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991.
The epidermal growth factor receptor (EGFR) is a well-established target for cancer treatment. EGFR tyrosine kinase (TK) inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK), a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R]), or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R]) in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv) phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor) and U0126 (a MEK inhibitor) were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs. 相似文献
992.
Chunbo Hao Hongxun Zhang Richard Haas Zhihui Bai Baoguo Zhang 《World journal of microbiology & biotechnology》2007,23(1):15-21
A sediment sample (pH 2.5) was collected at an acid mine drainage site in Anhui, China. The present acidophilic microbial
community in the sediment was studied with a 16S rRNA gene clone library. Small-subunit rRNA genes were PCR amplified, cloned
and screened by amplified rDNA restriction analysis (ARDRA). Subsequently, 10 different clones were identified and they were
affiliated with Acidobacteria, β/γ-Proteobacteria, δ-Proteobacteria, Nitrospira, Candidate division TM7, and Low G + C Gram-positives. Phylogenetic analysis of 16S rRNA gene sequences revealed a diversity
of acidophiles in the sediment that were mostly novel. Unexpectedly, 16S rRNA gene sequences affiliated with δ-Proteobacteria were found to constitute more than 60% of clone library. To our knowledge, this is the first occasion that bacteria of δ-Proteobacteria have been found dominant in the acidic habitat. Anaerobic sulfate- or metal reduction is the predominant physiological trait
of bacteria of this subdivision. The high sulfate, ferric iron and the presence of bioavailable carbon in the anaerobic microenvironment
may result in the dominance of bacteria of δ-Proteobacteria. 相似文献
993.
本研究用克隆的HCMV AD169株DNA片段,制备了生物素标记的DNA探针,建立了检测临床脐带血、尿标本中HCMV DNA的核酸探针杂交方法。该探针可测出100pg同源DNA,不与人胚肺细胞、Hep-2细胞DNA以及其他疱疹病毒的DNA发生反应。用核酸杂交方法检测了30份脐带血标本,有11例阳性,阳性率为33%。10例孕妇尿标本中,3例阳性,阳性率为30%。检测结果表明:我们建立的生物素标记的HCMV DNA探针的点杂交法,具有高度的特异性、敏感性,比分离病毒法更迅速,可用于HCMV感染的临床标本的病毒核酸检测。 相似文献
994.
A thermophilic bacterial strain GXN151 which could degrade Avicel efficiently was isolated and identified as Bacillus licheniformis. A genomic library of GXN151 was constructed and two novel endoglucanase genes designated cel9A and cel12A were isolated by screening the library on carboxylmethyl cellulase indicator plates. The analysis of amino acid sequences deduced from the genes indicated that Cel9A consisted of a catalytic domain belonging to glycosyl hydrolase family 9, a linker domain, and a carbohydrate binding module family 3 from N-terminal to C-terminal; Cel12A had only one catalytic domain belonging to glycosyl hydrolase family 12. The combinations of Cel9A and Cel12A produced by the recombinant E. coli exhibited synergistic action against substrates of carboxylmethyl cellulose as well as Avicel. 相似文献
995.
Sediment quality criteria in use around the world 总被引:20,自引:0,他引:20
There have been numerous sediment quality guidelines (SQGs) developed during the past 20 years to assist regulators in dealing
with contaminated sediments. Unfortunately, most of these have been developed in North America. Traditionally, sediment contamination
was determined by assessing the bulk chemical concentrations of individual compounds and often comparing them with background
or reference values. Since the 1980s, SQGs have attempted to incorporate biological effects in their derivation approach.
These approaches can be categorized as empirical, frequency-based approaches to establish the relationship between sediment
contamination and toxic response, and theoretically based approaches that attempt to account for differences in bioavailability
through equilibrium partitioning (EqP) (i.e., using organic carbon or acid volatile sulfides). Some of these guidelines have
been adopted by various regulatory agencies in several countries and are being used as cleanup goals in remediation activities
and to identify priority polluted sites. The original SQGs, which compared bulk chemical concentrations to a reference or
to background, provided little insight into the ecosystem impact of sediment contaminants. Therefore, SQGs for individual
chemicals were developed that relied on field sediment chemistry paired with field or laboratory-based biological effects
data. Although some SQGs have been found to be relatively good predictors of significant site contamination, they also have
several limitations. False positive and false negative predictions are frequently in the 20% to 30% range for many chemicals
and higher for others. The guidelines are chemical specific and do not establish causality where chemical mixtures occur.
