37 resultados para Lyons, Martyn


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Mesoproterozoic marine successions worldwide record a shift in average delta(13)C values from 0 to +3.5parts per thousand, with the latter value evident in successions younger than 1250 Ma. New carbon isotope data from the similar to 1300 to 1270 Ma Dismal Lakes Group, Arctic Canada, provide further insight into this fundamental transition. Data reveal that the shift to higher VC values was gradual and marked by occasional excursions to values less than 0 parts per thousand. When compared to records from older and younger marine successions, it is evident that the difference between isotopic minima and maxima increased with time, indicating that the marine system evolved to become isotopically more variable. We interpret these patterns to record an increase in the crustal inventory of organic carbon, reflecting eukaryotic diversification and a change in the locus of organic carbon burial to include anoxic deep marine sites where preservation potential was high. We speculate that the release of O-2 to Earth's surface environments associated with increased organic carbon storage induced irreversible changes in the Mesoproterozoic biosphere, presaging the more extreme environmental and evolutionary developments of the Neoproterozoic.

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The current RIKEN transcript set represents a significant proportion of the mouse transcriptome but transcripts expressed in the innate and acquired immune systems are poorly represented. In the present study we have assessed the complexity of the transcriptome expressed in mouse macrophages before and after treatment with lipopolysaccharide, a global regulator of macrophage gene expression, using existing RIKEN 19K arrays. By comparison to array profiles of other cells and tissues, we identify a large set of macrophage-enriched genes, many of which have obvious functions in endocytosis and phagocytosis. In addition, a significant number of LPS-inducible genes were identified. The data suggest that macrophages are a complex source of mRNA for transcriptome studies. To assess complexity and identify additional macrophage expressed genes, cDNA libraries were created from purified populations of macrophage and dendritic cells, a functionally related cell type. Sequence analysis revealed a high incidence of novel mRNAs within these cDNA libraries. These studies provide insights into the depths of transcriptional complexity still untapped amongst products of inducible genes, and identify macrophage and dendritic cell populations as a starting point for sampling the inducible mammalian transcriptome.

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Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells. Here we describe 36 nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C-terminus to benzylamine, at the N-terminus to a small library of carboxylic acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were cytotoxic at nanomolar concentrations against a particularly aggressive human melanoma cell line (MM96L), four compounds showed selectivities of greater than or equal to5:1 for human melanoma over normal human cells (NFF), and four of the most potent compounds were further tested and found to be cytotoxic for six other human cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7; ovarian JAM, CI80-13S). The most active compounds typically caused hyperacetylation of histones, induced p21 expression, and reverted phenotype of surviving tumor cells to a normal morphology. Only one compound was given orally at 5 mg/kg to healthy rats to look for bioavailaiblity, and it showed reasonably high levels in plasma (C-max 6 mug/mL, T-max 15 min) for at least 4 h. Results are sufficiently promising to support further work on refining this and related classes of compounds to an orally active, more tumor-selective, antitumor drug.

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The increased presence and participation in Australian society of people with an intellectual disability provides challenges for the provision of primary health care. General practitioners (GPs) identify themselves as ill equipped to provide for this heterogeneous population. A major obstacle to the provision of appropriate health care is seen as inadequate communication between the GP and the person with an intellectual disability, who may or may not be accompanied by a carer or advocate. This qualitative study in which five GPs, three people with intellectual disability, seven carers and two advocates (parent and friend) were interviewed was conducted in Brisbane, Australia. The aim was to better understand the factors that have an impact upon the success of communication in a medical consultation. Findings suggested that GPs were concerned with the aspects of communication difficulties which influenced their ability to adequately diagnose, manage and inform patients. Implications for practice management were also identified. People with intellectual disability reported frustration when they felt that they could not communicate adequately with the GP and annoyance when they were not included in the communication exchange. Carers were strong advocates for the person with intellectual disability, but indicated insufficient skill and knowledge to provide the level of assistance required in the consultation. The outcome was a model of cooperation that outlined the responsibilities of all players in the medical encounter, prior to, during and after the event.

