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Pamela J. Weathers Shereen Elkholy Kristin K. Wobbe 《In vitro cellular & developmental biology. Plant》2006,42(4):309-317
Summary Artemisinin is a sesquiterpene lactone isolated from the aerial parts of Artemisia annua L. plants. Besides being currently the best therapeutic against both drug-resistant and cerebral malaria-causing strains
of Plasmodium falciparum, the drug has also been shown to be effective against other infections diseases including schistosomiasis and hepatitis.
More recently, it has also been shown to be effective against numerous types of tumors. Although chemical synthesis of artemisinin
is possible, it is not economically feasible. The relatively low yield (0.01–0.8%) of artemisinin in A. annua is a further serious limitation to the commercialization of the drug. Therffore, the enhanced production of artemisinin either
in cell/tissue culture or in the whole plant of A. annua is highly desirable. A better understanding of the biochemical pathway leading to the synthesis of artemisinin and its regulation
by both exogenous and endogenous factors is essential for facilitating increased yield. Two genes of the artemisinin biosynthetic
pathway have now been identified. This critical review covers recent developments related to the biosynthesis of this important
compound and related terpenoids, their regulation, and the production of these compounds both in vitro and in whole plants. 相似文献
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Xunjun Xiao Michael R. Ferguson Kelsey E. Magee Pamela D. Hale Yan Wang Mark E. Lowe 《Journal of lipid research》2013,54(2):514-521
Colipase is essential for efficient fat digestion. An arginine-to-cysteine polymorphism at
position 92 of colipase (Arg92Cys) associates with an increased risk for developing type-2 diabetes
through an undefined mechanism. To test our hypothesis that the extra cysteine increases colipase
misfolding, thereby altering its intracellular trafficking and function, we expressed Cys92 colipase
in HEK293T cells. Less Cys92 colipase is secreted and more is retained intracellularly in an
insoluble form compared with Arg92 colipase. Nonreducing gel electrophoresis suggests the folding of
secreted Cys92 colipase differs from Arg92 colipase. Cys92 colipase misfolding does not trigger the
unfolded protein response (UPR) or endoplasmic reticulum (ER) stress. The ability of secreted Cys92
colipase to stimulate pancreatic triglyceride lipase (PTL) is reduced with all substrates tested,
particularly long-chain triglycerides. The reaction of Cys92 colipase with triolein and Intralipid
has a much longer lag time, reflecting decreased ability to anchor PTL on those substrates. Our data
predicts that humans with the Arg92Cys substitution will secrete less functional colipase into the
duodenum and have less efficient fat digestion. Whether inefficient fat digestion or another
property of colipase contributes to the risk for developing diabetes remains to be clarified. 相似文献
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Jean-Baptiste Ramond Pamela J. Welz Marla I. Tuffin Stephanie G. Burton Don A. Cowan 《Microbial ecology》2013,66(3):563-570
Agri effluents such as winery or olive mill wastewaters are characterized by high phenolic concentrations. These compounds are highly toxic and generally refractory to biodegradation. Biological sand filters (BSFs) represent inexpensive, environmentally friendly, and sustainable wastewater treatment systems which rely vastly on microbial catabolic processes. Using denaturing gradient gel electrophoresis and terminal-restriction fragment length polymorphism, this study aimed to assess the impact of increasing concentrations of synthetic phenolic-rich wastewater, ranging from 96 mg L?1 gallic acid and 138 mg L?1 vanillin (i.e., a total chemical oxygen demand (COD) of 234 mg L?1) to 2,400 mg L?1 gallic acid and 3,442 mg L?1 vanillin (5,842 mg COD L?1), on bacterial communities and the specific functional diazotrophic community from BSF mesocosms. This amendment procedure instigated efficient BSF phenolic removal, significant modifications of the bacterial communities, and notably led to the selection of a phenolic-resistant and less diverse diazotrophic community. This suggests that bioavailable N is crucial in the functioning of biological treatment processes involving microbial communities, and thus that functional alterations in the bacterial communities in BSFs ensure provision of sufficient bioavailable nitrogen for the degradation of wastewater with a high C/N ratio. 相似文献
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Zoe Barclay Louise Dickson Derek Robertson Melanie Johnson Pamela Holland Roberta Rosie Liting Sun Helen Jerina Eve Lutz Sue Fleetwood-Walker Rory Mitchell 《Cellular signalling》2013,25(4):814-821
The 5-HT2A receptor (5-HT2AR) is implicated in psychotropic changes within the central nervous system (CNS). A number of polymorphisms have been reported in the 5-HT2AR gene; one of these results in a non-synonymous change, H452Y, in the carboxy-terminal tail of the receptor protein. The minor allele (9% occurrence) has been statistically associated with CNS dysfunction such as impaired memory processing and resistance to neuroleptic treatment in schizophrenic patients. We investigated the impact of H452Y mutation of the 5-HT2AR expressed in COS7 cells on distinctly coupled intracellular signalling pathways from the receptor, focusing on the heterotrimeric G protein-independent phospholipase D (PLD) pathway, compared to the conventional Gq/11-linked phospholipase C (PLC) pathway. The H452Y mutation selectively attenuated PLD signalling, which as in the wild-type receptor, was mediated by a molecular complex involving PLD1 docked to the receptor's carboxy-terminal tail domain. Co-immunoprecipitation and GST-fusion protein experiments revealed that the H452Y mutation selectively reduced PLD1 binding to the receptor. Experiments with blocking peptides to mimic short sections of the 5-HT2AR tail sequence revealed that the peptide spanning residue 452 strongly reduced PLD but not PLC responses of the receptor. Similar observations were made when assessing both PLD responses and PLD-dependent cellular proliferation elicited by activation of 5-HT2ARs natively expressed in MCF-7 cells. Overall these findings indicate that the H452Y polymorphic variant of the 5-HT2AR displays selective disruption of its PLD signalling pathway. This may potentially play a role in the CNS dysfunction associated with the H452Y allele of the 5-HT2AR. 相似文献
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Kevin Anderson Yi Chen Zhi Chen Romyr Dominique Kelli Glenn Yang He Cheryl Janson Kin-Chun Luk Christine Lukacs Ann Polonskaia Qi Qiao Aruna Railkar Pamela Rossman Hongmao Sun Qing Xiang Masha Vilenchik Peter Wovkulich Xiaolei Zhang 《Bioorganic & medicinal chemistry letters》2013,23(24):6610-6615
DYRK1B is a kinase over-expressed in certain cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented. 相似文献