bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin
Authors: Meyer Danilo , Neumann Piotr , Koers Eline , Sjuts Hanno , Lüdtke Stefan , Sheldrick George M. , Ficner Ralf , Tittmann Kai 
Published: June 2012

Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 Å resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than
π
-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms.
ChromoHub: a data hub for navigators of chromatin-mediated signalling
Authors: Liu Lihua , Zhen Xi Ting , Denton Emily , Marsden Brian D. , Schapira Matthieu 
Published: June 2012

Abstract
Summary: The rapidly increasing research activity focused on chromatin-mediated regulation of epigenetic mechanisms is generating waves of data on writers, readers and erasers of the histone code, such as protein methyltransferases, bromodomains or histone deacetylases. To make these data easily accessible to communities of research scientists coming from diverse horizons, we have created ChromoHub, an online resource where users can map on phylogenetic trees disease associations, protein structures, chemical inhibitors, histone substrates, chromosomal aberrations and other types of data extracted from public repositories and the published literature. The interface can be used to define the structural or chemical coverage of a protein family, highlight domain architectures, interrogate disease relevance or zoom in on specific genes for more detailed information. This open-access resource should serve as a hub for cell biologists, medicinal chemists, structural biologists and other navigators that explore the biology of chromatin signalling.
Availability: http://www.thesgc.org/chromohub/.
Contact: matthieu.schapira@utoronto.ca
Supplementary Information: Supplementary data are available at Bioinformatics online.
miRcode: a map of putative microRNA target sites in the long non-coding transcriptome
Authors: Jeggari Ashwini , Marks Debora S , Larsson Erik 
Published: June 2012

Abstract
Summary: Although small non-coding RNAs, such as microRNAs, have well-established functions in the cell, long non-coding RNAs (lncRNAs) have only recently started to emerge as abundant regulators of cell physiology, and their functions may be diverse. A small number of studies describe interactions between small and lncRNAs, with lncRNAs acting either as inhibitory decoys or as regulatory targets of microRNAs, but such interactions are still poorly explored. To facilitate the study of microRNA–lncRNA interactions, we implemented miRcode: a comprehensive searchable map of putative microRNA target sites across the complete GENCODE annotated transcriptome, including 10 419 lncRNA genes in the current version.
Availability: http://www.mircode.org
Contact: erik.larsson@gu.se
Supplementary Information: Supplementary data are available at Bioinformatics online.
Accelerated protein structure comparison using TM-score-GPU
Authors: Hung Ling-Hong , Samudrala Ram 
Published: June 2012

Abstract
Motivation: Accurate comparisons of different protein structures play important roles in structural biology, structure prediction and functional annotation. The root-mean-square-deviation (RMSD) after optimal superposition is the predominant measure of similarity due to the ease and speed of computation. However, global RMSD is dependent on the length of the protein and can be dominated by divergent loops that can obscure local regions of similarity. A more sophisticated measure of structure similarity, Template Modeling (TM)-score, avoids these problems, and it is one of the measures used by the community-wide experiments of critical assessment of protein structure prediction to compare predicted models with experimental structures. TM-score calculations are, however, much slower than RMSD calculations. We have therefore implemented a very fast version of TM-score for Graphical Processing Units (TM-score-GPU), using a new and novel hybrid Kabsch/quaternion method for calculating the optimal superposition and RMSD that is designed for parallel applications. This acceleration in speed allows TM-score to be used efficiently in computationally intensive applications such as for clustering of protein models and genome-wide comparisons of structure.
Results: TM-score-GPU was applied to six sets of models from Nutritious Rice for the World for a total of 3 million comparisons. TM-score-GPU is 68 times faster on an ATI 5870 GPU, on average, than the original CPU single-threaded implementation on an AMD Phenom II 810 quad-core processor.
Availability and implementation: The complete source, including the GPU code and the hybrid RMSD subroutine, can be downloaded and used without restriction at http://software.compbio.washington.edu/misc/downloads/tmscore/. The implementation is in C++/OpenCL.
Contact: ram@compbio.washington.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
Topology of functional networks predicts physical binding of proteins
Authors: Saraç Ömer Sinan , Pancaldi Vera , Bähler Jürg , Beyer Andreas 
Published: June 2012

