bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5‐HT3 receptors
Authors: Thompson A J , Lochner M , Lummis S C R 
Published: May 2007

Background and Purpose:The antimalarial compounds quinine, chloroquine and mefloquine affect the electrophysiological properties of Cys‐loop receptors and have structural similarities to 5‐HT3 receptor antagonists. They may therefore act at 5‐HT3 receptors.Experimental Approach:The effects of quinine, chloroquine and mefloquine on electrophysiological and ligand binding properties of 5‐HT3A receptors expressed in HEK 293 cells and Xenopus oocytes were examined. The compounds were also docked into models of the binding site.Key Results:5‐HT3 responses were blocked with IC50 values of 13.4 μM, 11.8 μM and 9.36 μM for quinine, chloroquine and mefloquine. Schild plots indicated quinine and chloroquine behaved competitively with pA2 values of 4.92 (KB=12.0 μM) and 4.97 (KB=16.4 μM). Mefloquine displayed weakly voltage‐dependent, non‐competitive inhibition consistent with channel block. On and off rates for quinine and chloroquine indicated a simple bimolecular reaction scheme. Quinine, chloroquine and mefloquine displaced [3H]granisetron with Ki values of 15.0, 24.2 and 35.7 μM. Docking of quinine into a homology model of the 5‐HT3 receptor binding site located the tertiary ammonium between W183 and Y234, and the quinoline ring towards the membrane, stabilised by a hydrogen bond with E129. For chloroquine, the quinoline ring was positioned between W183 and Y234 and the tertiary ammonium stabilised by interactions with F226.Conclusions and Implications:This study shows that quinine and chloroquine competitively inhibit 5‐HT3 receptors, while mefloquine inhibits predominantly non‐competitively. Both quinine and chloroquine can be docked into a receptor binding site model, consistent with their structural homology to 5‐HT3 receptor antagonists.British Journal of Pharmacology (2007) 151, 666–677; doi:10.1038/sj.bjp.0707238
Augmentation of spinal morphine analgesia and inhibition of tolerance by low doses of μ‐ and δ‐opioid receptor antagonists
Authors: Abul‐Husn N S , Sutak M , Milne B , Jhamandas K 
Published: May 2007

Background and purpose:Ultralow doses of naltrexone, a non‐selective opioid antagonist, have previously been found to augment acute morphine analgesia and block the development of tolerance to this effect. Since morphine tolerance is dependent on the activity of μ and δ receptors, the present study investigated the effects of ultralow doses of antagonists selective for these receptor types on morphine analgesia and tolerance in tests of thermal and mechanical nociception.Experimental approach:Effects of intrathecal administration of μ‐receptor antagonists, CTOP (0.01 ng) or CTAP (0.001 ng), or a δ‐receptor antagonist, naltrindole (0.01 ng), on spinal morphine analgesia and tolerance were evaluated using the tail‐flick and paw‐pressure tests in rats.Key results:Both μ and δ antagonists augmented analgesia produced by a sub‐maximal (5 μg) or maximal (15 μg) dose of morphine. Administration of the antagonists with morphine (15 μg) for 5 days inhibited the progressive decline of analgesia and prevented the loss of morphine potency. In animals exhibiting tolerance to morphine, administration of the antagonists with morphine produced a recovery of the analgesic response and restored morphine potency.Conclusions and implications:Combining ultralow doses of μ‐ or δ‐receptor antagonists with spinal morphine augmented the acute analgesic effects, inhibited the induction of chronic tolerance and reversed established tolerance. The remarkably similar effects of μ‐ and δ‐opioid receptor antagonists on morphine analgesia and tolerance are interpreted in terms of blockade of the latent excitatory effects of the agonist that limit expression of its full activity.British Journal of Pharmacology (2007) 151, 877–887; doi:10.1038/sj.bjp.0707277
Data reduction of isotope-resolved LC-MS spectra
Authors: Du Peicheng , Sudha Rajagopalan , Prystowsky Michael B. , Angeletti Ruth Hogue 
Published: May 2007

