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91.
Harikrishnan LS Kamau MG Herpin TF Morton GC Liu Y Cooper CB Salvati ME Qiao JX Wang TC Adam LP Taylor DS Chen AY Yin X Seethala R Peterson TL Nirschl DS Miller AV Weigelt CA Appiah KK O'Connell JC Michael Lawrence R 《Bioorganic & medicinal chemistry letters》2008,18(8):2640-2644
2-Arylbenzoxazole 5 was identified as a hit from a fluorescence-based high-throughput screen for CETP inhibitors. The synthesis and SAR investigation employing array synthesis of the A- and B-rings are described. 相似文献
92.
Li JJ Wang H Li J Qu F Swartz SG Hernández AS Biller SA Robl JA Tino JA Slusarchyk D Seethala R Sleph P Yan M Grover G Flynn N Murphy BJ Gordon D 《Bioorganic & medicinal chemistry letters》2008,18(8):2536-2539
A novel series of N1 substituted tetrazole amides were prepared and showed to be potent growth hormone (GH) secretagogues. Among them, hydroxyl containing analog 31 displayed excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model. 相似文献
93.
Critical leaf nutrient concentrations have often been used to diagnose the nutritional causes of crop underperformance. Unfortunately, these diagnostic criteria are not available for mature, tuber-bearing sweet potato plants (the word ‘tuber’ being used to describe a swollen root rather than a swollen stem). The Diagnosis and Recommendation Integrated System (DRIS), however, provides a reliable means of linking leaf nutrient concentrations to the yield of sweet potato tubers, and may be developed for this crop using existing data from regional crop surveys. In the present study, tuber yield and leaf nutrient concentration data from a survey of sweet potato gardens conducted in the Papua New Guinea (PNG) highlands in 2005 were used to establish DRIS N, P, K, and S norms and statistical parameters for sweet potato. Although the database was relatively small, the norms derived for nutrient ratios of key biological significance, i.e. N/S and K/N, were within the expected narrow ranges for higher plants, giving credibility to both the database and the DRIS model. Data from future surveys and field trials may subsequently be used to enlarge the database allowing the refinement of model parameters and hopefully an expansion of diagnostic scope to include other macro and micro-nutrients. As it stands, though, this preliminary DRIS model for sweet potato is possibly the best diagnostic tool currently available for evaluating the N, P, K and S statuses of sweet potato crops in the pacific region. 相似文献
94.
Dynein light chain (DLC8) is the smallest subunit of the dynein motor complex, which is known to act as a cargo adaptor in intracellular trafficking. The protein exists as a pure dimer at physiological pH and a completely folded monomer below pH 4. Here, we have determined the energy landscape of the dimeric protein using a combination of optical techniques and native-state hydrogen exchange of amide groups, the former giving the global features and the latter yielding the residue level details. The data indicated the presence of intermediates along the equilibrium unfolding transition. The hydrogen exchange data suggested that the molecule has differential stability in its various segments. We deduce from the free energy data that the antiparallel beta-sheets (beta4 and beta5) that form the hydrophobic core of the protein and the alpha2 helix, all of which are highly protected with regard to hydrogen exchange, contribute significantly to the initial step of the protein folding mechanism. Denaturant-dependent hydrogen exchange indicated further that some amides exchange via local fluctuations, whereas there are others which exchange via global unfolding events. Implications of these to cargo adaptability of the dimer are discussed. 相似文献
95.
Ch. Srinivas Ch.N.S. Sai Pavan Kumar B. China Raju V. Jayathirtha Rao V.G.M. Naidu S. Ramakrishna Prakash V. Diwan 《Bioorganic & medicinal chemistry letters》2009,19(20):5915-5918
The first stereoselective total synthesis of new natural amide alkaloids 1–3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a trans regioselective opening of 2,3-epoxy alcohol, Horner–Wadsworth–Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids 1–3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time. 相似文献
96.
Tasir S. Haque Ningning Liang Rajasree Golla Ramakrishna Seethala Zhengping Ma William R. Ewing Christopher B. Cooper Mary Ann Pelleymounter Michael A. Poss Dong Cheng 《Bioorganic & medicinal chemistry letters》2009,19(20):5872-5876
We report the synthesis and enzymatic evaluation of potent inhibitors of acetyl-CoA carboxylases (ACCs) containing biphenyl or 3-phenyl pyridine cores. These compounds inhibit both ACC1 and ACC2, or are moderately selective for either enzyme, depending on side chain substitution. Typical activities of the most potent compounds in this class are in the low double-digit to single-digit nanomolar range in in vitro assays using human ACC1 and ACC2 enzymes. 相似文献
97.
Gene order and content differ among homologous regions of closely related genomes. Similarities in the expression profiles of physically adjacent genes suggest that the proper functioning of these genes depends on maintaining a specific position relative to each other. To better understand the results of the interaction of these two genomic forces, convergent, divergent, and tandem gene pairs in rice and sorghum, as well as their homologs in rice, sorghum, maize, and Brachypodium were analyzed. The status of each pair in all four species: whether it was conserved, inverted, rearranged, or missing homologs was determined. We observed that divergent gene pairs had lower rates of conservation than convergent or tandem pairs, but higher rates of rearranged pairs and missing homologs in maize than in any other species. We also discovered species-specific gene pairs in rice and sorghum. In rice, gene pairs with strongly correlated expression levels were conserved significantly more often than those with little or no correlation. We assigned three types of gene pair to one of 14 possible evolutionary history categories to uncover their evolutionary dynamics during the evolution of grass genomes. 相似文献
98.
Gravitt PE Paul P Katki HA Vendantham H Ramakrishna G Sudula M Kalpana B Ronnett BM Vijayaraghavan K Shah KV;CATCH Study Team 《PloS one》2010,5(10):e13711
Background
While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness.Methods and Findings
A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity = 78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures.Conclusions
We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. 相似文献99.
100.
Satish K. Madala Ramakrishna Edukulla Mukta Phatak Stephanie Schmidt Cynthia Davidson Thomas H. Acciani Thomas R. Korfhagen Mario Medvedovic Timothy D. LeCras Kimberly Wagner William D. Hardie 《PloS one》2014,9(1)
Pulmonary fibrosis is often triggered by an epithelial injury resulting in the formation of fibrotic lesions in the lung, which progress to impair gas exchange and ultimately cause death. Recent clinical trials using drugs that target either inflammation or a specific molecule have failed, suggesting that multiple pathways and cellular processes need to be attenuated for effective reversal of established and progressive fibrosis. Although activation of MAPK and PI3K pathways have been detected in human fibrotic lung samples, the therapeutic benefits of in vivo modulation of the MAPK and PI3K pathways in combination are unknown. Overexpression of TGFα in the lung epithelium of transgenic mice results in the formation of fibrotic lesions similar to those found in human pulmonary fibrosis, and previous work from our group shows that inhibitors of either the MAPK or PI3K pathway can alter the progression of fibrosis. In this study, we sought to determine whether simultaneous inhibition of the MAPK and PI3K signaling pathways is a more effective therapeutic strategy for established and progressive pulmonary fibrosis. Our results showed that inhibiting both pathways had additive effects compared to inhibiting either pathway alone in reducing fibrotic burden, including reducing lung weight, pleural thickness, and total collagen in the lungs of TGFα mice. This study demonstrates that inhibiting MEK and PI3K in combination abolishes proliferative changes associated with fibrosis and myfibroblast accumulation and thus may serve as a therapeutic option in the treatment of human fibrotic lung disease where these pathways play a role. 相似文献