Abstract
Motivation: It has been recognized that the topology of molecular networks provides information about the certainty and nature of individual interactions. Thus, network motifs have been used for predicting missing links in biological networks and for removing false positives. However, various different measures can be inferred from the structure of a given network and their predictive power varies depending on the task at hand.
Results: Herein, we present a systematic assessment of seven different network features extracted from the topology of functional genetic networks and we quantify their ability to classify interactions into different types of physical protein associations. Using machine learning, we combine features based on network topology with non-network features and compare their importance of the classification of interactions. We demonstrate the utility of network features based on human and budding yeast networks; we show that network features can distinguish different sub-types of physical protein associations and we apply the framework to fission yeast, which has a much sparser known physical interactome than the other two species. Our analysis shows that network features are at least as predictive for the tasks we tested as non-network features. However, feature importance varies between species owing to different topological characteristics of the networks. The application to fission yeast shows that small maps of physical interactomes can be extended based on functional networks, which are often more readily available.
Availability and implementation: The R-code for computing the network features is available from www.cellularnetworks.org
Contacts: andreas.beyer@biotec.tu-dresden.de
Supplementary Information: Supplementary data are available at Bioinformatics online.
ModuLand plug-in for Cytoscape: determination of hierarchical layers of overlapping network modules and community centrality
Authors: Szalay-Bekő Máté , Palotai Robin , Szappanos Balázs , Kovács István A. , Papp Balázs , Csermely Péter 
Published: June 2012

Abstract
Summary: The ModuLand plug-in provides Cytoscape users an algorithm for determining extensively overlapping network modules. Moreover, it identifies several hierarchical layers of modules, where meta-nodes of the higher hierarchical layer represent modules of the lower layer. The tool assigns module cores, which predict the function of the whole module, and determines key nodes bridging two or multiple modules. The plug-in has a detailed JAVA-based graphical interface with various colouring options. The ModuLand tool can run on Windows, Linux or Mac OS. We demonstrate its use on protein structure and metabolic networks.
Availability: The plug-in and its user guide can be downloaded freely from: http://www.linkgroup.hu/modules.php.
Contact: csermely.peter@med.semmelweis-univ.hu
Supplementary information: Supplementary data are available at Bioinformatics online.
Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design
Authors: Ghio Stefano , Bonderman Diana , Felix Stephan B. , Ghofrani Hossein A. , Michelakis Evangelos D. , Mitrovic Veselin , Oudiz Ronald J. , Frey Reiner , Roessig Lothar , Semigran Marc J. 
Published: June 2012

AimsPulmonary hypertension (PH) due to systolic left ventricular dysfunction (PH‐sLVD) frequently complicates heart failure (HF), and greatly worsens the prognosis of patients with sLVD, but as yet has no approved treatment. The LEPHT study aims to characterize the haemodynamic profile, safety, tolerability, and pharmacokinetic profile of riociguat (BAY 63‐2521), an oral stimulator of soluble guanylate cyclase, in patients with PH‐sLVD.Methods and resultsThis 16‐week, phase IIb, randomized, placebo‐controlled, double‐blind study enrols patients with PH‐sLVD, defined as left ventricular ejection fraction (LVEF) ≤40% and mean pulmonary arterial pressure (PAPmean) ≥25 mmHg at rest. Patients using optimized HF medication will receive placebo or riociguat 0.5 mg, 1 mg, or up to 2 mg three times daily. The dose will be titrated for 8 weeks, based on systolic blood pressure and well‐being, followed by 8 weeks of treatment at a stable dose. The primary efficacy variable is PAPmean, while secondary efficacy endpoints include LVEF, exercise capacity, quality of life, and other haemodynamic and echocardiographic measurements. Safety and pharmacokinetics will also be assessed. After the 16‐week study, patients will have the opportunity to be treated with riociguat in a long‐term extension phase.ConclusionThe LEPHT study will provide valuable information on the haemodynamic, echocardiographic, and preliminary clinical effects of riociguat in patients with PH‐sLVD.Trial registrationNCT01065454
The predictive values of beta1‐adrenergic and M2 muscarinic receptor autoantibodies for sudden cardiac death in patients with chronic heart failure
Authors: Pei Juanhui , Li Ning , Chen Jingzhou , Li Xian , Zhang Yinhui , Wang Zengwu , Zhang Ping , Cao Kejiang , Pu Jielin 
Published: June 2012