AbstractMotivation: Data reduction of liquid chromatography-mass spectrometry (LC-MS) spectra can be a challenge due to the inherent complexity of biological samples, noise and non-flat baseline. We present a new algorithm, LCMS-2D, for reliable data reduction of LC-MS proteomics data.Results: LCMS-2D can reliably reduce LC-MS spectra with multiple scans to a list of elution peaks, and subsequently to a list of peptide masses. It is capable of noise removal, and deconvoluting peaks that overlap in m/z, in retention time, or both, by using a novel iterative peak-picking step, a ‘rescue’ step, and a modified variable selection method. LCMS-2D performs well with three sets of annotated LC-MS spectra, yielding results that are better than those from PepList, msInspect and the vendor software BioAnalyst.Availability: The software LCMS-2D is available under the GNU general public license from http://www.bioc.aecom.yu.edu/labs/angellab/as a standalone C program running on LINUX.Contact: pdu@us.ibm.com
WilcoxCV: an R package for fast variable selection in cross-validation
Authors: Boulesteix Anne-Laure 
Published: May 2007

Abstract
Summary: In the last few years, numerous methods have been proposed for microarray-based class prediction. Although many of them have been designed especially for the case n ≪ p (much more variables than observations), preliminary variable selection is almost always necessary when the number of genes reaches several tens of thousands, as usual in recent data sets. In the two-class setting, the Wilcoxon rank sum test statistic is, with the t-statistic, one of the standard approaches for variable selection. It is well known that the variable selection step must be seen as a part of classifier construction and, as such, be performed based on training data only. When classifier accuracy is evaluated via cross-validation or Monte–Carlo cross-validation, it means that we have to perform p Wilcoxon or t-tests for each iteration, which becomes a daunting task for increasing p. As a consequence, many authors often perform variable selection only once using all the available data, which can induce a dramatic underestimation of error rate and thus lead to misleadingly reporting predictive power. We propose a very fast implementation of variable selection based on the Wilcoxon test for use in cross-validation and Monte Carlo cross-validation (also known as random splitting into learning and test sets). This implementation is based on a simple mathematical formula using only the ranks calculated from the original data set.
Availability: Our method is implemented in the freely available R package WilcoxCV which can be downloaded from the Comprehensive R Archive Network at http://cran.r-project.org/src/contrib/Descriptions/WilcoxCV.html
Contact: boulesteix@slcmsr.org
MutationFinder: a high-performance system for extracting point mutation mentions from text
Authors: Caporaso J. Gregory , Baumgartner William A. , Randolph David A. , Cohen K. Bretonnel , Hunter Lawrence 
Published: May 2007

AbstractSummary: Discussion of point mutations is ubiquitous in biomedical literature, and manually compiling databases or literature on mutations in specific genes or proteins is tedious. We present an open-source, rule-based system, MutationFinder, for extracting point mutation mentions from text. On blind test data, it achieves nearly perfect precision and a markedly improved recall over a baseline.Availability: MutationFinder, along with a high-quality gold standard data set, and a scoring script for mutation extraction systems have been made publicly available. Implementations, source code and unit tests are available in Python, Perl and Java. MutationFinder can be used as a stand-alone script, or imported by other applications.Project URL: http://bionlp.sourceforge.netContact: gregcaporaso@gmail.com
PLMaddon: a power-law module for the Matlab™ SBToolbox
Authors: Vera Julio , Sun Cheng , Oertel Yvonne , Wolkenhauer Olaf 
Published: May 2007

AbstractSummary: PLMaddon is a General Public License (GPL) software module designed to expand the current version of the SBToolbox (a Matlab ™ toolbox for systems biology; www.sbtoolbox.org) with a set of functions for the analysis of power-law models, a specific class of kinetic models, set in ordinary differential equations (ODE) and in which the kinetic orders can have positive/negative non-integer values. The module includes functions to generate power-law Taylor expansions of other ODE models (e.g. Michaelis-Menten type models), as well as algorithms to estimate steady-states. The robustness and sensitivity of the models can also be analysed and visualized by computing the power-law's logarithmic gains and sensitivities.Availability: PLMaddon is an open source module for the analysis of power-law models based on the SBToolbox. The latest version of PLMaddon is freely available from:www.sbi.uni-rostock.de/plmaddonThe website contains a tutorial with examples, as well as an interactive introductory course on power-law models in systems biology.Contact: olaf.wolkenhauer@uni-rostock.de
Nucleotide composition string selection in HIV-1 subtyping using whole genomes
Authors: Wu Xiaomeng , Cai Zhipeng , Wan Xiu-Feng , Hoang Tin , Goebel Randy , Lin Guohui 
Published: May 2007

