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Moderate Decrease (moderate + decrease)
Selected AbstractsThe proteasome inhibitor, MG132, promotes the reprogramming of translation in C2C12 myoblasts and facilitates the association of hsp25 with the eIF4F complexFEBS JOURNAL, Issue 17 2004Joanne L. Cowan The eukaryotic translation initiation factor (eIF) 4E, is regulated by modulating both its phosphorylation and its availability to interact with the scaffold protein, eIF4G, to form the mature eIF4F complex. Here we show that treatment of C2C12 myoblasts with the proteasomal inhibitor, MG132 (N -carbobenzoxyl-Leu-Leu-leucinal), resulted in an early decrease in protein synthesis rates followed by a partial recovery, reflecting the reprogramming of translation. The early inhibition of protein synthesis was preceded by a transient increase in eIF2, phosphorylation, followed by a sustained increase in eIF4E phosphorylation. Inhibition of eIF4E phosphorylation with CGP57380 failed to prevent translational reprogramming or the moderate decrease in eIF4F complexes at later times. Prolonged incubation with MG132 resulted in the increased expression of heat shock protein (hsp)25, ,B-crystallin and hsp70, with a population of hsp25 associating with the eIF4F complex in a p38 mitogen-activated protein kinase-dependent manner. Under these conditions, eIF4GI, and to a lesser extent eIF4E, re-localized from a predominantly cytoplasmic distribution to a more perinuclear and granular staining. Although MG132 had little effect on the colocalization of eIF4E and eIF4GI, it promoted the SB203580-sensitive association of eIF4GI and hsp25, an effect not observed with ,B-crystallin. Addition of recombinant hsp25 to an in vitro translation assay resulted in stimulation of on-going translation and a moderate decrease in de novo translation, indicating that this modified eIF4F complex containing hsp25 has a role to play in recovery of mRNA translation following cellular stress. [source] Synthesis and Enzymic Hydrolysis of Oligoribonucleotides Incorporating 3-Deazaguanosine: The Importance of the Nitrogen-3 Atom of Single Conserved Guanosine Residues on the Catalytic Activity of the Hammerhead RibozymeHELVETICA CHIMICA ACTA, Issue 8 2003Frank Seela Four base-modified hammerhead ribozyme/substrate complexes were constructed in which single guanosine (1) residues were replaced by 3-deazaguanosine (2) in the positions G5, G8, GL2.1, and G12. The base-modified ribozyme complexes were prepared by solid-phase synthesis of oligoribonucleotides employing the novel phosphoramidite 3 derived from 2. Phosphoramidite 3 carried a phenoxyacetyl group at the amino function and a diphenylcarbamoyl residue at the oxo group of the nucleobase. The 2,-hydroxy group was blocked with a triisopropylsilyl residue. Kinetic analysis of the phosphodiester hydrolysis showed a moderate decrease of the ribozyme catalytic activity when the residues G5 or G8 were replaced by 3-deazaguanosine and a 200-fold decrease when G12 was substituted. A 6-fold catalytic increase occurred when 3-deazaguanosine was replacing GL2.1 in the loop region. The data indicate that the N(3) atom of compound 2, in particular at position G12 is critical for the ribozyme activity. [source] Hot Isostatic Pressing of Cubic Boron Nitride,Tungsten Carbide/Cobalt (cBN,WC/Co) Composites: Effect of cBN Particle Size and Some Processing Parameters on their Microstructure and PropertiesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2 2007V. Martínez Cubic boron nitride (cBN)-cemented carbide composites have gained attraction over the last few years because of their potential uses as wear parts. The densification behavior of cBN,hard metal composites by glass encapsulation hot isostatic pressing,has been investigated. Composites with different cBN grades (from 0/0.5 to 6/12 ,m particle sizes) and cBN content (up to 50 vol%) were selected for this study. Near-full densification was obtained at temperatures between 1100° and 1200°C, and pressures between 150 and 200 MPa, respectively, while no phase transformation of cBN into the low-hardness hexagonal form has been detected by X-ray diffraction. The addition of cBN to the hard metal base material led to an increase of hardness, a significant increase of fracture toughness (KIC measured by Vickers indentation), and a moderate decrease of mechanical strength (determined by three-point bending). [source] The P2Y1 receptor plays an essential role in the platelet shape change induced by collagen when TxA2 formation is preventedJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2004P. Mangin Summary., ADP and TxA2 are secondary agonists which play an important role as cofactors when platelets are activated by agonists such as collagen or thrombin. The aim of the present study was to characterize the role of the ADP receptor P2Y1 in collagen-induced activation of washed platelets. Inhibition of P2Y1 alone with the selective antagonist MRS2179 prolonged the lag phase preceding aggregation in response to low or high concentrations of fibrillar collagen, without affecting the maximum amplitude of aggregation or secretion. A combination of MRS2179 and aspirin resulted in complete inhibition of platelet shape change at low and high collagen concentrations, together with a profound decrease in