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11.
Uric Acid Amplifies Aβ Amyloid Effects Involved in the Cognitive Dysfunction/Dementia: Evidences From an Experimental Model In Vitro 下载免费PDF全文
12.
Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrP(Sc)). Disease is transmitted by the autocatalytic propagation of PrP(Sc) misfolding at the expense of the normal prion protein. The biggest challenge of the prion hypothesis has been to explain the molecular mechanism by which prions can exist as different strains, producing diseases with distinguishable characteristics. Here, we show that PrP(Sc) generated in vitro by protein misfolding cyclic amplification from five different mouse prion strains maintains the strain-specific properties. Inoculation of wild-type mice with in vitro-generated PrP(Sc) caused a disease with indistinguishable incubation times as well as neuropathological and biochemical characteristics as the parental strains. Biochemical features were also maintained upon replication of four human prion strains. These results provide additional support for the prion hypothesis and indicate that strain characteristics can be faithfully propagated in the absence of living cells, suggesting that strain variation is dependent on PrP(Sc) properties. 相似文献
13.
Platinum toxicity and gene expression in Xenopus embryos: analysis by FETAX and differential display
Monetti C Bernardini G Vigetti D Prati M Fortaner S Sabbioni E Gornati R 《Alternatives to laboratory animals : ATLA》2003,31(4):401-408
Since the level of platinum in the environment is destined to increase, because of its use in vehicle catalytic converters, the toxicity of platinum needs further investigation. In this study, the frog embryo teratogenesis assay-Xenopus (FETAX) was used to compare the embryotoxicity and teratogenicity of two common platinum species, (NH4)2PtCl4 and (NH4)2PtCl6. The uptake rates of the two platinum species were studied, and also their effects on the expression of genes encoding metallothionein and heat-shock protein 70, which are known to be induced by several stress factors. In addition, the differential display technique was used to search for genes that were specifically induced by platinum. A gene for the type I collagen alpha-chain and a novel gene were identified. 相似文献
14.
The reaction of [Ni(pftp)] [pftp = N,N-propane-1,3-diyl-(6-formyl-4-methyliminatothiophenolato)] with hydroxylamine hydrochloride in the presence potassium acetate in MeOH resulted in the formation of the complex [Ni(LH2)] [L = N,N-propane-1,3-diyl-(4-methyl-2-methyliminato-6-methyloxime-thiophenolato)] in good yield. A single crystal X-ray diffraction structural determination showed a mononuclear nickel(II) complex with the new acyclic ligand LH2 that had been functionalised with two oxime groups containing an empty N(oxime)2S2 pocket to which another metal ion could be added. A further reaction of [Ni(LH2)] with NiCl2·6H2O, triethylamine and ammonium hexafluorophosphate in MeOH gave a dark red product that yielded red crystals of [Ni2(LH)]PF6·DMF via slow recrystallisation from a DMF/PriOH solvent mixture. A single crystal X-ray diffraction study of these crystals confirmed the presence of a dinuclear nickel(II) complex linked by a dithiolato-bridge. Both nickel(II) ions exhibited square-planar geometry where the metal centres are coordinated in two distinct cis-S2N(imine)2 and cis-S2N(oxime)2 binding sites provided by the new dicompartmental oxime/thiolate-containing ligand LH. 相似文献
15.
Eugene M. Rinchik Terry Magnuson Bernadette Holdener-Kenny Gavin Kelsey Albert Bianchi Claudio J. Conti Fran?ois Chartier Kathryn A. Brown Stephen D. M. Brown Josephine Peters 《Mammalian genome》1992,3(Z1):S104-S120
Chair of Committee for Mouse Chromosome 7 相似文献
16.
Anna Corcione Elisa Ferretti Maria Bertolotto Franco Fais Lizzia Raffaghello Andrea Gregorio Claudya Tenca Luciano Ottonello Claudio Gambini Glaucia Furtado Sergio Lira Vito Pistoia 《PloS one》2009,4(12)
Background
Fractalkine/CX3CL1, a surface chemokine, binds to CX3CR1 expressed by different lymphocyte subsets. Since CX3CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX3CR1 expression and function in human naïve, germinal centre and memory B cells isolated from tonsil or peripheral blood.Methodology/Principal Findings
We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX3CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays. In particular, naïve, germinal centre and memory B cells expressed CX3CR1 but only germinal centre B cells were attracted by soluble CX3CL1 in a transwell assay. CX3CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and Src phosphorylation, as assessed by Western blot experiments. CX3CR1+ germinal centre B cells were devoid of centroblasts and enriched for centrocytes that migrated to soluble CX3CL1. ELISA assay showed that soluble CX3CL1 was secreted constitutively by follicular dendritic cells and T follicular helper cells, two cell populations homing in the germinal centre light zone as centrocytes. At variance with that observed in humans, soluble CX3CL1 did not attract spleen B cells from wild type mice. OVA immunized CX3CR1−/− or CX3CL1−/− mice showed significantly decreased specific IgG production compared to wild type mice.Conclusion/Significance
We propose a model whereby human follicular dendritic cells and T follicular helper cells release in the light zone of germinal centre soluble CX3CL1 that attracts centrocytes. The functional implications of these results warrant further investigation. 相似文献17.
PIAS proteins as repressors of Oct4 function 总被引:1,自引:0,他引:1
Tolkunova E Malashicheva A Parfenov VN Sustmann C Grosschedl R Tomilin A 《Journal of molecular biology》2007,374(5):1200-1212
18.