AbstractMotivation: The availability of the whole genomic sequences of HIV-1 viruses provides an excellent resource for studying the HIV-1 phylogenies using all the genetic materials. However, such huge volumes of data create computational challenges in both memory consumption and CPU usage.Results: We propose the complete composition vector representation for an HIV-1 strain, and a string scoring method to extract the nucleotide composition strings that contain the richest evolutionary information for phylogenetic analysis. In this way, a large-scale whole genome phylogenetic analysis for thousands of strains can be done both efficiently and effectively. By using 42 carefully curated strains as references, we apply our method to subtype 1156 HIV-1 strains (10.5 million nucleotides in total), which include 825 pure subtype strains and 331 recombinants. Our results show that our nucleotide composition string selection scheme is computationally efficient, and is able to define both pure subtypes and recombinant forms for HIV-1 strains using the 5000 top ranked nucleotide strings.Availability: The Java executable and the HIV-1 datasets are accessible through ‘http://www.cs.ualberta.ca/~ghlin/src/WebTools/hiv.phpContact: ghlin@cs.ualberta.caSupplementary information: Supplementary data are available at Bioinformatics online.
HAWAIIAN SKIRT: An F-Box Gene That Regulates Organ Fusion and Growth in Arabidopsis
Authors: González-Carranza Zinnia H. , Rompa Unchalee , Peters Janny L. , Bhatt Anuj M. , Wagstaff Carol , Stead Anthony D. , Roberts Jeremy A. 
Published: May 2007

AbstractA fast neutron-mutagenized population of Arabidopsis (Arabidopsis thaliana) Columbia-0 wild-type plants was screened for floral phenotypes and a novel mutant, termed hawaiian skirt (hws), was identified that failed to shed its reproductive organs. The mutation is the consequence of a 28 bp deletion that introduces a premature amber termination codon into the open reading frame of a putative F-box protein (At3g61590). The most striking anatomical characteristic of hws plants is seen in flowers where individual sepals are fused along the lower part of their margins. Crossing of the abscission marker, ProPGAZAT:β-glucuronidase, into the mutant reveals that while floral organs are retained it is not the consequence of a failure of abscission zone cells to differentiate. Anatomical analysis indicates that the fusion of sepal margins precludes shedding even though abscission, albeit delayed, does occur. Spatial and temporal characterization, using ProHWS:β-glucuronidase or ProHWS:green fluorescent protein fusions, has identified HWS expression to be restricted to the stele and lateral root cap, cotyledonary margins, tip of the stigma, pollen, abscission zones, and developing seeds. Comparative phenotypic analyses performed on the hws mutant, Columbia-0 wild type, and Pro35S:HWS ectopically expressing lines has revealed that loss of HWS results in greater growth of both aerial and below-ground organs while overexpressing the gene brings about a converse effect. These observations are consistent with HWS playing an important role in regulating plant growth and development.
Identification of a Bipartite Jasmonate-Responsive Promoter Element in the Catharanthus roseus ORCA3 Transcription Factor Gene That Interacts Specifically with AT-Hook DNA-Binding Proteins
Authors: Vom Endt Débora , Soares e Silva Marina , Kijne Jan W. , Pasquali Giancarlo , Memelink Johan 
Published: May 2007

Abstract
Jasmonates are plant signaling molecules that play key roles in defense against certain pathogens and insects, among others, by controlling the biosynthesis of protective secondary metabolites. In Catharanthus roseus, the APETALA2-domain transcription factor ORCA3 is involved in the jasmonate-responsive activation of terpenoid indole alkaloid biosynthetic genes. ORCA3 gene expression is itself induced by jasmonate. By loss- and gain-of-function experiments, we located a 74-bp region within the ORCA3 promoter, which contains an autonomous jasmonate-responsive element (JRE). The ORCA3 JRE is composed of two important sequences: a quantitative sequence responsible for a high level of expression and a qualitative sequence that appears to act as an on/off switch in response to methyl jasmonate. We isolated 12 different DNA-binding proteins having one of four different types of DNA-binding domains, using the ORCA3 JRE as bait in a yeast (Saccharomyces cerevisiae) one-hybrid transcription factor screening. The binding of one class of proteins bearing a single AT-hook DNA-binding motif was affected by mutations in the quantitative sequence within the JRE. Two of the AT-hook proteins tested had a weak activating effect on JRE-mediated reporter gene expression, suggesting that AT-hook family members may be involved in determining the level of expression of ORCA3 in response to jasmonate.
Comparative Cross-Species Alternative Splicing in Plants
Authors: Ner-Gaon Hadas , Leviatan Noam , Rubin Eitan , Fluhr Robert 
Published: May 2007

