Showing papers by "University of Aberdeen published in 1999"

Spatial population dynamics: analyzing patterns and processes of population synchrony

Abstract: The search for mechanisms behind spatial population synchrony is currently a major issue in population ecology. Theoretical studies highlight how synchronizing mechanisms such as dispersal, regionally correlated climatic variables and mobile enemies might interact with local dynamics to produce different patterns of spatial covariance. Specialized statistical methods, applied to large-scale survey data, aid in testing the theoretical predictions with empirical estimates. Observational studies and experiments on the demography of local populations are paramount to identify the true ecological mechanisms. The recent achievements illustrate the power of combining theory, observation and/or experimentation and statistical modeling in the ecological research protocol.

Matrix metalloproteinases in tumour invasion and metastasis

Abstract: The matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. The MMPs have been classified into different groups including collagenases, gelatinases, stromelysins, and others, particularly membrane-type MMPs, based mainly on the in vitro substrate specificity of individual MMPs. There is increasing evidence to indicate that individual MMPs have important roles in tumour invasion and metastasis. However, the current concept of the role of MMPs in tumour invasion is that they not only have a direct role in tumour invasion by facilitating extracellular matrix degradation, but as a consequence they also have an important role in maintaining the tumour micro-environment and thus promoting tumour growth. Inhibiting the action of MMPs represents a new therapeutic approach for the treatment of individual types of cancer and several broad-spectrum, low-molecular-weight MMP inhibitors are currently being assessed for clinical use. This review examines the role of MMPs in tumour invasion and metastasis, with an emphasis on studies of clinical relevance.

Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity.

Abstract: Mechanosensitive channels are ubiquitous amongst bacterial cells and have been proposed to have major roles in the adaptation to osmotic stress, in particular in the management of transitions from high to low osmolarity environments. Electrophysiological measurements have identified multiple channels in Escherichia coli cells. One gene, mscL, encoding a large conductance channel has previously been described, but null mutants were without well-defined phenotypes. Here, we report the characterization of a new gene family required for MscS function, YggB and KefA, which has enabled a rigorous test of the role of the channels. The channel determined by KefA does not appear to have a major role in managing the transition from high to low osmolarity. In contrast, analysis of mutants of E.coli lacking YggB and MscL shows that mechanosensitive channels are designed to open at a pressure change just below that which would cause cell disruption leading to death.

Pharmacology of cannabinoid receptor ligands.

Abstract: Mammalian tissues contain at least two types of cannabinoid receptor, CB 1 and CB 2 , both coupled to G proteins. CB 1 receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB 2 receptors occur in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this 'endogenous cannabinoid system' has been paralleled by a renewed interest in possible therapeutic applications of cannabinoids, for example in the management of pain and in the suppression of muscle spasticity/spasm associated with multiple sclerosis or spinal cord injury. It has also prompted the development of a range of novel cannabinoid receptor ligands, including several that show marked selectivity for CB 1 or CB 2 receptors. This review summarizes current knowledge about the in vitro pharmacological properties of important CB 1 and CB 2 receptor ligands. Particular attention is paid to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [ 35 S]GTPγS binding assays, and to selected examples of how these pharmacological properties can be influenced by chemical structure. The in vitro pharmacological properties of ligands that can potently and selectively oppose the actions of CB 1 or CB 2 receptor agonists are also described. When administered by themselves, some of these ligands produce effects in certain tissue preparations that are opposite in direction to those produced by cannabinoid receptor agonists and the possibility that the ligands producing such 'inverse cannabimimetic effects' are inverse agonists rather than pure antagonists is discussed.

Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials

Abstract: OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.

Reversible neural inactivation reveals hippocampal participation in several memory processes.

Abstract: Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes—encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

Pharmacology of Cannabinoid Receptor Ligands

Abstract: Mammalian tissues contain at least two types of cannabinoid receptor, CB 1 and CB 2 , both coupled to G proteins. CB 1 receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB 2 receptors occur in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this 'endogenous cannabinoid system' has been paralleled by a renewed interest in possible therapeutic applications of cannabinoids, for example in the management of pain and in the suppression of muscle spasticity/spasm associated with multiple sclerosis or spinal cord injury. It has also prompted the development of a range of novel cannabinoid receptor ligands, including several that show marked selectivity for CB 1 or CB 2 receptors. This review summarizes current knowledge about the in vitro pharmacological properties of important CB 1 and CB 2 receptor ligands. Particular attention is paid to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [ 35 S]GTPγS binding assays, and to selected examples of how these pharmacological properties can be influenced by chemical structure. The in vitro pharmacological properties of ligands that can potently and selectively oppose the actions of CB 1 or CB 2 receptor agonists are also described. When administered by themselves, some of these ligands produce effects in certain tissue preparations that are opposite in direction to those produced by cannabinoid receptor agonists and the possibility that the ligands producing such 'inverse cannabimimetic effects' are inverse agonists rather than pure antagonists is discussed.

