Refining orthologue groups at the transcript level

<p>Abstract</p> <p>Background</p> <p>Orthologues are genes in different species that are related through divergent evolution from a common ancestor and are expected to have similar functions. Many databases have been created to describe orthologous genes based on existing sequence data. However, alternative splicing (in eukaryotes) is usually disregarded in the determination of orthologue groups and the functional consequences of alternative splicing have not been considered. Most multi-exon genes can encode multiple protein isoforms which often have different functions and can be disease-related. Extending the definition of orthologue groups to take account of alternate splicing and the functional differences it causes requires further examination.</p> <p>Results</p> <p>A subset of the orthologous gene groups between human and mouse was selected from the InParanoid database for this study. Each orthologue group was divided into sub-clusters, at the transcript level, using a method based on the sequence similarity of the isoforms. Transcript based sub-clusters were verified by functional signatures of the cluster members in the InterPro database. Functional similarity was higher within than between transcript-based sub-clusters of a defined orthologous group. In certain cases, cancer-related isoforms of a gene could be distinguished from other isoforms of the gene. Predictions of intrinsic disorder in protein regions were also correlated with the isoform sub-clusters within an orthologue group.</p> <p>Conclusions</p> <p>Sub-clustering of orthologue groups at the transcript level is an important step to more accurately define functionally equivalent orthologue groups. This work appears to be the first effort to refine orthologous groupings of genes based on the consequences of alternative splicing on function. Further investigation and refinement of the methodology to classify and verify isoform sub-clusters is needed, particularly to extend the technique to more distantly related species.</p

Refining orthologue groups at the transcript level

<p>Abstract</p> <p>Background</p> <p>Orthologues are genes in different species that are related through divergent evolution from a common ancestor and are expected to have similar functions. Many databases have been created to describe orthologous genes based on existing sequence data. However, alternative splicing (in eukaryotes) is usually disregarded in the determination of orthologue groups and the functional consequences of alternative splicing have not been considered. Most multi-exon genes can encode multiple protein isoforms which often have different functions and can be disease-related. Extending the definition of orthologue groups to take account of alternate splicing and the functional differences it causes requires further examination.</p> <p>Results</p> <p>A subset of the orthologous gene groups between human and mouse was selected from the InParanoid database for this study. Each orthologue group was divided into sub-clusters, at the transcript level, using a method based on the sequence similarity of the isoforms. Transcript based sub-clusters were verified by functional signatures of the cluster members in the InterPro database. Functional similarity was higher within than between transcript-based sub-clusters of a defined orthologous group. In certain cases, cancer-related isoforms of a gene could be distinguished from other isoforms of the gene. Predictions of intrinsic disorder in protein regions were also correlated with the isoform sub-clusters within an orthologue group.</p> <p>Conclusions</p> <p>Sub-clustering of orthologue groups at the transcript level is an important step to more accurately define functionally equivalent orthologue groups. This work appears to be the first effort to refine orthologous groupings of genes based on the consequences of alternative splicing on function. Further investigation and refinement of the methodology to classify and verify isoform sub-clusters is needed, particularly to extend the technique to more distantly related species.</p

Effect of polyphenol extract from Zanthoxylum bungeanum Maxim. on endocrine hormones and monoamine oxidase activity in a mouse model of climacteric depression

Purpose: To investigate the effects of polyphenol extract from Zanthoxylum bungeanum Maxim. (ZPPC) on endocrine hormones, monoamine&nbsp; oxidase activity and behavior in a mouse model of climacteric depression.Methods: Institute of Cancer Research (ICR) female albino mice (n = 50) weighing 24 – 26 g (mean wt = 25.0 ± 1.0 g) were randomly assigned to five groups of ten rats each: normal control group, negative control, and ZPPC (50 mg/kg), ZPPC (100 mg/kg) and ZPPC (200 mg/kg) groups. Depression was induced in the mice via oral administration of moclobemide at a dose of 20 mg/kg, and intraperitoneal injection of imipramine (20 mg/kg) 1 h and 30 min, before treatment. Tail suspension, forced swimming and voluntary activity tests were performed on the mice. The activity of monoamine oxidase (MAO) in mouse brain and the levels of endocrine hormones were also determined.Results: Treatment of depressed mice with ZPPC significantly and dose-dependently increased their tail suspension and immobility time (p &lt; 0.05). The activity of monoamine oxidase in the brains of mice in the negative control group was significantly higher than that of normal control mice, but was significantly and dose-dependently reduced by ZPPC treatment (p &lt; 0.05). Similarly, treatment of depressed mice with ZPPC significantly and dose-dependently reduced their serum adrenocorticotropin and corticosterone levels (p &lt; 0.05).Conclusion: The results of this study indicate that ZPPC exerts antidepressant effect via suppression of brain MAO activity. Keywords: Climacteric depression, Endocrine hormones, Menopause, Monoamine oxidase, Polyphenol

A Novel Synthetic Analog of 5, 8-Disubstituted Quinazolines Blocks Mitosis and Induces Apoptosis of Tumor Cells by Inhibiting Microtubule Polymerization

