Increased concentrations of the oxidative DNA adduct 7, 8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes

The effects of diabetes mellitus on male reproductive health have not been clearly defined. A previous publication from this group reported significantly higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in spermatozoa from men with type 1 diabetes. This study compared semen profiles, sperm DNA fragmentation and levels of oxidative DNA modification in spermatozoa of diabetic and non-diabetic men. Semen samples from 12 non-diabetic, fertile men and 11 type 1 diabetics were obtained and subjected to conventional light microscopic semen analysis. Nuclear DNA fragmentation was assessed using an alkaline Comet assay and concentrations of 7,8-dihydro-8-oxo-2-deoxyguanosine (8-OHdG), an oxidative adduct of the purine guanosine, were assessed by high-performance liquid chromatography. Conventional semen profiles were similar in both groups, whilst spermatozoa from type 1 diabetics showed significantly higher levels of DNA fragmentation (44% versus 27%; P < 0.05) and concentrations of 8-OHdG (3.6 versus 2.0 molecules of 8-OHdG per 105 molecules of deoxyguanosine; P < 0.05). Furthermore, a positive correlation was observed between DNA fragmentation and concentrations of 8-OHdG per 105 molecules of deoxyguanosine (rs = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type 1 diabetics may have important implications for their fertility and the outcome of pregnancies fathered by these individuals.

Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.

Epitaxial ferroelectric Pb(Mg1/3Nb2/3)O3-PbTiO3 thin films on La0.7Sr0.3MnO3 bottom electrode

Epitaxial (001)-oriented 0.7Pb(Mg_0.33Nb_0.67)O₃-0.3PbTiO₃ (PMN-PT) thin films were deposited by pulsed laser deposition on vicinal SrTiO₃ (001) substrates using La_0.7Sr_0.3MnO₃ as bottom electrode. Detailed microstructural investigations of these films were carried out using X-ray diffraction (XRD), atomic force microscopy (AFM) and transmission electron microscopy (TEM). Polarization-field hysteresis curves were measured at room temperature. Spontaneous polarization P s , remnant polarization P r and coercive voltage V c were found to be 25 μC/cm², 15 μC/cm² and 0.81 V, respectively. Field dependent dielectric constant measurements exhibited butterfly shaped curves, indicating the true ferroelectric nature of these films at room temperature. The dielectric constant and the dielectric loss at 100 kHz were found to be 238 and 0.14, respectively. The local piezoelectric properties of PMN-PT films were investigated by piezoelectric force microscopy and were found to exhibit a local piezoelectric coefficient of 7.8 pm/V.

ALBUM AMICORUM de Jean Durand (1583-1592). In-8 de 2 f. lim. et 380 p., mar. r., comp. de mos. de mar. v., riche dorure à petits fers, tr. dor. et ciselée. (Rel. du XVIe siècle.)

Durand (Jean). Album amicorum (1583-1592)

6,6 '-bis (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-yl) [2,2 ']bipyridine, an effective extracting agent for the separation of americium(III) and curium(III) from the lanthanides

The extraction of americium(III), curium(III), and the lanthanides(III) from nitric acid by 6,6'- bis (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-yl)-[2,2'] bipyridine (CyMe4-BTBP) has been studied. Since the extraction kinetics were slow, N,N'-dimethyl-N,N'-dioctyl-2-(2-hexyloxy-ethyl)malonamide (DMDOHEMA) was added as a phase transfer reagent. With a mixture of 0.01 M CyMe4-BTBP + 0.25 M DMDOHEMA in n -octanol, extraction equilibrium was reached within 5 min of mixing. At a nitric acid concentration of 1 M, an americium(III) distribution ratio of approx. 10 was achieved. Americium(III)/lanthanide(III) separation factors between 50 (dysprosium) and 1500 (lanthanum) were obtained. Whereas americium(III) and curium(III) were extracted as disolvates, the stoichiometries of the lanthanide(III) complexes were not identified unambiguously, owing to the presence of DMDOHEMA. In the absence of DMDOHEMA, both americium(III) and europium(III) were extracted as disolvates. Back-extraction with 0.1 M nitric acid was thermodynamically possible but rather slow. Using a buffered glycolate solution of pH=4, an americium(III) distribution ratio of 0.01 was obtained within 5 min of mixing. There was no evidence of degradation of the extractant, for example, the extraction performance of CyMe4-BTBP during hydrolylsis with 1 M nitric acid did not change over a two month contact.

