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1.
C S Nicoll 《The Physiologist》1991,34(6):303, 306-308, 315
2.
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
3.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
4.
Graham DI Gentleman SM Nicoll JA Royston MC McKenzie JE Roberts GW Mrak RE Griffin WS 《Cellular and molecular neurobiology》1999,19(1):19-30
1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the 4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease.2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of -amyloid protein (A), a protein that is thought to be central to the pathogenesis of Alzheimer's disease.3. Recent studies have revealed an over-representation of the apoE 4 allele in those head-injured patients displaying A pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology. 相似文献
5.
Iris M Costa Tallybia HT Nasser Marilene Demasi Rafaella MP Nascimento Luis ES Netto Sayuri Miyamoto Fernanda M Prado Gisele Monteiro 《BMC microbiology》2011,11(1):268
Background
The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recently been described as a cell component involved in yeast filamentous growth. The objective of this work is to understand the molecular and biological function of this gene.Results
Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of the Saccharomyces cerevisiae protein quality control pathway. According to the results, Δpof1 cells showed increased sensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such as dithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Δpct1, a strain that lacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however, that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalytic efficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins (ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction between Pof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo.Conclusions
Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.6.
Ann Trevallion R. Johnston D.M. Finlayson N.T. Nicoll 《Journal of experimental marine biology and ecology》1973,11(2):189-206
Tellina tennis Da Costa was kept for four months in four large outdoor tanks containing sand and sea water. There was a 10 % daily exchange of sea water, pumped directly from the sea. Three tanks received daily addition of nutrients in the form of sodium nitrate and sodium dihydrogen phosphate, giving enrichment of approximately 3, 10, and 30 times natural sea-water levels of nitrate in the different tanks. Phosphate, nitrate, chlorophyll, and organic carbon in the water were measured regularly, the nitrate by Autoanalyser. Water temperature and solar radiation were recorded. Zooplankton samples were taken daily and Tellina were sampled monthly for length, weight, and biochemical analysis of tissues.Phosphate was always present in excess. The lowest level of nitrogen enrichment resulted in almost complete utilisation of nitrate, with a significant increase of organic carbon and chlorophyll above control levels. Zooplankton occurred in the greatest numbers in this tank, and Tellina showed the best survival, growth, and condition. In the tanks with the higher levels of enrichment, excess nutrients led to growth of macrophytic algae on the surface and sides of tank. This had an adverse effect on the phytoplankton production: zooplankton numbers were lower, as was growth of Tellina. 相似文献
7.
Dispersal is a key process in population and evolutionary ecology. Individual decisions are affected by fitness consequences of dispersal, but these are difficult to measure in wild populations. A long‐term dataset on a geographically closed bird population, the Mauritius kestrel, offers a rare opportunity to explore fitness consequences. Females dispersed further when the availability of local breeding sites was limited, whereas male dispersal correlated with phenotypic traits. Female but not male fitness was lower when they dispersed longer distances compared to settling close to home. These results suggest a cost of dispersal in females. We found evidence of both short‐ and long‐term fitness consequences of natal dispersal in females, including reduced fecundity in early life and more rapid aging in later life. Taken together, our results indicate that dispersal in early life might shape life history strategies in wild populations. 相似文献
8.
Purple Sandpipers wintering on the Kincardine coast had a protracted autumn arrival (one-quarter and three-quarters of the birds arrived on 30 July and 21 October respectively, 83 days) but a faster spring departure (one-quarter and three-quarters departed on 9 April and 27 May respectively, 48 days). The long arrival period was partly due to differences in the migration phenology of the two main wintering populations: short-billed birds from Norway arrived before the long-billed birds, probably from Canada. There was a smaller difference in departure times of the two populations: short-billed birds left before the long-billed birds. Minimum annual survival was estimated from resightings of 92 marked birds. There was no evidence that survival differed between adults and first-years or between birds of different bill-size classes, which were of different sex and geographical origin. Minimum annual survival was estimated to be 79.5%(se = 2.8%). The similarity between the mortality rate (20.5%) and the percentage of first-year birds in populations of Purple Sandpipers probably reflects balanced population dynamics. 相似文献
9.
10.
Excitatory synaptic transmission in the mammalian brain is mediated primarily by alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors that are thought to be co-localized at individual synapses. However, recent electrophysiological and anatomical data suggest that the synaptic localization of AMPA and NMDA receptors may be independently regulated by neural activity. These data are reviewed here and the implications of these findings for the mechanisms underlying synaptic plasticity are discussed. 相似文献