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131.
132.
Recognizing the forest for the trees: testing temporal patterns of cladogenesis using a null model of stochastic diversification 总被引:2,自引:1,他引:1
Computer simulations are developed and employed to examine the expected
temporal distributions of nodes under a null model of stochastic lineage
bifurcation and extinction. These Markovian models of phylogenetic process
were constructed so as to permit direct comparisons against empirical
phylogenetic trees generated from molecular or other information available
solely from extant species. For replicate simulated phylads with n extant
species, cumulative distribution functions (cdf's) of branching times were
calculated, and compared (using the Kolmogorov-Smirnov test statistic D) to
those from three published empirical trees. Molecular phylogenies for
columbine plants and avian cranes showed statistically significant
departures from the null expectations, in directions indicating recent and
ancient species' radiations, respectively, whereas a molecular phylogeny
for the Drosophila virilis species group showed no apparent historical
clustering of branching events. Effects of outgroup choice and phylogenetic
frame of reference were investigated for the columbines and found to have a
predictable influence on the types of conclusions to be drawn from such
analyses. To enable other investigators to statistically test for
nonrandomness in temporal cladogenetic pattern in empirical trees generated
from data on extant species, we present tables of mean cdf's and associated
probabilities under the null model for expected branching times in phylads
of varying size. The approaches developed in this report complement and
extend those of other recent methods for employing null models to assess
the statistical significance of pattern in evolutionary trees.
相似文献
133.
134.
Manoalide, an unusual nonsteroidal sesterterpenoid recently isolated from sponge, antagonizes phorbol-induced inflammation but not that induced by arachidonic acid, suggesting that manoalide acts prior to the cyclooxygenase step in prostaglandin synthesis, possibly by inhibiting phospholipase A2. We have now studied the inhibitory effect of manoalide on a homogeneous preparation of phospholipase A2 from cobra venom. For a given concentration of manoalide, the inhibition of phospholipase A2 activity toward dipalmitoylphosphatidylcholine/Triton X-100 mixed micelles is time-dependent and plateaus at about 85% inhibition of the initial velocity even after extensive preincubation. Metal ions (Ca2+, Ba2+, Mn2+) increase the inhibition, while lysophosphatidylcholine and substrate micelles protect. Increasing manoalide concentration shows increasing inhibition of the initial velocity until a plateau is reached, giving a typical saturation curve with a linear double-reciprocal plot. Under typical conditions (20-min preincubation, 40 degrees C, pH 7.1), 50% inhibition is achieved at a manoalide concentration of about 2 X 10(-6) M. The data indicate that manoalide is a potent inhibitor of the cobra venom phospholipase A2. Manoalide is now shown to react irreversibly with lysine residues in the enzyme. Surprisingly, the cobra venom phospholipase normally acts poorly on phosphatidylethanolamine as substrate, but after reaction with manoalide, the enzyme is somewhat more active toward this substrate rather than being inhibited. This suggests that a lysine residue may be important in understanding the substrate specificity of phospholipase A2. 相似文献
135.
Human pancreatic carboxyl ester hydrolase is shown to catalyse the esterification of cholesterol and lipid-soluble vitamins A, E and D3 with oleic acid. The acitivity requires the presence of bile salts, and the trihydroxylated or the 3 alpha, 7 alpha dihydroxylated bile salts are better activators than the 3 alpha, 12 alpha dihydroxylated bile salts. The hydrolyzing and synthetizing activities of human pancreatic carboxyl ester hydrolase are separated by a large pH range since the synthesis of cholesterol esters is optimal at pH 5.25 and the hydrolysis of cholesterol and vitamin E esters is optimal at pH 8.0. From the comparison of the catalytic constants determined for the hydrolyzing and synthetizing activities and from the pH dependence of the two activities, it appears that human carboxyl ester hydrolase plays an important part in the intestinal lumen. The role of the enzyme in the esterification of cholesterol and lipid-soluble vitamins is questionable. 相似文献
136.
137.
Kim KS Lu S Cornelius LA Lombardo LJ Borzilleri RM Schroeder GM Sheng C Rovnyak G Crews D Schmidt RJ Williams DK Bhide RS Traeger SC McDonnell PA Mueller L Sheriff S Newitt JA Pudzianowski AT Yang Z Wild R Lee FY Batorsky R Ryder JS Ortega-Nanos M Shen H Gottardis M Roussell DL 《Bioorganic & medicinal chemistry letters》2006,16(15):3937-3942
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein. 相似文献
138.
McClure KF Letavic MA Kalgutkar AS Gabel CA Audoly L Barberia JT Braganza JF Carter D Carty TJ Cortina SR Dombroski MA Donahue KM Elliott NC Gibbons CP Jordan CK Kuperman AV Labasi JM Laliberte RE McCoy JM Naiman BM Nelson KL Nguyen HT Peese KM Sweeney FJ Taylor TJ Trebino CE Abramov YA Laird ER Volberg WA Zhou J Bach J Lombardo F 《Bioorganic & medicinal chemistry letters》2006,16(16):4339-4344
The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates. 相似文献
139.
F. Amato M. Cannataro C. Cosentino A. Garozzo N. Lombardo C. Manfredi F. Montefusco G. Tradigo P. Veltri 《Biomedical signal processing and control》2009,4(3):206-211
Voice is the result of the coordination of the whole pneumophonoarticulatory apparatus. The analysis of the voice allows the identification of the diseases of the vocal apparatus and currently is carried out from an expert doctor through methods based on the auditory analysis. The paper presents a web-based system for the acquisition and automatic analysis of vocal signals. Vocal signals are submitted by the users through a simple web-interface and are analyzed in real-time by using state-of-the art signal processing techniques, providing first-level information on possible voice alterations. The system offers different analysis functions to the doctors that may analyze suspected cases in detail. The system is currently being tested in the otorhinolaryngologist setting to carry out mass prevention via screening at a regional scale. 相似文献
140.
Arcà B Lombardo F Capurro M della Torre A Spanos L Dimopoulos G Louis C James AA Coluzzi M 《Parassitologia》1999,41(1-3):483-487
Molecular studies on the tissue-specific gene expression in the salivary glands of Anopheles gambiae may provide useful tools for the development of new strategies for the control of the most efficient malaria vector in the sub-Saharan Africa. We summarize here the results of a recent investigation focused on the isolation of secreted factors and putative receptors from the salivary glands of An. gambiae. Using the Signal Sequence Trap technique we have identified the first cDNAs specifically expressed in the An. gambiae salivary glands. Among these, four are exclusively expressed in female glands and encode factors presumably involved in blood-feeding, whereas two other cDNAs seem to be expressed both in male and in female glands and are likely implicated in sugar-feeding. Homologues of genes previously identified in the yellow fever mosquito Aedes aegypti, like the apyrase and D7, as well as novel salivary gland-specific cDNAs, were identified. The isolation and characterization of promoter sequences from the corresponding genes may prove useful for the expression of anti parasitic agents in the salivary glands of transgenic mosquitoes. 相似文献