Lack of association between central adiposity and lipaemia in UK Sikh men

OBJECTIVE: To determine whether the positive statistical associations between measures of total and regional adiposity and measures of glucose, insulin and triacylglycerol ( TAG) metabolism reported in Caucasian men, are also observed in UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer provided a blood sample after a 12-h overnight fast and had anthropometric measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK Sikh men were recruited. The Caucasian and Sikh men were matched for age ( 48.7 +/- 10.9 and 48.3 +/- 10.0 y, respectively) and body mass index (BMI) ( 26.1 +/- 2.8 and 26.3 +/- 3.2 kg/m(2), respectively). MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat depots. The concentrations of plasma total cholesterol, high-density cholesterol (HDL- C), low-density cholesterol (LDL-C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA ( RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat, with the sum of the four skinfold measurements (Ssk) ( P = 0.0001) and subscapular skinfold value (P = 0.009) higher compared with the Caucasian men. The Sikh volunteers also had characteristics of the metabolic syndrome: lower HDL-C (P = 0.07), higher TAG (P = 0.004), higher % LDL3 (P = 0.0001) and insulin resistance (P = 0.05). Both ethnic groups demonstrated positive correlations between insulin and waist circumference (Caucasian: r = 0.661, P = 0.0001; Sikh: r = 0.477, P = 0.0001). The Caucasian men also demonstrated significant positive correlations between central adiposity (r = 0.275, P = 0.04), other measures of adiposity (BMI and suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation for central adiposity (r = 0.019, ns) and TAG with a trend to a negative relationship between other measures ( Ssk and suprailiac) which reached near significance for subscapular skinfold and TAG (r = - 0.246, P = 0.007). The expected positive association between insulin and TAG was observed in the Caucasian men (r = 0.318, P = 0.04) but not in the Sikh men (r = 0.011, ns). CONCLUSIONS: In the Caucasian men, the expected positive association between plasma TAG and centralized body fat was observed. However, a lack of association between centralized, or any other measure of adiposity, and plasma TAG was observed in the matched Sikh men, although both ethnic groups showed the positive association between centralized body fat and insulin resistance, which was less strong for Sikhs. These findings in the Sikh men were not consistent with the hypothesis that there is a clear causal relationship between body fat and its distribution, insulin resistance, and lipid abnormalities associated with the metabolic syndrome, in this ethnic group.

Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians

Background: Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white populations, and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Objective: The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome. Design: Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial. Volunteers were randomly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period. After this 6-wk period, both groups were supplemented with 4.0 g fish oil/d (2.5 g eicosapentaenoic acid + docosahexaenoic acid) for an additional 6 wk in combination with the dietary treatment. Volunteers participated in a postprandial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period. Results: There was no significant time X treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil. After the 6-wk period of fish oil supplementation, fasting and postprandial plasma triacylglycerol concentrations decreased significantly. Conclusion: The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group.

Lack of effect of dietary n-6 : n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Background: Indian Asians living in Western Countries have an over 50% increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim: To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods: Twenty-nine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL- cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results: Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n-3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/22.5] (P = 0.02) reaching significance. Conclusion: The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia.

Validation of short tandem repeat analysis for the investigation of cases of disputed paternity

This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.

