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Butterfield DA Howard B Yatin S Koppal T Drake J Hensley K Aksenov M Aksenova M Subramaniam R Varadarajan S Harris-White ME Pedigo NW Carney JM 《Life sciences》1999,65(18-19):1883-1892
Age-associated neurodegenerative disorders are becoming more prevalent as the mean age of the population increases in the United States over the next few decades. Both normal brain aging and Alzheimer's disease (AD) are associated with oxidative stress. Our laboratory has used a wide variety of physical and biochemical methods to investigate free radical oxidative stress in several models of aging and AD. Beta-amyloid (A beta), the peptide that constitutes the central core of senile plaques in AD brain, is associated with free radical oxidative stress and is toxic to neurons. This review summarizes some of our studies in aging and A beta-associated free radical oxidative stress and on the modulating effects of free radical scavengers on neocortical synaptosomal membrane damage found in aging and A beta-treated systems. 相似文献
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Bimolecular fluorescence quenching reactions of the biologically active coumarin composite 2‐acetyl‐3H‐benzo[f]chromen‐3‐one in different solvents 下载免费PDF全文
A study on fluorescence quenching was carried out for the coumarin derivative 2‐acetyl‐3H‐benzo[f]chromen‐3‐one (2AHBC) with aniline at room temperature. Efficient fluorescence quenching was observed and Stern–Volmer (S–V) plots showed upward curves from linearity in all solvents of different polarities. For the solute 2AHBC, ground state complex formation does not hold in our study. The kinetic distance (r) value was found to be greater than the encounter distance (R) and indicated that the quenching reaction was held within the sphere of action. Diffusion‐limited reactions were found to be more prominent in high polarity solvents, namely dimethyl sulfoxide (DMSO), DMF, ACN, methanol, ethanol, propanol and DCM. The relationships between quenching constant (KSV) and dielectric constants (ε) of the different solvents were studied. 相似文献
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Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites
Doron Betel Anjali Koppal Phaedra Agius Chris Sander Christina Leslie 《Genome biology》2010,11(8):R90
mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains
a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation,
miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of
their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally
determined non-canonical and non-conserved sites. 相似文献
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The astrocytic protein S100B stimulates neurite outgrowth and neuronal survival during CNS development. S100B can also stimulate glial activation, leading to induction of pro-inflammatory molecules like interleukin-1 beta (IL-1 beta) and inducible nitric oxide synthase (iNOS). Although it is known that S100B's neurotrophic activity requires a disulfide-linked dimeric form of the protein, the structural features of S100B that are important for glial activation have not been defined. As an initial step towards understanding the structural features of S100B required for its action on glia and to determine if these features are different from those required for its action on neurons, we tested two mutants of S100B for their ability to activate glia. The C68VC84S mutant lacks S100B's two cysteine residues (cys68, cys84) and lacks neurotrophic activity (Winningham-Major et al., 1989, J. Cell Biol. 109 3063-3071), and the truncation mutant S100B83stop lacks the C-terminal nine residues (including cys84) that have been shown to be important for some S100B:target protein interactions. We report here that both C68VC84S and S100B83stop stimulate glial activation, as determined by induction of iNOS and IL-1 beta in rat primary astrocyte and microglial cultures. C68VC84S showed activation profiles similar to those of wild-type S100B, demonstrating that a disulfide-linked dimer is not required for glial activation. S100B83stop also stimulated both iNOS and IL-1 beta, although S100B83stop was significantly less effective than wild-type S100B in inducing iNOS. These results indicate that the C-terminal region of S100B is not required for glial activation; however, its presence may influence the degree of activation by the protein. Altogether, these studies demonstrate that the structural features required for S100B's neurotrophic activity are distinct from those affecting its glial activation activity. 相似文献
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Raveendra Melavanki Vijaya Kumar Diksha Singh Nishant Dhiman Varsha V. Koppal N. R. Patil 《Luminescence》2022,37(6):907-912
Quinoline derivative, i.e. quinilone yellow with the scientific name [sodium 2-(2,3-dihydro-1,3-dioxo-1H-inden-2-yl)quinoline-6,8-disulphonate] (SQDS) is analysed for fluorescence resonance energy transfer (FRET). Fluorescence quenching mechanism is studied by employing steady state and transient state spectroscopic measurements. Cobalt chloride is used as quencher in the present study. Linearity was observed in Stern–Volmer plots for transient state as well as steady state. This was further attributed to a mechanism of collisional quenching. Efficiency in fluorescence quenching is observed as there is a correlation between quenching constants of both transient and steady state. A significant energy transfer is reported between metal ions and SQDS molecule, according to FRET theory. Characterization results are studied and analysed. Application in the field of non-linear optics are predicted for SQDS. With Kurtz and Perry powder technique, SHG (second harmonic generation) efficiency was measured using Q-switched mode locked Nd:YAG laser emitting 1064 nm the first time with this compound. 相似文献
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Subramaniam Ram Koppal Tanuja Green Michael Yatin Servet Jordan Brad Drake Jennifer Butterfield D. Allan 《Neurochemical research》1998,23(11):1403-1410
Amyloid -peptide (A) is a key factor in the neurotoxicity of Alzheimer's disease (AD). Recent research has shown that A-mediated neurotoxicity involves free radicals and that A peptides can initiate multiple membrane alterations, including protein oxidation and lipid peroxidation, eventually leading to neuronal cell death. Research also has emphasized the role of 4-hydroxynonenal (HNE), a downstream product of lipid peroxidation, in being able to mimic some of the effects of A peptides. In the current investigation, electron paramagnetic resonance (EPR) studies of spin labeled cortical synaptosomal membrane proteins has been employed to study conformational changes in proteins, spectrophotometric methods have been used to measure protein carbonyl content, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for mitochondrial function has been used to study the effect of vitamin E on samples that were treated with A or HNE. The free radical dependence of -amyloid-associated toxicity was confirmed by the ability of the free radical scavenger vitamin E to prevent the toxic effects of A. In contrast, HNE was still toxic in the presence of vitamin E. These results support our A-associated free radical model for neurotoxicity in AD brain and are discussed with reference to potential therapeutic strategies for AD. 相似文献
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