A novel BLAST-Based Relative Distance (BBRD) method can effectively group members of protein arginine methyltransferases and suggest their evolutionary relationship.

We developed a novel BLAST-Based Relative Distance (BBRD) method by Pearson's correlation coefficient to avoid the problems of tedious multiple sequence alignment and complicated outgroup selection. We showed its application on reconstructing reliable phylogeny for nucleotide and protein sequences as exemplified by the fmr-1 gene and dihydrolipoamide dehydrogenase, respectively. We then used BBRD to resolve 124 protein arginine methyltransferases (PRMTs) that are homologues of nine mammalian PRMTs. The tree placed the uncharacterized PRMT9 with PRMT7 in the same clade, outside of all the Type I PRMTs including PRMT1 and its vertebrate paralogue PRMT8, PRMT3, PRMT6, PRMT2 and PRMT4. The PRMT7/9 branch then connects with the type II PRMT5. Some non-vertebrates contain different PRMTs without high sequence homology with the mammalian PRMTs. For example, in the case of Drosophila arginine methyltransferase (DART) and Trypanosoma brucei methyltransferases (TbPRMTs) in the analyses, the BBRD program grouped them with specific clades and thus suggested their evolutionary relationships. The BBRD method thus provided a great tool to construct a reliable tree for members of protein families through evolution.

Combination Therapy Using Chelating Agent and Zinc for Wilson's Disease.

There is no clear international consensus regarding the optimal medication therapy for treating Wilson's disease (WD). This study systematically reviews the effectiveness of various medication therapies in common use, specifically focusing on preliminary findings concerning the combination of a chelating agent and zinc. A systematic PubMed search was executed to locate original studies on the effectiveness of commonly used medications for WD published between January 1989 and August 2014. The results were used to conduct a systematic review of studies on combination therapies. A total of 17 combination therapy studies involving 1056 patients were reviewed. These were analyzed in terms of data on effectiveness, adverse effects, and mortality. Results from a pooled analysis indicate that combination therapies for hepatic patients were significantly less effective than the same therapies for neurological manifestations (47.1 vs. 78.6 %; pooled relative risk ratio (RR): 0.63, 95 % confidence interval CI 0.43-0.94; p = 0.02). Data from a subgroup analysis show that the combination therapy of penicillamine plus zinc sulfate resulted in a significantly higher mortality rate compared to all other combination therapy types (16.3 vs. 4.7 %; RR: 3.51, 95 % CI 1.54-8.00; p < 0.001). The use of combination therapies involving zinc and a chelator should be carefully monitored with close clinical observations and frequent biochemical tests, especially for WD patients with hepatic manifestations.

Mining for representative regions of virus genuses via protein sequences clustering.

Highly conserved sequences (regions or domains) play an important role in phylogenetic analysis. In this study, a novel approach to extract highly conserved sequences as representative regions for the genuses of viruses via protein sequences clustering is proposed. A representative region of one genus is extracted from one distinctive protein sequence group and appears in all members of that genus; a distinctive feature of a protein sequence group formed by a graph-based clustering method is that the sequences within that group appear in all members of one genus but none of the other genuses. Experimental results showed that there were 64 representative regions belonging to 20 genuses extracted in this study. This study not only creates a methodology to extract highly conserved sequences for phylogenetic analysis across taxa, but also provides the materials for investigating viral taxonomy from a molecular biology point of view, instead of traditional morphology.

Comparing virus classification using genomic materials according to different taxonomic levels.

In this paper, three genomic materials--DNA sequences, protein sequences, and regions (domains) are used to compare methods of virus classification. Virus classes (categories) are divided by various taxonomic level of virus into three datasets for 6 order, 42 family, and 33 genera. To increase the robustness and comparability of experimental results of virus classification, the classes are selected that contain at least 10 instances, and meanwhile each instance contains at least one region name. Experimental results show that the approach using region names achieved the best accuracies--reaching 99.9%, 97.3%, and 99.0% for 6 orders, 42 families, and 33 genera, respectively. This paper not only involves exhaustive experiments that compare virus classifications using different genomic materials, but also proposes a novel approach to biological classification based on molecular biology instead of traditional morphology.

Lose weight with traditional chinese medicine? Potential suppression of fat mass and obesity-associated protein.

Overweight and obesity are common health problems in modern society, particularly in developed countries. Excessive body mass has been linked to numerous diseases, such as cardiovascular diseases, diabetes, and cancer. Fat mass and obesity-associated protein (FTO) activity have direct impact on food intake and results in obesity. Inhibition of FTO activity may cause weight loss and reduce obese-linked health risks. We investigated the potential weight loss effects of traditional Chinese medicine (TCM), particularly by inhibiting FTO functions. Molecular docking was performed to screen TCM compounds from TCM Database@Taiwan (http://tcm.cmu.edu.tw). Three candidates were identified that contained either a tetrahydropyridine group or potent electronegative phenol group in the structure scaffold. Molecular dynamics simulation analysis of the docking poses of each complex indicated stabilizing trends in the protein-ligand complex movements. In addition, the number of hydrogen bonds increased throughout the 20 ns simulation. These results suggest that these TCM candidates could be potential FTO inhibitors through competitive inhibition.