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排序方式: 共有214条查询结果,搜索用时 31 毫秒
61.
Rangarajan M Kim JS Jin S Sim SP Liu A Pilch DS Liu LF LaVoie EJ 《Bioorganic & medicinal chemistry》2000,8(6):1371-1382
5-Phenylterbenzimidazole (1) is active as a topoisomerase I poison (topo I) and is cytotoxic to human tumor cells. No cross-resistance was observed for 1 when it was evaluated against the camptothecin-resistant cell line, CPT-K5. Derivatives of 1 substituted at the 2"-position, however, did exhibit cross-resistance to this cell line. The basis for the resistance of this cell line towards CPT is that it possesses a mutant form of topo I. These results suggest that substituents at the 2"-position may be in proximity to the wild-type enzyme. Therefore, we hypothesized that terbenzimidazoles with 2"-substituents could be capable of interacting with the enzyme and thereby influence activity within this class of topo I poisons. 5-Phenylterbenzimidazoles with a hydroxy, hydroxymethyl, mercapto, amino, N-benzoylaminomethyl, chloro, and trifluoromethyl group at the 2"-position were synthesized. In addition, several 2"-ethyl-5-phenylterbenzimidazoles were prepared containing either a methoxy, hydroxy, amino, or N-acetylamino group at the 2-position of the ethyl side-chain. These 2"-substituted 5-phenylterbenzimidazoles were evaluated as topo I poisons and for cytotoxic activity. The presence of a strong electron-withdrawing group at the 2"-position, such as a chloro or trifluoromethyl group, did enhance both topo I poisoning activity and cytotoxicity. Studies on the relative DNA binding affinity of 1 to its 2"-amino and 2"-trifluoromethyl derivatives did exhibit a correlation with their relative differences in biological activity. 相似文献
62.
Reddy RC Vatsala PG Keshamouni VG Padmanaban G Rangarajan PN 《Biochemical and biophysical research communications》2005,326(2):472-474
Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection. 相似文献
63.
The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents 总被引:1,自引:0,他引:1
David J Ecker Rangarajan Sampath Paul Willett Jacqueline R Wyatt Vivek Samant Christian Massire Thomas A Hall Kumar Hari John A McNeil Cornelia Büchen-Osmond Bruce Budowle 《BMC microbiology》2005,5(1):1-17
Background
Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks.Results
We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents.Conclusion
The Microbial Rosetta Stone is available at http://www.microbialrosettastone.com/. The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases. 相似文献64.
Mani SA Harish S Vathsala PG Rangarajan PN Padmanaban G 《Biochemical and biophysical research communications》2000,268(3):734-739
The phenobarbitone (PB) responsiveness of the 5'-proximal region of the CYP2B1/B2 gene was examined in detail with plasmid DNA constructs containing G-free cassette as reporter, using in vivo targeting of the same DNA constructs into rat liver as galactosylated-polylysine complexes. The contribution of the proximal region (-1 to -179 bp) and the positive element (-69 to -98 bp) identified earlier in this laboratory to PB responsiveness was assessed. The results obtained on PB treatment of rats subjected to receptor-mediated gene delivery to liver were conclusive and dramatic, with the control (saline-treated) rats manifesting very little expression of the reporter, reflecting the in vivo picture of CYP2B1/B2 gene expression. The positive element conferred PB responsiveness to homologous and heterologous promoters. Deletion of the positive element led to elimination of PB response. The entire -179 bp region was significantly more effective in responding to PB treatment than the region up to -98 bp, both containing one copy of the positive element. Thus, the positive element and its flanking sequences in the 5'-proximal region are involved in conferring PB responsiveness to the CYP2B1/B2 gene. 相似文献
65.
BackgroundIntrinsically disordered proteins (IDPs) lack a stable tertiary structure in isolation. Remarkably, however, a substantial portion of IDPs undergo disorder-to-order transitions upon binding to their cognate partners. Structural flexibility and binding plasticity enable IDPs to interact with a broad range of partners. However, the broader network properties that could provide additional insights into the functional role of IDPs are not known.ResultsHere, we report the first comprehensive survey of network properties of IDP-induced sub-networks in multiple species from yeast to human. Our results show that IDPs exhibit greater-than-expected modularity and are connected to the rest of the protein interaction network (PIN) via proteins that exhibit the highest betweenness centrality and connect to fewer-than-expected IDP communities, suggesting that they form critical communication links from IDP modules to the rest of the PIN. Moreover, we found that IDPs are enriched at the top level of regulatory hierarchy.ConclusionOverall, our analyses reveal coherent and remarkably conserved IDP-centric network properties, namely, modularity in IDP-induced network and a layer of critical nodes connecting IDPs with the rest of the PIN. 相似文献
66.
Vivek Rangarajan 《Biotechnology & genetic engineering reviews》2015,31(1-2):46-68
The growing interest in Bacillus lipopeptides for high-value applications has driven process design, development and optimization for enhanced lipopeptide production. Traditional optimization approaches have been directed towards improving the overall titres by modification of media components and environmental parameters, almost exclusively in submerged cultures. Carbon and nitrogen sources, trace elements and oxygen availability have all been demonstrated to exhibit significant influences on lipopeptide yield, productivity and selectivity. This insight into process-linked kinetics, especially selectivity, has led to the introduction of novel process intensification and integration strategies which further promote process efficiency, and which include foam fractionation, inverse fluidization, rotating disc contacting and microfiltration with recycle. These strategies have not only transformed the production capabilities, but have also successfully integrated upstream production with downstream purification through cell retention and in situ product removal. This review analyses and critically discusses the impact of process conditions and process optimization strategies for improving lipopeptide production kinetics, specifically highlighting the emerging trend of process intensification and integration strategies and further, proposes a heuristic route to enhance lipopeptide production. 相似文献
67.
