1,122 research outputs found

    Sparse tree-based clustering of microbiome data to characterize microbiome heterogeneity in pancreatic cancer

    Full text link
    There is a keen interest in characterizing variation in the microbiome across cancer patients, given increasing evidence of its important role in determining treatment outcomes. Here our goal is to discover subgroups of patients with similar microbiome profiles. We propose a novel unsupervised clustering approach in the Bayesian framework that innovates over existing model-based clustering approaches, such as the Dirichlet multinomial mixture model, in three key respects: we incorporate feature selection, learn the appropriate number of clusters from the data, and integrate information on the tree structure relating the observed features. We compare the performance of our proposed method to existing methods on simulated data designed to mimic real microbiome data. We then illustrate results obtained for our motivating data set, a clinical study aimed at characterizing the tumor microbiome of pancreatic cancer patients

    How to Get the Most from Microarray Data: Advice from Reverse Genomics

    Get PDF
    Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results were consistent across 4 major types of cancer: breast, colorectal, lung, and prostate. We used recently reported cancer-associated genes (2011–2012) for validation and found that novel cancer-associated genes can be best identified by elevated variance of the gene expression in tumor samples

    Cloning, expression in Pichia pastoris, and characterization of a thermostable GH5 mannan endo-1,4-β-mannosidase from Aspergillus niger BK01

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Mannans are key components of lignocellulose present in the hemicellulosic fraction of plant primary cell walls. Mannan endo-1,4-β-mannosidases (1,4-β-<smcaps>D</smcaps>-mannanases) catalyze the random hydrolysis of β-1,4-mannosidic linkages in the main chain of β-mannans. Biodegradation of β-mannans by the action of thermostable mannan endo-1,4-β-mannosidase offers significant technical advantages in biotechnological industrial applications, <it>i.e</it>. delignification of kraft pulps or the pretreatment of lignocellulosic biomass rich in mannan for the production of second generation biofuels, as well as for applications in oil and gas well stimulation, extraction of vegetable oils and coffee beans, and the production of value-added products such as prebiotic manno-oligosaccharides (MOS).</p> <p>Results</p> <p>A gene encoding mannan endo-1,4-β-mannosidase or 1,4-β-<smcaps>D</smcaps>-mannan mannanohydrolase (E.C. 3.2.1.78), commonly termed β-mannanase, from <it>Aspergillus niger </it>BK01, which belongs to glycosyl hydrolase family 5 (GH5), was cloned and successfully expressed heterologously (up to 243 μg of active recombinant protein per mL) in <it>Pichia pastoris</it>. The enzyme was secreted by <it>P. pastoris </it>and could be collected from the culture supernatant. The purified enzyme appeared glycosylated as a single band on SDS-PAGE with a molecular mass of approximately 53 kDa. The recombinant β-mannanase is highly thermostable with a half-life time of approximately 56 h at 70°C and pH 4.0. The optimal temperature (10-min assay) and pH value for activity are 80°C and pH 4.5, respectively. The enzyme is not only active towards structurally different mannans but also exhibits low activity towards birchwood xylan. Apparent K<sub>m </sub>values of the enzyme for konjac glucomannan (low viscosity), locust bean gum galactomannan, carob galactomannan (low viscosity), and 1,4-β-<smcaps>D</smcaps>-mannan (from carob) are 0.6 mg mL<sup>-1</sup>, 2.0 mg mL<sup>-1</sup>, 2.2 mg mL<sup>-1 </sup>and 1.5 mg mL<sup>-1</sup>, respectively, while the k<sub>cat </sub>values for these substrates are 215 s<sup>-1</sup>, 330 s<sup>-1</sup>, 292 s<sup>-1 </sup>and 148 s<sup>-1</sup>, respectively. Judged from the specificity constants k<sub>cat</sub>/K<sub>m</sub>, glucomannan is the preferred substrate of the <it>A. niger</it> β -mannanase. Analysis by thin layer chromatography showed that the main product from enzymatic hydrolysis of locust bean gum is mannobiose, with only low amounts of mannotriose and higher manno-oligosaccharides formed.</p> <p>Conclusion</p> <p>This study is the first report on the cloning and expression of a thermostable mannan endo-1,4-β-mannosidase from <it>A. niger </it>in <it>Pichia pastoris</it>. The efficient expression and ease of purification will significantly decrease the production costs of this enzyme. Taking advantage of its acidic pH optimum and high thermostability, this recombinant β-mannanase will be valuable in various biotechnological applications.</p

    Dietary patterns and risk factors for Type 2 diabetes mellitus in Fijian, Japanese and Vietnamese populations

    Get PDF
    Diabetes mellitus is now a serious and increasing problem in Asian countries, where dietary patterns have shifted toward Westernized foods and people are becoming more sedentary. In order to elucidate the relationship of dietary habits to the development of diabetic risk factors, the dietary patterns of 200 Fijian, 171 Japanese and 181 Vietnamese women of 30–39 years of age were investigated using 3 day–24 h recall or dietary records. Anthropometric measurements and glycosuria tests were also conducted. The dietary trends of Fijians and Japanese have changed drastically in the past 50 years, while Vietnamese have been minimally influenced by Western dietary habits. The mean 24 h dietary intake showed that Fijians had the highest energy intake. Energy intake from fat was only 13% for Vietnamese, but over 30% for Japanese and Fijians. Percentage of body fat was higher in Vietnamese than in Japanese, though there were no significant differences in body mass index (BMI). In the overweight and obese women, Vietnamese had higher abdominal obesity than Japanese. The prevalence of obesity (BMI � 30 kg/m2) was 63.0% for Fijians, 1.8% for Japanese and 1.1% for Vietnamese. Glycosuria testing yielded the most positive cases among Fijians. Dietary transition and dietary excess appear to be potential risk factors for diabetes in Fijian women

    Can data from paediatric cohorts solve the COVID-19 puzzle?

    Get PDF
    COVID-19, caused by SARS-CoV-2, is significantly more severe in adults than in children. The biological reasons for this difference remain to be elucidated. We have compared the most recent virological and immunological data related to COVID-19 between adults and children and contrasted this with earlier data from severe acute respiratory syndrome (SARS) caused by the related SARS-CoV-1 in 2003. Based on these available data, a number of hypotheses are proposed to explain the difference in COVID-19 clinical outcomes between adults and children. NF-kB may be a key factor that could explain the severe clinical manifestations of COVID-19 in adults as well as rare complications associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in paediatric COVID-19 patients

    Calculation of Temperature-Dependent Thermal Expansion Coefficient of Metal Crystals Based on Anharmonic Correlated Debye Model

    Get PDF
    This study aims to calculate the anharmonic thermal expansion (TE) coefficient of metal crystals in the temperature dependence. The calculation model is derived from the anharmonic correlated Debye (ACD) model that is developed using the many-body perturbation approach and correlated Debye model based on the anharmonic effective potential. This potential has taken into account the influence on the absorbing and backscattering atoms of all their nearest neighbors in the crystal lattice. The numerical results for the crystalline zinc (Zn) and crystalline copper (Cu) are in agreement with those obtained by the other theoretical model and experiments at several temperatures. The analytical results show that the ACD model is useful and efficient in analyzing the TE of coefficient of metal crystals
    corecore