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991.
Although great progress in genome-wide association studies (GWAS) has been made,
the significant SNP associations identified by GWAS account for only a few
percent of the genetic variance, leading many to question where and how we can
find the missing heritability. There is increasing interest in genome-wide
interaction analysis as a possible source of finding heritability unexplained by
current GWAS. However, the existing statistics for testing interaction have low
power for genome-wide interaction analysis. To meet challenges raised by
genome-wide interactional analysis, we have developed a novel statistic for
testing interaction between two loci (either linked or unlinked). The null
distribution and the type I error rates of the new statistic for testing
interaction are validated using simulations. Extensive power studies show that
the developed statistic has much higher power to detect interaction than
classical logistic regression. The results identified 44 and 211 pairs of SNPs
showing significant evidence of interactions with FDR<0.001 and
0.001<FDR<0.003, respectively, which were seen in two independent studies
of psoriasis. These included five interacting pairs of SNPs in genes LST1/NCR3,
CXCR5/BCL9L, and GLS2, some of which were located in the target sites of
miR-324-3p, miR-433, and miR-382, as well as 15 pairs of interacting SNPs that
had nonsynonymous substitutions. Our results demonstrated that genome-wide
interaction analysis is a valuable tool for finding remaining missing
heritability unexplained by the current GWAS, and the developed novel statistic
is able to search significant interaction between SNPs across the genome. Real
data analysis showed that the results of genome-wide interaction analysis can be
replicated in two independent studies. 相似文献
992.
Zhengdong Zhang Luo Wang Sheng Wei Zhensheng Liu Li-E. Wang Erich M. Sturgis Qingyi Wei 《DNA Repair》2010,9(5):558-566
Methylating agents are involved in carcinogenesis, and the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O6-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case–control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C > T and 16286C > T and two in the promoter region, 45996G > T and 46346C > A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT + TT, and 46346CA + AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) = 1.05–1.53). This increased risk was also more pronounced among young subjects (OR = 1.81; 95% CI = 1.11–2.96), men (OR = 1.24; 95% CI = 1.00–1.55), ever smokers (OR = 1.25; 95% = 1.01–1.56), ever drinkers (OR = 1.29; 95% CI = 1.04–1.60), patients with oropharyngeal cancer (OR = 1.45; 95% CI = 1.12–1.87), and oropharyngeal cancer with regional lymph node metastasis (OR = 1.52; 95% CI = 1.16–1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites. 相似文献
993.
Insulin-like peptide 3 (INSL3) is an insulin superfamily peptide hormone, primarily expressed in the testes and playing a
key role in the fetus testes descent and suppression of male germ cell apoptosis. Insulin-degrading enzyme (IDE) is a zinc-metalloprotease,
responsible for in vivo degradation of insulin, Aβ, and other peptide hormones. IDE has high expression level in the testes,
implying it might be involved in INSL3 turnover in vivo. In present work, we studied in vitro degradation of INSL3 by IDE.
Recombinant human IDE degraded human INSL3, but its degradation rate for INSL3 is more than a magnitude lower than that for
insulin. However, IDE bound INSL3 and insulin with almost same affinity. IDE cleaved the peptide bond between B26R and B27W
of INSL3, and released a pentapeptide, WSTEA, from the C-terminal of B-chain. Our present work suggested that IDE might play
a role in INSL3 degradation in vivo. 相似文献
994.
Reentrant loops are an important structural motif in alpha-helical transmembrane proteins. A reentrant loop is a structural
motif that goes only halfway through the membrane and then turns back to the side from which it originates. The question of
what causes the reentrant loops to form such a unique topology is still unanswered. In this study, we try to answer this question
by analyzing the hydrophobicity distribution on the amino acid sequences of the reentrant loops. Our results show that reentrant
loops have very low hydrophobicity around the deepest point buried in the membrane and relative high hydrophobicity close
to the membrane surfaces. We speculate that this hydrophobicity distribution is a major force that stabilizes the unique reentrant
loop structure. Our results also show that this hydrophobicity distribution results in special patterns on protein sequences,
which can be captured using profile hidden Markov models (HMMs). The resulting profile HMMs can detect reentrant loops on
protein sequences with high sensitivity and perfect specificity. 相似文献
995.
