bluuebunny/crossref_metadata_2025_split huggingface dataset:
α7 nicotinic acetylcholine receptor agonist properties of tilorone and related tricyclic analogues
Authors: Briggs C A , Schrimpf M R , Anderson D J , Gubbins E J , Grønlien J H , Håkerud M , Ween H , Thorin‐Hagene K , Malysz J , Li J , Bunnelle W H , Gopalakrishnan M , Meyer M D 
Published: December 2007

Background and purpose:The α7 nicotinic acetylcholine receptor (nAChR) has attracted considerable interest as a target for cognitive enhancement in schizophrenia and Alzheimer's Disease. However, most recently described α7 agonists are derived from the quinuclidine structural class. Alternatively, the present study identifies tilorone as a novel α7‐selective agonist and characterizes analogues developed from this lead.Experimental approach:Activity and selectivity were determined from rat brain α7 and α4β2 nAChR binding, recombinant nAChR activation, and native α7 nAChR mediated stimulation of ERK1/2 phosphorylation in PC12 cells.Key results:Tilorone bound α7 nAChR (IC50110 nM) with high selectivity relative to α4β2 (IC5070 000 nM), activated human α7 nAChR with an EC50value of 2.5 μMand maximal response of 67% relative to acetylcholine, and showed little agonist effect at human α3β4 or α4β2 nAChRs. However, the rat α7 nAChR maximal response was only 34%. Lead optimization led to 2‐(5‐methyl‐hexahydro‐pyrrolo[3,4‐c]pyrrol‐2‐yl)‐xanthen‐9‐one (A‐844606) with improved binding (α7 IC5011 nM, α4β2 IC50>30 000 nM) and activity at both human and rat α7 nAChR (EC50s 1.4 and 2.2 μMand apparent efficacies 61 and 63%, respectively). These compounds also activated native α7 nAChR, stimulating ERK1/2 phosphorylation in PC12 cells.Conclusions and implications:Tilorone, known as an interferon inducer, is a selective α7 nAChR agonist, suggesting utility of the fluorenone pharmacophore for the development of α7 nAChR selective agonists. Whether α7 stimulation mediates interferon induction, or whether interferon induction may influence the potential anti‐inflammatory properties of α7 nAChR agonists remains to be elucidated.British Journal of Pharmacology(2008)153, 1054–1061; doi:10.1038/sj.bjp.0707649; published online 24 December 2007
Glutamate Receptor Subtypes Evidenced by Differences in Desensitization and Dependence on theGLR3.3andGLR3.4Genes
Authors: Stephens Nicholas R. , Qi Zhi , Spalding Edgar P. 
Published: December 2007

AbstractIonotropic glutamate (Glu) receptors in the central nervous system of animals are tetrameric ion channels that conduct cations across neuronal membranes upon binding Glu or another agonist. Plants possess homologous molecules encoded by GLR genes. Previous studies of Arabidopsis thaliana root cells showed that the amino acids alanine (Ala), asparagine (Asn), cysteine (Cys), Glu, glycine (Gly), and serine trigger transient Ca2+ influx and membrane depolarization by a mechanism that depends on the GLR3.3 gene. This study of hypocotyl cells demonstrates that these six effective amino acids are not equivalent agonists. Instead, they grouped into hierarchical classes based on their ability to desensitize the response mechanism. Sequential treatment with two different amino acids separated by a washout phase demonstrated that Glu desensitized the depolarization mechanism to Gly, but Gly did not desensitize the mechanism to Glu. All 36 possible pairs of agonists were tested to characterize the desensitization hierarchy. The results could be explained by a model in which one class of channels contained a subunit that was activated and therefore desensitized only by Glu, while a second class could be activated and desensitized by Ala, Cys, Glu, or Gly. A third class could be activated and desensitized by any of the six effective amino acids. Analysis of knockout mutants indicated that GLR3.3 was a required component of all three classes of channels, while the related GLR3.4 molecule specifically affected only two of the classes. The resulting model is an important step toward understanding the biological roles of these enigmatic ion channels.
Structural, Biochemical, and Phylogenetic Analyses Suggest That Indole-3-Acetic Acid Methyltransferase Is an Evolutionarily Ancient Member of the SABATH Family
Authors: Zhao Nan , Ferrer Jean-Luc , Ross Jeannine , Guan Ju , Yang Yue , Pichersky Eran , Noel Joseph P. , Chen Feng 
Published: December 2007

