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211.
Erin Milner William McCalmont Jayendra Bhonsle Diana Caridha Dustin Carroll Sean Gardner Lucia Gerena Montip Gettayacamin Charlotte Lanteri ThuLan Luong Victor Melendez Jay Moon Norma Roncal Jason Sousa Anchalee Tungtaeng Peter Wipf Geoffrey Dow 《Bioorganic & medicinal chemistry letters》2010,20(4):1347-1351
Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood–brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure–activity relationship for this library of quinoline methanols. 相似文献
212.
Andrea F. Moon Geoffrey A. Mueller Xuejun Zhong Lars C. Pedersen 《Protein science : a publication of the Protein Society》2010,19(5):901-913
Protein crystallographers are often confronted with recalcitrant proteins not readily crystallizable, or which crystallize in problematic forms. A variety of techniques have been used to surmount such obstacles: crystallization using carrier proteins or antibody complexes, chemical modification, surface entropy reduction, proteolytic digestion, and additive screening. Here we present a synergistic approach for successful crystallization of proteins that do not form diffraction quality crystals using conventional methods. This approach combines favorable aspects of carrier‐driven crystallization with surface entropy reduction. We have generated a series of maltose binding protein (MBP) fusion constructs containing different surface mutations designed to reduce surface entropy and encourage crystal lattice formation. The MBP advantageously increases protein expression and solubility, and provides a streamlined purification protocol. Using this technique, we have successfully solved the structures of three unrelated proteins that were previously unattainable. This crystallization technique represents a valuable rescue strategy for protein structure solution when conventional methods fail. 相似文献
213.
Thuy-Ai Nguyen Scott D. Slattery Sung-Hwan Moon Yolanda F. Darlington Xiongbin Lu Lawrence A. Donehower 《DNA Repair》2010,9(7):813-823
Nucleotide excision repair (NER) is the only mechanism in humans to repair UV-induced DNA lesions such as pyrimidine (6-4) pyrimidone photoproducts and cyclobutane pyrimidine dimers (CPDs). In response to UV damage, the ataxia telangiectasia mutated and Rad3-related (ATR) kinase phosphorylates and activates several downstream effector proteins, such as p53 and XPA, to arrest cell cycle progression, stimulate DNA repair, or initiate apoptosis. However, following the completion of DNA repair, there must be active mechanisms that restore the cell to a prestressed homeostatic state. An important part of this recovery must include a process to reduce p53 and NER activity as well as to remove repair protein complexes from the DNA damage sites. Since activation of the damage response occurs in part through phosphorylation, phosphatases are obvious candidates as homeostatic regulators of the DNA damage and repair responses. Therefore, we investigated whether the serine/threonine wild-type p53-induced phosphatase 1 (WIP1/PPM1D) might regulate NER. WIP1 overexpression inhibits the kinetics of NER and CPD repair, whereas WIP1 depletion enhances NER kinetics and CPD repair. This NER suppression is dependent on WIP1 phosphatase activity, as phosphatase-dead WIP1 mutants failed to inhibit NER. Moreover, WIP1 suppresses the kinetics of UV-induced damage repair largely through effects on NER, as XPD-deficient cells are not further suppressed in repairing UV damage by overexpressed WIP1. Wip1 null mice quickly repair their CPD and undergo less UV-induced apoptosis than their wild-type counterparts. In vitro phosphatase assays identify XPA and XPC as two potential WIP1 targets in the NER pathway. Thus WIP1 may suppress NER kinetics by dephosphorylating and inactivating XPA and XPC and other NER proteins and regulators after UV-induced DNA damage is repaired. 相似文献
214.
Jeong-Whun Kim Gwang Lee Seung-Min Moon Myung-June Park Sung Kyu Hong Young-Hwan Ahn Kyoung-Rae Kim Man-Jeong Paik 《Metabolomics : Official journal of the Metabolomic Society》2010,6(2):202-206
Metabolomic analysis of urinary amino acids (AAs) from patients with bladder cancer was performed by gas chromatography–mass
spectrometry. The β-aminoisobutyric acid (P < 0.05) and pyroglutamic acid (P < 0.03) levels among 21 AAs had relatively low P-values in the cancer group. The distorted star pattern of the cancer group was different from the heneicosagonal shape of
the control mean. The present metabolomic screening combined with star pattern recognition method as clinical monitoring tool
might be useful for the visual discrimination of bladder cancer group from normal group. 相似文献
215.
216.
Min Kyoung Jang Sae-Hoon Kim Ki-Young Lee Keun Ae Moon Yun Jeong Bae Hee-Bom Moon 《Biochemical and biophysical research communications》2010,393(1):137-1479
Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as asthma and Chronic obstructive pulmonary disease (COPD). Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292 carcinoma cells were transfected with specific siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with hydrogen peroxide (H2O2), and Mucin 5AC(MUC5AC) gene expression and mucin production were determined. Activation of p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated. N-acetylcysteine (NAC) was employed to determine whether antioxidants could block MUC5AC production. To establish the precise role of p38, mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H2O2, compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of p38 MAPK led to suppression of MUC5AC mRNA expression. Notably, mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway mucin production through regulating oxidative stress. 相似文献
217.
