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  • 1
    Publication Date: 2014-10-08
    Description: Mutations in the gene encoding ubiquilin2 (UBQLN2) cause amyotrophic lateral sclerosis (ALS), frontotemporal type of dementia, or both. However, the molecular mechanisms are unknown. Here, we show that ALS/dementia-linked UBQLN2P497H transgenic mice develop neuronal pathology with ubiquilin2/ubiquitin/p62-positive inclusions in the brain, especially in the hippocampus, recapitulating several key pathological features...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2012-08-08
    Description: The complex and coordinated regulation of flowering has high ecological and agricultural significance. The maturity locus E1 has a large impact on flowering time in soybean, but the molecular basis for the E1 locus is largely unknown. Through positional cloning, we delimited the E1 locus to a 17.4-kb region containing an intron-free gene (E1). The E1 protein contains a putative bipartite nuclear localization signal and a region distantly related to B3 domain. In the recessive allele, a nonsynonymous substitution occurred in the putative nuclear localization signal, leading to the loss of localization specificity of the E1 protein and earlier flowering. The early-flowering phenotype was consistently observed in three ethylmethanesulfonate-induced mutants and two natural mutations that harbored a premature stop codon or a deletion of the entire E1 gene. E1 expression was significantly suppressed under short-day conditions and showed a bimodal diurnal pattern under long-day conditions, suggesting its response to photoperiod and its dominant effect induced by long day length. When a functional E1 gene was transformed into the early-flowering cultivar Kariyutaka with low E1 expression, transgenic plants carrying exogenous E1 displayed late flowering. Furthermore, the transcript abundance of E1 was negatively correlated with that of GmFT2a and GmFT5a, homologues of FLOWERING LOCUS T that promote flowering. These findings demonstrated the key role of E1 in repressing flowering and delaying maturity in soybean. The molecular identification of the maturity locus E1 will contribute to our understanding of the molecular mechanisms by which a short-day plant regulates flowering time and maturity.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2013-06-07
    Description: miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer Cell Death and Disease 4, e659 (June 2013). doi:10.1038/cddis.2013.193 Authors: M Karaayvaz, H Zhai & J Ju
    Keywords: miR-129BCL25-fluorouracilcolorectal cancer
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 4
    Publication Date: 2016-06-16
    Description: Motivation: Medical Subject Headings (MeSH) indexing, which is to assign a set of MeSH main headings to citations, is crucial for many important tasks in biomedical text mining and information retrieval. Large-scale MeSH indexing has two challenging aspects: the citation side and MeSH side. For the citation side, all existing methods, including Medical Text Indexer (MTI) by National Library of Medicine and the state-of-the-art method, MeSHLabeler, deal with text by bag-of-words, which cannot capture semantic and context-dependent information well. Methods: We propose DeepMeSH that incorporates deep semantic information for large-scale MeSH indexing. It addresses the two challenges in both citation and MeSH sides. The citation side challenge is solved by a new deep semantic representation, D2V-TFIDF, which concatenates both sparse and dense semantic representations. The MeSH side challenge is solved by using the ‘learning to rank’ framework of MeSHLabeler, which integrates various types of evidence generated from the new semantic representation. Results: DeepMeSH achieved a Micro F-measure of 0.6323, 2% higher than 0.6218 of MeSHLabeler and 12% higher than 0.5637 of MTI, for BioASQ3 challenge data with 6000 citations. Availability and Implementation: The software is available upon request. Contact: zhusf@fudan.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2015-06-14
    Description: Motivation: Systematically predicting gene (or protein) function based on molecular interaction networks has become an important tool in refining and enhancing the existing annotation catalogs, such as the Gene Ontology (GO) database. However, functional labels with only a few (〈10) annotated genes, which constitute about half of the GO terms in yeast, mouse and human, pose a unique challenge in that any prediction algorithm that independently considers each label faces a paucity of information and thus is prone to capture non-generalizable patterns in the data, resulting in poor predictive performance. There exist a variety of algorithms for function prediction, but none properly address this ‘overfitting’ issue of sparsely annotated functions, or do so in a manner scalable to tens of thousands of functions in the human catalog. Results: We propose a novel function prediction algorithm, clusDCA, which transfers information between similar functional labels to alleviate the overfitting problem for sparsely annotated functions. Our method is scalable to datasets with a large number of annotations. In a cross-validation experiment in yeast, mouse and human, our method greatly outperformed previous state-of-the-art function prediction algorithms in predicting sparsely annotated functions, without sacrificing the performance on labels with sufficient information. Furthermore, we show that our method can accurately predict genes that will be assigned a functional label that has no known annotations, based only on the ontology graph structure and genes associated with other labels, which further suggests that our method effectively utilizes the similarity between gene functions. Availability and implementation: https://github.com/wangshenguiuc/clusDCA . Contact: jianpeng@illinois.edu Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 6
    Publication Date: 2011-02-25
    Description: : Knowledge of the characteristics of the extensive late Palaeozoic volcanic rocks across the northern China–Mongolia tract is essential for understanding the tectonic evolution and continental crustal growth in the Central Asian Orogenic Belt. This geochronological and geochemical study documents the Early Permian mafic and felsic volcanic rocks from northwestern Inner Mongolia. The mafic rocks form two magma series with distinctive geochemical characteristics; one showing large ion lithophile element (LILE) enrichment relative to high field strength elements (HFSE) and an asthenosphere-like Sr–Nd–Pb isotopic signature, and the other featuring an elevated Nb and lithospheric isotopic signature. This result indicates that two mantle source components are involved in the magma generation: the subduction-related metasomatized asthenosphere and lithospheric mantle. The felsic rocks show strong enrichment of LILE and light REE, depletion in HFSE, and indistinguishable isotopic compositions from mafic ones. Such features are consistent with partial melts of mixed sources composed of predominant juvenile basaltic underplates and minor ancient crustal materials. These mafic and felsic rocks constitute a post-subduction high-potassium calc-alkaline magmatic suite possibly under a geodynamic regime of Palaeo-Asian Ocean slab breakoff. This regime not only provides a feasible trigger for the flipping of subduction polarity in the Solonker suture zone, but also presents a favourable venue for vertical continental crustal growth.
