483 research outputs found

    Nucleon resonances in the constituent quark model with chiral symmetry

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    The mass spectra of nucleon resonances with spin 1/2, 3/2, and 5/2 are systematically studied in the constituent quark model with meson-quark coupling, which is inspired by the spontaneous breaking of chiral symmetry of QCD. The meson-quark coupling gives rise not only to the one-meson-exchange potential between quarks but also to the self-energy of baryon resonances due to the existence of meson-baryon decay channels. The two contributions are consistently taken into account in the calculation. The gross properties of the nucleon resonance spectra are reproduced fairly well although the predicted mass of N(1440) is too high.Comment: 14 pages, 6 figures, Late

    Orientation and solvatochromism of dyes in liquid crystals.

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    The orientation and solvatochromism of some dye molecules in a liquid crystal have been investigated. Interactions with the host and the structure of the dye molecule affect the macroscopic alignment of dichroic dye molecules in a liquid crystal: It was observed that some dye molecules show a large bathochromic shift of their absorption maxima in the liquid crystal host relative to the situation in isotropic solvents. It is suggested that this is due to the occurrence of a much weaker reaction field in the anisotropic, rigid host. These dye molecules show little or no apparent order in the anisotropic host despite the observation of a reduction in the electro optic switching time when the dye is present. The highest degree of macroscopic alignment was observed for a merocyanine compound, which showed the smallest solvatochromic shift in the liquid crystal host. These results are discussed in terms of the steric, dipolar and hydrogen bond interactions between the guest and the host

    Structure and mechanism of human DNA polymerase η

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    The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

    Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

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    Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

    Branching ratio change in K- absorption at rest and the nature of the Lambda(1405)

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    We investigate in-medium corrections to the branching ratio in K- absorption at rest and their effect on the (positively and negatively) charged pion spectrum. The in-medium corrections are due to Pauli blocking, which arises if the Lambda(1405) is assumed to be a Kˉ\bar{K}-nucleon bound state and leads to a density and momentum dependent mass shift of the Lambda(1405). Requiring that the optical potential as well as the branching ratio are derived from the same elementary T-matrix, we find that the in-medium corrected, density dependent T-matrix gives a better description of the K- absorption reaction than the free, density-independent one. This result suggests that the dominant component of the Lambda(1405) wave function is the KˉN\bar{K}N bound state.Comment: 8 Pages, Revtex with epsf, and embedded 8 ps figure

    Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome

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    hHR23B is one of two human homologs of the Saccharomyces cerevisiae nucleotide excision repair (NER) gene product RAD23 and a component of a protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-C) cell extracts in vitro. Although a small proportion of hHR23B is tightly complexed with the XP-C responsible gene product, XPC protein, a vast majority exists as an XPC-free form, indicating that hHR23B has additional functions other than NER in vivo. Here we demonstrate that the human NER factor hHR23B as well as another human homolog of RAD23, hHR23A, interact specifically with S5a, a subunit of the human 26 S proteasome using the yeast two-hybrid system. Furthermore, hHR23 proteins were detected with S5a at the position where 26 S proteasome sediments in glycerol gradient centrifugation of HeLa S100 extracts. Intriguingly, hHR23B showed the inhibitory effect on the degradation of (125)I-lysozyme in the rabbit reticulocyte lysate. hHR23 proteins thus appear to associate with 26 S proteasome in vivo. From co-precipitation experiments using several series of deletion mutants, we defined the domains in hHR23B and S5a that mediate this interaction. From these results, we propose that part of hHR23 proteins are involved in the proteolytic pathway in cells

    A rapid non-radioactive technique for measurement of repair synthesis in primary human fibroblasts by incorporation of ethynyl deoxyuridine (EdU)

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    Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder. Afflicted patients show extreme sun-sensitivity and skin cancer predisposition. XP is in most cases associated with deficient nucleotide excision repair (NER), which is the process responsible for removing photolesions from DNA. Measuring NER activity by nucleotide incorporation into repair patches, termed ‘unscheduled DNA synthesis (UDS)’, is one of the most commonly used assays for XP-diagnosis and NER research. We have established a rapid and accurate procedure for measuring UDS by replacement of thymidine with 5-ethynyl-2'-deoxyuridine (EdU). EdU incorporated into repair patches can be directly conjugated to fluorescent azide derivatives, thereby obviating the need for either radiolabeled thymidine or denaturation and antibody detection of incorporated bromodeoxyuridine (BrdU). We demonstrate that the EdU incorporation assay is compatible with conventional techniques such as immunofluorescent staining and labeling of cells with micro-latex beads. Importantly, we can complete the entire UDS assay within half a day from preparation of the assay coverslips; this technique may prove useful as a method for XP diagnosis

    The uses of coherent structure (Dryden Lecture)

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    The concept of coherent structure in turbulent flow is a revolutionary idea which is being developed by evolutionary means. The main objective of this review is to list some solid achievements, showing what can be done by using the concept of coherent structure that cannot be done without it. The nature of structure is described in terms of some related concepts, including celerity, topology, and the phenomenon of coalescence and splitting of structure. The main emphasis is on the mixing layer, as the one flow whose structure is well enough understood so that technical applications are now being made in problems of mixing and chemistry. An attempt is made to identify some conceptual and experimental obstacles that stand in the way of progress in other technically important flows, particularly the turbulent boundary layer. A few comments are included about the role of structure in numerical simulations and in current work on manipulation and control of turbulent flow. Some recent developments are cited which suggest that the time is nearly right for corresponding advances to occur in turbulence modeling

    PolyADP-Ribosylation Is Required for Pronuclear Fusion during Postfertilization in Mice

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    BACKGROUND: During fertilization, pronuclear envelope breakdown (PNEB) is followed by the mingling of male and female genomes. Dynamic chromatin and protein rearrangements require posttranslational modification (PTM) for the postfertilization development. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of poly(ADP-ribose) polymerase activity (PARylation) by either PJ-34 or 5-AIQ resulted in developmental arrest of fertilized embryos at the PNEB. PARylation inhibition affects spindle bundle formation and phosphorylation of Erk molecules of metaphase II (MII) unfertilized oocytes. We found a frequent appearance of multiple pronuclei (PN) in the PARylation-inhibited embryos, suggesting defective polymerization of tubulins. Attenuated phosphorylation of lamin A/C by PARylation was detected in the PARylation-inhibited embryos at PNEB. This was associated with sustained localization of heterodomain protein 1 (HP1) at the PN of the one-cell embryos arrested by PARylation inhibition. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that PARylation is required for pronuclear fusion during postfertilization processes. These data further suggest that PARylation regulates protein dynamics essential for the beginning of mouse zygotic development. PARylation and its involving signal-pathways may represent potential targets as contraceptives
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