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排序方式: 共有245条查询结果,搜索用时 31 毫秒
101.
Reid PR Bridges TM Sheffler DJ Cho HP Lewis LM Days E Daniels JS Jones CK Niswender CM Weaver CD Conn PJ Lindsley CW Wood MR 《Bioorganic & medicinal chemistry letters》2011,21(9):2697-2701
This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M1 PAM with an in vitro profile comparable to the prototypical M1 PAM, BQCA, but with an improved brain to plasma ratio. 相似文献
102.
Lamb JP Engers DW Niswender CM Rodriguez AL Venable DF Conn PJ Lindsley CW 《Bioorganic & medicinal chemistry letters》2011,21(9):2711-2714
This Letter describes a chemical lead optimization campaign directed at a weak mGlu5 NAM discovered while developing SAR for the mGlu5 PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu5 NAMs, mGlu5 PAMs as well as mGlu5 partial antagonists. 相似文献
103.
Sams AG Mikkelsen GK Brodbeck RM Pu X Ritzén A 《Bioorganic & medicinal chemistry letters》2011,21(11):3407-3410
A series of metabotropic glutamate 5 receptor (mGluR5) allosteric ligands with positive, negative or no modulatory efficacy is described. The ability of this series to yield both mGluR5 PAMs and NAMs with single-digit nanomolar potency is unusual, and the underlying SAR is detailed. 相似文献
104.
H. Anu Kramer Kevin G. Kelly Sheila A. Whitmore William J. Berigan Dana S. Reid Connor M. Wood Holger Klinck Stefan Kahl Patricia N. Manley Sarah C. Sawyer M. Zachariah Peery 《The Journal of wildlife management》2024,88(2):e22533
The California spotted owl (Strix occidentalis occidentalis) is an older-forest associated species that resides at the center of forest management planning in the Sierra Nevada and Southern California, USA, which are experiencing increasingly large and severe wildfires and drought-related tree mortality. We leveraged advances in passive acoustic survey technologies to develop an acoustically assisted survey design that could increase the efficiency and effectiveness of project-level surveys for spotted owls, allowing surveys to be completed in a single year instead of in multiple years. We deployed an array of autonomous recording units (ARUs) across a landscape and identified spotted owl vocalizations in the resulting audio using BirdNET. We then evaluated spatio-temporal patterns in spotted owl vocalizations near occupied territories and the ability of a crew naïve to the location of occupied territories to locate spotted owls based on patterns of acoustic detections. After only 3 weeks of acoustic surveys, ≥1 ARU within 750 m of all 17 occupied territories obtained spotted owl detections across ≥2 nights. When active surveys using broadcast calling were conducted near ARUs with spotted owl detections by surveyors naïve to territory occupancy status and locations, surveyors located owls in 93% to 100% of occupied territories with ≤3 surveys. To further improve the efficiency of spotted owl surveys, we developed a statistical model to identify and prioritize areas across the Sierra Nevada for different survey methods (active only, acoustically assisted, no surveys) based on the expected probability of occupancy predicted from remotely sensed measurements of tree height and historical occupancy. Depending on managers' tolerance for false negatives, this model could help identify large areas that might not benefit from surveys based on low expected occupancy probabilities and areas where acoustically assisted surveys might enhance survey effectiveness and efficiency. Collectively, these findings can help managers streamline the survey process and thus increase the pace of forest restoration while minimizing potential near-term adverse effects on California spotted owls. 相似文献
105.
The NMDA receptor (NMDAR) family of l-glutamate receptors are well known to have diverse roles in CNS function as well as in various neuropathological and psychiatric conditions. Until recently, the types of agents available to pharmacologically regulate NMDAR function have been quite limited in terms of mechanism of action and subtype selectivity. This has changed significantly in the past two years. The purpose of this review is to summarize the many drug classes now available for modulating NMDAR activity. Previously, this included competitive antagonists at the l-glutamate and glycine binding sites, high and low affinity channel blockers, and GluN2B-selective N-terminal domain binding site antagonists. More recently, we and others have identified new classes of NMDAR agents that are either positive or negative allosteric modulators (PAMs and NAMs, respectively). These compounds include the pan potentiator UBP646, the GluN2A-selective potentiator/GluN2C and GluN2D inhibitor UBP512, the GluN2D-selective potentiator UBP551, the GluN2C/GluN2D-selective potentiator CIQ as well as the new NMDAR-NAMs such as the pan-inhibitor UBP618, the GluN2C/GluN2D-selective inhibitor QZN46 and the GluN2A inhibitors UBP608 and TCN201. These new agents do not bind within the l-glutamate or glycine binding sites, the ion channel pore or the N-terminal regulatory domain. Collectively, these new allosteric modulators appear to be acting at multiple novel sites on the NMDAR complex. Importantly, these agents display improved subtype-selectivity and as NMDAR PAMs and NAMs, they represent a new generation of potential NMDAR therapeutics. 相似文献
106.
