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排序方式: 共有613条查询结果,搜索用时 15 毫秒
521.
Tania Muller Laurent Demizieux Stphanie Troy-Fioramonti Chlo Buch Julia Leemput Christine Belloir Jean-Paul Pais de Barros Tony Jourdan Patricia Passilly-Degrace Xavier Fioramonti Anne-Marie Le Bon Bruno Vergs Jean-Michel Robert Pascal Degrace 《International journal of molecular sciences》2022,23(6)
Targeting cannabinoid 1 receptors (CB1R) with peripherally restricted antagonists (or inverse agonists) shows promise to improve metabolic disorders associated with obesity. In this context, we designed and synthetized JM-00266, a new CB1R blocker with limited blood–brain barrier (BBB) permeability. Pharmacokinetics were tested with SwissADME and in vivo in rodents after oral and intraperitoneal administration of JM-00266 in comparison with Rimonabant. In silico predictions indicated JM-00266 is a non-brain penetrant compound and this was confirmed by brain/plasma ratios and brain uptake index values. JM-00266 had no impact on food intake, anxiety-related behavior and body temperature suggesting an absence of central activity. cAMP assays performed in CB1R-transfected HEK293T/17 cells showed that the drug exhibited inverse agonist activity on CB1R. In addition, JM-00266 counteracted anandamide-induced gastroparesis indicating substantial peripheral activity. Acute administration of JM-00266 also improved glucose tolerance and insulin sensitivity in wild-type mice, but not in CB1R−/− mice. Furthermore, the accumulation of JM-00266 in adipose tissue was associated with an increase in lipolysis. In conclusion, JM-00266 or derivatives can be predicted as a new candidate for modulating peripheral endocannabinoid activity and improving obesity-related metabolic disorders. 相似文献
522.
In this work, we investigated the frictional behavior of copper CMP. Using a laboratory polishing set up, we polished Cu with
designed polishing media. After that the copper surface and the fumed silica particles Cu were analyzed. The surface analysis
techniques used are the field emission SEM, the field-emission high-resolution analytical TEM, x-ray spectroscopy, and XPS.
We found evident difference in friction value using different polishing media. Discussions lead to three mechanisms during
copper CMP. The nature of copper oxides has a profound influence on friction and might be directly related to defects.
Argonne National Laboratory 相似文献
523.
Competing destinations and intervening opportunities interaction models of inter-city telecommunication flows 总被引:3,自引:0,他引:3
Jean-Michel Guldmann 《Papers in Regional Science》1999,78(2):179-194
This research makes use of a large sample of individual telephone calls between local exchanges (cities, towns, villages)
within a U.S. region. The interlocational flows, measured in conversation seconds, are analyzed by estimating, in a simultaneous
equation framework, spatial interaction models that account for (1) the role of the spatial structure, which reflects the
competition and agglomeration effects that take place among the flow destinations, and (2) the role of the reverse flows,
which reflect the process of information creation necessary to complete economic and social transactions. A particular focus
is set on Fotheringham's competing destinations model and Stouffer's intervening opportunities model. The implications of
the results are discussed and areas for further research are outlined.
Received: 1 September 1998 / Accepted: 18 December 1998 相似文献
524.
Sergiel JP Chardigny JM Sébédio JL Berdeaux O Juaneda P Loreau O Pasquis B Noel JP 《Lipids》2001,36(12):1327-1329
To assess the oxidative metabolism of conjugated linoleic acid (CLA) isomers, rats were force-fed 1.5–2.6 MBq of [1-14C]-linoleic acid (9c,12c-18∶2),-rumenic acid (9c,11t-18∶2), or-10trans, 12cis-18∶2 (10t, 12c-18∶2), and 14CO2 production was monitored for 24 h. The animals were then necropsied and the radioactivity determined in different tissues.
Both CLA isomers were oxidized significantly more than linoleic acid. Moreover, less radioactivity was recovered in most tissues
after CLA intake than after linoleic acid intake. The substantial oxidation of CLA isomers must be considered when assessing
the putative health benefits of CLA supplements. 相似文献
525.
Sufficient availability of both n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) is required for optimal structural
and functional development in infancy. The question has been raised as to whether infant formulae would benefit from enrichment
with 20 and 22 carbon fatty acids. To address this issue, we determined the effect of fish oil and phospholipid (LCPUFA) sources
on the fatty acid composition of brain cortical areas and nonneural tissues of newborn piglets fed artificially for 2 wk.
They were fed sow milk, a control formula, or the formula enriched with n-3 fatty acids from a low-20:5n-3 fish oil added
at a high or a low concentration, or the formula enriched with n-3 and n-6 fatty acids from either egg yolk- or pig brain-phospholipids.
