228 resultados para calcium-dependent proteolysis
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Self-organized Bi lines that are only 1.5 nm wide can be grown without kinks or breaks on Si(0 0 1) surfaces to lengths of up to 500 nm. Constant-current topographical images of the lines, obtained with the scanning tunneling microscope, have a striking bias dependence. Although the lines appear darker than the Si terraces at biases below ≈∣1.2∣ V, the contrast reverses at biases above ≈∣1.5∣ V. Between these two ranges the lines and terraces are of comparable brightness. It has been suggested that this bias dependence may be due to the presence of a semiconductor-like energy gap within the line. Using ab initio calculations it is demonstrated that the energy gap is too small to explain the experimentally observed bias dependence. Consequently, at this time, there is no compelling explanation for this phenomenon. An alternative explanation is proposed that arises naturally from calculations of the tunneling current, using the Tersoff–Hamann approximation, and an examination of the electronic structure of the line.
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The elastic properties of the arterial wall have been the subject of physiological, clinical and biomedical research for many years. There is convincing evidence that the elastic properties of the large arteries are seriously impaired in the presence of cardiovascular disease (CVD), due to alterations in the intrinsic structural and functional characteristics of vessels [1]. Early detection of changes in the elastic modulus of arteries would provide a powerful tool for both monitoring patients at high cardiovascular risk and testing the effects of pharmaceuticals aimed at stabilizing existing plaques by stiffening them or lowering the lipids.
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Coronary calcium scoring (CCS) has been a topic of great interest lately. In a large population-based study comprising 6,722 patients, Detrano et al. (1) have effectively shown that CCS can be a strong predictor of incident coronary heart disease among different racial groups. Henneman et al. (2) have, however, reported that CCS does not reliably exclude the presence of (significant) atherosclerosis. This topic is quite controversial as there is significant evidence from Detrano's work that higher CCS is associated with an increased risk of acute coronary events. We think that the location of calcium within the coronary arteries should also be considered. Li et al. (3,4) have shown that the position of the calcium in the plaque is a better determinant of plaque vulnerability than the total calcium load. Using a biomechanical model, predicted maximum stress was found to increase by 47.5% when calcium deposits were located in the thin fibrous cap. The presence of calcium deposits in the lipid core or remote from the fibrous cap resulted in no increase in maximum stress. It was also noted that the presence of calcification within the lipid core may even stabilize the plaque. Integration of calcium location in CCS will, therefore, enable better assessment of severity of atherosclerosis and prediction of future cardiovascular events.
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Background: Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The role of calcium deposition and its contribution to plaque stability is controversial. This study uses both an idealized and a patient-specific model to evaluate the effect of a calcium deposit on the stress distribution within an atheromatous plaque. Methods: Using a finite-element method, structural analysis was performed on an idealized plaque model and the location of a calcium deposit within it was varied. In addition to the idealized model, in vivo high-resolution MR imaging was performed on 3 patients with carotid atheroma and stress distributions were generated. The individual plaques were chosen as they had calcium at varying locations with respect to the lumen and the fibrous cap. Results: The predicted maximum stress was increased by 47.5% when the calcium deposit was located in the thin fibrous cap in the model when compared with that in a model without a deposit. The result of adding a calcium deposit either to the lipid core or remote from the lumen resulted in almost no increase in maximal stress. Conclusion: Calcification at the thin fibrous cap may result in high stress concentrations, ultimately increasing the risk of plaque rupture. Assessing the location of calcification may, in the future, aid in the risk stratification of patients with carotid stenosis.
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Robust estimation often relies on a dispersion function that is more slowly varying at large values than the square function. However, the choice of tuning constant in dispersion functions may impact the estimation efficiency to a great extent. For a given family of dispersion functions such as the Huber family, we suggest obtaining the "best" tuning constant from the data so that the asymptotic efficiency is maximized. This data-driven approach can automatically adjust the value of the tuning constant to provide the necessary resistance against outliers. Simulation studies show that substantial efficiency can be gained by this data-dependent approach compared with the traditional approach in which the tuning constant is fixed. We briefly illustrate the proposed method using two datasets.
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A class of growth models incorporating time-dependent factors and stochastic perturbations are introduced. The proposed model includes the existing growth models used in fisheries as special cases. Particular attention is given to growth of a population (in average weight or length) from which observations are taken randomly each time and the analysis of tag-recapture data. Two real data sets are used for illustration: (a) to estimate the seasonal effect and population density effect on growth of farmed prawn (Penaeus monodon) from weight data and (b) to assess the effect of tagging on growth of barramundi (Lates calcarifer)
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Natural mortality of marine invertebrates is often very high in the early life history stages and decreases in later stages. The possible size-dependent mortality of juvenile banana prawns, P. merguiensis (2-15 mm carapace length) in the Gulf of Carpentaria was investigated. The analysis was based on the data collected at 2-weekly intervals by beam trawls at four sites over a period of six years (between September 1986 and March 1992). It was assumed that mortality was a parametric function of size, rather than a constant. Another complication in estimating mortality for juvenile banana prawns is that a significant proportion of the population emigrates from the study area each year. This effect was accounted for by incorporating the size-frequency pattern of the emigrants in the analysis. Both the extra parameter in the model required to describe the size dependence of mortality, and that used to account for emigration were found to be significantly different from zero, and the instantaneous mortality rate declined from 0.89 week(-1) for 2 mm prawns to 0.02 week(-1) for 15 mm prawns.
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A case report of a 920 g infant developing a small intestinal obstruction following therapy for congestive cardiac failure is presented. Although the causation was thought to be milk curd obstruction, subsequent analysis revealed high concentration of calcium and phosphate in the stools. The possible pathogenesis is discussed in relation to the inspissated milk syndrome.
