bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma
Authors: Maarsingh Harm , Leusink John , Bos I Sophie T , Zaagsma Johan , Meurs Herman 
Published: January 2006

AbstractBackgroundUsing guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production – due to competition with neuronal NO-synthase (nNOS) for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR), leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity.In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation.MethodsElectrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nω-nitro-L-arginine (L-NNA, 100 μM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA, 10 μM). Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM).ResultsAt 6 h after ovalbumin-challenge (after the EAR), EFS-induced relaxation (ranging from 3.2 ± 1.1% at 0.5 Hz to 58.5 ± 2.2% at 16 Hz) was significantly decreased compared to unchallenged controls (7.1 ± 0.8% to 75.8 ± 0.7%;P< 0.05 all). In contrast to unchallenged controls, the NOS inhibitor L-NNA did not affect EFS-induced relaxation after allergen challenge, indicating that NO deficiency underlies the impaired relaxation. Remarkably, the specific arginase inhibitor nor-NOHA normalized the impaired relaxation to unchallenged control (P< 0.05 all), which effect was inhibited by L-NNA (P< 0.01 all). Moreover, the effect of nor-NOHA was mimicked by exogenous L-arginine.ConclusionThe results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.
Tooth loss and obstructive sleep apnoea
Authors: Bucca Caterina , Cicolin Alessandro , Brussino Luisa , Arienti Andrea , Graziano Alessandra , Erovigni Francesco , Pera Paolo , Gai Valerio , Mutani Roberto , Preti Giulio , Rolla Giovanni , Carossa Stefano 
Published: January 2006

Abstract

Background
Complete tooth loss (edentulism) produces anatomical changes that may impair upper airway size and function. The aim of this study was to evaluate whether edentulism favours the occurrence of obstructive sleep apnoea (OSA).

Methods
Polysomnography was performed in 48 edentulous subjects on two consecutive nights, one slept with and the other without dentures. Upper airway size was assessed by cephalometry and by recording forced mid-inspiratory airflow rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as markers of airway and oropharyngeal inflammation.

Results
The apnoea/hypopnoea index (AHI) without dentures was significantly higher than with dentures (17·4 ± 3·6 versus 11·0 ± 2·3. p = 0·002), and was inversely related to FIF50 (p = 0·017) and directly related to eNO (p = 0·042). Sleeping with dentures, 23 subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without dentures the number of subjects with abnormal AHI rose to 34 (71%). At cephalometry, removing dentures produced a significant decrease in retropharyngeal space (from 1·522 ± 0·33 cm to 1·27 ± 0·42 cm, p = 0·006). Both morning eNO and oNO were higher after the night slept without dentures (eNO 46·1 ± 8·2 ppb versus 33·7 ± 6·3 ppb, p = 0·035, oNO 84·6 ± 13·7 ppb versus 59·2 ± 17·4 ppb, p = 0·001).

Conclusion
These findings suggest that complete tooth loss favours upper airway obstruction during sleep. This untoward effect seems to be due to decrease in retropharyngeal space and is associated with increased oral and exhaled NO concentration.
Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells
Authors: Growcott Ellena J , Spink Karen G , Ren Xiaohui , Afzal Saliha , Banner Kathy H , Wharton John 
Published: January 2006