Genistein protects human mammary epithelial cells from benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and 4-hydroxy-2-nonenal genotoxicity by modulating the glutathione/glutathione S-transferase system

Epidemiological studies have shown that ingestion of isoflavone-rich soy products is associated with a reduced risk for the development of breast cancer. In the present study, we investigated the hypothesis that genistein modulates the expression of glutathione S-transferases (GSTs) in human breast cells, thus conferring protection towards genotoxic carcinogens which are GST substrates. Our approach was to use human mammary cell lines MCF-10A and MCF-7 as models for non-neoplastic and neoplastic epithelial breast cells, respectively. MCF-10A cells expressed hGSTA1/2, hGSTA4-4, hGSTM1-1 and hGSTP1-1 proteins, but not hGSTM2-2. In contrast, MCF-7 cells only marginally expressed hGSTA1/2, hGSTA4-4 and hGSTM1-1. Concordant to the protein expression, the hGSTA4 and hGSTP1 mRNA expression was higher in the non-neoplastic cell line. Exposure to genistein significantly increased hGSTP1 mRNA (2.3-fold), hGSTP1-1 protein levels (3.1-fold), GST catalytic activity (4.7-fold) and intracellular glutathione concentrations (1.4-fold) in MCF-10A cells, whereas no effects were observed on GST expression or glutathione concentrations in MCF-7 cells. Preincubation of MCF-10A cells with genistein decreased the extent of DNA damage by 4-hydroxy-2-nonenal (150 mu M) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (50 mu M), compounds readily detoxified by hGSTA4-4 and hGSTP1-1. In conclusion, genistein pretreatment protects non-neoplastic mammary cells from certain carcinogens that are detoxified by GSTs, suggesting that dietary-mediated induction of GSTs may be a mechanism contributing to prevention against genotoxic injury in the aetiology of breast cancer.

Interaction of 6,6′′-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2′:6′,2′′-terpyridine (CyMe4-BTTP) with some trivalent ions such as lanthanide(iii) ions and americium(iii)

The new ligand 6,6 ''-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)2,2':6 ',2 ''-terpyridine (CyMe4-BTTP) has been synthesized in 4 steps from 2,2':6',2 ''-terpyridine. Detailed NMR and mass spectrometry studies indicate that the ligand forms 1 : 2 complexes with lanthanide(III) perchlorates where the aliphatic rings are conformationally constrained whereas 1 : 1 complexes are formed with lanthanide(III) nitrates where the rings are conformationally mobile. An optimized structure of the 1 : 2 solution complex with Yb(III) was obtained from the relative magnitude of the induced paramagnetic shifts. X-Ray crystallographic structures of the ligand and of its 1 : 1 complex with Y(III) were also obtained. The NMR and mass spectra of [Pd(CyMe4-BTTP)](n)(2n+) are consistent with a dinuclear double helical structure (n = 2). In the absence of a phase-modifier, CyMe4-BTTP in n-octanol showed a maximum distribution coefficient of Am(III) of 0.039 (+/-20%) and a maximum separation factor of Am(III) over Eu(III) of 12.0 from nitric acid. The metal(III) cations are extracted as the 1 : 1 complex from nitric acid. The generally low distribution coefficients observed compared with the BTBPs arise because the 1 : 1 complex of CyMe4-BTTP is considerably less hydrophobic than the 1 : 2 complexes formed by the BTBPs. In M(BTTP)(3+) complexes, there is a competition between the nitrate ions and the ligand for the complexation of the metal.

