Showing papers by "University of Aberdeen published in 2006"

Archaea predominate among ammonia-oxidizing prokaryotes in soils

Abstract: Ammonia oxidation is the first step in nitrification, a key process in the global nitrogen cycle that results in the formation of nitrate through microbial activity. The increase in nitrate availability in soils is important for plant nutrition, but it also has considerable impact on groundwater pollution owing to leaching. Here we show that archaeal ammonia oxidizers are more abundant in soils than their well-known bacterial counterparts. We investigated the abundance of the gene encoding a subunit of the key enzyme ammonia monooxygenase (amoA) in 12 pristine and agricultural soils of three climatic zones. amoA gene copies of Crenarchaeota (Archaea) were up to 3,000-fold more abundant than bacterial amoA genes. High amounts of crenarchaeota-specific lipids, including crenarchaeol, correlated with the abundance of archaeal amoA gene copies. Furthermore, reverse transcription quantitative PCR studies and complementary DNA analysis using novel cloning-independent pyrosequencing technology demonstrated the activity of the archaea in situ and supported the numerical dominance of archaeal over bacterial ammonia oxidizers. Our results indicate that crenarchaeota may be the most abundant ammonia-oxidizing organisms in soil ecosystems on Earth.

The restless mind

Abstract: This article reviews the hypothesis that mind wandering can be integrated into executive models of attention. Evidence suggests that mind wandering shares many similarities with traditional notions of executive control. When mind wandering occurs, the executive components of attention appear to shift away from the primary task, leading to failures in task performance and superficial representations of the external environment. One challenge for incorporating mind wandering into standard executive models is that it often occurs in the absence of explicit intention--a hallmark of controlled processing. However, mind wandering, like other goal-related processes, can be engaged without explicit awareness; thus, mind wandering can be seen as a goal-driven process, albeit one that is not directed toward the primary task.

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN

Abstract: Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.

The evolutionary ecology of the major histocompatibility complex.

Abstract: The major histocompatibility complex (MHC) has become a paradigm for how selection can act to maintain adaptively important genetic diversity in natural populations. Here, we review the contribution of studies on the MHC in non-model species to our understanding of how selection affects MHC diversity, emphasising how ecological and ethological processes influence the tempo and mode of evolution at the MHC, and conversely, how variability at the MHC affects individual fitness, population dynamics and viability. We focus on three main areas: the types of information that have been used to detect the action of selection on MHC genes; the relative contributions of parasite-mediated and sexual selection on the maintenance of MHC diversity; and possible future lines of research that may help resolve some of the unanswered issues associated with MHC evolution.

What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies.

Abstract: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.

Thrombophilia in pregnancy: a systematic review

Abstract: Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Subtropical Arctic Ocean temperatures during the Palaeocene/Eocene thermal maximum

Abstract: The Palaeocene/Eocene thermal maximum, ~55 million years ago, was a brief period of widespread, extreme climatic warming1, 2, 3, that was associated with massive atmospheric greenhouse gas input4. Although aspects of the resulting environmental changes are well documented at low latitudes, no data were available to quantify simultaneous changes in the Arctic region. Here we identify the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence obtained during the Arctic Coring Expedition5. We show that sea surface temperatures near the North Pole increased from ~18 °C to over 23 °C during this event. Such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming. At the same time, sea level rose while anoxic and euxinic conditions developed in the ocean's bottom waters and photic zone, respectively. Increasing temperature and sea level match expectations based on palaeoclimate model simulations6, but the absolute polar temperatures that we derive before, during and after the event are more than 10 °C warmer than those model-predicted. This suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms—perhaps polar stratospheric clouds7 or hurricane-induced ocean mixing8—to amplify early Palaeogene polar temperatures.

Functional Specialization within Rostral Prefrontal Cortex (Area 10): A Meta-analysis

Abstract: One of the least well understood regions of the human brain is rostral prefrontal cortex, approximating Brodmann's area 10. Here, we investigate the possibility that there are functional subdivisions within this region by conducting a meta-analysis of 104 functional neuroimaging studies (using positron emission tomography/functional magnetic resonance imaging). Studies involving working memory and episodic memory retrieval were disproportionately associated with lateral activations, whereas studies involving mentalizing (i.e., attending to one's own emotions and mental states or those of other agents) were disproportionately associated with medial activations. Functional variation was also observed along a rostral-caudal axis, with studies involving mentalizing yielding relatively caudal activations and studies involving multiple-task coordination yielding relatively rostral activations. A classification algorithm was trained to predict the task, given the coordinates of each activation peak. Performance was well above chance levels (74% for the three most common tasks; 45% across all eight tasks investigated) and generalized to data not included in the training set. These results point to considerable functional segregation within rostral prefrontal cortex.