Both the fish oil- and the phospholipid-enriched formula produced significantly higher plasma phospholipid 22:6n-3 concentrations
than did the control formula. The 22:6n-3 levels in the brain, hepatic, and intestinal phospholipids were significantly correlated
with plasma values, whereas cardiac 22:6n-3 content appeared to follow a saturable dose-response. Feeding sow milk resulted
in a much higher 20:4n-6 content in nonneural tissues than did feeding formula. Supplementation with egg phospholipid increased
the 20:4n-6 content in the heart, red blood cells, plasma, and intestine in comparison to the control formula, while pig brain
phospholipids exerted this effect in the heart only. The addition of 4.5% fish oil in the formula was associated with a decline
in 20:4n-6 in the cortex, cerebellum, heart, liver, and plasma phospholipids, whereas using this source at 1.5% limited the
decline to the cerebellum, liver, and plasma. Whatever the dietary treatment, the phosphatidylethanolamine 20:4n-6 level was
10–20% higher in the brain temporal lobe than in the parietal, frontal, and occipital lobes in the temporal lobe by administering
the formula enriched with egg or brain phospholipids.
In conclusion, feeding egg phospholipids to neonatal pigs increased both the 22:6n-3 content in the brain and the 20:4n-6
content in the temporal lobe cortex. This source also increased the 22:6n-3 levels in nonneural tissues with only minor alterations
of 20:4n-6. These data support the notion that infant formulae should be supplemented with both 22:6n-3 and 20:4n-6 rather
than with 22:6n-3 alone. 相似文献
526.
Significance of Coprophagy for the Fatty Acid Profile in Body Tissues of Rabbits Fed Different Diets
Four groups of eight New Zealand hybrid rabbits were fattened with ad libitum access to the following pelleted experimental diets: ryegrass meal or alfalfa meal fed either alone or with oats meal in a ratio of 1:1. After 25 weeks they were slaughtered and dissected. Fatty acid (FA) profiles of caecotrophs (re-ingested fermentation products of the caecum), perirenal adipose tissue and intramuscular fat in the Musculus quadriceps were determined. With high proportions of branched-chain FA (BFA) and trans FA, and increased proportions of saturated FA relative to the diets, the caecotroph FA profile showed a clear fingerprint of anaerobe microbial lipid metabolism including biohydrogenation. By contrast, the FA profiles of adipose and lean tissue comprised high proportions of polyunsaturated FA (PUFA), whilst BFA and trans FA occurred in much lower proportions compared to the caecotrophs. Thus, coprophagy did not substantially modify the FA composition of the tissues investigated. Use of forage-only diets, compared to the oats supplemented diets, led to extraordinary high proportions of n-3 PUFA (including 18:3 and long-chain n-3) in the fat of adipose (21.3 vs. 6.7%) and lean tissue (15.4 vs. 5.7%). The forage type diet (grass vs. alfalfa) had smaller effects on the FA profiles. Indications of diet effects on endogenous desaturation, chain elongation and differential distribution of functional FA between the two tissues investigated were found. 相似文献
527.
Anne Mignotte Jean-Michel Muller Olivier Peyran 《Design Automation for Embedded Systems》2000,5(1):29-60
The primary goal of this paper is to show that a clever use of redundant number systems in some parts of designs can significantly increase their speed, without noticeably increasing their area and power consumption. This can be achieved by automatically using, in the same design, redundant (e.g., carry save or borrow save) as well as non-redundant (i.e., conventional) number systems: this approach can be called mixed arithmetic. This implies specific constraints in the scheduling process. We propose an integer linear programming (ILP) formulation. It finds an optimal solution for examples of reasonable sizes. In some cases, the ILP computational delay may become huge. To solve this problem, we introduce a general solution, based on a constraint graph partitioning. This leads to an ILP formulation partitioning. This partitioning approach can be used for other similar problems in synthesis, also formulated as ILPs. 相似文献
528.
Fairbrother Wayne J.; Minard Philippe; Hall Len; Betton Jean-Michel; Missiakas Dominique; Yon Jeannine M.; Williams Robert J.P. 《Protein engineering, design & selection : PEDS》1989,3(1):5-11
The structural integrity and substrate binding properties ofthe two genetically engineered domains of yeast phosphoglyceratekinase were investigated using one- and two-dimensional nuclearmagnetic resonance techniques. Both domains were found to foldwith regions of native-like structure, with the N-domain showinggreater conformational flexibility than the C-domain. The basicpatch region of the N-domain is, however, clearly perturbedby removal of the C-domain. This is most likely due to the absenceof stabilizing interactions between the C-terminal peptide (including-helices XIII and XIV) and the N-domain. The C-domain is ableto bind nucleotide with an affinity only three times less thanthat of the native protein. 相似文献
529.
Jean-Michel Dance 《Materials Research Bulletin》1981,16(5):599-606
ESR and magnetic susceptibility measurements performed on the ACuF4 copper 2+ fluorides (A = Ca, Sr, Ba) show that antiferrodistortive ordering of the copper orbitals in CaCuF4 and SrCuF4 (of KBrF4-type structure with square planar coordination of the Cu2+ ions) leads to paramagnetism down to 4.2 K. Ferrodistortive ordering in BaCuF4 (BaMnF4 type - elongated octahedral coordination with parallel dz2 orbitals) gives a 1-D antiferromagnetic behavior. 相似文献
530.