Many mitosis inhibitors are powerful anticancer drugs. Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs. We have identified LJK-11, a synthetic analog of 5, 8-disubstituted quinazolines, as a novel mitotic blocker. LJK-11 inhibited growth and induced apoptosis of many different types of tumor cells. It prevented mitotic spindle formation and arrested cells at early phase of mitosis. Detailed in vitro analysis demonstrated that LJK-11 inhibited microtubule polymerization. In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole. Therefore, LJK-11 represents a novel anti-microtubule structure. Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs

Autotoxicity in Pogostemon cablin and their allelochemicals

AbstractThe effects of allelochemicals and aqueous extracts from different Pogostemon cablin (Blanco) Benth., Lamiaceae, parts and rhizosphere soil on growth parameters, leaf membrane peroxidation and leaf antioxidant enzymes were investigated in patchouli. P. cablin seedlings were incubated in solutions containing allelochemicals and aqueous extracts from different patchouli parts and its rhizosphere soil at several concentrations. Firstly, the growth parameters were significantly reduced by the highest concentration of leaves, roots and stems extracts (p<0.05). As compared to the control, plant height was reduced by 99.8% in the treatment with leaves extracts (1:10). The malondialdehyde content increased greatly when patchouli seedlings were subject to different concentrations of leaves, roots and stems extracts; meanwhile, the superoxide dismutase and peroxidase activities showed an increase trend at the low concentration, followed by a decline phase at the high concentration of roots and leaves extracts (1:10). What's more, leaves and roots extracts had a more negative effect on patchouli growth than stems extracts at the same concentrations. Secondly, the total fresh mass, root length and plant height were greatly reduced by the highest strength of soil extracts. Their decrements were 22.7, 74.9, and 33.1%, respectively. Thirdly, growth parameters and enzymatic activities varied considerably with the kinds of allelochemicals and with the different concentrations. Plant height, root length and total fresh weight of patchouli were greatly reduced by p-hydroxybenzoic acid (200μM), and their decrements were 77.0, 42.0 and 70.0%, respectively. Finally, three useful measures on reducing the autotoxicity during the sustainable patchouli production were proposed

Separation, Purification, Structure-Activity Relationship and Molecular Docking of Sesame Angiotension Converting Enzyme Inhibitory Peptides Prepared by Subcritical Water Hydrolysis

Angiotension converting enzyme (ACE) inhibitory peptides from high-temperature sesame meal protein hydrolyzed by subcritical water were separated and purified by sequential nanofiltration, ultrafiltration and liquid chromatography, and their structures were identified by liquid chromatography-mass spectrometry (LC-MS). The ACE inhibitory activity was verified using the synthetic oligopeptides. The absorption and metabolism characteristics of the oligopeptides were predicted, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established, and molecular docking analysis was carried out. The peptide fraction with molecular mass less than 3 kDa had the strongest ACE inhibitory effect. After further purification, nine ACE inhibitory peptides were identified from peak 1. These peptides could not interfere with the normal physiological activities of the human body. The 3D-QSAR model for LFRAF was successfully established using the comparative molecular force field analysis (CoMFA) method. The positively charged amino acid residues and the introduced large groups on the side chain at the C-terminus of the ACE inhibitory peptides could improve their activity. LFRAF occupied the S2 and S1’ active pockets of the ACE peptides and bund to Zn2+ to inhibit ACE activity. These results indicate that it is feasible to use subcritical water technology to degrade high-temperature sesame meal proteins to prepare ACE inhibitory peptides

lncRNA profile study reveals the mRNAs and lncRNAs associated with docetaxel resistance in breast cancer cells

Abstract Resistance to adjuvant systemic treatment, including taxanes (docetaxel and paclitaxel) is a major clinical problem for breast cancer patients. lncRNAs (long non-coding RNAs) are non-coding transcripts, which have recently emerged as important players in a variety of biological processes, including cancer development and chemotherapy resistance. However, the contribution of lncRNAs to docetaxel resistance in breast cancer and the relationship between lncRNAs and taxane-resistance genes are still unclear. Here, we performed comprehensive RNA sequencing and analyses on two docetaxel-resistant breast cancer cell lines (MCF7-RES and MDA-RES) and their docetaxel-sensitive parental cell lines. We identified protein coding genes and pathways that may contribute to docetaxel resistance. More importantly, we identified lncRNAs that were consistently up-regulated or down-regulated in both the MCF7-RES and MDA-RES cells. The co-expression network and location analyses pinpointed four overexpressed lncRNAs located within or near the ABCB1 (ATP-binding cassette subfamily B member 1) locus, which might up-regulate the expression of ABCB1. We also identified the lncRNA EPB41L4A-AS2 (EPB41L4A Antisense RNA 2) as a potential biomarker for docetaxel sensitivity. These findings have improved our understanding of the mechanisms underlying docetaxel resistance in breast cancer and have provided potential biomarkers to predict the response to docetaxel in breast cancer patients