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991.
Romeo Romagnoli Pier Giovanni Baraldi Maria Dora Carrion Carlota Lopez Cara Olga Cruz-Lopez Manlio Tolomeo Stefania Grimaudo Antonietta Di Cristina Maria Rosaria Pipitone Jan Balzarini Nicola Zonta Andrea Brancale Ernest Hamel 《Bioorganic & medicinal chemistry》2009,17(19):6862-6871
The biological importance of microtubules in mitosis and cell division makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. Thus, a new class of inhibitors of tubulin polymerization based on the 2-(3′,4′,5′-trimethoxybenzoyl)-benzo[b]furan molecular skeleton, with electron-donating (Me, OMe or OH) or electron-withdrawing (F, Cl and Br) substituents on the benzene ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. Adding a methyl group at the C-3 position resulted in increased activity. The most promising compound in this series was 2-(3′,4′,5′-trimethoxybenzoyl)-3-methyl-6-ethoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site. 相似文献
992.
Gemma Comellas Zusanna Kaczmarska Teresa Tarragó Meritxell Teixidó Ernest Giralt 《PloS one》2009,4(7)
Here we describe the design, synthesis and evaluation of the first solid-phase substrates for prolyl oligopeptidase (POP), a cytosolic serine peptidase associated with schizophrenia, bipolar affective disorder and related neuropsychiatric disorders. This study seeks to contribute to the future design of a one-bead one-compound (OBOC) peptide library of POP substrates, based on an intramolecular energy transfer substrate. Unexpectedly, the enzymatic evaluation of the substrates attached on solid-phase by means of the HMBA linker were cleaved through the ester bond, thereby suggesting an unknown esterase activity of POP, in addition to its known peptidase activity. By performing multiple activity assays, we have confirmed the esterase activity of this enzyme and its capacity to process the substrates on solid-phase. Finally, we tested a new linker, compatible with both the solid-phase peptide-synthesis used and the enzymatic assay, for application in the future design of an OBOC library. 相似文献
993.
Jose Eduardo de la Torre-Bárcena Sergios-Orestis Kolokotronis Ernest K. Lee Dennis Wm. Stevenson Eric D. Brenner Manpreet S. Katari Gloria M. Coruzzi Rob DeSalle 《PloS one》2009,4(6)
Background
Genome level analyses have enhanced our view of phylogenetics in many areas of the tree of life. With the production of whole genome DNA sequences of hundreds of organisms and large-scale EST databases a large number of candidate genes for inclusion into phylogenetic analysis have become available. In this work, we exploit the burgeoning genomic data being generated for plant genomes to address one of the more important plant phylogenetic questions concerning the hierarchical relationships of the several major seed plant lineages (angiosperms, Cycadales, Gingkoales, Gnetales, and Coniferales), which continues to be a work in progress, despite numerous studies using single, few or several genes and morphology datasets. Although most recent studies support the notion that gymnosperms and angiosperms are monophyletic and sister groups, they differ on the topological arrangements within each major group.Methodology
We exploited the EST database to construct a supermatrix of DNA sequences (over 1,200 concatenated orthologous gene partitions for 17 taxa) to examine non-flowering seed plant relationships. This analysis employed programs that offer rapid and robust orthology determination of novel, short sequences from plant ESTs based on reference seed plant genomes. Our phylogenetic analysis retrieved an unbiased (with respect to gene choice), well-resolved and highly supported phylogenetic hypothesis that was robust to various outgroup combinations.Conclusions
We evaluated character support and the relative contribution of numerous variables (e.g. gene number, missing data, partitioning schemes, taxon sampling and outgroup choice) on tree topology, stability and support metrics. Our results indicate that while missing characters and order of addition of genes to an analysis do not influence branch support, inadequate taxon sampling and limited choice of outgroup(s) can lead to spurious inference of phylogeny when dealing with phylogenomic scale data sets. As expected, support and resolution increases significantly as more informative characters are added, until reaching a threshold, beyond which support metrics stabilize, and the effect of adding conflicting characters is minimized. 相似文献994.
Ernest Nlandu Kamavuako Ken Yoshida Winnie Jensen 《Biomedical signal processing and control》2009,4(2):118-126
Detection of single unit action potentials (APs) from peripheral nerve recordings is complicated by low signal-to-noise ratio (SNR) due to the activity of nearby muscles, interference from more distant nerve fibers, and thermal noise from the neural interface. In this study, we propose a novel signal conditioning technique for multiunit signals (i.e. a signal comprised of multiple units coming from different nerve fibers), based on the variance to be applied prior to detection of APs. The proposed technique was tested on experimental and simulated intrafascicular recordings; and was compared to a wavelet-based conditioning (also applied before AP detection). The outputs of both conditioning schemes were sent to an AP detection algorithm that used a simple threshold (equal to the standard deviation of the signal). The overall performance of the detection phase was superior when using the wavelet-based conditioned signal especially for SNR ≤ 2 dB. However, when using the variance-based conditioned signal, the AP detection phase resulted in lower number of false positives for SNR > 2 dB. The novel variance-based method improves the SNR by attenuating the background noise between APs and can be applied as pre-conditioning processing for AP detection. 相似文献
995.
