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Selected AbstractsPossible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Association of Molecular Variants, Haplotypes, and Linkage Disequilibrium Within the Human Vitamin D-Binding Protein (DBP) Gene With Postmenopausal Bone Mineral Density,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2003Yoichi Ezura Abstract Possible contribution of vitamin D-binding protein (DBP) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T-C-C-G-T-C in ,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E, and IVS11+1097G>C) displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. Introduction: Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D-binding protein (DBP), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. Methods: To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. Results and Conclusions: Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D, and r2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) at various levels. An intronic SNP (IVS11+1097G>C) with the highest significance of association (p = 0.006) showed significant LD with four SNPs located around the first exon (r2 values >0.18, D, > 0.5). A non-synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G>C. The chromosomal dosage of one haplotype (T-C-C-G-T-C in ,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E and IVS11+1097G>C) estimated in each subject displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. [source] Confidence and decision type under matched stimulus conditions: overconfidence in perceptual but not conceptual decisionsJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 3 2008Sara Kvidera Abstract Within the domain of metacognition, there is disagreement whether different processes underlie evaluations of confidence in perceptual versus conceptual decisions. The relationship between confidence and accuracy for perceptual and conceptual decisions was compared using newly created stimuli that could be used to elicit either decision type. Based on theories of Brunswikian and Thurstonian uncertainties, significant underconfidence for perceptual decisions and overconfidence for conceptual decisions were predicted. Three within-subjects experiments did not support this hypothesis. Participants showed significant overconfidence for perceptual decisions and no overconfidence for conceptual decisions. In addition, significant hard-easy effects were consistently found for both decision types. Incorporating our findings with past results reveals that both over- and underconfidence are attainable on perceptual tasks. This conclusion, in addition to the common presence of hard-easy effects and significant across-task correlations in over/underconfidence, suggests that confidence judgments for the two decision types may depend on largely shared processes. Possible contributions to confidence and over/underconfidence are explored, focusing on response time factors and participants' knowledge bases. Copyright © 2007 John Wiley & Sons, Ltd. [source] HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible contributions to drug resistance and a potential new target site for drugsPROTEIN SCIENCE, Issue 5 2004Alexander L. Perryman No abstract is available for this article. [source] Spectral composition of electromagnetic fluctuations induced by a lossy layered systemANNALEN DER PHYSIK, Issue 7-8 2003I. Dorofeyev Abstract We calculate the spectral characteristics of fluctuating electromagnetic fields generated by a half-space covered with a film of an arbitrary thickness. Materials of the half-space and the film are described by different complex permittivities. Expressions for spectral power densities of fluctuating fields and all spatial derivatives expressed via Fresnel coefficients for "p" and "s" waves are derived. Various limiting cases for propagating and evanescent waves in cases of different film thickness are considered. Possible contributions to spectral power densities from interface excitations and wave-guide modes are discussed by analyzing the Fresnel factors in the expressions. Using the results for spatial derivatives a closed analytical expression for a multipolar force acting on a small particle near a half-space is found for multipoles of all orders. The case for a dipole interaction follows directly from a general solution. [source] REVIEW: Role of adipokines in obesity-associated hypertensionACTA PHYSIOLOGICA, Issue 2 2010M. Vlasova Abstract It has been well documented that obesity is a major risk factor for the development of the hypertensive state. The correlation between body mass index and blood pressure level is well established. Nevertheless, the exact mechanisms which contribute to obesity-related hypertension remain poorly understood. In the last years, we have realized that the white adipose tissue is not just an inert organ for nutrient storage and isolation but rather depending on the body mass index the biggest endocrinological organ. Thus, the possible contribution of adipokines to the blood pressure elevation becomes an attractive hypothesis to explain the hypertensive state that often occurs in obesity. In this review, we consider direct and indirect effects of main adipokines on structural and functional changes in the cardiovascular system. [source] Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patientsDIABETIC MEDICINE, Issue 10 2005U. R. Kuppusamy Abstract Aims Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant,antioxidant levels in these patients. Methods Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods. Results Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA1c, fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant,antioxidant parameters as a function of HbA1c in each ethnic group revealed a strong association of HbA1c with oxidative indices. Conclusions The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA1c remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration. [source] Metabolism of uniconazole-P in water-sediment systems under illuminationENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Rika Kodaka Abstract Aerobic soil metabolism of uniconazole-P ([S]- E -1-[4-chlorophenyl]-4,4-dimethyl-2-[1,2,4-triazole-1-yl]-penten-3-ol) and the effect of illumination on metabolic profiles were studied in the water,sediment system when spiked to water. Uniconazole-P was gradually partitioned to the sediment with an aquatic half-life of 6.9 d in darkness with formation of bound residues. Illumination of the system from a xenon lamp (>290 nm) greatly accelerated the degradation of uniconazole-P via photoinduced isomerization between E- and Z-isomers with a subsequent intramolecular cyclization, and its aquatic half-life was greatly reduced to 0.6 d. Kinetic analysis based on compartment models suggested the possible contribution of photodegradation at the water-sediment interface, leading to more formation of the cyclized derivative in the sediment. [source] Attention , oscillations and neuropharmacologyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Gustavo Deco Abstract Attention is a rich psychological and neurobiological construct that influences almost all aspects of cognitive behaviour. It enables enhanced processing of behaviourally relevant stimuli at the expense of irrelevant stimuli. At the cellular level, rhythmic synchronization at local and long-range spatial scales complements the attention-induced firing rate changes of neurons. The former is hypothesized to enable efficient communication between neuronal ensembles tuned to spatial and featural aspects of the attended stimulus. Recent modelling studies suggest that the rhythmic synchronization in the gamma range may be mediated by a fine balance between N -methyl- d -aspartate and ,-amino-3-hydroxy-5-methylisoxazole-4-propionate postsynaptic currents, whereas other studies have highlighted the possible contribution of the neuromodulator acetylcholine. This review summarizes some recent modelling and experimental studies investigating mechanisms of attention in sensory areas and discusses possibilities of how glutamatergic and cholinergic systems could contribute to increased processing abilities at the cellular and network level during states of top-down attention. [source] Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Eduardo D. Martín Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source] Calcium modulates endopeptidase 24.15 (EC 3.4.24.15) membrane association, secondary structure and substrate specificityFEBS JOURNAL, Issue 12 2005Vitor Oliveira The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the extracellular environment as a secreted protein. Outside the cell, this enzyme degrades several neuropeptides containing from 5 to 17 amino acids (e.g. gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be stimulated linearly by reduced concentrations of extracellular calcium. In the present report we demonstrate that extracellular calcium concentration has no effect on the total amount of the extracellular (cell associated + medium) enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy suggested that the absence of calcium favors the enzyme shedding from the plasma membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and D159) were altered by site-directed mutagenesis to investigate their possible contribution to binding of the enzyme at the cell surface. These mutated recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. However, immunocytochemical analyses by confocal microscopy consistently show a reduced ability of the D93A mutant to associate with the plasma membrane of glioma C6 cells when compared with the wild-type enzyme. These data and the model of the enzyme's structure as determined by X-ray diffraction suggest that D93 is located at the enzyme surface and is consistent with membrane association of EP24.15. Moreover, calcium was also observed to induce a major change in the EP24.15 cleavage site on distinctive fluorogenic substrates. These data suggest that calcium may be an important modulator of ep24.15 cell function. [source] Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patientsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Sanna K. Ylisaukko-oja Abstract Germline mutations in fumarate hydratase (FH) gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. In HLRCC, the most common clinical features are leiomyomas of the skin and uterus, and in a subset of the families, renal cell cancer (RCC) and uterine leiomyosarcoma (ULMS) occur frequently at young age. This study was conducted to evaluate the possible contribution of FH mutations in a population-based series of early onset (,45 years) ULMSs. Eighty-one cases were identified through the national cancer registry, and samples from 67 cases (83%) were available for FH mutation screening and analysis of allelic imbalance (AI) at the FH locus. Seventeen percent of tumors showed AI. In the mutation analysis, a novel missense mutation K424R was found. The