The mammalian centromere-associated protein B (CENP-B) shares significant sequence similarity with 3 proteins in fission yeast (Abp1, Cbh1, and Cbh2) that also bind centromeres and have essential function for chromosome segregation and centromeric heterochromatin formation. Each of these proteins displays extensive sequence similarity with pogo-like transposases, which have been previously identified in the genomes of various insects and vertebrates, in the protozoan Entamoeba and in plants. Based on this distribution, it has been proposed that the mammalian and fission yeast centromeric proteins are derived from "domesticated" pogo-like transposons. Here we took advantage of the vast amount of sequence information that has become recently available for a wide range of fungal and animal species to investigate the origin of the mammalian CENP-B and yeast CENP-B-like genes. A highly conserved ortholog of CENP-B was detected in 31 species of mammals, including opossum and platypus, but was absent from all nonmammalian species represented in the databases. Similarly, no ortholog of the fission yeast centromeric proteins was identified in any of the various fungal genomes currently available. In contrast, we discovered a plethora of novel pogo-like transposons in diverse invertebrates and vertebrates and in several filamentous fungi. Phylogenetic analysis revealed that the mammalian and fission yeast CENP-B proteins fall into 2 distinct monophyletic clades, each of which includes a different set of pogo-like transposons. These results are most parsimoniously explained by independent domestication events of pogo-like transposases into centromeric proteins in the mammalian and fission yeast lineages, a case of "convergent domestication." These findings highlight the propensity of transposases to give rise to new host proteins and the potential of transposons as sources of genetic innovation. 相似文献
19.
Montero-Morán GM Li M Rendòn-Huerta E Jourdan F Lowe DJ Stumpff-Kane AW Feig M Scazzocchio C Hausinger RP 《Biochemistry》2007,46(18):5293-5304
His6-tagged xanthine/alpha-ketoglutarate (alphaKG) dioxygenase (XanA) of Aspergillus nidulans was purified from both the fungal mycelium and recombinant Escherichia coli cells, and the properties of the two forms of the protein were compared. Evidence was obtained for both N- and O-linked glycosylation on the fungus-derived XanA, which aggregates into an apparent dodecamer, while bacterium-derived XanA is free of glycosylation and behaves as a monomer. Immunological methods identify phosphothreonine in both forms of XanA, with phosphoserine also detected in the bacterium-derived protein. Mass spectrometric analysis confirms glycosylation and phosphorylation of the fungus-derived sample, which also undergoes extensive truncation at its amino terminus. Despite the major differences in the properties of these proteins, their kinetic parameters are similar (kcat = 30-70 s-1, Km of alphaKG = 31-50 muM, Km of xanthine approximately 45 muM, and pH optima at 7.0-7.4). The enzyme exhibits no significant isotope effect when [8-2H]xanthine is used; however, it demonstrates a 2-fold solvent deuterium isotope effect. CuII and ZnII potently inhibit the FeII-specific enzyme, whereas CoII, MnII, and NiII are weaker inhibitors. NaCl decreases the kcat and increases the Km of both alphaKG and xanthine. The alphaKG cosubstrate can be substituted with alpha-ketoadipate (9-fold decrease in kcat and 5-fold increase in the Km compared to those of the normal alpha-keto acid), while the alphaKG analogue N-oxalylglycine is a competitive inhibitor (Ki = 0.12 muM). No alternative purines effectively substitute for xanthine as a substrate, and only one purine analogue (6,8-dihydroxypurine) results in significant inhibition. Quenching of the endogenous fluorescence of the two enzyme forms by xanthine, alphaKG, and DHP was used to characterize their binding properties. A XanA homology model was generated on the basis of the structure of the related enzyme TauD (PDB entry 1OS7) and provided insights into the sites of posttranslational modification and substrate binding. These studies represent the first biochemical characterization of purified xanthine/alphaKG dioxygenase. 相似文献
20.
Aintzane Urbizu Claudio Toma Maria A. Poca Juan Sahuquillo Ester Cuenca-León Bru Cormand Alfons Macaya 《PloS one》2013,8(2)
Chiari malformation type I (CMI) is a disorder characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa (PCF), often causing progressive neurological symptoms. The etiology of CMI remains unclear and is most likely multifactorial. A putative genetic contribution to CMI is suggested by familial aggregation and twin studies. Experimental models and human morphometric studies have suggested an underlying paraxial mesoderm insufficiency. We performed a case-control association study of 303 tag single nucleotide polymorphisms (SNP) across 58 candidate genes involved in early paraxial mesoderm development in a sample of 415 CMI patients and 524 sex-matched controls. A subgroup of patients diagnosed with classical, small-PCF CMI by means of MRI-based PCF morphometry (n = 186), underwent additional analysis. The genes selected are involved in signalling gradients occurring during segmental patterning of the occipital somites (FGF8, Wnt, and retinoic acid pathways and from bone morphogenetic proteins or BMP, Notch, Cdx and Hox pathways) or in placental angiogenesis, sclerotome development or CMI-associated syndromes. Single-marker analysis identified nominal associations with 18 SNPs in 14 genes (CDX1, FLT1, RARG, NKD2, MSGN1, RBPJ1, FGFR1, RDH10, NOG, RARA, LFNG, KDR, ALDH1A2, BMPR1A) considering the whole CMI sample. None of these overcame corrections for multiple comparisons, in contrast with four SNPs in CDX1, FLT1 and ALDH1A2 in the classical CMI group. Multiple marker analysis identified a risk haplotype for classical CMI in ALDH1A2 and CDX1. Furthermore, we analyzed the possible contributions of the most significantly associated SNPs to different PCF morphometric traits. These findings suggest that common variants in genes involved in somitogenesis and fetal vascular development may confer susceptibility to CMI. 相似文献