Abstract
The plant SABATH protein family encompasses a group of related small-molecule methyltransferases (MTs) that catalyze the S-adenosyl-l-methionine-dependent methylation of natural chemicals encompassing widely divergent structures. Indole-3-acetic acid (IAA) methyltransferase (IAMT) is a member of the SABATH family that modulates IAA homeostasis in plant tissues through methylation of IAA's free carboxyl group. The crystal structure of Arabidopsis (Arabidopsis thaliana) IAMT (AtIAMT1) was determined and refined to 2.75 Å resolution. The overall tertiary and quaternary structures closely resemble the two-domain bilobed monomer and the dimeric arrangement, respectively, previously observed for the related salicylic acid carboxyl methyltransferase from Clarkia breweri (CbSAMT). To further our understanding of the biological function and evolution of SABATHs, especially of IAMT, we analyzed the SABATH gene family in the rice (Oryza sativa) genome. Forty-one OsSABATH genes were identified. Expression analysis showed that more than one-half of the OsSABATH genes were transcribed in one or multiple organs. The OsSABATH gene most similar to AtIAMT1 is OsSABATH4. Escherichia coli-expressed OsSABATH4 protein displayed the highest level of catalytic activity toward IAA and was therefore named OsIAMT1. OsIAMT1 exhibited kinetic properties similar to AtIAMT1 and poplar IAMT (PtIAMT1). Structural modeling of OsIAMT1 and PtIAMT1 using the experimentally determined structure of AtIAMT1 reported here as a template revealed conserved structural features of IAMTs within the active-site cavity that are divergent from functionally distinct members of the SABATH family, such as CbSAMT. Phylogenetic analysis revealed that IAMTs from Arabidopsis, rice, and poplar (Populus spp.) form a monophyletic group. Thus, structural, biochemical, and phylogenetic evidence supports the hypothesis that IAMT is an evolutionarily ancient member of the SABATH family likely to play a critical role in IAA homeostasis across a wide range of plants.
Overexpression of AtMYB44 Enhances Stomatal Closure to Confer Abiotic Stress Tolerance in Transgenic Arabidopsis
Authors: Jung Choonkyun , Seo Jun Sung , Han Sang Won , Koo Yeon Jong , Kim Chung Ho , Song Sang Ik , Nahm Baek Hie , Choi Yang Do , Cheong Jong-Joo 
Published: December 2007

Abstract
AtMYB44 belongs to the R2R3 MYB subgroup 22 transcription factor family in Arabidopsis (Arabidopsis thaliana). Treatment with abscisic acid (ABA) induced AtMYB44 transcript accumulation within 30 min. The gene was also activated under various abiotic stresses, such as dehydration, low temperature, and salinity. In transgenic Arabidopsis carrying an AtMYB44 promoter-driven β-glucuronidase (GUS) construct, strong GUS activity was observed in the vasculature and leaf epidermal guard cells. Transgenic Arabidopsis overexpressing AtMYB44 is more sensitive to ABA and has a more rapid ABA-induced stomatal closure response than wild-type and atmyb44 knockout plants. Transgenic plants exhibited a reduced rate of water loss, as measured by the fresh-weight loss of detached shoots, and remarkably enhanced tolerance to drought and salt stress compared to wild-type plants. Microarray analysis and northern blots revealed that salt-induced activation of the genes that encode a group of serine/threonine protein phosphatases 2C (PP2Cs), such as ABI1, ABI2, AtPP2CA, HAB1, and HAB2, was diminished in transgenic plants overexpressing AtMYB44. By contrast, the atmyb44 knockout mutant line exhibited enhanced salt-induced expression of PP2C-encoding genes and reduced drought/salt stress tolerance compared to wild-type plants. Therefore, enhanced abiotic stress tolerance of transgenic Arabidopsis overexpressing AtMYB44 was conferred by reduced expression of genes encoding PP2Cs, which have been described as negative regulators of ABA signaling.
Arabidopsis Branched-Chain Aminotransferase 3 Functions in Both Amino Acid and Glucosinolate Biosynthesis
Authors: Knill Tanja , Schuster Joachim , Reichelt Michael , Gershenzon Jonathan , Binder Stefan 
Published: December 2007

