19 resultados para Reparative and reactive fibrosis

em CentAUR: Central Archive University of Reading - UK


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Background In many species floral senescence is coordinated by ethylene. Endogenous levels rise, and exogenous application accelerates senescence. Furthermore, floral senescence is often associated with increased reactive oxygen species, and is delayed by exogenously applied cytokinin. However, how these processes are linked remains largely unresolved. Erysimum linifolium (wallflower) provides an excellent model for understanding these interactions due to its easily staged flowers and close taxonomic relationship to Arabidopsis. This has facilitated microarray analysis of gene expression during petal senescence and provided gene markers for following the effects of treatments on different regulatory pathways. Results In detached Erysimum linifolium (wallflower) flowers ethylene production peaks in open flowers. Furthermore senescence is delayed by treatments with the ethylene signalling inhibitor silver thiosulphate, and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of cytokinin oxidase), delay petal senescence. However, treatment with cytokinin also increases ethylene biosynthesis. Despite the similar effects on senescence, transcript abundance of gene markers is affected differentially by the treatments. A significant rise in transcript abundance of WLS73 (a putative aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl purine treatments. In contrast, WFSAG12 transcript (a senescence marker) continued to accumulate significantly, albeit at a reduced rate. Silver thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and WLS73. Activity of reactive oxygen species scavenging enzymes changed during senescence. Treatments that increased cytokinin levels, or inhibited ethylene action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin levels rose with senescence, treatments that delayed early senescence did not affect transcript abundance of WPS46, an auxin-induced gene. Conclusions A model for the interaction between cytokinins, ethylene, reactive oxygen species and auxin in the regulation of floral senescence in wallflowers is proposed. The combined increase in ethylene and reduction in cytokinin triggers the initiation of senescence and these two plant growth regulators directly or indirectly result in increased reactive oxygen species levels. A fall in conjugated auxin and/or the total auxin pool eventually triggers abscission.

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1. The production of food for human consumption has led to an historical and global conflict with terrestrial carnivores, which in turn has resulted in the extinction or extirpation of many species, although some have benefited. At present, carnivores affect food production by: (i) killing human producers; killing and/or eating (ii) fish/shellfish; (iii) game/wildfowl; (iv) livestock; (v) damaging crops; (vi) transmitting diseases; and (vii) through trophic interactions with other species in agricultural landscapes. Conversely, carnivores can themselves be a source of dietary protein (bushmeat). 2. Globally, the major areas of conflict are predation on livestock and the transmission of rabies. At a broad scale, livestock predation is a customary problem where predators are present and has been quantified for a broad range of carnivore species, although the veracity of these estimates is equivocal. Typically, but not always, losses are small relative to the numbers held, but can be a significant proportion of total livestock mortality. Losses experienced by producers are often highly variable, indicating that factors such as husbandry practices and predator behaviour may significantly affect the relative vulnerability of properties in the wider landscape. Within livestock herds, juvenile animals are particularly vulnerable. 3. Proactive and reactive culling are widely practised as a means to limit predation on livestock and game. Historic changes in species' distributions and abundance illustrate that culling programmes can be very effective at reducing predator density, although such substantive impacts are generally considered undesirable for native predators. However, despite their prevalence, the effectiveness, efficiency and the benefit:cost ratio of culling programmes have been poorly studied. 4. A wide range of non-lethal methods to limit predation has been studied. However, many of these have their practical limitations and are unlikely to be widely applicable. 5. Lethal approaches are likely to dominate the management of terrestrial carnivores for the foreseeable future, but animal welfare considerations are increasingly likely to influence management strategies. The adoption of non-lethal approaches will depend upon proof of their effectiveness and the willingness of stakeholders to implement them, and, in some cases, appropriate licensing and legislation. 6. Overall, it is apparent that we still understand relatively little about the importance of factors affecting predation on livestock and how to manage this conflict effectively. We consider the following avenues of research to be essential: (i) quantified assessments of the loss of viable livestock; (ii) landscape-level studies of contiguous properties to quantify losses associated with variables such as different husbandry practices; (iii) replicated experimental manipulations to identify the relative benefit of particular management practices, incorporating (iv) techniques to identify individual predators killing stock; and (v) economic analyses of different management approaches to quantify optimal production strategies.

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Plant annexins are ubiquitous, soluble proteins capable of Ca2+-dependent and Ca2+-independent binding to endomembranes and the plasma membrane. Some members of this multigene family are capable of binding to F-actin, hydrolysing ATP and GTP, acting as peroxidases or cation channels. These multifunctional proteins are distributed throughout the plant and throughout the life cycle. Their expression and intracellular localization are under developmental and environmental control. The in vitro properties of annexins and their known, dynamic distribution patterns suggest that they could be central regulators or effectors of plant growth and stress signalling. Potentially, they could operate in signalling pathways involving cytosolic free calcium and reactive oxygen species.

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The structural and reactive properties of the acetyl-protected "one-legged" manganese porphyrin [SAc]P-Mn(III)Cl on Ag(100) have been studied by NEXAFS, synchrotron XPS and STM Spontaneous surface-mediated deprotection occurs at 300 K accompanied by spreading of the resulting thio-tethered porphyrin across the metal surface Loss of the axial chlorine ligand occurs at 498 K, without any demetalation of the macrocycle, leaving the Mn center in a low co-ordination state At low coverages the macrocycle is markedly tilted toward the silver surface, as is the phenyl group that forms part of the tethering "leg". In the monolayer region a striking transition occurs whereby the molecule rolls over, preserving the tilt angle of the phenyl group, strongly increasing that of the macrocycle, decreasing the apparent height of the molecule and decreasing its footprint, thus enabling closer packing These findings are in marked contrast with those previously reported for the corresponding more rigidly bound four-legged porphyrin [Turner, M., Vaughan, O. P. H., Kyriakou, G., Watson, D. J., Scherer, L. J; Davidson, G J. E, Sanders, J. K. M.; Lambert, R. M J. Am. Chem Soc 2009, 131, 1910] suggesting that the physicochemical :)properties and potential applications of these versatile systems should be strongly dependent on the mode of tethering to the surface.

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Myoglobin has been studied in considerable detail using different experimental and computational techniques over the past decades. Recent developments in time-resolved spectroscopy have provided experimental data amenable to detailed atomistic simulations. The main theme of the present review are results on the structures, energetics and dynamics of ligands ( CO, NO) interacting with myoglobin from computer simulations. Modern computational methods including free energy simulations, mixed quantum mechanics/molecular mechanics simulations, and reactive molecular dynamics simulations provide insight into the dynamics of ligand dynamics in confined spaces complementary to experiment. Application of these methods to calculate and understand experimental observations for myoglobin interacting with CO and NO are presented and discussed.

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In this paper we describe how to cope with the delays inherent in a real time control system for a steerable stereo head/eye platform. A purposive and reactive system requires the use of fast vision algorithms to provide the controller with the error signals to drive the platform. The time-critical implementation of these algorithms is necessary, not only to enable short latency reaction to real world events, but also to provide sufficiently high frequency results with small enough delays that controller remain stable. However, even with precise knowledge of that delay, nonlinearities in the plant make modelling of that plant impossible, thus precluding the use of a Smith Regulator. Moreover, the major delay in the system is in the feedback (image capture and vision processing) rather than feed forward (controller) loop. Delays ranging between 40msecs and 80msecs are common for the simple 2D processes, but might extend to several hundred milliseconds for more sophisticated 3D processes. The strategy presented gives precise control over the gaze direction of the cameras despite the lack of a priori knowledge of the delays involved. The resulting controller is shown to have a similar structure to the Smith Regulator, but with essential modifications.

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Climate change is inevitable and will continue into the next century. Since the agricultural sector in Sri Lanka is one of the most vulnerable to climate change, a thorough understanding of climate transition is critical for formulating effective adaptation strategies. This paper provides an overview of the status of climate change and adaptation in the agricultural sector in Sri Lanka. The review clearly indicates that climate change is taking place in Sri Lanka in terms of rainfall variability and an increase in climate extremes and warming. A number of planned and reactive adaptation responses stemming from policy and farm-level decisions are reported. These adaptation efforts were fragmented and lacked a coherent connection to the national development policies and strategies. Research efforts are needed to develop and identify adaptation approaches and practices that are feasible for smallholder farmers, particularly in the dry zone where paddy and other food crops are predominately cultivated. To achieve the envisaged growth in the agricultural sector, rigorous efforts are necessary to mainstream climate change adaptation into national development policies and ensure that they are implemented at national, regional and local levels.

