussions. Mechanisms of Action: Researchers hypothesized that engagement with ArtontheBrain would benefit perceived quality of life in the domains of meaningful activity engagement and personal relationships and secondarily, improvements in functional performance, mood state, and cognitive performance may occur. Outcomes: Application of a quality of life survey pre and post ArtontheBrain intervention revealed significant improvements within the individual subsample for two activity options: engagement in enjoyable activities on weekends and evenings and explore new skills and interests. Total scores for the personal relationship scale had significant improvements post-intervention for the individual and group subsamples. The individual subsample demonstrated improvement in cognitive performance, which worsened for the group subsample. Mood and functional ability worsened for the entire sample.[Research in Gerontological Nursing, 14(5), 235-243.].

The Musical Ear Test: Norms and correlates from a large sample of Canadian undergraduates.

We sought to establish norms and correlates for the Musical Ear Test (MET), an objective test of musical ability. A large sample of undergraduates at a Canadian university (N > 500) took the 20-min test, which provided a Total score as well as separate scores for its Melody and Rhythm subtests. On each trial, listeners judged whether standard and comparison auditory sequences were the same or different. Norms were derived as percentiles, Z-scores, and T-scores. The distribution of scores was approximately normal without floor or ceiling effects. There were no gender differences on either subtest or the total score. As expected, scores on both subtests were correlated with performance on a test of immediate recall for nonmusical auditory stimuli (Digit Span Forward). Moreover, as duration of music training increased, so did performance on both subtests, but starting lessons at a younger age was not predictive of better musical abilities. Listeners who spoke a tone language exhibited enhanced performance on the Melody subtest but not on the Rhythm subtest. The MET appears to have adequate psychometric characteristics that make it suitable for researchers who seek to measure musical abilities objectively.

The Pivotal Role of Hot Carriers in Plasmonic Catalysis of C-N Bond Forming Reaction of Amines.

Here, we demonstrate the simultaneous utilization of both the hot carriers (electrons and holes) in the photocatalytic transformation of benzylamine to N-benzylidenebenzylamine and the scope of reaction has also been successfully demonstrated with catalytic oxidation of 4-methoxybenzylamine. The wavelength-dependent excitation of AuNP allows us to tune the potential energy of charge carriers relative to the redox potential of the reactants which leads to energetically favorable product formation on the nanoparticle surface. We capture the formation of reaction intermediates and products by using in situ Raman spectroscopy, complemented by NMR spectroscopy and GC-MS. Based on the experimental substantiations, a plausible reaction mechanism has been proposed.

Individual differences in musical ability are stable over time in childhood.

The development of human abilities stems from a complex interplay between genetic predispositions and environmental factors. Numerous studies have compared musicians with non-musicians on measures of musical and non-musical ability, frequently attributing musicians' superior performance to their training. By ignoring preexisting differences, however, this view assumes that taking music lessons is akin to random assignment. In the present longitudinal study, the musical ability of 5- to 10-year-olds was measured at Time 1 with a test of music perception and cognition. Five years later, at Time 2, the children took the same test and a second test designed for older listeners. The test-retest correlation for aggregate scores was remarkably high, r ≈ 0.7, and remained strong when confounding variables (age, cognitive abilities, personality) were held constant. At both time points, music training was associated with musical ability, but the association at Time 2 became nonsignificant when musical ability at Time 1 was held constant. Time 1 musical ability also predicted duration of subsequent music training. These data are consistent with results from genetic studies, which implicate genes in all aspects of musical behavior and achievement, and with meta-analyses, which indicate that transfer effects from music training are weak. In short, early musical abilities significantly predicted later abilities, demonstrating that individual differences are stable over time. We found no evidence, however, to suggest that music training predicted musical ability after accounting for prior ability. The results underscore the importance of considering preexisting abilities in any type of learning.

Accessible Virtual Arts Recreation for Wellbeing Promotion in Long-Term Care Residents.

The efficacy of a technology-driven visual arts recreation activity, delivered virtually, was evaluated for its potential to achieve positive impacts, similar to traditional arts-interventions, on wellbeing in long-term care residents. Thirty-one residents (average age 86.8 years; SD = 9.4) engaged with the arts-intervention for 30-minutes, twice weekly, for 6 weeks with either a partner or as part of a group. Wellbeing indicators included self-reported psychological and health-related wellness, and attention capacity. Binomial tests of postintervention change revealed a significant above-chance probability of improvement in one or more wellbeing indicators (p < .05). Postparticipation feedback survey scores were positive (p < .05). Cognitive status did not influence outcome; however, other participant characteristics such as younger age, higher openness-to-experience (personality trait), and lower baseline mood were significantly associated with positive response to the intervention (p < .05). Findings demonstrate technology may be an effective platform for promoting accessibility to beneficial arts-interventions for older adults.

Direct Bioprinting of 3D Multicellular Breast Spheroids onto Endothelial Networks.

Bioprinting is emerging as a promising tool to fabricate 3D human cancer models that better recapitulate critical hallmarks of in vivo tissue architecture. In current layer-by-layer extrusion bioprinting, individual cells are extruded in a bioink together with complex spatial and temporal cues to promote hierarchical tissue self-assembly. However, this biofabrication technique relies on complex interactions among cells, bioinks and biochemical and biophysical cues. Thus, self-assembly may take days or even weeks, may require specific bioinks, and may not always occur when there is more than one cell type involved. We therefore developed a technique to directly bioprint pre-formed 3D breast epithelial spheroids in a variety of bioinks. Bioprinted pre-formed 3D breast epithelial spheroids sustained their viability and polarized architecture after printing. We additionally printed the 3D spheroids onto vascular endothelial cell networks to create a co-culture model. Thus, the novel bioprinting technique rapidly creates a more physiologically relevant 3D human breast model at lower cost and with higher flexibility than traditional bioprinting techniques. This versatile bioprinting technique can be extrapolated to create 3D models of other tissues in additional bioinks.

Musical ability, music training, and language ability in childhood.

We tested theories of links between musical expertise and language ability in a sample of 6- to 9-year-old children. Language ability was measured with tests of speech perception and grammar. Musical expertise was measured with a test of musical ability that had 3 subtests (melody discrimination, rhythm discrimination, and long-term memory for music) and as duration of music training. Covariates included measures of demographics, general cognitive ability (IQ, working memory), and personality (openness-to-experience). Music training was associated positively with performance on the grammar test, musical ability, IQ, openness, and age. Musical ability predicted performance on the tests of speech perception and grammar, as well as IQ, working memory, openness, and age. Regression analyses-with other variables held constant-revealed that language abilities had significant partial associations with musical ability and IQ but not with music training. Rhythm discrimination was a better predictor of language skills compared with melody discrimination, but memory for music was equally good. Bayesian analyses confirmed the results from the standard analyses. The implications of the findings are threefold: (a) musical ability predicts language ability, and the association is independent of IQ and other confounding variables; (b) links between music and language appear to arise primarily from preexisting factors and not from formal training in music; and (c) evidence for a special link between rhythm and language may emerge only when rhythm discrimination is compared with melody discrimination. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Orienting Attention to Auditory and Visual Short-term Memory: The Roles of Age, Hearing Loss, and Cognitive Status.

Background/Study Context: Attention can be reflectively oriented to a visual or auditory representation in short-term memory, but it is not clear how aging and hearing acuity affects reflective attention. The purpose of the present study was to examine whether performance in auditory and visual reflective attention tasks varies as a function of participants' age and hearing status.Methods: Young (19 to 33 years) and older adults with normal or mild to moderate hearing loss (62-90 years) completed a delayed match-to-sample task in which participants were first presented with a memory array of four different digits to hold in memory. Two digits were presented visually (left and right hemifield), and two were presented aurally (left and right ears simultaneously). During the retention interval, participants were presented with a cue (dubbed retro-cue), which could be either uninformative or indicated to the participants to retrospectively orient their attention to either auditory short-term memory (ASTM) or visual short-term memory (VSTM). The cue was followed by another delay, after which a single item was presented (i.e., test probe) for comparison (match or no match) with the items held in ASTM and/or VSTM.Results: Overall, informative retro-cue yielded faster response time than uninformative retro-cue. The retro-cue benefit in response time was comparable for auditory and visual-orienting retro-cue and similar in young and older adults. Regression analyses showed that only the auditory-orienting retro-cue benefit was predicted by hearing status rather than age per se.Conclusion: Both younger and older adults can benefit from visual and auditory-orienting retro-cues, but the auditory-orienting retro-cue benefit decreases with poorer hearing acuity. This finding highlights changes in cognitive processes that come with age even in those with just mild-to-moderate hearing loss, and suggest that older adults' performance in working memory tasks is sensitive to low level auditory scene analysis (i.e., concurrent sound segregation).

A Three-Dimensional In Vitro Coculture Model to Quantify Breast Epithelial Cell Adhesion to Endothelial Cells.

