984 resultados para Cardiac mechanics, active strain


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Mega-scale glacial lineations (MSGLs) are longitudinally aligned corrugations (ridge-groove structures 6-100 km long) in sediment produced subglacially. They are indicators of fast flow and a common signature of ice-stream beds. We develop a qualitative theory that accounts for their formation, and use numerical modelling, and observations of ice-stream beds to provide supporting evidence. Ice in contact with a rough (scale of 10-10(3) m) bedrock surface will mimic the form of the bed. Because of flow acceleration and convergence in ice-stream onset zones, the ice-base roughness elements experience transverse strain, transforming them from irregular bumps into longitudinally aligned keels of ice protruding downwards. Where such keels slide across a soft sedimentary bed, they plough through the sediments, carving elongate grooves, and deforming material up into intervening ridges. This explains MSGLs and has important implications for ice-stream mechanics. Groove ploughing provides the means to acquire new lubricating sediment and to transport large volumes of it downstream. Keels may provide basal drag in the force budget of ice streams, thereby playing a role in flow regulation and stability We speculate that groove ploughing permits significant ice-stream widening, thus facilitating high-magnitude ice discharge.

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Multiply antibiotic-resistant (MAR) mutants of Escherichia coli and Salmonella enterica are characterized by reduced susceptibility to several unrelated antibiotics, biocides and other xenobiotics. Porin loss and/or active efflux have been identified as a key mechanisms of MAR. A single rapid test was developed for MAR. The intracellular accumulation of the fluorescent probe Hoechst (H) 33342 (bisbenzimide) by MAR mutants and those with defined disruptions in efflux pump and porin genes was determined in 96-well plate format. The accumulation of H33342 was significantly (P < 0.0001) reduced in MAR mutants of S. enterica serovar Typhimurium (n = 4) and E. coli (n = 3) by 41 +/- 8% and 17.3 +/- 7.2%, respectively, compared with their parental strains, which was reversed by the transmembrane proton gradient-collapsing agent carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) and the efflux pump inhibitor phenylalanine-arginine-beta-naphthylamide (PA beta N). The accumulation of H33342 was significantly reduced in mutants of Salmonella Typhimurium with defined disruptions in genes encoding the porins OmpC, OmpF, OmpX and OmpW, but increased in those with disruptions in efflux pump components TolC, AcrB and AcrF. Reduced accumulation of H33342 in three other MAR mutants of Salmonella Typhimurium correlated with the expression of porin and efflux pump proteins. The intracellular accumulation of H33342 provided a sensitive and specific test for MAR that is cheap and relatively rapid. Differential sensitivity to CCCP and PA beta N provided a further means to phenotypically identify MAR mutants and the role of active efflux in each strain.

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The quantitative effects of uniform strain and background rotation on the stability of a strip of constant vorticity (a simple shear layer) are examined. The thickness of the strip decreases in time under the strain, so it is necessary to formulate the linear stability analysis for a time-dependent basic flow. The results show that even a strain rate γ (scaled with the vorticity of the strip) as small as 0.25 suppresses the conventional Rayleigh shear instability mechanism, in the sense that the r.m.s. wave steepness cannot amplify by more than a certain factor, and must eventually decay. For γ < 0.25 the amplification factor increases as γ decreases; however, it is only 3 when γ e 0.065. Numerical simulations confirm the predictions of linear theory at small steepness and predict a threshold value necessary for the formation of coherent vortices. The results help to explain the impression from numerous simulations of two-dimensional turbulence reported in the literature that filaments of vorticity infrequently roll up into vortices. The stabilization effect may be expected to extend to two- and three-dimensional quasi-geostrophic flows.

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[1] A method is presented to calculate the continuum-scale sea ice stress as an imposed, continuum-scale strain-rate is varied. The continuum-scale stress is calculated as the area-average of the stresses within the floes and leads in a region (the continuum element). The continuum-scale stress depends upon: the imposed strain rate; the subcontinuum scale, material rheology of sea ice; the chosen configuration of sea ice floes and leads; and a prescribed rule for determining the motion of the floes in response to the continuum-scale strain-rate. We calculated plastic yield curves and flow rules associated with subcontinuum scale, material sea ice rheologies with elliptic, linear and modified Coulombic elliptic plastic yield curves, and with square, diamond and irregular, convex polygon-shaped floes. For the case of a tiling of square floes, only for particular orientations of the leads have the principal axes of strain rate and calculated continuum-scale sea ice stress aligned, and these have been investigated analytically. The ensemble average of calculated sea ice stress for square floes with uniform orientation with respect to the principal axes of strain rate yielded alignment of average stress and strain-rate principal axes and an isotropic, continuum-scale sea ice rheology. We present a lemon-shaped yield curve with normal flow rule, derived from ensemble averages of sea ice stress, suitable for direct inclusion into the current generation of sea ice models. This continuum-scale sea ice rheology directly relates the size (strength) of the continuum-scale yield curve to the material compressive strength.

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BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients. METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker β7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with β7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFβ production by T cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.

