bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Frequent’ ventricular bigeminy – A reversible cause of dilated cardiomyopathy. How frequent is ‘frequent’?
Authors: Shanmugam N. , Chua T.P. , Ward D. 
Published: March 2006

AbstractAn interesting development in the field of heart failure has been the link between frequent premature ventricular contractions and cardiomyopathy. We report a patient whose frequent ventricular bigeminy resulted in left ventricular impairment that resolved after the use of non‐contact mapping during radiofrequency ablation. A review of the literature regarding possible mechanisms is discussed. For the practicing clinician, the question of ‘frequent’ should be taken in context of symptoms and LV function. A single 24‐h Holter monitor may not truly reflect the ectopic load. We recommend that if there is associated LV dysfunction and a causal link to frequent PVCs then suppression with radiofrequency ablation is a safe and effective treatment strategy.
Thermal behaviour of crustaceans
Authors: Lagerspetz Kari Y. H. , Vainio Liisa A. 
Published: March 2006

ABSTRACTSpecific thermoreceptors or putative multimodal thermoreceptors are not known in Crustacea. However, behavioural studies on thermal avoidance and preference and on the effects of temperature on motor activity indicate that the thermosensitivity of crustaceans may be in the range 0.2–2°C. Work on planktonic crustaceans suggests that they respond particularly to changes in temperature by klinokinesis and orthokinesis. The thermal behaviour of crustaceans is modified by thermal acclimation among other factors. The acclimation of the critical maximum temperature is an example of resistance acclimation, while the acclimation of preference behaviour may be classified as capacity acclimation of some other function. In crustaceans, the use of the concepts stenothermy and eurythermy at the species level is questionable, and it is not possible to divide crustacean species into thermal guilds as suggested for fishes. Thermal preference behaviour contributes to fitness in different ways in different species, often by maximising the aerobic metabolic scope for activity. In crustaceans the peripheral nervous system seems to have retained the capacity for thermosensitivity and thermal acclimation independently of the central nervous system control of behaviour.
A calibration method for estimating absolute expression levels from microarray data
Authors: Engelen Kristof , Naudts Bart , De Moor Bart , Marchal Kathleen 
Published: March 2006

Abstract
Motivation: We describe an approach to normalize spotted microarray data, based on a physically motivated calibration model. This model consists of two major components, describing the hybridization of target transcripts to their corresponding probes on the one hand, and the measurement of fluorescence from the hybridized, labeled target on the other hand. The model parameters and error distributions are estimated from external control spikes.
Results: Using a publicly available dataset, we show that our procedure is capable of adequately removing the typical non-linearities of the data, without making any assumptions on the distribution of differences in gene expression from one biological sample to the next. Since our model links target concentration to measured intensity, we show how absolute expression values of target transcripts in the hybridization solution can be estimated up to a certain degree.
Contact: kathleen.marchal@biw.kuleuven.be
Supplementary information: Supplementary data are available at Bioinformatics online.
Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response
Authors: Becker Emmanuelle , Meyer Vincent , Madaoui Hocine , Guerois Raphaël 
Published: March 2006

Abstract
Motivation: Human Nbs1 and its homolog Xrs2 in Saccharomyces cerevisiae are part of the conserved MRN complex (MRX in yeast) which plays a crucial role in maintaining genomic stability. NBS1 corresponds to the gene mutated in the Nijmegen breakage syndrome (NBS) known as a radiation hyper-sensitive disease. Despite the conservation and the importance of the MRN complex, the high sequence divergence between Nbs1 and Xrs2 precluded the identification of common domains downstream of the N-terminal Fork-Head Associated (FHA) domain.
Results: Using HMM–HMM profile comparisons and structure modelling, we assessed the existence of a tandem BRCT in both Nbs1 and Xrs2 after the FHA. The structure-based conservation analysis of the tandem BRCT in Nbs1 supports its function as a phosphoserine binding domain. Remarkably, the 5 bp deletion observed in 95% of NBS patients cleaves the tandem at the linker region while preserving the structural integrity of each BRCT domain in the resulting truncated gene products.
Contact: guerois@cea.fr
Supplementary information:
Convergence of the proteomic pattern in cancer
Authors: Müller Ute , Ernst Günther , Melle Christian , Guthke Reinhard , von Eggeling Ferdinand 
Published: March 2006

