The neuroprotective potential of flavonoids: a multiplicity of effects

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

Style, experimentation and Jingju (Beijing Opera) as a decentered multiplicity

Jingju (Beijing Opera) is widely considered to be a fundamentally non-naturalistic practice that became known in the West after it caught the attention of western practitioners in 1935 following Mei Lanfang’s performance in Moscow. Given the implication that its importance is largely historical, some non-specialists have implied that Jingju has little relevance to contemporary modes of thinking, particularly the multiplicities of experience as outlined by philosophers such as Deleuze and Guattari. This article seeks to demonstrate the multiplicity of Jingju for a wider readership through both a historical analysis and a deconstruction of the form. It will show how, at the same time that Mei Lanfang was providing a ‘non-realistic’ model for western practitioners eager to displace the dominance of naturalism, realistic settings were becoming an integral part of Jingju performances in Shanghai. The article also engages with the various acting pai/styles that weave Jingju into a complex, multiple form. The article demonstrates how Deleuzian models actually facilitate a greater understanding of Jingju.

Infection of human airway epithelium by human and avian strains of influenza a virus

We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.

Theoretical calculation of absorption intensities of C2H and C2D

The theory of dipole-allowed absorption intensities in triatomic molecules is presented for systems with three close-lying electronic states of doublet multiplicity. Its derivation is within the framework of a recently developed variational method [CARTER, S., HANDY, N. C., PUZZARINI, C., TARRONI, R., and PALMIERI, P., 2000, Molec. Phys., 98,1967]. The method has been applied to the calculation of the infrared absorption spectrum of the C2H radical and its deuterated isotopomer for energies up to 10000 cm(-1) above the ground state, using highly accurate ab initio diabatic potential energy and dipole moment surfaces. The calculated spectra agree very well with those recorded experimentally in a neon matrix [FORNEY, D., JACOX, M. E., and THOMPSON, W. E., 1995, J. molee. Spectrosc., 170, 178] and assignments in the high energy region of the IR spectra are proposed for the first time.

Flavonoids and brain health: multiple effects underpinned by common mechanisms

The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two processes. Firstly, they interact with important neuronal signalling cascades leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and differentiation. These interactions include selective actions on a number of protein kinase and lipid kinase signalling cascades, most notably the PI3K/Akt and MAP kinase pathways which regulate pro-survival transcription factors and gene expression. Secondly, they induce peripheral and cerebral vascular blood flow in a manner which may lead to the induction of angiogenesis, and new nerve cell growth in the hippocampus. Therefore, the consumption of flavonoid-rich foods, such as berries and cocoa, throughout life holds a potential to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance.

Prebiotics and resistance to gastrointestinal infections

Acute gut disorder is a cause for significant medicinal and economic concern. Certain individual pathogens of the gut, often transmitted in food or water, have the ability to cause severe discomfort. There is a need to manage such conditions more effectively. The route of reducing the risk of intestinal infections through diet remains largely unexplored. Antibiotics are effective at inhibiting pathogens; however, these should not be prescribed in the absence of disease and therefore cannot be used prophylactically. Moreover, their indiscriminate use has reduced effectiveness. Evidence has accumulated to suggest that some of the health-promoting bacteria in the gut (probiotics) can elicit a multiplicity of inhibitory effects against pathogens. Hence, an increase in their numbers should prove effective at repressing pathogen colonisation if/when infectious agents enter the gut. As such, fortification of indigenous bifidobacteria/lactobacilli by using prebiotics should improve protection. There are a number of potential mechanisms for lactic acid bacteria to reduce intestinal infections. Firstly, metabolic endproducts such as acids excreted by these micro-organisms may lower the gut pH to levels below those at which pathogens are able to effectively compete. Also, many lactobacilli and bifidobacteria species are able to excrete natural antibiotics, which can have a broad spectrum of activity. Other mechanisms include an improved immune stimulation, competition for nutrients and blocking of pathogen adhesion sites in the gut. Many intestinal pathogens like type 1 fimbriated Escherichia coli, salmonellae and campylobacters utilise oligosaccharide receptor sites in the gut. Once established, they can then cause gastroenteritis through invasive and/or toxin forming properties. One extrapolation of the prebiotic concept is to simulate such receptor sites in the gut lumen. Hence, the pathogen is 'decoyed' into not binding at the host mucosal interface. The combined effects of prebiotics upon the lactic acid flora and anti-adhesive strategies may lead towards new dietary interventions against food safety agents.

Can drug-bearing liposomes penetrate intact skin?

Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin appendages (hair follicles and sweat glands). Liposomes may also enhance transdermal drug delivery, increasing systemic drug concentrations. With such a multiplicity of functions, it is not surprising that mechanisms of liposomal delivery of therapeutic agents to and through the skin are unclear. Accordingly, this article provides an overview of the modes and mechanisms of action of different vesicles as drug delivery vectors in human skin. Our conclusion is that vesicles, depending on the composition and method of preparation, can vary with respect to size, lamellarity, charge, membrane fluidity or elasticity and drug entrapment. This variability allows for multiple functions ranging from local to transdermal effects. Application to dissimilar skins (animal or human) via diverse protocols may reveal different mechanisms of action with possible vesicle skin penetration reaching different depths, from surface assimilation to (rarely) the viable tissue and subsequent systemic absorption.

Transformation of plant cells

Plant cells are transformed by bringing them into contact with a a multiplicity of needle-like bodies on which the cells may be impaled. This causes a rupture in the cell wall allowing entry of transforming DNA either from a surrounding liquid medium or of DNA previously bound to or otherwise entrapped in the needle-like projections.