Inheritance, access to resources and poverty in Serer families in Senegal

This research explores the relationship between inheritance, access to resources and the intergenerational transmission of poverty among the Serer ethnic group in rural and urban environments in Senegal. In many Sub-Saharan African countries, customary law excludes women from owning and inheriting assets, such as land and property. Yet, assets controlled by women often result in increased investments in the next generation's health, nutrition and schooling and reduce the intergenerational transmission of poverty. Qualitative research with 60 participants in Senegal reveals the important role that land, housing and financial assets may play in building resilience to household shocks and interrupting the intergenerational transmission of poverty. However, the protection afforded by these assets was often dependent on other factors, including human, social and environmental capital. The death of a spouse or parent had major emotional and material impacts on many Serer families. The inheritance and control of assets and resources was strongly differentiated among family members along lines of gender, age and generation. Younger widows and their children were particularly vulnerable to chronic poverty. Although inheritance disputes were rare, the research suggests they are more likely between co-wives in polygamous unions and their children, particularly in urban areas. In addition to experiencing economic and health-related shocks, many interviewees were exposed to a range of climate-related risks and environmental pressures which increased their vulnerability. Family members coped with these shocks and risks by diversifying livelihoods, migrating to urban areas and other regions for work, participating in women's co-operatives and associations and developing supportive social networks with extended family and community members. Policies and practices that may help to alleviate poverty, safeguard women's and young people's inheritance and build resilience to financial, health-related and environmental shocks and risks include: - Social protection measures targeted towards poor widows and orphaned children, such as social and cash transfers to pay for basic needs including food, healthcare and children's schooling. - Micro-finance initiatives and credit and savings schemes, alongside training and capacity-building targeted to women and young people to develop income-generation activities and skills. - Free legal advice, support and advocacy for women and young people to pursue inheritance claims through the legal system. - Raising awareness about women's and children's legal rights and working with government and community and religious leaders to tackle discriminatory inheritance practices and contradictions caused by legal pluralism. - Increasing women's control of land and access to inputs, enhancing their business, organisational, and leadership skills and promoting civic participation in local, regional and national decision-making processes. - Improving access to basic services in rural areas, particularly healthcare, building the quality of education and promoting girls' access to education - Enhancing agricultural production and providing more employment opportunities, apprenticeships and vocational training for young people, particularly in rural areas.

Achieving market segmentation from B2B sectorisation

Purpose – The creation of a target market strategy is integral to developing an effective business strategy. The concept of market segmentation is often cited as pivotal to establishing a target market strategy, yet all too often business-to-business marketers utilise little more than trade sectors or product groups as the basis for their groupings of customers, rather than customers' characteristics and buying behaviour. The purpose of this paper is to offer a solution for managers, focusing on customer purchasing behaviour, which evolves from the organisation's existing criteria used for grouping its customers. Design/methodology/approach – One of the underlying reasons managers fail to embrace best practice market segmentation is their inability to manage the transition from how target markets in an organisation are currently described to how they might look when based on customer characteristics, needs, purchasing behaviour and decision-making. Any attempt to develop market segments should reflect the inability of organisations to ignore their existing customer group classification schemes and associated customer-facing operational practices, such as distribution channels and sales force allocations. Findings – A straightforward process has been derived and applied, enabling organisations to practice market segmentation in an evolutionary manner, facilitating the transition to customer-led target market segments. This process also ensures commitment from the managers responsible for implementing the eventual segmentation scheme. This paper outlines the six stages of this process and presents an illustrative example from the agrichemicals sector, supported by other cases. Research implications – The process presented in this paper for embarking on market segmentation focuses on customer purchasing behaviour rather than business sectors or product group classifications - which is true to the concept of market segmentation - but in a manner that participating managers find non-threatening. The resulting market segments have their basis in the organisation's existing customer classification schemes and are an iteration to which most managers readily buy-in. Originality/value – Despite the size of the market segmentation literature, very few papers offer step-by-step guidance for developing customer-focused market segments in business-to-business marketing. The analytical tool for assessing customer purchasing deployed in this paper originally was created to assist in marketing planning programmes, but has since proved its worth as the foundation for creating segmentation schemes in business marketing, as described in this paper.

Soil phosphorus supply affects nodulation and N:P ratio in 11 perennial legume seedlings