Abstract
Motivation: On the histological level the differentiation of normal epithelial tissues is well known. The phenomenon of dedifferentiation, which occurs as cells develop towards malignancy is also well described. To identify an epithelial tumor-specific proteomic profile as well as to measure the proximities between we used data from tumor tissue and adjacent normal tissue microdissected from head and neck and colon cancer samples which were analyzed using ProteinChip technology and performed a bioinformatic meta-analysis on the resulting four complex datasets.
Results: All four groups could be identified based on their proteomic signatures and the tumor tissues were found to be more similar to one another than to the normal epithelial tissue from which they progressed. This study shows at the proteomic level that changes in the histological features of tumors as compared to the tissues from which they arise are reflected in the convergence of proteomic pattern during the development to cancer.
Contact: fegg@mti.uni-jena.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Predicting protein interaction sites: binding hot-spots in protein–protein and protein–ligand interfaces
Authors: Burgoyne Nicholas J. , Jackson Richard M. 
Published: March 2006

Abstract
Motivation: Protein assemblies are currently poorly represented in structural databases and their structural elucidation is a key goal in biology. Here we analyse clefts in protein surfaces, likely to correspond to binding ‘hot-spots’, and rank them according to sequence conservation and simple measures of physical properties including hydrophobicity, desolvation, electrostatic and van der Waals potentials, to predict which are involved in binding in the native complex.
Results: The resulting differences between predicting binding-sites at protein–protein and protein–ligand interfaces are striking. There is a high level of prediction accuracy (≤93%) for protein–ligand interactions, based on the following attributes: van der Waals potential, electrostatic potential, desolvation and surface conservation. Generally, the prediction accuracy for protein–protein interactions is lower, with the exception of enzymes. Our results show that the ease of cleft desolvation is strongly predictive of interfaces and strongly maintained across all classes of protein-binding interface.
Contact: r.m.jackson@leeds.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
MACGT: multi-dimensional automated clustering genotyping tool for analysis of microarray-based mini-sequencing data
Authors: Walley David C. , Tripp Ben W. , Song Young C. , Walley Keith R. , Tebbutt Scott J. 
Published: March 2006

Abstract
Summary: Multi-dimensional Automated Clustering Genotyping Tool (MACGT) is a Java application that clusters complex multi-dimensional vector data derived from single nucleotide polymorphism (SNP) genotyping experiments using mini-sequencing based microarray chemistries such as arrayed primer extension (APEX). Spot intensity output files from microarray experiments across multiple samples are imported into MACGT. The datasets can include four channels of intensity data for each spot, replica spots for each SNP probe and multiple probe types (APEX and allele-specific APEX probes) on both DNA strands for each SNP. MACGT automatically clusters these multi-dimensionality datasets for each SNP across multiple samples. Incorporation of additional array datasets from known samples that have previously validated SNP genotype calls allows unknown samples to be automatically assigned a genotype based on the clustering, along with numerical measures of confidence for each genotype call. Calling accuracy by MACGT exceeds 98% when applied to genotyping data from APEX microarrays, and can be increased to &gt;99.5% by applying thresholds to the confidence measures.
Availability: MACGT is open source and is freely available (under a GNU General Public License) from the iCAPTURE Centre web site, .
Contact: stebbutt@mrl.ubc.ca
Supplementary information: Additional information, including Supplementary Figure S1, test data and a user's manual, is available from the iCAPTURE Centre web site (see above).
AGRIS and AtRegNet. A Platform to Link cis-Regulatory Elements and Transcription Factors into Regulatory Networks
Authors: Palaniswamy Saranyan K. , James Stephen , Sun Hao , Lamb Rebecca S. , Davuluri Ramana V. , Grotewold Erich 
Published: March 2006

