Aging, Proteotoxicity, Mitochondria, Glycation, NAD+ and Carnosine: Possible Inter-Relationships and Resolution of the Oxygen Paradox

It is suggested that NAD+ availability strongly affects cellular aging and organism lifespan: low NAD+ availability increases intracellular levels of glycolytic triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate) which, if not further metabolized, decompose spontaneously into methylglyoxal (MG), a glycating agent and source of protein and mitochondrial dysfunction and reactive oxygen species (ROS). MG-damaged proteins and other aberrant polypeptides can induce ROS generation, promote mitochondrial dysfunction and inhibit proteasomal activity. Upregulation of mitogenesis and mitochondrial activity by increased aerobic exercise, or dietary manipulation, helps to maintain NAD+availability and thereby decreases MG-induced proteotoxicity. These proposals can explain the apparent paradox whereby aging is seemingly caused by increased ROS-mediated macromolecular damage but is ameliorated by increased aerobic activity. It is also suggested that increasing mitochondrial activity decreases ROS generation, while excess numbers of inactive mitochondria are deleterious due to increased ROS generation. The muscle- and brain-associated dipeptide, carnosine, is an intracellular buffer which can delay senescence in cultured human fibroblasts and delay aging in senescence-accelerated mice. Carnosine's ability to react with MG and possibly other deleterious carbonyl compounds, and scavenge various ROS, may account for its protective ability towards ischemia and ageing

To Play or Not to Play: An Investigation Into The Effect of Video Game Use on Executive Functions

Findings in experimental psychology research suggest that individuals who engage in video game play outperform those who do not play video games on a range of cognitions, in particular visual selective attention. It was predicted that the source of the differences observed in video game players (VGP) compared to non-video game players (NVGP) is the result of additional executive function resources. Findings suggest that only when the task is sufficiently demanding are the additional attentional and executive function resources in VGP observable compared to NVGP. Across three experimental paradigms, the executive functions of VGP were compared to those of NVGP. In Experiments One and Two, a hybrid response inhibition task was used to assess the response inhibition performance in the subcomponents of action cancellation, action withholding, and interference resolution in VGP compared to NVGP. In Experiment Two, measures of γ-aminobutyric acid (GABA), glutamate, and glutamine were recorded using magnetic resonance spectroscopy. In Experiment One, VGP significantly outperformed NVGP in measures of action cancellation and interference resolution, but the HRIT failed to measure action withholding. In Experiment Two, the results of Experiment One were not replicated, and there was no significant difference between VGP and NVGP in the subcomponents of response inhibition. A combined analysis of participants in Experiments One and Two replicated the effects observed in Experiment One, VGP outperformed NVGP on measures of interference resolution and action withholding. In Experiment Three, the ability to sustain attention was assessed using a continuous performance task with manipulations of cognitive load. The aim was to elucidate the inconsistent results observed in Experiments One and Two by manipulating cognitive load to allow observation of the increased executive function resources in VGP. The results of Experiment Three showed no significant difference between VGP and NVGP in metrics of sustained attention performance. Moreover, there was no difference between groups in their ability to sustain attention regardless of cognitive load. This thesis emphasises the potential for video game use to train and improve executive function capabilities, but that findings and directions for future research are constrained by methodological and theoretical limitations

"My body shall pay recompense": the embodiment of Margaret in selected staged and televised cycles of the first tetralogy

This is a critical study of the body of Queen Margaret in performance in selected cycles of the first tetralogy (the three parts of 'Henry VI' and 'Richard III'). Focussing on four major British cycles (two by the Royal Shakespeare Company and two by the British Broadcasting Corporation), the study places each cycle within its cultural and theatrical or televisual context and analyses how these selected productions present Margaret and her theatrical mirrors, and how they embody (or refuse to embody) contemporaneous concepts of female transgression. The introduction provides an overview of the aims and objectives of the work and an introduction to the methodological approaches used. The first chapter analyses the presentation of Margaret's hair in production photographs from two Royal Shakespeare Company cycles either side of the sexual revolution (1963 and 1977), and creates a theorised performance history that explores how the cycles interacted with prevalent cultural ideas of female sexuality, as well as representing a change in Royal Shakespeare Company management. The second chapter examines Jane Howell's 1983 BBC cycle­ - part of the BBC/Time-Life complete works project - and how Howell used televisual and theatrical techniques to create a cycle that both literally and figuratively centred Margaret and her theatrical mirrors. The third and final chapter analyses Dominic Cooke's 2016 BBC cycle 'The Hollow Crown: The Wars of the Roses', and how the creative direction of the cycle, its star actors, and its existence in a time of large scale cinematically realistic and bombastic television, made for a cycle that both allowed characters to marginalise and use female bodies, and did so itself. The conclusion of the study draws together these analytical threads, and outlines how each of the approaches contribute to a larger critical study of the body of Margaret in performance