Developing new perennial pasture legumes for low-P soils is a priority for Australian Mediterranean agro-ecosystems, where soil P availability is naturally low. As legumes tend to require higher P inputs than non-legumes, the ability of these plants to fix N2 under varying soil P levels must be determined. Therefore, the objective of this study was to investigate the influence of soil P supply on plant N status and nodule formation in 11 perennial legumes, including some novel pasture species. We investigated the effect of applying soil P, ranging from 0 to 384 μg P/g dry soil, on plant N status and nodulation in a glasshouse. Without exogenous P supply, shoot N concentration and N : P ratio were higher than at 6 μg P/g soil. Shoot N concentration and N : P ratio then changed little with further increase in P supply. There was a close positive correlation between the number of nodules and shoot P concentration in 7 of the 11 species. Total nodule dry weight and the percentage of plant dry weight that consisted of nodules increased when P supply increased from 6 to 48 μg P/g. Without exogenous P addition, N : P ratios partitioned into a two-group distribution, with species having a N : P ratio of either >70 or <50 g/g. We suggest that plants with a high N : P ratio may take up N from the soil constitutively, while those with a low N : P ratio may regulate their N uptake in relation to internal P concentration. The flexibility of the novel pasture legumes in this study to adjust their leaf N concentrations under different levels of soil P supplements other published evidence of good growth and high P uptake and P-use efficiency under low soil P supply and suggests their potential as pasture plants in low-P soils in Australian Mediterranean agro-ecosystems warrants further attention.

Gender, childhood and children’s literature: the CIRCL approach

This paper explores the unique approach to childhood and children’s literature of the research and teaching of the ‘Graduate Centre for International Research in Childhood: Literature, Culture, Media (CIRCL)’. CIRCL follows in its work the arguments of UK critical theorist Jacqueline Rose in her seminal 1984 book The case of Peter Pan or the impossibility of children’s fiction. Rose’s work has been widely and routinely referenced in Children’s Literature studies particularly, but CIRCL interprets her arguments as having quite different implications than those usually assumed. Rose is generally attributed with having pointed out that ‘childhood’ is not one, homogenous category, but that childhood is divided by gender, race, and ethnic, political and religious (and so on) identities. But for CIRCL this is only a first step in Rose’s arguments and certainly one not unique to her work anyway: the perception of various cultural and historical childhoods is widely held. Instead, my paper explores how Rose’s arguments are centrally about how ‘childhood’ itself cannot be maintained in the face of division, a division, moreover, which operates inevitably at every level, and which derives from Rose’s interpretation of psychoanalysis as formulated by Sigmund Freud, which Rose derives in turn from her readings of the interpretations of Freud by French analyst Jacques Lacan and French critical theorist Jacques Derrida. Finally, my paper argues how Rose’s position is about any ‘identity’, including gender and that this allies her work closely to that of the famous gender theorist Judith Butler, whose arguments are often (mis) understood in the same ways as those of Rose.

Does changing the taxonomical resolution alter the value of soil macroinvertebrates as bioindicators of metal pollution?

Ecological indicators are taxa that are affected by, and indicate effects of, anthropogenic environmental stress or disturbance on ecosystems. There is evidence that some species of soil macrofauna (i.e. diameter > 2 min) constitute valuable biological indicators of certain types of soil perturbations. This study aims to determine which level of taxonomic resolution, (species, family or ecological group) is the best to identify indicator of soil disturbance. Macrofauna were sampled in a set of sites encompassing different land-use systems (e.g. forests, pastures, crops) and different levels of pollution. Indicator taxa were sought using the IndVal index proposed by Dufrene and Legendre [Dufrene, M., Legendre, P., 1997. Species assemblages and indicator species: the need for a flexible asymetrical approach. Ecological Monographs 67, 345-3661. This approach is based on a hierarchical typology of sites. The index value changes along the typology and decreases (increases) for generalist (specialist) faunal units (species, families or ecological groups). Of the 327 morphospecies recorded, 19 were significantly associated with a site type or a group of sites (5.8%). Similarly, species were aggregated to form 59 families among which 17 (28.8%) displayed a significant indicator value. Gathering species into 28 broad ecological assemblages led to 14 indicator groups (50%). Beyond the simple proportion of units having significant association with a given level of the site typology, the proportion of specialist and generalist groups changed dramatically when the level of taxonomic resolution was altered. At the species level 84% of the indicator units were specialist, whereas this proportion decreased to 70 and 43% when families and ecological groups were considered. Because specialist groups are the most interesting type of indicators either in terms of conservation or for management purposes we come to the conclusion that the species level is the most accurate taxonomic level in bioindication studies although it requires a high amount of labour and operator knowledge and is time-consuming. (c) 2005 Published by Elsevier Ltd.

