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SNAC-tag for sequence-specific chemical protein cleavage.
Site-specific protein cleavage is essential for many protein-production protocols and typically requires proteases. We report the development of a chemical protein-cleavage method that is achieved through the use of a sequence-specific nickel-assisted cleavage (SNAC)-tag. We demonstrate that the SNAC-tag can be inserted before both water-soluble and membrane proteins to achieve fusion protein cleavage under biocompatible conditions with efficiency comparable to that of enzymes, and that the method works even when enzymatic cleavages fail
Imaging of Myocardial Fatty Acid Oxidation
Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide noninvasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function
Designability of alpha-helical Proteins
A typical protein structure is a compact packing of connected alpha-helices
and/or beta-strands. We have developed a method for generating the ensemble of
compact structures a given set of helices and strands can form. The method is
tested on structures composed of four alpha-helices connected by short turns.
All such natural four-helix bundles that are connected by short turns seen in
nature are reproduced to closer than 3.6 Angstroms per residue within the
ensemble. Since structures with no natural counterpart may be targets for ab
initio structure design, the designability of each structure in the ensemble --
defined as the number of sequences with that structure as their lowest energy
state -- is evaluated using a hydrophobic energy. For the case of four
alpha-helices, a small set of highly designable structures emerges, most of
which have an analog among the known four-helix fold families, however several
novel packings and topologies are identified.Comment: 21 pages, 6 figures, to appear in PNA
Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity.
Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials
Novel Cyclotron-Based Radiometal Production
Accomplishments: (1) Construction of prototype solution target for radiometal production; (2) Testing of prototype target for production of following isotopes: a. Zr-89. Investigation of Zr-89 production from Y-89 nitrate solution. i. Defined problems of gas evolution and salt precipitation. ii. Solved problem of precipitation by addition of nitric acid. iii. Solved gas evolution problem with addition of backpressure regulator and constant degassing of target during irradiations. iv. Investigated effects of Y-89 nitrate concentration and beam current. v. Published abstracts at SNM and ISRS meetings; (3) Design of 2nd generation radiometal solution target. a. Included reflux chamber and smaller target volume to conserve precious target materials. b. Included aluminum for prototype and tantalum for working model. c. Included greater varicosities for improved heat transfer; and, (4) Construction of 2nd generation radiometal solution target started
Two models of the influenza A M2 channel domain: verification by comparison
Background: The influenza M2 protein is a simple membrane protein, containing a single transmembrane helix. It is representative of a very large family of single-transmembrane helix proteins. The functional protein is a tetramer, with the four transmembrane helices forming a proton-permeable channel across the bilayer. Two independently derived models of the M2 channel domain are compared, in order to assess the success of applying molecular modelling approaches to simple membrane proteins.Results: The Cα RSMD between the two models is 1.7 å. Both models are composed of a left-handed bundle of helices, with the helices tilted roughly 15° relative to the (presumed) bilayer normal. The two models have similar pore radius profiles, with a pore cavity lined by the Ser31 and Gly34 residues and a pore constriction formed by the ring of His37 residues.Conclusions:Independent studies of M2 have converged on the same structural model for the channel domain. This model is in agreement with solid state NMR data. In particular, both model and NMR data indicate that the M2 helices are tilted relative to the bilayer normal and form a left-handed bundle. Such convergence suggests that, at least for simple membrane proteins, restraints-directed modelling might yield plausible models worthy of further computational and experimental investigation
Genre perspective in the reception of soap operas
La igualdad entre hombres y mujeres se ha convertido hoy en dÃa en uno de los valores prioritarios o que más relevancia está adquiriendo en el actual contexto socio-mediático que vivimos. No cabe duda que el mundo televisivo es un importante agente de socialización, cuantitativa y cualitativamente, con el que conviven diariamente niños y niñas. En este sentido, las telenovelas son uno de los géneros televisivos con mayor visionado y preferencia por parte de niños y jóvenes. Este trabajo recoge una sÃntesis breve de una investigación realizada en un centro escolar durante el año 2007, reflejando no sólo los hábitos de consumo televisivo de niñas y niños de 11 y 12 años, sino también sus estereotipos de género.Nowadays, equality between men and women has become one of the main values due to the present circumstances we all live. Also, the world of the television is an important socialization agent which boys and girls confront every day, both quantitatively and qualitatively. Among others, one of the television programmes children face daily are soap operas series. This article is intended to present the results obtained after a school research in 2007 and it is pretended to reflect eleven and twelve year old young children’ consumerism habits
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