bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atelectasis and survival after bronchoscopic lung volume reduction for COPD
Authors: Hopkinson N.S. , Kemp S.V. , Toma T.P. , Hansell D.M. , Geddes D.M. , Shah P.L. , Polkey M.I. 
Published: October 2010

Bronchoscopic therapies to reduce lung volumes in chronic obstructive pulmonary disease are intended to avoid the risks associated with lung volume reduction surgery (LVRS) or to be used in patient groups in whom LVRS is not appropriate. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves to target unilateral lobar occlusion can improve lung function and exercise capacity in patients with emphysema. The benefit is most pronounced in, though not confined to, patients where lobar atelectasis has occurred. Few data exist on their long-term outcome.19 patients (16 males; mean±sdforced expiratory volume in 1 s 28.4±11.9% predicted) underwent BLVR between July 2002 and February 2004. Radiological atelectasis was observed in five patients. Survival data was available for all patients up to February 2010.None of the patients in whom atelectasis occurred died during follow-up, whereas eight out of 14 in the nonatelectasis group died (Chi-squared p = 0.026). There was no significant difference between the groups at baseline in lung function, quality of life, exacerbation rate, exercise capacity (shuttle walk test or cycle ergometry) or computed tomography appearances, although body mass index was significantly higher in the atelectasis group (21.6±2.9versus28.4±2.9 kg·m−2; p<0.001).The data in the present study suggest that atelectasis following BLVR is associated with a survival benefit that is not explained by baseline differences.
Clinical management of tuberculosis and HIV-1 co-infection
Authors: Schutz C. , Meintjes G. , Almajid F. , Wilkinson R.J. , Pozniak A. 
Published: October 2010

In many parts of the world the commonest serious opportunistic infection that occurs in HIV-1 infected persons is tuberculosis (TB). HIV-1 co-infection modifies the natural history and clinical presentation, and adversely affects the outcome of TB. Severe disseminated disease is well-recognised but it is increasingly appreciated that early disease characterised by very few or no symptoms is also common. Immunodiagnostic methods to ascertain latent TB in HIV-1 infected persons are compromised in sensitivity.Chemoprevention of HIV-1-associated TB is effective, its benefits are restricted to those which have evidence of immune sensitisation and appear short-lived in areas of high TB burden. Although promising advances in the microbiological diagnosis of TB have recently occurred, the diagnosis of HIV-1-associated TB remains difficult because of more frequent presentation as sputum negative or extrapulmonary disease.Management of co-infected patients can be complex because of overlapping drug toxicities and interactions. Nevertheless consensus is developing that antiretroviral therapy should be provided as soon as practicable after starting TB treatment in HIV-1 co-infected persons. This has the consequence of increasing the frequency of immune reconstitution inflammatory syndrome, the pathogenesis and management of which is poorly defined.
Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats
Authors: Dumitrascu R. , Kulcke C. , Königshoff M. , Kouri F. , Yang X. , Morrell N. , Ghofrani H.A. , Weissmann N. , Reiter R. , Seeger W. , Grimminger F. , Eickelberg O. , Schermuly R.T. , Pullamsetti S.S. 
Published: October 2010

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by vasoconstriction and remodelling of the pulmonary vasculature. The serotonin (5-hydroxytryptamine (5-HT)) pathway has been shown to play a major role in the pathogenesis of PAH, but pharmacological modulation of this pathway for treatment of PAH is, to date, at a pre-clinical level. Terguride is a 5-HT receptor (5-HTR) antagonist that is well tolerated and clinically approved for ovulation disorders.Immunohistochemistry against 5-HTR2A/Bon human lungs revealed their localisation to the vascular smooth muscle layer and quantitative RT-PCR showed 5-HTR2Bupregulation in pulmonary artery smooth muscle cells (PASMC) isolated from PAH patients. Proliferation and migration of cultured primary human PASMC were dose-dependently blocked by terguride. Therapeutic 5-HT signalling inhibition was 1) demonstrated in isolated, ventilated and perfused rat lungs and 2) by chronic terguride treatment of rats with monocrotaline (MCT)-induced pulmonary hypertension in a preventive or curative approach.Terguride inhibited proliferation of PASMCs and abolished 5-HT-induced pulmonary vasoconstriction. Chronic terguride treatment prevented dose-dependently the development and progression of MCT-induced PAH in rats. Thus, terguride represents a valuable novel therapeutic approach in PAH.
Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans
Authors: Brugniaux J.V. , Pialoux V. , Foster G.E. , Duggan C.T.C. , Eliasziw M. , Hanly P.J. , Poulin M.J. 
Published: October 2010

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice.In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day−1, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (PET,O2) 88 Torr, nadirPET,O245 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR).We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (VT) increased, respiratory frequency remained unchanged, and minute ventilation (V′E) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR andVT(r = -0.331; p = 0.02). EPO was positively correlated withV′E(r = 0.458; p = 0.001).In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.
MetAssimulo:Simulation of Realistic NMR Metabolic Profiles
Authors: Muncey Harriet J , Jones Rebecca , De Iorio Maria , Ebbels Timothy MD 
Published: October 2010

Abstract

Background
Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics), the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development.

Results
MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control') specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms.

Conclusions
No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with which to develop and test new data analysis techniques. MetAssimulo is freely available for academic use at http://cisbic.bioinformatics.ic.ac.uk/metassimulo/.
DiScRIBinATE: a rapid method for accurate taxonomic classification of metagenomic sequences
Authors: Ghosh Tarini Shankar , Haque M Monzoorul , Mande Sharmila S 
Published: October 2010

Abstract

Background
In metagenomic sequence data, majority of sequences/reads originate from new or partially characterized genomes, the corresponding sequences of which are absent in existing reference databases. Since taxonomic assignment of reads is based on their similarity to sequences from known organisms, the presence of reads originating from new organisms poses a major challenge to taxonomic binning methods. The recently published SOrt-ITEMS algorithm uses an elaborate work-flow to assign reads originating from hitherto unknown genomes with significant accuracy and specificity. Nevertheless, a significant proportion of reads still get misclassified. Besides, the use of an alignment-based orthology step (for improving the specificity of assignments) increases the total binning time of SOrt-ITEMS.

Results
In this paper, we introduce a rapid binning approach called DiScRIBinATE (Di stance Sc ore R atio for I mproved Bin ning A nd T axonomic E stimation). DiScRIBinATE replaces the orthology approach of SOrt-ITEMS with a quicker 'alignment-free' approach. We demonstrate that incorporating this approach reduces binning time by half without any loss in the specificity and accuracy of assignments. Besides, a novel reclassification strategy incorporated in DiScRIBinATE results in reducing the overall misclassification rate to around 3 - 7%. This misclassification rate is 1.5 - 3 times lower as compared to that by SOrt-ITEMS, and 3 - 30 times lower as compared to that by MEGAN.

Conclusions
A significant reduction in binning time, coupled with a superior assignment accuracy (as compared to existing binning methods), indicates the immense applicability of the proposed algorithm in rapidly mapping the taxonomic diversity of large metagenomic samples with high accuracy and specificity.

Availability
The program is available on request from the authors.
T3SEdb: data warehousing of virulence effectors secreted by the bacterial Type III Secretion System
Authors: Tay Daniel Ming Ming , Govindarajan Kunde Ramamoorthy , Khan Asif M , Ong Terenze Yao Rui , Samad Hanif M , Soh Wei Wei , Tong Minyan , Zhang Fan , Tan Tin Wee 
Published: October 2010

Abstract

Background
Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments.

Results
Herein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE) sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i) comprehensive annotation of experimental status of effectors, ii) submission and curation review of records by users of the database, and iii) the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression) are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%). Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours.

Conclusions
T3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors. The T3SEdb represents a platform for inclusion of additional annotations of metadata for future developments of sophisticated effector prediction models for screening and selection of putative novel effectors from bacterial genomes/proteomes that can be validated by a small number of key experiments.
Pdlim7 is required for maintenance of the mesenchymal/epidermal Fgf signaling feedback loop during zebrafish pectoral fin development
Authors: Camarata Troy , Snyder Diana , Schwend Tyler , Klosowiak Julian , Holtrup Brandon , Simon Hans-Georg 
Published: October 2010

Abstract

Background
Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER). Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop. Recent findings have revealed that Tbx5 transcriptional activity is regulated by dynamic nucleocytoplasmic shuttling and interaction with Pdlim7, a PDZ-LIM protein family member, along actin filaments. This Tbx5 regulation is critical in heart formation, but the coexpression of both proteins in other developing tissues suggests a broader functional role.