Implicit and explicit processes in a second-language learning task

Two experiments examined the learning of a set of Greek pronunciation rules through explicit and implicit modes of rule presentation. Experiment 1 compared the effectiveness of implicit and explicit modes of presentation in two modalities, visual and auditory. Subjects in the explicit or rule group were presented with the rule set, and those in the implicit or natural group were shown a set of Greek words, composed of letters from the rule set, linked to their pronunciations. Subjects learned the Greek words to criterion and were then given a series of tests which aimed to tap different types of knowledge. The results showed an advantage of explicit study of the rules. In addition, an interaction was found between mode of presentation and modality. Explicit instruction was more effective in the visual than in the auditory modality, whereas there was no modality effect for implicit instruction. Experiment 2 examined a possible reason for the advantage of the rule groups by comparing different combinations of explicit and implicit presentation in the study and learning phases. The results suggested that explicit presentation of the rules is only beneficial when it is followed by practice at applying them.

Iron Uptake and Homeostasis in Microorganisms

Preface. Iron is considered to be a minor element employed, in a variety of forms, by nearly all living organisms. In some cases, it is utilised in large quantities, for instance for the formation of magnetosomes within magnetotactic bacteria or during use of iron as a respiratory donor or acceptor by iron oxidising or reducing bacteria. However, in most cases the role of iron is restricted to its use as a cofactor or prosthetic group assisting the biological activity of many different types of protein. The key metabolic processes that are dependent on iron as a cofactor are numerous; they include respiration, light harvesting, nitrogen fixation, the Krebs cycle, redox stress resistance, amino acid synthesis and oxygen transport. Indeed, it is clear that Life in its current form would be impossible in the absence of iron. One of the main reasons for the reliance of Life upon this metal is the ability of iron to exist in multiple redox states, in particular the relatively stable ferrous (Fe2+) and ferric (Fe3+) forms. The availability of these stable oxidation states allows iron to engage in redox reactions over a wide range of midpoint potentials, depending on the coordination environment, making it an extremely adaptable mediator of electron exchange processes. Iron is also one of the most common elements within the Earth’s crust (5% abundance) and thus is considered to have been readily available when Life evolved on our early, anaerobic planet. However, as oxygen accumulated (the ‘Great oxidation event’) within the atmosphere some 2.4 billion years ago, and as the oceans became less acidic, the iron within primordial oceans was converted from its soluble reduced form to its weakly-soluble oxidised ferric form, which precipitated (~1.8 billion years ago) to form the ‘banded iron formations’ (BIFs) observed today in Precambrian sedimentary rocks around the world. These BIFs provide a geological record marking a transition point away from the ancient anaerobic world towards modern aerobic Earth. They also indicate a period over which the bio-availability of iron shifted from abundance to limitation, a condition that extends to the modern day. Thus, it is considered likely that the vast majority of extant organisms face the common problem of securing sufficient iron from their environment – a problem that Life on Earth has had to cope with for some 2 billion years. This struggle for iron is exemplified by the competition for this metal amongst co-habiting microorganisms who resort to stealing (pirating) each others iron supplies! The reliance of micro-organisms upon iron can be disadvantageous to them, and to our innate immune system it represents a chink in the microbial armour, offering an opportunity that can be exploited to ward off pathogenic invaders. In order to infect body tissues and cause disease, pathogens must secure all their iron from the host. To fight such infections, the host specifically withdraws available iron through the action of various iron depleting processes (e.g. the release of lactoferrin and lipocalin-2) – this represents an important strategy in our defence against disease. However, pathogens are frequently able to deploy iron acquisition systems that target host iron sources such as transferrin, lactoferrin and hemoproteins, and thus counteract the iron-withdrawal approaches of the host. Inactivation of such host-targeting iron-uptake systems often attenuates the pathogenicity of the invading microbe, illustrating the importance of ‘the battle for iron’ in the infection process. The role of iron sequestration systems in facilitating microbial infections has been a major driving force in research aimed at unravelling the complexities of microbial iron transport processes. But also, the intricacy of such systems offers a challenge that stimulates the curiosity. One such challenge is to understand how balanced levels of free iron within the cytosol are achieved in a way that avoids toxicity whilst providing sufficient levels for metabolic purposes – this is a requirement that all organisms have to meet. Although the systems involved in achieving this balance can be highly variable amongst different microorganisms, the overall strategy is common. On a coarse level, the homeostatic control of cellular iron is maintained through strict control of the uptake, storage and utilisation of available iron, and is co-ordinated by integrated iron-regulatory networks. However, much yet remains to be discovered concerning the fine details of these different iron regulatory processes. As already indicated, perhaps the most difficult task in maintaining iron homeostasis is simply the procurement of sufficient iron from external sources. The importance of this problem is demonstrated by the plethora of distinct iron transporters often found within a single bacterium, each targeting different forms (complex or redox state) of iron or a different environmental condition. Thus, microbes devote considerable cellular resource to securing iron from their surroundings, reflecting how successful acquisition of iron can be crucial in the competition for survival. The aim of this book is provide the reader with an overview of iron transport processes within a range of microorganisms and to provide an indication of how microbial iron levels are controlled. This aim is promoted through the inclusion of expert reviews on several well studied examples that illustrate the current state of play concerning our comprehension of how iron is translocated into the bacterial (or fungal) cell and how iron homeostasis is controlled within microbes. The first two chapters (1-2) consider the general properties of microbial iron-chelating compounds (known as ‘siderophores’), and the mechanisms used by bacteria to acquire haem and utilise it as an iron source. The following twelve chapters (3-14) focus on specific types of microorganism that are of key interest, covering both an array of pathogens for humans, animals and plants (e.g. species of Bordetella, Shigella, , Erwinia, Vibrio, Aeromonas, Francisella, Campylobacter and Staphylococci, and EHEC) as well as a number of prominent non-pathogens (e.g. the rhizobia, E. coli K-12, Bacteroides spp., cyanobacteria, Bacillus spp. and yeasts). The chapters relay the common themes in microbial iron uptake approaches (e.g. the use of siderophores, TonB-dependent transporters, and ABC transport systems), but also highlight many distinctions (such as use of different types iron regulator and the impact of the presence/absence of a cell wall) in the strategies employed. We hope that those both within and outside the field will find this book useful, stimulating and interesting. We intend that it will provide a source for reference that will assist relevant researchers and provide an entry point for those initiating their studies within this subject. Finally, it is important that we acknowledge and thank wholeheartedly the many contributors who have provided the 14 excellent chapters from which this book is composed. Without their considerable efforts, this book, and the understanding that it relays, would not have been possible. Simon C Andrews and Pierre Cornelis