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Endogenous oxidative stress is a likely cause of cardiac myocyte death in vivo. We examined the early (0-2 h) changes in the proteome of isolated cardiac myocytes from neonatal rats exposed to H2O2 (0.1 mM), focussing on proteins with apparent molecular masses of between 20 and 30 kDa. Proteins were separated by two-dimensional gel electrophoresis (2DGE), located by silver-staining and identified by mass spectrometry. Incorporation of [35S]methionine or 32Pi was also studied. For selected proteins, transcript abundance was examined by reverse transcriptase-polymerase chain reaction. Of the 38 protein spots in the region, 23 were identified. Two families showed changes in 2DGE migration or abundance with H2O2 treatment: the peroxiredoxins and two small heat shock protein (Hsp) family members: heat shock 27 kDa protein 1 (Hsp25) and alphaB-crystallin. Peroxiredoxins shifted to lower pI values and this was probably attributable to 'over-oxidation' of active site Cys-residues. Hsp25 also shifted to lower pI values but this was attributable to phosphorylation. alphaB-crystallin migration was unchanged but its abundance decreased. Transcripts encoding peroxiredoxins 2 and 5 increased significantly. In addition, 10 further proteins were identified. For two (glutathione S-transferase pi, translationally-controlled tumour protein), we could not find any previous references indicating their occurrence in cardiac myocytes. We conclude that exposure of cardiac myocytes to oxidative stress causes post-translational modification in two protein families involved in cytoprotection. These changes may be potentially useful diagnostically. In the short term, oxidative stress causes few detectable changes in global protein abundance as assessed by silver-staining.

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The last 10–15 years have seen an expansion in the understanding of the intracellular signalling pathways activated in cardiac myocytes in response to hypertrophic or lethal stimuli. The mitogen-activated protein kinases (MAPKs) were identified as potential key mediators of cardiac myocyte responses in the early to mid-1990's, with the extracellular signal-regulated kinases 1/2 (ERK1/2) being potently activated by heterotrimeric Gq protein-coupled receptor (GqPCR) agonists, and the c-Jun N-terminal kinases (JNKs) and p38-MAPKs being potently activated by cell stresses.

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The toxic effects of oxidative stress on cells (including cardiac myocytes, the contractile cells of the heart) are well known. However, an increasing body of evidence has suggested that increased production of reactive oxygen species (ROS) promotes cardiac myocyte growth. Thus, ROS may be 'second messenger' molecules in their own right, and growth-promoting neurohumoral agonists might exert their effects by stimulating production of ROS. The authors review the principal growth-promoting intracellular signaling pathways that are activated by ROS in cardiac myocytes, namely the mitogen-activated protein kinase cascades (extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinases, and p38-mitogen-activated protein kinases) and the phosphoinositide 3-kinase/protein kinase B (Akt) pathway. Possible mechanisms are discussed by which these pathways are activated by ROS, including the oxidation of active site cysteinyl residues of protein and lipid phosphatases with their consequent inactivation, the potential involvement of protein kinase C or the apoptosis signal-regulating kinase 1, and the current models for the activation of the guanine nucleotide binding protein Ras.

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The conidia-mycelia transformation is an essential step during the life cycle of the fungal human pathogens of the Pseudallescheria boydii complex. In the present study, we have analyzed the protein and peptidase profiles in two distinct morphological stages, conidia and mycelia, of Scedosporium apiospermum sensu stricto. Proteins synthesized by the mycelia, migrating at the ranges of 62-48 and 22-18 kDa, were not detected from the conidial extract. Conidia produced a single cellular peptidase of 28 kDa able to digest copolymerized albumin, while mycelia yielded 6 distinct peptidases ranging from 90 to 28 kDa. All proteolytic enzymes were active at acidic pH and fully inhibited by 1,10-phenanthroline, characterizing these activities as metallo-type peptidases. Quantitative peptidase assay, using soluble albumin, showed a high metallopeptidase production in mycelial cells in comparison with conidia. The regulated expression of proteins and peptidases in different morphological stages of S. apiospermum represents a potential target for isolation of stage-specific markers for biochemical and immunological analysis.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The 1.7 angstrom resolution crystal structure of recombinant family G/11 beta-1,4-xylanase (rXynA) from Bacillus subtilis 1A1 shows a jellyroll fold in which two curved P-sheets form the active-site and substrate-binding cleft. The onset of thermal denaturation of rXynA occurs at 328 K, in excellent agreement with the optimum catalytic temperature. Molecular dynamics simulations at temperatures of 298-328 K demonstrate that below the optimum temperature the thumb loop and palm domain adopt a closed conformation. However, at 328 K these two domains separate facilitating substrate access to the active-site pocket, thereby accounting for the optimum catalytic temperature of the rXynA. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.

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The aim of the present study was to investigate the potential benefits of cold water immersion (CWI) and active recovery (AR) on blood lactate concentration ([Lac]) and heart rate variability (HRV) indices following high-intensity exercise. 20 male subjects were recruited. on the first visit, an incremental test was performed to determine maximal oxygen consumption and the associated speed (MAS). The remaining 3 visits for the performance of constant velocity exhaustive tests at MAS and different recovery methods (6 min) were separated by 7-day intervals [randomized: CWI, AR or passive recovery (PR)]. The CWI and AR lowered [Lac] (p < 0.05) at 11, 13 and 15 min after exercise cessation in comparison to PR. There was a 'time' and 'recovery mode' interaction for 2 HRV indices: standard deviation of normal R-R intervals (SDNN) (partial eta squared = 0.114) and natural log of low-frequency power density (lnLF) (partial eta squared = 0.090). CWI presented significantly higher SDNN compared to PR at 15 min of recovery (p < 0.05). In addition, greater SDNN values were found in CWI vs. AR during the application of recovery interventions, and at 30 and 75 min post-exercise (p < 0.05 for all differences). The lnLF during the recovery interventions and at 75 min post-exercise was greater using CWI compared with AR (p < 0.05). For square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD) and natural log of high-frequency power density (lnHF), a moderate effect size was found between CWI and PR during the recovery interventions and at 15 min post-exercise. Our findings show that AR and CWI offer benefits regarding the removal of [Lac] following high-intensity exercise. While limited, CWI results in some improvement in post-exercise cardiac autonomic regulation compared to AR and PR. Further, AR is not recommended if the aim is to accelerate the parasympathetic reactivation.