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Multiple Targets (multiple + target)
Selected AbstractsVisual search in typically developing toddlers and toddlers with Fragile X or Williams syndromeDEVELOPMENTAL SCIENCE, Issue 1 2004Gaia Scerif Visual selective attention is the ability to attend to relevant visual information and ignore irrelevant stimuli. Little is known about its typical and atypical development in early childhood. Experiment 1 investigates typically developing toddlers' visual search for multiple targets on a touch-screen. Time to hit a target, distance between successively touched items, accuracy and error types revealed changes in 2- and 3-year-olds' vulnerability to manipulations of the search display. Experiment 2 examined search performance by toddlers with Fragile X syndrome (FXS) or Williams syndrome (WS). Both of these groups produced equivalent mean time and distance per touch as typically developing toddlers matched by chronological or mental age; but both produced a larger number of errors. Toddlers with WS confused distractors with targets more than the other groups; while toddlers with FXS perseverated on previously found targets. These findings provide information on how visual search typically develops in toddlers, and reveal distinct search deficits for atypically developing toddlers. [source] CE combined with rolling circle amplification for sensitive DNA detectionELECTROPHORESIS, Issue 2 2008Ni Li Abstract Here we describe an assay which combines CE with rolling circle amplification (RCA) for sensitive DNA detection and quantification. RCA is an isothermal DNA replication technique that generates a long ssDNA with tandem repeats. It requires simpler temperature control in reaction and offers higher sequence specificity and greater quantitation capability compared to other amplification technologies. In this study, RCA amplified the DNA target via a circular template, and the product was digested into monomers for CE analysis. Less than 2,fmol of the DNA target could easily be detected using this RCA-CE assay and the assay has a dynamic range of two orders of magnitudes. Moreover, simultaneous detection of both the target DNA and the internal standard was achieved by designing two padlock probes with different sizes, which could significantly improve the quantification accuracy. The RCA-CE assay is easy to perform, readily adaptable for detection of multiple targets because of the high resolution power of CE, and is compatible with other applications employing RCA as a signal amplification tool. Additionally, this assay can be used with a capillary array system to perform sensitive, high-throughput genetic screening. [source] Social Group and Moral Orientation Factors as Mediators of Religiosity and Multiple Attitude TargetsJOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION, Issue 3 2008KENNETH I. MAVOR Although there is a tradition of examining generalized discrimination against multiple targets, recent studies have tended to consider race and homosexuality as separate targets without considering their relationship with each other. Recent studies have also argued for a moral dimension in attitudes to homosexuality, but this has not yet been explicitly modeled as an explanation for patterns of social attitudes. In a questionnaire study of practicing Australian Christians (N= 143), we examined the relationship of religious orientation and ideology (intrinsic, extrinsic, fundamentalism, orthodoxy, and quest) with four attitude targets (Aboriginal Australians, women, homosexual persons, and abortion). Using structural equation modeling (SEM), we develop a two-factor model, incorporating group and moral orientation factors, which completely mediates the relationships between the religiosity variables and the social attitudes. Religiosity variables exhibit different patterns of correlation with the two factors. The two-factor model provides a useful framework for further exploration of socially and politically contested attitudes. [source] Mechanisms involved in the photosensitized inactivation of Acanthamoeba palestinensis trophozoitesJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2009S. Ferro Abstract Aims:, To advance our understanding of the mechanisms involved in the RLP068 phthalocyanine-photosensitized inactivation of Acanthamoeba palestinensis trophozoites through a precise identification of the targets of the photoprocess in both the cytosolic and mitochondrial compartments. Methods and Results:, We followed the activities of selected marker enzymes as well as we performed fluorescence and transmission electron microscopy investigations