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991.
Balunas MJ Jones WP Chin YW Mi Q Farnsworth NR Soejarto DD Cordell GA Swanson SM Pezzuto JM Chai HB Kinghorn AD 《化学与生物多样性》2006,3(8):897-915
In an attempt to determine the relationships between the plant profiles (country of collection, taxonomy, plant part) and the compound classes isolated with cytotoxic activity against a panel of human tumor cell lines, the data compiled from a 15-year anticancer drug-discovery project were subjected to an analysis of variance (ANOVA). The results indicate significant trends in cytotoxic activity relative to collection location, taxonomy, plant part, and compound classes isolated. Plant collections were made in tropical forests in six countries, with collections from Ecuador resulting in higher activity than those from Indonesia and Peru. Interestingly, collections from Florida were not statistically different than those from the countries with higher biodiversity. One hundred and forty-five families were represented in the collections, with the Clusiaceae, Elaeocarpaceae, Meliaceae, and Rubiaceae having low ED50 (half maximal effective dose) values. Especially active genera included Aglaia, Casearia, Exostema, Mallotus, and Trichosanthes. Roots and below-ground plant materials were significantly more active than above-ground materials. Cucurbitacins, flavaglines, anthraquinones, fatty acids, tropane alkaloids, lignans, and sesquiterpenoids were significantly more active than xanthones and oligorhamnosides. The results from this study should serve as a guide for future plant collection endeavors for anticancer drug discovery. 相似文献
992.
The histamine H3 receptor is an attractive G protein-coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a role in cognitive and homeostatic functions. Drug discovery efforts by numerous pharmaceutical companies have focused on the preclinical development of H3 receptor antagonists for the potential treatment of attention-deficit hyperactivity disorder, dementias, schizophrenia, as well as obesity and sleep disorders. This receptor exhibits molecular, pharmacological, and functional heterogeneity that informs the preclinical development of effective antagonists. Herein, we describe the biological and chemical implications for developing H3 receptor antagonists and their therapeutic potential as disclosed through animal models of cognition, sleep, and obesity. 相似文献
993.
Local flexibility in molecular function paradigm 总被引:1,自引:0,他引:1
Bhalla J Storchan GB MacCarthy CM Uversky VN Tcherkasskaya O 《Molecular & cellular proteomics : MCP》2006,5(7):1212-1223
994.
Miller LA Romitti PA Cunniff C Druschel C Mathews KD Meaney FJ Matthews D Kantamneni J Feng ZF Zemblidge N Miller TM Andrews J Fox D Ciafaloni E Pandya S Montgomery A Kenneson A 《Birth defects research. Part A, Clinical and molecular teratology》2006,76(11):793-797
BACKGROUND: This report focuses on the common protocol developed by the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) for population-based surveillance of Duchenne and Becker muscular dystrophy (DBMD) among 4 states (Arizona, Colorado, Iowa, and New York). METHODS: The network sites have developed a case definition and surveillance protocol along with software applications for medical record abstraction, clinical review, and pooled data. Neuromuscular specialists at each site review the pooled data to determine if a case meets the case criteria. Sources of potential cases of DBMD include neuromuscular specialty clinics, service sites for children with special healthcare needs, and hospital discharge databases. Each site also adheres to a common information assurance protocol. RESULTS: A population-based surveillance system for DBMD was created and implemented in participating states. CONCLUSIONS: The development and implementation of the population-based system will allow for the collection of information that is intended to provide a greater understanding of DBMD prevalence and health outcomes. 相似文献
995.
996.
Robert Geoffrey Harcourt Emma Turner Ailsa Hall Joseph R. Waas Mark Hindell 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(2):147-154
Physiological stress responses to capture may be an indicator of welfare challenges induced by animal handling. Simultaneously,
blood chemistry changes induced by stress responses may confound experimental design by interacting with the biological parameters
being measured. Cortisol elevation is a common indicator of stress responses in mammals and reproductive condition can profoundly
influence endocrine response. We measured changes in blood cortisol and testosterone induced by handling reproductively active
male Weddell seals (Leptonychotes weddellii) early and late in the breeding season. Weddell seals have the highest resting cortisol levels of all mammals yet showed
a clear, prolonged elevation in cortisol in response to capture. Responses were similar when first caught and when caught
a second time, later in the breeding season. Baseline testosterone levels declined over the breeding season but were not altered
by capture. Administering a light dose of diazepam significantly ameliorated the cortisol response of handled animals without
affecting testosterone levels. This may be an effective way of reducing acute capture stress responses. Male breeding success
in years males were handled was no different to the years they were not, despite the acute capture response, suggesting no
long-term impact of handling on male reproductive output. 相似文献
997.
Graham D. Raby Lee F. G. Gutowsky Michael G. Fox 《Environmental Biology of Fishes》2010,89(2):143-150
We assessed density, gut fullness and prey composition of round goby (Neogobius melanostomus) from three areas in the Trent River (Ontario) representing areas of initial introduction and subsequent expansion. Round
goby had been present at the area of original introduction since 2003, and by 2007/2008, their range had expanded upstream
and downstream into the outermost reaches sampled in the study. Catch per unit angling effort in nearshore sites indicated
that round goby density in the area of original introduction was more than double their density in the upstream expansion
area and nearly three times the density in the downstream expansion area. Gut fullness index was lower in gobies from the
area of original introduction than for those at the upstream and downstream edges of their expanded range. The most dramatic
difference in diet composition was with dreissenids, where large gobies (≥70 mm) occupying the area of original introduction
had almost no dreissenid biomass in their guts, whereas dreissenids were the predominant prey type in gobies occupying the
two expansion areas. Post-hoc zebra mussel density in the area of original introduction was an order of magnitude lower than
in the two expansion areas which, combined with the differences in stomach fullness and prey composition, suggest that local,
density-related reduction of this prey type was occurring in the river. 相似文献
998.
Geoffrey E. Hinton 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1537):177-184
One of the central problems in computational neuroscience is to understand how the object-recognition pathway of the cortex learns a deep hierarchy of nonlinear feature detectors. Recent progress in machine learning shows that it is possible to learn deep hierarchies without requiring any labelled data. The feature detectors are learned one layer at a time and the goal of the learning procedure is to form a good generative model of images, not to predict the class of each image. The learning procedure only requires the pairwise correlations between the activations of neuron-like processing units in adjacent layers. The original version of the learning procedure is derived from a quadratic ‘energy’ function but it can be extended to allow third-order, multiplicative interactions in which neurons gate the pairwise interactions between other neurons. A technique for factoring the third-order interactions leads to a learning module that again has a simple learning rule based on pairwise correlations. This module looks remarkably like modules that have been proposed by both biologists trying to explain the responses of neurons and engineers trying to create systems that can recognize objects. 相似文献
999.
Michael L. Ginger Geoffrey I. McFadden Paul A. M. Michels 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1541):831-845
Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation. 相似文献
1000.
Geoffrey A. Mueller Rajendrakumar A. Gosavi Joseph M. Krahn Lori L. Edwards Matthew J. Cuneo Jill Glesner Anna Pomés Martin D. Chapman Robert E. London Lars C. Pedersen 《The Journal of biological chemistry》2010,285(33):25394-25401
Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of ∼3000 Å3 that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses. 相似文献