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971.
972.
Qingmei Hong Raman K. Bakshi James Dellureficio Shuwen He Zhixiong Ye Peter H. Dobbelaar Iyassu K. Sebhat Liangqin Guo Jian Liu Tianying Jian Rui Tang Rubana N. Kalyani Tanya MacNeil Aurawan Vongs Charles I. Rosenblum David H. Weinberg Qingping Peng Constantin Tamvakopoulos Randy R. Miller Ralph A. Stearns Ravi P. Nargund 《Bioorganic & medicinal chemistry letters》2010,20(15):4483-4486
Design, syntheses and structure–activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties. 相似文献
973.
974.
Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis 下载免费PDF全文
Raman S Puyang X Cheng TY Young DC Moody DB Husson RN 《Journal of bacteriology》2006,188(24):8460-8468
The Mycobacterium tuberculosis genome encodes 12 alternative sigma factors, several of which regulate stress responses and are required for virulence in animal models of acute infection. In this work we investigated M. tuberculosis SigM, a member of the extracytoplasmic function subfamily of alternative sigma factors. This sigma factor is expressed at low levels in vitro and does not appear to function in stress response regulation. Instead, SigM positively regulates genes required for the synthesis of surface or secreted molecules. Among these are genes encoding two pairs of Esx secreted proteins, a multisubunit nonribosomal peptide synthetase operon, and genes encoding two members of the proline-proline-glutamate (PPE) family of proteins. Genes up regulated in a sigM mutant strain include a different PPE gene, as well as several genes involved in surface lipid synthesis. Among these are genes involved in synthesis of phthiocerol dimycocerosate (PDIM), a surface lipid critical for virulence during acute infection, and the kasA-kasB operon, which is required for mycolic acid synthesis. Analysis of surface lipids showed that PDIM synthesis is increased in a sigM-disrupted strain and is undetectable in a sigM overexpression strain. These findings demonstrate that SigM positively and negatively regulates cell surface and secreted molecules that are likely to function in host-pathogen interactions. 相似文献
975.
Manuel Zander Dhwani A. Patel Angela Van de Wouw Kaitao Lai Michal T. Lorenc Emma Campbell Alice Hayward David Edwards Harsh Raman Jacqueline Batley 《Functional & integrative genomics》2013,13(3):295-308
Next generation sequencing technology allows rapid re-sequencing of individuals, as well as the discovery of single nucleotide polymorphisms (SNPs), for genomic diversity and evolutionary analyses. By sequencing two isolates of the fungal plant pathogen Leptosphaeria maculans, the causal agent of blackleg disease in Brassica crops, we have generated a resource of over 76 million sequence reads aligned to the reference genome. We identified over 21,000 SNPs with an overall SNP frequency of one SNP every 2,065 bp. Sequence validation of a selection of these SNPs in additional isolates collected throughout Australia indicates a high degree of polymorphism in the Australian population. In preliminary phylogenetic analysis, isolates from Western Australia clustered together and those collected from Brassica juncea stubble were identical. These SNPs provide a novel marker resource to study the genetic diversity of this pathogen. We demonstrate that re-sequencing provides a method of validating previously characterised SNPs and analysing differences in important genes, such as the disease related avirulence genes of L. maculans. Understanding the genetic characteristics of this devastating pathogen is vital in developing long-term solutions to managing blackleg disease in Brassica crops. 相似文献
976.
