Neuroinflammation and its modulation by flavonoids

There is increasing evidence to suggest that neuroinflammatory processes contribute to the cascade of events that lead to the progressive neuronal damage observed in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Therefore, treatment regimes aimed at modulating neuroinflammatory processes may act to slow the progression of these debilitating brain disorders. Recently, a group of dietary polyphenols known as flavonoids have been shown to exert neuroprotective effects in vivo and in neuronal cell models. In this review we discuss the evidence relating to the modulation of neuroinflammation by flavonoids. We highlight the evidence which suggests their mechanism of action involves: 1) attenuation of the release of cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α); 2) an inhibitory action against inducible nitric oxide synthase (iNOS) induction and subsequent nitric oxide (NO•) production; 3) inhibition of the activation of NADPH oxidase and subsequent reactive oxygen species generation; 4) a capacity to down-regulate the activity of pro-inflammatory transcription factors such as nuclear factor-κB (NF-κB); and 5) the potential to modulate signalling pathways such as mitogen-activated protein kinase (MAPK) cascade. We also consider the potential of these dietary compounds to represent novel therapeutic agents by considering their metabolism in the body and their ability to access the brain via the blood brain barrier. Finally, we discuss future areas of study which are necessary before dietary flavonoids can be established as therapeutic agents against neuroinflammation.

New scientific paradigms for probiotics and prebiotics

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics. Humans have evolved in symbiosis with an estimated 1014 resident microorganisms. However, as medicine has widely defined and explored the perpetrators of disease, including those of microbial origin, it has paid relatively little attention to the microbial cells that constitute the most abundant life forms associated with our body. Microbial metabolism in humans and animals constitutes an intense biochemical activity in the body, with profound repercussions for health and disease. As understanding of the human genome constantly expands, an important opportunity will arise to better determine the relationship between microbial populations within the body and host factors (including gender, genetic background, and nutrition) and the concomitant implications for health and improved quality of life. Combined human and microbial genetic studies will determine how such interactions can affect human health and longevity, which communication systems are used, and how they can be influenced to benefit the host. Probiotics are defined as live microorganisms which, when administered in adequate amounts confer a health benefit on the host.1 The probiotic concept dates back over 100 years, but only in recent times have the scientific knowledge and tools become available to properly evaluate their effects on normal health and well being, and their potential in preventing and treating disease. A similar situation exists for prebiotics, defined by this group as non-digestible substances that provide a beneficial physiological effect on the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics function complementary to, and possibly synergistically with, probiotics. Numerous studies are providing insights into the growth and metabolic influence of these microbial nutrients on health. Today, the science behind the function of probiotics and prebiotics still requires more stringent deciphering both scientifically and mechanistically. The explosion of publications and interest in probiotics and prebiotics has resulted in a body of collective research that points toward great promise. However, this research is spread among such a diversity of organisms, delivery vehicles (foods, pills, and supplements), and potential health targets such that general conclusions cannot easily be made. Nevertheless, this situation is rapidly changing on a number of important fronts. With progress over the past decade on the genetics of lactic acid bacteria and the recent, 2,3 and pending, 4 release of complete genome sequences for major probiotic species, the field is now armed with detailed information and sophisticated microbiological and bioinformatic tools. Similarly, advances in biotechnology could yield new probiotics and prebiotics designed for enhanced or expanded functionality. The incorporation of genetic tools within a multidisciplinary scientific platform is expected to reveal the contributions of commensals, probiotics, and prebiotics to general health and well being and explicitly identify the mechanisms and corresponding host responses that provide the basis for their positive roles and associated claims. In terms of human suffering, the need for effective new approaches to prevent and treat disease is paramount. The need exists not only to alleviate the significant mortality and morbidity caused by intestinal diseases worldwide (especially diarrheal diseases in children), but also for infections at non-intestinal sites. This is especially worthy of pursuit in developing nations where mortality is too often the outcome of food and water borne infection. Inasmuch as probiotics and prebiotics are able to influence the populations or activities of commensal microflora, there is evidence that they can also play a role in mitigating some diseases. 5,6 Preliminary support that probiotics and prebiotics may be useful as intervention in conditions including inflammatory bowel disease, irritable bowel syndrome, allergy, cancer (especially colorectal cancer of which 75% are associated with diet), vaginal and urinary tract infections in women, kidney stone disease, mineral absorption, and infections caused by Helicobacter pylori is emerging. Some metabolites of microbes in the gut may also impact systemic conditions ranging from coronary heart disease to cognitive function, suggesting the possibility that exogenously applied microbes in the form of probiotics, or alteration of gut microecology with prebiotics, may be useful interventions even in these apparently disparate conditions. Beyond these direct intervention targets, probiotic cultures can also serve in expanded roles as live vehicles to deliver biologic agents (vaccines, enzymes, and proteins) to targeted locations within the body. The economic impact of these disease conditions in terms of diagnosis, treatment, doctor and hospital visits, and time off work exceeds several hundred billion dollars. The quality of life impact is also of major concern. Probiotics and prebiotics offer plausible opportunities to reduce the morbidity associated with these conditions. The following addresses issues that emerged from 8 workshops (Definitions, Intestinal Flora, Extra-Intestinal Sites, Immune Function, Intestinal Disease, Cancer, Genomics, and Second Generation Prebiotics), reflecting the current scientific state of probiotics and prebiotics. This is not a comprehensive review, however the study emphasizes pivotal knowledge gaps, and recommendations are made as to the underlying scientific and multidisciplinary studies that will be required to advance our understanding of the roles and impact of prebiotics, probiotics, and the commensal microflora upon health and disease management.