Climate change and coastal waterbird populations – past declines and future impacts

Considerable attention has been given to the impact of climate change on avian populations over the last decade. In this paper we examine two issues with respect to coastal bird populations in the UK: (1) is there any evidence that current populations are declining due to climate change, and (2) how might we predict the response of populations in the future? We review the cause of population decline in two species associated with saltmarsh habitats. The abundance of Common Redshank Tringa totanus breeding on saltmarsh declined by about 23% between the mid-1980s and mid-1990s, but the decline appears to have been caused by an increase in grazing pressure. The number of Twite Carduelis flavirostris wintering on the coast of East Anglia has declined dramatically over recent decades; there is evidence linking this decline with habitat loss but a causal role for climate change is unclear. These examples illustrate that climate change could be having population-level impacts now, but also show that it is dangerous to become too narrowly focused on single issues affecting coastal birds. Making predictions about how populations might respond to future climate change depends on an adequate understanding of important ecological processes at an appropriate spatial scale. We illustrate this with recent work conducted on the Icelandic population of Black-tailed Godwits Limosa limosa islandica that shows large-scale regulatory processes. Most predictive models to date have focused on local populations (single estuary or a group of neighbouring estuaries). We discuss the role such models might play in risk assessment, and the need for them to be linked to larger-scale ecological processes. We argue that future work needs to focus on spatial scale issues and on linking physical models of coastal environments with important ecological processes.