Sealice on Salmonids: Their Biology and Control

Abstract: Lepeophtheirus salmonis and Caligus elongatus are the two common species of sealice responsible for serious disease problems in salmonid aquaculture. L. salmonis in particular is the most serious parasitic infection on Atlantic salmon farms in the Northern Hemisphere and is the best-known species. This review examines the voluminous literature on the biology and control of sealice and brings together ideas for developing our knowledge of these organisms. Research on the distribution, host range, structure, life cycle, epidemiology, laboratory maintenance, reproductive biology, physiology and pathogenesis is reviewed in depth. The control strategy and economic cost to the industry is discussed. The interactions between wild and cultured salmonids are examined.

Estimating size and assessing trends in a coastal bottlenose dolphin population

Abstract: We used a case study of a coastal bottlenose dolphin population to present a framework for determining the number of individuals present and assessing the likely time scale over which trends in abundance may be determined. Such a framework is appropriate for animal species that possess natural markings sufficient for individual recognition, and may be valuable in the development and implementation of management and monitoring programs for vulnerable populations. Population abundance was estimated using mark–recapture methods applied to photoidentification data. This experiment was designed to minimize violation of method assumptions so as to allow use of the most parsimonious model for analysis. The data were examined critically to investigate mark–recapture assumptions, while analytical methods and data were selected to minimize and, where necessary, account for violations. The estimated number of animals with long-lasting marks from left and right side estimates were 73 ± 12 and 80 ± 11 individuals, res...

Entrepreneurship education within the enterprise culture: Producing reflective practitioners

Abstract: The enterprise culture is founded on the premise that entrepreneurship is the engine that drives the economy One aspect of this cultural pervasion is the increase in the numbers of educational institutions teaching entrepreneurship courses Yet this hegemony of the encouragement of new business start‐up, almost for its own sake, needs to be critically reviewed One aspect is the enigmatic nature of entrepreneurship itself; what is it, and can it be taught? Another aspect is the very different expectations of those stakeholders promoting entrepreneurship education Argues that the process of entrepreneurship involves both art and science; consequently our students need more than SME management skills Graduating enterprise students must be innovative and creative to satisfy the need for entrepreneurial novelty ‐ the art Yet, paradoxically they also need to be competent and multifunctional managers ‐ the science Explores both these areas to argue that theory can bridge the art and science The final section explains briefly how the recent research and practice at Aberdeen University attempts this synthesis The intended outcome of our educational process are reflective practitioners, fit for an entrepreneurial career

Molecular analysis of bacterial community structure and diversity in unimproved and improved upland grass pastures.

Abstract: Bacterial community structure and diversity in rhizospheres in two types of grassland, distinguished by both plant species and fertilization regimen, were assessed by performing a 16S ribosomal DNA (rDNA) sequence analysis of DNAs extracted from triplicate soil plots. PCR products were cloned, and 45 to 48 clones from each of the six libraries were partially sequenced. Phylogenetic analysis of the resultant 275 clone sequences indicated that there was considerable variation in abundance in replicate unfertilized, unimproved soil samples and fertilized, improved soil samples but that there were no significant differences in the abundance of any phylogenetic group. Several clone sequences were identical in the 16S rDNA region analyzed, and the clones comprised eight pairs of duplicate clones and two sets of triplicate clones. Many clones were found to be most closely related to environmental clones obtained in other studies, although three clones were found to be identical to culturable species in databases. The clones were clustered into operational taxonomic units at a level of sequence similarity of >97% in order to quantify diversity. In all, 34 clusters containing two or more sequences were identified, and the largest group contained nine clones. A number of diversity, dominance, and evenness indices were calculated, and they all indicated that diversity was high, reflecting the low coverage of rDNA libraries achieved. Differences in diversity between sample types were not observed. Collector's curves, however, indicated that there were differences in the underlying community structures; in particular, there was reduced diversity of organisms of the alpha subdivision of the class Proteobacteria (alpha-proteobacteria) in improved soils.