mutation was also found from the patient's normal tissue. To study whether this variant has functional consequences, FH enzyme activity assay was performed in a cell model. The activity of the mutated protein was significantly reduced as compared to wild type (p = 0.009). This study shows that FH germline mutations can occur in seemingly nonsyndromic cases of ULMS (1/67, 1.5%). It appears that on the population level hereditary FH defects do play a role in pathogenesis of sporadic early onset ULMSs, albeit rarely. © 2006 Wiley-Liss, Inc. [source] Patterns of species richness on very small islands: the plants of the Aegean archipelagoJOURNAL OF BIOGEOGRAPHY, Issue 7 2006Maria Panitsa Abstract Aim, To investigate the species,area relationship (SAR) of plants on very small islands, to examine the effect of other factors on species richness, and to check for a possible Small Island Effect (SIE). Location, The study used data on the floral composition of 86 very small islands (all < 0.050 km2) of the Aegean archipelago (Greece). Methods, We used standard techniques for linear and nonlinear regression in order to check several models of the SAR, and stepwise multiple regression to check for the effects of factors other than area on species richness (,habitat diversity', elevation, and distance from nearest large island), as well as the performance of the Choros model. We also checked for the SAR of certain taxonomic and ecological plant groups that are of special importance in eastern Mediterranean islands, such as halophytes, therophytes, Leguminosae and Gramineae. We used one-way anova to check for differences in richness between grazed and non-grazed islands, and we explored possible effects of nesting seabirds on the islands' flora. Results, Area explained a small percentage of total species richness variance in all cases. The linearized power model of the SAR provided the best fit for the total species list and several subgroups of species, while the semi-log model provided better fits for grazed islands, grasses and therophytes. None of the nonlinear models explained more variance. The slope of the SAR was very high, mainly due to the contribution of non-grazed islands. No significant SIE could be detected. The Choros model explained more variance than all SARs, although a large amount of variance of species richness still remained unexplained. Elevation was found to be the only important factor, other than area, to influence species richness. Habitat diversity did not seem important, although there were serious methodological problems in properly defining it, especially for plants. Grazing was an important factor influencing the flora of small islands. Grazed islands were richer than non-grazed, but the response of their species richness to area was particularly low, indicating decreased floral heterogeneity among islands. We did not detect any important effects of the presence of nesting seabird colonies. Main conclusions, Species richness on small islands may behave idiosyncratically, but this does not always lead to a typical SIE. Plants of Aegean islets conform to the classical Arrhenius model of the SAR, a result mainly due to the contribution of non-grazed islands. At the same time, the factors examined explain a small portion of total variance in species richness, indicating the possible contribution of other, non-standard factors, or even of stochastic effects. The proper definition of habitat diversity as pertaining to the taxon examined in each case is a recurrent problem in such studies. Nevertheless, the combined effect of area and a proxy for environmental heterogeneity is once again superior to area alone in explaining species richness. [source] Association of Molecular Variants, Haplotypes, and Linkage Disequilibrium Within the Human Vitamin D-Binding Protein (DBP) Gene With Postmenopausal Bone Mineral Density,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2003Yoichi Ezura Abstract Possible contribution of vitamin D-binding protein (DBP) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T-C-C-G-T-C in ,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E, and IVS11+1097G>C) displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. Introduction: Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D-binding protein (DBP), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. Methods: To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. Results and Conclusions: Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D, and r2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) at various levels. An intronic SNP (IVS11+1097G>C) with the highest significance of association (p = 0.006) showed significant LD with four SNPs located around the first exon (r2 values >0.18, D, > 0.5). A non-synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G>C. The chromosomal dosage of one haplotype (T-C-C-G-T-C in ,39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E and IVS11+1097G>C) estimated in each subject displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. [source] Thrombin induces cyclooxygenase-2 expression and prostaglandin E2 release via PAR1 activation and ERK1/2- and p38 MAPK-dependent pathway in murine macrophagesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2009Huey-Ming Lo Abstract Thrombin levels increase at sites of vascular injury and during acute coronary syndromes. It is also increased several fold by sepsis with a reciprocal decrease in the anti-thrombin III levels. In this