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排序方式: 共有81条查询结果,搜索用时 250 毫秒
41.
Samson Mani Katarzyna Szymańska Cyrille Cuenin David Zaridze Karen Balassiano Sheila CS Lima Elena Matos Alexander Daudt Sergio Koifman Victor Wunsch Filho Ana MB Menezes Maria Paula Curado Gilles Ferro Thomas Vaissière Bakary S Sylla Massimo Tommasino Luis Felipe Ribeiro Pinto Paolo Boffetta Pierre Hainaut Paul Brennan Zdenko Herceg 《Epigenetics》2012,7(3):270-277
Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.Key words: DNA methylation, upper aerodigestive tract, cancer, risk factors, biomarkers 相似文献
42.
J. O'Grady MB ChB MRCP. S. Warrington MB BChir MA MRCP. M.J. Moti S. Bunting BSc. R. Flower BSc PhD. A.S.E. Fowle MD MRCP. E.A. Higgs BSc MSc. S. Moncada MD PhD. 《Prostaglandins & other lipid mediators》1980,19(2):319-332
Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects.The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting.Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio. 相似文献
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JS Agerholm O Andersen MB Almskou C Bendixen J Arnbjerg GP Aamand US Nielsen F Panitz AH Petersen 《Acta veterinaria Scandinavica》2004,45(3):133
To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were
performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and
insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after
insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if
the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected
calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses.
The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders. 相似文献
46.
This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system. 相似文献
47.
A C-terminal disulfide bridge in pediocin-like bacteriocins renders bacteriocin activity less temperature dependent and is a major determinant of the antimicrobial spectrum 总被引:9,自引:0,他引:9
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Fimland G Johnsen L Axelsson L Brurberg MB Nes IF Eijsink VG Nissen-Meyer J 《Journal of bacteriology》2000,182(9):2643-2648
Several lactic acid bacteria produce so-called pediocin-like bacteriocins that share sequence characteristics, but differ in activity and target cell specificity. The significance of a C-terminal disulfide bridge present in only a few of these bacteriocins was studied by site-directed mutagenesis of pediocin PA-1 (which naturally contains the bridge) and sakacin P (which lacks the bridge). Introduction of the C-terminal bridge into sakacin P broadened the target cell specificity of this bacteriocin, as illustrated by the fact that the mutants were 10 to 20 times more potent than the wild-type toward certain indicator strains, whereas the potency toward other indicator strains remained essentially unchanged. Like pediocin PA-1, disulfide-containing sakacin P mutants had the same potency at 20 and 37 degrees C, whereas wild-type sakacin P was approximately 10 times less potent at 37 degrees C than at 20 degrees C. Reciprocal effects on target cell specificity and the temperature dependence of potency were observed upon studying the effect of removing the C-terminal disulfide bridge from pediocin PA-1 by Cys-->Ser mutations. These results clearly show that a C-terminal disulfide bridge in pediocin-like bacteriocins contributes to widening of the antimicrobial spectrum as well as to higher potency at elevated temperatures. Interestingly, the differences between sakacin P and pediocin PA-1 in terms of the temperature dependency of their activities correlated well with the optimal temperatures for bacteriocin production and growth of the bacteriocin-producing strain. 相似文献
48.
Functional analysis of promoters involved in quorum sensing-based regulation of bacteriocin production in Lactobacillus 总被引:2,自引:0,他引:2
Bacteriocin production in Lactobacillus sake LTH673 involves at least four operons: a regulatory operon (sppIPKR); two operons encoding bacteriocins and their immunity proteins (sppAiA and orfX); and an operon needed for secretion (sppTE). We show here that the response regulator encoded by sppR in L. sake LTH673, as well as the homologous response regulators encoded by plnC and plnD in Lactobacillus plantarum C11, bind to characteristic repeats found in the -80 to -40 regions of spp operons. The promoters controlling bacteriocin operons are strictly regulated, and their activity is increased more than 1000-fold upon activation. Constitutive expression for the regulatory and transport operons is driven, at least in part, by promoters upstream of the -80 to -40 regions. Peak promoter activity of the regulatory and transporter operons precedes that of the two bacteriocin operons. The results reveal how promoters involved in quorum sensing-based regulation of bacteriocin production in Lactobacillus differ in strength, leakiness and timing of their activity. 相似文献
49.
Jahn Davik Daniel James Sargent May Bente Brurberg Sigbj?rn Lien Matthew Kent Muath Alsheikh 《PloS one》2015,10(9)
The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array’s construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. ×ananassa genome. Here, we have developed the first linkage map for F. ×ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. 相似文献
50.
Elevated ammonium concentrations in the medium of cultivated cells have
been shown to increase the intracellular levels of uridine-5'-diphospho-
N-acetylglucosamine (UDP-GlcNAc) and uridine-5'-diphospho-N-
acetylgalactosamine (UDP-GalNAc; Ryll et al., 1994). These sugar
nucleotides are substrates for glycosyltransferases in the glycosylation
pathway. In our experiments, recombinant Chinese hamster ovary cells
producing an immunoadhesin glycoprotein (GP1-IgG) have been cultivated
under controlled cell culture conditions in the presence of different
ammonium concentrations.15N-Labeled ammonium chloride (15NH4Cl) was added
exogenously to the cell culture media to determine if ammonium was
incorporated into UDP-GlcNAc and cytidine-5'-
monophospho-N-acetylneuraminic acid (CMP-NANA) pools, and subsequently
incorporated into GP1-IgG as N-linked glycans. The intracellular pools of
UDP-activated hexosamines (UDP-GNAc) were followed during the time course
of the experiment. To assess the extent of15NH4+incorporation into the
glycans of GP1-IgG, the glycoprotein was first purified to homogeneity by
protein A chromatography. Enzymatically released N- glycans were then
analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry. N-Glycans synthesized in the presence of15NH4Cl revealed an
N-glycan-dependent increase in mass-to-charge of 2.5-4.8 Da. These results
indicate that 60-70% of the total nitrogen containing monosaccharides had
incorporated15N. Presumably,15NH4+was incorporated into GlcNAc and N-
acetylneuraminic acid as proposed earlier (Ryll et al., 1994). This might
be a universal and previously not described reaction in mammalian cells
when exposed to nonphysiological but in cell culture commonly found
concentrations of ammonium. The data presented here are of significance for
glycoprotein production in mammalian cell culture, since it has been shown
previously that elevated levels of UDP- activated hexosamines affect
N-glycan characteristics such as branching and degree of amino sugar
incorporation. In addition, our results demonstrate that isotope labeling
in combination with MALDI-TOF-MS can be used as an alternate tool to
radioactive labeling of sugar substrates in metabolic studies.
相似文献