AbstractBackgroundPulmonary arterial hypertension is a proliferative vascular disease, characterized by aberrant regulation of smooth muscle cell proliferation and apoptosis in distal pulmonary arteries. Prostacyclin (PGI2) analogues have anti-proliferative effects on distal human pulmonary artery smooth muscle cells (PASMCs), which are dependent on intracellular cAMP stimulation. We therefore sought to investigate the involvement of the main cAMP-specific enzymes, phosphodiesterase type 4 (PDE4), responsible for cAMP hydrolysis.MethodsDistal human PASMCs were derived from pulmonary arteries by explant culture (n = 14, passage 3–12). Responses to platelet-derived growth factor-BB (5–10 ng/ml), serum, PGI2analogues (cicaprost, iloprost) and PDE4 inhibitors (roflumilast, rolipram, cilomilast) were determined by measuring cAMP phosphodiesterase activity, intracellular cAMP levels, DNA synthesis, apoptosis (as measured by DNA fragmentation and nuclear condensation) and matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) production.ResultsExpression of all fourPDE4A-Dgenes was detected in PASMC isolates. PDE4 contributed to the main proportion (35.9 ± 2.3%, n = 5) of cAMP-specific hydrolytic activity demonstrated in PASMCs, compared to PDE3 (21.5 ± 2.5%), PDE2 (15.8 ± 3.4%) or PDE1 activity (14.5 ± 4.2%). Intracellular cAMP levels were increased by PGI2analogues and further elevated in cells co-treated with roflumilast, rolipram and cilomilast. DNA synthesis was attenuated by 1 μM roflumilast (49 ± 6% inhibition), rolipram (37 ± 6%) and cilomilast (30 ± 4%) and, in the presence of 5 nM cicaprost, these compounds exhibited EC50values of 4.4 (2.6–6.1) nM (Mean and 95% confidence interval), 59 (36–83) nM and 97 (66–130) nM respectively. Roflumilast attenuated cell proliferation and gelatinase (MMP-2 and MMP-9) production and promoted the anti-proliferative effects of PGI2analogues. The cAMP activators iloprost and forskolin also induced apoptosis, whereas roflumilast had no significant effect.ConclusionPDE4 enzymes are expressed in distal human PASMCs and the effects of cAMP-stimulating agents on DNA synthesis, proliferation and MMP production is dependent, at least in part, on PDE4 activity. PDE4 inhibition may provide greater control of cAMP-mediated anti-proliferative effects in human PASMCs and therefore could prove useful as an additional therapy for pulmonary arterial hypertension.
An improved procedure for gene selection from microarray experiments using false discovery rate criterion
Authors: Yang James J , Yang Mark CK 
Published: January 2006

AbstractBackgroundA large number of genes usually show differential expressions in a microarray experiment with two types of tissues, and thep-values of a proper statistical test are often used to quantify the significance of these differences. The genes with smallp-values are then picked as the genes responsible for the differences in the tissue RNA expressions. One key question is what should be the threshold to consider thep-values small. There is always a trade off between this threshold and the rate of false claims. Recent statistical literature shows that the false discovery rate (FDR) criterion is a powerful and reasonable criterion to pick those genes with differential expression. Moreover, the power of detection can be increased by knowing the number of non-differential expression genes. While this number is unknown in practice, there are methods to estimate it from data. The purpose of this paper is to present a new method of estimating this number and use it for the FDR procedure construction.ResultsA combination of test functions is used to estimate the number of differentially expressed genes. Simulation study shows that the proposed method has a higher power to detect these genes than other existing methods, while still keeping the FDR under control. The improvement can be substantial if the proportion of true differentially expressed genes is large. This procedure has also been tested with good results using a real dataset.ConclusionFor a given expected FDR, the method proposed in this paper has better power to pick genes that show differentiation in their expression than two other well known methods.
GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins
Authors: Durand Patrick , Labarre Laurent , Meil Alain , Divol Jean-Louis , Vandenbrouck Yves , Viari Alain , Wojcik Jérôme 
Published: January 2006

Abstract

Background
A large variety of biological data can be represented by graphs. These graphs can be constructed from heterogeneous data coming from genomic and post-genomic technologies, but there is still need for tools aiming at exploring and analysing such graphs. This paper describes GenoLink, a software platform for the graphical querying and exploration of graphs.

Results
GenoLink provides a generic framework for representing and querying data graphs. This framework provides a graph data structure, a graph query engine, allowing to retrieve sub-graphs from the entire data graph, and several graphical interfaces to express such queries and to further explore their results. A query consists in a graph pattern with constraints attached to the vertices and edges. A query result is the set of all sub-graphs of the entire data graph that are isomorphic to the pattern and satisfy the constraints. The graph data structure does not rely upon any particular data model but can dynamically accommodate for any user-supplied data model. However, for genomic and post-genomic applications, we provide a default data model and several parsers for the most popular data sources. GenoLink does not require any programming skill since all operations on graphs and the analysis of the results can be carried out graphically through several dedicated graphical interfaces.