Abstract
Alternative splicing (AS) can add significantly to genome complexity. Plants are thought to exhibit less AS than animals. An algorithm, based on expressed sequence tag (EST) pairs gapped alignment, was developed that takes advantage of the relatively small intron and exon size in plants and directly compares pairs of ESTs to search for AS. EST pairs gapped alignment was first evaluated in Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and tomato (Solanum lycopersicum) for which annotated genome sequence is available and was shown to accurately predict splicing events. The method was then applied to 11 plant species that include 17 cultivars for which enough ESTs are available. The results show a large, 3.7-fold difference in AS rates between plant species with Arabidopsis and rice in the lower range and lettuce (Lactuca sativa) and sorghum (Sorghum bicolor) in the upper range. Hence, compared to higher animals, plants show a much greater degree of variety in their AS rates and in some plant species the rates of animal and plant AS are comparable although the distribution of AS types may differ. In eudicots but not monocots, a correlation between genome size and AS rates was detected, implying that in eudicots the mechanisms that lead to larger genomes are a driving force for the evolution of AS.
Patterns of Selection and Tissue-Specific Expression among Maize Domestication and Crop Improvement Loci
Authors: Hufford Kristina M. , Canaran Payan , Ware Doreen H. , McMullen Michael D. , Gaut Brandon S. 
Published: May 2007

Abstract
The domestication of maize (Zea mays sp. mays) from its wild progenitors represents an opportunity to investigate the timing and genetic basis of morphological divergence resulting from artificial selection on target genes. We compared sequence diversity of 30 candidate selected and 15 reference loci between the three populations of wild teosintes, maize landraces, and maize inbred lines. We inferred an approximately equal ratio of genes selected during early domestication and genes selected during modern crop breeding. Using an expanded dataset of 48 candidate selected and 658 neutral reference loci, we tested the hypothesis that candidate selected genes in maize are more likely to have transcriptional functions than neutral reference genes, but there was no overrepresentation of regulatory genes in the selected gene dataset. Electronic northern analysis revealed that candidate genes are significantly overexpressed in the maize ear relative to vegetative tissues such as maize shoot, leaf, and root tissue. The maize ear underwent dramatic morphological alteration upon domestication and has been a continuing target of selection for maize yield. Therefore, we hypothesize that genes targeted by selection are more likely to be expressed in tissues that experienced high levels of morphological divergence during domestication and crop improvement.
Deletion of Glycine Decarboxylase in Arabidopsis Is Lethal under Nonphotorespiratory Conditions
Authors: Engel Nadja , van den Daele Kirsten , Kolukisaoglu Üner , Morgenthal Katja , Weckwerth Wolfram , Pärnik Tiit , Keerberg Olav , Bauwe Hermann 
Published: May 2007

Abstract
The mitochondrial multienzyme glycine decarboxylase (GDC) catalyzes the tetrahydrofolate-dependent catabolism of glycine to 5,10-methylene-tetrahydrofolate and the side products NADH, CO2, and NH3. This reaction forms part of the photorespiratory cycle and contributes to one-carbon metabolism. While the important role of GDC for these two metabolic pathways is well established, the existence of bypassing reactions has also been suggested. Therefore, it is not clear to what extent GDC is obligatory for these processes. Here, we report on features of individual and combined T-DNA insertion mutants for one of the GDC subunits, P protein, which is encoded by two genes in Arabidopsis (Arabidopsis thaliana). The individual knockout of either of these two genes does not significantly alter metabolism and photosynthetic performance indicating functional redundancy. In contrast, the double mutant does not develop beyond the cotyledon stage in air enriched with 0.9% CO2. Rosette leaves do not appear and the seedlings do not survive for longer than about 3 to 4 weeks under these nonphotorespiratory conditions. This feature distinguishes the GDC-lacking double mutant from all other known photorespiratory mutants and provides evidence for the nonreplaceable function of GDC in vital metabolic processes other than photorespiration.
Monoacylglycerols Are Components of Root Waxes and Can Be Produced in the Aerial Cuticle by Ectopic Expression of a Suberin-Associated Acyltransferase
Authors: Li Yonghua , Beisson Fred , Ohlrogge John , Pollard Mike 
Published: May 2007

