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Articles 1 - 9 of 9
Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin
Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin
Celia A. Schiffer
The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …
Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer
Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer
Celia A. Schiffer
HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional …
Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren
Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren
Celia A. Schiffer
Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …
Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer
Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer
Celia A. Schiffer
The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.
Non-Viral Enos Gene Delivery And Transfection With Stents For The Treatment Of Restenosis, Luis A. Brito, Saradha Chandrasekhar, Steven R. Little, Mansoor M. Amiji
Non-Viral Enos Gene Delivery And Transfection With Stents For The Treatment Of Restenosis, Luis A. Brito, Saradha Chandrasekhar, Steven R. Little, Mansoor M. Amiji
Mansoor M. Amiji
Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR …
Phasic Activity Of Urinary Bladder Smooth Muscle In The Streptozotocin-Induced Diabetic Rat: Effect Of Potassium Channel Modulators, Bahareh Vahabi, Kim Lawson, Neil G. Mckay, Donna Sellers
Phasic Activity Of Urinary Bladder Smooth Muscle In The Streptozotocin-Induced Diabetic Rat: Effect Of Potassium Channel Modulators, Bahareh Vahabi, Kim Lawson, Neil G. Mckay, Donna Sellers
Donna Sellers
Increased phasic activity in the bladder smooth muscle of animal models and patients with detrusor overactivity has been suggested to underlie the pathophysiology of overactive bladder. Potassium (K+) channels are key regulators of bladder smooth muscle tone and thus may play a role in this altered phasic activity. In this study the effects of K+ channel modulators on the phasic activity of bladder strips from the streptozotocin-induced diabetic rat model of bladder dysfunction were investigated. Bladder strips from rats 1 week following streptozotocin administration and age-matched controls were mounted in tissue baths at 37 °C and the effects of K+ …
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
Syam Mohan
Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) …
Comparison Of Renal Effects Of Ibuprofen Versus Indomethacin During Treatment Of Patent Ductus Arteriosus In Contiguous Historical Cohorts, Alla Kushnir, Joaquim Mb Pinheiro
Comparison Of Renal Effects Of Ibuprofen Versus Indomethacin During Treatment Of Patent Ductus Arteriosus In Contiguous Historical Cohorts, Alla Kushnir, Joaquim Mb Pinheiro
Alla Kushnir
No abstract provided.
Spatial Distribution Of Commercial Banks In Ilorin Metropolis, Kwara State, Nigeria, I B. Abdullahi, M A. Ijaiya, A Abdulraheem, R I. Abdulkadir, R O. Ibrahim
Spatial Distribution Of Commercial Banks In Ilorin Metropolis, Kwara State, Nigeria, I B. Abdullahi, M A. Ijaiya, A Abdulraheem, R I. Abdulkadir, R O. Ibrahim
Confluence Journal of Environmental Studies (CJES), Kogi State University, Nigeria
The spatial distribution of banks in any geographic entity determines the level of accessibility to its services by the public. This study examined the pattern of banks distribution in Ilorin metropolis. Field survey was employed in determining the number of available commercial banks and their respective distances between each other. The spatial analysis technique such as the nearest neighbour analysis as used ascertain the degree of clustering, density and the average distance taken to access these services. The study revealed that about 96% of the total number of banks are situated in the Central Business District which exhibited a very …