Arginine-rich cell-penetrating peptides

AbstractArginine-rich cell-penetrating peptides are short cationic peptides capable of traversing the plasma membranes of eukaryotic cells. While successful intracellular delivery of many biologically active macromolecules has been accomplished using these peptides, their mechanisms of cell entry are still under investigation. Recent dialogue has centered on a debate over the roles that direct translocation and endocytotic pathways play in internalization of cell-penetrating peptides. In this paper, we review the evidence for the broad range of proposed mechanisms, and show that each distinct process requires negative Gaussian membrane curvature as a necessary condition. Generation of negative Gaussian curvature by cell-penetrating peptides is directly related to their arginine content. We illustrate these concepts using HIV TAT as an example

Application of Knowledge-based Tools in Environmental Decision Support Systems

Decision support system often requires the combined knowledge of multiple domains. A knowledge-based approach is proposed to include not only the process modelling knowledge but also the descriptive knowledge in the integration. Descriptive knowledge such as survey statistics and expert opinions forms the core of a study on the uncertainty of the combined knowledge. It was found that the use of expert systems, neural network and belief causal network assist greatly in the implementation of these concepts. Examples are drawn from the combination of scientific and economic knowledge to solve some acid rain problems.decision support system; knowledge-based system; expert system; causal network

Lamellar Phase of Stacked Two-Dimensional Rafts of Actin Filaments

We examined liquid crystalline phases of the cytoskeletal polyelectrolyte filamentous (F-)actin in the presence of multivalent counterions. As a function of increasing ion concentration, the F-actin rods in either an isotropic or a nematic phase will transform into a new and unexpected lamellar phase of crosslinked rafts (LXR phase), before condensing into a bundled phase of parallel, close-packed rods. This behavior is generic for alkali earth divalent ions Mg2+, Ca2+, Sr2+, and Ba2+, and the structural transitions are achieved without any architecture-specific actin-binding linker proteins

Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides

AbstractNovel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration-dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova

Casein Kinase 1 Promotes Initiation of Clathrin-Mediated Endocytosis

SummaryIn budding yeast, over 60 proteins functioning in at least five modules are recruited to endocytic sites with predictable order and timing. However, how sites of clathrin-mediated endocytosis are initiated and stabilized is not well understood. Here, the casein kinase 1 (CK1) Hrr25 is shown to be an endocytic protein and to be among the earliest proteins to appear at endocytic sites. Hrr25 absence or overexpression decreases or increases the rate of endocytic site initiation, respectively. Ede1, an early endocytic Eps15-like protein important for endocytic initiation, is an Hrr25 target and is required for Hrr25 recruitment to endocytic sites. Hrr25 phosphorylation of Ede1 is required for Hrr25-Ede1 interaction and promotes efficient initiation of endocytic sites. These observations indicate that Hrr25 kinase and Ede1 cooperate to initiate and stabilize endocytic sites. Analysis of the mammalian homologs CK1δ/ε suggests a conserved role for these protein kinases in endocytic site initiation and stabilization

Spin- and charge-density oscillations in spin chains and quantum wires

We analyze the spin- and charge-density oscillations near impurities in spin chains and quantum wires. These so-called Friedel oscillations give detailed information about the impurity and also about the interactions in the system. The temperature dependence of these oscillations explicitly shows the renormalization of backscattering and conductivity, which we analyze for a number of different impurity models. We are also able to analyze screening effects in one dimension. The relation to the Kondo effect and experimental consequences are discussed.Comment: Final published version. 15 pages in revtex format including 22 epsf-embedded figures. The latest version in PDF format is available from http://fy.chalmers.se/~eggert/papers/density-osc.pd

Recent experimental results in sub- and near-barrier heavy ion fusion reactions

Recent advances obtained in the field of near and sub-barrier heavy-ion fusion reactions are reviewed. Emphasis is given to the results obtained in the last decade, and focus will be mainly on the experimental work performed concerning the influence of transfer channels on fusion cross sections and the hindrance phenomenon far below the barrier. Indeed, early data of sub-barrier fusion taught us that cross sections may strongly depend on the low-energy collective modes of the colliding nuclei, and, possibly, on couplings to transfer channels. The coupled-channels (CC) model has been quite successful in the interpretation of the experimental evidences. Fusion barrier distributions often yield the fingerprint of the relevant coupled channels. Recent results obtained by using radioactive beams are reported. At deep sub-barrier energies, the slope of the excitation function in a semi-logarithmic plot keeps increasing in many cases and standard CC calculations over-predict the cross sections. This was named a hindrance phenomenon, and its physical origin is still a matter of debate. Recent theoretical developments suggest that this effect, at least partially, may be a consequence of the Pauli exclusion principle. The hindrance may have far-reaching consequences in astrophysics where fusion of light systems determines stellar evolution during the carbon and oxygen burning stages, and yields important information for exotic reactions that take place in the inner crust of accreting neutron stars.Comment: 40 pages, 63 figures, review paper accepted for EPJ

PO-0698: Clinical outcomes of 4D CBCT-guided stereotactic body radiotherapy for inoperable hepatocellular carcinomas

Poster: Clinical track: Gastrointestinal tumours (upper and lower GI)published_or_final_version3rd ESTRO Forum, Barcelona, Spain, 24-28 April 2015. In Radiotherapy & Oncology, 2015, v. 115, p. S342-S34

Neutrino and axion hot dark matter bounds after WMAP-7

We update cosmological hot dark matter constraints on neutrinos and hadronic axions. Our most restrictive limits use 7-year data from the Wilkinson Microwave Anisotropy Probe for the cosmic microwave background anisotropies, the halo power spectrum (HPS) from the 7th data release of the Sloan Digital Sky Survey, and the Hubble constant from Hubble Space Telescope observations. We find 95% C.L. upper limits of \sum m_\nu<0.44 eV (no axions), m_a<0.91 eV (assuming \sum m_\nu=0), and \sum m_\nu<0.41 eV and m_a<0.72 eV for two hot dark matter components after marginalising over the respective other mass. CMB data alone yield \sum m_\nu<1.19 eV (no axions), while for axions the HPS is crucial for deriving m_a constraints. This difference can be traced to the fact that for a given hot dark matter fraction axions are much more massive than neutrinos.Comment: 9 pages, 3 figures, uses iopart.cls; v2: one additional figure, references added, version accepted by JCA