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Specific Effects (specific + effects)
Selected AbstractsSpecific Effects of Synthetic Oligopeptides on Cultured Animal Cells,BIOTECHNOLOGY PROGRESS, Issue 1 2002Franti, ek Fran Synthetic oligopeptides, tri- to pentaglycine and tri- and tetraalanine, were found to enhance viable cell density and culture viability when applied at concentrations higher than milllimolar to the cultures of a model hybridoma line. Oligoalanines, in addition, enhanced monoclonal antibody yields. Oligoglycines promoted solely the cell growth, unless the batch culture was fed with a medium concentrate. Examination of the effects of various tripeptides composed of glycine, alanine, serine, threonine, lysine, and histidine showed that some of the peptides promoted the growth of the culture, while other peptides suppressed the growth and enhanced the monoclonal antibody yield. Determination of the levels of amino acids and peptides in culture media indicated that the observed changes of culture parameters were caused by intact peptide molecules, rather than by amino acids liberated from the peptides by enzymic cleavage. [source] Moral prototypes and moral behavior: Specific effects on emotional precursors of moral behavior and on moral behavior by the activation of moral prototypesEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 6 2010Silvia Osswald The present studies investigated the extent to which three basic moral prototypes, "just," "brave", and "caring", are related to moral, prosocial behavior. In five studies, we tested (a) whether people would associate three basic types of moral behavior (helping behavior, moral courage, and heroism) with three moral prototypes, and (b) whether specific emotional precursors of moral behavior and moral behavior itself could be promoted by activating the respective moral prototype. As expected, Studies 1,3 revealed that people associated helping behavior with the caring prototype, moral courage with the just prototype, and heroism with the brave prototype. Studies 4 and 5 showed that the activation of the three prototypes differentially influenced emotional precursors of the three types of moral behavior (Study 4) as well as actual moral behavior (Study 5). Thus, the five studies revealed that people associate different moral behaviors with different moral prototypes and that a certain moral behavior can be activated by the priming of the related prototype. Copyright © 2010 John Wiley & Sons, Ltd. [source] Role of electrostatics in the interaction between plastocyanin and photosystem I of the cyanobacterium Phormidium laminosumFEBS JOURNAL, Issue 23 2002Beatrix G. Schlarb-Ridley The interactions between photosystem I and five charge mutants of plastocyanin from the cyanobacterium Phormidium laminosum were investigated in vitro. The dependence of the overall rate constant of reaction, k2, on ionic strength was investigated using laser flash photolysis. The rate constant of the wild-type reaction increased with ionic strength, indicating repulsion between the reaction partners. Removing a negative charge on plastocyanin (D44A) accelerated the reaction and made it independent of ionic strength; removing a positive charge adjacent to D44 (K53A) had little effect. Neutralizing and inverting the charge on R93 slowed the reaction down and increased the repulsion. Specific effects of MgCl2 were observed for mutants K53A, R93Q and R93E. Thermodynamic analysis of the transition state revealed positive activation entropies, suggesting partial desolvation of the interface in the transition state. In comparison with plants, plastocyanin and photosystem I of Phormidium laminosum react slowly at low ionic strength, whereas the two systems have similar rates in the range of physiological salt concentrations. We conclude that in P. laminosum, in contrast with plants in vitro, hydrophobic interactions are more important than electrostatics for the reactions of plastocyanin, both with photosystem I (this paper) and with cytochrome f[Schlarb-Ridley, B.G., Bendall, D.S. & Howe, C.J. (2002) Biochemistry41, 3279,3285]. We discuss the implications of this conclusion for the divergent evolution of cyanobacterial and plant plastocyanins. [source] Ethanol Alters the Osteogenic Differentiation of Amniotic Fluid-Derived Stem CellsALCOHOLISM, Issue 10 2010Jennifer A. Hipp Background:, Fetal alcohol spectrum disorder (FASD) is a set of developmental defects caused by prenatal alcohol exposure. Clinical manifestations of FASD are highly variable and include mental retardation and developmental defects of the heart, kidney, muscle, skeleton, and craniofacial structures. Specific effects of ethanol on fetal cells include induction of apoptosis as well as inhibition of proliferation, differentiation, and migration. This complex set of responses suggests that a bioinformatics approach could clarify some of the pathways involved in these responses. Methods:, In this study, the responses of fetal stem cells derived from the amniotic fluid (AFSCs) to treatment with ethanol have been examined. Large-scale transcriptome analysis of ethanol-treated AFSCs indicates that genes involved in skeletal development and ossification are up-regulated in these cells. Therefore, the effect of ethanol on osteogenic differentiation of AFSCs was studied. Results:, Exposure to ethanol during the first 48 hours of an osteogenic differentiation protocol increased in vitro calcium deposition by AFSCs and increased alkaline phosphatase activity. In contrast, ethanol treatment later in the