SciCombinator

We report a draft genome sequence of Dickeya zeae strain MS1, which is the causative agent of banana soft rot in China, and we show several of its specific properties compared with those of other D. zeae strains. Genome sequencing provides a tool for understanding the genomic determination of the pathogenicity and phylogeny placement of this pathogen.

Microcystis aeruginosa is a dominant bloom-forming cyanobacterium in many freshwater lakes. This report describes the first whole-genome sequence of the nontoxic strain of M. aeruginosa TAIHU98, which was isolated from Taihu Lake in eastern China.

Neofusicoccum parvum, a member of the Botryosphaeriaceae family, is a vascular pathogen that causes severe decline and dieback symptoms in grapevines worldwide. The draft genome of the grapevine isolate N. parvum UCR-NP2 provides a first glimpse into the complex set of putative virulence factors that this pathogen may use to rapidly colonize plants.

Noroviruses, members of the family Caliciviridae, are genetically diverse. We report the first complete genome sequence of a genogroup II genotype 18 porcine norovirus, strain QW125. A protein BLAST search revealed that identity scores of this strain compared to other norovirus strains were highest in the predicted protease region.

Here, we report the 3.2-Mbp draft genome sequence of Bhargavaea cecembensis strain DSE10(T), isolated from a sediment sample collected from the Chagos-Laccadive ridge system in the Indian Ocean at a depth of 5,904 m.

We report here the 4.3-Mb genome of Arthrobacter gangotriensis strain Lz1y(T), isolated from a penguin rookery soil sample collected in Antarctica, near the Indian station Dakshin Gangotri.

We report here the draft genome sequences of Mycoplasma alkalescens, Mycoplasma arginini, and Mycoplasma bovigenitalium. These three species are regularly isolated from bovine clinical specimens, although their role in disease is unclear.

Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium that was first recognized as a causative agent of bovine mastitis. S. agalactiae has subsequently emerged as a significant cause of human diseases. Here, we report the draft genome sequence of S. agalactiae PR06, which was isolated from a septicemic patient in a local hospital in Malaysia.

Mycoplasma putrefaciens is one of the etiologic agents of contagious agalactia in goats. We report herein the complete genome sequence of Mycoplasma putrefaciens strain 9231.

OBJECTIVE: Expression of microRNA-22 (miR-22) and ezrin protein (a membrane-cytoskeleton linking protein) in hepatocellular carcinoma (HCC) was investigated. METHODS: Specimens of HCC and paracancerous tissue (control; ∼5 cm away from tumour tissue) were collected from 192 patients. miR-22 expression was detected by real-time polymerase chain reaction; ezrin protein expression in tumour tissue was assessed immunohistochemically. Associations between miR-22 expression and clinicopathological features of HCC and ezrin expression were analysed. RESULTS: miR-22 expression was lower in HCC tissue than in paracancerous tissue samples (median relative expression 0.676 versus 1.000 for control tissue). Expression of miR-22 was significantly associated with histological differentiation (relative expression 0.431 for lower grades of differentiation versus 0.918 for higher grades), and was associated with lymphatic metastasis (relative expression 0.518 if metastasis was present, 0.919 if absent). Survival time was shorter in patients with low miR-22 expression than in those with high expression (31.0 ± 2.6 versus 52.2 ± 5.1 months). There was a significant negative correlation between the expression of miR-22 and that of ezrin. CONCLUSIONS: miR-22 is downregulated in HCC and its expression is associated with the differentiation, metastasis and prognosis of the carcinoma. Ezrin is a potential regulatory protein of miR-22.

OBJECTIVE: To compare the efficacy of ramosetron, midazolam, and the combination of ramosetron and midazolam in the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing thyroidectomy. METHODS: Patients were randomized to receive 0.3 mg ramosetron (Group R), 75 µg/kg midazolam (Group M) or 0.3 mg ramosetron combined with 75 µg/kg midazolam (Group RM) before the induction of anaesthesia. PONV, use of rescue antiemetics, pain severity and fentanyl consumption were assessed for 24 h after thyroidectomy. RESULTS: A total of 100 patients were enrolled; 94 patients completed the study. The severity of nausea was statistically significantly reduced at 0-2 h in Group RM compared with Groups R and M, and at 2-6 h in Group RM compared with Group M. The incidence of retching and vomiting was significantly lower at 0-2 h, 2-6 h, 6-12 h in Group RM than in Group M, and lower in Group R than Group M at 6-12 h. The requirement for rescue antiemetics was significantly lower at 0-2 h in group RM than in group M. CONCLUSION: The combination therapy of ramosetron and midazolam provided superior antiemetic efficacy compared with midazolam single therapy, but did not show any significant additional benefits compared with ramosetron single therapy.

