A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids

Background and purpose: Molecular mechanisms underlying the links between dietary intake of flavonoids and reduced cardiovascular disease risk are only partially understood. Key events in the pathogenesis of cardiovascular disease, particularly thrombosis, are inhibited by these polyphenolic compounds via mechanisms such as inhibition of platelet activation and associated signal transduction, attenuation of generation of reactive oxygen species, enhancement of nitric oxide production and binding to thromboxane A2 receptors. In vivo, effects of flavonoids are mediated by their metabolites, but the effects and modes of action of these compounds are not well-characterized. A good understanding of flavonoid structure–activity relationships with regard to platelet function is also lacking. Experimental approach: Inhibitory potencies of structurally distinct flavonoids (quercetin, apigenin and catechin) and plasma metabolites (tamarixetin, quercetin-3′-sulphate and quercetin-3-glucuronide) for collagen-stimulated platelet aggregation and 5-hydroxytryptamine secretion were measured in human platelets. Tyrosine phosphorylation of total protein, Syk and PLCγ2 (immunoprecipitation and Western blot analyses), and Fyn kinase activity were also measured in platelets. Internalization of flavonoids and metabolites in a megakaryocytic cell line (MEG-01 cells) was studied by fluorescence confocal microscopy. Key results: The inhibitory mechanisms of these compounds included blocking Fyn kinase activity and the tyrosine phosphorylation of Syk and PLCγ2 following internalization. Principal functional groups attributed to potent inhibition were a planar, C-4 carbonyl substituted and C-3 hydroxylated C ring in addition to a B ring catechol moiety. Conclusions and implications: The structure–activity relationship for flavonoids on platelet function presented here may be exploited to design selective inhibitors of cell signalling.

Knowing who likes who: The early developmental basis of coalition understanding

Group biases based on broad category membership appear early in human development. However, like many other primates humans inhabit social worlds also characterised by small groups of social coalitions which are not demarcated by visible signs or social markers. A critical cognitive challenge for a young child is thus how to extract information concerning coalition structure when coalitions are dynamic and may lack stable and outwardly visible cues to membership. Therefore, the ability to decode behavioural cues of affiliations present in everyday social interactions between individuals would have conferred powerful selective advantages during our evolution. This would suggest that such an ability may emerge early in life, however, little research has investigated the developmental origins of such processing. The present paper will review recent empirical research which indicates that in the first 2 years of life infants achieve a host of social-cognitive abilities that make them well adapted to processing coalition-affiliations of others. We suggest that such an approach can be applied to better understand the origins of intergroup attitudes and biases. Copyright © 2010 John Wiley & Sons, Ltd.

A new approach for the solution of the optimal set-point tracking problem for nonlinear systems

In this paper, a discrete time dynamic integrated system optimisation and parameter estimation algorithm is applied to the solution of the nonlinear tracking optimal control problem. A version of the algorithm with a linear-quadratic model-based problem is developed and implemented in software. The algorithm implemented is tested with simulation examples.

The long and the short of it: negotiating the right space for Asian theatre in the university drama curriculum

This article compares two approaches to teaching Asian theatre at undergraduate level in the United Kingdom. One approach samples a variety of different traditions as a means to challenge students to produce performance for a combined audience of hearing and deaf, whereas the other focuses on the effect of exploring one geographical area intensively over the course of one academic year. The article seeks to highlight the merits and pitfalls of both approaches, and questions whether student work that actively questions ethnicity and identity, as well as the tension between innovation and tradition, might be considered diasporic in character.

