193 research outputs found

    Local structural alignment of RNA with affine gap model

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    Predicting new non-coding RNAs (ncRNAs) of a family can be done by aligning the potential candidate with a member of the family with known sequence and secondary structure. Existing tools either only consider the sequence similarity or cannot handle local alignment with gaps. In this paper, we consider the problem of finding the optimal local structural alignment between a query RNA sequence (with known secondary structure) and a target sequence (with unknown secondary structure) with the affine gap penalty model. We provide the algorithm to solve the problem. Based on a preliminary experiment, we show that there are ncRNA families in which considering local structural alignment with gap penalty model can identify real hits more effectively than using global alignment or local alignment without gap penalty model.The project is partially supported by the Seed Funding Programme for Basic Research (Project number: 200911159065) of the University of Hong Kong

    Reduced CD27-IgD- B cells in blood and raised CD27-IgD- B cells in gut-associated lymphoid tissue in inflammatory bowel disease.

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    The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analyzed B cells in blood of patients with Crohn's disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analyzed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27−IgD− B cells expressing all Ig isotypes in the blood in IBD (independent of severity of disease and treatment) compared to healthy controls. Successful treatment of patients with biologic therapies did not change the profile of B cell subsets in blood. By mass cytometry we demonstrated that CD27−IgD− B cells were proportionately enriched in the gut-associated lymphoid tissue (GALT) in IBD. Since production of TNFα is a feature of IBD relevant to therapies, we sought to determine whether B cells in GALT or the CD27−IgD− subset in particular could contribute to pathology by secretion of TNFα or IL-10. We found that donor matched GALT and blood B cells are capable of producing TNFα as well as IL-10, but we saw no evidence that CD27−IgD− B cells from blood expressed more TNFα compared to other subsets. The reduced proportion of CD27−IgD− B cells in blood and the increased proportion in the gut implies that CD27−IgD− B cells are recruited from the blood to the gut in IBD. CD27−IgD− B cells have been implicated in immune responses to intestinal bacteria and recruitment to GALT, and may contribute to the intestinal inflammatory milieu in IBD

    Local structural alignment of RNA with affine gap model

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    BACKGROUND: Predicting new non-coding RNAs (ncRNAs) of a family can be done by aligning the potential candidate with a member of the family with known sequence and secondary structure. Existing tools either only consider the sequence similarity or cannot handle local alignment with gaps. RESULTS: In this paper, we consider the problem of finding the optimal local structural alignment between a query RNA sequence (with known secondary structure) and a target sequence (with unknown secondary structure) with the affine gap penalty model. We provide the algorithm to solve the problem. CONCLUSIONS: Based on an experiment, we show that there are ncRNA families in which considering local structural alignment with gap penalty model can identify real hits more effectively than using global alignment or local alignment without gap penalty model.published_or_final_versio

    A Brief Mindfulness-Based Family Psychoeducation Intervention for Chinese Young Adults With First Episode Psychosis: A Study Protocol

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    Family psychoeducation (FPE) has been recommended as a major component in the treatment of psychosis. Many previous studies have implemented an intensive program design that often only emphasized improvements in patients’ illness outcomes but the benefits for caregivers were limited. There have been calls for a time-limited but cost-effective FPE program to mitigate the looming reality of the suffering of people with psychosis and their families. A Brief Mindfulness-Based Family Psychoeducation for psychosis program is developed to reduce caregivers’ burden and promote young adult’s recovery. A randomized controlled trial will be conducted to compare this intervention with an ordinary FPE intervention. Both arms will involve six sessions, with a total contact time of 12 h. 300 caregivers of young adults who have experienced first episode psychosis within last 3 years will be recruited. Program effectiveness will be assessed by comparing outcomes measuring the caregivers’ burden, mental health symptoms, positive well-being, and the young adult’s mental health symptoms during the study and at 9-month post-randomization. The role of expressed emotions, interpersonal mindfulness, and non-attachment in mediating these outcomes will be explored. An additional qualitative approach Photovoice is selected to explore the complex family experiences and the benefits of mindfulness from the caregivers’ personal perspectives.Trial Registration: The trial is registered with the United States Clinical Trials Registry (ClinicalTrials.gov): NCT03688009

    Glyoxalase-I Is a Novel Prognosis Factor Associated with Gastric Cancer Progression

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    Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the progression of human malignancies. The role of GLO1 in gastric cancer development or progression is currently unclear. The expression of GLO1 was determined in primary gastric cancer specimens using quantitative polymerase chain reaction, immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. Elevated expression of GLO1 was significantly associated with gastric wall invasion, lymph node metastasis, and pathological stage, suggesting a novel role of GLO1 in gastric cancer development and progression. The 5-year survival rate of the lower GLO1 expression groups was significantly greater than that of the higher expression groups (log rank P = 0.0373) in IHC experiments. Over-expression of GLO1 in gastric cancer cell lines increases cell proliferation, migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to a marked reduction in the migration and invasion abilities. Our data strongly suggest that high expression of GLO1 in gastric cancer enhances the metastasis ability of tumor cells in vitro and in vivo, and support its efficacy as a potential marker for the detection and prognosis of gastric cancer

    Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein

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    Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%–83% decrease in AUC0-∞ and 38%–78% reduction in Cmax. The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products

    GIW and InCoB, two premier bioinformatics conferences in Asia with a combined 40 years of history

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    Knowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016

    A quantitative model for estimating risk from multiple interacting natural hazards: an application to northeast Zhejiang, China

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    Multi-hazard risk assessment is a major concern in risk analysis, but most approaches do not consider all hazard interactions when calculating possible losses. We address this problem by developing an improved quantitative model - Model for multi-hazard Risk assessment with a consideration of Hazard Interaction (MmhRisk-HI). This model calculates the possible loss caused by multiple hazards, with an explicit consideration of interaction between those hazards. There are two main components to the model. In the first, based on the hazard-forming environment, relationships among hazards are classified into four types for calculation of the exceedance probability of multiple hazards occurrence. In the second, a Bayesian network is used to calculate possible loss caused by multiple hazards with different exceedance probabilities. A multi-hazard risk map can then be drawn addressing the probability of multi-hazard occurrence and corresponding loss. This model was applied in northeast Zhejiang, China and validated by comparison against an observed multi-hazard sequence. The validation results show that the model can more effectively represent the real world, and that the modelled outputs, possible loss caused by multiple hazards, are reliable. The outputs can additionally help to identify areas at greatest risk, and allows a determination of the factors that contribute to that risk, and hence the model can provide useful further information for planners and decision-makers concerned with risk mitigation
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