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Chunyan Zhao Rajiv Kumar Kolbjorn Zahlsen Heidi Bager Sundmark Kari Hemminki Ingvar Eide 《Biomarkers》1997,2(6):355-360
Quantification of 7 2 hydroxyethyl guanine 7 HEG adduct in DNA of livers and lymphocytes of male Sprague-Dawley rats exposed to 300 ppm ethene by inhalation 12 h a day for three consecutive days was performed to evaluate the potential of ethene to produce DNA adducts in these tissues. The persistence of 7 HEG in livers and lymphocytes was studied in rats sacrificed 0, 1, 5, and 20 days after the last exposure. DNA samples from control and treated animals were analysed for 7 HEG and 7 methylguanine 7 MG adducts by thin layer chromatography TLC combined with a high pressure liquid chromatography HPLC assay. After a 3 day exposure to ethene, 7 HEG accumulated to a similar extent in liver and lymphocytes, with the mean adduct level of 7.0 0.7 adducts per 107 nucleotides in liver and 7.4 0.7 adducts per 107 nucleotides in lymphocytes of rats sacrificed immediately after cessation of exposure. The approximate half life of 7 HEG was 5 days in liver and 3 days in lymphocytes, which is consistent with the loss of adduct primarily by spontaneous depurination. In addition, the background levels of 7 HEG and 7 MG were determined in the liver and lymphocytes from the control rats. 相似文献
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Adults of the human parasitic trematode Schistosoma mansoni, which causes
hepatosplenic/intestinal complications in humans, synthesize
glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1--
>3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now
report on our analyses of Lexand sLexexpression in S.haematobium and
S.japonicum, which are two other major species of human schistosomes that
cause disease, and the possible autoimmunity to these antigens in infected
individuals. Antigen expression was evaluated by both ELISA and Western
blot analyses of detergent extracts of parasites using monoclonal
antibodies. Several high molecular weight glycoproteins in both S.
haematobium and S. japonicum contain the Lexantigen, but no sialyl
Lexantigen was detected. In addition, sera from humans and rodents infected
with S.haematobium and S.japonicum contain antibodies reactive with Lex.
These results led us to investigate whether Lexantigens are expressed in
other helminths, including the parasitic trematode Fasciola hepatica , the
parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant
nematode Haemonchus contortus , and the free-living nematode Caenorhabditis
elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths.
Furthermore, none of the helminths, including schistosomes, express Lea,
Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all
helminths analyzed are bound by Lotus tetragonolobus agglutinin , which
binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which
binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be
unique among helminths in expressing the Lexantigen, whereas many different
helminths may express alpha1,3-fucosylated glycans and the LDN motif.
相似文献
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Maxim VC Greenberg Israel Ausin Simon WL Chan Shawn J Cokus Josh T Cuperus Suhua Feng Julie A Law Carolyn Chu Matteo Pellegrini James C Carrington Steven E Jacobsen 《Epigenetics》2011,6(3):344-354
De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 is targeted to DNA by small interfering RNAs (siRNAs) in a process known as RNA-directed DNA Methylation (RdDM). While several components of the RdDM pathway are known, a functional understanding of the underlying mechanism is far from complete. We employed both forward and reverse genetic approaches to identify factors involved in de novo methylation. We utilized the FWA transgene, which is methylated and silenced when transformed into wild-type plants, but unmethylated and expressed when transformed into de novo methylation mutants. Expression of FWA is marked by a late-flowering phenotype, which is easily scored in mutant versus wild-type plants. By reverse genetics we discovered the requirement for known RdDM effectors AGO6 and NRPE5a for efficient de novo methylation. A forward genetic approach uncovered alleles of several components of the RdDM pathway, including alleles of clsy1, ktf1 and nrpd/e2, which have not been previously shown to be required for the initial establishment of DNA methylation. Mutations were mapped and genes cloned by both traditional and whole genome sequencing approaches. The methodologies and the mutant alleles discovered will be instrumental in further studies of de novo DNA methylation.Key words: DNA methylation, Arabidopsis, de novo, genetic screen, whole-genome sequencing 相似文献
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Lotte Heimans Kirsten VC Wevers-de Boer KK Michel Koudijs Karen Visser Yvonne P Goekoop-Ruiterman Joop B Harbers Gerda M Steup-Beekman Leroy R Lard Bernard AM Grillet Tom WJ Huizinga Cornelia F Allaart 《Arthritis research & therapy》2013,15(5):R173
Introduction
The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment.Methods
In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models.Results
During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL.Conclusions
In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms.Trial registrations
ISRCTN11916566 and EudraCT2006-006186-16 相似文献8.
Núbia Boechat Alcione S Carvalho Kelly Salom?o Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe 《Memórias do Instituto Oswaldo Cruz》2015,110(4):492-499
Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and
cytotoxic properties have been attributed to the presence of the nitro group.
However, we synthesised nitroimidazoles with activity against the trypomastigotes of
Trypanosoma cruzi, but that were not genotoxic. Herein,
nitroimidazoles (11-19) bearing different substituent groups were investigated for
their potential induction of genotoxicity (comet assay) and mutagenicity
(Salmonella/Microsome assay) and the correlations of these
effects with their trypanocidal effect and with megazol were investigated. The
compounds were designed to analyse the role played by the position of the nitro group
in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable
groups at N-1 as an anion receptor group and the role of a methyl group at C-2.
Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to
those bearing NO2 at C-5. However, when there was a CH3
at C-2, the position of the NO2 group had no influence on the genotoxic activity.
Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3
at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl)
and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on
genotoxicity. This study contributes to the future search for new and safer
prototypes and provide. 相似文献
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Elsa Sverrisdóttir Stephen Byrne Ea Høegh Riis Sundmark Heidi Øllegaard Johnsen Hanne Grethe Kirk Torben Asp Luc Janss Kåre L. Nielsen 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2017,130(10):2091-2108
Key message
Genomic prediction models for starch content and chipping quality show promising results, suggesting that genomic selection is a feasible breeding strategy in tetraploid potato.Abstract
Genomic selection uses genome-wide molecular markers to predict performance of individuals and allows selections in the absence of direct phenotyping. It is regarded as a useful tool to accelerate genetic gain in breeding programs, and is becoming increasingly viable for crops as genotyping costs continue to fall. In this study, we have generated genomic prediction models for starch content and chipping quality in tetraploid potato to facilitate varietal development. Chipping quality was evaluated as the colour of a potato chip after frying following cold induced sweetening. We used genotyping-by-sequencing to genotype 762 offspring, derived from a population generated from biparental crosses of 18 tetraploid parents. Additionally, 74 breeding clones were genotyped, representing a test panel for model validation. We generated genomic prediction models from 171,859 single-nucleotide polymorphisms to calculate genomic estimated breeding values. Cross-validated prediction correlations of 0.56 and 0.73 were obtained within the training population for starch content and chipping quality, respectively, while correlations were lower when predicting performance in the test panel, at 0.30–0.31 and 0.42–0.43, respectively. Predictions in the test panel were slightly improved when including representatives from the test panel in the training population but worsened when preceded by marker selection. Our results suggest that genomic prediction is feasible, however, the extremely high allelic diversity of tetraploid potato necessitates large training populations to efficiently capture the genetic diversity of elite potato germplasm and enable accurate prediction across the entire spectrum of elite potatoes. Nonetheless, our results demonstrate that GS is a promising breeding strategy for tetraploid potato.10.
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