Conclusion
GenoLink is a generic and interactive tool allowing biologists to graphically explore various sources of information. GenoLink is distributed either as a standalone application or as a component of the Genostar/Iogma platform. Both distributions are free for academic research and teaching purposes and can be requested at academy@genostar.com. A commercial licence form can be obtained for profit company at info@genostar.com. See also http://www.genostar.org.
NOXclass: prediction of protein-protein interaction types
Authors: Zhu Hongbo , Domingues Francisco S , Sommer Ingolf , Lengauer Thomas 
Published: January 2006

Abstract

Background
Structural models determined by X-ray crystallography play a central role in understanding protein-protein interactions at the molecular level. Interpretation of these models requires the distinction between non-specific crystal packing contacts and biologically relevant interactions. This has been investigated previously and classification approaches have been proposed. However, less attention has been devoted to distinguishing different types of biological interactions. These interactions are classified as obligate and non-obligate according to the effect of the complex formation on the stability of the protomers. So far no automatic classification methods for distinguishing obligate, non-obligate and crystal packing interactions have been made available.

Results
Six interface properties have been investigated on a dataset of 243 protein interactions. The six properties have been combined using a support vector machine algorithm, resulting in NOXclass, a classifier for distinguishing obligate, non-obligate and crystal packing interactions. We achieve an accuracy of 91.8% for the classification of these three types of interactions using a leave-one-out cross-validation procedure.

Conclusion
NOXclass allows the interpretation and analysis of protein quaternary structures. In particular, it generates testable hypotheses regarding the nature of protein-protein interactions, when experimental results are not available. We expect this server will benefit the users of protein structural models, as well as protein crystallographers and NMR spectroscopists. A web server based on the method and the datasets used in this study are available at http://noxclass.bioinf.mpi-inf.mpg.de/.
A new pooling strategy for high-throughput screening: the Shifted Transversal Design
Authors: Thierry-Mieg Nicolas 
Published: January 2006

Abstract

Background
In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem.

Results
In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates). Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs.

Conclusion
This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design.
Recrafting the neighbor-joining method
Authors: Mailund Thomas , Brodal Gerth S , Fagerberg Rolf , Pedersen Christian NS , Phillips Derek 
Published: January 2006

AbstractBackgroundThe neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n3) algorithm upon which all existing implementations are based.ResultsIn this paper we present techniques for speeding up the canonical neighbor-joining method. Our algorithms construct the same phylogenetic trees as the canonical neighbor-joining method. The best-case running time of our algorithms areO(n2) but the worst-case remainsO(n3). We empirically evaluate the performance of our algoritms on distance matrices obtained from the Pfam collection of alignments. The experiments indicate that the running time of our algorithms evolve as Θ(n2) on the examined instance collection. We also compare the running time with that of the QuickTree tool, a widely used efficient implementation of the canonical neighbor-joining method.ConclusionThe experiments show that our algorithms also yield a significant speed-up, already for medium sized instances.
Missing value estimation for DNA microarray gene expression data by Support Vector Regression imputation and orthogonal coding scheme
Authors: Wang Xian , Li Ao , Jiang Zhaohui , Feng Huanqing 
Published: January 2006

Abstract

Background
Gene expression profiling has become a useful biological resource in recent years, and it plays an important role in a broad range of areas in biology. The raw gene expression data, usually in the form of large matrix, may contain missing values. The downstream analysis methods that postulate complete matrix input are thus not applicable. Several methods have been developed to solve this problem, such as K nearest neighbor impute method, Bayesian principal components analysis impute method, etc. In this paper, we introduce a novel imputing approach based on the Support Vector Regression (SVR) method. The proposed approach utilizes an orthogonal coding input scheme, which makes use of multi-missing values in one row of a certain gene expression profile and imputes the missing value into a much higher dimensional space, to obtain better performance.

Results
A comparative study of our method with the previously developed methods has been presented for the estimation of the missing values on six gene expression data sets. Among the three different input-vector coding schemes we tried, the orthogonal input coding scheme obtains the best estimation results with the minimum Normalized Root Mean Squared Error (NRMSE). The results also demonstrate that the SVR method has powerful estimation ability on different kinds of data sets with relatively small NRMSE.