Le Li Alden King-Yung Leung Tsz-Piu Kwok Yvonne Y. Y. Lai Iris K. Pang Grace Tin-Yun Chung Angel C. Y. Mak Annie Poon Catherine Chu Menglu Li Jacob J. K. Wu Ernest T. Lam Han Cao Chin Lin Justin Sibert Siu-Ming Yiu Ming Xiao Kwok-Wai Lo Pui-Yan Kwok Ting-Fung Chan Kevin Y. Yip 《Genome biology》2017,18(1):230
We present a new method, OMSV, for accurately and comprehensively identifying structural variations (SVs) from optical maps. OMSV detects both homozygous and heterozygous SVs, SVs of various types and sizes, and SVs with or without creating or destroying restriction sites. We show that OMSV has high sensitivity and specificity, with clear performance gains over the latest method. Applying OMSV to a human cell line, we identified hundreds of SVs >2 kbp, with 68 % of them missed by sequencing-based callers. Independent experimental validation confirmed the high accuracy of these SVs. The OMSV software is available at http://yiplab.cse.cuhk.edu.hk/omsv/. 相似文献
996.
Do persistent rare species experience stronger negative frequency dependence than common species? 下载免费PDF全文
Understanding why so many species are rare yet persistent remains a significant challenge for both theoretical and empirical ecologists. Yenni et al. (2012, Ecology, 93, 456–461) proposed that strong negative frequency dependence causes species to be rare while simultaneously buffering them against extinction. This hypothesis predicts that, on average, rare species should experience stronger negative frequency dependence than common species. However, it is unknown if ecological communities generally show this theoretical pattern. We discuss the implications of this phenomenon for community dynamics, and develop a method to test for a non‐random relationship between negative frequency dependence and relative abundance using species abundance data from 90 communities across a broad range of environments and taxonomic groups. To account for biases introduced by measurement error, we compared the observed correlation between species relative abundance and the strength of frequency dependence against expectations from a randomization procedure. In approximately half of the analysed communities, we found increasingly strong negative frequency dependence with decreasing relative abundance: rare species experienced stronger frequency dependence than common species. The randomization test never detected stronger negative frequency dependence in more common species. Our results suggest that strong negative frequency dependence is a signature of persistent, rare species in many communities. 相似文献
997.
998.
Mui EJ Schiehser GA Milhous WK Hsu H Roberts CW Kirisits M Muench S Rice D Dubey JP Fowble JW Rathod PK Queener SF Liu SR Jacobus DP McLeod R 《PLoS neglected tropical diseases》2008,2(3):e190
BACKGROUND AND METHODOLOGY: Toxoplasma gondii causes substantial morbidity, mortality, and costs for healthcare in the developed and developing world. Current medicines are not well tolerated and cause hypersensitivity reactions. The dihydrotriazine JPC-2067-B (4, 6-diamino-1, 2-dihydro-2, 2-dimethyl-1-(3'(2-chloro-, 4-trifluoromethoxyphenoxy)propyloxy)-1, 3, 5-triazine), which inhibits dihydrofolate reductase (DHFR), is highly effective against Plasmodium falciparum, Plasmodium vivax, and apicomplexans related to T. gondii. JPC-2067-B is the primary metabolite of the orally active biguanide JPC-2056 1-(3'-(2-chloro-4-trifluoromethoxyphenyloxy)propyl oxy)- 5-isopropylbiguanide, which is being advanced to clinical trials for malaria. Efficacy of the prodrug JPC-2056 and the active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as toxicity toward mammalian cells were tested. PRINCIPAL FINDINGS AND CONCLUSIONS: Herein, we found that JPC-2067-B is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056) are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. SIGNIFICANCE: JPC-2056/JPC-2067-B have potential to be more effective and possibly less toxic treatments for toxoplasmosis than currently available medicines. 相似文献
999.
Al-Ghaithi Fatma El-Ridi Mamdouh R. Adeghate Ernest Amiri Mohamed H. 《Molecular and cellular biochemistry》2004,261(1):143-149
Diabetes mellitus is one of the most common endocrine diseases. In UAE many traditional plants such as the Citrullus colocynthis (Handal) are used as antidiabetic remedies. The aim of this study was to examine the effect of the aqueous extract of the seed of C. colocynthis on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal (60 mg/kg body wt1) injection of STZ. Normal and diabetic rats were fed with the plant extract daily by oral intubation for 2 weeks. Blood sample were collected at the beginning and end of the experiment for the measurement of biochemical parameters. The plasma level of alanine aminotranferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactic dehydrogenase (LDH) increased significantly after the onset of diabetes. Oral administration of the plant extract reduced the plasma level of AST and LDH significantly. However, the plant extract failed to reduce the increased blood level of GGT and ALP in diabetic rats. Blood urea nitrogen (BUN) increased significantly after the onset of diabetes. No significant difference was observed in the blood creatinine, K+, Na+, Ca2+ and P levels of normal and diabetic rats. The plant extract did not have any effect on BUN level, however, it caused an increase in the level of K+, Na+ in diabetic rats. In conclusion, oral administration of the aqueous extract of the C. colocynthis can ameliorate some of the toxic effects of streptozotocin. (Mol Cell Biochem 261: 143–149, 2004) 相似文献
1000.
Mircea Podar Iain Anderson Kira S Makarova James G Elkins Natalia Ivanova Mark A Wall Athanasios Lykidis Kostantinos Mavromatis Hui Sun Matthew E Hudson Wenqiong Chen Cosmin Deciu Don Hutchison Jonathan R Eads Abraham Anderson Fillipe Fernandes Ernest Szeto Alla Lapidus Nikos C Kyrpides Milton H Saier Jr Paul M Richardson Reinhard Rachel Harald Huber Jonathan A Eisen Eugene V Koonin Martin Keller Karl O Stetter 《Genome biology》2008,9(11):R158-18