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C S Nicoll 《The Physiologist》1991,34(6):303, 306-308, 315
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Jonas G. Barlind Linda K. Buckett Sharon G. Crosby Öjvind Davidsson Hans Emtenäs Anne Ertan Ulrik Jurva Malin Lemurell Pablo Morentin Gutierrez Karolina Nilsson Gavin O’Mahony Annika U. Petersson Alma Redzic Fredrik Wågberg Zhong-Qing Yuan 《Bioorganic & medicinal chemistry letters》2013,23(9):2721-2726
[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration. 相似文献
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Barbara A. Stewart Gavin Gouws Savel R. Daniels & Conrad A. Matthee 《Zoologica scripta》2004,33(1):45-55
Stewart, B. A., Gouws, G., Daniels, S. R. & Matthee, C. A. (2004). Delimitation of morphologically similar sponge crab species of the genus Pseudodromia (Crustacea, Decapoda, Dromiidae) from South Africa. — Zoologica Scripta , 33 , 45–55.
Presently, three Pseudodromia sponge crab species are recognized, all of which are endemic to the continental shelf off the coast of South Africa. Two of these differ only in the morphology of their rostral teeth, making them difficult to distinguish, and can thus be considered as cryptic species. In addition they have very similar distribution ranges, thus raising doubts as to their specific status. Discriminant function analysis of morphometric data, differentiation at 10 allozyme loci, and sequence data derived from the 12S rRNA mitochondrial gene were used to test whether specimens identified as P. latens and P. rotunda are morphological forms of a single, widespread species, or represent two, distinct, reproductively isolated species, and to establish whether these two taxa are sister species, and thus form a monophyletic entity. The presence of fixed allele differences at three, and strong genetic heterogeneity at five other allozyme loci, indicating no gene flow occurring between sympatric populations, as well as the relatively high degree of 12S rRNA and allozyme genetic differentiation observed, supported the recognition of P. latens and P. rotunda as separate species. The 12S rRNA topology suggested that the genus Pseudodromia , as presently constituted, is paraphyletic, thus inferring that the morphological characters used to define this taxon might not be useful for phylogenetic inferences. It was concluded that in view of the uncertainties raised regarding the designation and composition of certain genera within the family Dromiidae, further rigorous analyses of morphological and genetic data are needed to further our understanding of the taxonomy of the sponge crabs. 相似文献
Presently, three Pseudodromia sponge crab species are recognized, all of which are endemic to the continental shelf off the coast of South Africa. Two of these differ only in the morphology of their rostral teeth, making them difficult to distinguish, and can thus be considered as cryptic species. In addition they have very similar distribution ranges, thus raising doubts as to their specific status. Discriminant function analysis of morphometric data, differentiation at 10 allozyme loci, and sequence data derived from the 12S rRNA mitochondrial gene were used to test whether specimens identified as P. latens and P. rotunda are morphological forms of a single, widespread species, or represent two, distinct, reproductively isolated species, and to establish whether these two taxa are sister species, and thus form a monophyletic entity. The presence of fixed allele differences at three, and strong genetic heterogeneity at five other allozyme loci, indicating no gene flow occurring between sympatric populations, as well as the relatively high degree of 12S rRNA and allozyme genetic differentiation observed, supported the recognition of P. latens and P. rotunda as separate species. The 12S rRNA topology suggested that the genus Pseudodromia , as presently constituted, is paraphyletic, thus inferring that the morphological characters used to define this taxon might not be useful for phylogenetic inferences. It was concluded that in view of the uncertainties raised regarding the designation and composition of certain genera within the family Dromiidae, further rigorous analyses of morphological and genetic data are needed to further our understanding of the taxonomy of the sponge crabs. 相似文献
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Nigel J. Fuller Dorothy M. Stirling Stephen Dunnett Gavin P. Reynolds Margaret Ashwell 《Bioscience reports》1987,7(2):121-127
The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake. 相似文献
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1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD. 相似文献
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Saraswati Manda Nicoll Lerner-Marmarosh Mazzaz Hashmi Leo G. Abood 《Neurochemical research》1992,17(12):1191-1194
The present study, utilizing thioglycolamido as the reactive group, describes the synthesis and pharmacology of a new opioid antagonist affinity ligand, 6-thioglycolamido-6-desoxynaltrexone (TAN) and compares TAN with a related known compound, 6-bromoacetamido-6-desoxynaltrexone (BAN). Both compounds were tested for their reversible and irreversible inhibition of [3H]naloxone binding to calf brain membranes. Reversible binding of BAN and TAN had Ki values of 1×10–9 and 1×10–10 M, respectively as determined by log probit plots. Irreversible binding was determined after extensive washing to remove all non-covalently bound ligand. At a concentration of 5×10–8 and 1×10–8 M for BAN and TAN irreversible binding was inhibited 50% of the maximum value. A study of the time course of irreversible inhibition of [3H]naloxone binding revealed that maximal inhibition occurred within 5 min with a concentration of 1×10–7 M of either agent. TAN but not BAN when administered systematically to mice produced an antinociceptive effect as measured by the writhing test. When administered intracerebraventricularly BAN did not block morphine-induced analgesia for more than 2 hr; whereas, with a single ED50 dose of 20 nmoles of TAN i.c.v. morphine-induced analgesia was almost completely blocked for a period of over 24 hr, as determined by the tail flick test. Although the SH group of TAN were required for the covalent interaction with opioid receptors, the site of TAN's interaction appears to involve other than protein SH groups. 相似文献