Chemicals isolated from Justicia adhatoda Linn reduce fitness of the mosquito,Aedes aegypti L 下载免费PDF全文
Annamalai Thanigaivel Sengottayan Senthil‐Nathan Prabhakaran Vasantha‐Srinivasan Edward‐Sam Edwin Athirstam Ponsankar Selvaraj Selin‐Rani Venkatraman Pradeepa Muthiah Chellappandian Kandaswamy Kalaivani Ahmed Abdel‐Megeed Raman Narayanan Kadarkarai Murugan 《Archives of insect biochemistry and physiology》2017,94(4)
Extracts from Justicia adhatoda L. (Acanthaceae) strongly reduced the fitness of the mosquito, Aedes aegypti Linn. The methanolic extracts inhibited several enzymes responsible for protecting insects from oxidative and other damage, including glutathione‐S‐transferase, superoxide dismutase, cytochrome P450, and α‐ and β‐esterases. They increased repellency (maximum repellency at 100 ppm) in host‐seeking adult females using the “arm‐in cage assay.” Histopathological examination showed the extracts led to serious midgut cell damage. Justicia adhatoda extracts led to reduced fecundity and oviposition of gravid females compared to controls. The extracts led to substantially reduced A. aegypti survival. We infer that the extracts have potential to reduce pathogen transmission by suppressing population growth of A. aegypti, and possibly other mosquito species. 相似文献
977.
A simple technique for staining synaptonemal complexes with Coomassie brilliant blue for light microscopy has been described. The testis cells were exposed to prolonged hypotonic treatment and dropped on Formvar-coated slides. Following fixation with paraformaldehyde the slides were stained with Coomassie brilliant blue for 15 min to 1 h at room temperature and rinsed in distilled water. For its simplicity and rapidity this technique may serve as an effective alternative to silver staining for light microscopic observation of synaptonemal complexes. 相似文献
978.
Dynamic association between the catalytic and lectin domains of human UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-2 总被引:1,自引:0,他引:1
The family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs) is unique among glycosyltransferases, containing both catalytic and lectin domains that we have previously shown to be closely associated. Here we describe the x-ray crystal structures of human ppGalNAcT-2 (hT2) bound to the product UDP at 2.75 A resolution and to UDP and an acceptor peptide substrate EA2 (PTTDSTTPAPTTK) at 1.64 A resolution. The conformations of both UDP and residues Arg362-Ser372 vary greatly between the two structures. In the hT2-UDP-EA2 complex, residues Arg362-Ser373 comprise a loop that forms a lid over UDP, sealing it in the active site, whereas in the hT2-UDP complex this loop is folded back, exposing UDP to bulk solvent. EA2 binds in a shallow groove with threonine 7 positioned consistent with in vitro data showing it to be the preferred site of glycosylation. The relative orientations of the hT2 catalytic and lectin domains differ dramatically from that of murine ppGalNAcT-1 and also vary considerably between the two hT2 complexes. Indeed, in the hT2-UDP-EA2 complex essentially no contact is made between the catalytic and lectin domains except for the peptide bridge between them. Thus, the hT2 structures reveal an unexpected flexibility between the catalytic and lectin domains and suggest a new mechanism used by hT2 to capture glycosylated substrates. Kinetic analysis of hT2 lacking the lectin domain confirmed the importance of this domain in acting on glycopeptide but not peptide substrates. The structure of the hT2-UDP-EA2 complex also resolves long standing questions regarding ppGalNAcT acceptor substrate specificity. 相似文献
979.
Parkesh R Lewis AM Aley PK Arredouani A Rossi S Tavares R Vasudevan SR Rosen D Galione A Dowden J Churchill GC 《Cell calcium》2008,43(6):531-538
NAADP (nicotinic acid adenine dinucleotide phosphate) is a recently discovered second messenger, and as such, we have much yet to learn about its functions in health and disease. A bottleneck in this basic research is due to NAADP, like all second messengers, being charged to prevent it from leaking out of cells. This makes for effective biology, but imposes difficulties in experiments, as it must be injected, loaded via liposomes, or electroporated, techniques that are highly technically demanding and are possible only in certain single cell preparations. For the better understood second messenger inositol 1,4,5-trisphosphate, great success has been obtained with cell-permeant derivatives where the charged groups are masked through esterification. We now report NAADP-AM as a cell-permeant analogue of NAADP that is taken up into cells and induces NAADP-mediated Ca(2+) signalling. NAADP-AM is a powerful chemical tool that will be of enormous biological utility in a wide range of systems and will greatly facilitate research into the role of NAADP in health and disease. 相似文献
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