Three new compounds, 1 – 3 , and 20 known compounds were isolated from the AcOEt and BuOH extract of edible Opuntia Milpa Alta. The petroleum ether extract was examined by GC and MS. A total of 26 compounds were identified, representing 95.6% of the total extract, phytosterol (36.03%) being the most abundant component, and polyunsaturated fatty acids (18.57%) represented the second largest group, followed by phytol (12.28%), palmitic acid, palmitate (13.54%), vitamin E (4.51%), and other compounds (7.47%). The effects of various extracts from edible Opuntia Milpa Alta (petroleum ether extract, AcOEt extract, BuOH extract, aqueous extract, H2O parts) and the positive control (received dimethylbiguanide) were tested on streptozotocin (STZ)‐induced diabetic mice. The results indicated that all the treatment groups could significantly decrease blood glucose levels in STZ‐induced diabetic mice compared to the model control group (P<0.01), except the aqueous extract group (P<0.05). Especially, the petroleum ether extract group and the positive control group showed remarkable decrease of blood glucose levels. Taken together, the results indicate that the petroleum ether extract is the major hypoglycemic part in edible Opuntia Milpa Alta, which may be developed to a potential natural hypoglycemic functional ingredient. 相似文献
996.
997.
998.
Li YZ Pan YH Sun CB Dong HT Luo XL Wang ZQ Tang JL Chen B 《Plant molecular biology》2010,74(6):573-590
A cDNA library was constructed from the root tissues of cassava variety Huanan 124 at the root bulking stage. A total of 9,600
cDNA clones from the library were sequenced with single-pass from the 5′-terminus to establish a catalogue of expressed sequence
tags (ESTs). Assembly of the resulting EST sequences resulted in 2,878 putative unigenes. Blastn analysis showed that 62.6%
of the unigenes matched with known cassava ESTs and the rest had no ‘hits’ against the cassava database in the integrative
PlantGDB database. Blastx analysis showed that 1,715 (59.59%) of the unigenes matched with one or more GenBank protein entries
and 1,163 (40.41%) had no ‘hits’. A cDNA microarray with 2,878 unigenes was developed and used to analyze gene expression
profiling of Huanan 124 at key growth stages including seedling, formation of root system, root bulking, and starch maturity.
Array data analysis revealed that (1) the higher ratio of up-regulated ribosome-related genes was accompanied by a high ratio
of up-regulated ubiquitin, proteasome-related and protease genes in cassava roots; (2) starch formation and degradation simultaneously
occur at the early stages of root development but starch degradation is declined partially due to decrease in UDP-glucose
dehydrogenase activity with root maturity; (3) starch may also be synthesized in situ in roots; (4) starch synthesis, translocation,
and accumulation are also associated probably with signaling pathways that parallel Wnt, LAM, TCS and ErbB signaling pathways
in animals; (5) constitutive expression of stress-responsive genes may be due to the adaptation of cassava to harsh environments
during long-term evolution. 相似文献
999.
Shichun Cai Jiabao Li Fen Ze Hu Kegui Zhang Yuanming Luo Benjamin Janto Robert Boissy Garth Ehrlich Xiuzhu Dong 《Applied and environmental microbiology》2010,76(12):3818-3824
Cellulosilyticum ruminicola H1 is a newly described bacterium isolated from yak (Bos grunniens) rumen and is characterized by its ability to grow on a variety of hemicelluloses and degrade cellulosic materials. In this study, we performed the whole-genome sequencing of C. ruminicola H1 and observed a comprehensive set of genes encoding the enzymes essential for hydrolyzing plant cell wall. The corresponding enzymatic activities were also determined in strain H1; these included endoglucanases, cellobiohydrolases, xylanases, mannanase, pectinases, and feruloyl esterases and acetyl esterases to break the interbridge cross-link, as well as the enzymes that degrade the glycosidic bonds. This bacterium appears to produce polymer hydrolases that act on both soluble and crystal celluloses. Approximately half of the cellulytic activities, including cellobiohydrolase (50%), feruloyl esterase (45%), and one third of xylanase (31%) and endoglucanase (36%) activities were bound to cellulosic fibers. However, only a minority of mannase (6.78%) and pectinase (1.76%) activities were fiber associated. Strain H1 seems to degrade the plant-derived polysaccharides by producing individual fibrolytic enzymes, whereas the majority of polysaccharide hydrolases contain carbohydrate-binding module. Cellulosome or cellulosomelike protein complex was never isolated from this bacterium. Thus, the fibrolytic enzyme production of strain H1 may represent a different strategy in cellulase organization used by most of other ruminal microbes, but it applies the fungal mode of cellulose production.The ruminant rumens are long believed to be the anaerobic environments efficiently degrading the plant-derived polysaccharides, which is attributed to the inhabited abundant rumen microorganisms. They implement the fibrolytic