AimsClinical and animal studies suggest that beta1‐adrenergic and M2 muscarinic receptor autoantibodies (beta1‐AAbs and M2‐AAbs) play important roles in the pathophysiological process of chronic heart failure (CHF). Removal of these autoantibodies improved haemodynamic parameters and left ventricular ejection fraction patients with CHF. The goal of this project is to evaluate whether beta1‐AAbs and M2‐AAbs predict prognosis and sudden cardiac death (SCD) in CHF.Methods and resultsA total of 2062 patients with CHF and 824 control subjects were recruited. Beta1‐AAbs and M2‐AAbs were detected by the enzyme‐linked immunosorbent assay (ELISA) method, and the correlation between these autoantibodies and the prognosis of CHF was analysed. During a median follow‐up period of 36 months (0.40 ± 65 months), 379 (21.56%) cases died—164 had dilated cardiomyopathy (DCM) and 215 had ischaemic cardiomyopathy (ICM). Of these, SCD occurred in 69 cases (40.37%) of DCM and in 84 cases (39.07%) of ICM. Positivity for beta1‐AAbs in DCM and ICM was significantly higher than for the controls (8.1% and 8.25% v.s 2.2%, both P < 0.01). However, positive M2‐AAbs did not show any statistical difference between the three groups. Cox regression analysis revealed that positive beta1‐AAbs were associated with higher mortality in CHF and that it predicted SCD for DCM [hazard ratio (HR) 4.51, 95% confidence interval (CI) 2.405–8.471] and ICM (HR 3.749, 95% CI 2.389–5.884) patients, but not non‐SCD (NSCD) patients.ConclusionsThe rates of positive beta1‐AAbs were higher in CHF patients than in the controls. Positive beta1‐AAbs might serve as an independent predictor for SCD in patients with CHF.
Prognostic impact of sleep‐disordered breathing and its treatment with nocturnal ventilation for chronic heart failure
Authors: Damy Thibaud , Margarit Laurent , Noroc Ala , Bodez Diane , Guendouz Soulef , Boyer Laurent , Drouot Xavier , Lamine Aurélia , Paulino Alexandra , Rappeneau Stéphane , Stoica Maria‐Hermann , Dubois‐Randé Jean‐Luc , Adnot Serge , Hittinger Luc , d'Ortho Marie Pia 
Published: June 2012