Corneal avascularity is due to soluble VEGF receptor-1

Abstract: Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

Cannabinoid pharmacology: the first 66 years

Abstract: Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB1 and CB2 receptors and of endogenous ligands for these receptors, to the development of CB1- and CB2-selective agonists and antagonists and to the realization that the endogenous cannabinoid systemhas significant roles in both health and disease, and that drugs which mimic, augment or block the actions of endogenously released cannabinoids must have important therapeutic applications. Some goals for future research are identified. British Journal of Pharmacology (2006) 147, S163–S171. doi:10.1038/sj.bjp.0706406

Molecular mechanisms of action of bisphosphonates: current status.

Abstract: Purpose: Bisphosphonates are currently the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia. These compounds have high affinity for calcium ions and therefore target bone mineral, where they are internalized by bone-resorbing osteoclasts and inhibit osteoclast function. Experimental Design: This article reviews the pharmacology of bisphosphonates and the relationship between chemical structure and antiresorptive potency. We also describe new insights into their intracellular molecular mechanisms of action, methods for assessing the effects of bisphosphonates on protein prenylation, and their potential as direct antitumor agents. Results: Nitrogen-containing bisphosphonates act intracellularly by inhibiting farnesyl diphosphate synthase, an enzyme of the mevalonate pathway, thereby preventing prenylation of small GTPase signaling proteins required for normal cellular function. Inhibition of farnesyl diphosphate synthase also seems to account for their antitumor effects observed in vitro and for the activation of γ,δ T cells, a feature of the acute-phase response to bisphosphonate treatment in humans. Bisphosphonates that lack a nitrogen in the chemical structure do not inhibit protein prenylation and have a different mode of action that seems to involve primarily the formation of cytotoxic metabolites in osteoclasts. Conclusions: Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts in vivo but could also have direct effects on other cell types, such as tumor cells. After >30 years of clinical use, their molecular mechanisms of action on osteoclasts are finally becoming clear but their exact antitumor properties remain to be clarified.

Strategy as Practical Coping: A Heideggerian Perspective

Abstract: What strategic actors actually do in practice has become increasingly the focus of strategy research in recent years. This paper argues that, in furthering such practice-based views of strategy, we need a more adequate re-conceptualization of agency, action and practice and how they interrelate. We draw from the work of the continental philosopher Martin Heidegger to articulate a relational theory of human agency that is better suited to explaining everyday purposive actions and practices. Specifically, we argue that the dominant ‘building’ mode of strategizing that configures actors (whether individual or organizational) as distinct entities deliberately engaging in purposeful strategic activities derives from a more basic ‘dwelling’ mode in which strategy emerges non-deliberately through everyday practical coping. Whereas, from the building perspective, strategy is predicated upon the prior conception of plans that are then orchestrated to realize desired outcome, from a dwelling perspective strategy do...

The Cenozoic palaeoenvironment of the Arctic Ocean.

Abstract: The history of the Arctic Ocean during the Cenozoic era (0–65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm ‘greenhouse’ world, during the late Palaeocene and early Eocene epochs, to a colder ‘icehouse’ world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent ~14 Myr, we find sedimentation rates of 1–2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (~3.2 Myr ago) and East Antarctic ice (~14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (~45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at ~49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (~55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

Increase in Rice Grain Arsenic for Regions of Bangladesh Irrigating Paddies with Elevated Arsenic in Groundwaters