differentiation protocol (day 8) had no significant effect on the activity of alkaline phosphatase. Conclusions:, These results suggest that transient exposure of AFSCs to ethanol during early differentiation enhances osteogenic differentiation of the cells. [source] Activation of the basal forebrain by the orexin/hypocretin neuronesACTA PHYSIOLOGICA, Issue 3 2010E. Arrigoni Abstract The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurones promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurones may promote arousal by exciting cortically projecting neurones of the BF. Orexin fibres synapse on BF cholinergic neurones and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurones, induces cortical release of acetylcholine and promotes wakefulness. The orexin neurones also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurones that project to the cortex. Cholinergic neurones were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurones that project to the cortex seem to comprise at least two populations with some directly excited by orexin-A that may represent wake-active, GABAergic neurones, whereas others did not respond to orexin-A but were inhibited by dynorphin and may be sleep-active, GABAergic neurones. This evidence suggests that the BF is a key site through which orexins activate the cortex and promote behavioural arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. [source] Watching moving images specifically promotes development of medial area of secondary visual cortex in ratDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009Baonan Sun Abstract It is generally accepted that the cortex can be divided into numerous regions depending on the type of information each processes, and that specific input is effective in improving the development of related regions. In visual cortex, many subareas are distinguished on the basis of their adequate information. However, whether the development of a subarea can be specifically improved by its particular input is still largely unknown. Here, we show the specific effects of motion information on the development of the medial area of secondary visual cortex (V2M), a subarea associated with processing the movement component of visual information. Although watching a moving or a still image had similar effects in primary visual cortex, the moving image induced multistage development of V2M in dark-reared rats: both mRNA and protein levels of GluR2 were upregulated, the density and protein content of GluR2-positive synapses increased, and the spine density and the frequency of spontaneous excitatory postsynaptic currents (EPSCs) of pyramidal neurons in Layer 5 were elevated. Our results suggest that rats are able to identify motion information, distribute it to V2M, and then use this input to specifically improve the development of V2M. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Effects of the estrogen agonist 17,-estradiol and antagonist tamoxifen in a partial life-cycle assay with zebrafish (Danio rerio)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Leo T. M. van der Ven Abstract A partial life-cycle assay (PLC) with zebrafish (Danio rerio) was conducted to identify endocrine-disrupting effects of 17,-estradiol (E2) and tamoxifen (TMX) as reference for estrogen agonist and antagonist activity. Adult zebrafish were exposed for 21 d and offspring for another 42 d, allowing differentiation of gonads in control animals. The assessed end points included reproductive variables (egg production, fertilization, and hatching), gonad differentiation of juveniles, histopathology, and vitellogenin (VTG) expression. With E2, the most sensitive end points were feminization of offspring (at 0.1 nM) and increased VTG production in males (at 0.32 nM). At 1 nM, decreased F1 survival, increased F1 body length and weight, VTG-related edema and kidney lesions, and inhibited spermatogenesis were observed. Oocyte atresia occurred at even higher concentrations. Exposure to TMX resulted in specific effects at an intermediate test concentration (87 nM), including oocyte atresia with granulosa cell transformation and disturbed spermatogenesis (asynchrony within cysts). In F1, decreased hatching, survival, and body weight and length as well as decreased feminization were observed. Decreased vitellogenesis and egg production in females and clustering of Leydig cells in males occurred at higher concentrations. Toxicological profiles of estrogen agonists and antagonists are complex and specific; a valid and refined characterization of endocrine activity of field samples therefore can be obtained only by using a varied set of end points, including histology, as applied in the presented PLC. Evaluation of only a single end point can easily produce under- or overestimation of the actual hazard. [source] Acute toxicity of triorganotin compounds: Different specific effects on the energy metabolism and role of pHENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002René W. Hunziker Abstract Triorganotin compounds exhibit several modes of toxic action on the energy metabolism in energy-transducing membranes. The inhibition of the adenosine triphosphate (ATP) synthase and the hydroxide/chloride-antiport have been extensively investigated, but debate still exists on whether further mechanisms are relevant. In this work, two possible further effects have been investigated: inhibition of the bc1 complex and the hydroxide uniport, and in addition, the overall inhibition of the ATP synthesis was investigated in chromatophores of the photosynthetic purple