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731.
732.
Lovell KM Vasiljevik T Araya JJ Lozama A Prevatt-Smith KM Day VW Dersch CM Rothman RB Butelman ER Kreek MJ Prisinzano TE 《Bioorganic & medicinal chemistry》2012,20(9):3100-3110
Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as Grignard and Stille conditions, have met with limited success. We report a palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a boronic acid that occurs at neutral pH and ambient temperature to produce ketone analogs at C-12. To the best of our knowledge, this is the first reported usage of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through microwave irradiation. Previously, this synthetically challenging process has required multiple steps. Additionally, we report in this study that alkene 9 and aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2-yl analog of 1 (31) has similar affinity to 1. Collectively, these findings suggest that different aromatic groups appended directly to the decalin core may be well tolerated by KOP receptors, and may generate further ligands with affinity and activity at KOP receptors. 相似文献
733.
Facilitation and interference of seedling establishment by a native legume before and after wildfire
In semi-arid ecosystems, heterogeneous resources can lead to variable seedling recruitment. Existing vegetation can influence
seedling establishment by modifying the resource and physical environment. We asked how a native legume, Lupinus argenteus, modifies microenvironments in unburned and burned sagebrush steppe, and if L. argenteus presence facilitates seedling establishment of native species and the non-native annual grass, Bromus tectorum. Field treatments examined mechanisms by which L. argenteus likely influences establishment: (1) live L. argenteus; (2) dead L. argenteus; (3) no L. argenteus; (4) no L. argenteus with L. argenteus litter; (5) no L. argenteus with inert litter; and (6) mock L. argenteus. Response variables included soil nitrogen, moisture, temperature, solar radiation, and seedling establishment of the natives
Elymus multisetus and Eriogonum umbellatum, and non-native B. tectorum. In both unburned and burned communities, there was higher spring soil moisture, increased shade and reduced maximum temperatures
under L. argenteus canopies. Adult L. argenteus resulted in greater amounts of soil nitrogen (N) only in burned sagebrush steppe, but L. argenteus litter increased soil N under both unburned and burned conditions. Although L. argenteus negatively affected emergence and survival of B. tectorum overall, its presence increased B. tectorum biomass and reproduction in unburned plots. However, L. argenteus had positive facilitative effects on size and survival of E. multisetus in both unburned and burned plots. Our study indicates that L. argenteus can facilitate seedling establishment in semi-arid systems, but net effects depend on the species examined, traits measured,
and level of abiotic stress. 相似文献
734.
Addiction to drugs is a chronic, relapsing brain disease that has major medical, social, and economic complications. It has been established that genetic factors contribute to the vulnerability to develop drug addiction and to the effectiveness of its treatment. Identification of these factors may increase our understanding of the disorders, help in the development of new treatments and advance personalized medicine. In this review, we will describe the genetics of the major genes of the opioid system (opioid receptors and their endogenous ligands) in connection to addiction to opioids, cocaine, alcohol and methamphetamines. Particular emphasis is given to association and functional studies of specific variants. We will provide information on the sample populations and the size of each study, as well as a list of the variants implicated in association with addiction-related phenotypes, and with the effectiveness of pharmacotherapy for addiction. 相似文献
735.
736.
Peng YJ Nanduri J Zhang X Wang N Raghuraman G Seagard J Kumar GK Prabhakar NR 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(1):187-196
The objectives of the present study were to examine the effects of intermittent hypoxia (IH) on arterial baroreflex function and assess the underlying mechanism(s). Experiments were performed on adult male rats treated with 14 days of IH (15 s of hypoxia, 5 min of normoxia; 8 h/day) or normoxia (control). Arterial blood pressures were elevated in IH-treated rats, and this effect was associated with attenuated heart rate and splanchnic sympathetic nerve responses to arterial baroreflex activation. In IH-treated rats, carotid baroreceptor responses to elevated sinus pressures were attenuated. Endothelin-1 (ET-1) levels were elevated in the carotid sinus region of IH-treated rats, and this effect was associated with increased endothelin converting enzyme (ECE) activity, which generates biologically active ET-1. ET(A) receptor antagonist prevented the effects of IH on carotid baroreceptor activity. In IH-treated rats, reactive oxygen species (ROS) levels were elevated in the carotid sinus region, and antioxidant treatment prevented the effects of IH on ET-1 levels, ECE activity, carotid baroreceptor activity, and baroreflex function. These results demonstrate that 1) IH attenuates arterial baroreflex function, which is in part due to reduced carotid baroreceptor responses to elevated carotid sinus pressure, and 2) IH-induced carotid baroreceptor dysfunction involves reactive oxygen species-dependent upregulation of ET-1 signaling in the carotid sinus region. 相似文献
737.