Abstract
Gene regulatory pathways converge at the level of transcription, where interactions among regulatory genes and between regulators and target genes result in the establishment of spatiotemporal patterns of gene expression. The growing identification of direct target genes for key transcription factors (TFs) through traditional and high-throughput experimental approaches has facilitated the elucidation of regulatory networks at the genome level. To integrate this information into a Web-based knowledgebase, we have developed the Arabidopsis Gene Regulatory Information Server (AGRIS). AGRIS, which contains all Arabidopsis (Arabidopsis thaliana) promoter sequences, TFs, and their target genes and functions, provides the scientific community with a platform to establish regulatory networks. AGRIS currently houses three linked databases: AtcisDB (Arabidopsis thaliana cis-regulatory database), AtTFDB (Arabidopsis thaliana transcription factor database), and AtRegNet (Arabidopsis thaliana regulatory network). AtTFDB contains 1,690 Arabidopsis TFs and their sequences (protein and DNA) grouped into 50 (October 2005) families with information on available mutants in the corresponding genes. AtcisDB consists of 25,806 (September 2005) promoter sequences of annotated Arabidopsis genes with a description of putative cis-regulatory elements. AtRegNet links, in direct interactions, several hundred genes with the TFs that control their expression. The current release of AtRegNet contains a total of 187 (September 2005) direct targets for 66 TFs. AGRIS can be accessed at http://Arabidopsis.med.ohio-state.edu.
Identification of correct regions in protein models using structural, alignment, and consensus information
Authors: Wallner Björn , Elofsson Arne 
Published: March 2006

AbstractIn this study we present two methods to predict the local quality of a protein model: ProQres and ProQprof. ProQres is based on structural features that can be calculated from a model, while ProQprof uses alignment information and can only be used if the model is created from an alignment. In addition, we also propose a simple approach based on local consensus, Pcons‐local. We show that all these methods perform better than state‐of‐the‐art methodologies and that, when applicable, the consensus approach is by far the best approach to predict local structure quality. It was also found that ProQprof performed better than other methods for models based on distant relationships, while ProQres performed best for models based on closer relationship, i.e., a model has to be reasonably good to make a structural evaluation useful. Finally, we show that a combination of ProQprof and ProQres (ProQlocal) performed better than any other nonconsensus method for both high‐ and low‐quality models. Additional information and Web servers are available at:http://www.sbc.su.se/∼bjorn/ProQ/.
Solvation of the folding‐transition state in Pseudomonas aeruginosa azurin is modulated by metal
Authors: Wilson Corey J. , Apiyo David , Wittung‐Stafshede Pernilla 
Published: March 2006

AbstractThe role of water in protein folding, specifically its presence or not in the transition‐state structure, is an unsolved question. There are two common classes of folding‐transition states: diffuse transition states, in which almost all side chains have similar, rather low phi (φ) values, and polarized transition states, which instead display distinct substructures with very high φ‐values. Apo‐and zinc‐forms of Pseudomonas aeruginosa azurin both fold in two‐state equilibrium and kinetic reactions; while the apo‐form exhibits a polarized transition state, the zinc form entails a diffuse, moving transition state. To examine the presence of water in these two types of folding‐transition states, we probed the equilibrium and kinetic consequences of replacing core valines with isosteric threonines at six positions in azurin. In contrast to regular hydrophobic‐to‐alanine φ‐value analysis, valine‐to‐threonine mutations do not disrupt the core packing but stabilize the unfolded state and can be used to assess the degree of solvation in the folding‐transition state upon combination with regular φ‐values. We find that the transition state for folding of apo‐azurin appears completely dry, while that for zinc‐azurin involves partially formed interactions that engage water molecules. This distinct difference between the apo‐and holo‐folding nuclei can be rationalized in terms of the shape of the free‐energy barrier.
New Escherichia coli outer membrane proteins identified through prediction and experimental verification
Authors: Marani Paola , Wagner Samuel , Baars Louise , Genevaux Pierre , De Gier Jan‐Willem , Nilsson Ingmarie , Casadio Rita , Von Heijne Gunnar 
Published: March 2006

