Identification of agonists for a group of human odorant receptors

Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs) which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10%) have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs

Sense-antisense pairs in mammals: functional and evolutionary considerations

Analysis of a catalog of S-AS pairs in the human and mouse genomes revealed several putative roles for natural antisense transcripts and showed that some are artifacts of cDNA library construction

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

MiRIAD update: using alternative polyadenylation, protein interaction network analysis and additional species to enhance exploration of the role of intragenic miRNAs and their host genes

MicroRNAs have established their role as potent regulators of the epigenome. Interestingly, most miRNAs are located within protein-coding genes with functional consequences that have yet to be fully investigated. MiRIAD is a database with an interactive and user-friendly online interface that has been facilitating research on intragenic miRNAs. In this article, we present a major update. First, data for five additional species (chimpanzee, rat, dog, cow and frog) were added to support the exploration of evolutionary aspects of the relationship between host genes and intragenic miRNAs. Moreover, we integrated data from two different sources to generate a comprehensive alternative polyadenylation dataset. The miRIAD interface was therefore redesigned and provides a completely new gene model representation, including an interactive visualization of the 30 untranslated region (UTR) with alternative polyadenylation sites, corresponding signals and potential miRNA binding sites. Furthermore, we expanded on functional host gene network analysis. Although the previous version solely reported protein interactions, the update features a separate network analysis view that can either be accessed through the submission of a list of genes of interest or directly from a gene's list of protein interactions. In addition to statistical properties of the submitted gene set, the interaction network graph is presented and miRNAs with seed site over- and underrepresentation are identified. In summary, the update of miRIAD provides novel datasets and bioinformatics resources with a significant increase in functionality to facilitate intragenic miRNA research in a user-friendly and interactive way

Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing

Abstract Background To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL. Results By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate in DNA repair pathways. Conclusions Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities

Adenine interaction with and adsorption on Fe-ZSM-5 zeolites: A prebiotic chemistry study using different techniques

Most adsorption experiments are performed under conditions that did not exist on Earth before the life arose on it. Because adsorption is the first step for all other processes (protection against degradation and polymerization), it is important that it is performed under conditions that existed on prebiotic Earth. In this paper, we use an artificial seawater (seawater 4.0 Ga), which contains major cations and anions that could present on the oceans of the prebiotic Earth. In addition, zeolites, with substituted Fe in the framework, and adenine were probably common substances on the prebiotic Earth. Thus, study the interaction between them is an important issue in prebiotic chemistry. There are two main findings described in this paper. Firstly, zeolites with different Si/Fe ratios adsorbed adenine differently. Secondly, XAFS showed that, after treatments with seawater 4.0 Ga and adenine, an increase in the complexity of the system occurred. In general, salts of seawater 4.0 Ga did not affect the adsorption of adenine onto zeolites and adenine adsorbed less onto zeolites with iron isomorphically substituted. The C=C and NH2 groups of adenine interacted with the zeolites. Gypsum, formed from aqueous species dissolved in seawater 4.0 Ga, precipitated onto zeolites. EPR spectra of zeolites showed lines caused by Fe framework and Fe3+ species. TG curves of zeolites showed events caused by loss of water weakly bound to zeolite (in the 30-140 °C range), water bounded to iron species or cations from seawater 4.0 Ga or located in the cavities of zeolites (157-268 °C) and degradation of adenine adsorbed onto zeolites (360-600 °C). Mass loss follows almost the same order as the amount of adenine adsorbed onto zeolites. The XAFS spectrum showed that Fe3+ could be substituted into the framework of the Fe7-ZSM-5 zeolite

C-reactive protein in degenerative aortic valve stenosis

Degenerative aortic valve stenosis includes a range of disorder severity from mild leaflet thickening without valve obstruction, "aortic sclerosis", to severe calcified aortic stenosis. It is a slowly progressive active process of valve modification similar to atherosclerosis for cardiovascular risk factors, lipoprotein deposition, chronic inflammation, and calcification. Systemic signs of inflammation, as wall and serum C-reactive protein, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis and may be expression of a common disease, useful in monitoring of stenosis progression