bacterium Rhodobacter sphaeroides at pH = 7.5 and pH = 6.1. Experimental conditions were chosen in order to exclude the hydroxide/anion antiport as a possible effect. Inhibition of the cytochromes bc1 complex was detected, but at such high concentrations that it is not relevant for acute toxicity. Tributyltin was found to induce a decrease of the membrane potential, which can be attributed to a hydroxide uniport, whereas for triphenyltin no such activity was observed. For both compounds, inhibition of the ATP synthesis was higher at pH = 6.1 than at pH = 7.5. Also the hydroxide uniport activity of tributyltin was higher at lower pH. The contribution of the hydroxide uniport of tributyltin to the overall inhibition of the ATP synthesis cannot be quantified; however, hydroxide uniport occurred in the same concentration range as inhibition of the ATP synthesis. For triphenyltin, inhibition of the ATP synthesis can be attributed to the inhibition of the ATP synthase. It was concluded that chromatophores of R. sphaeroides are a useful system to discriminate various effects of toxicants on the energy metabolism of a cell. [source] Improvement in quality of life for cancer patients treated with epoetin alfaEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2001S.E. Libretto PHD BSC MIBIOL CBIOL Anaemia is a common complication of cancer and cancer therapies, and fatigue is one of the most common symptoms of anaemia, disrupting functional performance and reducing overall quality of life. The positive effects of treating renal patients with recombinant human erythropoietin are well documented. This case report series details the specific effects of fatigue on individual patients with cancer and their way of life, and describes their significant improvement in lifestyle following the reversal of anaemia using recombinant human erythropoietin, epoetin alfa. [source] Fatty acid incorporation in endothelial cells and effects on endothelial nitric oxide synthaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2007S. Couloubaly Abstract Background The nature of fatty acids provided by the diet as well as plasma lipid metabolism can modify the composition and properties of plasma membrane and thus the activity of membrane proteins. In humans, as well as in experimental models, diabetes is associated with both an alteration in serum lipid profile and a documented endothelial dysfunction. This in vitro study investigated on an immortalized human endothelial cell line (EA.hy 926) the specific effects of several free fatty acids (FFAs) on the composition of cellular membranes and the regulation of endothelial nitric oxide synthase (eNOS). Materials and methods 0·1% of lipid deprived serum was added to the incubation medium with 25 mm glucose in order to study the effects of individual fatty acids: myristic acid, palmitic acid, stearic acid, oleic acid or linoleic acid at 100 µm bound with albumin. The effects of the FFAs on the endothelial nitric oxide synthase were investigated on mRNA level by quantitative PCR, on protein level and Ser1177 phosphorylation by Western blot and on enzymatic activity on living cells using radiolabelled arginine. Results Free linoleic acid increased the membrane content in n-6 fatty acids (mainly C18: n-6 and its metabolites) with a decrease in saturated and monounsaturated fatty acids. These conditions decreased the basal eNOS activity and reduced the phosphorylation of eNOS-Ser1177 due to activation by histamine. Free palmitic acid enriched the membranes with 16 : 0 with a slight decrease in monounsaturated fatty acids. These conditions increased eNOS activation without increasing Ser1177 phosphorylation upon histamine activation. The addition of the other FFAs also resulted in modifications of membrane composition, which did not to affect eNOS-Ser1177 phosphorylation. Conclusion Among the fatty acids used, only modification of the membrane composition due to linoleic acid supply disturbed the basal enzymatic activity and Ser1177 phosphorylation of eNOS in a way that limited the role of histamine activation. Linoleic acid might involve the dysfunction of both eNOS basal activity and its phosphorylation status and may then contribute to an impaired vasodilatation in vivo. [source] CREB function is required for normal thymic cellularity and post-irradiation recoveryEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2004Sven Baumann Abstract Recent generation of genetically modified Creb1 mutant mice has revealed an important role for CREB (cAMP responsive element binding protein) and the related proteins CREM (cAMP responsive element modulator) and ATF1 (activating transcription factor 1) in cell survival, in agreement with previous studies using overexpression of dominant-negative CREB (dnCREB). CREB and ATF1 are abundantly expressed in T cells and are rapidly activated by phosphorylation when T cells are stimulated through the T cell antigen receptor. We show that T cell-specific loss of CREB in mice, in combination with the loss of ATF1, results in reduced thymic cellularity and delayed thymic recovery following sublethal irradiation but no changes in T cell development or activation. These data show that loss of CREB function has specific effects on thymic T lymphocyte proliferation and homeostasis in vivo. [source] Ascending visceral regulation of cortical affective information processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Gary G. Berntson Abstract Over a century ago, William James proposed that strong emotions represent the perceptual consequences of somato-visceral