Benjamin J. Taylor Erik V. Nordheim Robert L. Jeanne 《Ethology : formerly Zeitschrift fur Tierpsychologie》2012,118(6):594-605
In social insects, selection takes place primarily at the level of the colony. Therefore, unlike solitary insects, social species are expected to forage at rates that maximize colony fitness rather than individual fitness. Workers can increase the net benefit of foraging by responding to increased resource availability, by responding more strongly to higher‐quality resources, and by decreasing the uncertainty with which nestmates find resources. Unlike many ants and social bees, no social wasp is known to utilize a nest‐based recruitment signal to inform nestmates of food location. On the other hand, wasps do learn the odor of food brought to the nest and use this cue to locate the food source outside the nest. Here, we quantify the effects of three food‐associated variables on the allocation of foraging effort in the yellowjacket Vespula germanica. We used an experimental approach to assess whether resource quantity, quality, or associated olfactory information affect the probability that a forager will leave the nest on a foraging trip. We addressed these questions by inserting a known amount of sucrose solution directly into nests and recording foraging effort (departure rate) over the subsequent hour‐long observation period. No differences were found in foraging effort because of the presence/absence of olfactory cues, but there was strong evidence that foraging effort increased in response to resource influx and resource quality. Thus, while olfactory cues are learned in the nest, only resource quality and the cue of increased amount of food in the nest factor into a forager's decision of whether or not to depart on a foraging trip. However, as prior work has shown, once a wasp forager leaves the nest, it uses the learned olfactory cues to aid in finding resources. 相似文献
738.
Jeanne Vallet Maëlle Rambaud Loïc Coquel Laurent Poncet Frédéric Hendoux 《Comptes rendus biologies》2012,335(12):753-763
Floristic atlases have an important input to flora conservation planning even though their data quality varied greatly across countries. This study aimed to assess survey completeness of cells of floristic atlases. Then, a surveying guide is designed to overcome as efficiently as possible sampling biases. A review and analyses on a wide dataset were carried out to select an estimator of the true species richness of surveyed cells. The Jackknife 1, a non-parametric estimator, appeared as the best compromise for regional floristic atlases. The number of records in each cell was used as an estimator of sampling effort. The ratio between the observed species richness and the estimated species richness measures the completeness of inventories in each surveyed cell. Eighteen variables were selected to describe current inventories and design new surveys. These variables highlight locations, periods and species to be given priority in future studies. 相似文献
739.
Jeanne Scardini Marinho-Prado A L Louren??o R N C. Guedes A Pallini J A Oliveira M G A. Oliveira 《Neotropical Entomology》2012,41(5):420-425
Ingestion of proteinase inhibitors leads to hyperproduction of digestive proteinases, limiting the bioavailability of essential amino acids for protein synthesis, which affects insect growth and development. However, the effects of proteinase inhibitors on digestive enzymes can lead to an adaptive response by the insect. In here, we assessed the biochemical response of midgut proteinases from the eucalypt defoliator Thyrinteina arnobia (Stoll) to different concentrations of berenil, a bis-benzamidine proteinase inhibitor, on eucalyptus. Eucalyptus leaves were immersed in berenil solutions at different concentrations and fed to larvae of T. arnobia. Mortality was assessed daily. The proteolytic activity in the midgut of T. arnobia was assessed after feeding on plants sprayed with aqueous solutions of berenil, fed to fifth instars of T. arnobia for 48?h before midgut removal for enzymatic assays. Larvae of T. arnobia were able to overcome the effects of the lowest berenil concentrations by increasing their trypsin-like activity, but not as berenil concentration increased, despite the fact that the highest berenil concentration resulted in overproduction of trypsin-like proteinases. Berenil also prevented the increase of the cysteine proteinases activity in response to trypsin inhibition. 相似文献