The basis of valuations for secured commercial property lending in the UK

In the context of the financial crash and the commercial property market downturn, this paper examines the basis of valuation used in the UK commercial property lending process. Post-crisis there is discussion of countercyclical measures including the monitoring of asset prices; however there is no consideration of a different approach to property valuation. This paper questions this omission, given the role that valuations play in the bank regulatory process. The different bases of valuation available to lenders within International Valuation Standards are identified as Market Value (MV), Mortgage Lending Value (MLV) and Investment Value (IV), with MV being the most used in the UK. Using the different bases in the period before the financial crisis, the UK property market is modelled at a national office, retail and industrial/warehouse sector level to determine the performance of each alternative valuation basis within the context of counter-cyclical pressures on lending. Both MLV and IV would have produced lower valuations and could have provided lenders with tools for more informed and prudent lending. The paper concludes by recognising some of the practical issues involved in adopting the different bases for the bank lending role but recommends a change to IV.

On the operator space structure of Hilbert spaces

Operator spaces of Hilbertian JC∗ -triples E are considered in the light of the universal ternary ring of operators (TRO) introduced in recent work. For these operator spaces, it is shown that their triple envelope (in the sense of Hamana) is the TRO they generate, that a complete isometry between any two of them is always the restriction of a TRO isomorphism and that distinct operator space structures on a fixed E are never completely isometric. In the infinite-dimensional cases, operator space structure is shown to be characterized by severe and definite restrictions upon finite-dimensional subspaces. Injective envelopes are explicitly computed.

The music instinct: the evolutionary basis of musicality

Why does music pervade our lives and those of all known human beings living today and in the recent past? Why do we feel compelled to engage in musical activity, or at least simply enjoy listening to music even if we choose not to actively participate? I argue that this is because musicality—communication using variations in pitch, rhythm, dynamics and timbre, by a combination of the voice, body (as in dance), and material culture—was essential to the lives of our pre-linguistic hominin ancestors. As a consequence we have inherited a desire to engage with music, even if this has no adaptive benefit for us today as a species whose communication system is dominated by spoken language. In this article I provide a summary of the arguments to support this view.

Spectral theory of Toeplitz and Hankel operators on the Bergman space A1

The Fredholm properties of Toeplitz operators on the Bergman space A2 have been well-known for continuous symbols since the 1970s. We investigate the case p=1 with continuous symbols under a mild additional condition, namely that of the logarithmic vanishing mean oscillation in the Bergman metric. Most differences are related to boundedness properties of Toeplitz operators acting on Ap that arise when we no longer have 1of Hankel operators on A1.

Neural basis of the undermining effect of monetary reward on intrinsic motivation

Contrary to the widespread belief that people are positively motivated by reward incentives, some studies have shown that performance-based extrinsic reward can actually undermine a person's intrinsic motivation to engage in a task. This “undermining effect” has timely practical implications, given the burgeoning of performance-based incentive systems in contemporary society. It also presents a theoretical challenge for economic and reinforcement learning theories, which tend to assume that monetary incentives monotonically increase motivation. Despite the practical and theoretical importance of this provocative phenomenon, however, little is known about its neural basis. Herein we induced the behavioral undermining effect using a newly developed task, and we tracked its neural correlates using functional MRI. Our results show that performance-based monetary reward indeed undermines intrinsic motivation, as assessed by the number of voluntary engagements in the task. We found that activity in the anterior striatum and the prefrontal areas decreased along with this behavioral undermining effect. These findings suggest that the corticobasal ganglia valuation system underlies the undermining effect through the integration of extrinsic reward value and intrinsic task value.

Grouping of 24 apple cultivars on the basis of starch degradation rate and their fruit pattern

The ripening processes of 24 apple cultivars were examined in the United Kingdom National Fruit Collection in 2010. Basically the starch content, and additionally ground colour, water-soluble solids content and flesh firmness were studied during ripening. The degradation of the starch content was evaluated using a 0–10 scale. A starch degradation value of 50% was taken to be the optimum harvest date, with harvest beginning at a value of 40% and finishing at 60%. Depending on the cultivar, this represented a harvest window of 9 to 21 days. Later ripening cultivars matured more slowly, leading to a longer harvesting period, with the exception of cv. Feuillemorte. Pronounced differences were observed among the cultivars on the basis of the starch degradation pattern, allowing them to be divided into four groups. Separate charts were elaborated for each group that are recommended for use in practice.