DCMD: Distance-based Classification Using Mixture Distributions on Microbiome Data

Current advances in next generation sequencing techniques have allowed researchers to conduct comprehensive research on microbiome and human diseases, with recent studies identifying associations between human microbiome and health outcomes for a number of chronic conditions. However, microbiome data structure, characterized by sparsity and skewness, presents challenges to building effective classifiers. To address this, we present an innovative approach for distance-based classification using mixture distributions (DCMD). The method aims to improve classification performance when using microbiome community data, where the predictors are composed of sparse and heterogeneous count data. This approach models the inherent uncertainty in sparse counts by estimating a mixture distribution for the sample data, and representing each observation as a distribution, conditional on observed counts and the estimated mixture, which are then used as inputs for distance-based classification. The method is implemented into a k-means and k-nearest neighbours framework and we identify two distance metrics that produce optimal results. The performance of the model is assessed using simulations and applied to a human microbiome study, with results compared against a number of existing machine learning and distance-based approaches. The proposed method is competitive when compared to the machine learning approaches and showed a clear improvement over commonly used distance-based classifiers. The range of applicability and robustness make the proposed method a viable alternative for classification using sparse microbiome count data.Comment: 27 pages, 3 figure

Identification of miRNAs in a Liver of a Human Fetus by a Modified Method

BACKGROUND: miRNAs are 17-25 nucleotides long RNA molecules that have been found to regulate gene expression in human cells. There are studies showing that different groups of miRNAs are involved in development of different tissues. In hepatocytes there are reported particular types of miRNAs that regulate gene expression. METHODS: We established a human fetal liver cDNA library by a modified cloning protocol. Then plasmid isolation from the colonies was performed. After sequencing and database searching, the miRNAs were recognized. RT-PCR and sequencing were carried out to validate the miRNAs detected. Real-time PCR was used to analyze the expression of each miRNA. RESULTS: One novel miRNA was discovered, together with another 35 previously-known miRNAs in the fetal liver. Some of them existed in variants. The miRNAs identified were validated by RT-PCR and sequencing. Quantitative analysis showed that they have variable expression. CONCLUSION: Our results indicate that a special group of miRNAs may play an important role in fetal liver development in a synergistic manner

Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis

AbstractEvidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Copper treatment alone showed no significant learning and memory impairments in behavioral tasks. However, copper-induced neurotoxicity was significantly increased in mice given elevated-cholesterol diet. Trace amounts of copper decreased the activity of SOD and increased the level of malondialdehyde (MDA) in the brain of cholesterol-fed mouse. Copper also caused an increase in amyloid precursor protein (APP) mRNA level and the activation of caspase-3 in the brain of cholesterol-fed mice. The apoptosis-induced nuclear DNA fragmentation was detected in the brain of those mice by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling staining. These findings suggest that trace amounts of copper induce neurotoxicity in cholesterol-fed mice through apoptosis caused by oxidative stress

1-Benzoyl-3-chloro­azepan-2-one

In the crystal structure of the title compound, C13H14ClNO2, inter­molecular C—H⋯O inter­actions link the mol­ecules into a two-dimensional network

3-Chloro­azepan-2-one

In the title compound, C6H10ClNO, an inter­mediate for the production of lysine, there are intra­molecular C—H⋯Cl hydrogen bonds

4-(4-Nitro­benzene­sulfonamido)pyridinium trifluoro­acetate

In the title compound, C11H10N3O4S+·C2F3O2 −, the benzene ring makes an angle of 87.3 (2)° with the pyridinium ring. The nitro group is essentially coplanar with the benzene ring. The F atoms of the CF3 group are disordered over two positions with almost equal occupancy [0.531 (12)/0.469 (12)]. The crystal structure is stabilized by N—H⋯O and C—H⋯O hydrogen bonds

Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production

Monocytes/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral blood from RA patients was higher than that in normal control and ankylosing spondylitis (AS) patients. The MFI of CD147 expression on the CD14+ monocytes in RA synovial fluid was higher than that in RA peripheral blood. Immunohistochemical staining shows that CD147 expression in RA synovium correlated with matrix metalloproteinase (MMP)-1 expression. A double immunofluorescent assay shows that CD147 was expressed on CD68+ cells in RA synovium. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using a chemotaxis assay in vitro and it was found that the addition of anti-CD147 antibody or a CD147 antagonistic peptide significantly decreased the chemotactic index of the mononuclear cells. The role of CD147 in MMP production and cell invasion in vitro were studied through the co-culture of human CD14+ monocytes or monocytic line THP-1 cells and human fibroblasts, as well as by gel zymography and an invasion assay. Significantly elevated release and activation of MMP-9 and/or MMP-2 were seen in the co-culture of human monocytes/THP-1 cells and fibroblasts compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays was also observed in the co-cultured cells. The addition of CD147 antagonistic peptide had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture. Our study demonstrates that the increased expression of CD147 on monocytes/macrophages in RA may be responsible for elevated MMP secretion, cell invasion and CyPA-mediated cell migration into the joints, all of which may contribute to the cartilage and bone destruction of RA. These findings, together with a better understanding of CD147, CyPA and RA, will help in the development of innovative therapeutic interventions for RA