Three-dimensional (3D) in vitro culture models better recapitulate the tissue microenvironment, and therefore may provide a better platform to evaluate therapeutic effects on adhesive cell-cell interactions. The objective of this study was to determine if AD-01, a peptide derivative of FK506-binding protein like that is reported to bind to the adhesion receptor CD44, would induce a greater reduction in breast epithelial spheroid adhesion to endothelial tube-like networks in our 3D coculture model system compared to two-dimensional (2D) culture. MCF10A, MCF10A-NeuN, MDA-MB-231, and MCF7 breast epithelial cells were pretreated with AD-01 either as single cells or as spheroids. Breast epithelial cell adhesion to 2D tissue culture substrates was first measured, followed by spheroid formation (breast cell-cell adhesion) and spheroid adhesion to Matrigel or endothelial networks. Finally, CD44 expression was quantified in breast epithelial cells in 2D and 3D culture. Our results show that AD-01 had the largest effect on spheroid formation, specifically in breast cancer cell lines. AD-01 also inhibited breast cancer spheroid adhesion to and migration along endothelial networks. The different breast epithelial cell lines expressed more CD44 when cultured as 3D spheroids, but this did not universally translate into higher protein levels. This study shows that 3D coculture models can enable unique insights into cell adhesion, migration, and cell-cell interactions, thereby enhancing understanding of basic biological mechanisms. Furthermore, such 3D coculture systems may also represent a more relevant testing platform for understanding the mechanism-of-action of new therapeutic agents. Impact Statement Cell adhesion is inherently different in two dimensional (2D) compared to three dimensional (3D) culture; yet, most adhesion assays in academia and industry are still conducted in 2D because few simple, yet effective, adhesion models exist in 3D. Recently we developed a 3D in vitro coculture model to examine breast epithelial spheroid interactions with endothelial tubes. We now show that this 3D coculture model can effectively be used to interrogate and quantify drug-induced differences in breast epithelial cell adhesion that are unique to 3D cocultures. This 3D coculture adhesion model can furthermore be modified for use with other cell types to better predict drug effects on cell-vasculature adhesion.

Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation.

Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.

Biofabrication strategies for creating microvascular complexity.

Design and fabrication of effective biomimetic vasculatures constitutes a relevant and yet unsolved challenge, lying at the heart of tissue repair and regeneration strategies. Even if cell growth is achieved in 3D tissue scaffolds or advanced implants, tissue viability inevitably requires vascularization, as diffusion can only transport nutrients and eliminate debris within a few hundred microns. This engineered vasculature may need to mimic the intricate branching geometry of native microvasculature, referred to herein as vascular complexity, to efficiently deliver blood and recreate critical interactions between the vascular and perivascular cells as well as parenchymal tissues. This review first describes the importance of vascular complexity in labs- and organs-on-chips, the biomechanical and biochemical signals needed to create and maintain a complex vasculature, and the limitations of current 2D, 2.5D, and 3D culture systems in recreating vascular complexity. We then critically review available strategies for design and biofabrication of complex vasculatures in cell culture platforms, labs- and organs-on-chips, and tissue engineering scaffolds, highlighting their advantages and disadvantages. Finally, challenges and future directions are outlined with the hope of inspiring researchers to create the reliable, efficient and sustainable tools needed for design and biofabrication of complex vasculatures.

Bioprinting of 3D breast epithelial spheroids for human cancer models.

3D human cancer models provide a better platform for drug efficacy studies than conventional 2D culture, since they recapitulate important aspects of the in vivo microenvironment. While biofabrication has advanced model creation, bioprinting generally involves extruding individual cells in a bioink and then waiting for these cells to self-assemble into a hierarchical 3D tissue. This self-assembly is time consuming and requires complex cellular interactions with other cell types, extracellular matrix components, and growth factors. We therefore investigated if we could directly bioprint pre-formed 3D spheroids in alginate-based bioinks to create a model tissue that could be used almost immediately. Human breast epithelial cell lines were bioprinted as individual cells or as pre-formed spheroids, either in monoculture or co-culture with vascular endothelial cells. While individual breast cells only spontaneously formed spheroids in Matrigel-based bioink, pre-formed breast spheroids maintained their viability, architecture, and function after bioprinting. Bioprinted breast spheroids were more resistant to paclitaxel than individually printed breast cells; however, this effect was abrogated by endothelial cell co-culture. This study shows that 3D cellular structure bioprinting has potential to create tissue models that quickly replicate the tumor microenvironment.

Musical Competence is Predicted by Music Training, Cognitive Abilities, and Personality.

Individuals differ in musical competence, which we defined as the ability to perceive, remember, and discriminate sequences of tones or beats. We asked whether such differences could be explained by variables other than music training, including socioeconomic status (SES), short-term memory, general cognitive ability, and personality. In a sample of undergraduates, musical competence had positive simple associations with duration of music training, SES, short-term memory, general cognitive ability, and openness-to-experience. When these predictors were considered jointly, musical competence had positive partial associations with music training, general cognitive ability, and openness. Nevertheless, moderation analyses revealed that the partial association between musical competence and music training was evident only among participants who scored below the mean on our measure of general cognitive ability. Moreover, general cognitive ability and openness had indirect associations with musical competence by predicting music training, which in turn predicted musical competence. Musical competence appears to be the result of multiple factors, including but not limited to music training.