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61.
Nictaba, a lectin accumulating in tobacco (Nicotiana tabacum) leaves treated with jasmonate, is considered to act as a signaling protein in the stress physiology of the plant. Immunolocalization studies revealed that Nictaba has a nucleocytoplasmic localization. In previous research, histones were identified as primary interaction partners for Nictaba. Here, the interaction between Nictaba and tobacco histones was scrutinized in vivo. Localization studies, performed in stably transformed Nicotiana benthamiana plants, confirmed the nucleocytoplasmic localization of the lectin and colocalization with the presumed binding partners in the nucleus. Furthermore, bimolecular fluorescence complementation (BiFC) assays confirmed the interaction in vivo. Since BiFC signals were also observed for a Nictaba mutant incapable of binding sugar moieties, this interaction may be mediated by alternative binding sites. The interaction of Nictaba with core histones possibly reflects a role of this stress inducible lectin in gene regulation or chromatin remodeling. 相似文献
62.
Erik J. M. Toonen Anke J. Laskewitz Theo H. van Dijk Aycha Bleeker Aldo Grefhorst Annelies E. Schouten Ellen A. J. Bastiaanssen Dov B. Ballak Marije I. Koenders Cindy van Doorn Monique A. J. van der Vleuten Marie-Jose C. van Lierop Albert K. Groen Wim H. A. Dokter 《PloS one》2014,9(9)
Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there is an urgent medical need for improved GCs that are as effective as classical GCs but have a better safety profile. A well-established model to assess anti-inflammatory efficacy is the chronic collagen-induced arthritis (CIA) model in mice, a model with features resembling rheumatoid arthritis. Models to quantify undesired effects of glucocorticoids on glucose kinetics are less well-established. Recently, we have described a model to quantify basal blood glucose kinetics using stably-labeled glucose. In the present study, we have integrated this blood glucose kinetic model in the CIA model to enable quantification of both efficacy and adverse effects in one animal model. Arthritis scores were decreased after treatment with prednisolone, confirming the anti-inflammatory properties of GCs. Both inflammation and prednisolone induced insulin resistance as insulin secretion was strongly increased whereas blood glucose concentrations and hepatic glucose production were only slightly decreased. This insulin resistance did not directly resulted in hyperglycemia, indicating a highly adaptive compensatory mechanism in these mice. In conclusion, this ‘all-in-one’ model allows for studying effects of (novel) GC compounds on the development of arthritis and glucose kinetics in a single animal. This integrative model provides a valuable tool for investigating (drug-induced) metabolic dysregulation in an inflammatory setting. 相似文献
63.
Fraaije MW Kamerbeek NM Heidekamp AJ Fortin R Janssen DB 《The Journal of biological chemistry》2004,279(5):3354-3360
EtaA is a newly identified FAD-containing monooxygenase that is responsible for activation of several thioamide prodrugs in Mycobacterium tuberculosis. It was found that purified EtaA displays a remarkably low activity with the antitubercular prodrug ethionamide. Hinted by the presence of a Baeyer-Villiger monooxygenase sequence motif in the EtaA sequence, we have been able to identify a large number of novel EtaA substrates. It was discovered that the enzyme converts a wide range of ketones to the corresponding esters or lactones via a Baeyer-Villiger reaction, indicating that EtaA represents a Baeyer-Villiger monooxygenase. With the exception of aromatic ketones (phenylacetone and benzylacetone), long-chain ketones (e.g. 2-hexanone and 2-dodecanone) also are converted. EtaA is also able to catalyze enantioselective sulfoxidation of methyl-p-tolylsulfide. Conversion of all of the identified substrates is relatively slow with typical k(cat) values of around 0.02 s(-1). The best substrate identified so far is phenylacetone (K(m) = 61 microM, k(cat) = 0.017 s(-1)). Redox monitoring of the flavin cofactor during turnover of phenylacetone indicates that a step in the reductive half-reaction is limiting the rate of catalysis. Intriguingly, EtaA activity could be increased by one order of magnitude by adding bovine serum albumin. This reactivity and substrate acceptance-profiling study provides valuable information concerning this newly identified prodrug activator from M. tuberculosis. 相似文献
64.
van der Heijde D Landewé R Boonen A Einstein S Herborn G Rau R Wassenberg S Weissman BN Winalski CS Sharp JT 《Arthritis research & therapy》2007,9(4):R62
The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine
which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method
detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest
at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded
whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified
Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel
agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately
assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse'
(78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features
were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts
were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent
readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All
22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired
images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent
project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size
was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features
to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or
was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers
applying the van der Heijde-modified Sharp scoring method and was reflected in their scores. 相似文献
65.
66.
67.
Annelies De Paepe Sylvie De Buck Katleen Hoorelbeke Jonah Nolf Ingrid Peck Anna Depicker 《The Plant journal : for cell and molecular biology》2009,59(4):517-527
For genetic transformation of plants, floral dip with Agrobacterium often results in integration of multiple T-DNA copies at a single locus and frequently in low and unstable transgene expression. To obtain efficient single-copy T-DNA transformants, two CRE/ loxP recombinase-based simplifying strategies for complex T-DNA loci were compared. A T-DNA vector with oppositely oriented loxP sites was transformed into CRE -expressing and wild-type control Arabidopsis thaliana plants. Of the primary CRE -expressing transformants, 55% harboured a single copy of the introduced T-DNA, but only 15% in the wild-type plants. However, 73% of the single-copy transformants in the CRE background showed continuous somatic inversion of the DNA segment between the two loxP sites. To avoid inversion of the loxP -flanked T-DNA segment, two T-DNA vectors harbouring only one loxP site were investigated for their suitability for CRE/ loxP recombinase-mediated resolution upon floral-dip transformation into CRE -expressing plants. On average, 70% of the transformants in the CRE background were single-copy transformants, whereas the single-copy T-DNA frequency was only 11% for both vectors in the wild-type background. Both resolution strategies yielded mostly Cre transformants in which the 35S-driven transgene expression was stable and uniform in the progeny and remarkably, also in Cre transformants with multiple T-DNA copies. Therefore, a role is proposed for the CRE recombinase in preventing inverted T-DNA repeat formation or modifying the locus chromatin structure, resulting in a reduced sensitivity for silencing. 相似文献
68.
Michiel?B?HaesekerEmail author Evelien?Pijpers Nicole?HTM?Dukers-Muijrers Patty?Nelemans Christian?JPA?Hoebe Cathrien?A?Bruggeman Annelies?Verbon Valère?J?Goossens 《Immunity & ageing : I & A》2013,10(1):30
Background
Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.Results
Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.Conclusions
Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.69.