Particulate air pollution and the blood.

Abstract: BACKGROUND Particulate air pollution has been associated with excess deaths from, and increases in hospital admissions for, cardiovascular disease among older people. A study was undertaken to determine whether this may be a consequence of alterations in the blood, secondary to pulmonary inflammation caused by the action of fine particles on alveolar cells, by repeatedly measuring haematological factors in older people and relating them to measurements of exposure to airborne particles. METHODS One hundred and twelve individuals aged 60+ years in two UK cities provided repeated blood samples over 18 months, 108 providing the maximum of 12 samples. Estimates of individual exposure to particles of less than 10 μm diameter (PM10), derived from a mathematical model based on activity diaries and comparative measurements of PM10 at multiple sites and during a variety of activities, were made for each three day period prior to blood sampling. The relationships between blood values and estimates of both personal exposure and city centre measurements of PM10 were investigated by analysis of covariance, adjusting for city, season, temperature, and repeated individual measurements. RESULTS Estimated personal exposure to PM10 over the previous three days showed negative correlations with haemoglobin concentration, packed cell volume (PCV), and red blood cell count (p<0.001), and with platelets and factor VII levels (p<0.05). The changes in red cell indices persisted after adjustment for plasma albumin in a sample of 60 of the subjects. City centre PM10 measurements over three days also showed negative correlations with haemoglobin and red cell count (p<0.001) and with PCV and fibrinogen (p<0.05), the relationship with haemoglobin persisting after adjustment for albumin. C reactive protein levels showed a positive association with city centre measurements of PM10 (p<0.01). Based on a linear relationship, the estimated change in haemoglobin associated with an alteration in particle concentration of 100 μg/m3 is estimated to have been 0.44 g/dl (95% CI 0.62 to 0.26) for personal PM10 and 0.73 g/dl (95% CI 1.11 to 0.36) for city centre PM10 measurements. CONCLUSIONS This investigation is the first to estimate personal exposures to PM10 and to demonstrate associations between haematological indices and air pollution. The changes in haemoglobin adjusted for albumin suggest that inhalation of some component of PM10may cause sequestration of red cells in the circulation. We propose that an action of such particles either on lung endothelial cells or on erythrocytes themselves may be responsible for changing red cell adhesiveness. Peripheral sequestration of red cells offers an explanation for the observed cardiovascular effects of particulate air pollution.

Evidence-Based Implementation of Evidence-Based Medicine

Abstract: Article-at-a-Glance Background The slow and haphazard process of translating research findings into clinical practice compromises the potential benefits of clinical research. Most quality improvement (QI) initiatives are based on the beliefs of decision makers rather than on the growing theoretical and empirical knowledge about organizational and provider behavior change. If future QI activities are to improve the translation of evidence into practice, they should be based on an understanding of the different models and strategies for implementing research evidence and the evidence base supporting their use. Evidence-based medicine should be complemented by evidence-based implementation. The evidence for different strategies of implementing change A general framework for changing practice based on theoretical perspectives and research evidence considers a variety of theoretical approaches and their contribution to an understanding of provider behavior change. The framework summarizes evidence from systematic reviews of provider behavior change, which suggest the potential of several dissemination and implementation strategies that are effective under certain conditions. Passive dissemination approaches are largely ineffective; specific strategies to implement research-based recommendations appear to be necessary to ensure practice change. Multifaceted interventions that address specific barriers to change are more likely to lead to changes in practice. Practical, five-stage framework A practical, five-stage framework for changing practice, which is illustrated with experiences from a comprehensive program on implementing evidence-based clinical guidelines in primary care, includes development of a concrete proposal for change; analysis of the target setting and group to identify obstacles to change; linking interventions to needs, facilitators, and obstacles to change; development of an implementation plan; and monitoring progress with implementation.

Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630.