of the alterations induced by the photoprocess in the fine structure of subcellular compartments. RLP068 is preferentially located in the contractile vacuole: the fluorescence in that site is particularly evident in the unirradiated cells and becomes more diffused after irradiation. Electron microscopic analysis of photosensitized A. palestinensis cells clearly shows that the swelling of trophozoites and the appearance of vacuoles spread throughout the cytoplasm after phototreatment. The activity of a typical cytoplasmic enzyme, such as lactate dehydrogenase, underwent a 35% decrease as a consequence of the photoprocess, reflecting the photodamage induced by migrating phthalocyanine molecules in their micro-environment. Conclusions:, The presence of multiple targets for the phthalocyanine-photosensitized process is of utmost importance because this pattern of cell damage makes it unlikely that photoresistant A. palestinensis strains are gradually selected or mutagenic phenomena are developed as a consequence of the photoinduced damage. Significance and Impact of the Study:, Photosensitization via phthalocyanines appears to represent an efficient and safe approach for achieving a close control of the population of a potentially pathogenic protozoan such as A. palestinensis, opening new perspectives for the disinfection of microbiologically polluted waters. [source] MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in MiceALCOHOLISM, Issue 10 2009Angela Dolganiuc Background:, Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation. Methods:, We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, and microRNA profile by microarray. Results:, Both Lieber-DeCarli and MCD diets lead to development of liver steatosis, liver injury, indicated by increased ALT, and elevated levels of serum TNF,, suggesting that animal models portray the pathophysiological features of alcoholic and nonalcoholic fatty liver, respectively. We identified that Lieber-deCarli diet up-regulated 1% and down-regulated 1% of known miRNA; MCD diet up-regulated 3% and down-regulated 1% of known miRNA, compared to controls. Of miRNAs that changed expression levels, 5 miRNAs were common in alcoholic and nonalcoholic fatty livers: the expression of both miR-705 and miR-1224 was increased after Lieber-DeCarli or MCD diet feeding. In contrast, miR-182, miR-183, and miR-199a-3p were down-regulated in Lieber-deCarli feeding, while MCD diet lead to their up-regulation, compared to corresponding controls. Conclusions:, Our findings indicate etiology-specific changes in miRNA expression profile during steatohepatitis models, which opens new avenues for research in the pathophysiology of alcoholic and nonalcoholic fatty liver disease. [source] MILP modelling for the time optimal control problem in the case of multiple targetsOPTIMAL CONTROL APPLICATIONS AND METHODS, Issue 2 2006H. H. Mehne Abstract Optimal guidance for a dynamical system from a given point to a set of targets is discussed. Detecting for the best target is done in such a way that the capture time is minimized and desirability of targets is maximized. By extending measure theoretical approach for the classical optimal control problem to this case, the nearly optimal control is constructed from the solution of a mixed integer linear programming problem. To find the lower bound of the optimal time a search algorithm is proposed. Numerical examples are also given. Copyright © 2005 John Wiley & Sons, Ltd. [source] Atomic-resolution crystal structure of thioredoxin from the acidophilic bacterium Acetobacter acetiPROTEIN SCIENCE, Issue 1 2007Courtney M. Starks Abstract The crystal structure of thioredoxin (AaTrx) from the acetic acid bacterium Acetobacter aceti was determined at 1 Å resolution. This is currently the highest resolution crystal structure available for any thioredoxin. Thioredoxins facilitate thiol-disulfide exchange, a process that is expected to be slow at the low pH values encountered in the A. aceti cytoplasm. Despite the apparent need to function at low pH, neither the active site nor the surface charge distribution of AaTrx is notably different from that of Escherichia coli thioredoxin. Apparently the ancestral thioredoxin was sufficiently stable for use in A. aceti or the need to interact with multiple targets constrained the variation of surface residues. The AaTrx structure presented here provides a clear view of all ionizable protein moieties and waters, a first step in understanding how thiol-disulfide exchange might occur in a low pH cytoplasm, and is a basis for biophysical studies of the mechanism of acid-mediated unfolding. The high resolution of this