Low-Frequency Acoustic Microscopy

Since acoustic microscopy was first invented by Quate and Lemons,1 many workers in the field have built acoustic microscopes ranging in frequency from tens of megahertz to hundreds of gigahertz, nd for a wide variety of applications in materials characterization, integrated circuits evaluation, and medical applications. In this work, we use the acoustic microscope as a quantitative nondestructive evaluation tool, our main purpose being the detection and characterization of defects present within 1 mm of the surface of a sample

L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner

The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types. © 2012 Cartwright et al

Dialysis vs conservative management decision aid: a study protocol

When patients' kidney function deteriorates to chronic kidney disease stage 5, services offer patients a choice for the next phase of their care. Renal replacement therapies may not have survival benefits, and conservative management may have less treatment burden for older patients with associated comorbidities or frailty. Anna E Winterbottom et al discuss the development of a patient decision aid

Carnosine:can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide's influence on cellular ATP concentrations. Carnosine's ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine's mode of action on human cells. © 2013 Hipkiss et al.; licensee Chemistry Central Ltd

Critical review of leaflets about conservative management used in UK renal services

Background: Written information supplements nurse‐led education about treatment options. It is unclear if this information enhances patients’ reasoning about conservative management (CM) and renal replacement therapy decisions. Aim: This study describes a critical review of resources U.K. renal staff use when providing CM options to people with Established Kidney Disease (EKD) during usual pre‐dialysis education. Design: A survey using mixed methods identified and critically analysed leaflets about CM. Participants & measurements: All 72 renal units in the United Kingdom received an 11‐item questionnaire to elicit how CM education is delivered, satisfaction and/or needs with patient resources and staff training. Copies of leaflets were requested. A coding frame was utilised to produce a quality score for each leaflet. Results: Fifty‐four (75%) units participated. Patients discuss CM with a nephrologist (98%) or nurse (100%). Eighteen leaflets were reviewed, mean scores were 8.44 out of 12 (range 5–12, SD = 2.49) for information presentation; 3.50 out of 6 (range 0–6, SD = 1.58) for inclusion of information known to support shared decision‐making and 2.28 out of 6 (range 1–4, SD = 0.96) for presenting non‐biased information. Conclusions: Nurses preferred communicating via face‐to‐face contact with patients and/or families because of the emotional consequences and complexity of planning treatment for the next stage of a person's worsening kidney disease. Conversations were supplemented with written information; 66% of which were produced locally. Staff perceived a need for using leaflets, and spend time and resources developing them to support their services. However, no leaflets included the components needed to help people reason about conservative care and renal replacement therapy options during EKD education consultations

Teaching in Flexible Spatial and Digital Conditions

This study explores the opportunities and challenges of teaching under flexible spatial and digital conditions of the learning environment of a newly build school analyzing how teaching is organized and what curricular genres can be discerned, what resources and practices are offered to stimulate students meaning-making and what framing, relations and accessibility can be discerned in the flexibility of furniture and classroom space. The analyses of one teacher team’s planning and teaching of the thematic work project on Space in years 2-3 (8-9 old children) reveals varied teaching strategies between teacher-led and student-centered forms offering students linguistic, visual and audiovisual resources to make meaning of shared content via different subjects. Spatial framing allows for free movement or static and focused teaching strategies of rather traditional forms of assignments and assessment. These young students practice reading comprehension, both of written texts and films, that also serves building their knowledge about space, thus engaging in skills discourse in combination with thinking and learning discourse.