AimsTo determine whether severity patterns or nocturnal ventilation to treat sleep‐disordered breathing (SDB) during chronic heart failure (CHF) is associated with adverse outcomes. Although SDB is frequent during CHF, the relationships between SDB and CHF outcomes are unknown.Methods and resultsA total of 384 CHF patients (82% men, mean age 59 ± 13 years) with a left ventricular ejection fraction (LVEF) of ≤45% (mean LVEF 29 ± 9%) were assessed by polygraphy in our clinic between 2001 and 2009. Nocturnal ventilation was started according to the severity of SDB. Combined endpoints were death, heart transplant, and implant of a ventricular assist device. The prevalence of obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and Cheyne–Stokes respiration (CSR) was 62, 26, and 29%, respectively. A primary endpoint occurred in 31%. Mean follow‐up for survivors was 47 ± 25 months. Those with moderate [apnoea–hypopnoea index (AHI) ≤5–20/h] and severe SDB (AHI ≥20/h), and OSA and CSA, had poor prognoses compared with patients without SDB (P = 0.036, P = 0.003, respectively). A total of 31% of SDB patients were treated with nocturnal ventilation. Treated SDB had a better outcome than untreated severe SDB after adjustment for confounding factors [P = 0.031; hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.33–0.95]. Subgroup analysis that included only OSA showed a similar result after adjustment (P = 0.017; HR 0.40; 95% CI 0.19–0.95).ConclusionsIn CHF, SDB is associated with a poor prognosis whatever the SDB pattern, and nocturnal ventilation is associated with a better outcome.
Development and initial validation of a simple clinical decision tool to predict the presence of heart failure in primary care: the MICE (Male, Infarction, Crepitations, Edema, MICE) rule
Authors: Roalfe Andrea K. , Mant Jonathan , Doust Jenny A. , Barton Pelham , Cowie Martin R. , Glasziou Paul , Mant David , McManus Richard J. , Holder Roger , Deeks Jonathan J. , Doughty Robert N. , Hoes Arno W. , Fletcher Kate , Hobbs F.D. Richard 
Published: June 2012

AimsDiagnosis of heart failure in primary care is often inaccurate, and access to and use of echocardiography is suboptimal. This study aimed to develop and provisionally validate a clinical prediction rule to optimize referral for echocardiography of people identified in primary care with suspected heart failure.Methods and resultsA systematic review identified studies of diagnosis of heart failure set in primary care. The individual patient data for five of these studies were obtained. Logistic regression models to predict heart failure were developed on one of the data sets and validated on the others using area under the receiver operating characteristic curve (AUROC), and goodness‐of‐fit calibration plots. A model based upon four simple clinical features (Male, history of myocardial Infarction, Crepitations, Edema: MICE) and natriuretic peptide had good validity when applied to other data sets, with AUROCs between 0.84 and 0.93, and reasonable calibration. The rule performed well across the data sets, with sensitivity between 81% and 96% and specificity between 57% and 74%.ConclusionsA simple clinical rule based upon gender, history of myocardial infarction, presence of ankle oedema, and presence of basal lung crepitations can discriminate between people with suspected heart failure who should be referred straight for echocardiography and people for whom referral should depend upon the result of a natriuretic peptide test. Prospective validation and an implementation evaluation of the rule is now warranted.
Cinaciguat, a soluble guanylate cyclase activator: results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes
Authors: Gheorghiade Mihai , Greene Stephen J. , Filippatos Gerasimos , Erdmann Erland , Ferrari Roberto , Levy Phillip D. , Maggioni Aldo , Nowack Christina , Mebazaa Alexandre ,   on behalf of the COMPOSE Investigators and Coordinators
Published: June 2012

AimsCinaciguat (BAY 58‐2667) is a soluble guanylate cyclase (sGC) activator that, in a previous study among patients with acute heart failure syndromes (AHFS), improved pulmonary capillary wedge pressure (PCWP) at the expense of significant hypotension at doses ≥200 µg/h. The aim of the COMPOSE programme was to investigate the safety and efficacy of fixed, low doses of intravenous cinaciguat (<200 µg/h for 24–48 h) as add‐on to standard therapy in adults hospitalized with AHFS.Methods and resultsCOMPOSE comprised three randomized, double‐blind, placebo‐controlled studies in patients with [COMPOSE 1 and 2 (NCT01065077 and NCT01067859)] or without [COMPOSE EARLY (NCT01064037)] a requirement for invasive haemodynamic monitoring. COMPOSE 1 and COMPOSE EARLY assessed the effects of cinaciguat (50, 100, and 150 µg/h) on haemodynamics and dyspnoea, respectively. COMPOSE 2 assessed the haemodynamic effects of 10 and 25 µg/h cinaciguat. COMPOSE was terminated early due to an excess of non‐fatal hypotension and recruitment difficulties. In COMPOSE 1 (n = 12), cinaciguat reduced PCWP at 8 h compared with placebo, but there was no relevant change in cardiac index. In COMPOSE EARLY (n = 62), no meaningful difference in dyspnoea was shown between cinaciguat and placebo.ConclusionIn this limited database, short‐term use of intravenous cinaciguat decreased blood pressure without improving dyspnoea or cardiac index. Given the lack of effect on dyspnoea and cardiac index and the hypotensive effect seen even with low doses, it is doubtful that further studies with intravenous cinaciguat would prove beneficial in this patient population.
Left ventricular dysfunction due to diffuse multiple vessel coronary artery spasm can be concealed in dilated cardiomyopathy
Authors: Inami Takumi , Kataoka Masaharu , Shimura Nobuhiko , Ishiguro Haruhisa , Kohshoh Hideyasu , Taguchi Hiroki , Yanagisawa Ryoji , Hara Yukiko , Satoh Toru , Yoshino Hideaki 
Published: June 2012

