Peptide hybrids containing α- and β-amino acids: Structure of a decapeptide β-hairpin with two facing β-phenylalanine residues

A β-hairpin conformation has been characterized in crystals of the decapeptide t-butoxycarbonyl-Leu-Val-βPhe-Val-DPro-Gly-Leu-βPhe-Val-Val-methyl ester [βPhe; (S)-β3 homophenylalanine] by x-ray diffraction. The polypeptide chain reversal is nucleated by the centrally positioned DPro-Gly segment, which adopts a type-I′ β-turn conformation. Four intramolecular cross-strand hydrogen bonds stabilize the peptide fold. The βPhe(3) and βPhe(8) residues occupy facing positions on the hairpin, with the side chains projecting on opposite faces of the β-sheet. At the site of insertion of β-residues, the polarity of the peptide units along each strand reverses, as compared with the α-peptide segments. In this analog, a small segment of a polar sheet is observed, where adjacent CO and NH groups line up in opposite directions in each strand. In the crystal, an extended β-sheet is formed by hydrogen bonding between strands of antiparallel pairs of β-hairpins. The crystallographic parameters for C65H102N10O13⋅ 3H2O are: space group P212121; a = 19.059(8) Å, b = 19.470(2) Å, c = 21.077(2) Å; Z = 4; agreement factor R1 = 9.12% for 3,984 data observed >4σ(F) and a resolution of 0.90 Å.

Prediction of protein deamidation rates from primary and three-dimensional structure

A method for the quantitative estimation of instability with respect to deamidation of the asparaginyl (Asn) residues in proteins is described. The procedure involves the observation of several simple aspects of the three-dimensional environment of each Asn residue in the protein and a calculation that includes these observations, the primary amino acid residue sequence, and the previously reported complete set of sequence-dependent rates of deamidation for Asn pentapeptides. This method is demonstrated and evaluated for 23 proteins in which 31 unstable and 167 stable Asn residues have been reported and for 7 unstable and 63 stable Asn residues that have been reported in 61 human hemoglobin variants. The relative importance of primary structure and three-dimensional structure in Asn deamidation is estimated.

Multiple maternal origins and weak phylogeographic structure in domestic goats

Domestic animals have played a key role in human history. Despite their importance, however, the origins of most domestic species remain poorly understood. We assessed the phylogenetic history and population structure of domestic goats by sequencing a hypervariable segment (481 bp) of the mtDNA control region from 406 goats representing 88 breeds distributed across the Old World. Phylogeographic analysis revealed three highly divergent goat lineages (estimated divergence >200,000 years ago), with one lineage occurring only in eastern and southern Asia. A remarkably similar pattern exists in cattle, sheep, and pigs. These results, combined with recent archaeological findings, suggest that goats and other farm animals have multiple maternal origins with a possible center of origin in Asia, as well as in the Fertile Crescent. The pattern of goat mtDNA diversity suggests that all three lineages have undergone population expansions, but that the expansion was relatively recent for two of the lineages (including the Asian lineage). Goat populations are surprisingly less genetically structured than cattle populations. In goats only ≈10% of the mtDNA variation is partitioned among continents. In cattle the amount is ≥50%. This weak structuring suggests extensive intercontinental transportation of goats and has intriguing implications about the importance of goats in historical human migrations and commerce.

Galaxies and large scale structure at high redshifts

It is now straightforward to assemble large samples of very high redshift (z ∼ 3) field galaxies selected by their pronounced spectral discontinuity at the rest frame Lyman limit of hydrogen (at 912 Å). This makes possible both statistical analyses of the properties of the galaxies and the first direct glimpse of the progression of the growth of their large-scale distribution at such an early epoch. Here I present a summary of the progress made in these areas to date and some preliminary results of and future plans for a targeted redshift survey at z = 2.7–3.4. Also discussed is how the same discovery method may be used to obtain a “census” of star formation in the high redshift Universe, and the current implications for the history of galaxy formation as a function of cosmic epoch.

Increased histone H1 phosphorylation and relaxed chromatin structure in Rb-deficient fibroblasts.

Fibroblasts derived from embryos homozygous for a disruption of the retinoblastoma gene (Rb) exhibit a shorter G1 than their wild-type counterparts, apparently due to highly elevated levels of cyclin E protein and deregulated cyclin-dependent kinase 2 (CDK2) activity. Here we demonstrate that the Rb-/- fibroblasts display higher levels of phosphorylated H1 throughout G1 with the maximum being 10-fold higher than that of the Rb+/+ fibroblasts. This profile of intracellular H1 phosphorylation corresponds with deregulated CDK2 activity observed in in vitro assays, suggesting that CDK2 may be directly responsible for the in vivo phosphorylation of H1. H1 phosphorylation has been proposed to lead to a relaxation of chromatin structure due to a decreased affinity of this protein for chromatin after phosphorylation. In accord with this, chromatin from the Rb-/- cells is more susceptible to micrococcal nuclease digestion than that from Rb+/+ fibroblasts. Increased H1 phosphorylation and relaxed chromatin structure have also been observed in cells expressing several oncogenes, suggesting a common mechanism in oncogene and tumor suppressor gene function.

