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21.
Multiple-locus variable-number tandem repeat analysis reveals genetic relationships within Bacillus anthracis 总被引:10,自引:0,他引:10 下载免费PDF全文
Keim P Price LB Klevytska AM Smith KL Schupp JM Okinaka R Jackson PJ Hugh-Jones ME 《Journal of bacteriology》2000,182(10):2928-2936
Bacillus anthracis is one of the most genetically homogeneous pathogens described, making strain discrimination particularly difficult. In this paper, we present a novel molecular typing system based on rapidly evolving variable-number tandem repeat (VNTR) loci. Multiple-locus VNTR analysis (MLVA) uses the combined power of multiple alleles at several marker loci. In our system, fluorescently labeled PCR primers are used to produce PCR amplification products from eight VNTR regions in the B. anthracis genome. These are detected and their sizes are determined using an ABI377 automated DNA sequencer. Five of these eight loci were discovered by sequence characterization of molecular markers (vrrC(1), vrrC(2), vrrB(1), vrrB(2), and CG3), two were discovered by searching complete plasmid nucleotide sequences (pXO1-aat and pXO2-at), and one was known previously (vrrA). MLVA characterization of 426 B. anthracis isolates identified 89 distinct genotypes. VNTR markers frequently identified multiple alleles (from two to nine), with Nei's diversity values between 0.3 and 0.8. Unweighted pair-group method arithmetic average cluster analysis identified six genetically distinct groups that appear to be derived from clones. Some of these clones show worldwide distribution, while others are restricted to particular geographic regions. Human commerce doubtlessly has contributed to the dispersal of particular clones in ancient and modern times. 相似文献
22.
Jingjing Zang Jennifer Keim Edda Kastenhuber Matthias Gesemann Stephan C. F. Neuhauss 《Open biology》2015,5(8)
The neuronal Ca2+-binding protein Recoverin has been shown to regulate phototransduction termination in mammalian rods. Here we identify four recoverin genes in the zebrafish genome, rcv1a, rcv1b, rcv2a and rcv2b, and investigate their role in modulating the cone phototransduction cascade. While Recoverin-1b is only found in the adult retina, the other Recoverins are expressed throughout development in all four cone types, except Recoverin-1a, which is expressed only in rods and UV cones. Applying a double flash electroretinogram (ERG) paradigm, downregulation of Recoverin-2a or 2b accelerates cone photoresponse recovery, albeit at different light intensities. Exclusive recording from UV cones via spectral ERG reveals that knockdown of Recoverin-1a alone has no effect, but Recoverin-1a/2a double-knockdowns showed an even shorter recovery time than Recoverin-2a-deficient larvae. We also showed that UV cone photoresponse kinetics depend on Recoverin-2a function via cone-specific kinase Grk7a. This is the first in vivo study demonstrating that cone opsin deactivation kinetics determine overall photoresponse shut off kinetics. 相似文献
23.
Alice R. Wattam Jeffrey T. Foster Shrinivasrao P. Mane Stephen M. Beckstrom-Sternberg James M. Beckstrom-Sternberg Allan W. Dickerman Paul Keim Talima Pearson Maulik Shukla Doyle V. Ward Kelly P. Williams Bruno W. Sobral Renee M. Tsolis Adrian M. Whatmore David O'Callaghan 《Journal of bacteriology》2014,196(5):920-930
Brucella species include important zoonotic pathogens that have a substantial impact on both agriculture and human health throughout the world. Brucellae are thought of as “stealth pathogens” that escape recognition by the host innate immune response, modulate the acquired immune response, and evade intracellular destruction. We analyzed the genome sequences of members of the family Brucellaceae to assess its evolutionary history from likely free-living soil-based progenitors into highly successful intracellular pathogens. Phylogenetic analysis split the genus into two groups: recently identified and early-dividing “atypical” strains and a highly conserved “classical” core clade containing the major pathogenic species. Lateral gene transfer events brought unique genomic regions into Brucella that differentiated them from Ochrobactrum and allowed the stepwise acquisition of virulence factors that include a type IV secretion system, a perosamine-based O antigen, and systems for sequestering metal ions that are absent in progenitors. Subsequent radiation within the core Brucella resulted in lineages that appear to have evolved within their preferred mammalian hosts, restricting their virulence to become stealth pathogens capable of causing long-term chronic infections. 相似文献
24.
Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents
Saleem Ahmad Khehyong Ngu Keith J. Miller Ginger Wu Chen-pin Hung Sarah Malmstrom Ge Zhang Eva O’Tanyi William J. Keim Mary Jane Cullen Kenneth W. Rohrbach Michael Thomas Thao Ung Qinling Qu Jinping Gan Rangaraj Narayanan Mary Ann Pelleymounter Jeffrey A. Robl 《Bioorganic & medicinal chemistry letters》2010,20(3):1128-1133
Agonists of the 5-HT2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT2C agonists with no detectable agonism of the 5-HT2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing. 相似文献
25.
Magnetospirillum magnetotacticum are magnetotactic bacteria that form a single chain of magnetite magnetosomes within its cytoplasm. Here, we studied the
ultrastructure of M. magnetotacticum by freeze-fracture and deep-etching to understand the spatial correlation between the
magnetosome chain and the cell envelope and its possible implications for magnetotaxis. Magnetosomes were found mainly near
the cell envelope, forming chains that were closely associated with the granular cytoplasmic material. The membrane surrounding
the magnetosomes could be visualized in deep-etching preparations. Thin connections between magnetosome chains and the cell
envelope were observed in deep-etching images. These results strengthen the hypothesis for the existence of structures that
transfer the torque from the magnetosome chains to the whole cell during the orientation of magnetotactic bacteria to a magnetic
field lines. 相似文献
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Yang Y Miller KJ Zhu Y Hong Y Tian Y Murugesan N Gu Z O'Tanyi E Keim WJ Rohrbach KW Johnghar S Behnia K Pelleymounter MA Carlson KE Ewing WR 《Bioorganic & medicinal chemistry letters》2011,21(22):6856-6860
Obesity remains a significant public health issue leading to Type II diabetes and cardiovascular disease. CB1 antagonists have been shown to suppress appetite and reduce body weight in animal models as well as in humans. Evaluation of pre-clinical CB1 antagonists to establish relationships between in vitro affinity and in vivo efficacy parameters are enhanced by ex vivo receptor occupancy data. Synthesis and biological evaluation of a novel and highly selective radiolabeled CB1 antagonist is described. The radioligand was used to conduct ex vivo receptor occupancy studies. 相似文献