aggregation and secretion. Scanning electron microscopy showed that these platelets had conserved the discoid morphology typical of the resting state. A lack of shape change was also observed in aspirin-treated P2Y1 - and G,q -deficient mouse platelets and in ,-storage pool-deficient platelets from Fawn Hooded rats. In contrast, when the second ADP receptor P2Y12 was inhibited with AR-C69931MX, aspirin-treated platelets were still able to change shape and displayed only a moderate decrease in aggregation and secretion. In conclusion, this study provides evidence that collagen requires not only the TxA2 receptor Tp,, but also P2Y1, to induce platelet shape change. [source] Theoretical Simulation of Oxygen Transport to Brain by Networks of Microvessels: Effects of Oxygen Supply and Demand on Tissue HypoxiaMICROCIRCULATION, Issue 4 2000T.W. SECOMB ABSTRACT Objective: Simulations of oxygen delivery by a three-dimensional network of microvessels in rat cerebral cortex were used to examine how the distribution of partial pressure of oxygen (PO2) in tissue depends on blood flow and oxygen consumption rates. Methods: Network geometry was deduced from previously published scanning electron micrographs of corrosion casts. A nonlinear least-squares method, using images obtained at three different angles, was used to estimate vessel locations. The network consisted of 50 segments in a region 140 µm × 150 µm × 160 µm. A Green's function method was used to predict the PO2 distribution. Effects of varying perfusion and consumption were examined, relative to a control state with consumption 10 cm3O2/100 g per min and perfusion 160 cm3/100 g per min. Results: In the control state, minimum tissue PO2 was 7 mm Hg. A Krogh-type model with the same density of vessels, but with uniform spacing, predicted a minimum tissue PO2 of 23 mm Hg. For perfusion below 60% of control, tissue hypoxia (PO2 <1 mm Hg) was predicted. When perfusion was reduced by 75%, the resulting hypoxia could be eliminated by a 31% reduction in oxygen consumption rate. Conclusions: The simulations suggest that tissue hypoxia resulting from a severe decrease in brain perfusion, as can occur in stroke, may be avoided by a moderate decrease in oxygen consumption rate. [source] Quantitative morphological analysis of the Hubble Deep Field North and Hubble Deep Field South , I. Early- and late-type luminosity,size relations of galaxies out to z, 1MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2004I. Trujillo ABSTRACT Based on drizzled F606W and F814W images, we present quantitative structural parameters in the V -band rest-frame for all galaxies with z < 1 and I814(AB) < 24.5 mag in the Hubble Deep Fields North and South. Our structural parameters are based on a two-component surface brightness distribution using a Sérsic bulge and an exponential disc. Detailed simulations and comparisons with previous work are presented. The luminosity,size distribution of early-type galaxies is consistent with the hypothesis that their structural properties were already in place by z, 1 and have evolved passively since then; early-type galaxies were ,1.35(±0.1) mag brighter in rest-frame V -band luminosity at z, 0.7 than now. Compared with present-day late-type galaxies, those at z, 0.7 with LV > 0.2 × 1010 h,2 L, show a moderate decrease [,30(±10) per cent] in size [or interpreted differently, a decrease of ,0.77(±0.30) mag in the central surface brightness] at a given luminosity. Finally, we make a comparison of our results with the infall and hierarchical models. [source] Homocysteine levels after acute levodopa intake in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 9 2009Thomas Müller MD Abstract Levodopa (L -dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis-related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long-term effect of chronic L -dopa/DDI treatment. Little is known about the acute effects of L -dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L -dopa and homocysteine after acute L -dopa/DDI administration in PD patients with different L -dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L -dopa absorption after standardized intake of 125 mg L -dopa/benserazide with determination of L -dopa, 3- O -methyl-dopa (3-OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3-OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L -dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L -dopa metabolism is an important component for homocysteine elevation after one time L -dopa/DDI administration in PD patients. © 2009 Movement Disorder Society [source] Blue-Violet Excited Autofluorescence Spectroscopy and Imaging of Normal and Cancerous Human Bronchial Tissue after Formalin FixationPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2007Tanja Gabrecht Autofluorescence (AF) imaging is a powerful tool for the detection of (pre-)neoplastic lesions in the bronchi. Several endoscopic imaging systems exploit the spectral and intensity contrast of AF between healthy and (pre-)neoplastic bronchial tissues, yet, the mechanisms underlying these contrasts are poorly understood. In this report, the effect of formalin fixation on the human bronchi AF, hence on the contrast, was studied by spectrofluorometric point measurements and DAFE (Diagnostic AutoFluorescence Endoscopy) broad field