Unification and large-scale structure.

The hypothesis of relativistic flow on parsec scales, coupled with the symmetrical (and therefore subrelativistic) outer structure of extended radio sources, requires that jets decelerate on scales observable with the Very Large Array. The consequences of this idea for the appearances of FRI and FRII radio sources are explored.

Adenoviral E1B-55kDa protein inhibits yeast mRNA export and perturbs nuclear structure.

The mechanisms of export of RNA from the nucleus are poorly understood; however, several viral proteins modulate nucleocytoplasmic transport of mRNA. Among these are the adenoviral proteins E1B-55kDa and E4-34kDa. Late in infection, these proteins inhibit export of host transcripts and promote export of viral mRNA. To investigate the mechanism by which these proteins act, we have expressed them in Saccharomyces cerevisiae. Overexpression of either or both proteins has no obvious effect on cell growth. By contrast, overexpression of E1B-55kDa bearing a nuclear localization signal (NLS) dramatically inhibits cell growth. In this situation, the NLS-E1B-55kDa protein is localized to the nuclear periphery, fibrous material is seen in the nucleoplasm, and poly(A)+ RNA accumulates in the nucleus. Simultaneous overexpression of E4-34kDa bearing or lacking an NLS does not modify these effects. We discuss the mechanisms of selective mRNA transport.

The antioxidant activity of novel chromones and xanthones: a structure-activity relationship

Chromones and xanthones are oxygen-containing heterocyclic compounds with bioactive properties widely reported in the literature, specially concerning to their antioxidant properties. The search for new natural and synthetic chromone and xanthone derivatives order to evaluate and discover new structural features rendering optimized biological effects has been a challenge. Thus, the aim of this work was to evaluate the scavenging activity of reactive oxygen (ROS) and nitrogen (RNS) species of new synthetic hydroxylated chromones and xanthones (Fig. 1) using in vitro non-cellular systems. These compounds exhibited scavenger effects dependent on the concentration, with IC50 values found at the micromolar range. The overall scavenging activity of chromones was better than xanthones, specially the one of chromone 3A. In conclusion, the novel tested chromone and xanthone scaffolds proved to be promising pharmacophores with potential therapeutic applications as antioxidant agents.

Pickup and van side structure baseline assessment test no. 4 - vehicle-to-vehicle 60 degree right side impact. Task 3. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Pickup and van side structure baseline assessment, tests 1, 2, and 3, vehicle-to-vehicle 60 degree left side impact. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Pre-shot and post-shot structure survey :b Project Gnome, preliminary report /

"U.S. Atomic Energy Commission Plowshare Program"--Cover.

More maximal arcs in Desarguesian projective planes and their geometric structure

In a previous paper R. Mathon gave a new construction method for maximal arcs in finite Desarguesian projective planes via closed sets of conics, as well as giving many new examples of maximal arcs. In the current paper, new classes of maximal arcs are constructed, and it is shown that every maximal arc so constructed gives rise to an infinite class of maximal arcs. Apart from when they are of Denniston type or dual hyperovals, closed sets of conics are shown to give maximal arcs that are not isomorphic to the known constructions. An easy characterisation of when a closed set of conics is of Denniston type is given. Results on the geometric structure of the maximal arcs and their duals are proved, as well as on elements of their collineation stabilisers.

Industry-specific human capital, knowledge labour, and industry wage structure in Taiwan

This paper investigates the role of industry-specific human capital (ISHC) in determining industry wage structure. The model presented in this paper distinguishes between knowledge labour and physical labour. Knowledge labour is physical labour embodied with ISHC. It is postulated that more ISHC-intensive industries, such as high-tech industries, pay higher wages and the wage premiums increase with workers' experience. The hypothesis is tested using a merged sample of 1997 - 1999 manpower utilization survey data from a newly industrialized economy - Taiwan. The findings show support for the effect of ISHC.

Targeted delivery of heparin and LMWH using a fibrin antibody prevents restenosis

This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dinner (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 mug/k,g 1D2-heparin (26-70 mug/kg heparin) or 1D2-LMWH (29-80 mug/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 mug/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose. (C) 2004 Elsevier Ireland Ltd. All rights reserved.