AbstractIn Arabidopsis thaliana, transamination steps in the leucine biosynthetic and catabolic pathways and the methionine (Met) chain elongation cycle of aliphatic glucosinolate formation are catalyzed by branched-chain aminotransferases (BCATs) that are encoded by a small gene family of six members. One member of this family, the plastid-located BCAT3, was shown to participate in both amino acid and glucosinolate metabolism. In vitro activity tests with the recombinant protein identified highest activities with the 2-oxo acids of leucine, isoleucine, and valine, but also revealed substantial conversion of intermediates of the Met chain elongation pathway. Metabolite profiling of bcat3-1 single and bcat3-1/bcat4-2 double knockout mutants showed significant alterations in the profiles of both amino acids and glucosinolates. The changes in glucosinolate proportions suggest that BCAT3 most likely catalyzes the terminal steps in the chain elongation process leading to short-chain glucosinolates: the conversion of 5-methylthiopentyl-2-oxo and 6-methylthiohexyl-2-oxo acids to their respective Met derivatives, homomethionine and dihomo-methionine, respectively. The enzyme can also at least partially compensate for the loss of BCAT4, which catalyzes the initial step of Met chain elongation by converting Met to 4-methylthio-2-oxobutanoate. Our results show the interdependence of amino acid and glucosinolate metabolism and demonstrate that a single enzyme plays a role in both processes.
Specificity of RCN1-Mediated Protein Phosphatase 2A Regulation in Meristem Organization and Stress Response in Roots
Authors: Blakeslee Joshua J. , Zhou Hong-Wei , Heath Jeffrey T. , Skottke Kyle R. , Barrios Jorge A. Rodriguez , Liu Su-Yang , DeLong Alison 
Published: December 2007

Abstract
Protein dephosphorylation by the serine/threonine protein phosphatase 2A (PP2A) modulates a broad array of cellular functions. PP2A normally acts as a heterotrimeric holoenzyme complex comprising a catalytic subunit bound by regulatory A and B subunits. Characterization of the regulatory A subunit isoforms (ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1 [RCN1], PP2AA2, and PP2AA3) of Arabidopsis thaliana PP2A has shown that RCN1 plays a primary role in controlling root and hypocotyl PP2A activity in seedlings. Here we show that hypocotyl and root growth exhibit different requirements for RCN1-mediated regulation of PP2A activity. Roots of rcn1 mutant seedlings exhibit characteristic abnormalities in cell division patterns at the root apical meristem, as well as reduced growth under ionic, osmotic, and oxidative stress conditions. We constructed chimeric A subunit genes and found that restoration of normal root tip development in rcn1 plants requires both regulatory and coding sequences of RCN1, whereas the hypocotyl elongation defect of rcn1 plants can be complemented by either RCN1 or PP2AA3 transgenes. Furthermore, the RCN1 and PP2AA3 proteins exhibit ubiquitous subcellular localization patterns in seedlings and both associate with membrane compartments. Together, these results show that RCN1-containing PP2A has unique functions that cannot be attributed to isoform-specific expression and localization patterns. Postembryonic RCN1 function is required to maintain normal auxin distribution and stem cell function at the root apex. Our data show that RCN1-regulated phosphatase activity plays a unique role in regulating postembryonic root development and stress response.
High Temperature-Induced Abscisic Acid Biosynthesis and Its Role in the Inhibition of Gibberellin Action in Arabidopsis Seeds
Authors: Toh Shigeo , Imamura Akane , Watanabe Asuka , Nakabayashi Kazumi , Okamoto Masanori , Jikumaru Yusuke , Hanada Atsushi , Aso Yukie , Ishiyama Kanako , Tamura Noriko , Iuchi Satoshi , Kobayashi Masatomo , Yamaguchi Shinjiro , Kamiya Yuji , Nambara Eiji , Kawakami Naoto 
Published: December 2007

