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排序方式: 共有232条查询结果,搜索用时 31 毫秒
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Abstract Pseudomonas fluorescens appeared to circumvent the challenge imposed by millimolar amounts of metals (5 mM Al3+ , 5 mM Fe3+ , 2 mM Ca2+ , 1 mM Ga3+ and 3 mM Zn2+ ) by the formation of phosphatidylethanolamine. This lipid moiety constituted an important organic component of an insoluble gelatinous residue in which most of the test metals were immobilized at stationary phase of growth. Ultracentrifugation and dialysis experiments showed that the metals were associated with phosphatidylethanolamine from early stages of growth. Transmission electron microscopy revealed metal rich bodies in the cytoplasm prior to their secretion in the spent fluid. These results demonstrate a role of phosphatidylethanolamine in multiple-metal homeostasis. 相似文献
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Qi J Lang W Geisler JG Wang P Petrounia I Mai S Smith C Askari H Struble GT Williams R Bhanot S Monia BP Bayoumy S Grant E Caldwell GW Todd MJ Liang Y Gaul MD Demarest KT Connelly MA 《Journal of lipid research》2012,53(6):1106-1116
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride (TG) synthesis. There are two isoforms, DGAT1 and DGAT2, with distinct protein sequences and potentially different physiological functions. To date, the ability to determine clear functional differences between DGAT1 and DGAT2, especially with respect to hepatic TG synthesis, has been elusive. To dissect the roles of these two key enzymes, we pretreated HepG2 hepatoma cells with (13)C(3)-D(5)-glycerol or (13)C(18)-oleic acid, and profiled the major isotope-labeled TG species by liquid chromatography tandem mass spectrometry. Selective DGAT1 and DGAT2 inhibitors demonstrated that (13)C(3)-D(5)-glycerol-incorporated TG synthesis was mediated by DGAT2, not DGAT1. Conversely, (13)C(18)-oleoyl-incorporated TG synthesis was predominantly mediated by DGAT1. To trace hepatic TG synthesis and VLDL triglyceride (VLDL-TG) secretion in vivo, we administered D(5)-glycerol to mice and measured plasma levels of D(5)-glycerol-incorporated TG. Treatment with an antisense oligonucleotide (ASO) to DGAT2 led to a significant reduction in D(5)-glycerol incorporation into VLDL-TG. In contrast, the DGAT2 ASO had no effect on the incorporation of exogenously administered (13)C(18)-oleic acid into VLDL-TG. Thus, our results indicate that DGAT1 and DGAT2 mediate distinct hepatic functions: DGAT2 is primarily responsible for incorporating endogenously synthesized FAs into TG, whereas DGAT1 plays a greater role in esterifying exogenous FAs to glycerol. 相似文献
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Kumar AB Anderson JM Melendez AL Manetsch R 《Bioorganic & medicinal chemistry letters》2012,22(14):4740-4744
A library of 1,3-disubstituted 2-propanols was synthesized and evaluated as low molecular weight probes for β-secretase inhibition. By screening a library of 121 1,3-disubstituted 2-propanol derivatives, we identified few compounds inhibiting the enzyme at low micromolar concentrations. The initial hits were optimized to yield a potent BACE-1 inhibitor exhibiting an IC(50) constant in the nanomolar range. Exploration of the pharmacological properties revealed that these small molecular inhibitors possessed a high selectivity over cathepsin D and desirable physicochemical properties beneficial to cross the blood-brain barrier. 相似文献
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Fluckey JD Knox M Smith L Dupont-Versteegden EE Gaddy D Tesch PA Peterson CA 《American journal of physiology. Endocrinology and metabolism》2006,290(6):E1205-E1211
Recent studies have implicated the mTOR-signaling pathway as a primary component for muscle growth in mammals. The purpose of this investigation was to examine signaling pathways for muscle protein synthesis after resistance exercise. Sprague-Dawley rats (male, 6 mo old) were assigned to either resistance exercise or control groups. Resistance exercise was accomplished in operantly conditioned animals using a specially designed flywheel apparatus. Rats performed two sessions of resistance exercise, separated by 48 h, each consisting of 2 sets of 25 repetitions. Sixteen hours after the second session, animals were killed, and soleus muscles were examined for rates of protein synthesis with and without insulin and/or rapamycin (mTOR inhibitor) and/or PD-098059 (PD; MEK kinase inhibitor). Results of this study demonstrated that rates of synthesis were higher (P < 0.05) with insulin after exercise compared with without insulin, or to control muscles, regardless of insulin. Rapamycin lowered (P < 0.05) rates of synthesis in controls, with or without insulin, and after exercise without insulin. However, insulin was able to overcome the inhibition of rapamycin after exercise (P < 0.05). PD had no effect on protein synthesis in control rats, but the addition of PD to exercised muscle resulted in lower (P < 0.05) rates of synthesis, and this inhibition was not rescued by insulin. Western blot analyses demonstrated that the inhibitors used in the present study were selective and effective for preventing activation of specific signaling proteins. Together, these results suggest that the insulin-facilitated increase of muscle protein synthesis after resistance exercise requires multiple signaling pathways. 相似文献
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BACKGROUND: Cytologic diagnosis of malignant fibrous histiocytoma can be problematic, as these neoplasms are known to mimic multiple other conditions. CASE: A fine needle aspirate from a 60-year-old woman was diagnosed at 2 institutions as medullary carcinoma of the breast. The patient received neo-adjuvant chemoradiotherapy before the tumor war excised. Gross pathologic examination and histomorphology on routine staining were compatible with the cytologic diagnosis. The accurate diagnosis of pleomorphic-storiform-type malignant fibrous histiocytoma was a surprise and was established with immunocytochemical stains. In retrospect, it was thought that clinical and radiologic overlap, creating a high index of suspicion for a breast neoplasm and compounding the cytologic appearance of a medullary carcinoma with spindle cell metaplasia and syncytial cells, was responsible for the error. CONCLUSION: This case highlights a potential cytodiagnostic pitfall and the importance of establishing a definitive tissue diagnosis in the face of equivocal cytologic findings. 相似文献
59.
We assessed effects of groundwater pumping to elevate lake levels on lake water chemistry and fish population metrics at seven
Florida lakes. Following groundwater pumping, lake level fluctuation was reduced and lake water samples increased in mean
pH, total alkalinity, total phosphorus, chloride and Secchi depth compared to historical means, indicating a close resemblance
to the chemistry of aquifer water in the region. Fish community metrics from the augmented lakes were compared to 36 non-augmented
lakes in Florida. The mean values for catch per unit effort, species richness and biomass of harvestable fishes, determined
by electrofishing, were lower in augmented lakes compared to non-augmented lakes. Canonical correspondence analysis (CCA)
indicated a high probability of a low abundance of individual species in augmented lakes compared to a majority of non-augmented
lakes. The augmented lake with the lowest pumping rate exhibited less of a shift in limnological variables from historical
values, and had fish population characteristics more closely resembling those of non-augmented lakes. Thus, reduced volumes
of groundwater introduction could lower impacts to limnological and fish population characteristics. Augmentation allows for
lakes to be utilized for recreational activities, and without augmentation some lakes in central Florida would likely go dry
due to groundwater withdrawals for water supply. Therefore, allowing more natural water level fluctuations and possible reductions
in total pumpage are recommended to reduce impacts to limnological and fish population characteristics, while still allowing
sufficient groundwater pumping to preserve lake habitats. 相似文献
60.
Jun Pu Anthony F. Kreft Suzan H. Aschmies Kevin P. Atchison Joshua Berkowitz Thomas J. Caggiano Micheal Chlenov George Diamantidis Boyd L. Harrison Yun Hu Donna Huryn J. Steven Jacobsen Mei Jin Kerri Lipinski Peimin Lu Robert L. Martone Koi Morris June Sonnenberg-Reines Dave R. Riddell Joan Sabalski Lynn Resnick 《Bioorganic & medicinal chemistry》2009,17(13):4708-4717
γ-Secretase inhibitors have been shown to reduce the production of β-amyloid, a component of the plaques that are found in brains of patients with Alzheimer’s disease. A novel series of heterocyclic sulfonamide γ-secretase inhibitors that reduce β-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative γ-secretase substrate. 相似文献