feedback. Although the strong form of this conception is no longer viable, considerable evidence has accumulated indicating a range of visceral influences on higher neurobehavioural processes. This literature has only recently begun to consolidate, because earlier reports generally remained at the demonstration level, and pathways and mechanisms for such influences were uncertain. Recently, specific effects of visceral feedback have become apparent on cortical activity, cerebral auditory-evoked responses, anxiety, memory and behavioural aspects of immunological sickness. Moreover, considerable progress has been made recently in determining the specific neural pathways and systems underlying these actions, especially the role of noradrenergic projections from the nucleus of the tractus solitarius and the locus coeruleus to the amygdala in memory processes, and to the basal forebrain in the processing of anxiety-related information. The present paper highlights selected recent findings in this area, and outlines relevant structures and pathways involved in the ascending visceral influence on higher neurobehavioural processes. [source] Reduced operant ethanol self-administration and in vivo mesolimbic dopamine responses to ethanol inPKC,-deficient miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000M. Foster Olive Abstract There is increasing evidence that individual protein kinase C (PKC) isozymes mediate specific effects of ethanol on the nervous system. In addition, multiple lines of evidence suggest that the mesoaccumbens dopamine reward system is critically involved in the rewarding and reinforcing effects of ethanol. Yet little is known about the role of individual PKC isozymes in ethanol reinforcement processes or in regulation of mesolimbic systems. In this study, we report that mice lacking the epsilon isoform of PKC (PKC,) show reduced operant ethanol self-administration and an absence of ethanol-induced increase in extracellular dopamine levels in the nucleus accumbens. PKC, null mice exhibited a 53% decrease in alcohol-reinforced operant responses under basal conditions, as well as following ethanol deprivation. Behavioural analysis revealed that while both genotypes had the same number of drinking bouts following deprivation, PKC, null mice demonstrated a 61% reduction in number of ethanol reinforcers per bout and a 57% reduction in ethanol-reinforced response rate. In vivo microdialysis experiments showed that, in contrast to wild-type mice, PKC, null mice exhibited no change in extracellular levels of dopamine in the nucleus accumbens following acute administration of ethanol (1 and 2 g/kg i.p.), while mesolimbic dopamine responses to cocaine (20 mg/kg i.p.) or high potassium (100 m m) in these mice were comparable with that of wild-types. These data provide further evidence that increases in extracellular mesolimbic dopamine levels contribute to the reinforcing effects of ethanol, and indicate that pharmacological agents inhibiting PKC, may be useful in the treatment of alcohol dependence. [source] Identification of novel splice variants of the human catalytic subunit c, of cAMP-dependent protein kinaseFEBS JOURNAL, Issue 19 2001Sigurd Ørstavik Four different isoforms of the catalytic subunit of cAMP-dependent protein kinase, termed C,, C,, C, and PrKX have been identified. Here we demonstrate that the human C, gene encodes six splice variants, designated C,1, C,2, C,3, C,4, C,4ab and C,4abc. The C, splice variants differ in their N-terminal ends due to differential splicing of four different forms of exon 1 designated exon 1-1, 1-2, 1-3, 1-4 and three exons designated a, b and c. All these exons are located upstream of exon 2 in the C, gene. The previously identified human C, variant has been termed C,1, and is similar to the C, isoform identified in the mouse, ox, pig and several other mammals. Human C,2, which is the homologue of bovine C,2, has no homologue in the mouse. Human C,3 and C,4 are homologous to the murine C,3 and C,2 splice variants, whereas human C,4ab and C,4abc represent novel isofoms previously not identified in any other species. At the mRNA level, the C, splice variants reveal tissue specific expression. C,1 was most abundantly expressed in the brain, with low-level expression in several other tissues. The C,3 and C,4 splice variants were uniquely expressed in human brain in contrast to C,2, which was most abundantly expressed in tissues of the immune system, with no detectable expression in brain. We suggest that the various C, splice variants when complexed with regulatory subunits may give rise to novel holoenzymes of protein kinase A that may be important for mediating specific effects of cAMP. [source] Pharmaceutical promotion and GP prescription behaviourHEALTH ECONOMICS, Issue 1 2006Frank Windmeijer Abstract The aim of this paper is to empirically analyse the responses by general practitioners to promotional activities for ethical drugs by pharmaceutical companies. Promotion can be beneficial as a means of providing information, but it can also be harmful in the sense that it lowers price sensitivity of doctors and it merely is a means of maintaining market share, even when cheaper, therapeutically equivalent drugs are available. A model is estimated that includes interactions of promotion expenditures and prices and that explicitly exploits the panel structure of the data, allowing for drug specific effects and dynamic adjustments, or habit persistence. The data used are aggregate monthly GP prescriptions per drug together with monthly outlays on drug