AbstractSuppression of seed germination at supraoptimal high temperature (thermoinhibiton) during summer is crucial for Arabidopsis (Arabidopsis thaliana) to establish vegetative and reproductive growth in appropriate seasons. Abscisic acid (ABA) and gibberellins (GAs) are well known to be involved in germination control, but it remains unknown how these hormone actions (metabolism and responsiveness) are altered at high temperature. Here, we show that ABA levels in imbibed seeds are elevated at high temperature and that this increase is correlated with up-regulation of the zeaxanthin epoxidase gene ABA1/ZEP and three 9-cis-epoxycarotenoid dioxygenase genes, NCED2, NCED5, and NCED9. Reverse-genetic studies show that NCED9 plays a major and NCED5 and NCED2 play relatively minor roles in high temperature-induced ABA synthesis and germination inhibition. We also show that bioactive GAs stay at low levels at high temperature, presumably through suppression of GA 20-oxidase genes, GA20ox1, GA20ox2, and GA20ox3, and GA 3-oxidase genes, GA3ox1 and GA3ox2. Thermoinhibition-tolerant germination of loss-of-function mutants of GA negative regulators, SPINDLY (SPY) and RGL2, suggests that repression of GA signaling is required for thermoinibition. Interestingly, ABA-deficient aba2-2 mutant seeds show significant expression of GA synthesis genes and repression of SPY expression even at high temperature. In addition, the thermoinhibition-resistant germination phenotype of aba2-1 seeds is suppressed by a GA biosynthesis inhibitor, paclobutrazol. We conclude that high temperature stimulates ABA synthesis and represses GA synthesis and signaling through the action of ABA in Arabidopsis seeds.
The Intense Lee-Wave Rotor Event of Sierra Rotors IOP 8
Authors: Grubišić Vanda , Billings Brian J. 
Published: December 2007

Abstract
A large-amplitude lee-wave rotor event observationally documented during Sierra Rotors Project Intensive Observing Period (IOP) 8 on 24–26 March 2004 in the lee of the southern Sierra Nevada is examined. Mountain waves and rotors occurred over Owens Valley in a pre-cold-frontal environment. In this study, the evolution and structure of the observed and numerically simulated mountain waves and rotors during the event on 25 March, in which the horizontal circulation associated with the rotor was observed as an opposing, easterly flow by the mesonetwork of surface stations in Owens Valley, are analyzed.
The high-resolution numerical simulations of this case, performed with the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) run with multiple nested-grid domains, the finest grid having 333-m horizontal spacing, reproduced many of the observed features of this event. These include small-amplitude waves above the Sierra ridge decoupled from thermally forced flow within the valley, and a large-amplitude mountain wave, turbulent rotor, and strong westerlies on the Sierra Nevada lee slopes during the period of the observed surface easterly flow. The sequence of the observed and simulated events shows a pronounced diurnal variation with the maximum wave and rotor activity occurring in the early evening hours during both days of IOP 8.
The lee-wave response, and thus indirectly the appearance of lee-wave rotor during the core IOP 8 period, is found to be strongly controlled by temporal changes in the upstream ambient wind and stability profiles. The downstream mountain range exerts strong control over the lee-wave horizontal wavelength during the strongest part of this event, thus exhibiting the control over the cross-valley position of the rotor and the degree of strong downslope wind penetration into the valley.
Predictability and Error Growth Dynamics in Cloud-Resolving Models
Authors: Hohenegger Cathy , Schär Christoph 
Published: December 2007

Abstract
While the benefits of ensemble techniques over deterministic numerical weather predictions (NWP) are now widely recognized, the prospects of ensemble prediction systems (EPS) at high computational resolution are still largely unclear. Difficulties arise due to the poor knowledge of the mechanisms promoting rapid perturbation growth and propagation, as well as the role of nonlinearities. In this study, the dynamics associated with the growth and propagation of initial uncertainties is investigated by means of real-case high-resolution (cloud resolving) NWP integrations. The considered case is taken from the Mesoscale Alpine Programme intensive observing period 3 (MAP IOP3) and involves convection of intermediate intensity. To assess the underlying mechanisms and the degree of linearity upon the predictability of the flow, vastly different initial perturbation methodologies are compared, while all simulations use identical lateral boundary conditions to mimic a perfectly predictable synoptic-scale flow.
Comparison of the perturbation methodologies indicates that the ensuing patterns of ensemble spread converge within 11 h, irrespective of the initial perturbations employed. All methodologies pinpoint the same meso-beta-scale regions of the flow as suffering from predictability limitations. This result reveals the important role of nonlinearities. Analysis also shows that hot spots of error growth can quickly (1–2 h after initialization) develop far away from the initial perturbations. This rapid radiation of the initial uncertainties throughout the computational domain is due to both sound and gravity waves, followed by the triggering and/or growth of perturbations over regions of convective instability. The growth of the uncertainties is then limited by saturation effects, which in turn are controlled by the larger-scale atmospheric environment.
From a practical point of view, it is suggested that the combined effects of rapid propagation, sizeable amplification, and inherent nonlinearities may pose severe difficulties for the design of EPS or data assimilation techniques related to high-resolution quantitative precipitation forecasting.
Evaluating Clouds in Long-Term Cloud-Resolving Model Simulations with Observational Data
Authors: Zeng Xiping , Tao Wei-Kuo , Zhang Minghua , Peters-Lidard Christa , Lang Stephen , Simpson Joanne , Kumar Sujay , Xie Shaocheng , Eastman Joseph L. , Shie Chung-Lin , Geiger James V. 
Published: December 2007