Glycogen phosphorylase inhibitors: a free energy perturbation analysis of glucopyranose spirohydantoin analogues

GP catalyzes the phosphorylation of glycogen to Glc-1-P. Because of its fundamental role in the metabolism of glycogen, GP has been the target for a systematic structure-assisted design of inhibitory compounds, which could be of value in the therapeutic treatment of type 2 diabetes mellitus. The most potent catalytic-site inhibitor of GP identified to date is spirohydantoin of glucopyranose (hydan). In this work, we employ MD free energy simulations to calculate the relative binding affinities for GP of hydan and two spirohydantoin analogues, methyl-hydan and n-hydan, in which a hydrogen atom is replaced by a methyl- or amino group, respectively. The results are compared with the experimental relative affinities of these ligands, estimated by kinetic measurements of the ligand inhibition constants. The calculated binding affinity for methyl-hydan (relative to hydan) is 3.75 +/- 1.4 kcal/mol, in excellent agreement with the experimental value (3.6 +/- 0.2 kcal/mol). For n-hydan, the calculated value is 1.0 +/- 1.1 kcal/mol, somewhat smaller than the experimental result (2.3 +/- 0.1 kcal/mol). A free energy decomposition analysis shows that hydan makes optimum interactions with protein residues and specific water molecules in the catalytic site. In the other two ligands, structural perturbations of the active site by the additional methyl- or amino group reduce the corresponding binding affinities. The computed binding free energies are sensitive to the preference of a specific water molecule for two well-defined positions in the catalytic site. The behavior of this water is analyzed in detail, and the free energy profile for the translocation of the water between the two positions is evaluated. The results provide insights into the role of water molecules in modulating ligand binding affinities. A comparison of the interactions between a set of ligands and their surrounding groups in X-ray structures is often used in the interpretation of binding free energy differences and in guiding the design of new ligands. For the systems in this work, such an approach fails to estimate the order of relative binding strengths, in contrast to the rigorous free energy treatment.

Climate change and coastal waterbird populations - past declines and future impacts

Considerable attention has been given to the impact of climate change on avian populations over the last decade. In this paper we examine two issues with respect to coastal bird populations in the UK: (1) is there any evidence that current populations are declining due to climate change, and (2) how might we predict the response of populations in the future? We review the cause of population decline in two species associated with saltmarsh habitats. The abundance of Common Redshank Tringa totanus breeding on saltmarsh declined by about 23% between the mid-1980s and mid-1990s, but the decline appears to have been caused by an increase in grazing pressure. The number of Twite Carduelis flavirostris wintering on the coast of East Anglia has declined dramatically over recent decades; there is evidence linking this decline with habitat loss but a causal role for climate change is unclear. These examples illustrate that climate change could be having population-level impacts now, but also show that it is dangerous to become too narrowly focused on single issues affecting coastal birds. Making predictions about how populations might respond to future climate change depends on an adequate understanding of important ecological processes at an appropriate spatial scale. We illustrate this with recent work conducted on the Icelandic population of Black-tailed Godwits Limosa limosa islandica that shows large-scale regulatory processes. Most predictive models to date have focused on local populations (single estuary or a group of neighbouring estuaries). We discuss the role such models might play in risk assessment, and the need for them to be linked to larger-scale ecological processes. We argue that future work needs to focus on spatial scale issues and on linking physical models of coastal environments with important ecological processes.

Are definitions of adiposity appropriate for identification of cardiovascular disease risk in South Asian populations?

South Asian populations living in the UK have a high prevalence of the metabolic syndrome, cardiovascular disease (CVD) and type 2 diabetes which impacts greatly on the morbidity and mortality of this ethnic group. The identification of ‘at risk’ individuals is essential to initiate reventative treatment. However, this is considerably hindered by the lack of appropriate cut-off values for anthropometric measures. CVD risk is significantly higher at a lower body mass index (BMI) in many Asian groups compared with Caucasians and adiposity (particularly central deposition) is higher at similar BMI levels. The definition of adiposity in Asians needs to be firmly established and appropriate lower BMI and waist circumference cut-offs implemented in ethnic subpopulations to facilitate appropriate treatment strategies.