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991.
The MOXD2 gene encodes a membrane-bound monooxygenase similar to dopamine-β-hydroxylase, and has been proposed to be associated with olfaction. In this study, we analyzed MOXD2 genes from 64 mammalian species, and identified loss-of-function mutations in apes (humans, Sumatran and Bornean orangutans, and five gibbon species from the four major gibbon genera), toothed whales (killer whales, bottlenose dolphins, finless porpoises, baijis, and sperm whales), and baleen whales (minke whales and fin whales). We also identified a shared 13-nt deletion in the last exon of Old World cercopithecine monkeys that results in conversion of a membrane-bound protein to a soluble form. We hypothesize that the frequent inactivation and alteration of MOXD2 genes in catarrhines and whales may be associated with the evolution of olfaction in these clades. 相似文献
992.
In everyday life, we regularly choose among multiple items serially such as playing music in a playlist or determining priorities in a to-do list. However, our behavioral strategy to determine the order of choice is poorly understood. Here we defined ‘the sushi problem’ as how we serially choose multiple items of different degrees of preference when multiple sequences are possible, and no particular order is necessarily better than another, given that all items will eventually be chosen. In the current study, participants selected seven sushi pieces sequentially at the lunch table, and we examined the relationship between eating order and preference. We found two dominant selection strategies, with one group selecting in order from most to least preferred, and the other doing the opposite, which were significantly different from patterns generated from a random strategy. Interestingly, we found that more females tended to employ the favorite-first rather than favorite-last strategy. These two choice sequences appear to reflect two opposing behavioral strategies that might provide selective advantages in their own right, while also helping to provide solutions to otherwise unconstrained problems. 相似文献
993.
Sohyun Yun Su Ui Lee Jung Min Kim Hyun-Jun Lee Hae Young Song Young Kyeung Kim Haiyoung Jung Young-Jun Park Suk Ran Yoon Sei-Ryang Oh Tae-Don Kim Inpyo Choi 《PloS one》2014,9(10)
Natural killer (NK) cells are innate immune effector cells that protect against cancer and some viral infections. Until recently, most studies have investigated the molecular signatures of human or mouse NK cells to identify genes that are specifically expressed during NK cell development. However, the mechanism regulating NK cell development remains unclear. Here, we report a regulatory network of potential interactions during in vitro differentiation of human NK cells, identified using genome-wide mRNA and miRNA databases through hierarchical clustering analysis, gene ontology analysis and a miRNA target prediction program. The microRNA (miR)-583, which demonstrated the largest ratio change in mature NK cells, was highly correlated with IL2 receptor gamma (IL2Rγ) expression. The overexpression of miR-583 had an inhibitory effect on NK cell differentiation. In a reporter assay, the suppressive effect of miR-583 was ablated by mutating the putative miR-583 binding site of the IL2Rγ 3′ UTR. Therefore, we show that miR-583 acts as a negative regulator of NK cell differentiation by silencing IL2Rγ. Additionally, we provide a comprehensive database of genome-wide mRNA and miRNA expression during human NK cell differentiation, offering a better understanding of basic human NK cell biology for the application of human NK cells in immunotherapy. 相似文献
994.
Vishwendra Patel Anne Oh Antanina Voit Lester G. Sultatos Gopal J. Babu Brenda A. Wilson Mengfei Ho Joseph J. McArdle 《PloS one》2014,9(12)
Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG. 相似文献
995.
The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug) was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively) in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer’s disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer’s disease. 相似文献
996.
Min-Jung Kwak Haeyoung Jeong Munusamy Madhaiyan Yi Lee Tong-Min Sa Tae Kwang Oh Jihyun F. Kim 《PloS one》2014,9(9)
Pink-pigmented facultative methylotrophs in the Rhizobiales are widespread in the environment, and many Methylobacterium species associated with plants produce plant growth-promoting substances. To gain insights into the life style at the phyllosphere and the genetic bases of plant growth promotion, we determined and analyzed the complete genome sequence of Methylobacterium oryzae CBMB20T, a strain isolated from rice stem. The genome consists of a 6.29-Mb chromosome and four plasmids, designated as pMOC1 to pMOC4. Among the 6,274 coding sequences in the chromosome, the bacterium has, besides most of the genes for the central metabolism, all of the essential genes for the assimilation and dissimilation of methanol that are either located in methylotrophy islands or dispersed. M. oryzae is equipped with several kinds of genes for adaptation to plant surfaces such as defense against UV radiation, oxidative stress, desiccation, or nutrient deficiency, as well as high proportion of genes related to motility and signaling. Moreover, it has an array of genes involved in metabolic pathways that may contribute to promotion of plant growth; they include auxin biosynthesis, cytokine biosynthesis, vitamin B12 biosynthesis, urea metabolism, biosorption of heavy metals or decrease of metal toxicity, pyrroloquinoline quinone biosynthesis, 1-aminocyclopropane-1-carboxylate deamination, phosphate solubilization, and thiosulfate oxidation. Through the genome analysis of M. oryzae, we provide information on the full gene complement of M. oryzae that resides in the aerial parts of plants and enhances plant growth. The plant-associated lifestyle of M. oryzae pertaining to methylotrophy and plant growth promotion, and its potential as a candidate for a bioinoculant targeted to the phyllosphere and focused on phytostimulation are illuminated. 相似文献
997.