promotion for the period 1994,1999 for 11 therapeutic markets, covering more than half of the total prescription drug market in the Netherlands. Identification of price effects is aided by the introduction of the Pharmaceutical Prices Act, which established that Dutch drugs prices became a weighted average of the prices in surrounding countries after June 1996. We conclude that GP drug price sensitivity is small, but adversely affected by promotion. Copyright © 2005 John Wiley & Sons, Ltd. [source] Bayesian comparison of spatially regularised general linear modelsHUMAN BRAIN MAPPING, Issue 4 2007Will Penny Abstract In previous work (Penny et al., [2005]: Neuroimage 24:350,362) we have developed a spatially regularised General Linear Model for the analysis of functional magnetic resonance imaging data that allows for the characterisation of regionally specific effects using Posterior Probability Maps (PPMs). In this paper we show how it also provides an approximation to the model evidence. This is important as it is the basis of Bayesian model comparison and provides a unified framework for Bayesian Analysis of Variance, Cluster of Interest analyses and the principled selection of signal and noise models. We also provide extensions that implement spatial and anatomical regularisation of noise process parameters. Hum Brain Mapp 2007. © 2006 Wiley-Liss, Inc. [source] Effects of memantine on cognition in patients with moderate to severe Alzheimer's disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studiesINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2009Patrizia Mecocci Abstract Objectives The post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD. Methods Data from six multicentre, randomised, placebo-controlled, parallel-group, double-blind, 6-month studies were used as the basis for these post-hoc analyses. All patients with a Mini-Mental State Examination (MMSE) score of less than 20 were included. Analyses of patients with moderate AD (MMSE: 10,19), evaluated with the Alzheimer's disease Assessment Scale (ADAS-cog) and analyses of patients with moderate to severe AD (MMSE: 3,14), evaluated using the Severe Impairment Battery (SIB), were performed separately. Results The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog (p,<,0.01) and the SIB (p,<,0.001) total score at study end. The ADAS-cog single-item analyses showed significant benefits of memantine treatment, compared to placebo, for mean change from baseline for commands (p,<,0.001), ideational praxis (p,<,0.05), orientation (p,<,0.01), comprehension (p,<,0.05), and remembering test instructions (p,<,0.05) for observed cases (OC). The SIB subscale analyses showed significant benefits of memantine, compared to placebo, for mean change from baseline for language (p,<,0.05), memory (p,<,0.05), orientation (p,<,0.01), praxis (p,<,0.001), and visuospatial ability (p,<,0.01) for OC. Conclusion Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Time to extinction in relation to mating system and type of density regulation in populations with two sexesJOURNAL OF ANIMAL ECOLOGY, Issue 5 2004BERNT-ERIK SÆTHER Summary 1Population viability models usually consider only the female segment of the population. However, random variation in sex ratio as well as the mating system may also affect variation in fitness among females. Here we develop population models incorporating demographic stochasticity in both sexes. Furthermore, we consider the effects on the estimated time to extinction and whether density regulation acts only on females or on total population size. 2We applied these models to two populations of polygynous great reed warblers Acrocephalus arundinaceus L. with differences in population trends to investigate the importance of considering sex in population viability models. 3Demographic stochasticity was larger in a polygynous than in a monogamous mating system. 4The estimated time to extinction was considerably shorter for a monogamous than for a polygynous mating system, particularly if density regulation acted only on females than rather on the total population. 5This study demonstrates that structure of mating system must be included when making population viability analysis based on counts of total population sizes. It is especially important to model the specific effects of density regulation on the two sexes. [source] Midregion Parathyroid Hormone-Related Protein Inhibits Growth and Invasion In Vitro and Tumorigenesis In Vivo of Human Breast Cancer CellsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2001Claudio Luparello Abstract Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide hormone that undergoes extensive post-translational processing, and PTHrP(38,94)-amide is one of the mature secretory forms of the peptide. In this study, we explored the effect of PTHrP(38,94)-amide in a panel of six breast cancer cell lines "in vitro" and in MDA-MB231 cells "in vivo" specifically examining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38,94)-amide markedly inhibited proliferation and also caused striking toxicity and accelerated cell death in breast cancer cells. In addition, direct injection of PTHrP(38,94)-amide into MDA-MB231 breast cancer cells passaged in immunodeficient mice produced a marked reduction in tumor growth. These studies (i) indicate breast cancer cells are one of the few tissues in which specific effects of midregion PTHrP have been established to date, (ii) support a role for midregion secretory forms of PTHrP in modulating not only normal but also pathological mammary growth and