Byeong Cheol Moon Byung Kil Choo Myeong Sook Cheon Taesook Yoon Yunui Ji Bo Bae Kim A Young Lee Ho Kyoung Kim 《Plant biotechnology reports》2010,4(1):1-7
Definitive identification of original plant species is important for standardizing herbal medicine. The herbal medicines Cynanchi
Wilfordii Radix (Baekshuoh in Korean and Beishuwu in Chinese) and Polygoni Multiflori Radix (Hashuoh in Korean and Heshuwu in Chinese) are often misidentified in the Korean herbal market due to morphological similarities and similar names. Therefore,
we developed a reliable molecular marker for the identification of Cynanchi Wilfordii Radix and Polygoni Multiflori Radix.
We used random amplified polymorphic DNA (RAPD) analysis of three plant species, Polygoni multiflorum, Cynanchum wilfordii, and Cynanchum auriculatum, to obtain several species-specific RAPD amplicons. From nucleotide sequences of these RAPD amplicons, we developed six sequence
characterized amplification region (SCAR) markers for distinguishing Polygoni Multiflori Radix and Cynanchi Wilfordii Radix.
Furthermore, we established SCAR markers for the simultaneous discrimination of the three species within a single reaction
by using multiplex-PCR. These SCAR markers can be used for efficient and rapid authentication of these closely related species,
and will be useful for preventing the distribution of adulterants. 相似文献
218.
Martín Mata-Rosas Rosario J. Baltazar-García Pamela Moon Peter Hietz Víctor E. Luna-Monterrojo 《Plant biotechnology reports》2010,4(2):157-163
A protocol for in vitro propagation from pseudobulb sections of Lycaste armomatica (Graham ex Hook) Lindl., an ornamental and fragrant orchid, was developed. The effect of four cytokinins: kinetin (K), meta-topolin
(mT), N
6-benzyladenine (BA), and thidiazuron (TDZ), in equimolar concentrations, was investigated. Shoot formation from apical and
basal pseudobulb sections was obtained in all treatments. A few medial sections cultured in media supplemented with BA formed
protocorm-like bodies. Shoot formation was greater from the basal section than the apical, and mainly occurred in explants
cultured in media containing TDZ. The highest average numbers of shoots per explant were achieved from basal sections cultured
in media supplemented with TDZ at 4.4, 8.87 and 2.2 μM, forming on average 9.9, 8.6 and 7.3 shoots per explant, respectively.
Since the medial pseudobulb section was the worst explant for propagation of L. aromatica, we recommend that pseudobulbs be divided into two sections; the basal half should be cultured in MS medium supplemented
with TDZ at 4.4 μM and the apical half with TDZ at 2.2 μM. Subculturing individual shoots in MS medium without plant growth
regulators allows further development and rooting. A survival rate of more than 90% under greenhouse conditions was achieved.
This research represents a direct contribution to the conservation and sustainable use of this valuable natural resource. 相似文献
219.
A case of tick bite was found in the inguinal region of a 74-year-old Korean woman. She was attacked by the tick while working in her vegetable garden in the vicinity of mountain located in Suncheon City, the southern coastal area of the Korean Peninsula. On admission she complained of mild discomfort and itching around the bite area. The causative tick was 23 mm long and had slender pedipalps. The scutum was quite ornate and had eyes at the edge. The genital aperture was located anterior to the level of the coxa II. The spiracular plate was comma-shaped and the anus was surrounded posteriorly by the anal groove. The coxa I had subequal 2 spurs; the external one slightly larger. The spur of coxa IV was slightly longer than those of coxae II and III. The tarsus IV had 2 distinct subapical ventral spurs. It was identified as the fully engorged adult female of Amblyomma testudinarium. This is the first human case of Amblyomma bite in Korea. 相似文献
220.
Choi KM Kim JY Moon SU Lee HW Sattabongkot J Na BK Kim DW Suh EJ Kim YJ Cho SH Lee HS Rhie HG Kim TS 《The Korean journal of parasitology》2010,48(4):319-324
A family of calcium-dependent protein kinases (CDPKs) is a unique enzyme which plays crucial roles in intracellular calcium signaling in plants, algae, and protozoa. CDPKs of malaria parasites are known to be key regulators for stage-specific cellular responses to calcium, a widespread secondary messenger that controls the progression of the parasite. In our study, we identified a gene encoding Plasmodium vivax CDPK4 (PvCDPK4) and characterized its molecular property and cellular localization. PvCDPK4 was a typical CDPK which had well-conserved N-terminal kinase domain and C-terminal calmodulin-like structure with 4 EF hand motifs for calcium-binding. The recombinant protein of EF hand domain of PvCDPK4 was expressed in E. coli and a 34 kDa product was obtained. Immunofluorescence assay by confocal laser microscopy revealed that the protein was expressed at the mature schizont of P. vivax. The expression of PvCDPK4-EF in schizont suggests that it may participate in the proliferation or egress process in the life cycle of this parasite. 相似文献