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61.
Maize endosperm ADP-glucose pyrophosphorylase SHRUNKEN2 and BRITTLE2 subunit interactions 总被引:4,自引:0,他引:4 下载免费PDF全文
ADP-glucose pyrophosphorylase (AGP) represents a key regulatory step in polysaccharide synthesis in organisms ranging from bacteria to plants. Higher plant AGPs are complex in nature and are heterotetramers consisting of two similar but distinct subunits. How the subunits are assembled into enzymatically active polymers is not yet understood. Here, we address this issue by using naturally occurring null mutants of the Shrunken2 (Sh2) and Brittle2 (Bt2) loci of maize as well as the yeast two-hybrid expression system. In the absence of the maize endosperm large AGP subunit (SH2), the BT2 subunit remains as a monomer in the developing endosperm. In contrast, the SH2 protein, in the absence of BT2, is found in a complex of 100 kD. A direct interaction between SH2 and BT2 was proven when they were both expressed in yeast. Several motifs are essential for SH2:BT2 interaction because truncations removing the N or C terminus of either subunit eliminate SH2:BT2 interactions. Analysis of subunit interaction mutants (sim) also identified motifs essential for protein interactions. 相似文献
62.
Serine protease inhibitors are widely distributed in the plant kingdom. Many of them have been purified and characterized from different species. While the physicochemical properties of these protease inhibitors have been extensively investigated, their biological effects, e.g. immunomodulatory effect, remain relatively unexplored. Recently, we isolated a chymotrypsin-specific inhibitor (MCoCI) from the seeds of Momordica cochinchinensis (Lour) Spreng (Family Cucurbitaceae), the traditional Chinese medicine known as Mubiezhi, which has been used as an antiinflammatory agent. In the present study, the effects of MCoCI on different types of cells of the immune system, including splenocytes, splenic lymphocytes, neutrophils, bone marrow cells and macrophages, were investigated. MCoCI was shown to possess immuno-enhancing and antiinflammatory effects. MCoCI could stimulate the proliferation of different cells of the immune system, e.g. splenocytes, splenic lymphocytes and bone marrow cells, in a manner comparable to that of Concanavalin A. Moreover, MCoCI could also suppress the formation of hydrogen peroxide in neutrophils and macrophages. These immunomodulatory effects may explain some of the therapeutic actions of Mubiezhi. 相似文献
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Tingting Qin Nabil Matmati Lam C. Tsoi Bidyut K. Mohanty Nan Gao Jijun Tang Andrew B. Lawson Yusuf A. Hannun W. Jim Zheng 《Nucleic acids research》2014,42(18):e138
To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes’ Ontology Fingerprints—a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms’ corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. 相似文献
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Yukinori Okada Buhm Han Lam?C. Tsoi Philip?E. Stuart Eva Ellinghaus Trilokraj Tejasvi Vinod Chandran Fawnda Pellett Remy Pollock Anne?M. Bowcock Gerald?G. Krueger Michael Weichenthal John?J. Voorhees Proton Rahman Peter?K. Gregersen Andre Franke Rajan?P. Nair Gon?alo?R. Abecasis Dafna?D. Gladman James?T. Elder Paul?I.W. de?Bakker Soumya Raychaudhuri 《American journal of human genetics》2014,95(2):162-172
Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C∗06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10−364). Stepwise analysis revealed multiple HLA-C∗06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C∗12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p < 5.0 × 10−8), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (pomnibus = 2.2 × 10−11), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC. 相似文献
67.
Rodrigues JL Kachel CA Aiello MR Quensen JF Maltseva OV Tsoi TV Tiedje JM 《Applied and environmental microbiology》2006,72(4):2476-2482
Burkholderia xenovorans strain LB400, which possesses the biphenyl pathway, was engineered to contain the oxygenolytic ortho dehalogenation (ohb) operon, allowing it to grow on 2-chlorobenzoate and to completely mineralize 2-chlorobiphenyl. A two-stage anaerobic/aerobic biotreatment process for Aroclor 1242-contaminated sediment was simulated, and the degradation activities and genetic stabilities of LB400(ohb) and the previously constructed strain RHA1(fcb), capable of growth on 4-chlorobenzoate, were monitored during the aerobic phase. The population dynamics of both strains were also followed by selective plating and real-time PCR, with comparable results; populations of both recombinants increased in the contaminated sediment. Inoculation at different cell densities (10(4) or 10(6) cells g(-1) sediment) did not affect the extent of polychlorinated biphenyl (PCB) biodegradation. After 30 days, PCB removal rates for high and low inoculation densities were 57% and 54%, respectively, during the aerobic phase. 相似文献
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Objective
A meta-analysis may provide more conclusive results than a single trial. The major cost of meta-analysis is the time of waiting before the meta-analysis becomes available and resources spent on consequent trials that may not be necessary. The objective of this study is to address how often the result of a single trial, in particular the first trial, differs from that of its corresponding meta-analysis so as to reduce unnecessary waiting time and subsequent trials.Study Design and Settings
A meta-epidemiologic study was conducted by collecting meta-analyses from the Cochrane Database of Systematic Reviews and five major medical journals. Effect size of a single trial was compared with that of its corresponding meta-analysis. The single trial includes the first trial, last trial and any trial randomly selected from the meta-analysis.Results
647 meta-analyses are included and the median number of trials in a meta-analysis is 5. 233 (36.0%) meta-analyses have the first trial with a statistically significant result. When the first trial is statistically significant, 84.1% (95% CI: 79.4%, 88.8%) of the corresponding meta-analyses is both in the same direction and statistically significant. When the first trial is statistically insignificant, 57.9% (95% CI: 53.2%, 62.8%) of the meta-analysis is also statistically insignificant regardless of direction. The median number of years is 6.5 years from the first to the 5th trial.Conclusion
The conclusion of the first trial that the treatment is effective or harmful is mostly likely correct. A statistically significant trial agrees more often with its corresponding meta-analysis than a large trial. These findings imply that particularly in some urgent, life-saving or other critical circumstances for which no other effective methods are available, cautious recommendation based on the significant result of the first trial seems justifiable and could start use of an effective intervention by 5–8 years earlier. 相似文献70.
Xavier Didelot David W Eyre Madeleine Cule Camilla LC Ip M Azim Ansari David Griffiths Alison Vaughan Lily O'Connor Tanya Golubchik Elizabeth M Batty Paolo Piazza Daniel J Wilson Rory Bowden Peter J Donnelly Kate E Dingle Mark Wilcox A Sarah Walker Derrick W Crook Tim E A Peto Rosalind M Harding 《Genome biology》2012,13(12):R118