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51.
ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. 总被引:11,自引:0,他引:11
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B Panaretou C Prodromou S M Roe R O''Brien J E Ladbury P W Piper L H Pearl 《The EMBO journal》1998,17(16):4829-4836
Hsp90 is an abundant molecular chaperone essential to the establishment of many cellular regulation and signal transduction systems, but remains one of the least well described chaperones. The biochemical mechanism of protein folding by Hsp90 is poorly understood, and the direct involvement of ATP has been particularly contentious. Here we demonstrate in vitro an inherent ATPase activity in both yeast Hsp90 and the Escherichia coli homologue HtpG, which is sensitive to inhibition by the Hsp90-specific antibiotic geldanamycin. Mutations of residues implicated in ATP binding and hydrolysis by structural studies abolish this ATPase activity in vitro and disrupt Hsp90 function in vivo. These results show that Hsp90 is directly ATP dependent in vivo, and suggest an ATP-coupled chaperone cycle for Hsp90-mediated protein folding. 相似文献
52.
G. B. Cox F. Gibson R. K. J. Luke N. A. Newton I. G. O''Brien H. Rosenberg 《Journal of bacteriology》1970,104(1):219-226
A mutant of Escherichia coli K-12 unable to form an essential component of the enterochelin-dependent iron transport system has been isolated. This strain carries a mutation in a gene designated fep, mapping close to two genes, entA and entD, concerned with enterochelin synthesis. Strain AN102, which carries the fep(-) allele, accumulates large quantities of enterochelin and gives a growth response to sodium citrate. The cytochrome b(1) and total iron content, and the measurement of the uptake of (55)Fe(3+), indicate an impairment of the enterochelin-dependent iron transport system. The growth response to sodium citrate is related to the presence, in strain AN102, of an inducible citrate-dependent iron transport system. 相似文献
53.
Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6 总被引:6,自引:0,他引:6
The human methylmalonyl CoA mutase (MCM) cDNA has been used to localize the MUT locus on the short arm of chromosome 6 proximal to the glyoxalase locus in 6p deletion cell lines. A HindIII polymorphism identified by the MCM cDNA was used to study linkage relationships of MUT to HLA (A-B-DQ-DR) and D6S4 in the reference CEPH families. The maximum lod score for MUT versus HLA was 3.04 at a recombination fraction of 0.28. The maximum lod score for MUT versus D6S4 was 22.93 at a recombination fraction of 0.01. These data suggest that MUT and D6S4 loci are tightly linked and may be used as one locus in a haplotype form for linkage studies on proximal 6p and diagnostic analysis of pedigrees with mut methylmalonic acidemia. 相似文献
54.
55.
BINDING OF MUSCARONE BY EXTRACTS OF HOUSEFLY BRAIN: RELATIONSHIP TO RECEPTORS FOR ACETYLCHOLINE 总被引:9,自引:3,他引:6
The supernatant fluid fraction isolated by centrifugation from a homogenate of heads of houseflies bound muscarone reversibly, with a binding constant of 2·4 × 10?6m and an amount of 70 nmol/g of protein. Studies with 28 drugs demonstrated strong blockade by the 17 cholinergic agents, suggesting both nicotinic and muscarinic characteristics in the mode of binding. The binding appeared to involve acetylcholine receptors. 相似文献
56.
Raffael AC Oliveira Ricardo VM Almeida Márcia DA Dantas Felipe N Castro Jo?o Paulo MS Lima Daniel CF Lanza 《BMC bioinformatics》2014,15(1)
Background
The PCR technique and its variations have been increasingly used in the clinical laboratory and recent advances in this field generated new higher resolution techniques based on nucleic acid denaturation dynamics. The principle of these new molecular tools is based on the comparison of melting profiles, after denaturation of a DNA double strand. Until now, the secondary structure of single-stranded nucleic acids has not been exploited to develop identification systems based on PCR. To test the potential of single-strand RNA denaturation as a new alternative to detect specific nucleic acid variations, sequences from viruses of the Totiviridae family were compared using a new in silico melting curve approach. This family comprises double-stranded RNA virus, with a genome constituted by two ORFs, ORF1 and ORF2, which encodes the capsid/RNA binding proteins and an RNA-dependent RNA polymerase (RdRp), respectively.Results
A phylogenetic tree based on RdRp amino acid sequences was constructed, and eight monophyletic groups were defined. Alignments of RdRp RNA sequences from each group were screened to identify RNA regions with conserved secondary structure. One region in the second half of ORF2 was identified and individually modeled using the RNAfold tool. Afterwards, each DNA or RNA sequence was denatured in silico using the softwares MELTSIM and RNAheat that generate melting curves considering the denaturation of a double stranded DNA and single stranded RNA, respectively. The same groups identified in the RdRp phylogenetic tree were retrieved by a clustering analysis of the melting curves data obtained from RNAheat. Moreover, the same approach was used to successfully discriminate different variants of Trichomonas vaginalis virus, which was not possible by the visual comparison of the double stranded melting curves generated by MELTSIM.Conclusion
In silico analysis indicate that ssRNA melting curves are more informative than dsDNA melting curves. Furthermore, conserved RNA structures may be determined from analysis of individuals that are phylogenetically related, and these regions may be used to support the reconstitution of their phylogenetic groups. These findings are a robust basis for the development of in vitro systems to ssRNA melting curves detection.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-243) contains supplementary material, which is available to authorized users. 相似文献57.