Equilibrium-based guidelines do not consider sediment ingestion as an exposure route. The guidelines do not consider spatial
and temporal variability, and they may not apply in dynamic or larger-grained sediments. Finally, sediment chemistry and bioavailability
are easily altered by sampling and subsequent manipulation processes, and therefore, measured SQGs may not reflect in situ
conditions. All the assessment tools provide useful information, but some (such as SQGs, laboratory toxicity and bioaccumulation,
and benthic indices) are prone to misinterpretation without the availability of specific in situ exposure and effects data.
SQGs should be used only in a “screening” manner or in a “weight-of-evidence” approach. Aquatic ecosystems (including sediments)
must be assessed in a “holistic” manner in which multiple components are assessed (e.g., habitat, hydrodynamics, resident
biota, toxicity, and physicochemistry, including SQGs) by using integrated approaches.
Received: December 26, 2000 / Accepted: December 28, 2001 相似文献
996.
Suk Hee Lee Suk Oh Young Il Kim Sang Cheol Jun Sang Sup So Hwan Gyu Kim 《Biotechnology and Bioprocess Engineering》2007,12(2):100-105
Phellinus linteus is a fungus which is found primarily in tropical regions of the Americas, Africa, and Asia.P. linteus has been used in traditional medical practice for the treatment of arthritis, liver damage and cancer. Angiogenesis is a
process that involves migration, proliferation and cell differentiation, as well as the formation of new capillary structures.
The anti-angiogenic activities evidenced by natural compounds may actually be a critical effect for the inhibition of angiogenesis-dependent
disease by these agents via the blockage of vascular development. This study assessed the effects of water extracts fromP. linteus (Phellinus extracts) on primary cultured porcine coronary artery endothelial cells (PCAECs).Phellinus extracts induced no changes in DNA synthesis or cell numbers, but inhibited the migration of PCAECs.Phellinus extracts also induced a reduction in the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results show that,
in endothelial cells,Phellinus extracts may inhibit angiogenesis by reducing levels of MMP-2 and MMP-9 secretion. 相似文献
997.
Eutrophication assessment and bioremediation strategy in a marine fish cage culture area in Nansha Bay,China 总被引:3,自引:0,他引:3
On the basis of field data measured during four cruises from January to November 2007, variations in the characteristics of
dissolved inorganic nitrogen and phosphate were analyzed in Nansha marine fish cage culture area, Ningbo City, China. Dissolved
inorganic nitrogen (DIN) was selected as the parameter to balance seaweed absorption and fish DIN production. The contents
of DIN and phosphate varied with different seasons, and eutrophication index (E) value ranged from 2.41 to 15.99, indicating serious eutrophication conditions; the annual average value of N/P of 32.95
indicates a nitrogen surplus in this system. The eutrophication condition in Nansha Bay was mainly caused by the fish cage
culture activities. Based on their biological characteristics, Laminaria and Gracilaria were selected as the bioremediation species in winter and spring and summer and autumn, respectively. The optimal co-cultivation
proportion of fish cage to Laminaria and Gracilaria in this bay was 1 cage, 450 m2 and one cage, 690 m2, respectively. 相似文献
998.
Ron Milo 《Photosynthesis research》2009,101(1):59-67
The sun’s spectrum harvested through photosynthesis is the primary source of energy for life on earth. Plants, green algae, and cyanobacteria—the major primary producers on earth—utilize reaction centers that operate at wavelengths of 680 and 700 nm. Why were these wavelengths “chosen” in evolution? This study analyzes the efficiency of light conversion into chemical energy as a function of hypothetical reaction center absorption wavelengths given the sun’s spectrum and the overpotential cost associated with charge separation. Surprisingly, it is found here that when taking into account the empirical charge separation cost the range 680–720 nm maximizes the conversion efficiency. This suggests the possibility that the wavelengths of photosystem I and II were optimized at some point in their evolution for the maximal utilization of the sun’s spectrum. 相似文献
999.
Fungal contamination is a major problem in cell culture, and the antifungal compounds currently in use can affect cultured
cells. Echinocandins are antifungal drugs that inhibit fungal cell wall synthesis by targeting an enzyme that has no counterpart
in mammalian cells. We evaluated whether the echinocandin caspofungin affected the growth or morphology of six murine cell
lines (a macrophage-like cell line (J774.16) and five hybridoma lines), or primary human endothelial cells. The antifungal
did not influence cellular characteristics at concentrations less than 512 μg/ml, while effectively reducing the incidence
of fungal contamination. Also, caspofungin did not affect the production of antibody by hybridoma cells, or alter the cytokine
production of J774.16 cells, although modest increases in IL-4 and IFN-γ occurred upon LPS stimulation. Hence, echinocandins
appear to be relatively non-toxic, and protect against fungal contamination in cell culture. 相似文献
1000.