study we investigate the effects of thrombin on the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PG) production in macrophages. Thrombin-induced COX-2 protein and mRNA expression in RAW264.7 and primary cultured peritoneal macrophages. A serine proteinase, trypsin, also exerted a similar effect. The inducing effect by thrombin in macrophages was not affected by a lipopolysaccharide (LPS)-binding antibiotic, polymyxin B, excluding the possibility of LPS contamination. The increase of COX-2 expression by thrombin was functionally linked to release of PGE2 and PGI2 but not thromboxane A2 into macrophage culture medium. Thrombin-induced COX-2 expression and PGE2 production were significantly attenuated by PD98059 and SB202190 but not by SP600125, suggesting that ERK1/2 and p38 MAPK activation were involved in this process. This was supported by the observation that thrombin could directly activate ERK1/2 and p38 MAPK in macrophages. A further analysis indicated that the proteinase-activated receptor 1 (PAR1)-activating agonist induced effects similar to those induced by thrombin in macrophages and the PAR1 antagonist-SCH79797 could attenuate thrombin-induced COX-2 expression and PGE2 release. Taken together, we provided evidence demonstrating that thrombin can induce COX-2 mRNA and protein expression and PGE2 production in macrophages through PAR1 activation and ERK1/2 and p38 MAPK-dependent pathway. The results presented here may explain, at least in part, the possible contribution of thrombin and macrophages in these pathological conditions. J. Cell. Biochem. 108: 1143,1152, 2009. © 2009 Wiley-Liss, Inc. [source] Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget's diseaseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2009Si-Yuan Chen Background:, Activating transcription factor 2 (ATF2) and signal transducer and activator of transcription 3 (STAT3) play important roles in the pathogenesis of various tumors, but ATF2 expression/activation and the relationship with STAT3 activation have not yet been investigated in extramammary Paget's disease (EMPD). Objective:, To investigate potential contributions of ATF2 and STAT3 pathways to the pathogenesis of EMPD. Method:, Paraffin-embedded 45 EMPD specimens (43 primary EMPD and 2 nodal metastases) were subjected to immunohistochemical staining for ATF2, phosphorylated (p)-ATF2 and p-STAT3. Results:, P-ATF2 expression in advanced EMPD, non-invasive EMPD and normal skin (NS) controls were 97.9 ± 1.8%, 82.0 ± 23.4% and 45.8 ± 3.2%, respectively, and p-STAT3 expression in advanced EMPD, non-invasive EMPD and NS were 97.0 ± 2.9%, 83.2 ± 23.3% and 50.1 ± 6.7%, respectively. P-ATF2 and p-STAT3 expressions in EMPD were significantly higher than those in NS, indicating a possible contribution of these pathways to the tumor development. P-ATF2 and p-STAT3 expressions in advanced EMPD were significantly higher than those in non-invasive EMPD, possibly indicating that these pathways might also contribute to the tumor invasion and/or metastasis. We also found an exceptionally high positive correlation between p-ATF2 and p-STAT3 expressions in EMPD. Conclusions:, P-ATF2 and p-STAT3 are concordantly overexpressed in EMPD and their expressions may possibly be associated with the tumor stage. [source] Retrograde axonal transport and motor neuron diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Anna-Lena Ström Abstract Transport of material between extensive neuronal processes and the cell body is crucial for neuronal function and survival. Growing evidence shows that deficits in axonal transport contribute to the pathogenesis of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here we review recent data indicating that defects in dynein-mediated retrograde axonal transport are involved in ALS etiology. We discuss how mutant copper-zinc superoxide dismutase (SOD1) and an aberrant interaction between mutant SOD1 and dynein could perturb retrograde transport of neurotrophic factors and mitochondria. A possible contribution of axonal transport to the aggregation and degradation processes of mutant SOD1 is also reviewed. We further consider how the interference with axonal transport and protein turnover by mutant SOD1 could influence the function and viability of motor neurons in ALS. [source] Extended charge delocalization to 4-phenoxy substituent in benzhydryl solvolysis: possible contribution of non-canonical resonance structure in the cationic transition stateJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 1 2002Kwang-Ting Liu Abstract Solvolytic reactivities of 4-nitrobenzhydryl bromides (2b,5b) and chlorides (2c,5c) were studied using single- and dual-parameter Grunwald,Winstein-type correlation analyses with YBnX and YxBnX scales, respectively. Extended charge delocalization over two aryl rings at cationic transition states were found for 3 and 5, but not for 2 or 4. Calculations of the charge distributions in 3c and in the corresponding cation 3a were performed using a Hartree,Fock approximation (RHF/6-31G* basis set) and density functional models (pBP/DN** and other basis sets), respectively, on Mulliken population analysis and on electrostatic potential analysis. The possible contribution of non-canonical resonance structure is discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source] Proton release by N2 -fixing plant roots: A possible contribution to phytoremediation of calcareous sodic soilsJOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 1 2003Manzoor