Transformation of plant cells

Plant cells are transformed by bringing them into contact with a a multiplicity of needle-like bodies on which the cells may be impaled. This causes a rupture in the cell wall allowing entry of transforming DNA either from a surrounding liquid medium or of DNA previously bound to or otherwise entrapped in the needle-like projections.

Interior Life

Interior Life was curated by Tim Renshaw, Mary Maclean and Bernice Donszelmann who together form ‘Outside Architecture’. The aim of this project was to argue that interior space should not be negatively defined as a retreat from the public realm. Instead, following the thought of the philosopher Peter Slotterdijk, interior space was proposed as a human need. The five artists selected by ‘Outside Architecture’ each visualized this need differently. A contention here was that interiors give rise to a multiplicity of experiences that potentially change the way we dwell in contemporary man-made space. This contention was primarily figured in relation to the materiality of contemporary interiors. Each gave attention to the effects of contemporary materials and surfaces and each considered that these forms produce new modes of sensing and immersion in a place. The exhibition included two talks by the members of ‘Outside Architecture. The project was supported by an Arts Council of England grant of £6,323 www.ucreative.ac.uk/galleries

Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate pro-survival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects.

Considering heteroglossia in language and development in Sub-Saharan Africa

Countries throughout the sub-Saharan (SSA) region have a complex linguistic heritage having their origins in opportunistic boundary changes effected by Western colonial powers at the Berlin Conference 1884-85. Postcolonial language-in-education policies valorizing ex-colonial languages have contributed at least in part to underachievement in education and thus the underdevelopment of human resources in SSA countries. This situation is not likely to improve whilst unresolved questions concerning the choice of language(s) that would best support social and economic development remain. Whilst policy attempts to develop local languages have been discussed within the framework of the African Union, and some countries have experimented with models of multilingual education during the past decade, the goalposts have already changed as a result of migration and trade. This paper argues that language policy makers need to be cognizant of changing language ecologies and their relationship with emerging linguistic and economic markets. The concept of language, within such a framework, has to be viewed in relation to the multiplicity of language markets within the shifting landscapes of people, culture, economics and the geo-politics of the 21st Century. Whilst, on the one hand, this refers to the hegemony of dominant powerful languages and the social relations of disempowerment, on the other hand, it also refers to existing and evolving social spaces and local language capabilities and choices. Within this framework the article argues that socially constructed dominant macro language markets need to be viewed also in relation to other, self-defined, community meso- and individual micro- language markets and their possibilities for social, economic and political development. It is through pursuing this argument that this article assesses the validity of Omoniyi’s argument in this volume, for the need to focus on the concept of language capital within multilingual contexts in the SSA region as compared to Bourdieu’s concept of linguistic capital.  

Innovation in construction: a sociology of technology approach

An alternative approach to understanding innovation is made using two intersecting ideas. The first is that successful innovation requires consideration of the social and organizational contexts in which it is located. The complex context of construction work is characterized by inter-organizational collaboration, a project-based approach and power distributed amongst collaborating organizations. The second is that innovations can be divided into two modes: ‘bounded’, where the implications of innovation are restricted within a single, coherent sphere of influence, and ‘unbounded’, where the effects of implementation spill over beyond this. Bounded innovations are adequately explained within the construction literature. However, less discussed are unbounded innovations, where many firms' collaboration is required for successful implementation, even though many innovations can be considered unbounded within construction's inter-organizational context. It is argued that unbounded innovations require an approach to understand and facilitate the interactions both within a range of actors and between the actors and technological artefacts. The insights from a sociology of technology approach can be applied to the multiplicity of negotiations and alignments that constitute the implementation of unbounded innovation. The utility of concepts from the sociology of technology, including ‘system building’ and ‘heterogeneous engineering’, is demonstrated by applying them to an empirical study of an unbounded innovation on a major construction project (the new terminal at Heathrow Airport, London, UK). This study suggests that ‘system building’ contains outcomes that are not only transformations of practices, processes and systems, but also the potential transformation of technologies themselves.

Alverata: Latin, Greek and Cyrillic typeface

Alverata: a typeface design for Europe This typeface is a response to the extraordinarily diverse forms of letters of the Latin alphabet in manuscripts and inscriptions in the Romanesque period (c. 1000–1200). While the Romanesque did provide inspiration for architectural lettering in the nineteenth century, these letterforms have not until now been systematically considered and redrawn as a working typeface. The defining characteristic of the Romanesque letterform is variety: within an individual inscription or written text, letters such as A, C, E and G might appear with different forms at each appearance. Some of these forms relate to earlier Roman inscriptional forms and are therefore familiar to us, but others are highly geometric and resemble insular and uncial forms. The research underlying the typeface involved the collection of a large number of references for lettering of this period, from library research and direct on-site ivestigation. This investigation traced the wide dispersal of the Romanesque lettering tradition across the whole of Europe. The variety of letter widths and weights encountered, as well as variant shapes for individual letters, offered both direct models and stylistic inspiration for the characters and for the widths and weight variants of the typeface. The ability of the OpenType format to handle multiple stylistic variants of any one character has been exploited to reflect the multiplicity of forms available to stonecutters and scribes of the period. To make a typeface that functions in a contemporary environment, a lower case has been added, and formal and informal variants supported. The pan-European nature of the Romanesque design tradition has inspired an pan-European approach to the character set of the typeface, allowing for text composition in all European languages, and the typeface has been extended into Greek and Cyrillic, so that the broadest representation of European languages can be achieved.