A transcription frame-based analysis of the genomic DNA sequence of a hyper-thermophilic archaeon for the identification of genes, pseudo-genes and operon structures

AbstractAn algorithm for identifying transcription units, independently regulated genes and operons, and pseudo-genes that are not expected to be expressed, has been developed by combining a system for predicting transcription and translation signals, and a system for scoring the triplet periodicity in ORF candidates. By using the algorithm, the 1.09 Mb sequence that covers approximately 60% of the genome of Pyrococcus sp. OT3 has been analyzed. The identified ORFs show the expected biological and physical characteristics, while the rejected ORF candidates do not. Frequent use of operon structures for transcription, and gene duplication followed by mutation or termination of the duplicated genes, are discussed

A CellML simulation compiler and code generator using ODE solving schemes

Models written in description languages such as CellML are becoming a popular solution to the handling of complex cellular physiological models in biological function simulations. However, in order to fully simulate a model, boundary conditions and ordinary differential equation (ODE) solving schemes have to be combined with it. Though boundary conditions can be described in CellML, it is difficult to explicitly specify ODE solving schemes using existing tools. In this study, we define an ODE solving scheme description language-based on XML and propose a code generation system for biological function simulations. In the proposed system, biological simulation programs using various ODE solving schemes can be easily generated. We designed a two-stage approach where the system generates the equation set associating the physiological model variable values at a certain time t with values at t + Δt in the first stage. The second stage generates the simulation code for the model. This approach enables the flexible construction of code generation modules that can support complex sets of formulas. We evaluate the relationship between models and their calculation accuracies by simulating complex biological models using various ODE solving schemes. Using the FHN model simulation, results showed good qualitative and quantitative correspondence with the theoretical predictions. Results for the Luo-Rudy 1991 model showed that only first order precision was achieved. In addition, running the generated code in parallel on a GPU made it possible to speed up the calculation time by a factor of 50. The CellML Compiler source code is available for download at http://sourceforge.net/projects/cellmlcompiler

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients

Comprehensive Sequence Analysis of 24,783 Barley Full-Length cDNAs Derived from 12 Clone Libraries

Full-length cDNA (FLcDNA) libraries consisting of 172,000 clones were constructed from a two-row malting barley cultivar (Hordeum vulgare 'Haruna Nijo') under normal and stressed conditions. After sequencing the clones from both ends and clustering the sequences, a total of 24,783 complete sequences were produced. By removing duplicates between these and publicly available sequences, 22,651 representative sequences were obtained: 17,773 were novel barley FLcDNAs, and 1,699 were barley specific. Highly conserved genes were found in the barley FLcDNA sequences for 721 of 881 rice (Oryza sativa) trait genes with 50% or greater identity. These FLcDNA resources from our Haruna Nijo cDNA libraries and the full-length sequences of representative clones will improve our understanding of the biological functions of genes in barley, which is the cereal crop with the fourth highest production in the world, and will provide a powerful tool for annotating the barley genome sequences that will become available in the near future

Open Abdominal Management Among Non-Trauma Patients: The Appropriate Duration and a New Clinical Index

Purpose Despite widespread adoption of open abdominal management (OAM), there is currently no threshold criterion for OAM duration for non-trauma patients. Moreover, there is a positive relationship between morbidity and the duration of OAM, but an uncertain relationship with patients’ age. Therefore, a novel clinical index for the duration of open abdominal management (IDOM) was developed based on the patient’s age and risk of severe complications following OAM to indicate the maximum tolerable number of days of OAM based on the individual’s age. The utility of this new index was evaluated. Methods This retrospective study included 65 non-trauma patients managed with an open abdomen (OA) from August 2015 to August 2018. The IDOM was developed based on the patient’s age. The result indicated the maximum number of OA days. Patients’ demographic and operative variables were examined and patient data was assigned to one of two groups according to whether the actual number of OA days was above or below the calculated IDOM. Prevalence of complications between these groups was compared. Measures of validity were employed to assess the utility of the IDOM for patient complications. Results Sixty-five patients were included. The above-the calculated IDOM group exhibited a significantly longer OA and higher rates of wound complications and postoperative respiratory complications compared with the below the calculated IDOM group. The IDOM predicted the incidence of OA-related complications with a sensitivity of 72.4%, and a specificity of 80.6%. Conclusion The IDOM is a potentially useful tool for appropriate duration at the outset of OA

Efficacy of erlotinib and imatinib in a patient with a rectal gastrointestinal stromal tumor and synchronous pulmonary adenocarcinoma : A case report

The synchronous existence of lung cancer and gastrointestinal stromal tumors (GIST) is considered to be extremely rare. To the best of our knowledge, this is the first report about the treatment of lung cancer and GIST with two kinds of molecular targeting drugs. An 83-year-old woman with a rectal GIST, which carried a c-kit mutation, and pulmonary adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) mutation, was treated alternately with imatinib and erlotinib. Good control over both diseases was achieved for two years. The present case is not only of interest due to the rare co-occurrence of GIST and lung cancer, but also because it involved two tumors carrying different gene mutations, and both tumors were brought under control using different molecular targeting drugs

Retinol Supplements Antiviral Action of Interferon in Patients with Chronic Hepatitis C: A Prospective Pilot Study

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon α-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon α-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon α-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p<0.01). Furthermore, serum 2,5'AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon α-2b plus ribavirin only during the administration of IFN α-2b, ribavirin and retinol in patients with chronic hepatitis C

TriAnnot: A Versatile and High Performance Pipeline for the Automated Annotation of Plant Genomes

In support of the international effort to obtain a reference sequence of the bread wheat genome and to provide plant communities dealing with large and complex genomes with a versatile, easy-to-use online automated tool for annotation, we have developed the TriAnnot pipeline. Its modular architecture allows for the annotation and masking of transposable elements, the structural, and functional annotation of protein-coding genes with an evidence-based quality indexing, and the identification of conserved non-coding sequences and molecular markers. The TriAnnot pipeline is parallelized on a 712 CPU computing cluster that can run a 1-Gb sequence annotation in less than 5 days. It is accessible through a web interface for small scale analyses or through a server for large scale annotations. The performance of TriAnnot was evaluated in terms of sensitivity, specificity, and general fitness using curated reference sequence sets from rice and wheat. In less than 8 h, TriAnnot was able to predict more than 83% of the 3,748 CDS from rice chromosome 1 with a fitness of 67.4%. On a set of 12 reference Mb-sized contigs from wheat chromosome 3B, TriAnnot predicted and annotated 93.3% of the genes among which 54% were perfectly identified in accordance with the reference annotation. It also allowed the curation of 12 genes based on new biological evidences, increasing the percentage of perfect gene prediction to 63%. TriAnnot systematically showed a higher fitness than other annotation pipelines that are not improved for wheat. As it is easily adaptable to the annotation of other plant genomes, TriAnnot should become a useful resource for the annotation of large and complex genomes in the future