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Cardiac hypertrophy is associated with hypertrophic growth of cardiac myocytes and increased fibrosis. Much is known of the stimuli which promote myocyte hypertrophy and the changes associated with the response, but the links between the two are largely unknown. Using subtractive hybridization, we identified three genes which are acutely (<1 h) upregulated in neonatal rat ventricular myocytes exposed to the alpha-adrenergic agonist, phenylephrine. One represented connective tissue growth factor (CTGF) which is implicated in fibrosis and promotes hypertrophy in other cells. We further examined the expression of CTGF mRNA and protein in cardiac myocytes using quantitative PCR and immunoblotting, confirming that phenylephrine increased CTGF mRNA (maximal within 1 h) and protein (increased over 4 - 24 h). Endothelin-1 promoted a greater, though transient, increase in CTGF mRNA, but the increase in CTGF protein was sustained over 8 h. Neither agonist increased CTGF mRNA in cardiac non-myocytes. By increasing the expression of CTGF in cardiac myocytes, hypertrophic agonists such as phenylephrine and endothelin-1 may promote fibrosis. CTGF may also propagate the hypertrophic response initiated by these agonists.

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Objective: In recent years the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In the present study we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Methods: Cytotoxicity studies were performed using MTT, NR and TEER assays whereas 3H-thymidine incorporation and western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Results: Rhein (0.1-10μg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 μg/ml) significantly reduced cell proliferation as well as MAP kinase activation; by contrast, at the high concentration (10μg/ml) rhein significantly increased cell proliferation and ERK phosphorylation. Moreover, rhein (0.1-10μg/ml) (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function, (ii) did not induce DNA damage rather it was able to reduce H2O2-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and ROS levels induced by H2O2/Fe2+. Conclusions: Rhein, was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism which seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.

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CO stimulates formation of NO and reactive oxygen species which, via peroxynitrite formation, inhibit Ca(2+) extrusion via PMCA, leading to disruption of Ca(2+) signaling. We propose this contributes to the neurological damage associated with CO toxicity.

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The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

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Laboratory determined mineral weathering rates need to be normalised to allow their extrapolation to natural systems. The principle normalisation terms used in the literature are mass, and geometric- and BET specific surface area (SSA). The purpose of this study was to determine how dissolution rates normalised to these terms vary with grain size. Different size fractions of anorthite and biotite ranging from 180-150 to 20-10 mu m were dissolved in pH 3, HCl at 25 degrees C in flow through reactors under far from equilibrium conditions. Steady state dissolution rates after 5376 h (anorthite) and 4992 h (biotite) were calculated from Si concentrations and were normalised to initial- and final- mass and geometric-, geometric edge- (biotite), and BET SSA. For anorthite, rates normalised to initial- and final-BET SSA ranged from 0.33 to 2.77 X 10(-10) mol(feldspar) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 5.74 to 8.88 X 10(-10) mol(feldspar) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.11 to 1.65 mol(feldspar) g(-1) s(-1). For biotite, rates normalised to initial- and final-BET SSA ranged from 1.02 to 2.03 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 3.26 to 16.21 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric edge SSA ranged from 59.46 to 111.32 x 10(-12) mol(biotite) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.81 to 6.93 X 10(-12) mol(biotite) g(-1) s(-1). For all normalising terms rates varied significantly (p <= 0.05) with grain size. The normalising terms which gave least variation in dissolution rate between grain sizes for anorthite were initial BET SSA and initial- and final-geometric SSA. This is consistent with: (1) dissolution being dominated by the slower dissolving but area dominant non-etched surfaces of the grains and, (2) the walls of etch pits and other dissolution features being relatively unreactive. These steady state normalised dissolution rates are likely to be constant with time. Normalisation to final BET SSA did not give constant ratios across grain size due to a non-uniform distribution of dissolution features. After dissolution coarser grains had a greater density of dissolution features with BET-measurable but unreactive wall surface area than the finer grains. The normalising term which gave the least variation in dissolution rates between grain sizes for biotite was initial BET SSA. Initial- and final-geometric edge SSA and final BET SSA gave the next least varied rates. The basal surfaces dissolved sufficiently rapidly to influence bulk dissolution rate and prevent geometric edge SSA normalised dissolution rates showing the least variation. Simple modelling indicated that biotite grain edges dissolved 71-132 times faster than basal surfaces. In this experiment, initial BET SSA best integrated the different areas and reactivities of the edge and basal surfaces of biotite. Steady state dissolution rates are likely to vary with time as dissolution alters the ratio of edge to basal surface area. Therefore they would be more properly termed pseudo-steady state rates, only appearing constant because the time period over which they were measured (1512 h) was less than the time period over wich they would change significantly. (c) 2006 Elsevier Inc. All rights reserved.

