Ferroelectricity in artificial bicolor oxide superlattices

We report on the growth and properties of high quality bicolor oxide superlattices, composed of two perovskites out of BaTiO3, CaTiO3, and SrTiO3. The artificially grown superlattices are structurally unique and have a macroscopically homogeneous phase, which is not feasible to recreate in bulk form. By artificial structuring, it is found that the polarization of such superlattices can be highly increased as compared to pseudo-binary ceramics with the same overall composition. Such strong enhancement in superlattice is attributed to newly-developed ionic motions of A-site cations at the hetero-interfaces due to the interfacial coupling of electrostatic and elastic interactions, which cannot be found in single phase materials.Comment: 15 pages, 4 figure

Intrinsic Structural Disorder and the Magnetic Ground State in Bulk EuTiO3

The magnetic properties of single-crystal EuTiO3 are suggestive of nanoscale disorder below its cubic-tetragonal phase transition. We demonstrate that electric field cooling acts to restore monocrystallinity, thus confirming that emergent structural disorder is an intrinsic low-temperature property of this material. Using torque magnetometry, we deduce that tetragonal EuTiO3 enters an easy-axis antiferromagnetic phase at 5.6 K, with a first-order transition to an easy-plane ground state below 3 K. Our data is reproduced by a 3D anisotropic Heisenberg spin model.Comment: 5 pages, 4 figure

The hemolytic and cytolytic activities of Serratia marcescens phospholipase A (PhlA) depend on lysophospholipid production by PhlA

<p>Abstract</p> <p>Background</p> <p><it>Serratia marcescens </it>is a gram-negative bacterium and often causes nosocomial infections. There have been few studies of the virulence factors of this bacterium. The only <it>S. marcescens </it>hemolytic and cytotoxic factor reported, thus far, is the hemolysin ShlA.</p> <p>Results</p> <p>An <it>S. marcescens shl</it>AB deletion mutant was constructed and shown to have no contact hemolytic activity. However, the deletion mutant retained hemolytic activity on human blood agar plates, indicating the presence of another <it>S. marcescens </it>hemolytic factor. Functional cloning of <it>S. marcescens </it>identified a phospholipase A (PhlA) with hemolytic activity on human blood agar plates. A <it>phl</it>AB deletion mutant lost hemolytic activity on human blood agar plates. Purified recombinant PhlA hydrolyzed several types of phospholipids and exhibited phospholipase A1 (PLA1), but not phospholipase A2 (PLA2), activity. The cytotoxic and hemolytic activities of PhlA both required phospholipids as substrates.</p> <p>Conclusion</p> <p>We have shown that the <it>S. marcescens phlA </it>gene produces hemolysis on human blood agar plates. PhlA induces destabilization of target cell membranes in the presence of phospholipids. Our results indicated that the lysophospholipids produced by PhlA affected cell membranes resulting in hemolysis and cell death.</p

Binding affinities and activation of Asp712Ala and Cys100Ser mutated kinin B1 receptor forms suggest a bimodal scheme for the molecule of bound-DABK

AbstractMutant forms of kinin B1 receptor (B1R) and analogs of the full agonist des-Arg9-bradykinin (DABK) were investigated aiming to verify the importance of selected receptor residues and of each agonist-peptide residue in the specific binding and activation. Linked by a specific disulfide bond (Cys100–Cys650), the N-terminal (Nt) and the EC3 loop C-terminal (Ct) segments of angiotensin II (AngII) receptor 1 (AT1R) have been identified to form an extracellular site for binding the agonist Nt segment (Asp1 and Arg2 residues). Asp712 residue at the receptor EC3 loop binds the peptide Arg2 residue. By homology, a similar site might be considered for DABK binding to B1R since this receptor contains the same structural elements for composing the site in AT1R, namely the disulfide bond and the EC3 loop Asp712 residue. DABK, Alan-DABK analogs (n=Ala1-, Ala2-, Ala3-, Ala4-, Ala5-, Ala6-, Ala7-, Ala8-DABK), and other analogs were selected to binding wild-type, Asp712Ala and Cys100Ser mutated B1R receptors. The results obtained suggested that the same bimodal scheme adopted for AngII-AT1R system may be applied to DABK binding to B1R. The most crucial similarity in the two cases is that the Nt segments of peptides equally bind to the homologous Asp712 residue of both AT1R and B1R extracellular sites. Confirming this preliminary supposition, mutation of residues located at the B1R extracellular site as EC3 loop Asp712 and Cys100 caused the same modifications in biological assays observed in AT1R submitted to homologous mutations, such as significant weakening of agonist binding and reduction of post-receptor-activation processes. These findings provided enough support for defining a site that determines the specific binding of DABK to B1R receptors