Abstract: We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and also investigated whether L759633 and L759656, are CB2 receptor agonists. Binding assays with membranes from CHO cells stably transfected with human CB1 or CB2 receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and L759656 (CB2/CB1 affinity ratios = 163 and 414 respectively) and showed AM630 to have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165. In CB2-transfected cells, L759633 and L759656 were potent inhibitors of forskolin-stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively and CB1/CB2 EC50 ratios of > 1000 and > 3000 respectively. AM630 inhibited [35S]-GTPgammaS binding to CB2 receptor membranes (EC50 = 76.6 nM), enhanced forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 microM), and antagonized the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940. In CB1-transfected cells, forskolin-stimulated cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 microM and 45.9% at 10 microM) and by L759633 at 10 microM (48%) but not 1 microM. L759656 (10 microM) was not inhibitory. AM630 also produced a slight decrease in the mean inhibitory effect of CP55940 on cyclic AMP production which was not statistically significant. We conclude that AM630 is a CB2-selective ligand that behaves as an inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors. L759633 and L759656 are both potent CB2-selective agonists.

Changing incidence of Achilles tendon rupture in Scotland: a 15-year study.

Abstract: ObjectiveTo determine the incidence of Achilles tendon rupture in Scotland from 1980 to 1995.Design:Retrospective analysis of prospectively collected data.Setting:Data were obtained from the National Health Service Information and Statistics Division and analyzed in terms of age- and gender-specific

The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations.

Abstract: Thiopurine methyltransferase metabolizes 6-mercaptopurine, thioguanine and azathioprine, thereby regulating cytotoxicity and clinical response to these thiopurine drugs. In healthy Caucasian populations, 89–94% of individuals have high thiopurine methyltransferase activity, 6–11% intermediate and 0.

Assessing the state of organizational safety-culture or climate?

Abstract: This article explores the concepts of safety culture and safety climate in an attempt to determine which is the more useful for describing an organization's “state of safety.” From a review of the literature purporting to measure safety culture or safety climate, it is argued that, although the two terms are often interchangeable, they are actually distinct but related concepts and should be treated accordingly. The term “safety climate” best describes employees' perceptions, attitudes, and beliefs about risk and safety, typically measured by questionnaire surveys and providing a “snapshot” of the current state of safety. “Safety culture” is a more complex and enduring trait reflecting fundamental values, norms, assumptions and expectations, which to some extent reside in societal culture. The expression of these “cultural” elements, perhaps, can be seen through safety management practices which are reflected in the safety climate. Basically, measurement of safety culture requires in-depth investigation including an analysis of how organizational members interact to form a shared view of safety.

The black box inside the glass box

Abstract: Simplicity and visibility are two important characteristics of programming languages for novices. Novices start programming with very little idea of the properties of the notional machine implied by the language they are learning. To help them learn these properties, the notional machine should be simple. That is, it should consist of a small number of parts that interact in ways that can be easily understood, possibly by analogy to other mechanisms with which the novice is more familiar. A notional machine is the idealized model of the computer implied by the constructs of the programming language. Visibility is concerned with methods for viewing selected parts and processes of this notional machine in action. We introduce the term “commentary” which is the system's dynamic characterization of the notional machine, expressed in either text or pictures on the user's terminal. We examine the simplicity and visibility of three systems, each designed to provide programming experience to different populations of novices.

An in vitro model of angiogenesis: basic features.

Abstract: This report describes a model of angiogenesis which develops in admixtures (co-cultures) of human umbilical vein endothelial cells (HUVEC) and human diploid fibroblasts of dermal origin from adult patients. The system does not require the addition of further growth factors other than those normally present in endothelial growth medium (EGM), nor matrix proteins, and cell growth and proliferation are allowed to occur in a standard low (2%) concentration of fetal calf serum. Angiogenesis was specifically stimulated in response to vascular endothelial growth factor (VEGF), resulting in an increased development of structures resembling a microvasculature bed. Alternatively, angiogenesis was inhibited by addition of an excess of neutralising anti-VEGF antibodies, and the anti-angiogenic drugs such as suramin. We briefly show that stimulatory and inhibitory activities can be easily and quickly quantified by image analysis. Tubule formation was confirmed by confocal and electron microscopy, and the development and disposition of these structures within the co-cultures has been analysed immunochemically to show expression of specific endothelial cell determinants, such as PECAM-1. On this and a number of other criteria, the findings validate this in vitro process as a model of in vivo angiogenesis that can be quantified to assay stimulatory and inhibitory agents, signals and drugs.

Dietary nitrate in man: friend or foe?

Abstract: Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.