Laura Cella Giuseppe Palma Joseph O. Deasy Jung Hun Oh Raffaele Liuzzi Vittoria D’Avino Manuel Conson Novella Pugliese Marco Picardi Marco Salvatore Roberto Pacelli 《PloS one》2014,9(10)
Purpose
The purpose of this study is to compare different normal tissue complication probability (NTCP) models for predicting heart valve dysfunction (RVD) following thoracic irradiation.Methods
All patients from our institutional Hodgkin lymphoma survivors database with analyzable datasets were included (n = 90). All patients were treated with three-dimensional conformal radiotherapy with a median total dose of 32 Gy. The cardiac toxicity profile was available for each patient. Heart and lung dose-volume histograms (DVHs) were extracted and both organs were considered for Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP model fitting using maximum likelihood estimation. Bootstrap refitting was used to test the robustness of the model fit. Model performance was estimated using the area under the receiver operating characteristic curve (AUC).Results
Using only heart-DVHs, parameter estimates were, for the LKB model: D50 = 32.8 Gy, n = 0.16 and m = 0.67; and for the RS model: D50 = 32.4 Gy, s = 0.99 and γ = 0.42. AUC values were 0.67 for LKB and 0.66 for RS, respectively. Similar performance was obtained for models using only lung-DVHs (LKB: D50 = 33.2 Gy, n = 0.01, m = 0.19, AUC = 0.68; RS: D50 = 24.4 Gy, s = 0.99, γ = 2.12, AUC = 0.66). Bootstrap result showed that the parameter fits for lung-LKB were extremely robust. A combined heart-lung LKB model was also tested and showed a minor improvement (AUC = 0.70). However, the best performance was obtained using the previously determined multivariate regression model including maximum heart dose with increasing risk for larger heart and smaller lung volumes (AUC = 0.82).Conclusions
The risk of radiation induced valvular disease cannot be modeled using NTCP models only based on heart dose-volume distribution. A predictive model with an improved performance can be obtained but requires the inclusion of heart and lung volume terms, indicating that heart-lung interactions are apparently important for this endpoint. 相似文献998.
999.
Kangmin Kim Ye-Jin Jang Sang-Myeong Lee Byung-Taek Oh Jong-Chan Chae Kui-Jae Lee 《Molecules and cells》2014,37(2):109-117
Microbiota in the niches of the rhizosphere zones can affect plant growth and responses to environmental stress conditions via mutualistic interactions with host plants. Specifically, some beneficial bacteria, collectively referred to as Plant Growth Promoting Rhizobacteria (PGPRs), increase plant biomass and innate immunity potential. Here, we report that Enterobacter sp. EJ01, a bacterium isolated from sea china pink (Dianthus japonicus thunb) in reclaimed land of Gyehwa-do in Korea, improved the vegetative growth and alleviated salt stress in tomato and Arabidopsis. EJ01 was capable of producing 1-aminocy-clopropane-1-carboxylate (ACC) deaminase and also exhibited indole-3-acetic acid (IAA) production. The isolate EJ01 conferred increases in fresh weight, dry weight, and plant height of tomato and Arabidopsis under both normal and high salinity conditions. At the molecular level, short-term treatment with EJ01 increased the expression of salt stress responsive genes such as DREB2b, RD29A, RD29B, and RAB18 in Arabidopsis. The expression of proline biosynthetic genes (i.e. P5CS1 and P5CS2) and of genes related to priming processes (i.e. MPK3 and MPK6) were also up-regulated. In addition, reactive oxygen species scavenging activities were enhanced in tomatoes treated with EJ01 in stressed conditions. GFP-tagged EJ01 displayed colonization in the rhizosphere and endosphere in the roots of Arabidopsis. In conclusion, the newly isolated Enterobacter sp. EJ01 is a likely PGPR and alleviates salt stress in host plants through multiple mechanisms, including the rapid up-regulation of conserved plant salt stress responsive signaling pathways. 相似文献
1000.
Su-Jin Oh Kyung-Ho Lee Ho-Cheol Kim Christy Catherine Hyungdon Yun Dong-Myung Kim 《Biotechnology and Bioprocess Engineering》2014,19(3):426-432
Nature uses 20 canonical amino acids as the standard building blocks of proteins; however, the incorporation of unnatural amino acids (Uaas) can endow polypeptide sequences with new structural and functional features. Although aminoacyl-tRNA synthetases (aaRSs) can accept an array of Uaas in place of their natural counterparts, Uaas generally are charged to tRNAs with substantially lower efficiencies. This particularly makes it difficult to incorporate multiple Uaas into a protein sequence. In this study, we discuss the use of a cell-free protein synthesis system as a versatile platform for the efficient incorporation of multiple Uaas into proteins. Taking advantage of the open nature of cell-free protein synthesis that allows flexible manipulation of its ingredients, we explored the application of Uaas in 10 mM range of concentrations to kinetically overcome the low affinity of aaRSs towards unnatural amino acids. Supplementation of recombinant aaRSs was also investigated to further increase the Uaa-tRNA pools. As a result, under the modified reaction conditions, as many as five different Uaas could be incorporated into a single protein without compromising the yield of protein synthesis. 相似文献