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Regular aerobic exercise is recommended by physicians to improve health and longevity. However, individuals exercising in urban regions are often in contact with air pollution, which includes particles and gases associated with respiratory disease and cancer. We describe the recent evidence on the cardiovascular effects of air pollution, and the implications of exercising in polluted environments, with a view to informing clinicians and other health professionals. There is now strong evidence that fine and ultra fine particulate matter present in air pollution increases cardiovascular morbidity and mortality. The main mechanisms of disease appear to be related to an increase in the pathogenic processes associated with atherosclerosis. People exercising in environments pervaded by air contaminants are probably at increased risk, due to an exercise-induced amplification in respiratory uptake, lung deposition and toxicity of inhaled pollutants. We make evidence-based recommendations for minimizing exposure to air-borne toxins while exercising, and suggest that this advice be passed on to patients where appropriate.

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Path analysis of attitudinal, motivational, demographic and behavioural factors influencing food choice among Australian consumers who had consumed at least some organic food in the preceding 12 months showed that concern with the naturalness of food and the sensory and emotional experience of eating were the major determinants of increasing levels of organic consumption. Increasing consumption was also related to other 'green consumption' behaviours such as recycling and to lower levels of concern with convenience in the purchase and preparation of food. Most of these factors were, in turn, strongly affected by gender and the level of responsibility taken by respondents for food provisioning within their households, a responsibility dominated by women. Education had a slightly negative effect on the levels of concern for sensory and emotional appeal due to lower levels of education among women. Income, age, political and ecological values and willingness to pay a premium for safe and environmentally friendly foods all had extremely minor effects. (C) 2004 Elsevier Ltd. All rights reserved.

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To investigate the role of the hepatitis C virus internal ribosome entry site (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES elements were constructed to contain the reciprocal domain IV in the otherwise HCV and classical swine fever virus IRES elements. This permitted an examination of the role of domain IV in the control of HCV translation. A specific inhibitor of the HCV IRES, vitamin B-12 was shown to inhibit translation directed by all IRES elements which contained domain IV from the HCV and the GB virus B IRES elements, whereas the HCV core protein could only suppress translation from the wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin B-12 and the core protein differ, and they target different regions of the IRES.

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Despite current findings that consumers, on average, have negative attitudes to biotechnologies such as cloning and genetic engineering, considerable variability can be found in the direction and strength of these attitudes. This paper presents a path analysis of attitudinal, motivational, demographic and behavioural variables that influence consumer dispositions towards biotechnology. Among these variables, those found to be most important were: consumers' level of motivation to find natural foods; the extent to which they were motivated by convenience; whether they did the shopping for their household on a regular basis; and their sex. In terms of direct effects on dispositions to biotechnology, motivation to find natural foods had a very strong negative effect while convenience had a very strong positive effect. Sex had a moderate direct effect with women less likely to be positively disposed towards biotechnology than men. In an apparent contradiction, taking responsibility for household shopping had an equally strong positive effect on both naturalness and convenience. However, sex also played a crucial role here with a very strong effect on motivation to find natural foods (women more motivated), a minor effect on convenience (women less motivated) and a strong effect on responsibility for household shopping (women more likely to shop). The policy implications of these findings are important, given the apparent oppositional trends of some sections of the food industry to endorse biotechnology, and of the supermarkets to deliver `clean and green' non-GM foods to consumers. (c) 2005 Elsevier Ltd. All rights reserved.

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This article presents three studies conducted in Canada and Australia that relate theory of mind (ToM) development to mental state discourse. In Study 1, mental state discourse was examined while parents and their 5-7-year-old children jointly read a storybook which had a surprise ending about the identity of the main character. Comments specific to the mental states of the story characters and discourse after the book had ended were positively related to children's ToM, and this was due to parent elaborations. Studies 2 and 3 examined children's mental state discourse during storytelling tasks, and in both, mental state discourse of children during narrative was concurrently related to ToM performance. While research has shown that mental state discourse of parents is related to children's ToM acquisition, the current research indicates that children's spontaneous use of mental state language examined outside of the interactional context is also a strong correlate.