Qadir Prof. Dr. Abstract With a world-wide occurrence on about 560 million hectares, sodic soils are characterized by the occurrence of excess sodium (Na+) to levels that can adversely affect crop growth and yield. Amelioration of such soils needs a source of calcium (Ca2+) to replace excess Na+ from the cation exchange sites. In addition, adequate levels of Ca2+ in ameliorated soils play a vital role in improving the structural and functional integrity of plant cell walls and membranes. As a low-cost and environmentally feasible strategy, phytoremediation of sodic soils , a plant-based amelioration , has gained increasing interest among scientists and farmers in recent years. Enhanced CO2 partial pressure (PCO2) in the root zone is considered as the principal mechanism contributing to phytoremediation of sodic soils. Aqueous CO2 produces protons (H+) and bicarbonate (HCO3 - ). In a subsequent reaction, H+ reacts with native soil calcite (CaCO3) to provide Ca2+ for Na+ Ca2+ exchange at the cation exchange sites. Another source of H+ may occur in such soils if cropped with N2 -fixing plant species because plants capable of fixing N2 release H+ in the root zone. In a lysimeter experiment on a calcareous sodic soil (pHs = 7.4, electrical conductivity of soil saturated paste extract (ECe) = 3.1 dS m -1, sodium adsorption ratio (SAR) = 28.4, exchangeable sodium percentage (ESP) = 27.6, CaCO3 = 50 g kg -1), we investigated the phytoremediation ability of alfalfa (Medicago sativa L.). There were two cropped treatments: Alfalfa relying on N2 fixation and alfalfa receiving NH4NO3 as mineral N source, respectively. Other treatments were non-cropped, including a control (without an amendment or crop), and soil application of gypsum or sulfuric acid. After two months of cropping, all lysimeters were leached by maintaining a water content at 130% waterholding capacity of the soil after every 24±1 h. The treatment efficiency for Na+ removal in drainage water was in the order: sulfuric acid > gypsum = N2 -fixing alfalfa > NH4NO3-fed alfalfa > control. Both the alfalfa treatments produced statistically similar root and shoot biomass. We attribute better Na+ removal by the N2 -fixing alfalfa treatment to an additional source of H+ in the rhizosphere, which helped to dissolve additional CaCO3 and soil sodicity amelioration. Protonenabgabe durch N2 -fixierende Pflanzenwurzeln: ein möglicher Beitrag zur Phytomelioration von kalkreichen Natriumböden Bei einem weltweiten Vorkommen auf etwa 560 Millionen Hektar sind Natriumböden durch einen Überschuss an Natrium (Na+) gekennzeichnet, der das Wachstum und den Ertrag von Kulturpflanzenbeständen nachteilig beeinflussen kann. Die Melioration solcher Böden erfordert Calcium (Ca2+), um überschüssiges Na+ von Kationen-Austauscherplätzen zu verdrängen. Außerdem spielt Ca2+ eine wichtige Rolle bei der Verbesserung der strukturellen und funktionellen Integrität pflanzlicher Zellwände und Membranen. Als kostengünstige und umweltfreundliche Strategie hat die Phytomelioration von Natriumböden , eine auf Pflanzen beruhende Melioration , in den letzten Jahren zunehmendes Interesse bei Wissenschaftlern und Landwirten gefunden. Ein erhöhter CO2 -Partialdruck (PCO2) in der Rhizosphäre wird als hauptsächlicher Mechanismus angesehen, der zur Phytomelioration von Natriumböden beiträgt. In Wasser gelöst, erzeugt CO2 Protonen (H+) und Bikarbonate (HCO3 - ). Anschließend reagiert H+ mit nativem Calcit (CaCO3), wobei sich Ca2+ löst und Na+ von Austauscherplätzen verdrängt. Eine weitere H+ -Quelle könnte die H+ -Abgabe von Wurzeln N2 -fixierender Pflanzen sein, da diese in der Lage sind, H+ in die Rhizosphäre abzugeben. In einem Lysimeterversuch mit einem kalkreichen Natriumboden (pHs = 7, 4; ECe = 3, 1 dS m -1; SAR = 28, 4; ESP = 27, 6; CaCO3 = 50 g kg -1) wurde die Möglichkeit einer Phytomelioration mit N2 -fixierender Luzerne (Medicago sativa L.) im Vergleich zu einer mit mineralischem N ernährten Luzerne (NH4NO3) untersucht. In weiteren Varianten (Applikation von Gips bzw. Schwefelsäure) wurde die chemische Melioration einer nicht behandelten Kontrolle gegenübergestellt. Beide Ernährungsformen führten zu statistisch ähnlicher Wurzelund Sprossmasse der Luzerne. Nach zweimonatigem Pflanzenwachstum erfolgte alle 24±1 h eine Dränung der Lysimeter durch Zugabe einer Wassermenge von 130% der maximalen Wasserkapazität zum Boden. Hinsichtlich der Effizienz, Na+ über Auswaschung aus dem Boden zu entfernen, zeigte sich folgende Reihenfolge: Schwefelsäure > Gips = N2 -fixierende Luzerne > NH4NO3 -ernährte Luzerne > Kontrolle. Wir führen das bessere Meliorationsergebnis in der Variante der N2 -fixierenden Luzerne auf eine zusätzliche H+ -Quelle in der Rhizosphäre zurück, die zur Lösung von zusätzlichem CaCO3 beitrug. [source] Acetaldehyde and the Hypothermic Effects of Ethanol in MiceALCOHOLISM, Issue 11 2009Catherine Closon Background:, Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of acetaldehyde or the contribution of acetaldehyde to ethanol-induced hypothermia. The aim of the present study is to better understand the hypothermic effects of acetaldehyde and the possible contribution of acetaldehyde in ethanol-induced hypothermia, especially under conditions leading to acetaldehyde accumulation. Methods:, Female Swiss mice were injected intraperitoneally with ethanol and acetaldehyde and their rectal temperatures were measured with a digital thermometer at various time points after the injections. Experiment 1 compared