AimsMany patients with idiopathic dilated cardiomyopathy (DCM) have been diagnosed on the basis of the exclusion of significant coronary stenosis and the presence of left ventricular (LV) dysfunction. In the present study, we investigated the possibility that coronary multispasm is one of the mechanisms leading to diffuse idiopathic DCM‐like LV dysfunction.Methods and resultsForty‐two patients with severely depressed LV function but without significant coronary stenosis were enrolled (baseline LV ejection fraction, 33 ±11%). An acetylcholine (ACh) provocation test was performed at the time of coronary angiography. In patients with a positive ACh provocation test (n = 20), coronary angiography revealed multivessel diffuse coronary spasm with marked electrocardiogram changes. In patients with a negative ACh provocation test (n = 22), significant findings compatible with idiopathic DCM were more frequently observed on magnetic resonance imaging (MRI) or in LV biopsies compared with the ACh‐positive group (MRI, 73% vs. 12%; and LV biopsy, 71% vs. 0%, respectively; P < 0.01). In the ACh‐positive group, LV function significantly improved after the administration of calcium channel blockers (LV ejection fraction, 34 ±12% vs. 54 ±10%; and brain natriuretic peptide, 803 ± 482 pg/mL vs. 69 ± 84 pg/mL, at baseline and 1 year, respectively; P < 0.01).ConclusionsOur results raise the possibility that patients with LV dysfunction due to repeated coronary multispasm are being diagnosed as idiopathic DCM, and that calcium channel blockers may prove to be a promising therapeutic strategy in those patients.
Spawning history influence on fecundity, egg size, and egg survival of Atlantic salmon (Salmo salar) from the Miramichi River, New Brunswick, Canada
Authors: Reid Jenny E. , Chaput Gérald 
Published: June 2012

Abstract
Reid, J. E., and Chaput, G. 2012. Spawning history influence on fecundity, egg size, and egg survival of Atlantic salmon (Salmo salar) from the Miramichi River, New Brunswick, Canada. – ICES Journal of Marine Science, 69: 1678–1685. There is an increasing abundance of repeat spawners in the Atlantic salmon (Salmo salar) population in the Miramichi River that, owing to their larger size, can be expected to contribute greater egg depositions and better offspring survival than primarily maiden spawning populations. Currently, there is little information on the reproductive contribution of repeat-spawning salmon. In this study, the fecundity, egg size, and egg survival for 235 maiden and repeat-spawning wild female Atlantic salmon were examined over a period of 3 years. Relative fecundity did not differ among the largest body size group of salmon, but consecutive repeat spawners had a higher fecundity than maiden 2SW salmon and alternate repeat spawners. Egg diameter also increased with body size, but consecutive repeat spawners had significantly smaller eggs, in absolute terms and relative to their body size, than maiden 2SW salmon and alternate repeat spawners. The egg survival rate of consecutive repeat spawners was significantly lower than that of 2SW maiden salmon and alternate repeat spawners. Consecutive repeat spawners are different in that egg diameter and egg survival did not follow the general positive association with female body size, probably because of the short time that they spend reconditioning in the ocean and consequently their available energy reserves.