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The kinetics of uptake of gaseous N2O5 on submicron aerosols containing NaCl and natural sea salt have been investigated in a flow reactor as a function of relative humidity (RH) in the range 30-80% at 295±2K and a total pressure of 1bar. The measured uptake coefficients, γ, were larger on the aerosols containing sea salt compared to those of pure NaCl, and in both cases increased with increasing RH. These observations are explained in terms of the variation in the size of the salt droplets, which leads to a limitation in the uptake rate into small particles. After correction for this effect the uptake coefficients are independent of relative humidity, and agree with those measured previously on larger droplets. A value of γ=0.025 is recommended for the reactive uptake coefficient for N2O5 on deliquesced sea salt droplets at 298K and RH>40%.

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The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4 carriers may benefit from alpha-tocopherol (alpha-Toc) supplementation. Targeted replacement mice expressing the human apoE3 and apoE4 were fed with a diet poor (0 mg/kg diet) or rich (200 mg/kg diet) in alpha-Toc for 12 weeks. Neither apoE genotype nor dietary alpha-Toc exerted any effects on the antioxidant defence system, including glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase activities. In addition, no differences were observed in mitogen-induced lymphocyte proliferation. alpha-Toc concentrations were modestly higher in plasma and lower in tissues of apoE4 compared with apoE3 mice, with the greatest differences evident in the lung, suggesting that an apoE4 genotype may reduce alpha-Toc delivery to tissues. A tendency towards increased plasma F-2-isoprostanes in apoE4 mice was observed, while liver thiobarbituric acid-reactive substances did not differ between apoE3 and apoE4 mice. In addition, C-reactive protein (CRP) concentrations were reduced in apoE4 mice indicating that this positive effect on CRP may in part negate the increased CVD risk associated with an apoE4 genotype.

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Background: The response of plasma lipids to dietary fat manipulation is highly heterogeneous, with some indications that APOE genotype may be important. Objective: The objective was to use a prospective recruitment approach to determine the effect of dietary fat quantity and composition on both lipid and nonlipid cardiovascular disease biomarkers according to APOE genotype. Design: Participants had a mean (±SD) age of 51 ± 9 y and a BMI (in kg/m2) of 26.0 ± 3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention (the SATgenϵ study) in which they were assigned to a low-fat diet, a high-fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8 wk. Fasting blood samples were collected at the end of each intervention arm. Results: An overall diet effect was evident for all cholesterol fractions (P < 0.01), with no significant genotype × diet interactions observed. A genotype × diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and 30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet relative to the low-fat diet. A significant genotype × diet interaction (P = 0.009) was also observed for C-reactive protein (CRP), with only significant increases in concentrations after the HSF and HSF-DHA diets relative to the low-fat diet in the APOE3/E4 group (P < 0.015). Conclusions: Relative to the wild-type APOE3/E3 group, our results indicate a greater sensitivity of fasting triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4 genotype (25% population), with no effect of this allelic profile on cholesterol concentrations. The SATgenϵ study was registered at clinicaltrials.gov as NCT01384032.