structure should be useful for computational studies of thioredoxin function, protein structure and dynamics, and side-chain ionization. [source] Detection of the Dinozoans Pfiesteria piscicida and P. shumwayae: A Review of Detection Methods and Geographic Distribution,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005PARKE A. RUBLEE Abstract. Molecular methods, including conventional PCR, real-time PCR, denaturing gradient gel electrophoresis, fluorescent fragment detection PCR, and fluorescent in situ hybridization, have all been developed for use in identifying and studying the distribution of the toxic dinoflagellates Pfiesteria piscicida and P. shumwayae. Application of the methods has demonstrated a worldwide distribution of both species and provided insight into their environmental tolerance range and temporal changes in distribution. Genetic variability among geographic locations generally appears low in rDNA genes, and detection of the organisms in ballast water is consistent with rapid dispersal or high gene flow among populations, but additional sequence data are needed to verify this hypothesis. The rapid development and application of these tools serves as a model for study of other microbial taxa and provides a basis for future development of tools that can simultaneously detect multiple targets. [source] The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen speciesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Darren C Phillips The mechanism of action by which methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effects remains unclear. The aim of this study is to investigate the hypothesis that MTX exerts these effects via the production of reactive oxygen species (ROS). Addition of MTX (100 nM,10 ,M) to U937 monocytes induced a time and dose dependent increase in cytosolic peroxide [peroxide]cyt from 6,16 h. MTX also caused corresponding monocyte growth arrest, which was inhibited (P<0.05) by pre-treatment with N-acetylcysteine (NAC; 10 mM) or glutathione (GSH; 10 mM). In contrast, MTX induction of [peroxide]cyt in Jurkat T cells was more rapid (4 h; P<0.05), but was associated with significant apoptosis at 16 h at all doses tested (P<0.05) and was significantly inhibited by NAC or GSH (P<0.05). MTX treatment of monocytes (10 nM,10 ,M) for 16 h significantly reduced total GSH levels (P<0.05) independently of dose (P>0.05). However, in T-cells, GSH levels were significantly elevated following 30 nM MTX treatment (P<0.05) but reduced by doses exceeding 1 ,M compared to controls (P<0.05). MTX treatment significantly reduced monocyte adhesion to 5 h and 24 h LPS (1 ,g ml,1) activated human umbilical vein endothelial cells (HUVEC; P<0.05) but not to resting HUVEC. Pre-treatment with GSH prevented MTX-induced reduction in adhesion. In conclusion, ROS generation by MTX is important for cytostasis in monocytes and cytotoxicity T-cells. Furthermore, MTX caused a reduction in monocyte adhesion to endothelial cells, where the mechanism of MTX action requires the production of ROS. Therefore its clinical efficacy can be attributed to multiple targets. British Journal of Pharmacology (2003) 138, 501,511. doi:10.1038/sj.bjp.0705054 [source] Entamoeba histolytica sirtuin EhSir2a deacetylates tubulin and regulates the number of microtubular assemblies during the cell cycleCELLULAR MICROBIOLOGY, Issue 7 2010Somasri Dam Summary We have discovered four sirtuin genes in Entamoeba histolytica, two of which are similar to eukaryotic sirtuins and two to bacterial and archaeal sirtuins. The eukaryotic sirtuin homologue, EhSir2a, showed NAD+ -dependent deacetylase activity and was sensitive to class III HDAC inhibitors. Localization of EhSir2a at different cellular sites suggested that this deacetylase could have multiple targets. Using an E. histolytica cDNA library in the yeast two-hybrid genetic screen, we identified several proteins that bound to EhSir2a. These proteins included Eh ,-tubulin, whose interaction with EhSir2a was validated in E. histolytica. We have shown that EhSir2a deacetylated tubulin and localized with microtubules in E. histolytica. Increased expression levels of EhSir2a in stable transformants led to reduced number of microtubular assemblies in serum synchronized cells. This effect was abrogated by mutations in the deacetylase domain of EhSir2a, showing that EhSir2a deacetylase activity affected the stability and number of microtubular assemblies during the cell cycle of E. histolytica. Our results suggest that epigenetic modification of tubulin by EhSir2a is one of the mechanisms that regulates microtubular assembly in E. histolytica. [source] | |||||||||||||