MOTIVATION: The advent of new sequencing technologies has led to increasing amounts of data being available to perform phylogenetic analyses, with genomic data giving rise to the field of phylogenomics. High-performance computing is becoming an indispensable research tool to fit complex evolutionary models, which take into account specific genomic properties, to large data sets. Here, we perform an extensive Bayesian phylogenetic model selection study, comparing codon and nucleotide substitution models, including codon position partitioning for nucleotide data as well gene-specific substitution models for both data types. For the best fitting partitioned models, we also compare independent partitioning with standard diffuse prior specification to conditional partitioning via hierarchical prior specification. To compare the different models, we use state-of-the-art marginal likelihood estimation techniques, including path sampling and stepping-stone sampling. RESULTS: We show that a full codon model best describes the features of a whole mitochondrial genome data set, consisting of 12 protein-coding genes, but only when each gene is allowed to evolve under a separate codon model. However, when using hierarchical prior specification for the partition-specific parameters instead of independent diffuse priors, codon position partitioned nucleotide models can still outperform standard codon models. We demonstrate the feasibility of fitting such a combination of complex models using the BEAGLE library for BEAST in combination with recent graphics cards. We argue that development and use of such models needs to be accompanied by state-of-the-art marginal likelihood estimators because the more traditional and computationally less demanding estimators do not offer adequate accuracy. CONTACT: [email protected]

MOTIVATION: The interaction between drugs and their targets, often proteins, and between antibodies and their targets is important for planning and analyzing investigational and therapeutic interventions in many biological systems. Although drug-target and antibody-target data sets are available in separate databases, they are not publically available in an integrated bioinformatics resource. As medical therapeutics, especially in cancer, increasingly uses targeted drugs and measures their effects on biomolecular profiles, there is an unmet need for a user-friendly toolset that allows researchers to comprehensively and conveniently access and query information about drugs, antibodies and their targets. SUMMARY: The PiHelper framework integrates human drug-target and antibody-target associations from publically available resources to help meet the needs of researchers in systems pharmacology, perturbation biology and proteomics. PiHelper has utilities to i) import drug- and antibody-target information; ii) search the associations either programmatically or through a web user interface (UI); iii) visualize the data interactively in a network; iv) export relationships for use in publications or other analysis tools. AVAILABILITY: PiHelper is free software under the GNU Lesser General Public License (LGPL) v3.0. Source code and documentation are at http://bit.ly/pihelper. We plan to coordinate contributions from the community by managing future releases. CONTACT: [email protected]

MOTIVATION: Mass spectrometry (MS) instruments and experimental protocols are rapidly advancing, but de novo peptide sequencing algorithms to analyze tandem mass (MS/MS) spectra are lagging behind. While existing de novo sequencing tools perform well on certain types of spectra (e.g., Collision Induced Dissociation (CID) spectra of tryptic peptides), their performance often deteriorates on other types of spectra, such as Electron Transfer Dissociation (ETD), Higher-energy Collisional Dissociation (HCD) spectra, or spectra of non-tryptic digests. Thus, rather than developing a new algorithm for each type of spectra, we develop a universal de novo sequencing algorithm called UniNovo that works well for all types of spectra or even for spectral pairs (e.g., CID/ETD spectral pairs). UniNovo uses an improved scoring function that captures the dependences between different ion types, where such dependencies are learned automatically using a modified offset frequency function (Dancik et al., 1999). RESULTS: The performance of UniNovo is compared with PepNovo+, PEAKS, and pNovo using various types of spectra. The results show that the performance of UniNovo is superior to other tools for ETD spectra and superior or comparable to others for CID and HCD spectra. UniNovo also estimates the probability that each reported reconstruction is correct, using simple statistics that are readily obtained from a small training dataset. We demonstrate that the estimation is accurate for all tested types of spectra (including CID, HCD, ETD, CID/ETD, and HCD/ETD spectra of trypsin, LysC, or AspN digested peptides). AVAILABILITY: UniNovo is implemented in JAVA and tested on Windows, Ubuntu, and OS X machines. UniNovo is available at http://proteomics.ucsd.edu/Software/UniNovo.html along with the manual. CONTACT: [email protected]; [email protected];[email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Genome-scale metabolic models often lack annotations that would allow them to be used for further analysis. Previous efforts have focused on associating metabolites in the model with a cross-reference but this can be problematic if the reference is not freely available, multiple resources are used or the metabolite was added from a literature review. Associating each metabolite with chemical structure provides unambiguous identification of the components and a more detailed view of the metabolism. We have developed an open-source desktop application that simplifies the process of adding database cross-references and chemical structures to genome-scale metabolic models. Annotated models can be exported to the Systems Biology Markup Language (SBML) open interchange format. AVAILABILITY: Source code, binaries, documentation and tutorials are freely available at http://johnmay.github.com/metingear. The application is implemented in Java with bundles available for MS Windows and Macintosh OS X. CONTACT: [email protected]

UPF1 is a DNA/RNA helicase with essential roles in nonsense-mediated mRNA decay (NMD) and embryonic development. How UPF1 regulates target abundance and the relationship between NMD and embryogenesis are not well understood. To explore how NMD shapes the embryonic transcriptome, we integrated genome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine embryonic stem cells (mESCs). We identified over 200 direct UPF1 binding targets using crosslinking/immunoprecipitation-sequencing (CLIP-seq) and revealed a repression pathway that involves 3' UTR binding by UPF1 and translation but is independent of canonical targeting features involving 3' UTR length and stop codon placement. Interestingly, NMD targeting of this set of mRNAs occurs in other mouse tissues and is conserved to human. We also show using ribosome footprint profiling that actively translated upstream open reading frames (uORFs) are enriched in transcription factor mRNAs and predict mRNA repression by NMD, while poorly translated mRNAs escape repression. Together, our results identify novel NMD determinants and targets and provide context for understanding the impact of UPF1 and NMD on the mESC transcriptome.