Abstract
Two 20-day, continental midlatitude cases are simulated with a three-dimensional (3D) cloud-resolving model (CRM) and are compared to Atmospheric Radiation Measurement Program (ARM) data. Surface fluxes from ARM ground stations and a land data assimilation system are used to drive the CRM. This modeling evaluation shows that the model simulates precipitation well but overpredicts clouds, especially in the upper troposphere. The evaluation also shows that the ARM surface fluxes can have noticeable errors in summertime.
Theoretical analysis reveals that buoyancy damping is sensitive to spatial smoothers in two-dimensional (2D) CRMs, but not in 3D ones. With this theoretical analysis and the ARM cloud observations as background, 2D and 3D simulations are compared, showing that the 2D CRM has not only rapid fluctuations in surface precipitation but also spurious dehumidification (or a decrease in cloud amount). The present study suggests that the rapid precipitation fluctuation and spurious dehumidification be attributed to the sensitivity of buoyancy damping to dimensionality.
MODIS Observations of Ship Tracks in Summertime Stratus off the West Coast of the United States
Authors: Segrin Matthew S. , Coakley James A. , Tahnk William R. 
Published: December 2007

Abstract
Three years of 1-km Moderate Resolution Imaging Spectroradiometer (MODIS) observations for morning (Terra) and afternoon (Aqua) summertime marine stratus off the west coast of the United States were analyzed to determine the response of the clouds to aerosols in the plumes of underlying ships. The polluted clouds were identified in pixels with elevated 2.1-μm reflectivities and 3.7-μm radiances when compared with nearby pixels that contained unpolluted clouds. An automated routine was developed to identify which of the pixels contained clouds polluted by underlying ships and then to select unpolluted control pixels on both sides of the ship track as near as was feasible to the polluted clouds, often with a separation of as little as 1 pixel. While no requirements were placed on the cloud cover fraction within the selected pixels, to facilitate comparisons with an earlier study based on 1-km Advanced Very High Resolution Radiometer (AVHRR) imagery, the results presented here are restricted to 20-pixel segments along the ship tracks in which all of the pixels identified as polluted and all of the pixels selected as controls on both sides of the tracks were found to be overcast. The pollution caused about a 20% reduction in droplet radius in both the MODIS and the AVHRR observations. In the MODIS observations, the increase in optical depth was about 15% and statistically significant at a confidence level greater than 99.5%. These changes were much larger than the 2% and statistically negligible increases found for the AVHRR observations. Like the AVHRR observations, the MODIS observations indicated that the majority of clouds (60%) lost liquid water when polluted, but consistent with the different outcomes for the optical depths, the losses for the MODIS observations were about half the nearly 20% loss found in the AVHRR observations. Cloud altitudes were unaffected by the pollution for both the MODIS and the AVHRR observations. For both morning and afternoon clouds, those with the largest increases in albedo in response to the pollution also showed the largest increases in cloud liquid water amount. The changes in droplet radii and liquid water amounts retrieved using the MODIS observations suggested that droplet growth was suppressed in the polluted clouds and that the rate of growth from cloud base to cloud top was also reduced when compared with nearby unpolluted clouds.
On the Definition of Precipitation Efficiency
Authors: Sui Chung-Hsiung , Li Xiaofan , Yang Ming-Jen 
Published: December 2007

Abstract
A modified definition of precipitation efficiency (PE) is proposed based on either cloud microphysics precipitation efficiency (CMPE) or water cycling processes including water vapor and hydrometeor species [large-scale precipitation efficiency (LSPE)]. These PEs are examined based on a two-dimensional cloud-resolving simulation. The model is integrated for 21 days with the imposed large-scale vertical velocity, zonal wind, and horizontal advections obtained from the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE). It is found that the properly defined PEs include all moisture and hydrometeor sources associated with surface rainfall processes so that they range from 0% to 100%. Furthermore, the modified LSPE and CMPE are highly correlated. Their linear correlation coefficient and root-mean-squared difference are insensitive to the spatial scales of averaged data and are moderately sensitive to the time period of averaged data.