Abstract
The interface between plants and the environment is provided for aerial organs by epicuticular waxes that have been extensively studied. By contrast, little is known about the nature, biosynthesis, and role of waxes at the root-rhizosphere interface. Waxes isolated by rapid immersion of Arabidopsis (Arabidopsis thaliana) roots in organic solvents were rich in saturated C18-C22 alkyl esters of p-hydroxycinnamic acids, but also contained significant amounts of both α- and β-isomers of monoacylglycerols with C22 and C24 saturated acyl groups and the corresponding free fatty acids. Production of these compounds in root waxes was positively correlated to the expression of sn-glycerol-3-P acyltransferase5 (GPAT5), a gene encoding an acyltransferase previously shown to be involved in aliphatic suberin synthesis. This suggests a direct metabolic relationship between suberin and some root waxes. Furthermore, when ectopically expressed in Arabidopsis, GPAT5 produced very-long-chain saturated monoacylglycerols and free fatty acids as novel components of cuticular waxes. The crystal morphology of stem waxes was altered and the load of total stem wax compounds was doubled, although the major components typical of the waxes found on wild-type plants decreased. These results strongly suggest that GPAT5 functions in vivo as an acyltransferase to a glycerol-containing acceptor and has access to the same pool of acyl intermediates and/or may be targeted to the same membrane domain as that of wax synthesis in aerial organs.
Phosphatidylinositol 4-Kinase Activation Is an Early Response to Salicylic Acid in Arabidopsis Suspension Cells
Authors: Krinke Ondřej , Ruelland Eric , Valentová Olga , Vergnolle Chantal , Renou Jean-Pierre , Taconnat Ludivine , Flemr Matyáš , Burketová Lenka , Zachowski Alain 
Published: May 2007

AbstractSalicylic acid (SA) has a central role in defense against pathogen attack. In addition, its role in such diverse processes as germination, flowering, senescence, and thermotolerance acquisition has been documented. However, little is known about the early signaling events triggered by SA. Using Arabidopsis (Arabidopsis thaliana) suspension cells as a model, it was possible to show by in vivo metabolic phospholipid labeling with 33Pi that SA addition induced a rapid and early (in few minutes) decrease in a pool of phosphatidylinositol (PI). This decrease paralleled an increase in PI 4-phosphate and PI 4,5-bisphosphate. These changes could be inhibited by two different inhibitors of type III PI 4-kinases, phenylarsine oxide and 30 μ m wortmannin; no inhibitory effect was seen with 1 μ m wortmannin, a concentration inhibiting PI 3-kinases but not PI 4-kinases. We therefore undertook a study of the effects of wortmannin on SA-responsive transcriptomes. Using the Complete Arabidopsis Transcriptome MicroArray chip, we could identify 774 genes differentially expressed upon SA treatment. Strikingly, among these genes, the response to SA of 112 of them was inhibited by 30 μ m wortmannin, but not by 1 μ m wortmannin.
Arabidopsis VIRE2 INTERACTING PROTEIN2 Is Required for Agrobacterium T-DNA Integration in Plants
Authors: Anand Ajith , Krichevsky Alexander , Schornack Sebastian , Lahaye Thomas , Tzfira Tzvi , Tang Yuhong , Citovsky Vitaly , Mysore Kirankumar S. 
Published: May 2007

Abstract
Agrobacterium tumefaciens–mediated genetic transformation is an efficient tool for genetic engineering of plants. VirE2 is a single-stranded DNA binding Agrobacterium protein that is transported into the plant cell and presumably protects the T-DNA from degradation. Using a yeast two-hybrid system, we identified Arabidopsis thaliana VIRE2-INTERACTING PROTEIN2 (VIP2) with a NOT domain that is conserved in both plants and animals. Furthermore, we provide evidence supporting VIP2 interaction with VIP1, a basic domain/leucine zipper motif–containing protein required for nuclear import and integration of T-DNA. Virus-induced gene silencing of VIP2 in Nicotiana benthamiana and characterization of the Arabidopsis vip2 mutant (At vip2) demonstrate that VIP2 is required for Agrobacterium-mediated stable transformation but not for transient transformation. Assays based upon a promoter-trap vector and quantification of T-DNA integration further confirmed VIP2 involvement in T-DNA integration. Interestingly, VIP2 transcripts were induced to a greater extent over prolonged periods after infection with a T-DNA transfer-competent Agrobacterium strain compared with the transfer-deficient Agrobacterium strain. Transcriptome analyses of At vip2 suggest that VIP2 is likely a transcriptional regulator, and the recalcitrancy to transformation in At vip2 is probably due to the combination of muted gene expression response upon Agrobacterium infection and repression of histone genes resulting in decreased T-DNA integration events.