the hypothermic effects of various acetaldehyde doses (0 to 300 mg/kg) with a reference dose of ethanol (3 g/kg). Experiment 2 tested the effects of a pretreatment with the aldehyde dehydrogenase (ALDH) inhibitor cyanamide (25 mg/kg) on ethanol- and acetaldehyde-induced hypothermia. In experiments 3 and 4, mice received a combined pretreatment with cyanamide and the alcohol dehydrogenase (ADH) inhibitor 4-Methylpyrazole (10 mg/kg) before the injection of ethanol or acetaldehyde. Results:, Acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but of shorter duration than ethanol-induced hypothermia. The inhibition of ALDH enzymes by cyanamide induced a strong potentiation of both ethanol- and acetaldehyde-induced hypothermia. The pretreatment with 4-MP prevented the potentiation of ethanol-induced hypothermia by cyanamide, but slightly increased the potentiation of acetaldehyde-induced hypothermia by cyanamide. Conclusions:, The results of the present study clearly show that acetaldehyde has hypothermic properties in mice at least at relatively high concentrations. Furthermore, the accumulation of acetaldehyde following ALDH inhibition strongly enhanced the hypothermic effects of ethanol. These latter results confirm the hypothermic properties of acetaldehyde and show that acetate, the next step in ethanol metabolism, is not involved in these hypothermic effects. Finally, the experiment with 4-MP indicates that the potentiating effects of cyanamide are mediated by the peripheral accumulation of acetaldehyde, which then reaches the brain to induce a severe hypothermia. [source] Assessment of the role of heparan sulfate in high molecular weight kininogen binding to human umbilical vein endothelial cellsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2003L.P. Fernando Summary., The assembly and activation of the kinin forming system components on human umbilical vein endothelial cells (HUVEC) have been studied in great detail. Proteins such as gC1qR, cytokeratin-1 and u-PAR have been identified to be responsible for Zn2+ -dependent binding of high molecular weight kininogen (HK) to HUVEC. Heparan sulfate has also been shown to have a major role in Zn2+ -dependent binding of HK to the endothelial cell line, Ea.hy 926. In this study, we have analyzed the possible contribution of heparan sulfate to high molecular weight kininogen binding to HUVEC using multiple approaches. The presence of heparan sulfate on HUVEC was analyzed by staining with an antibody specific for heparan sulfate. Incubation of the cells with bacterial heparinases removed the heparan sulfate from the cell surface to the level seen with a control antibody, however, the Zn2+ -dependent binding of HK was not affected. Further, blocking of heparan sulfate with a specific antibody to heparan sulfate even after digestion with heparinases did not reduce HK binding whereas antibodies to the proteins gC1qR and cytokeratin-1 consistently reduced the binding of HK to the endothelial cells. The binding intensities of FITC-labeled HK were similar in heparinase-treated and -untreated HUVEC. The rate of kallikrein formation by the assembly of factor XII, HK and PK were similar in both heparinase-treated and non-treated HUVEC. All of these data indicate that heparan sulfate does not contribute significantly to HK binding to HUVEC. [source] Neuronal nitric oxide synthase immunoreactivity in the guinea-pig liver: distribution and colocalization with neuropeptide Y and calcitonin gene-related peptideLIVER INTERNATIONAL, Issue 6 2001Francisco J. Esteban Abstract:Aims/Background: The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the guinea-pig liver and its colocalization with neuropeptides remain to be elucidated. Methods: The distribution of nNOS was studied in fixed guinea-pig liver by light microscopic immunohistochemistry. Confocal analysis was used to determine its colocalization with neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP). Results: nNOS-immunoreactive (nNOS-IR) nerves were observed in relation to hilar and interlobar vessels and in Glisson's capsule. A few nNOS-IR ganglia were observed in the extrahepatic bile duct and close to the interlobar portal triads. In addition, nNOS-IR fibers were located in the interlobular portal triads and pervading the parenchyma. Moreover, nNOS-IR nerves were demonstrated for the first time in the larger central veins and in the hepatic vein. nNOS-NPY and nNOS-CGRP colocalizations were detected in the fibromuscular layer of the bile duct and periductal plexus, respectively. Conclusions: These results support the phylogenetic conservation of the nNOS-IR hepatic innervation and its possible contribution to the regulation of hepatic blood flow and certain hepatic functions. [source] Geochemical characterization of moldavites from a new locality, the Cheb Basin, Czech RepublicMETEORITICS & PLANETARY SCIENCE, Issue 3 2008anda Detailed comparison of the Cheb Basin moldavites with moldavites from other substrewn fields in both major and trace element composition shows that the Cheb Basin is a separate substrewn field. The geochemical data obtained are discussed with respect to the source materials and processes leading to formation of moldavites. The data show that three groups of Cheb Basin moldavites exist. Ten samples of group 1 are characterized by the lowest content of Al, Fe, Na, and other elements representing phyllosilicate minerals, and by high Ca + Mg contents related probably to carbonates. They resemble the "poisonous green" moldavites, a subgroup of the Southern Bohemian moldavites. Seven samples of group 2 and 6 samples of group 3 are similar to typical moldavites of the Southern Bohemian substrewn field. These two groups differ from each other mainly in Al contents; with higher contents of Al and the elements associated with phyllosilicate minerals (namely Ba and Sr), group 3 also resembles the Moravian moldavites. Significant positive correlations between K, Ca, Mg, and Mn found in group 2 of the Cheb Basin moldavites and the enrichment in these elements observed generally in all moldavites, as well as other facts, e.g., high K/Na and K/Rb ratios and the reduced conditions during formation of moldavites, have been attributed to possible contribution to the moldavite source materials of the ash produced by burning of vegetation and soil organic matter present at the pre-impact area. [source] Hydrogen Peroxide-Dependent Arteriolar Dilation in Contracting Muscle of Rats Fed Normal and High Salt DietsMICROCIRCULATION, Issue 8 2007Paul J. Marvar ABSTRACT Objective: High dietary salt intake decreases the arteriolar dilation associated with skeletal muscle contraction. Because hydrogen peroxide (H2O2) can be released from contracting muscle fibers, this study was designed to assess the possible contribution of H2O2 to skeletal muscle functional hyperemia and its sensitivity to dietary salt. Methods: The authors investigated the effect of catalase treatment on arteriolar dilation and hyperemia in contracting spinotrapezius muscle of rats fed a normal salt (0.45%, NS) or high salt (4%, HS) diet for 4 weeks. Catalase-sensitive 2,,7,-dichlorofluorescein (DCF) fluorescence was measured as an index of H2O2 formation, and the mechanism of arteriolar dilation to H2O2 was probed in each group using pharmacological inhibitors. Results: DCF fluorescence increased with muscle contraction, but not if catalase was present. Catalase also reduced arteriolar dilation and hyperemia during contraction in both dietary groups. Exogenous H2O2 dilated arterioles in both groups, with greater responses in HS rats. Guanylate cyclase inhibition did not affect arteriolar responses to H2O2 in either group, but KCa or KATP channel inhibition equally reduced these responses, and KATP channel inhibition equally reduced functional hyperemia in both groups. Conclusions: These results indicate that locally produced H2O2 contributes to arteriolar dilation and hyperemia in contracting skeletal muscle, and that the effect of H2O2 on arteriolar tone in this vascular bed is mediated largely through K+ channel activation. High dietary salt intake does not reduce the contribution of H2O2 to active hyperemia, or alter the mechanism through which H2O2 relaxes arteriolar smooth muscle. [source] Involvement of the p110, isoform of PI3K in early development of mouse embryosMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2009Xiao-yan Xu Class I of phosphoinositide 3-kinases (PI3Ks) is characterized as a group of intracellular signal proteins possessing both protein and lipid kinase activities. Recent studies implicate class I of PI3Ks acts as indispensable mediators in early development of mouse embryos, but the molecular mechanisms are poorly defined. In this paper, mouse one-cell embryos were used to investigate a possible contribution of the catalytic subunit of PI3K, p110,, to cell cycle progression. The expression level of p110, was determined in four phases of one-cell embryos. Silencing of p110, by microinjection of p110, shRNA into one-cell embryos resulted in a G2/M arrest and prevented the activation of Akt and M-phase promoting factor (MPF). Further, microinjection of the synthesized mRNA coding for a constitutively active p110, into one-cell embryos induced cell cleavage more effectively than microinjection of wild-type p110, mRNA, whereas microinjection of mRNA of kinase-deficient p110, delayed the first mitotic cleavage. Taken together, this study demonstrates that p110, is significant for G2/M transition of mouse one-cell embryos and further emphasizes the importance of Akt in PI3K pathway. Mol. Reprod. Dev. 76: 389,398, 2009. © 2008 Wiley-Liss, Inc. [source] The PSCz dipole revisitedMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2006Spyros Basilakos ABSTRACT We re-examine the gravitational acceleration (dipole) induced on the Local Group of galaxies by the Infrared Astronomical Satellite (IRAS) galaxy distribution of the Point Source Catalog redshift (PSCz) survey. We treat the cirrus-affected low galactic latitudes by utilizing a spherical harmonic expansion of the galaxy surface density field up to the octapole order. We find strong indications for significant contributions to the Local Group motion from depths up to ,185 h,1 Mpc and a possible contribution even from ,210 h,1 Mpc, in agreement with the recent analysis of Kocevski & Ebeling of a whole-sky X-ray cluster survey. What changes with respect to the previous PSCz dipole analyses is: (i) the large-scale dipole contributions and (ii) an increase of the overall dipole amplitude due to the important contribution of the local volume (, 4 h,1 Mpc), which we now take into account. This results in a lower value of the , (,,0.6m/b) parameter, which we find to be ,IRAS, 0.49 in real space. Therefore, for the concordance cosmological model (,m= 1 ,,,= 0.3), the IRAS galaxies bias factor is bIRAS, 1, which means that IRAS galaxies are good tracers of the underlying matter distribution. [source] Enhanced