《Molecular cell》2020,77(1):39-50.e10
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107.
Global climate change is leading to the rise of ocean temperatures and is triggering mass coral bleaching events on reefs around the world. The expulsion of the symbiotic dinoflagellate algae is believed to occur as a result of damage to the photosynthetic apparatus of these symbionts, although the specific site of initial impact is yet to be conclusively resolved. Here, the sensitivity of the oxygen evolving complex (OEC) to bleaching stress was studied as well as its natural variation between seasons. The artificial electron donor, diphenyl carbazide (DPC), was added to cultured, freshly isolated and expelled (bleaching treatments only) zooxanthellae suspensions. Chl a fluorescence and oxygen production measurements showed that upon addition of DPC, no restoration of diminished photochemical efficiency occurred under control or bleaching conditions. This result was consistent between 12 h and 5 d bleaching treatments on Pocilloporadamicornis, indicating that the OEC is not the primary site of damage, and that zooxanthellae expulsion from the host is a nonselective process with respect to the functioning of the OEC. Further experiments measuring fast induction curves (FICs) revealed that in both summer and winter, the temperature when OEC function was lost occurred between 7°C and 14°C above the sea surface temperature. FIC and oxygen production measurements of P. damicornis during exposure to bleaching stress demonstrated that the thermotolerance of the OEC increased above the temperature of the bleaching treatment over a 4 h period. This finding indicates that the OEC has the capacity to acclimate between seasons and remains functional at temperatures well above bleaching thresholds. 相似文献
108.
109.
Kasper Hancke Torunn B. Hancke Lasse M. Olsen Geir Johnsen Ronnie N. Glud 《Journal of phycology》2008,44(2):501-514
Short‐term temperature effects on photosynthesis were investigated by measuring O2 production, PSII‐fluorescence kinetics, and 14C‐incorporation rates in monocultures of the marine phytoplankton species Prorocentrum minimum (Pavill.) J. Schiller (Dinophyceae), Prymnesium parvum f. patelliferum (J. C. Green, D. J. Hibberd et Pienaar) A. Larsen (Coccolithophyceae), and Phaeodactylum tricornutum Bohlin (Bacillariophyceae), grown at 15°C and 80 μmol photons · m?2 · s?1. Photosynthesis versus irradiance curves were measured at seven temperatures (0°C–30°C) by all three approaches. The maximum photosynthetic rate (PCmax) was strongly stimulated by temperature, reached an optimum for Pro. minimum only (20°C–25°C), and showed a similar relative temperature response for the three applied methods, with Q10 ranging from 1.7 to 3.5. The maximum light utilization coefficient (αC) was insensitive or decreased slightly with increasing temperature. Absolute rates of O2 production were calculated from pulse‐amplitude‐modulated (PAM) fluorometry measurements in combination with biooptical determination of absorbed quanta in PSII. The relationship between PAM‐based O2 production and measured O2 production and 14C assimilation showed a species‐specific correlation, with 1.2–3.3 times higher absolute values of PCmax and αC when calculated from PAM data for Pry. parvum and Ph. tricornutum but equivalent for Pro. minimum. The offset seemed to be temperature insensitive and could be explained by a lower quantum yield for O2 production than the theoretical maximum (due to Mehler‐type reactions). Conclusively, the PAM technique can be used to study temperature responses of photosynthesis in microalgae when paying attention to the absorption properties in PSII. 相似文献
110.
利用调制荧光仪在线监测叶绿素荧光 总被引:6,自引:1,他引:5
介绍了利用便携式调制荧光仪PAM-2100在线监测叶绿素荧光的技术。该技术不影响植物的自然光合状态,司以在线监测Ft、F′m、Y、rETR、qP、qN或NPQ、PAR和叶温等指标。以凤眼莲为例进行了在线监测,每隔5min监测一次,共进行了225min的监测。结果表明叶绿索荧光参数的变化依赖于PAR的变化。Ft、rETR、qN和NPQ的变化与PAR的变化趋势一致,F′m、Y和qP的变化与PAR的变化相反。通过对风眼莲的在线监测,说明该技术是可靠的,具有简单、快速、灵敏等特点。随着新型调制荧光仪的出现,该技术可能在植物生态学领域得到广泛应用。 相似文献