differentiation, (iii) add further evidence for the existence of a specific midregion PTHrP receptor, and (iv) provide a novel molecule for modeling of small molecule analogues that may have anti-breast cancer effects. [source] Increased CaV,1a expression with aging contributes to skeletal muscle weaknessAGING CELL, Issue 5 2009Jackson R. Taylor Summary Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation,contraction (E-C) coupling. Excitation,contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation,contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel ,1s (CaV1.1) and ,1a (CaV,1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaV,1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaV,1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaV,1a overexpression, a CaV,1a -YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaV,1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaV,1a -YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaV,1a -YFP electroporated muscle fibers compared with sham-electroporated, age-matched controls. siRNA interference of CaV,1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaV,1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaV,1a during old age may play a role in the loss of specific force. [source] Effects of Docosahexaenoic Acid Content in Triacylglycerol on Human Taste PerceptionJOURNAL OF FOOD SCIENCE, Issue 6 2002T. Koriyama ABSTRACT: To elucidate the contribution of docosahexaenoic acid (DHA) in triacylglycerol to tuna oil specific taste effects, suppression of bitterness and enhancement of umami, we conducted sensory analysis employing an oil-in-water emulsion prepared with taste substances and the oils differed in the DHA content. The tuna oil specific taste effects were linearly dependent on DHA content. The increase of DHA in oil also linearly enhanced umami and flavor (continuity and richness) of synthetic tuna extract. These results indicate that DHA, a major fatty acid of tuna oil, greatly contributes to tuna oil specific effects on basic tastes and flavor. [source] Poster Session BP07: Neurodegenerative DiseasesJOURNAL OF NEUROCHEMISTRY, Issue 2002F. Jayman Presynaptic terminals contain an abundant 140-amino acid phosphoprotein, dubbed ,-synuclein, which is accumulated in Lewy bodies typically observed in neurons in neurodegenerative diseases, such as Parkinson's disease. In this study, the role of ,-synuclein in regulating cycle, differentiation, and survival of neuronal cells was studied using a rat dopaminergic cell line ZN27D. To delineate specific effects of ,-synuclein the same cell line was engineered to express human ,-synuclein and a vector-transfected cell line RK27 was used as a second control. All three cell lines showed significant proliferation even in serum-free medium, and complete inhibition of cell division and differentiation could be achieved in the ZN27D cells only when both dibutyryl cAMP (dbcAMP) and retinoic acid were present. In contrast, the ,-synuclein expressing cells could be differentiated in the presence of only dbcAMP. Dose dependence of MPP+(1-methyl-4-phenylpyridinium iodide)-mediated caspase3 activation was studied in undifferentiated ZN27D cells. At 200 ,m MPP+ a significant cleavage of the caspase3 substrate PARP was observed and it was reversed in the presence of ,-synuclein. MPP+ also inhibited aminophospholipid translocase (APTL), a P-type ATPase that is responsible for inner plasma membrane localization of phophotidylserine in healthy cells. The role of ,-synuclein in regulating cell cycle, differentiation, APTL activity and cell death is being investigated further in the dopaminergic ZN27D cell line. [source] Adverse effects of Sudanese toombak vs.JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2010Swedish snuff on human oral cells J Oral Pathol Med (2010) 39 128,140 Background:, The high incidence of oral cancer in Sudan has been associated with the use of toombak, the local type of smokeless tobacco. However, its specific effects on human oral cells are not known. We aimed to investigate the effects of toombak on primary normal human oral keratinocytes, fibroblasts, and a dysplastic oral keratinocytic cell line, and to compare them with the effects induced by Swedish snuff. Method:, Aqueous extracts were prepared from moist toombak and Swedish snuff and added in serial dilutions on in vitro monolayer cultured cells. Cell viability, morphology and growth, DNA double-strand breaks (,H2AX staining), expression of phosphatidylserine (Annexin V staining), and cell cycle were assessed after various exposure time periods. Results:, Significant decrease in cell number, occurrence of DNA double-strain breaks, morphological and biochemical signs of programmed cell death were detected in all oral cell types exposed to clinically relevant dilutions of toombak extract, although to a lesser extent in normal oral fibroblasts and dysplastic keratinocytes. G2/M-block was also detected in normal oral keratinocytes and fibroblasts exposed to clinically relevant dilutions of toombak extract. Swedish snuff extract had less adverse effects on oral cells, mainly at non-clinically relevant dilutions. Conclusion:, This study indicates a potential for toombak, higher than for Swedish snuff, to damage human oral epithelium. Dysplastic oral keratinocytes were less sensitive than their normal counterparts, suggesting that they might have acquired a partially resistant phenotype to toombak -induced cytotoxic effects while still being prone to DNA damage that could lead to further malignant progression. [source] Verbal