Meteorology and climate inspire secondary school students

As part of its National Science and Engineering Week activities in 2009 and 2010, the University of Reading organised two open days for 60 local key stage 4 pupils. The theme of both open days was ‘How do we predict weather and climate?’ Making use of the students’ familiarity with weather and climate, several concepts of relevance to secondary science were investigated. The open days also provided an opportunity for more than 30 research staff from the university to interact with the students. Feedback from students and teachers was extremely positive. This article shows how meteorological science can be used to illustrate elements of the secondary science and mathematics curricula.

Advances in mucoadhesion and mucoadhesive polymers

Mucoadhesion is the ability of materials to adhere to mucosal membranes in the human body and provide a temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal drug delivery. Excellent mucoadhesive properties are typical for hydrophilic polymers possessing charged groups and/or non-ionic functional groups capable of forming hydrogen bonds with mucosal surfaces. This feature article considers recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview on the structure of mucosal membranes, properties of mucus gels and the nature of mucoadhesion. It describes the most common methods to evaluate mucoadhesive properties of various dosage forms and discusses the main classes of mucoadhesives.

Peripersonal space: a multisensory interface for body-object interactions

Research in the last four decades has brought a considerable advance in our understanding of how the brain synthesizes information arising from different sensory modalities. Indeed, many cortical and subcortical areas, beyond those traditionally considered to be ‘associative,’ have been shown to be involved in multisensory interaction and integration (Ghazanfar and Schroeder 2006). Visuo-tactile interaction is of particular interest, because of the prominent role played by vision in guiding our actions and anticipating their tactile consequences in everyday life. In this chapter, we focus on the functional role that visuo-tactile processing may play in driving two types of body-object interactions: avoidance and approach. We will first review some basic features of visuo-tactile interactions, as revealed by electrophysiological studies in monkeys. These will prove to be relevant for interpreting the subsequent evidence arising from human studies. A crucial point that will be stressed is that these visuo-tactile mechanisms have not only sensory, but also motor-related activity that qualifies them as multisensory-motor interfaces. Evidence will then be presented for the existence of functionally homologous processing in the human brain, both from neuropsychological research in brain-damaged patients and in healthy participants. The final part of the chapter will focus on some recent studies in humans showing that the human motor system is provided with a multisensory interface that allows for continuous monitoring of the space near the body (i.e., peripersonal space). We further demonstrate that multisensory processing can be modulated on-line as a consequence of interacting with objects. This indicates that, far from being passive, the monitoring of peripersonal space is an active process subserving actions between our body and objects located in the space around us.

Placentation and maternal investment in mammals

The mammalian placenta exhibits striking interspecific morphological variation, yet the implications of such diversity for reproductive strategies and fetal development remain obscure. More invasive hemochorial placentas, in which fetal tissues directly contact the maternal blood supply, are believed to facilitate nutrient transfer, resulting in higher fetal growth rates, and to be a state of relative fetal advantage in the evolution of maternal-offspring conflict. The extent of interdigitation between maternal and fetal tissues has received less attention than invasiveness but is also potentially important because it influences the surface area for exchange. We show that although increased placental invasiveness and interdigitation are both associated with shorter gestations, interdigitation is the key variable. Gestation times associated with highly interdigitated labyrinthine placentas are 44% of those associated with less interdigitated villous and trabecular placentas. There is, however, no relationship between placental traits and neonatal body and brain size. Hence, species with more interdigitated placentas produce neonates of similar body and brain size but in less than half the time. We suggest that the effects of placental interdigitation on growth rates and the way that these are traded off against gestation length may be promising avenues for understanding the evolutionary dynamics of parentoffspring conflict. Keywords: placenta, parent-offspring conflict, life history, brain evolution, reproductive strategies, gestation.

Interregional migration 'wage premia': the case of creative and science and technology graduates in the UK

We analyze the migration behavior of graduates from UK universities with a focus on the salary benefits they receive from the migration process. We focus on sequential interregional migration and specifically examine the case of Science, Technology, Engineering and Mathematics (STEM) and Creative subject graduates. Our analysis differs from previous studies in that it accounts explicitly for migrant selectivity through propensity score matching, and it also classifies graduates into different migration behavior categories. Graduates were classified according to their sequential migration behavior first from their pre-university domicile to university and then from university to first job post-graduation. Our results show that ‘repeat migration’, as expected, is associated with the highest wage premium (around 15%). Other migration behaviors are also advantageous although this varies across different types of graduates. Creative graduates, for instance, do not benefit much from migration behaviors other than repeat migration. STEM graduates, on the contrary, benefit from both late migration and staying in the university area to work.

Many-body effect in electrorheological responses

The many-body effect in the kinetic responses of ER fluids is studied by a molecular-dynamic simulation method. The mutual polarization effects of the particles are considered by self-consistently calculating the dipole strength on each particle according to the external field and the dipole field due to all the other particles in the fluids. The many-body effect is found to increase with the enhancement of the particle concentration and the permittivity ratio between the solvent and the particles. The calculated response times are shorter than that predicted with the 'point-dipole' model and agree very well with experimental results. The many-body effect enhances the shear stresses of the fluids by several times. But they are not proportional to the many-body correction factor lambda as expected. This is due to the fact that larger interaction forces between the particles lead to coarsening of the fibers formed in the suspensions. The results show that the many-body and multipolar interaction between the particles must be treated comprehensively in the simulations in order to get more reliable results.

Rethinking disability theory and practice: challenging essentialism

This edited volume argues that even in recent Critical Disability Studies which have sought to critique essentialist assumptions in relation to Disability, nevertheless essentialisms remain which predetermine and predirect definitions and arguments in the field. This volume analyses such essentialisms in a wide range of areas such as childhood, gender, sexuality, reproduction, ADHD, autism, the animal, d/Deafness, hirsutism, the body, and vision. Particularly issues such as 'agency', 'voice' and 'body' are explored in terms of their political implications.