Padronização de três ELISAs polivalentes com lipopolissacarídeos de cadeia longa dos sorotipos 1 e 5, 2, 3 e 7 ou 10 e 12 de Actinobacillus pleuropneumoniae

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

5a-Butyl-1,3,8,10-tetra-chloro-7,13-bis-(4-nitro-benzo-yl)-5a,6a,12a,12b-tetra-hydro-7H,13H-thieno[2,3-b:4,5-b']bis-(1,4-benzoxazine)

The title compound, C(34)H(24)Cl(4)N(4)O(8)S, is a linear penta-cyclic system formed of two substituted benzoxazinyl groups fused to 2-n-butyl-tetra-hydro-thio-phene. The oxazine ring, which is fused to the n-butyl-substituted side of the thio-phene ring, is in a boat conformation. The other fused oxazine ring and the tetra-hydro-thiene ring are each in an envelope conformation. The bridgehead C atom alpha to both the S and N atoms forms the flap of each envelope. This results in a twist of the penta-cyclic system such that the dihedral angle between the terminal dichloro-benzene rings is 82.92 (8)°. In the crystal, inversion-related mol-ecules form a weakly hydrogen-bonded dimer, with two C-H⋯O inter-actions between an H atom on the oxazine ring and an amide O atom. Additionally, C-H⋯O inter-actions occur between an H atom on a screw-related nitro-benzene ring and an O atom on the nitro-benzene ring of one mol-ecule. One of the Cl atoms and the butyl group are disordered over two sets of sites with occupancy ratios of 0.94 (2):0.06 (2) and 0.624 (4):0.376 (4), respectively.

Expeditious synthesis of 5,6,7 ,8-tetrahydro-imidazo[1,2-a ] pyrimidin-2-ones and 3,4,6,7 ,8,9-hexahydro-pyrimido[,2-a ] pyrimidin-2-ones

A convenient synthesis of new 5,6,7 ,8-tetrahydro-imidazo[ 1,2-a]pyrimidin-2-ones and 3,4,6,7 ,8,9-hexahydro-pyrimido[1 ,2a]pyrimidin-2- ones from the Baylis-Hillman adducts of acrylonitrile and their derivatives is described. A common strategy employed to achieve the syntheses of title compounds involved generation of diamines from different Baylis-Hillman derivatives followed by treatment with cyanogen bromide at reflux temperature to trigger a double intramolecular cyclization.

Mus Hs 2645 - Pièces d'harmonie : tirés de l'opéra: Figaro & entre acts ; pour deux clarinettes, deux cors & deux bassons ; [parthie 1, parthie 2, parthie 3] ; [no. 6, 7 & 8]

arr. par Stumpf

Blattformen : 1. Carduus, Distel - 2. Mulgedium alpinum - 3. + 4. Ranunculus alpestris - 5. Ranunculus glacialis - 6. Pedicularis sceptrum carolinum - 7.+8. Ranunculus auricomus - 9. Lactua muralis, Lattich - 10. Crepis pippau

AR

Ordenanzas de la ilustre Universidad y Casa de contratacion de la m.n. y m.l. Villa de Bilbao. Aprobadas y confirmadas por las magestades de los sres. d. Felipe V en 2 de diciembre de 1737, y d. Fernando VII en 27 de junio de 1814; con insercion de los reales privilegios, y la provision de 9 de julio de 1818 que contiene las alteraciones hechas á solicitud del mismo consulado y comercio sobre los numeros 3⁰, 5⁰, 8⁰, 9⁰, 16⁰ y 23⁰ del capítulo segundo, el número 16 del capítulo quinto, y los números 6⁰ y 7⁰ del capítulo sesto.

Half-title: Codigo de comercio y de navegacion, actualmente en vigor en los estados de América, conocido bajo el nombre de Ordenanzas de la ilustre Universidad y Casa de contratacion de la m. n. y m. l. villa de Bilbao.