OBJECTIVES: Superior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB). METHODS: Fourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100β. RESULTS: Both strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100β concentrations were similar in the two groups. CONCLUSIONS: Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.

Traditionally, the transcatheter aortic valve replacement is performed through a transapical, a transfemoral or a trans-subclavian approach. Recently, the transaortic approach for transcatheter aortic valve replacement through the distal part of the ascending aorta was successfully implemented in order to avoid peripheral vascular access-related complications and apical life-threatening haemorrhage. The Sapien™ stent valve has great transaortic potential because it can be loaded ‘upside down’ in different generations of delivery systems. However, because of their health regulatory systems and despite the launch, in 2012, of the latest generation of the Ascendra™ delivery system, the Ascendra+™, specifically designed for transapical and transaortic valve placements, several countries are still using the first generations of Ascendra™ (Ascendra™ 1 and 2). This device was specifically designed for transapical procedures, and retrograde stent-valve positioning through the stenotic aortic valve may be very challenging and risk the integrity of the aorta. We describe the manoeuvre required in order to pass the stenotic aortic valve safely in a retrograde direction using the Sapien™ stent valve and the first generations of Ascendra™.

BACKGROUND: Classic rapid sequence induction puts pediatric patients at risk of cardiorespiratory deterioration and traumatic intubation due to their reduced apnea tolerance and related shortened intubation time. A ‘controlled’ rapid sequence induction and intubation technique (cRSII) with gentle facemask ventilation prior to intubation may be a safer and more appropriate approach in pediatric patients. The aim of this study was to analyze the benefits and complications of cRSII in a large cohort. METHODS: Retrospective cohort analysis of all patients undergoing cRSII according to a standardized institutional protocol between 2007 and 2011 in a tertiary pediatric hospital. By means of an electronic patient data management system, vital sign data were reviewed for cardiorespiratory parameters, intubation conditions, general adverse respiratory events, and general anesthesia parameters. RESULTS: A total of 1001 patients with cRSII were analyzed. Moderate hypoxemia (SpO2 80-89%) during cRSII occurred in 0.5% (n = 5) and severe hypoxemia (SpO2 <80%) in 0.3% of patients (n = 3). None of these patients developed bradycardia or hypotension. Overall, one single gastric regurgitation was observed (0.1%), but no pulmonary aspiration could be detected. Intubation was documented as 'difficult' in two patients with expected (0.2%) and in three patients with unexpected difficult intubation (0.3%). The further course of anesthesia as well as respiratory conditions after extubation did not reveal evidence of 'silent aspiration' during cRSII. CONCLUSION: Controlled RSII with gentle facemask ventilation prior to intubation supports stable cardiorespiratory conditions for securing the airway in children with an expected or suspected full stomach. Pulmonary aspiration does not seem to be significantly increased.

BACKGROUND: Because the histological and biochemical progression of liver disease is similar in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH), we hypothesized that the genetic susceptibility to these liver diseases would be similar. To identify potential candidate genes that regulate the development of liver fibrosis, we studied a chromosome substitution strain (CSS-17) that contains chromosome 17 from the A/J inbred strain substituted for the corresponding chromosome on the C57BL/6J (B6) genetic background. Previously, we identified quantitative trait loci (QTLs) in CSS-17, namely obesity-resistant QTL 13 and QTL 15 (Obrq13 and Obrq15, respectively), that were associated with protection from diet-induced obesity and hepatic steatosis on a high-fat diet. METHODS: To test whether these or other CSS-17 QTLs conferred resistance to alcohol-induced liver injury and fibrosis, B6, A/J, CSS-17, and congenics 17C-1 and 17C-6 were either fed Lieber-DeCarli ethanol (EtOH)-containing diet or had carbon tetrachloride (CCl4 ) administered chronically. RESULTS: The congenic strain carrying Obrq15 showed resistance from alcohol-induced liver injury and liver fibrosis, whereas Obrq13 conferred susceptibility to liver fibrosis. From published deep sequencing data for chromosome 17 in the B6 and A/J strains, we identified candidate genes in Obrq13 and Obrq15 that contained single-nucleotide polymorphisms (SNPs) in the promoter region or within the gene itself. NADPH oxidase organizer 1 (Noxo1) and NLR family, CARD domain containing 4 (Nlrc4) showed altered hepatic gene expression in strains with the A/J allele at the end of the EtOH diet study and after CCl4 treatment. CONCLUSIONS: Aspects of the genetics for the progression of ASH are unique compared to NASH, suggesting that the molecular mechanisms for the progression of disease are at least partially distinct. Using these CSSs, we identified 2 candidate genes, Noxo1 and Nlrc4, which modulate genetic susceptibility in ASH.