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Full-Text Articles in Medicine and Health Sciences

Aminoacyl-Trna Synthetase Complexes: Molecular Multitasking Revealed, Corinne D. Hausmann, Michael Ibba Jul 2008

Aminoacyl-Trna Synthetase Complexes: Molecular Multitasking Revealed, Corinne D. Hausmann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process are the aminoacyl-tRNA synthetases (aaRSs), which provide amino acid substrates for the growing polypeptide chain in the form of aminoacyl-tRNAs. The aaRSs are essential for coupling the correct amino acid and tRNA molecules, but are also known to associate in higher order complexes with proteins involved in processes beyond translation. Multiprotein complexes containing aaRSs are found in all three domains of life playing roles in splicing, apoptosis, viral assembly, and regulation of transcription and translation. …


Structural And Functional Mapping Of The Archaeal Multi-Aminoacyl-Trna Synthetase Complex, Corinne D. Hausmann, Michael Ibba Jun 2008

Structural And Functional Mapping Of The Archaeal Multi-Aminoacyl-Trna Synthetase Complex, Corinne D. Hausmann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Methanothermobacter thermautotrophicus contains a multi-aminoacyl-tRNA synthetase complex (MSC) of LysRS, LeuRS and ProRS. Elongation factor (EF) 1A also associates to the MSC, with LeuRS possibly acting as a core protein. Analysis of the MSC revealed that LysRS and ProRS specifically interact with the idiosyncratic N- and C- termini of LeuRS, respectively. EF-1A instead interacts with the inserted CP1 proofreading domain, consistent with models for post-transfer editing by class I synthetases such as LeuRS. Together with previous genetic data, these findings show that LeuRS plays a central role in mediating interactions within the archaeal MSC by acting as a core scaffolding …


Monitoring Lys-TrnaLys Phosphatidylglycerol Transferase Activity, Michael Ibba Jan 2008

Monitoring Lys-TrnaLys Phosphatidylglycerol Transferase Activity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In some bacteria Lys-tRNALys is used both in translation and for the specific addition of Lys to phosphatidylglycerol in the cytoplasmic membrane. This reaction is catalyzed by the membrane protein MprF, and the lysyl-phosphatidylglycerol formed contributes to the resistance of these bacteria to various cationic antibacterial molecules. Obtaining proteins and reconstituting an in vitro system mimicking membrane conditions is a major challenge to studying the function of membrane proteins, especially when labile substrates such as Lys-tRNALys are required. Here we report methods to obtain a stable enriched membrane fraction containing MprF, and the techniques necessary to quantitatively monitor …


Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon Jan 2008

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …


Resistance Training And Bone Mineral Density During Growth, M. Z. Smith, B. M. Goettsch, R. D. Van Ramshorst, J. A. O'Brien, S. V. Jaque, Ken D. Sumida Jan 2008

Resistance Training And Bone Mineral Density During Growth, M. Z. Smith, B. M. Goettsch, R. D. Van Ramshorst, J. A. O'Brien, S. V. Jaque, Ken D. Sumida

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

This study examined the efficacy of two different resistance training programs in enhancing bone modeling and bone mineral density (BMD) in maturating rats. One exercise mode involved lifting a lighter weight with more repetitions (LI), while the other regimen involved lifting a heavier weight with fewer repetitions (HI) where the total volume of work between exercise programs was equivalent by design. Twenty-three male rats were randomly divided into control (Con, n = 8), LI (n = 7), and HI (n = 8) groups. The LI and HI groups were conditioned to climb a vertical ladder with weights appended to their …


Interrupted Vs. Uninterrupted Training On Bmd During Growth, B. M. Goettsch, M. Z. Smith, J. A. O'Brien, G. V. Gomez, S. V. Jaque, Ken D. Sumida Jan 2008

Interrupted Vs. Uninterrupted Training On Bmd During Growth, B. M. Goettsch, M. Z. Smith, J. A. O'Brien, G. V. Gomez, S. V. Jaque, Ken D. Sumida

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

This study compared a resistance training program where the exercise was uninterrupted (UT, i.e., continuous repetitions) against a resistance training program where the exercise was interrupted (IT, i.e., 3 exercise sessions during a training day) for enhancing bone modeling and bone mineral density (BMD) in maturating animals. The total volume of work performed between the two resistance training programs was equivalent by design. 24 young male rats were randomly divided into Control (Con, n = 8), UT (n = 8) and IT (n=8) resistance trained groups. The UT and IT groups were conditioned to climb a vertical ladder with weights …


Size-Controlled Synthesis Of Monodisperse Core/Shell Nanogels, William H. Blackburn, L. Andrew Lyon Jan 2008

Size-Controlled Synthesis Of Monodisperse Core/Shell Nanogels, William H. Blackburn, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Small, monodisperse nanogels (similar to 50-nm radius) were synthesized by free-radical precipitation polymerization and were characterized using a suite of light scattering and chromatography methods. Nanogels were synthesized with either N-isopropylacrylamide or N-isopropylmethacrylamide as the main monomer, with acrylic acid or 4-acrylamidofluorescein as a comonomer and N,N'-methylenebis(acrylamide) as a cross-linker. By varying the surfactant and initiator concentrations, particle size was controlled while maintaining excellent monodispersity. An amine-containing shell was added to these core particles to facilitate subsequent bioconjugation. Successful conjugation of folic acid to the particles was demonstrated as an example of how such materials might be employed in a …


Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García Jan 2008

Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Implantation of synthetic materials into the body elicits inflammatory host responses that limit medical device integration and biological performance. This inflammatory cascade involves protein adsorption, leukocyte recruitment and activation, cytokine release, and fibrous encapsulation of the implant. We present a coating strategy based on thin films of poly(N-isopropylacrylamide) hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol) diacrylate. These particles were grafted onto a clinically relevant polymeric material to generate conformal coatings that significantly reduced in vitro fibrinogen adsorption and primary human monocyte/macrophage adhesion and spreading. These microgel coatings also reduced leukocyte adhesion and expression of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, …