imaging. Generally, formalin-fixed samples have higher AF intensity than in vivo, whereas the emission spectral shape is similar. Additionally, the spectrofluorometric data showed a moderate decrease of the AF intensity on (pre-)neoplastic lesions relative to the healthy bronchial samples. However, this decrease was lower than that reported from in vivo measurements. Neither spectral measurements nor imaging revealed spectral contrast between healthy bronchial tissue and (pre-)neoplastic lesions in formalin. These results indicate that epithelial thickening and blood supply in the adjacent lamina propria are likely to play a key role in the generation of the AF contrast in bronchial tissues. Our results show that the AF contrast in bronchial tissues was significantly affected by standard, 10% buffered, formalin fixation. Therefore, these samples are not suited to AF contrast studies. [source] Effects of extracellular nucleotides and nucleosides on prostate carcinoma cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2001Rodolphe Janssens The purpose of this work was to characterize the receptors involved in the action of nucleotides on the human prostate carcinoma cell lines LNCaP, PC-3 and DU145. Northern blotting revealed the presence of P2Y2, P2Y6 and P2Y11 messengers in the three cell lines. P2Y1 mRNA was only observed in the DU145 cells. In both PC-3 and DU145 cells, ATP and UTP stimulated inositol phosphate accumulation in an equipotent, equiactive and non-additive way, suggesting the involvement of P2Y2 receptors. ATP also increased cyclic AMP, but this effect is likely to result from degradation into adenosine and activation of A2 receptor. A2 receptor activation led to a synergistic enhancement of prostate-specific antigen secretion induced by vasoactive intestinal peptide. RT , PCR experiments detected the expression of the P2X4 and P2X5 receptors in the DU145 cells and the P2X4, P2X5 and P2X7 receptors in the PC-3 cells. The calcium influx induced by BzATP confirmed the functional expression of P2X receptors. ATP inhibited the growth of PC-3 and DU145 cells. This effect was mimicked neither by UTP nor by adenosine, indicating that it does not result from phospholipase C or adenylyl cyclase activation. On the contrary, in PC-3 cells, BzATP reproduced the effect of ATP, which was associated to a moderate decrease of proliferation and an increase of apoptosis. In DU145 cells, ATP was more potent than BzATP and growth inhibition was mainly associated with necrosis. We suggest that P2X receptors might be involved in the inhibition by nucleotides of prostate carcinoma cell growth. British Journal of Pharmacology (2001) 132, 536,546; doi:10.1038/sj.bjp.0703833 [source] Function of macular area in retinopathy of prematurityACTA OPHTHALMOLOGICA, Issue 2007AM SHAMSHINOVA Purpose: To assess the bioelectric activity of the retina at different stages of the retinopathy of prematurity (RP). Methods: 21 children with RoP (stage 1-4, 6-14 years old, born at 27-32 week of gestation with the birth weight of 730-1800g) were examined. In 4 of children the prophylactic laser coagulation of avascular retina was performed in the active phase. Visual acuity (VA) at the stage 1 of RoP amounted to 0,75; at the stage 2: 0,5; at the stage 3: 0,25 and at the stage 4: 0,02. Macular (MBN Moscow) and mf ERG( Roland Concult Germany) were examined. Results: There was no correlation between VA values and parameters of multifocal (mf) and macular (m) ERG. Patients with RP of stage1 showed a moderate reduction of b-wave magnitude of mERG at its normal latency. This correlated with mfERG data in central hexagons 15 degrees. The magnitude and latency of mERG were changed to a great extent in RP patients of stages 2-3. The waves N1 and P1 of mERG were also heavily decreased at normal latency. The patients with severe retinal abnormalities, like retinal detachment, have subnormal mERG-values with prolonged latency, and moderate decrease of retinal density in the central ring and considerable changes with eccentricity in mfERG. Conclusions: RP patients 1-4 stages showed considerable impairment of macular function independent of the ophthalmoscopic changes. Even occult or weak-manifested of the diseases in the macula might be accompanied with the moderate decrease of macular bioelectric activity, including the abrupt abnormalities of the electrogenesis and neuronal interactions in the macular area. Decline VA d'not always had relation with RP. The pathophysiologic rationale of the latter needs to be elucidated in the future studies. [source] Interspecific differences in population trends of Spanish birds are related to habitat and climatic preferencesGLOBAL ECOLOGY, Issue 1 2008Javier Seoane ABSTRACT Aim, Animal monitoring programmes have allowed analyses of population trends, most of which now comment on the possible effect of global climate change. However, the relationship between the interspecific variation in population trends and species traits, such as habitat preferences, niche breadth or distribution patterns, has received little attention, in spite of its usefulness in the construction of ecological generalizations. The objectives of this study were: (1) to determine whether there are characteristics shared among species with upwards or downwards trends, and (2) to assess whether