AbstractMany new Escherichia coli outer membrane proteins have recently been identified by proteomics techniques. However, poorly expressed proteins and proteins expressed only under certain conditions may escape detection when wild‐type cells are grown under standard conditions. Here, we have taken a complementary approach where candidate outer membrane proteins have been identified by bioinformatics prediction, cloned and overexpressed, and finally localized by cell fractionation experiments. Out of eight predicted outer membrane proteins, we have confirmed the outer membrane localization for five—YftM, YaiO, YfaZ, CsgF, and YliI—and also provide preliminary data indicating that a sixth—YfaL—may be an outer membrane autotransporter.
Cofactor effects on the protein folding reaction: Acceleration of α‐lactalbumin refolding by metal ions
Authors: Bushmarina Natalia A. , Blanchet Clément E. , Vernier Grégory , Forge Vincent 
Published: March 2006

AbstractAbout 30% of proteins require cofactors for their proper folding. The effects of cofactors on the folding reaction have been investigated with α‐lactalbumin as a model protein and metal ions as cofactors. Metal ions accelerate the refolding of α‐lactalbumin by lessening the energy barrier between the molten globule state and the transition state, mainly by decreasing the difference of entropy between the two states. These effects are linked to metal ion binding to the protein in the native state. Hence, relationships between the metal affinities for the intermediate states and those for the native state are observed. Some residual specificity for the calcium ion is still observed in the molten globule state, this specificity getting closer in the transition state to that of the native state. The comparison between kinetic and steady‐state data in association with the Φ value method indicates the binding of the metal ions on the unfolded state of α‐lactalbumin. Altogether, these results provide insight into cofactor effects on protein folding. They also suggest new possibilities to investigate the presence of residual native structures in the unfolded state of protein and the effects of such structures on the protein folding reaction and on protein stability.
Dynamic motions of free and bound Ø29 scaffolding protein identified by hydrogen deuterium exchange mass spectrometry
Authors: Fu Chi‐Yu , Prevelige Peter E. 
Published: March 2006

AbstractIn the double‐stranded DNA containing bacteriophages, hundreds of copies of capsid protein subunits polymerize to form icosahedral shells, called procapsids, into which the viral genome is subsequently packaged to form infectious virions. High assembly fidelity requires the assistance of scaffolding protein molecules, which interact with the capsid proteins to insure proper geometrical incorporation of subunits into the growing icosahedral lattices. The interactions between the scaffolding and capsid proteins are transient and are subsequently disrupted during DNA packaging. Removal of scaffolding protein is achieved either by proteolysis or alternatively by some form of conformational switch that allows it to dissociate from the capsid. To identify the switch controlling scaffolding protein association and release, hydrogen deuterium exchange was applied to Bacillus subtilis phage Ø29 scaffolding protein gp7 in both free and procapsid‐bound forms. The H/D exchange experiments revealed highly dynamic and cooperative opening motions of scaffolding molecules in the N‐terminal helix‐loop‐helix (H‐L‐H) region. The motions can be promoted by destabilizing the hydrophobic contact between two helices. At low temperature where high energy motions were damped, or in a mutant in which the helices were tethered through the introduction of a disulfide bond, this region displayed restricted cooperative opening motions as demonstrated by a switch in the exchange kinetics from correlated EX1 exchange to uncorrelated EX2 exchange. The cooperative opening rate was increased in the procapsid‐bound form, suggesting this region might interact with the capsid protein. Its dynamic nature might play a role in the assembly and release mechanism.
NMR study of the tetrameric KcsA potassium channel in detergent micelles
Authors: Chill Jordan H. , Louis John M. , Miller Christopher , Bax Ad 
Published: March 2006