CONFORMATIONAL-CHANGES AT MEMBRANES of TARGET-CELLS INDUCED BY PEPTIDE HORMONE ANGIOTENSIN - SPIN LABEL STUDY

UNIV São Paulo,INST CHEM,São Paulo,BRAZILFAC MED SANTA CASA,DEPT BIOCHEM,São Paulo,BRAZILESCOLA PAULISTA MED,DEPT BIOPHYS,São Paulo,BRAZILESCOLA PAULISTA MED,DEPT BIOPHYS,São Paulo,BRAZILWeb of Scienc

The Effects of a Non-Ferroelectric Slab on the Polarization and the Susceptibility of the Ferroelectric Multilayer

The polarization and the susceptibility of a ferroelectric multilayer with a non-ferroelectric slab are investigated within the framework of transverse Ising model with a four-spin interaction term. The effect of the thickness and the position of the non-ferroelectric slab are investigated in this paper. We find that the increase of the thickness of the non-ferroelectric will decrease the polarization and the susceptibility of the film. If the position of the non-ferroelcetric slab shifts from the center of the film to the surface, the number of the peaks of the susceptibility will change. And a step-like polarization curve is found.Comment: 15 pages, 4 figure

The angiotensin II AT(1), receptor structure-activity correlations in the light of rhodopsin structure

The most prevalent physiological effects of ANG II, the main product of the renin-angiotensin system, are mediated by the AT(1) receptor, a rhodopsin-like AGPCR. Numerous studies of the cardiovascular effects of synthetic peptide analogs allowed a detailed mapping of ANG II's structural requirements for receptor binding and activation, which were complemented by site-directed mutagenesis studies on the AT(1) receptor to investigate the role of its structure in ligand binding, signal transduction, phosphorylation, binding to arrestins, internalization, desensitization, tachyphylaxis, and other properties. the knowledge of the high-resolution structure of rhodopsin allowed homology modeling of the AT(1) receptor. the models thus built and mutagenesis data indicate that physiological (agonist binding) or constitutive (mutated receptor) activation may involve different degrees of expansion of the receptor's central cavity. Residues in ANG II structure seem to control these conformational changes and to dictate the type of cytosolic event elicited during the activation. 1) Agonist aromatic residues (Phe(8) and Tyr(4)) favor the coupling to G protein, and 2) absence of these residues can favor a mechanism leading directly to receptor internalization via phosphorylation by specific kinases of the receptor's COOH-terminal Ser and Thr residues, arrestin binding, and clathrin-dependent coated-pit vesicles. On the other hand, the NH2-terminal residues of the agonists ANG II and [Sar(1)]-ANG II were found to bind by two distinct modes to the AT(1) receptor extracellular site flanked by the COOH-terminal segments of the EC-3 loop and the NH2-terminal domain. Since the [Sar(1)]-ligand is the most potent molecule to trigger tachyphylaxis in AT(1) receptors, it was suggested that its corresponding binding mode might be associated with this special condition of receptors.Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, BrazilUniv São Paulo, Inst Chem, Dept Biochem, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilWeb of Scienc

Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages

The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction