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71.
Julien C Berthiaume L Hadj-Tahar A Rajput AH Bédard PJ Di Paolo T Julien P Calon F 《Neurochemistry international》2006,48(5):404-414
Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0 .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (P < 0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism. 相似文献
72.
Characterization of Emetic Bacillus weihenstephanensis, a New Cereulide-Producing Bacterium
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Line Thorsen Bjarne Munk Hansen Kristian Fog Nielsen Niels Bohse Hendriksen Richard Kerry Phipps Birgitte Bjrn Budde 《Applied microbiology》2006,72(7):5118-5121
Cereulide production has until now been restricted to the species Bacillus cereus. Here we report on two psychrotolerant Bacillus weihenstephanensis strains, MC67 and MC118, that produce cereulide. The strains are atypical with regard to pheno- and genotypic characteristics normally used for identification of emetic B. cereus strains. MC67 and MC118 produced cereulide at temperatures of as low as 8°C. 相似文献
73.
Rohde LA Ahring PK Jensen ML Nielsen EØ Peters D Helgstrand C Krintel C Harpsøe K Gajhede M Kastrup JS Balle T 《The Journal of biological chemistry》2012,287(6):4248-4259
The α4β2 subtype of the nicotinic acetylcholine receptor has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of α4β2 agonists is lacking. Using binding experiments, electrophysiology and x-ray crystallography we have investigated a consecutive series of five prototypical pyridine-containing agonists derived from 1-(pyridin-3-yl)-1,4-diazepane. A correlation between binding affinities at α4β2 and the acetylcholine-binding protein from Lymnaea stagnalis (Ls-AChBP) confirms Ls-AChBP as structural surrogate for α4β2 receptors. Crystal structures of five agonists with efficacies at α4β2 from 21-76% were determined in complex with Ls-AChBP. No variation in closure of loop C is observed despite large efficacy variations. Instead, the efficacy of a compound appears tightly coupled to its ability to form a strong intersubunit bridge linking the primary and complementary binding interfaces. For the tested agonists, a specific halogen bond was observed to play a large role in establishing such strong intersubunit anchoring. 相似文献
74.
75.
Breiting LB Henriksen TF Kalialis LV Gramkow C Høyer AP 《Plastic and reconstructive surgery》2012,130(2):273-281
76.
77.
Line Blander Reinhardt David Pisinger 《Flexible Services and Manufacturing Journal》2012,24(3):349-374
The network design problem in liner shipping is of increasing importance in a strongly competitive market where potential cost reductions can influence market share and profits significantly. In this paper the network design and fleet assignment problems are combined into a mixed integer linear programming model minimizing the overall cost. To better reflect the real-life situation we take into account the cost of transhipment, a heterogeneous fleet, route dependent capacities, and butterfly routes. To the best of our knowledge it is the first time an exact solution method to the problem considers transhipment cost. The problem is solved with branch-and-cut using clover and transhipment inequalities. Computational results are reported for instances with up to 15 ports. 相似文献
78.
79.
The Revised Classification of Eukaryotes 总被引:1,自引:0,他引:1
Sina M. Adl Alastair G. B. Simpson Christopher E. Lane Julius Lukeš David Bass Samuel S. Bowser Matthew W. Brown Fabien Burki Micah Dunthorn Vladimir Hampl Aaron Heiss Mona Hoppenrath Enrique Lara Line le Gall Denis H. Lynn Hilary McManus Edward A. D. Mitchell Sharon E. Mozley‐Stanridge Laura W. Parfrey Jan Pawlowski Sonja Rueckert Laura Shadwick Conrad L. Schoch Alexey Smirnov Frederick W. Spiegel 《The Journal of eukaryotic microbiology》2012,59(5):429-514
This revision of the classification of eukaryotes, which updates that of Adl et al. [J. Eukaryot. Microbiol. 52 (2005) 399], retains an emphasis on the protists and incorporates changes since 2005 that have resolved nodes and branches in phylogenetic trees. Whereas the previous revision was successful in re‐introducing name stability to the classification, this revision provides a classification for lineages that were then still unresolved. The supergroups have withstood phylogenetic hypothesis testing with some modifications, but despite some progress, problematic nodes at the base of the eukaryotic tree still remain to be statistically resolved. Looking forward, subsequent transformations to our understanding of the diversity of life will be from the discovery of novel lineages in previously under‐sampled areas and from environmental genomic information. 相似文献
80.
Kristensen LH Nielsen AL Helgstrand C Lees M Cloos P Kastrup JS Helin K Olsen L Gajhede M 《The FEBS journal》2012,279(11):1905-1914
Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2-specific lysine demethylase belonging to the JmjC domain-containing family of histone demethylases (JHDMs). Several studies have linked KDM5B to breast, prostate and skin cancer, highlighting its potential as a drug target. However, most inhibitor studies have focused on other JHDMs, and inhibitors for KDM5B remain to be explored. Here, we report the expression, purification and characterization of the catalytic core of recombinant KDM5B (ccKDM5B, residues 1-769). We show that ccKDM5B, recombinantly expressed in insect cells, demethylates H3K4me3 and H3K4me2 in vitro. The kinetic characterization showed that ccKDM5B has an apparent Michaelis constant (K(m) (app) ) value of 0.5 μm for its trimethylated substrate H3(1-15)K4me3, a considerably increased apparent substrate affinity than reported for related HDMs. Despite the presence of a PHD domain, the catalytic activity was not affected by additional methylation at the H3K9 position, suggesting that in vitro chromatin cross-talk between H3K4 and H3K9 does not occur for ccKDM5B. Inhibition studies of ccKDM5B showed both in vitro and in cell inhibition of ccKDM5B by 2,4-pyridinedicarboxylic acid (2,4-PDCA) with a potency similar to that reported for the HDM KDM4C. Structure-guided sequence alignment indicated that the binding mode of 2,4-PDCA is conserved between KDM4A/C and KDM5B. 相似文献