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Purpose: Gamma-aminobutyric acid A (GABAA) receptors (GABAARs), which are ionotropic receptors involving chloride channels, have been identified in various neural (e.g., mouse retinal ganglion cells) and nonneural cells (e.g., mouse lens epithelial cells) regulating the intracellular calcium concentration ([Ca(2+)]i). GABAAR β-subunit protein has been isolated in the cultured human and rat RPE, and GABAAα1 and GABAAρ1 mRNAs and proteins are present in the chick RPE. The purpose of this study was to investigate the expression of GABAAα1 and GABAAρ1, two important subunits in forming functional GABAARs, in the cultured human RPE, and further to explore whether altering receptor activation modifies [Ca(2+)]i. Methods: Human RPE cells were separately cultured from five donor eye cups. Real-time PCR, western blots, and immunofluorescence were used to test for GABAAα1 and GABAAρ1 mRNAs and proteins. The effects of the GABAAR agonist muscimol, antagonist picrotoxin, or the specific GABAAρ antagonist 1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on [Ca(2+)]i in cultured human RPE were demonstrated using Fluo3-AM. Results: Both GABAAα1 and GABAAρ1 mRNAs and proteins were identified in cultured human RPE cells; antibody staining was mainly localized to the cell membrane and was also present in the cytoplasm but not in the nucleus. Muscimol (100 μM) caused a transient increase of the [Ca(2+)]i in RPE cells regardless of whether Ca(2+) was added to the buffer. Muscimol-induced increases in the [Ca(2+)]i were inhibited by pretreatment with picrotoxin (300 μM) or TPMPA (500 μM). Conclusions: GABAAα1 and GABAAρ1 are expressed in cultured human RPE cells, and GABAA agents can modify [Ca(2+)]i.
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Background CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14−/− mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14−/− mice. Exacerbation of infection in Cd14−/− mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.
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This paper is concerned with the study of the equilibrium exchange of ammonium ions with two natural zeolite samples sourced in Australia from Castle Mountain Zeolites and Zeolite Australia. A range of sorption models including Langmuir Vageler, Competitive Langmuir, Freundlich, Temkin, Dubinin Astakhov and Brouers–Sotolongo were applied in order to gain an insight as to the exchange process. In contrast to most previous studies, non-linear regression was used in all instances to determine the best fit of the experimental data. Castle Mountain natural zeolite was found to exhibit higher ammonium capacity than Zeolite Australia material when in the freshly received state, and this behavior was related to the greater amount of sodium ions present relative to calcium ions on the zeolite exchange sites. The zeolite capacity for ammonium ions was also found to be dependent on the solution normality, with 35–60% increase inuptake noted when increasing the ammonium concentration from 250 to 1000 mg/L. The optimal fit ofthe equilibrium data was achieved by the Freundlich expression as confirmed by use of Akaikes Information Criteria. It was emphasized that the bottle-point method chosen influenced the isotherm profile in several ways, and could lead to misleading interpretation of experiments, especially if the constant zeolite mass approach was followed. Pre-treatment of natural zeolite with acid and subsequently sodium hydroxide promoted the uptake of ammonium species by at least 90%. This paper highlighted the factors which should be taken into account when investigating ammonium ion exchange with natural zeolites.
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This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.
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This thesis introduces a new animal model, kangaroo, to biomechanical investigations of shoulder cartilage research. It examines the effect of cartilage structure and constituents on tissue behavior and its adaptation to mechanical loading. In doing so, the study explains the relationship of tissue's functional behaviors to its structure and constituents which has important implications for tissue engineering strategies catering joint specific cartilage tissue generation.
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Escherichia coli sequence type 131 (ST131) have emerged as a pandemic lineage of important multidrug resistant pathogens worldwide. Despite many studies examining the epidemiology of ST131, only a few studies to date have investigated the capacity of ST131 strains to form biofilms. Some of these studies have reported contrasting findings, with no specific ST131 biofilm-promoting factors identified. Here we examined a diverse collection of ST131 isolates for in vitro biofilm formation in different media and assay conditions, including urine from healthy adult women. We found significant differences among strains and assay conditions, which offers an explanation for the contrasting findings reported by previous studies using a single condition. Importantly, we showed that expression of type 1 fimbriae is a critical determinant for biofilm formation by ST131 strains and that inhibition of the FimH adhesin significantly reduces biofilm formation. We also offer direct genetic evidence for the contribution of type 1 fimbriae in biofilm formation by the reference ST131 strain EC958, a representative of the clinically dominant H30-Rx ST131 subgroup. This is the first study of ST131 biofilm formation in biologically relevant conditions and paves the way for the application of FimH inhibitors in treating drug resistant ST131 biofilm infections.
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Settling, dewatering and filtration of flocs are important steps in industry to remove solids and improve subsequent processing. The influence of non-sucrose impurities (Ca2+, Mg2+, phosphate and aconitic acid) on calcium phosphate floc structure (scattering exponent, Sf), size and shape were examined in synthetic and authentic sugar juices using X-ray diffraction techniques. In synthetic juices, Sf decreases with increasing phosphate concentration to values where loosely bound and branched flocs are formed for effective trapping and removal of impurities. Although, Sf did not change with increasing aconitic acid concentration, the floc size significantly decreased reducing the ability of the flocs to remove impurities. In authentic juices, the flocs structures were marginally affected by increasing proportions of non-sucrose impurities. However, optical microscopy indicated the formation of well-formed macro-floc network structures in sugar cane juices containing lower proportions of non-sucrose impurities. These structures are better placed to remove suspended colloidal solids.