Abstract: Concern has been raised by Bangladeshi and international scientists about elevated levels of arsenic in Bengali food, particularly in rice grain. This is the first inclusive food market-basket survey from Bangladesh, which addresses the speciation and concentration of arsenic in rice, vegetables, pulses, and spices. Three hundred thirty aman and boro rice, 94 vegetables, and 50 pulse and spice samples were analyzed for total arsenic, using inductivity coupled plasma mass spectrometry (ICP-MS). The districts with the highest mean arsenic rice grain levels were all from southwestern Bangladesh: Faridpur (boro) 0.51 > Satkhira (boro) 0.38 > Satkhira (aman) 0.36 > Chuadanga (boro) 0.32 > Meherpur (boro) 0.29 microg As g(-1). The vast majority of food ingested arsenic in Bangladesh diets was found to be inorganic; with the predominant species detected in Bangladesh rice being arsenite (AsIII) or arsenate (AsV) with dimethyl arsinic acid (DMAV) being a minor component. Vegetables, pulses, and spices are less important to total arsenic intake than water and rice. Predicted inorganic arsenic intake from rice is modeled with the equivalent intake from drinking water for a typical Bangladesh diet. Daily consumption of rice with a total arsenic level of 0.08 microg As g(-1) would be equivalent to a drinking water arsenic level of 10 microg L(-1).

Development of a rating system for surgeons' non-technical skills.

Abstract: BACKGROUND Analyses of adverse events in surgery reveal that many underlying causes are behavioural, such as communication failure, rather than technical. Non-technical (i.e. cognitive and interpersonal) skills are not addressed explicitly in surgical training. However, surgeons need to demonstrate these skills, which underpin their technical excellence, to maximise patient safety in the operating theatre. This paper describes the method used to identify surgeons' non-technical skills, and the development of a skills taxonomy and behavioural rating system to structure observation and feedback in surgical training. METHODS Cognitive task analyses (critical incident interviews) were conducted with 27 consultant surgeons in general, cardiac and orthopaedic surgery. The interviews were coded and a multidisciplinary group of surgeons and psychologists used an iterative process to develop a skills taxonomy. This was supported by data gathered from an attitude survey, literature review, analysis of surgical mortality reports and observations in theatre. RESULTS Five categories of non-technical skills were identified, including situation awareness, decision making, task management, leadership and communication and teamwork. This provided a structure for a prototype skill taxonomy (v1.1), which comprised 14 non-technical skill elements. Observable behaviours (markers) indicative of good and poor performance were developed for each element by 16 consultant surgeons to form a prototype behaviour rating system. CONCLUSIONS The prototype skills taxonomy and behaviour rating system are grounded empirically in surgery. The reliability of the system is currently being tested using standardised scenarios. If this evaluation proves successful, the system could be used to structure feedback and guide non-technical skills training.

The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs.

Abstract: Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting >50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. FPPS, a key branchpoint of the mevalonate pathway, catalyzes the successive condensation of isopentenyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. To understand the molecular events involved in inhibition of FPPS by N-BPs, we used protein crystallography, enzyme kinetics, and isothermal titration calorimetry. We report here high-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use. These agents bind to the dimethylallyl/geranyl pyrophosphate ligand pocket and induce a conformational change. The interactions of the N-BP cyclic nitrogen with Thr-201 and Lys-200 suggest that these inhibitors achieve potency by positioning their nitrogen in the proposed carbocation-binding site. Kinetic analyses reveal that inhibition is competitive with geranyl pyrophosphate and is of a slow, tight binding character, indicating that isomerization of an initial enzyme–inhibitor complex occurs with inhibitor binding. Isothermal titration calorimetry indicates that binding of N-BPs to the apoenzyme is entropy-driven, presumably through desolvation entropy effects. These experiments reveal the molecular binding characteristics of an important pharmacological target and provide a route for further optimization of these important drugs.

The pharmacology of cannabinoid receptors and their ligands: an overview.

