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Genetic constraints on protein evolution.

Manel Camps Herman, A Loh, E Loeb, La

Published in Critical Reviews in Biochemistry and Molecular Biology

Evolution requires the generation and optimization of new traits ("adaptation") and involves the selection of mutations that improve cellular function. These mutations were assumed to arise by selection of neutral mutations present at all times in the population. Here we review recent evidence that indicates that deleterious mutations are more freq...

Targeted mutagenesis in E. coli: A powerful tool for the generation of random mutant libraries.

Manel Camps Loeb, La

Published in Discovery medicine

Extract: Mutagenesis is widely used in the fields of genetics, enzyme catalysis, ligand-binding recognition, metabolic regulation, control of gene expression, and to study mechanisms of DNA repair. Mutations are also introduced to optimize enzyme performance. This area has attracted renewed interest with the increased use of biocatalysts in chemica...

Computational integration of homolog and pathway gene module expression reveals general stemness signatures. PDF available through Get Fulltext Research

Koeva, M Forsberg, Ec Josh Stuart

Published in PLoS ONE

The stemness hypothesis states that all stem cells use common mechanisms to regulate self-renewal and multi-lineage potential. However, gene expression meta-analyses at the single gene level have failed to identify a significant number of genes selectively expressed by a broad range of stem cell types. We hypothesized that stemness may be regulated...

Observation of intersubunit movement of the ribosome in solution using FRET.

Ermolenko, Dn Majumdar, Zk Hickerson, Rp Spiegel, Pc Clegg, Rm Harry Noller

Published in Journal of Molecular Biology

Protein synthesis is believed to be a dynamic process, involving structural rearrangements of the ribosome. Cryo-EM reconstructions of certain elongation factor G (EF-G)-containing complexes have led to the proposal that translocation of tRNA and mRNA through the ribosome, from the A to P to E sites, is accompanied by a rotational movement between ...

Induction of arthritis with monoclonal antibodies to collagen.

Terato, K Hasty, Ka Reife, Ra Cremer, Ma Kang, Ah Josh Stuart

Published in The Journal of Immunology

mAb were developed from DBA/1 mice immunized with chick type II collagen. A total of 69 IgG antibodies was isolated and characterized. The majority (36%) reacted with a CNBr-derived peptide CB11 previously identified as containing a major immunogenic and arthritogenic epitope(s). Seven of the antibodies reactive with CB11 crossreacted strongly with...

Unusual resistance of peptidyl transferase to protein extraction procedures.

Harry Noller Hoffarth, V Zimniak, L

Published in Science

Peptidyl transferase, the ribosomal activity responsible for catalysis of peptide bond formation, is resistant to vigorous procedures that are conventionally employed to remove proteins from protein-nucleic acid complexes. When the "fragment reaction" was used as a model assay for peptide bond formation, Escherichia coli ribosomes or 50S subunits r...

Genomic dissection and prioritizing of candidate genes of QTL for regulating spontaneous arthritis on chromosome 1 in mi...

Cao, Y Zhang, J Jiao, Y Yan, J Jiao, F Liu, X Williams, Rw Hasty, Ka Josh Stuart Gu, W ...

Published in Journal of Genetics

Rheumatoid arthritis is a heterogeneous disease with clinical and biological polymorphisms. IL-1RN is a protein that binds to interleukin-1 (IL-1) receptors and inhibits the binding of IL-1-alpha and IL-1-beta. IL-1RN levels are elevated in the blood of patients with a variety of infectious, immune, and traumatic conditions. Balb/c mice deficient i...

Network models of TEM β-lactamase mutations coevolving under antibiotic selection show modular structure and anticipate ... PDF available through Get Fulltext Research

Guthrie, Vb Allen, J Manel Camps Karchin, R

Published in PLoS Computational Biology

Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here...

Scanning microarray slides.

Ares M, Jr

Published in Cold Spring Harbor Protocols

Here we describe some practical concerns surrounding the scanning of microarray slides that have been hybridized with fluorescent dyes. We use a laser scanner that has two lasers, each set to excite a different fluor, and separate detectors to capture emission from each fluor. The laser passes over an address (position on the scanned surface) and t...

Antigenic modulation of junctional acetylcholine receptor is not sufficient to account for the development of myasthenia...

Phil Berman Heinemann, Sf

Published in The Journal of Immunology

Myasthenia gravis (MG) is a disease thought to result from an autoimmune response against the nicotinic acetylcholine receptor of the neuromuscular junction. Although there is little doubt that the muscular weakness characteristic of MG can be attributed to an antibody-mediated reduction in the density of AChR, the mechanism responsible for this re...

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