degradation by the combination of the enzymes comprising of cellulases, hemicellulases, and to a lesser extent pectinases and ligninases (12). The rumen bacteria are outnumbered of the other rumen microbes; however, only a few of cellulolytic bacteria have been isolated from rumens. Ruminococcus flavefaciens, Ruminococcus albus, and Fibrobacter succinogenes are considered to be the most important cellulose-degrading bacteria in the rumen (18), and they produce a set of cellulolytic enzymes, including endoglucanases, exoglucanases (generally cellobiohydrolase), and β-glucosidases, as well as hemicellulases. In addition, the predominant ruminal hemicellulose-digesting bacteria such as Butyrivibrio fibrisolvens and Prevotella ruminicola lack the ability to digest cellulose but degrade xylan and pectin and utilize the degraded soluble sugars as substrates (10, 14). Although the robust cellulolytic species F. succinogenes degrades xylan, it cannot use the pentose product as a carbon source (24). Culture-independent approaches indicate that the three cellulolytic bacterial species represent only ∼2% of the ruminal bacterial 16S rRNA (43). Therefore, many varieties of rumen microbes remain uncultured (2). In recent years, rumen metagenomics studies have revealed the vast diversity of fibrolytic enzymes, multiple domain proteins, and the complexity of microbial composition in the ecosystem (9, 17). Hence, it is likely that the entire microbial community is necessary for the implementation of an efficient fibrolytic process in the rumen, including the uncultured species.In the rumen and other fibrolytic ecosystems, cellulolytic bacteria have to cope with the structural complexity of lignocelluloses and the interspecies competition; thus, not only a variety of plant polymer-degrading enzymes but also a noncatalytic assistant strategy, such as including adhesion of cells to substrates by a variety of anchoring domains, is required (8, 33, 38, 39). The (hemi)cellulolytic enzyme systems have been intensively studied for nonrumen anaerobic bacteria, including Clostridium thermocellum (19, 40), Clostridium cellulolyticum (6), Clostridium cellulovorans (13), and Clostridium stercorarium (47), as well as the rumen species, Rumicoccocus albus (35), Ruminococcus flavefaciens (32), and Fibrobacter succinogenes (4). The results indicate that most of them, except for Fibrobacter succinogenes, produce multiple cellulolytic enzymes integrated in a complex, cellulosome, and free individual proteins.The yak (Bos grunniens) is a large ruminant (∼1,000 kg) in the bovine family that lives mainly on the Qinghai-Tibetan Plateau in China at an altitude of 3,000 m above sea level. It is a local species that lives mainly on the world''s highest plateau. Yaks live in a full-grazing style with grasses, straws, and lichens as their exclusive feed, so the yak rumen can harbor a microbial flora distinct from those of other ruminants due to their fiber-component diet, since diet can be a powerful factor in regulating mammalian gut microbiome (27). A very different prokaryote community structure was revealed for yak rumen in our previous work based on the 16S rRNA diversity, which showed fewer phyla than for cattle but that a higher ratio of sequences was related to uncultured bacteria (2).We previously isolated a novel anaerobic fibrolytic bacterium, Cellulosilyticum ruminicola H1, from the rumen of a domesticated yak (11). Strain H1 grew robustly on natural plant fibers such as corn cob, alfalfa, and ryegrass as the sole carbon and energy sources, as well as on a variety of polysaccharides, including cellulose, xylan, mannan, and pectin, but not monosaccharides such as glucose, which is preferred by most ruminal bacteria. In the present study, using a draft of its genome and enzymatic characterization, we analyzed the enzymatic activities and the structures of the polymer hydrolases of strain H1 that were involved in the hydrolysis of complex polysaccharides. 相似文献
1000.
Jun Liu Jianguang Luo Hong Ye Yi Sun Zhaoxin Lu Xiaoxiong Zeng 《Carbohydrate polymers》2010,79(1):206-213
In this study, response surface methodology was employed to optimize the medium compositions for the production of exopolysaccharides (EPS) from endophytic bacterium Paenibacillus polymyxa EJS-3. Firstly, fractional factorial design was applied to evaluate the effects of different components in the medium. It was found that sucrose, yeast extract and CaCl2 influenced significantly the production of EPS. Then, steepest ascent method and central composite design were used to optimize the concentrations of the three variables. As results, the optimal medium compositions were determined as following (g/L): sucrose 188.2, yeast extract 25.8, K2HPO4 5 and CaCl2 0.34, with a corresponding yield of 35.26 g/L. In addition, both polysaccharide fractions (EPS-1 and EPS-2) from crude EPS were mainly composed of (2 → 6)-linked β-d-fructofuranosyl residues backbone with (2 → 1)-linked branches based on their structural characterization by FT-IR spectroscopy, methylation analysis and 13C NMR spectroscopy. 相似文献