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151.
We present a novel dataset assessing the specificity of protein-protein interactions between 69 transmitter and receiver domains from two-component system (TCS)-signalling pathways. TCS require a conserved protein-protein interaction between partner transmitter and receiver domains for signal transduction. The complex prokaryote Myxococcus xanthus possesses an unusually large number of TCS genes, many of which have no obvious interaction partners. Interactions between TCS domains of M. xanthus were assessed using a yeast two-hybrid assay, in which domains were expressed as both bait and prey translational fusions. LacZ production was monitored as an indicator of protein-protein interaction, and the strength of interactions classified as weak, medium or strong. Two-hundred and fifty-five transmitter-receiver domain interactions were observed (46 strong), allowing identification of potential signalling partners for individual M. xanthus TCS proteins. In addition, the dataset provides interesting 'meta' information. For instance, many strong interactions were identified between different transmitter domain pairs (34) and receiver domain pairs (23), suggesting a surprisingly large degree of heterodimerisation of these domains. Proteins in our dataset that exhibited similar 'profiles' of interactions, often shared a similar biological function, suggesting that interaction profiles can provide information on biological function, even considering sets of homologous domains. 相似文献
152.
153.
Hodgson A Forgor AA Chandramohan D Reed Z Binka F Bevilacqua C Boutriau D Greenwood B 《PloS one》2008,3(5):e2159
Background
Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana.Methods and Findings
In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres ≥1∶8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres ≥ 1∶8 or SBA-MenC titres ≥1∶8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 μg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 μg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6–28.1] of doses vs 14.1%; 95% CI [10.9–17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study.Conclusions
Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt.Trial Registration
Controlled-Trials.com ISRCTN35754083 相似文献154.
Population impacts of collecting sea anemones and anemonefish for the marine aquarium trade in the Philippines 总被引:4,自引:0,他引:4
Tropical marine ornamentals comprise an increasingly important fishery worldwide. Although the potential for overexploitation
of marine ornamentals is great, few studies have addressed the population-level impacts of ornamental exploitation and few
ornamental fisheries are managed. Analysis of catch records obtained from collectors over a four-month period in the vicinity
of Cebu, Philippines, showed that anemonefish and anemones comprised close to 60% of the total catch. Underwater visual census
surveys revealed that both anemone and anemonefish densities were significantly lower in exploited areas than in protected
areas. The low density of anemones on exploited reefs accounted for over 80% of the reduced density of anemonefish at those
sites. There were similar numbers of anemonefish per unit area of anemone in protected and exploited sites; however, biomass
of anemonefish per unit area of anemone was lower in exploited areas. Reduction of anemone removals is recommended to support
the sustainable harvest of anemonefish from this region. 相似文献
155.
Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum 总被引:11,自引:0,他引:11
Jonathan M. Hodgson Kevin D. Croft Ian B. Puddey Trevor A. Mori Lawrie J. Beilin 《The Journal of nutritional biochemistry》1996,7(12):664-669
Isoflavonoids are compounds present in many legumes, but are derived in the human diet mainly from soybeans and various soybean-based food products. The major isoflavonoids occurring in soy are the glycosides of genistein and daidzein. The metabolic products of genistein metabolism in humans have not been clearly shown. The two main products of daidzein metabolism in humans appear to be equol and O-desmethylangolensin. Increasing evidence suggests that oxidative modification to low-density lipoprotein is involved in atherogenesis, and that natural antioxidants that prevent or inhibit oxidative damage to low-density lipoprotein may beneficially influence atherogenesis. In the present experiments, the effects of genistein and daidzein, and the daidzein metabolites equol and O-desmethylangolensin on Cu2+-induced oxidation of lipoproteins in serum were examined. Three concentrations of each compound (0.1 μM, 1 μM, 10 μM) were tested for antioxidant activity in six individual serum samples. All compounds tested inhibited lipoprotein oxidation. The minimum concentration for significant inhibition was 1 μM for genistein and daidzein (P < 0.05), and 0.1 μM equol and O-desmethylangolensin (P < 0.05). Equol and O-desmethylangolensin were more potent inhibitors of in vitro lipoprotein oxidation in serum than the two major dietary isoflavonoids. This study has demonstrated that soybean isoflavonoids and metabolic products of daidzein metabolism inhibit lipoprotein oxidation in vitro. Human intervention studies are needed to determine if these compounds can influence oxidation in vivo. 相似文献
156.
Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes 总被引:9,自引:0,他引:9
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Zhou XP Woodford-Richens K Lehtonen R Kurose K Aldred M Hampel H Launonen V Virta S Pilarski R Salovaara R Bodmer WF Conrad BA Dunlop M Hodgson SV Iwama T Järvinen H Kellokumpu I Kim JC Leggett B Markie D Mecklin JP Neale K Phillips R Piris J Rozen P Houlston RS Aaltonen LA Tomlinson IP Eng C 《American journal of human genetics》2001,69(4):704-711
Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype. 相似文献
157.
Jessica Royles Jérôme Ogée Lisa Wingate Dominic A. Hodgson Peter Convey Howard Griffiths 《Global Change Biology》2012,18(10):3112-3124
Signy Island, maritime Antarctic, lies within the region of the Southern Hemisphere that is currently experiencing the most rapid rates of environmental change. In this study, peat cores up to 2 m in depth from four moss banks on Signy Island were used to reconstruct changes in moss growth and climatic characteristics over the late Holocene. Measurements included radiocarbon dating (to determine peat accumulation rates) and stable carbon isotope composition of moss cellulose (to estimate photosynthetic limitation by CO 2 supply and model CO 2 assimilation rate). For at least one intensively 14C‐dated Chorisodontium aciphyllum moss peat bank, the vertical accumulation rate of peat was 3.9 mm yr?1 over the last 30 years. Before the industrial revolution, rates of peat accumulation in all cores were much lower, at around 0.6–1 mm yr?1. Carbon‐13 discrimination (Δ), corrected for background and anthropogenic source inputs, was used to develop a predictive model for CO 2 assimilation. Between 1680 and 1900, there had been a gradual increase in Δ, and hence assimilation rate. Since 1800, assimilation has also been stimulated by the changes in atmospheric CO 2 concentration, but a recent decline in Δ (over the past 50–100 years) can perhaps be attributed to documented changes in temperature and/or precipitation. The overall increase in CO 2 assimilation rate (13C proxy) and enhanced C accumulation (14C proxy) are consistent with warmer and wetter conditions currently generating higher growth rates than at any time in the past three millennia, with the decline in Δ perhaps compensated by a longer growing season. 相似文献
158.
Zingman LV Alekseev AE Bienengraeber M Hodgson D Karger AB Dzeja PP Terzic A 《Neuron》2001,31(2):233-245
ATP-sensitive potassium (K(ATP)) channels are bifunctional multimers assembled by an ion conductor and a sulfonylurea receptor (SUR) ATPase. Sensitive to ATP/ADP, K(ATP) channels are vital metabolic sensors. However, channel regulation by competitive ATP/ADP binding would require oscillations in intracellular nucleotides incompatible with cell survival. We found that channel behavior is determined by the ATPase-driven engagement of SUR into discrete conformations. Capture of the SUR catalytic cycle in prehydrolytic states facilitated pore closure, while recruitment of posthydrolytic intermediates translated in pore opening. In the cell, channel openers stabilized posthydrolytic states promoting K(ATP) channel activation. Nucleotide exchange between intrinsic ATPase and ATP/ADP-scavenging systems defined the lifetimes of specific SUR conformations gating K(ATP) channels. Signal transduction through the catalytic module provides a paradigm for channel/enzyme operation and integrates membrane excitability with metabolic cascades. 相似文献
159.
160.
H. Graham Hodgson 《BMJ (Clinical research ed.)》1944,1(4352):764-765