1,448 research outputs found
Structure of Polyelectrolytes in Poor Solvent
We present simulations on charged polymers in poor solvent. First we
investigate in detail the dilute concentration range with and without imposed
extension constraints. The resulting necklace polymer conformations are
analyzed in detail. We find strong fluctuations in the number of pearls and
their sizes leading only to small signatures in the form factor and the
force-extension relation. The scaling of the peak in the structure factor with
the monomer density shows a pertinent different behavior from good solvent
chains.Comment: 7 pages, 5 figures. submitted to EP
Analysis of Oligonucleotides by Electrospray Ionization Mass Spectrometry
Because of the high molecular weights and thermal lability of biomolecules such as nucleic acids and protein, they can be difficult to analyze by mass spectrometry. Such analyses require a âsoftâ ionization method that is capable of generating intact molecular ions. In addition, most mass analyzers have a limited upper mass range that is not sufficient for studying these large molecules. ESIâMS can be used to analyze molecules with a molecular weight that is larger than the massâtoâcharge ratio limit of the analyzer. This unit describes how ESI allows for analysis of highâmolecularâweight compounds through the generation of multiply charged ions in the gas phase. It discusses analyzer configurations, solvent selection, and gives protocols for sample preparation. For applications of ESIâMS, the unit discusses molecular weight determination and gives protocols for sequencing and for analyzing oligonucleotide modifications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143640/1/cpnc1002.pd
New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors.
RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen.
CONCLUSION: These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development
Finite Size Polyelectrolyte Bundles at Thermodynamic Equilibrium
We present the results of extensive computer simulations performed on
solutions of monodisperse charged rod-like polyelectrolytes in the presence of
trivalent counterions. To overcome energy barriers we used a combination of
parallel tempering and hybrid Monte Carlo techniques. Our results show that for
small values of the electrostatic interaction the solution mostly consists of
dispersed single rods. The potential of mean force between the polyelectrolyte
monomers yields an attractive interaction at short distances. For a range of
larger values of the Bjerrum length, we find finite size polyelectrolyte
bundles at thermodynamic equilibrium. Further increase of the Bjerrum length
eventually leads to phase separation and precipitation. We discuss the origin
of the observed thermodynamic stability of the finite size aggregates
Polyelectrolyte Bundles
Using extensive Molecular Dynamics simulations we study the behavior of
polyelectrolytes with hydrophobic side chains, which are known to form
cylindrical micelles in aqueous solution. We investigate the stability of such
bundles with respect to hydrophobicity, the strength of the electrostatic
interaction, and the bundle size. We show that for the parameter range relevant
for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle
size. In a more generic model we also show the influence of the length of the
precursor oligomer on the stability of the bundles. We also point out that our
model has close similarities to DNA solutions with added condensing agents,
hinting to the possibility that the size of DNA aggregates is under certain
circumstances thermodynamically limited.Comment: 10 pages, 8 figure
Identification of oxidized amino acid residues in the vicinity of the Mn \u3csub\u3e4\u3c/sub\u3eCaO \u3csub\u3e5\u3c/sub\u3e cluster of photosystem II: Implications for the identification of oxygen channels within the photosystem
As a light-driven water-plastoquinone oxidoreductase, Photosystem II produces molecular oxygen as an enzymatic product. Additionally, under a variety of stress conditions, reactive oxygen species are produced at or near the active site for oxygen evolution. In this study, Fourier-transform ion cyclotron resonance mass spectrometry was used to identify oxidized amino acid residues located in several core Photosystem II proteins (D1, D2, CP43, and CP47) isolated from spinach Photosystem II membranes. While the majority of these oxidized residues (81%) are located on the oxygenated solvent-exposed surface of the complex, several residues on the CP43 protein ( 354E, 355T, 356M, and 357R) which are in close proximity (\u3c15 \u3eĂ
) to the Mn 4CaO 5 active site are also modified. These residues appear to be associated with putative oxygen/reactive oxygen species exit channel(s) in the photosystem. These results are discussed within the context of a number of computational studies which have identified putative oxygen channels within the photosystem. © 2012 American Chemical Society
Association of the 17-kDa extrinsic protein with photosystem II in higher plants
The structural association of the spinach 17-kDa extrinsic protein of photosystem II with other extrinsic and membrane-bound components of the photosystem was investigated by labeling the 17-kDa extrinsic protein with the amino-group-specific reagent N-hydroxysuccinimidobiotin both on intact photosystem II membranes or as a free protein in solution. After isolation of the biotinylated molecules, the modified 17-kDa proteins were allowed to rebind to photosystem II membranes which were depleted of the 17-kDa component. Differential binding of the protein biotinylated in solution compared to unmodified 17-kDa protein or 17-kDa protein modified on PSII membranes was observed. This indicated possible steric or ionic interference because of biotinylated lysyl residues present on the protein modified in solution. Biotinylated sites on the different modified 17-kDa proteins were identified by trypsin and Staphylococcus V8 protease digestion, followed by affinity chromatography enrichment of the biotinylated peptides and analysis of the peptide fragment mixture by nanospray liquid chromatography-tandem mass spectrometry. Four lysyl residues that were modified when the protein was biotinylated in solution were not biotinylated when the protein was modified on the PS II membrane (90K, 96K, 101K, and 102K). These residues appear to identify a protein domain involved in the interaction of the 17-kDa protein with the other components of the photosystem. © 2005 American Chemical Society
Radiolytic mapping of solvent-contact surfaces in photosystem II of higher plants: Experimental identification of putative water channels within the photosystem
Background: Substrate water must reach the buried Mn4O 5Ca cluster in Photosystem II. Results: OH produced by radiolysis modified buried amino acid residues. These were mapped onto the PS II crystal structure. Conclusion: Two groups of oxidized residues were identified which form putative pathways to the Mn4O5Ca cluster. Significance: Identification of water and oxygen channels is crucial for our understanding of Photosystem II function. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc
Molecular Dynamics Simulation of Semiflexible Polyampholyte Brushes - The Effect of Charged Monomers Sequence
Planar brushes formed by end-grafted semiflexible polyampholyte chains, each
chain containing equal number of positively and negatively charged monomers is
studied using molecular dynamics simulations. Keeping the length of the chains
fixed, dependence of the average brush thickness and equilibrium statistics of
the brush conformations on the grafting density and the salt concentration are
obtained with various sequences of charged monomers. When similarly charged
monomers of the chains are arranged in longer blocks, the average brush
thickness is smaller and dependence of brush properties on the grafting density
and the salt concentration is stronger. With such long blocks of similarly
charged monomers, the anchored chains bond to each other in the vicinity of the
grafting surface at low grafting densities and buckle toward the grafting
surface at high grafting densities.Comment: 8 pages,7 figure
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