    Print ISSN: 0016-7649
    Topics: Geosciences
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  • 7
    Publication Date: 2019
    Description: 〈p〉Lysine 2-hydroxyisobutyrylation (Khib) has recently been shown to be an evolutionarily conserved histone mark. Here, we report that CobB serves as a lysine de-2-hydroxyisobutyrylation enzyme that regulates glycolysis and cell growth in prokaryotes. We identified the specific binding of CobB to Khib using a novel self-assembled multivalent photocrosslinking peptide probe and demonstrated that CobB can catalyze lysine de-2-hydroxyisobutyrylation both in vivo and in vitro. R58 of CobB is a critical site for its de-2-hydroxyisobutyrylase activity. Using a quantitative proteomics approach, we identified 99 endogenous substrates that are targeted by CobB for de-2-hydroxyisobutyrylation. We further demonstrated that CobB can regulate the catalytic activities of enolase (ENO) by removing K343hib and K326ac of ENO simultaneously, which account for changes of bacterial growth. In brief, our study dissects a Khib-mediated molecular mechanism that is catalyzed by CobB for the regulation of the activity of metabolic enzymes as well as the cell growth of bacteria.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2019
    Description: 〈p〉The transport of nanoparticles at bio-nano interfaces is essential for many cellular responses and biomedical applications. How two-dimensional nanomaterials, such as graphene and transition-metal dichalcogenides, diffuse along the cell membrane is, however, unknown, posing an urgent and important issue to promote their applications in the biomedical area. Here, we show that the transport of graphene oxides (GOs) sandwiched inside cell membranes varies from Brownian to Lévy and even directional dynamics. Specifically, experiments evidence sandwiched graphene–cell membrane superstructures in different cells. Combined simulations and analysis identify a sandwiched GO–induced pore in cell membrane leaflets, spanning unstable, metastable, and stable states. An analytical model that rationalizes the regimes of these membrane-pore states fits simulations quantitatively, resulting in a mechanistic interpretation of the emergence of Lévy and directional dynamics. We finally demonstrate the applicability of sandwiched GOs in enhanced efficiency of membrane-specific drug delivery. Our findings inform approaches to programming intramembrane transport of two-dimensional nanomaterials toward advantageous biomedical applications.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
    Publication Date: 2018-07-31
    Description: An intake duct for a waterjet system is treated to improve the hydraulic efficiency and the outflow nonuniformity together with its perpendicularity. A multi-objective optimization strategy is proposed by incorporating with design of experiments (DOE), computational fluid dynamics (CFD), inverse design method, Kriging model and non-dominated sorting genetic algorithm-II (NSGA-II). Optimal Latin hyper-cube design method is used in DOE to uniformly sample in variation ranges, and global optimization is then conducted by using NSGA-II based on the input-target approximation functions approximated by the Kriging model. Instead of randomly selecting one solution to implement, a technique for ordering preferences by similarity to ideal solution (TOPSIS) is introduced to select the best compromise solution (BCS) from pareto-front sets. Compared with the original duct, the optimized intake duct has a much better outflow quality at the design operation point with a comparative hydraulic ...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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  • 10
    Publication Date: 2018-07-31
    Description: This research investigates cavitation flow simulation and design optimization for a waterjet mixed flow pump whose design flow coefficient is 0.183 and rotational speed is 1450 r/min. Both the hydraulic and cavitation characteristics are predicted and compared with model test. In order to improve the pump performance, an optimized impeller is obtained with the blade thickness reducing by 0.6 mm and adjusting the blade inlet angle. The cavitating flow in a waterjet mixed flow pump is simulated using the SST k - ω turbulence model and homogeneous cavitation model with a single blade-to-blade flow passage. Compared with the experimental results, the numerical data are in reasonable agreement for predicting hydraulic characteristics and show a similar trend in cavitation performance prediction. Future work will focus on improving the cavitation model for better accuracy of cavitation prediction. Based on the experimental test and commercial software CFX simulation, it ca...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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