Abstract: Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2, both G protein coupled. CB1 receptors are found predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors occur mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous agonists for cannabinoid receptors also exist, and are all eicosanoids. The first-discovered of these 'endocannabinoids' was arachidonoylethanolamide and there is convincing evidence that this ligand and some of its metabolites can activate vanilloid VRI (TRPV1) receptors. Certain cannabinoids also appear to have TRPV1-like and/or non-CB1, non-CB2, non-TRPV1 targets. Several CB1- and CB2-selective agonists and antagonists have been developed. Antagonists include the CB1-selective SR141716A, AM251, AM281 and LY320135, and the CB2-selective SR144528 and AM630. These all behave as inverse agonists, one indication that CB1 and CB2 receptors can exist in a constitutively active state. 'Neutral' cannabinoid receptor antagonists have also been developed. CB1 and/or CB2 receptor activation appears to ameliorate inflammatory and neuropathic pain and certain multiple sclerosis symptoms. This might be exploited clinically by using CB1, CB2 or CB1/CB2 agonists, or inhibitors of the membrane transport or catabolism of endocannabinoids that are released in increased amounts, at least in animal models of pain and multiple sclerosis. We have recently discovered the presence of an allosteric site on the CB1 receptor. Consequently, it may also prove possible to enhance 'autoprotective' effects of released endocannabinoids with CB1 allosteric enhancers or, indeed, to reduce proposed 'autoimpairing' effects of released endocannabinoids such as excessive food intake with CB1 allosteric antagonists.

Energy crops: current status and future prospects

Abstract: Energy crops currently contribute a relatively small proportion to the total energy produced from biomass each year, but the proportion is set to grow over the next few decades. This paper reviews the current status of energy crops and their conversion technologies, assesses their potential to contribute to global energy demand and climate mitigation over the next few decades, and examines the future prospects. Previous estimates have suggested a technical potential for energy crops of?400?EJ?yr?1 by 2050. In a new analysis based on energy crop areas for each of the IPCC SRES scenarios in 2025 (as projected by the IMAGE 2.2 integrated assessment model), more conservative dry matter and energy yield estimates and an assessment of the impact on non-CO2 greenhouse gases were used to estimate the realistically achievable potential for energy crops by 2025 to be between 2 and 22?EJ?yr?1, which will offset?100-2070?Mt?CO2-eq.?yr?1. These results suggest that additional production of energy crops alone is not sufficient to reduce emissions to meet a 550??mol?mol?1 atmospheric CO2 stabilization trajectory, but is sufficient to form an important component in a portfolio of climate mitigation measures, as well as to provide a significant sustainable energy resource to displace fossil fuel resources. Realizing the potential of energy crops will necessitate optimizing the dry matter and energy yield of these crops per area of land through the latest biotechnological routes, with or without the need for genetic modification. In future, the co-benefits of bioenergy production will need to be optimized and methods will need to be developed to extract and refine high-value products from the feedstock before it is used for energy production.

Rethinking the Animate, Re-Animating Thought

Abstract: Animism is often described as the imputation of life to inert objects. Such imputation is more typical of people in western societies who dream of fi nding life on other planets than of indigenous peoples to whom the label of animism has classically been applied. These peoples are united not in their beliefs but in a way of being that is alive and open to a world in continuous birth. In this animic ontology, beings do not propel themselves across a ready-made world but rather issue forth through a world-in-formation, along the lines of their relationships. To its inhabitants this weather-world, embracing both sky and earth, is a source of astonishment but not surprise. Re-animating the 'western' tradition of thought means recovering the sense of astonishment banished from offi cial science.

Action plans and coping plans for physical exercise: A longitudinal intervention study in cardiac rehabilitation.

Abstract: Objectives. The aim of the present study was to test two brief planning interventions designed to encourage cardiac patients to engage in regular physical exercise following discharge from rehabilitation. The interventions comprised action plans on (a) when, where, and how to act, and (b) coping plans on how to deal with anticipated barriers. Design and method. An experimental longitudinal trial was conducted to test two interventions that either focused on action planning alone, or on a combination of action planning and coping planning. A total of 21 I participants completed assessments at baseline and 2 months after discharge. Participants were randomly assigned to either one of the intervention groups or a standard-care control group. Results. Participants in the combined planning group did significantly more physical exercise 2 months post-discharge than those in the other groups. Conclusions. The theoretical distinction between action planning and coping planning as introduced in the present study has proven useful in explaining changes in health-related behaviour. The combined planning intervention can be applied in the context of cardiac rehabilitation programmes. 23 The adoption and maintenance of health behaviours such as physical exercise have been studied in terms of goal setting and goal pursuit. While the former reflects an initial motivation process, the latter refers to self-regulation when it comes to translating a health goal into action. In this second phase, planning has proven useful. The present study addresses this particular issue by experimentally inducing two kinds of planning, labelled action planning and coping planning for improving adherence with prescribed exercise recommendations in patients discharged from cardiac rehabilitation.