Project description:Genotyping studies suggest that there is genetic variability among P. gingivalis strains, however the extent of variability remains unclear, and the regions of variability have only partially been identified. We previously used heteroduplex analysis of the ribosomal operon intergenic spacer region (ISR) to type P. gingivalis strains in several diverse populations, identifying 6 predominant heteroduplex types and many minor ones. In addition we used ISR sequence analysis to determine the relatedness of P. gingivalis strains to one another, and demonstrated a link between ISR sequence phylogeny and the disease-associated phenotype of P. gingivalis strains. The availability of whole genome microarrays based on the genomic sequence of strain W83 has allowed a more comprehensive analysis of P. gingivalis strain variability, using the entire genome. The objectives of this study were to define the phylogeny of P. gingivalis strains using the entire genome, to compare the phylogeny based on genome content to the phylogeny based on a single locus (ISR), and to identify genes that are associated with the strongly disease-associated strain W83 that could be important for virulence. Keywords: Comparative genomic hybridization
Project description:Genome-wide SNP genotyping array can genotyped SNP highthroughly. It can be used in many aspects, such as phylogeny relationships, genome-wide association studies, copy number identification.
Project description:Genotyping studies suggest that there is genetic variability among P. gingivalis strains, however the extent of variability remains unclear, and the regions of variability have only partially been identified. We previously used heteroduplex analysis of the ribosomal operon intergenic spacer region (ISR) to type P. gingivalis strains in several diverse populations, identifying 6 predominant heteroduplex types and many minor ones. In addition we used ISR sequence analysis to determine the relatedness of P. gingivalis strains to one another, and demonstrated a link between ISR sequence phylogeny and the disease-associated phenotype of P. gingivalis strains. The availability of whole genome microarrays based on the genomic sequence of strain W83 has allowed a more comprehensive analysis of P. gingivalis strain variability, using the entire genome. The objectives of this study were to define the phylogeny of P. gingivalis strains using the entire genome, to compare the phylogeny based on genome content to the phylogeny based on a single locus (ISR), and to identify genes that are associated with the strongly disease-associated strain W83 that could be important for virulence. Keywords: Comparative genomic hybridization Comparative genomic analysis of 7 clinically prevalent P. gingivalis strains was performed, using whole genome microarrays based on the sequence of strain W83. Strain W83 was the reference strains and there were 6 test strains. Flip-dye replicates were performed.
Project description:In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the treatment of obesity in the US. The tablet contains naltrexone SR 32 mg and bupropion SR 360 mg. The drug has been tested in four randomized, double-blind, placebo-controlled, phase III trials and the co-primary endpoints were met in each case. This review discusses the key development milestones and clinical trial program to date.
Project description:The title compounds, strontium perchlorate trihydrate {di-μ-aqua-aquadi-μ-perchlorato-strontium, [Sr(ClO4)2(H2O)3] n }, strontium perchlorate tetra-hydrate {di-μ-aqua-bis-(tri-aqua-diperchloratostrontium), [Sr2(ClO4)4(H2O)8]} and strontium perchlorate nona-hydrate {hepta-aqua-diperchloratostrontium dihydrate, [Sr(ClO4)2(H2O)7]·2H2O}, were crystallized at low temperatures according to the solid-liquid phase diagram. The structures of the tri- and tetra-hydrate consist of Sr(2+) cations coordinated by five water mol-ecules and four O atoms of four perchlorate tetra-hedra in a distorted tricapped trigonal-prismatic coordination mode. The asymmetric unit of the trihydrate contains two formula units. Two [SrO9] polyhedra in the trihydrate are connected by sharing water mol-ecules and thus forming chains parallel to [100]. In the tetra-hydrate, dimers of two [SrO9] polyhedra connected by two sharing water mol-ecules are formed. The structure of the nona-hydrate contains one Sr(2+) cation coordinated by seven water mol-ecules and by two O atoms of two perchlorate tetra-hedra (point group symmetry ..m), forming a tricapped trigonal prism (point group symmetry m2m). The structure contains additional non-coordinating water mol-ecules, which are located on twofold rotation axes. O-H⋯O hydrogen bonds between the water mol-ecules as donor and ClO4 tetra-hedra and water mol-ecules as acceptor groups lead to the formation of a three-dimensional network in each of the three structures.
Project description:The SR proteins, a group of abundant arginine/serine (RS)-rich proteins, are essential pre-mRNA splicing factors that are localized in the nucleus. The RS domain of these proteins serves as a nuclear localization signal. We found that RS domain-bearing proteins do not utilize any of the known nuclear import receptors and identified a novel nuclear import receptor specific for SR proteins. The SR protein import receptor, termed transportin-SR (TRN-SR), binds specifically and directly to the RS domains of ASF/SF2 and SC35 as well as several other SR proteins. The nuclear transport regulator RanGTP abolishes this interaction. Recombinant TRN-SR mediates nuclear import of RS domain- bearing proteins in vitro. TRN-SR has amino acid sequence similarity to several members of the importin beta/transportin family. These findings strongly suggest that TRN-SR is a nuclear import receptor for the SR protein family.
Project description:Genome-wide SNP genotyping array can genotyped SNP highthroughly. It can be used in many aspects, such as phylogeny relationships, genome-wide association studies, copy number identification. 9 Chinese indigenous pig, 4 commercial pigs and 1 wild pig were genotyped by PorcineSNP60 array (Illumina) for exploring the phylogeny relationships among them.
Project description:Clonal diversity contributes to treatment resistance and cancer recurrence. Precise delineation of clonal substructure is essential to understand the resistance mechanism, however, bulk DNA sequencing cannot accurately resolve the complex clonal architectures. Here we report the single-cell DNA sequencing of 123 acute myeloid leukemia (AML) patients and provide cell-level evidence of co-occurrence and mutual exclusivity among driver mutations. Reconstruction of tumor phylogeny uncovers linear and branching clonal evolution patterns, with the latter involving functional convergence. Single-cell DNA sequencing of xenotransplanted samples reveales clonal diversity in leukemia initiating cell populations. Simultaneous single-cell profiling of mutations and cell surface proteins provides cellular genotype-phenotype associations. Analysis of longitudinal samples visualizes the behavior of each individual clone in response to therapy, illustrating the underlying evolutionary process of therapeutic resistance and disease recurrence. Together, these data portray clonal diversity, architecture, and evolution of AML, and highlight their clinical relevance in the era of precision medicine.
Project description:We use genome-resolved metagenomics to build up an ecological model of SRMs in a lab-scale light-blocking methanogenic bioreactor system (ZVS-SR bioreactor) with stable operation for more than 400 days.