AbstractNuclear magnetic resonance (NMR) studies of large membrane‐associated proteins are limited by the difficulties in preparation of stable protein–detergent mixed micelles and by line broadening, which is typical of these macroassemblies. We have used the 68‐kDa homotetrameric KcsA, a thermostable N‐terminal deletion mutant of a bacterial potassium channel from Streptomyces lividans, as a model system for applying NMR methods to membrane proteins. Optimization of measurement conditions enabled us to perform the backbone assignment of KcsA in SDS micelles and establish its secondary structure, which was found to closely agree with the KcsA crystal structure. The C‐terminal cytoplasmic domain, absent in the original structure, contains a 14‐residue helix that could participate in tetramerization by forming an intersubunit four‐helix bundle. A quantitative estimate of cross‐ relaxation between detergent and KcsA backbone amide protons, together with relaxation and light scattering data, suggests SDS–KcsA mixed micelles form an oblate spheroid with ∼180 SDS molecules per channel. K+ ions bind to the micelle‐solubilized channel with a KD of 3 ± 0.5 mM, resulting in chemical shift changes in the selectivity filter. Related pH‐induced changes in chemical shift along the “outer” transmembrane helix and the cytoplasmic membrane interface hint at a possible structural explanation for the observed pH‐gating of the potassium channel.
Evolutionary links between FliH/YscL‐like proteins from bacterial type III secretion systems and second‐stalk components of the FoF1 and vacuolar ATPases
Authors: Pallen Mark J. , Bailey Christopher M. , Beatson Scott A. 
Published: March 2006

AbstractBacterial type III secretion drives flagellar biosynthesis and mediates bacterial‐eukaryotic interactions. Type III secretion is driven by an ATPase that is homologous to the catalytic subunits of proton‐translocating ATPases, such as the FoF1 ATPase. Here we use PSI‐BLAST searches to show that some noncalatytic components are also conserved between type III secretion systems and proton‐translocating ATPases. In particular, we show that the FliH/YscL‐like proteins and the E subunits of vacuolar ATPases represent fusions of domains homologous to second‐stalk components of the FoF1 ATPase (the b and δ subunits).
Crystal structure of 3‐hydroxyanthranilic acid 3,4‐dioxygenase from Saccharomyces cerevisiae: A special subgroup of the type III extradiol dioxygenases
Authors: Li Xiaowu , Guo Min , Fan Jun , Tang Wenying , Wang Deqiang , Ge Honghua , Rong Hui , Teng Maikun , Niu Liwen , Liu Qun , Hao Quan 
Published: March 2006

Abstract3‐Hydroxyanthranilic acid 3,4‐dioxygenase (3HAO) is a non‐heme ferrous extradiol dioxygenase in the kynurenine pathway from tryptophan. It catalyzes the conversion of 3‐hydroxyanthranilate (HAA) to quinolinic acid (QUIN), an endogenous neurotoxin, via the activation of N‐methyl‐D‐aspartate (NMDA) receptors and the precursor of NAD+ biosynthesis. The crystal structure of 3HAO from S. cerevisiae at 2.4 Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure represents the first eukaryotic 3HAO to be resolved. The enzyme forms homodimers, with two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous‐coordinated active site, which is located in a conserved double‐strand β‐helix domain. Examination of the structure reveals the participation of a series of residues in catalysis different from other extradiol dioxygenases. Together with two iron‐binding residues (His49 and Glu55), Asp120, Asn51, Glu111, and Arg114 form a hydrogen‐bonding network; this hydrogen‐bond network is key to the catalysis of 3HAO. Residues Arg101, Gln59, and the substrate‐binding hydrophobic pocket are crucial for substrate specificity. Structure comparison with 3HAO from Ralstonia metallidurans reveals similarities at the active site and suggests the same catalytic mechanism in prokaryotic and eukaryotic 3HAO. Based on sequence comparison, we suggest that bicupin of human 3HAO is the first example of evolution from a monocupin dimer to bicupin monomer in the diverse cupin superfamilies. Based on the model of the substrate HAA at the active site of Y3HAO, we propose a mechanism of catalysis for 3HAO.