population changes agree with what could be expected under global warming (a decrease in species typical of cooler environments). Location, The Spanish part of the Iberian Peninsula (c. 500,000 km2) in the south-western part of the Mediterranean Basin. Methods, We modelled recent breeding population changes (1996,2004), in areas without apparent land use changes, for 57 common passerine birds with species-specific ecological and distributional patterns as explanatory variables. Results, One-half of these species have shown a generalized pattern towards the increase of their populations, while only one-tenth showed a significant decrease. One half (54%) of the interspecific variability in yearly population trends is explained considering species-specific traits. Species showing more marked increases preferred wooded habitats, were habitat generalists and occupied warmer and wetter areas, while moderate decreases were found for open country habitats in drier areas. Main conclusions, The coherent pattern in population trends we found disagrees with the proposed detrimental effect of global warming on bird populations of western Europe, which is expected to be more intense in bird species inhabiting cooler areas and habitats. Such a pattern suggests that factors other than the increase in temperature may be brought to discussions on global change as relevant components to explain recent changes in biodiversity. [source] ,-Glutamyltranspeptidase,deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular functionHEPATOLOGY, Issue 4 2000Yvonne Will ,-Glutamyltranspeptidase (GGT)-deficient mice (GGT,/,) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by ,50% in GGT,/, mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT,/, mice liver mitochondria were ,60% those of wild-type mice primarily as a result of impaired state 3 respiration. Mitochondrial adenine nucleotide content was decreased by ,40% in mitochondria obtained from GGT,/, mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT,/, knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT,/, mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT,/, mice with N -acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT,/, mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice. [source] Nucleus pulposus glycosaminoglycan content is correlated with axial mechanics in rat lumbar motion segmentsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2006John I. Boxberger Abstract The unique biochemical composition and structure of the intervertebral disc allow it to support load, permit motion, and dissipate energy. With degeneration, both the biochemical composition and mechanical behavior of the disc are drastically altered, yet quantitative relationships between the biochemical changes and overall motion segment mechanics are lacking. The objective of this study was to determine the contribution of nucleus pulposus glycosaminoglycan content, which decreases with degeneration, to mechanical function of a rat lumbar spine motion segment in axial loading. Motion segments were treated with varying doses of Chondroitinase-ABC (to degrade glycosaminoglycans) and loaded in axial cyclic compression-tension, followed by compressive creep. Nucleus glycosaminoglycan content was significantly correlated (p,<,0.05) with neutral zone mechanical behavior, which occurs in low load transition between tension and compression (stiffness: r,=,0.59; displacement: r,=,,0.59), and with creep behavior (viscous parameter ,1: r,=,0.34; short time constant ,1: r,=,0.46). These results indicate that moderate decreases in nucleus glycosaminoglycan content consistent with early human degeneration affect overall mechanical function of the disc. These decreases may expose the disc to altered internal stress and strain patterns, thus contributing through mechanical or biological mechanisms to the degenerative cascade. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] The Geography of Opportunity and Unemployment: An Integrated Model of Residential Segregation and Spatial MismatchJOURNAL OF URBAN AFFAIRS, Issue 4 2005Michael Howell-Moroney Using National Longitudinal Survey of Youth (1979) data, I estimate a two-step model that separately models the effects of segregation and spatial mismatch. The first model predicts educational attainment as a function of exposure to residential segregation as a youth. The second model predicts unemployment probability as an adult as a function of educational attainment and spatial mismatch. The empirical results show that segregation does have discernable effects on educational attainment for blacks, but not for whites. I also find that spatial mismatch affects unemployment probability for blacks, but such an effect is hardly present for whites. A partial equilibrium analysis using predictions from the models shows that large changes in either segregation levels or the central city/suburban distribution of the black population would yield only moderate decreases in unemployment probability for the black population overall. Yet despite small predicted effects, these results should be viewed with caution because the general equilibrium effects of a large scale movement of blacks and whites across metropolitan space are largely impossible to predict with current data. [source] | ||||||||||||||||