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Role Of The N- And C-Lobes Of Calmodulin In The Activation Of Ca(2+)/Calmodulin-Dependent Protein Kinase Ii, Amelie Forest, Matthew T Swulius, Joyce K Y Tse, J Michael Bradshaw, Tara Gaertner, M Neal Waxham
Role Of The N- And C-Lobes Of Calmodulin In The Activation Of Ca(2+)/Calmodulin-Dependent Protein Kinase Ii, Amelie Forest, Matthew T Swulius, Joyce K Y Tse, J Michael Bradshaw, Tara Gaertner, M Neal Waxham
Journal Articles
Understanding the principles of calmodulin (CaM) activation of target enzymes will help delineate how this seemingly simple molecule can play such a complex role in transducing Ca (2+)-signals to a variety of downstream pathways. In the work reported here, we use biochemical and biophysical tools and a panel of CaM constructs to examine the lobe specific interactions between CaM and CaMKII necessary for the activation and autophosphorylation of the enzyme. Interestingly, the N-terminal lobe of CaM by itself was able to partially activate and allow autophosphorylation of CaMKII while the C-terminal lobe was inactive. When used together, CaMN and CaMC …
Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection., Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle
Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection., Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle
Journal Articles
In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell …
An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection., Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Yi Guo, Carmen Tellez, Marcos R H Estécio, Saira Ahmed, Jean-Pierre J. Issa
An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection., Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Yi Guo, Carmen Tellez, Marcos R H Estécio, Saira Ahmed, Jean-Pierre J. Issa
Journal Articles
Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.
Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana
Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana
Journal Articles
Diffusion tensor imaging (DTI) and immunohistochemistry were performed in spinal cord injured rats to understand the basis for activation of multiple regions in the brain observed in functional magnetic resonance imaging (fMRI) studies. The measured fractional anisotropy (FA), a scalar measure of diffusion anisotropy, along the region encompassing corticospinal tracts (CST) indicates significant differences between control and injured groups in the 3 to 4 mm area posterior to bregma that correspond to internal capsule and cerebral peduncle. Additionally, DTI-based tractography in injured animals showed increased number of fibers that extend towards the cortex terminating in the regions that were activated …
Dominance Of The Proximal Coordinate Frame In Determining The Locations Of Hippocampal Place Cell Activity During Navigation, Jennifer J Siegel, Joshua P Neunuebel, James J Knierim
Dominance Of The Proximal Coordinate Frame In Determining The Locations Of Hippocampal Place Cell Activity During Navigation, Jennifer J Siegel, Joshua P Neunuebel, James J Knierim
Journal Articles
The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform …