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121.
Graciela B. Arhancet Daniel P. Walker Sue Metz Yvette M. Fobian Steven E. Heasley Jeffrey S. Carter John R. Springer Darin E. Jones Michael J. Hayes Alexander F. Shaffer Gina M. Jerome Michael T. Baratta Ben Zweifel William M. Moore Jaime L. Masferrer Michael L. Vazquez 《Bioorganic & medicinal chemistry letters》2013,23(4):1114-1119
Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies. 相似文献
122.
O. A. Gutierrez M. J. Wubben M. Howard B. Roberts E. Hanlon J. R. Wilkinson 《Russian Journal of Plant Physiology》2009,56(1):1-5
The phytohormones ethylene and auxin regulate many important processes in plants, including cell differentiation, cell expansion,
and responses to abiotic stresses. These hormones also play important roles in many plant-pathogen interactions, including
regulation of plant defense responses and symptom development. Sedentary plant-parasitic nematodes, which require the formation
of a complex feeding site within the host root, are among the world’s most destructive plant pathogens. Nematode-induced feeding
sites show dramatic changes in host cell morphology and gene expression. These changes are likely mediated, at least in part,
by phytohormones. In the present review, current knowledge of the roles of ethylene and auxin will be explored in two main
areas: the specific role of phytohormones in mediating feeding site development by plant-parasitic nematodes and the general
role of phytohormones in affecting the ability of parasitic nematodes to cause disease.
Published in Russian in Fiziologiya Rastenii, 2009, Vol. 56, No. 1, pp. 3–7.
This article was presented in original. 相似文献
123.
Jaime Moreno Melissa Hidalgo Carolina Duarte Olga Sanabria Jean Marc Gabastou Ana Belén Ibarz-Pavon 《PloS one》2015,10(8)
Background
Meningococcal carriage studies are important to improve our understanding of the epidemiology of meningococcal disease. The aim of this study was to determine the prevalence of meningococcal carriage and the phenotypic and genotypic characteristics of isolates collected from a sample of students in the city of Bogotá, Colombia.Materials and Methods
A total of 1459 oropharyngeal samples were collected from students aged 15–21 years attending secondary schools and universities. Swabs were plated on a Thayer Martin agar and N. meningitidis was identified by standard microbiology methods and PCR.Results
The overall carriage prevalence was 6.85%. Carriage was associated with cohabitation with smokers, and oral sex practices. Non-groupable and serogroup Y isolates were the most common capsule types found. Isolates presented a high genetic diversity, and circulation of the hypervirulent clonal complexes ST-23, ST-32 and ST-41/44 were detected.Conclusion
The meningococcal carriage rate was lower than those reported in Europe and Africa, but higher than in other Latin American countries. Our data also revealed antigenic and genetic diversity of the isolates and the circulation of strains belonging to clonal complexes commonly associated with meningococcal disease. 相似文献124.
125.
LEA Gene Introns: is the Intron of Dehydrin Genes a Characteristic of the Serine-Segment? 总被引:1,自引:0,他引:1
Juan Francisco Jiménez-Bremont Israel Maruri-López Ana Erika Ochoa-Alfaro Pablo Delgado-Sánchez Jaime Bravo Margarita Rodríguez-Kessler 《Plant Molecular Biology Reporter》2013,31(1):128-140
Dehydrins, which belong to group 2 LEA proteins, are a family of intrinsically unstructured plant proteins that accumulate during the late stages of embryogenesis and in response to abiotic stresses. We have previously reported that the OpsDHN1 gene, encoding an SK3-type acidic dehydrin protein from Opuntia streptacantha, contains an intron inserted within the sequence encoding the S-motif. Herein, we present an in silico analysis of intron sequences in dehydrin genes from mono- and dicotyledonous plants that reveals a preference for insertion within the nucleotide sequence encoding the S-motif. Sequence comparison of ten Dhn genes from Arabidopsis thaliana and the orthologous genes in Arabidopsis lyrata revealed that introns maintain considerable sequence identity and conserve the insertion pattern. Furthermore, syntenic regions were identified among eight orthologous genes of A. thaliana and A. lyrata, showing that correlated gene arrangements are conserved between these Arabidopsis species. Our study shows that most SKn-type dehydrins contain one intron that is conserved in phase and location; this intron is linked to the nucleotide sequence that encodes the S-motif. 相似文献
126.
Maria A. Ledesma Sara A. Ochoa Ariadnna Cruz Luz M. Rocha-Ramírez Jaime Mas-Oliva Carlos A. Eslava Jorge A. Girón Juan Xicohtencatl-Cortes 《PloS one》2010,5(8)
Background
Enterohemorrhagic Escherichia coli (EHEC) O157:H7, the causative agent of hemorrhagic colitis and the hemolytic uremic syndrome (HUS), produces long bundles of type IV pili (TFP) called hemorrhagic coli pili (HCP). HCP are capable of mediating several phenomena associated with pathogenicity: i) adherence to human and bovine epithelial cells; ii) invasion of epithelial cells; iii) hemagglutination of rabbit erythrocytes; iv) biofilm formation; v) twitching motility; and vi) specific binding to laminin and fibronectin. HCP are composed of a 19 kDa pilin subunit (HcpA) encoded by the hcpA chromosomal gene (called prepilin peptidase-dependent gene [ppdD] in E. coli K-12).Methodology/Principal Findings
In this study we investigated the potential role of HCP of E. coli O157:H7 strain EDL933 in activating the release of pro- and anti-inflammatory cytokines from a variety of host epithelial cells. We found that purified HCP and a recombinant HcpA protein induced significant release of IL-8 and TNF-α, from cultured polarized intestinal cells (T84 and HT-29 cells) and non-intestinal HeLa cells. Levels of proinflammatory IL-8 and TNF-α, but not IL-2, IL6, or IL-10 cytokines, were increased in the presence of HCP and recombinant HcpA after 6 h of incubation with ≥50 ng/ml of protein, suggesting that stimulation of IL-8 and TNF-α are dose and time-dependent. In addition, we also demonstrated that flagella are potent inducers of cytokine production. Furthermore, MAPK activation kinetics studies showed that EHEC induces p38 phosphorylation under HCP-producing conditions, and ERK1/2 and JNK activation was detectable after 3 h of EHEC infection. HT-29 cells were stimulated with epidermal growth factor stimulation of HT-29 cells for 30 min leading to activation of three MAPKs.Conclusions/Significance
The HcpA pilin monomer of the HCP produced by EHEC O157:H7 is a potent inducer of IL-8 and TNF-α release, an event which could play a significant role in the pathogenesis of hemorrhagic colitis caused by this pathogen. 相似文献127.
Rotaviruses are the major cause of acute gastroenteritis in infants world-wide. The genome consists of eleven double stranded RNA segments. The major segment encodes the structural protein VP1, the viral RNA-dependent RNA polymerase (RdRp), which is a minor component of the viral inner core. This study is a detailed bioinformatic assessment of the VP1 sequence. Using various methods we have identified canonical motifs within the VP1 sequence which correspond to motifs previously identified within RdRps of other positive strand, double-strand RNA viruses. The study also predicts an overall structural conservation in the middle region that may correspond to the palm subdomain and part of the fingers and thumb subdomains, which comprise the polymerase core of the protein. Based on this analysis, we suggest that the rotavirus replicase has the minimal elements to function as an RNA-dependent RNA polymerase. VP1, besides having common RdRp features, also contains large unique regions that might be responsible for characteristic features observed in the Reoviridae family. 相似文献
128.
Methods for surveillance of fetal alcohol syndrome: The fetal alcohol syndrome surveillance network II (FASSNetII) – Arizona,Colorado, New York, 2009 ‐ 2014 下载免费PDF全文
Leslie A. O'Leary Linnette Ortiz April Montgomery Deborah J. Fox Christopher Cunniff Margaret Ruttenber April Breen Sydney Pettygrove Don Klumb Charlotte Druschel Jaime L. Frías Luther K. Robinson Jacquelyn Bertrand Kelly Ferrara Maureen Kelly Suzanne M. Gilboa F. John Meaney for the FASSNetII 《Birth defects research. Part A, Clinical and molecular teratology》2015,103(3):196-202
129.
130.