and Nonverbal Memory in Adults Prenatally Exposed to AlcoholALCOHOLISM, Issue 5 2010Claire D. Coles Background:, Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. Methods:, In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. Results:, Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. Conclusion:, These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account. [source] Structural modifications resulting from proton transfer in complexes of phenols with pyridine,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 8 2005Irena Majerz Abstract The structural consequences of proton transfer in complexes of phenol (1), 2,6-dichlorophenol (2), 4-nitrophenol (3) and 2,6-dichloro-4-nitrophenol (4) with pyridine were analyzed on the basis of results of B3LYP/6,31G** calculations. Three methods of describing the progress of proton transfer are proposed: the O,H [d(OH)] and C,O [d(CO)] bond lengths and the fraction XPT of the proton transfer form, calculated from the values of the dipole moments. The d(OH) parameter reveals behaviour near to XPT and can be used as a universal measure of the degree of proton transfer. The d(CO) parameter gives nearly linear dependences for various structural parameters, but independent estimation of the specific effects of the substituents is necessary, as separate correlations for each complex are found. A role of resonance interaction in systems containing a p -NO2 substituent is demonstrated. Copyright © 2005 John Wiley & Sons, Ltd. [source] Quantitative Lipid Metabolomic Changes in Alcoholic Micropigs With Fatty Liver DiseaseALCOHOLISM, Issue 4 2009Angela M. Zivkovic Background:, Chronic ethanol consumption coupled with folate deficiency leads to rapid liver fat accumulation and progression to alcoholic steatohepatitis (ASH). However, the specific effects of alcohol on key liver lipid metabolic pathways involved in fat accumulation are unknown. It is unclear whether lipid synthesis, lipid export, or a combination of both is contributing to hepatic steatosis in ASH. Methods:, In this study we estimated the flux of fatty acids (FA) through the stearoyl-CoA desaturase (SCD), phosphatidylethanolamine- N -methyltransferase (PEMT), and FA elongation pathways in relation to liver triacylglycerol (TG) content in Yucatan micropigs fed a 40% ethanol folate-deficient diet with or without supplementation with S -adenosyl methionine (SAM) compared with controls. Flux through the SCD and PEMT pathways was used to assess the contribution of lipid synthesis and lipid export respectively on the accumulation of fat in the liver. Liver FA composition within TG, cholesterol ester (CE), phosphatidylethanolamine, and phosphatidylcholine classes was quantified by gas chromatography. Results:, Alcoholic pigs had increased liver TG content relative to controls, accompanied by increased flux through the SCD pathway as indicated by increases in the ratios of 16:1n7 to 16:0 and 18:1n9 to 18:0. Conversely, flux through the elongation and PEMT pathways was suppressed by alcohol, as indicated by multiple metabolite ratios. SAM supplementation attenuated the TG accumulation associated with alcohol. Conclusions:, These data provide an in vivo examination of liver lipid metabolic pathways confirming that both increased de novo lipogenesis (e.g., lipid synthesis) and altered phospholipid metabolism (e.g., lipid export) contribute to the excessive accumulation of lipids in liver affected by ASH. [source] THE INFLUENCE OF SOLUTION VISCOSITY AND DIFFERENT VISCOSIFYING AGENTS ON APPLE JUICE FLAVORJOURNAL OF SENSORY STUDIES, Issue 3 2000SHANE WALKER ABSTRACT Viscosifying agents are used in foods as thickeners to produce improved mouthfeel and as stabilizers to prevent settling out of particulate matter. While viscosifying agents are also known to influence the sensory profile of the products in which they are used, previous studies have examined the effects of viscosifying agents at levels that are not typical of those used in foods. The current study used a descriptive analysis panel to examine the effects of both viscosity and viscosifying agent on the sensory properties of apple juice using three viscosifying agents (carboxymethylcellulose, xanthan and pectin) at levels of usage similar to those recommended for drink products. Gas chromatography-flame ionization detection and gas chromatography-mass spectrometry were conducted on the samples to relate alteration in physico-chemical parameters to changes in sensory profile. Results from the descriptive panel showed that increasing viscosity tended to decrease some aspects of flavor intensity (sourness and cooked apple odor). Individual viscosifying agents were shown to have specific effects on odor and flavor attributes, e.g. pectin enhanced cereal odor. Gas chromatography-flame ionization detection and mass spectrometry suggested that this effect was related to isopropyl alcohol contributed by the pectin in solution. Pectin also suppressed honey odor and flavor, lemon odor and cooked apple flavor. [source] A comparison between virus replication and abiotic stress (heat) as modifiers of host gene expression in peaMOLECULAR PLANT PATHOLOGY, Issue 3 2000Margarita Escaler Pea embryonic tissues respond to active replication of pea seed-borne mosaic potyvirus (PSbMV) by the down-regulation of a range of genes and the induction of others. Both of these responses can be seen when tissues are subjected to abiotic stress, particularly heat. We have compared the effects of the two inducers to assess whether the host alterations following virus replication