Results
Knock-down of Pdlim7 function leads to decreased pectoral fin cell proliferation resulting in a severely stunted fin phenotype. While early gene induction and patterning in the presumptive fin field appear normal, the pectoral fin precursor cells display compaction and migration defects between 18 and 24 hours post-fertilization (hpf). During fin growth fgf24 is sequentially expressed in the mesenchyme and then in the apical ectodermal ridge (AER). However, in pdlim7 antisense morpholino-treated embryos this switch of expression is prevented and fgf24 remains ectopically active in the mesenchymal cells. Along with the lack of fgf24 in the AER, other critical factors including fgf8 are reduced, suggesting signaling problems to the underlying mesenchyme. As a consequence of perturbed AER function in the absence of Pdlim7, pathway components in the fin mesenchyme are misregulated or absent, indicating a breakdown of the Fgf signaling feedback loop, which is ultimately responsible for the loss of fin outgrowth.

Conclusion
This work provides the first evidence for the involvement of Pdlim7 in pectoral fin development. Proper fin outgrowth requires fgf24 downregulation in the fin mesenchyme with subsequent activation in the AER, and Pdlim7 appears to regulate this transition, potentially through Tbx5 regulation. By controlling Tbx5 subcellular localization and transcriptional activity and possibly additional yet unknown means, Pdlim7 is required for proper development of the heart and the fins. These new regulatory mechanisms may have important implications how we interpret Tbx5 function in congenital hand/heart syndromes in humans.
Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay
Authors: McGlincy Nicholas J , Tan Lit-Yeen , Paul Nicodeme , Zavolan Mihaela , Lilley Kathryn S , Smith Christopher WJ 
Published: October 2010

Abstract

Background
In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD) plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate.

Results
In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs). Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1's role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3' UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms.

Conclusions
Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels.
Units of plasticity in bacterial genomes: new insight from the comparative genomics of two bacteria interacting with invertebrates, Photorhabdus and Xenorhabdus
Authors: Ogier Jean-Claude , Calteau Alexandra , Forst Steve , Goodrich-Blair Heidi , Roche David , Rouy Zoé , Suen Garret , Zumbihl Robert , Givaudan Alain , Tailliez Patrick , Médigue Claudine , Gaudriault Sophie 
Published: October 2010

Abstract

Background
Flexible genomes facilitate bacterial evolution and are classically organized into polymorphic strain-specific segments called regions of genomic plasticity (RGPs). Using a new web tool, RGPFinder, we investigated plasticity units in bacterial genomes, by exhaustive description of the RGPs in two Photorhabdus and two Xenorhabdus strains, belonging to the Enterobacteriaceae and interacting with invertebrates (insects and nematodes).

Results
RGPs account for about 60% of the genome in each of the four genomes studied. We classified RGPs into genomic islands (GIs), prophages and two new classes of RGP without the features of classical mobile genetic elements (MGEs) but harboring genes encoding enzymes catalyzing DNA recombination (RGPmob), or with no remarkable feature (RGPnone). These new classes accounted for most of the RGPs and are probably hypervariable regions, ancient MGEs with degraded mobilization machinery or non canonical MGEs for which the mobility mechanism has yet to be described. We provide evidence that not only the GIs and the prophages, but also RGPmob and RGPnone, have a mosaic structure consisting of modules. A module is a block of genes, 0.5 to 60 kb in length, displaying a conserved genomic organization among the different Enterobacteriaceae. Modules are functional units involved in host/environment interactions (22-31%), metabolism (22-27%), intracellular or intercellular DNA mobility (13-30%), drug resistance (4-5%) and antibiotic synthesis (3-6%). Finally, in silico comparisons and PCR multiplex analysis indicated that these modules served as plasticity units within the bacterial genome during genome speciation and as deletion units in clonal variants of Photorhabdus.

Conclusions
This led us to consider the modules, rather than the entire RGP, as the true unit of plasticity in bacterial genomes, during both short-term and long-term genome evolution.
Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice
Authors: Lim Adeline YL , Segarra Ignacio , Chakravarthi Srikumar , Akram Sufyan , Judson John P 
Published: October 2010

AbstractBackgroundSunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.ResultsGroup-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.ConclusionsParacetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.