Aquaporin-4 immunoreactivity in sporadic Creutzfeldt-Jakob diseaseNEUROPATHOLOGY, Issue 4 2007Yasushi Iwasaki Aquaporin-4 (AQP-4) is a water channel protein located on the plasma membrane of astrocytes and is regulated under various conditions. In the present study, a series of brains with sporadic Creutzfeldt-Jakob disease (sCJD) were investigated to determine the possible contribution of AQP-4 in the development of sCJD pathology. Six cases of subacute spongiform encephalopathy (SSE) and four cases of panencephalopathic (PE)-type sCJD were included. Increased AQP-4 immunoreactivity compared to that in controls was observed in all sCJD patients, particularly in the cerebral neocortex and cerebellar cortex. AQP-4 immunoreactivity was present in the cell bodies and processes of protoplasmic astrocytes in SSE and around cell bodies and processes of hypertrophic astrocytes in PE-type sCJD. Analysis of serial sections showed the development of sCJD pathology, particularly in neocortical lesions, as follows: PrP deposition; spongiform change and gliosis; enhanced staining for AQP-4; hypertrophic astrocytosis; and neuronal loss and tissue rarefaction. Strong AQP-4 immunoreactivity was present in burnt-out lesions such as those of status spongiosus. These results indicate that increased AQP-4 expression in sCJD is an early pathologic event and appears to remain until the late disease stage. We suggest that increased expression of AQP-4 is a pathologic feature of sCJD. [source] Control of Toxoplasma gondii infection by athymic LEW- Whnrnu ratsPARASITE IMMUNOLOGY, Issue 6-7 2008J. C. SEPULVEDA-ARIAS SUMMARY In immunocompetent rats and humans infection with Toxoplasma gondii remains mostly without overt clinical symptoms, but can be fatal, if the T-cell response is impaired. For a better understanding of the lack of control of T. gondii infection under immunosuppressed conditions, congenitally athymic rats were used as the experimental model. Whereas athymic F344- Whnrnu (F344 nude) rats die from a generalized infection during the first 3 weeks after peritoneal inoculation with 106 tachyzoites of T. gondii strain NTE, LEW- Whnrnu (LEW nude) rats and euthymic LEW rats infected with a 10-fold higher number of parasites developed chronic infection. To identify underlying mechanisms of LEW rats resistance to T. gondii infection and to investigate a possible contribution of residual T-cells to LEW- Whnrnu rat resistance, we characterized the immune response of LEW rats by determination of cellularity and composition of lymphocyte population, antigen-specific IgG2b response as well as assays of antigen-specific proliferation and production of IL-2, IFN-, and TNF-,. As only euthymic LEW rats developed production of antigen-specific IgG and cellular in vitro responses, these results strongly suggest that the genetic background of LEW rats permits a control of the infection independent of an adaptive immune response. [source] What can we learn from psychoanalysis and prospective studies about chemically dependent patients?THE INTERNATIONAL JOURNAL OF PSYCHOANALYSIS, Issue 2 2004Sérgio de Paula Ramos Despite the common occurrence of drug abusers in the psychoanalytic clinic, contemporary literature on the subject, particularly among publications in the IJP, is sparse. This paper aims to review the most important psychoanalytic contributions on drug dependency in the past 100 years, then attempts to compare their postulations to the findings ofpertinent prospective studies. In these patients, a persistent symbiotic object relationship is found, which ties them to narcissistic functioning, where drug use is viewed in the light of both pleasure without object and omnipotently controlled need. The author also discusses the possible contribution of the mother and father in the genesis of this condition, focusing on the compromise of the paternal function as the deciding factor. The theoretical and technical implications of this approach are illustrated by clinical material. [source] Pilot study of response inhibition and error processing in the posterior medial prefrontal cortex in healthy youthTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2008Kate Dimond Fitzgerald Background:, Recent neuroimaging work suggests that inhibitory and error processing in healthy adults share overlapping, but functionally distinct neural circuitries within the posterior medial frontal cortex (pMFC); however, it remains unknown whether the pMFC is differentially engaged by response inhibition compared to error commission in the developing brain. Developmental neuroimaging studies of response inhibition have found pMFC activation, but the possible contribution of error-related activation during inhibitory processing has not been well studied in youth. Method:, To examine the processing of correct response inhibition compared to errors in the developing brain, we performed functional magnetic resonance imaging scans in 11 healthy subjects, ages 8,14 years, during an antisaccade task while performance was monitored. Results:, Successful antisaccades activated the pre-supplementary motor area. In contrast, errors on the antisaccade task activated the dorsal anterior cingulate cortex. Conclusion:, The findings suggest the functional sub-specialization of inhibitory and error processing within the pMFC in this pilot sample of children and adolescents. Future neuroimaging studies of developing inhibitory control should examine both between correct and error trials. [source] |