Recombinant Collagen Engineered to Bind to Discoidin Domain Receptors Functions as a Receptor Inhibitor

A bacterial collagen-like protein Scl2 has been developed as a recombinant collagen model system to host human collagen ligand-binding sequences, with the goal of generating biomaterials with selective collagen bioactivities. Defined binding sites in human collagen for integrins, fibronectin, heparin, and MMP-1 have been introduced into the triple-helical domain of the bacterial collagen and led to the expected biological activities. The modular insertion of activities is extended here to the discoidin domain receptors (DDRs), which are collagen-activated receptor tyrosine kinases. Insertion of the DDR-binding sequence from human collagen III into bacterial collagen led to specific receptor binding. However, even at the highest testable concentrations, the construct was unable to stimulate DDR autophosphorylation. The recombinant collagen expressed in Escherichia coli does not contain hydroxyproline (Hyp), and complementary synthetic peptide studies showed that replacement of Hyp by Pro at the critical Gly-Val-Met-Gly-Phe-Hyp position decreased the DDR-binding affinity and consequently required a higher concentration for the induction of receptor activation. The ability of the recombinant bacterial collagen to bind the DDRs without inducing kinase activation suggested it could interfere with the interactions between animal collagen and the DDRs, and such an inhibitory role was confirmed in vitro and with a cell migration assay. This study illustrates that recombinant collagen can complement synthetic peptides in investigating structure-activity relationships, and this system has the potential for the introduction or inhibition of specific biological activities

Proton strangeness form factors in (4,1) clustering configurations

We reexamine a recent result within a nonrelativistic constituent quark model (NRCQM) which maintains that the uuds\bar s component in the proton has its uuds subsystem in P state, with its \bar s in S state (configuration I). When the result are corrected, contrary to the previous result, we find that all the empirical signs of the form factors data can be described by the lowest-lying uuds\bar s configuration with \bar s in P state that has its uuds subsystem in $S$ state (configuration II). Further, it is also found that the removal of the center-of-mass (CM) motion of the clusters will enhance the contributions of the transition current considerably. We also show that a reasonable description of the existing form factors data can be obtained with a very small probability P_{s\bar s}=0.025% for the uuds\bar s component. We further see that the agreement of our prediction with the data for G_A^s at low-q^2 region can be markedly improved by a small admixture of configuration I. It is also found that by not removing CM motion, P_{s\bar s} would be overestimated by about a factor of four in the case when transition dominates over direct currents. Then, we also study the consequence of a recent estimate reached from analyzing the existing data on quark distributions that P_{s\bar s} lies between 2.4-2.9% which would lead to a large size for the five-quark (5q) system, as well as a small bump in both G^s_E+\eta G^s_M and G^s_E in the region of q^2 =< 0.1 GeV^2.Comment: Prepared for The Fifth Asia-Pacific Conference on Few-Body Problems in Physics 2011 in Seoul, South Korea, 22-26 August 201

Strangeness in the proton and N*(1535)

The newest progress on the study of the strangeness in the proton and in the lowest negative parity nucleon excited state $N^*(1535)$ is reviewed. Implications on the internal quark structure of the proton, $N^*(1535)$ and other baryons are discussed. The diquark cluster picture for the 5-quark components in baryons gives a natural explanation not only to the empirical indications for a positive strangeness magnetic moment $\mu_s$ and positive strangeness radius of the proton but also the longstanding mass-reverse problem of $N^*(1535)$, $N^*(1440)$ and $\Lambda^*(1405)$ resonances as well as the unusual decay pattern of the $N^*(1535)$ resonance. Evidence for possible existence of $N^*(1535)$'s ${1/2}^-$ SU(3) nonet partners in this picture is pointed out, and suggestion is made to search for these $1/2^-$ hyperon excited states under the well known $\Sigma^*(1385)$, $\Lambda^*(1520)$ and $\Xi^*(1530)$ peaks in various reactions.Comment: 6 pages, 2 figures, Plenary talk at 18th International IUPAP Conference on Few-Body Problems in Physics August 21-26. 2006 Santos SP Brazil; to be published in Nuclear Physics

Gluon mass generation in the PT-BFM scheme

In this article we study the general structure and special properties of the Schwinger-Dyson equation for the gluon propagator constructed with the pinch technique, together with the question of how to obtain infrared finite solutions, associated with the generation of an effective gluon mass. Exploiting the known all-order correspondence between the pinch technique and the background field method, we demonstrate that, contrary to the standard formulation, the non-perturbative gluon self-energy is transverse order-by-order in the dressed loop expansion, and separately for gluonic and ghost contributions. We next present a comprehensive review of several subtle issues relevant to the search of infrared finite solutions, paying particular attention to the role of the seagull graph in enforcing transversality, the necessity of introducing massless poles in the three-gluon vertex, and the incorporation of the correct renormalization group properties. In addition, we present a method for regulating the seagull-type contributions based on dimensional regularization; its applicability depends crucially on the asymptotic behavior of the solutions in the deep ultraviolet, and in particular on the anomalous dimension of the dynamically generated gluon mass. A linearized version of the truncated Schwinger-Dyson equation is derived, using a vertex that satisfies the required Ward identity and contains massless poles belonging to different Lorentz structures. The resulting integral equation is then solved numerically, the infrared and ultraviolet properties of the obtained solutions are examined in detail, and the allowed range for the effective gluon mass is determined. Various open questions and possible connections with different approaches in the literature are discussed.Comment: 54 pages, 24 figure

Study of qqqccˉqqqc\bar{c} five quark system with three kinds of quark-quark hyperfine interaction

The low-lying energy spectra of five quark systems $uudc\bar{c}$ (I=1/2, S=0) and $udsc\bar{c}$ (I=0, S=-1) are investigated with three kinds of schematic interactions: the chromomagnetic interaction, the flavor-spin dependent interaction and the instanton-induced interaction. In all the three models, the lowest five quark state ($uudc\bar{c}$ or $udsc\bar{c}$) has an orbital angular momentum L=0 and the spin-parity $J^{P}=1/2^{-}$; the mass of the lowest $udsc\bar{c}$ state is heavier than the lowest $uudc\bar{c}$ state

Structural studies of tri-functional human GART

Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway

Expression of a malarial Hsp70 improves defects in chaperone-dependent activities in ssa1 mutant yeast

Plasmodium falciparum causes the most virulent form of malaria and encodes a large number of molecular chaperones. Because the parasite encounters radically different environments during its lifecycle, many members of this chaperone ensemble may be essential for P. falciparum survival. Therefore, Plasmodium chaperones represent novel therapeutic targets, but to establish the mechanism of action of any developed therapeutics, it is critical to ascertain the functions of these chaperones. To this end, we report the development of a yeast expression system for PfHsp70-1, a P. falciparum cytoplasmic chaperone. We found that PfHsp70-1 repairs mutant growth phenotypes in yeast strains lacking the two primary cytosolic Hsp70s, SSA1 and SSA2, and in strains harboring a temperature sensitive SSA1 allele. PfHsp70-1 also supported chaperone-dependent processes such as protein translocation and ER associated degradation, and ameliorated the toxic effects of oxidative stress. By introducing engineered forms of PfHsp70-1 into the mutant strains, we discovered that rescue requires PfHsp70-1 ATPase activity. Together, we conclude that yeast can be co-opted to rapidly uncover specific cellular activities mediated by malarial chaperones. © 2011 Bell et al

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years