represent generic responses to stress, or more specific effects. Five classes of response were identified: (i) genes induced by both stresses (e.g. heat shock protein 70, hsp70); (ii) genes induced by virus replication but unaffected by heat (e.g. glutathione reductase 2, gor2); (iii) genes induced by heat but unaffected by virus replication (e.g. heat shock factor, hsf); (iv) genes down-regulated by virus replication and unaffected by heat (e.g. vicilin, vic); and (v) genes unaffected by both inducers (e.g. actin, act and ,-tubulin, tub). A change in the appearance and organization of the endoplasmic reticulum (ER) was also seen in cells actively replicating PSbMV RNA. Heat treatment of pea embryonic tissues also produced altered ER, although the changes were different from those seen following virus infection. Collectively, these data show that, while there are some common features of the responses to virus infection and heat, there are also substantial differences. Hence, it appears that the host response to virus replication is not a general stress response. [source] Does maternal smoking during pregnancy cause childhood overweight?PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2 2003Marius Widerøe Summary The objective of this study was to examine a possible association between maternal smoking in pregnancy and childhood overweight. From a population-based cohort of 5722 women from Trondheim, Bergen (Norway) and Uppsala (Sweden) enrolled in early pregnancy during 1986,92, a random sample of 482 women was selected for participation. They were followed up throughout pregnancy, and their children from birth until 5 years of age. Data on maternal smoking and diet, socio-economic determinants and breast feeding were recorded prospectively. During pregnancy and childhood, anthropometric measures were also recorded. Maternal smoking status was based on reported number of cigarettes smoked in week 17 of pregnancy. Child overweight was defined by body mass index (BMI) and sum of skinfold thickness (SFT) , 85th percentile at 5 years of age. Children of mothers who smoked in pregnancy had increased risk of overweight at 5 years of age (RR 2.5, 95% CI 1.5, 4.2 for BMI; and RR 1.8, 95% CI 1.1, 3.0 for SFT). Adjusting for maternal diet, breast feeding, maternal obesity and socio-economic status did not suggest confounding. However, adjustment for birthweight increased the observed risk. A linear increase in BMI and SFT was observed with increasing number of cigarettes smoked. In conclusion, smoking during pregnancy may be a risk factor for development of childhood overweight. This study may support the hypothesis of ,fetal origin of adult disease', but the risk of overweight associated with smoking during pregnancy was independent of intrauterine growth retardation, and may thus be attributed to specific effects of cigarette smoke. [source] Spin dynamics of exciton polaritons in microcavitiesPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 11 2005I. A. Shelykh Abstract In this chapter we address a complex set of optical phenomena linked to the spin dynamics of exciton polaritons in semiconductor microcavities. When optically created, polaritons inherit the spin and dipole moment from the exciting light. Their state can be fully characterized by a so-called "pseudospin" accounting for both spin and dipole moment orientation. However, from the very beginning of their life in a microcavity, polaritons start changing their pseudospin state under effect of effective magnetic fields of different nature and due to scattering with acoustic phonons, defects, and other polaritons. This makes pseudospin dynamics of exciton polaritons rich and complex. It manifests itself in non-trivial changes in polarization of light emitted by the cavity versus time, pumping energy, pumping intensity and polarization. During the first years of theoretical research on exciton-polariton relaxation the polarization has been simply neglected. Later it has been understood that the energy and momentum-relaxation of exciton polaritons are spin-dependent. It is typically the case in the regime of stimulated scattering when the spin polarizations of initial and final polariton state have a huge effect on the scattering rate between these states. It appeared that critical conditions for polariton Bose-condensation are also polarization-dependent. In particular, the stimulation threshold (i.e. the pumping power needed to have a population exceeding 1 at the ground state of the lower polariton branch) has been experimentally shown to be lower under linear than under circular pumping. These experimental observations have stimulated the theoretical research toward understanding of mutually dependent polarization- and energy-relaxation mechanisms in microcavities. The authors of this chapter have been working on theoretical description of different specific effects of polariton spin-dynamics in microcavities for years. Here we attempted to put together all fragments and to formulate a general approach to the problem that would allow then to consider a variety of particular cases. We start from reminding the main spin-relaxation mechanisms known for free carriers and excitons. We then overview the most essential experimental results in this field before to present our original formalism which allowed us to interpret the key experimental findings. We are going to discuss only the strong coupling regime leaving aside all polarization effects in VCSELs. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | ||||||||||||||||||||||||||||||||||