Lisa GM van Baarsen Carla A Wijbrandts François Rustenburg Tineke Cantaert Tineke CTM van der Pouw Kraan Dominique L Baeten Ben AC Dijkmans Paul P Tak Cornelis L Verweij 《Arthritis research & therapy》2010,12(1):R11
Introduction
Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response. 相似文献58.
van Halm VP Nurmohamed MT Twisk JW Dijkmans BA Voskuyl AE 《Arthritis research & therapy》2006,8(5):R151-6
Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study
investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs)
in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data
on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of
the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or
methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD
group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant
CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX,
SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence
of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever'
and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased
CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated
with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in
particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and
subsequently clinically overt CVD. 相似文献
59.
Jo Moore Stephen AC Hawkins Anthony R Austin Timm Konold Robert B Green Ian W Blamire Ian Dexter Michael J Stack Melanie J Chaplin Jan PM Langeveld Marion M Simmons Yvonne I Spencer Paul R Webb Michael Dawson Gerald AH Wells 《BMC research notes》2011,4(1):1-13
Background
Escherichia coli O157:H7 is the most common serovar of enterohemorrhagic E. coli associated with serious human disease outbreaks. Cattle are the main reservoir with E. coli O157:H7 inducing hemorrhagic enteritis in persistent shedding beef cattle, however little is known about how this pathogen affects cattle health. Jejunal Hemorrhage Syndrome (JHS) has unclear etiology but the pathology is similar to that described for E. coli O157:H7 challenged beef cattle suggestive that E. coli O157:H7 could be involved. There are no effective treatments for JHS however new approaches to managing pathogen issues in livestock using prebiotics and probiotics are gaining support. The first objective of the current study was to characterize pathogen colonization in hemorrhaged jejunum of dairy cattle during natural JHS outbreaks. The second objective was to confirm the association of mycotoxigenic fungi in feeds with the development of JHS and also to identify the presence of potential mycotoxins. The third objective was to determine the impact of a prebiotic, Celmanax?, or probiotic, Dairyman's Choice? paste, on the cytotoxicity associated with feed extracts in vitro. The fourth objective was to determine the impact of a prebiotic or a probiotic on E. coli O157:H7 colonization of mucosal explants and a bovine colonic cell line in vitro. The final objective was to determine if prebiotic and probiotic feed additives could modify the symptoms that preceded JHS losses and the development of new JHS cases.Findings
Dairy cattle developed JHS after consuming feed containing several types of mycotoxigenic fungi including Fusarium culmorum, F. poae, F. verticillioides, F. sporotrichioides, Aspergillus flavus, Penicillium roqueforti, P. crustosum, P. paneum and P. citrinum. Mixtures of Shiga toxin - producing Escherichia coli (STEC) colonized the mucosa in the hemorrhaged tissues of the cattle and no other pathogen was identified. The STECs expressed Stx1 and Stx2, but more significantly, Stxs were also present in the blood clot blocking the jejunum. Mycotoxin analysis of the corn crop confirmed the presence of fumonisin, NIV, ZEAR, DON, 15-ADON, 3-ADON, NEO, DAS, HT-2 and T-2. Feed extracts were toxic to enterocytes and 0.1% Celmanax? removed the cytotoxicity in vitro. There was no effect of Dairyman's Choice? paste on feed-extract activity in vitro. Fumonisin, T-2, ZEAR and DON were toxic to bovine cells and 0.1% Celmanax? removed the cytotoxicity in vitro. Celmanax? also directly decreased E. coli O157:H7 colonization of mucosal explants and a colonic cell line in a dose-dependent manner. There was no effect of Dairyman's Choice? paste on E. coli O157:H7 colonization in vitro. The inclusion of the prebiotic and probiotic in the feed was associated with a decline in disease.Conclusion
The current study confirmed an association between mycotoxigenic fungi in the feed and the development of JHS in cattle. This association was further expanded to include mycotoxins in the feed and mixtures of STECs colonizing the severely hemorrhaged tissues. Future studies should examine the extent of involvement of the different STEC in the infection process. The prebiotic, Celmanax?, acted as an anti-adhesive for STEC colonization and a mycotoxin binder in vitro. Future studies should determine the extent of involvement of the prebiotic in altering disease. 相似文献60.
Abstract— Synaptic vesicles were isolated from rat cerebral cortex after an intraventricular injection of [3 H]acetate. The labelled substances bound to the synaptic vesicles were released by exposure to acid, separated from the vesicle membranes by Sephadex column chromatography and identified by thin-layer chromatography and thin-layer electrophoresis. The three major peaks of radioactivity were glutamate, glutamine and gamma-aminobutyric acid. Their presence in synaptic vesicles is consistent with the concept of an integration of energy metabolism, membrane regulation and synaptic transmission. 相似文献