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  • 1
    Publication Date: 2016-06-23
    Description: This study aimed to investigate the effects of dietary fibre sources on the gut microbiota in suckling piglets, and to test the hypothesis that a moderate increase of dietary fibre may affect the gut microbiota during the suckling period. Suckling piglets were fed different fibre-containing diets or a control diet from postnatal day 7 to 22. Digesta samples from cecum, proximal colon and distal colon were used for Pig Intestinal Tract Chip analysis. The data showed that the effects of fibre-containing diet on the gut microbiota differed in the fibre source and gut location. The alfalfa diet increased Clostridium cluster XIVb and Sporobacter termitidis in the cecum compared to the pure cellulose diet. Compared to the control diet, the alfalfa diet also increased Coprococcus eutactus in the distal colon, while the pure cellulose diet decreased Eubacterium pyruvativorans in the cecum. The pure cellulose diet increased Prevotella ruminicola compared to the wheat bran diet. Interestingly, the alfalfa group had the lowest abundance of the potential pathogen Streptococcus suis in the cecum and distal colon. These results indicated that a moderate increase in dietary fibres affected the microbial composition in suckling piglets, and that the alfalfa inclusion produced some beneficial effects on the microbial communities.
    Keywords: Environmental Microbiology
    Print ISSN: 0378-1097
    Electronic ISSN: 1574-6968
    Topics: Biology
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  • 2
    Publication Date: 2015-01-13
    Description: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant ( P 〈 5.0 x 10 –8 ) associations with blood pressure, which included variants at three new loci ( CACNA1D , CYP21A2 , and MED13L ) and a newly discovered variant near SLC4A7 . We also replicated 14 previously reported loci, 8 ( CASZ1 , MOV10 , FGF5 , CYP17A1 , SOX6 , ATP2B1 , ALDH2 , and JAG1 ) at genome-wide significance, and 6 ( FIGN , ULK4 , GUCY1A3 , HFE , TBX3-TBX5 , and TBX3 ) at a suggestive level of P = 1.81 x 10 –3 to 5.16 x 10 –8 . These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2014-03-28
    Description: Motivation:  One common task in structural biology is to assess the similarities and differences among protein structures. A variety of structure alignment algorithms and programs has been designed and implemented for this purpose. A major drawback with existing structure alignment programs is that they require a large amount of computational time, rendering them infeasible for pairwise alignments on large collections of structures. To overcome this drawback, a fragment alphabet learned from known structures has been introduced. The method, however, considers local similarity only, and therefore occasionally assigns high scores to structures that are similar only in local fragments. Method:  We propose a novel approach that eliminates false positives, through the comparison of both local and remote similarity, with little compromise in speed. Two kinds of contact libraries (ContactLib) are introduced to fingerprint protein structures effectively and efficiently. Each contact group of the contact library consists of one local or two remote fragments and is represented by a concise vector. These vectors are then indexed and used to calculate a new combined hit-rate score to identify similar protein structures effectively and efficiently. Results:  We tested our method on the high-quality protein structure subset of SCOP30 containing 3297 protein structures. For each protein structure of the subset, we retrieved its neighbor protein structures from the rest of the subset. The best area under the Receiver-Operating Characteristic curve, archived by ContactLib, is as high as 0.960. This is a significant improvement compared with 0.747, the best result achieved by FragBag. We also demonstrated that incorporating remote contact information is critical to consistently retrieve accurate neighbor protein structures for all- query protein structures. Availability and implementation:   https://cs.uwaterloo.ca/~xfcui/contactlib/ . Contact:   shuaicli@cityu.edu.hk or mli@uwaterloo.ca
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 4
    Publication Date: 2012-01-20
    Description: The matrix completion problem is to complete an unknown matrix from a small number of entries, and it captures many applications in diversified areas. Recently, it was shown that completing a low-rank matrix can be successfully accomplished by solving its convex relaxation problem using the nuclear norm. This paper shows that the alternating direction method (ADM) is applicable for completing a low-rank matrix including the noiseless case, the noisy case and the positive semidefinite case. The ADM approach for the matrix completion problem is easily implementable and very efficient. Numerical comparisons of the ADM approach with some state-of-the-art methods are reported.
    Print ISSN: 0272-4979
    Electronic ISSN: 1464-3642
    Topics: Mathematics
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  • 5
    Publication Date: 2015-01-16
    Description: NCBI's CDD, the Conserved Domain Database, enters its 15 th year as a public resource for the annotation of proteins with the location of conserved domain footprints. Going forward, we strive to improve the coverage and consistency of domain annotation provided by CDD. We maintain a live search system as well as an archive of pre-computed domain annotation for sequences tracked in NCBI's Entrez protein database, which can be retrieved for single sequences or in bulk. We also maintain import procedures so that CDD contains domain models and domain definitions provided by several collections available in the public domain, as well as those produced by an in-house curation effort. The curation effort aims at increasing coverage and providing finer-grained classifications of common protein domains, for which a wealth of functional and structural data has become available. CDD curation generates alignment models of representative sequence fragments, which are in agreement with domain boundaries as observed in protein 3D structure, and which model the structurally conserved cores of domain families as well as annotate conserved features. CDD can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2014-04-15
    Description: The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 ( Pou5f1 ) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around –120 to –80 bp, while highly effective sgRNAs targeted from –147 to –89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4 . Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2015-07-24
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
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  • 8
    Publication Date: 2018-03-06
    Description: Although any genotype–phenotype relationships are a result of evolution, little is known about how natural selection and neutral drift, two distinct driving forces of evolution, operate to shape the relationships. By analyzing ∼500 yeast quantitative traits, we reveal a basic “supervisor–worker” gene architecture underlying a trait. Supervisors are often identified by “perturbational” approaches (such as gene deletion), whereas workers, which usually show small and statistically insignificant deletion effects, are tracked primarily by “observational” approaches that examine the correlation between gene activity and trait value across a number of conditions. Accordingly, supervisors provide most of the genetic understandings of the trait whereas workers provide rich mechanistic understandings. Further analyses suggest that most observed supervisor–worker interactions may evolve largely neutrally, resulting in pervasive between-worker epistasis that suppresses the tractability of workers. In contrast, a fraction of supervisors are recruited/maintained by natural selection to build worker co-expression, boosting the tractability of workers. Thus, by revealing a supervisor–worker gene architecture underlying complex traits, the opposite roles of natural selection versus neutral drift in shaping the gene architecture, and the complementary strengths of the perturbational and observational research strategies in characterizing the gene architecture, this study may lay a new conceptual foundation for understanding the molecular basis of complex traits.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 176 (1991), S. 1408-1416 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Analytical Biochemistry 155 (1986), S. 188-192 
    ISSN: 0003-2697
    Keywords: ADP-ribosylation ; adenosine-5'-monophosphate ; cycling assay ; mono(adenosine-5'-diphosphoribose) conjugate ; mouse tissues ; nicotinamide adenine dinucleotide
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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