Do R Xie C Zhang X Männistö S Harald K Islam S Bailey SD Rangarajan S McQueen MJ Diaz R Lisheng L Wang X Silander K Peltonen L Yusuf S Salomaa V Engert JC Anand SS;INTERHEART investigators 《PLoS medicine》2011,8(10):e1001106
Background
One of the most robust genetic associations for cardiovascular disease (CVD) is the Chromosome 9p21 region. However, the interaction of this locus with environmental factors has not been extensively explored. We investigated the association of 9p21 with myocardial infarction (MI) in individuals of different ethnicities, and tested for an interaction with environmental factors.Methods and Findings
We genotyped four 9p21 SNPs in 8,114 individuals from the global INTERHEART study. All four variants were associated with MI, with odds ratios (ORs) of 1.18 to 1.20 (1.85×10−8≤p≤5.21×10−7). A significant interaction (p = 4.0×10−4) was observed between rs2383206 and a factor-analysis-derived “prudent” diet pattern score, for which a major component was raw vegetables. An effect of 9p21 on MI was observed in the group with a low prudent diet score (OR = 1.32, p = 6.82×10−7), but the effect was diminished in a step-wise fashion in the medium (OR = 1.17, p = 4.9×10−3) and high prudent diet scoring groups (OR = 1.02, p = 0.68) (p = 0.014 for difference). We also analyzed data from 19,129 individuals (including 1,014 incident cases of CVD) from the prospective FINRISK study, which used a closely related dietary variable. In this analysis, the 9p21 risk allele demonstrated a larger effect on CVD risk in the groups with diets low or average for fresh vegetables, fruits, and berries (hazard ratio [HR] = 1.22, p = 3.0×10−4, and HR = 1.35, p = 4.1×10−3, respectively) compared to the group with high consumption of these foods (HR = 0.96, p = 0.73) (p = 0.0011 for difference). The combination of the least prudent diet and two copies of the risk allele was associated with a 2-fold increase in risk for MI (OR = 1.98, p = 2.11×10−9) in the INTERHEART study and a 1.66-fold increase in risk for CVD in the FINRISK study (HR = 1.66, p = 0.0026).Conclusions
The risk of MI and CVD conferred by Chromosome 9p21 SNPs appears to be modified by a prudent diet high in raw vegetables and fruits. Please see later in the article for the Editors'' Summary 相似文献68.
MacInnes H Zhou Y Gouveia K Cromwell J Lowery K Layton RC Zubelewicz M Sampath R Hofstadler S Liu Y Cheng YS Koster F 《PloS one》2011,6(9):e24448
Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID50) of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system) and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID50 for A/New Caledonia/20/99 (H1N1) was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure. 相似文献
69.
Rangarajan ES Ruane KM Proteau A Schrag JD Valladares R Gonzalez CF Gilbert M Yakunin AF Cygler M 《Protein science : a publication of the Protein Society》2011,20(7):1208-1219
There is a high prevalence of sialic acid in a number of different organisms, resulting in there being a myriad of different enzymes that can exploit it as a fermentable carbon source. One such enzyme is NanS, a carbohydrate esterase that we show here deacetylates the 9 position of 9-O-sialic acid so that it can be readily transported into the cell for catabolism. Through structural studies, we show that NanS adopts a SGNH hydrolase fold. Although the backbone of the structure is similar to previously characterized family members, sequence comparisons indicate that this family can be further subdivided into two subfamilies with somewhat different fingerprints. NanS is the founding member of group II. Its catalytic center contains Ser19 and His301 but no Asp/Glu is present to form the classical catalytic triad. The contribution of Ser19 and His301 to catalysis was confirmed by mutagenesis. In addition to structural characterization, we have mapped the specificity of NanS using a battery of substrates. 相似文献
70.
Rangarajan ES Bhatia S Watson DC Munger C Cygler M Matte A Young NM 《Protein science : a publication of the Protein Society》2007,16(5):990-995
Campylobacter jejuni is unusual among bacteria in possessing a eukaryotic-like system for N-linked protein glycosylation at Asn residues in sequons of the type Asp/Glu-Xaa-Asn-Xaa-Ser/Thr. However, little is known about the structural context of the glycosylated sequons, limiting the design of novel recombinant glycoproteins. To obtain more information on sequon structure, we have determined the crystal structure of the PEB3 (Cj0289c) dimer. PEB3 has the class II periplasmic-binding protein fold, with each monomer having two domains with a ligand-binding site containing citrate located between them, and overall resembles molybdate- and sulfate-binding proteins. The sequon around Asn90 is located within a surface-exposed loop joining two structural elements. The three key residues are well exposed on the surface; hence, they may be accessible to the PglB oligosaccharyltransferase in the folded state. 相似文献