Conclusion
The SVR impute method shows better performance than, or at least comparable with, the previously developed methods in present research. The outstanding estimation ability of this impute method is partly due to the use of the most missing value information by incorporating orthogonal input coding scheme. In addition, the solid theoretical foundation of SVR method also helps in estimation of performance together with orthogonal input coding scheme. The promising estimation ability demonstrated in the results section suggests that the proposed approach provides a proper solution to the missing value estimation problem. The source code of the SVR method is available from http://202.38.78.189/downloads/svrimpute.html for non-commercial use.
The comprehensive updated regulatory network of Escherichia coli K-12
Authors: Salgado Heladia , Santos-Zavaleta Alberto , Gama-Castro Socorro , Peralta-Gil Martín , Peñaloza-Spínola Mónica I , Martínez-Antonio Agustino , Karp Peter D , Collado-Vides Julio 
Published: January 2006

Abstract

Background

Escherichia coli is the model organism for which our knowledge of its regulatory network is the most extensive. Over the last few years, our project has been collecting and curating the literature concerning E. coli transcription initiation and operons, providing in both the RegulonDB and EcoCyc databases the largest electronically encoded network available. A paper published recently by Ma et al. (2004) showed several differences in the versions of the network present in these two databases.
Discrepancies have been corrected, annotations from this and other groups (Shen-Orr et al., 2002) have been added, making the RegulonDB and EcoCyc databases the largest comprehensive and constantly curated regulatory network of E. coli K-12.

Results
Several groups have been using these curated data as part of their bioinformatics and systems biology projects, in combination with external data obtained from other sources, thus enlarging the dataset initially obtained from either RegulonDB or EcoCyc of the E. coli K12 regulatory network. We kindly obtained from the groups of Uri Alon and Hong-Wu Ma the interactions they have added to enrich their public versions of the E. coli regulatory network. These were used to search for original references and curate them with the same standards we use regularly, adding in several cases the original references (instead of reviews or missing references), as well as adding the corresponding experimental evidence codes. We also corrected all discrepancies in the two databases available as explained below.

Conclusion
One hundred and fifty new interactions have been added to our databases as a result of this specific curation effort, in addition to those added as a result of our continuous curation work. RegulonDB gene names are now based on those of EcoCyc to avoid confusion due to gene names and synonyms, and the public releases of RegulonDB and EcoCyc are henceforth synchronized to avoid confusion due to different versions. Public flat files are available providing direct access to the regulatory network interactions thus avoiding errors due to differences in database modelling and representation. The regulatory network available in RegulonDB and EcoCyc is the most comprehensive and regularly updated electronically-encoded regulatory network of E. coli K-12.
ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes
Authors: Guo Feng-Biao , Zhang Chun-Ting 
Published: January 2006

Abstract

Background
It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes.

Results
The new system ZCURVE_V has been run for 979 viral and 212 phage genomes, respectively, and satisfactory results are obtained. To have a fair comparison with the currently available software of similar function, GeneMark, a total of 30 viral genomes that have not been annotated by GeneMark are selected to be tested. Consequently, the average specificity of both systems is well matched, however the average sensitivity of ZCURVE_V for smaller viral genomes (< 100 kb), which constitute the main parts of viral genomes sequenced so far, is higher than that of GeneMark. Additionally, for the genome of Amsacta moorei entomopoxvirus, probably with the lowest genomic GC content among the sequenced organisms, the accuracy of ZCURVE_V is much better than that of GeneMark, because the later predicts hundreds of false-positive genes. ZCURVE_V is also used to analyze well-studied genomes, such as HIV-1, HBV and SARS-CoV. Accordingly, the performance of ZCURVE_V is generally better than that of GeneMark. Finally, ZCURVE_V may be downloaded and run locally, particularly facilitating its utilization, whereas GeneMark is not downloadable. Based on the above comparison, it is suggested that ZCURVE_V may serve as a preferred gene-finding tool for viral and phage genomes newly sequenced. However, it is also shown that the joint application of both systems, ZCURVE_V and GeneMark, leads to better gene-finding results. The system ZCURVE_V is freely available at: http://tubic.tju.edu.cn/Zcurve_V/.

Conclusion
ZCURVE_V may serve as a preferred gene-finding tool used for viral and phage genomes, especially for anonymous viral and phage genomes newly sequenced.