A systematic density-based clustering method using anchor points

National Research Foundation (NRF) Singapore under its AI Singapore Programme; Singapore Ministry of Health under its National Innovation Challenge on Active and Confident Agein

Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs

<p>Abstract</p> <p>Background</p> <p>Epitope vaccines have been suggested as a strategy to counteract viral escape and development of drug resistance. Multiple studies have shown that Cytotoxic T-Lymphocyte (CTL) and T-Helper (Th) epitopes can generate strong immune responses in Human Immunodeficiency Virus (HIV-1). However, not much is known about the relationship among different types of HIV epitopes, particularly those epitopes that can be considered potential candidates for inclusion in the multi-epitope vaccines.</p> <p>Results</p> <p>In this study we used association rule mining to examine relationship between different types of epitopes (CTL, Th and antibody epitopes) from nine protein-coding HIV-1 genes to identify strong associations as potent multi-epitope vaccine candidates. Our results revealed 137 association rules that were consistently present in the majority of reference and non-reference HIV-1 genomes and included epitopes of two different types (CTL and Th) from three different genes (<it>Gag, Pol </it>and <it>Nef</it>). These rules involved 14 non-overlapping epitope regions that frequently co-occurred despite high mutation and recombination rates, including in genomes of circulating recombinant forms. These epitope regions were also highly conserved at both the amino acid and nucleotide levels indicating strong purifying selection driven by functional and/or structural constraints and hence, the diminished likelihood of successful escape mutations.</p> <p>Conclusions</p> <p>Our results provide a comprehensive systematic survey of CTL, Th and Ab epitopes that are both highly conserved and co-occur together among all subtypes of HIV-1, including circulating recombinant forms. Several co-occurring epitope combinations were identified as potent candidates for inclusion in multi-epitope vaccines, including epitopes that are immuno-responsive to different arms of the host immune machinery and can enable stronger and more efficient immune responses, similar to responses achieved with adjuvant therapies. Signature of strong purifying selection acting at the nucleotide level of the associated epitopes indicates that these regions are functionally critical, although the exact reasons behind such sequence conservation remain to be elucidated.</p

The potential use of exhausted open pit mine voids as sinks for atmospheric CO2: insights from natural reedbeds and mine water treatment wetlands

Abandoned surface mine voids are often left to flood, forming pit lakes. Drawing simple but important lessons from experiences with compost-based passive remediation systems for acidic mine waters, an alternative end-use for open pit mine voids is proposed: gradual infilling with organic material, which can serve as a long-term sink for atmospheric CO2, whilst ameliorating or eventually eliminating sustained evaporative water loss and acidic water pollution. Key to the success of this approach is the suppression of methane release from organic sediments flooded with sulfate-rich mine waters: the presence of modest amounts of sulfate (which is typically abundant in mine waters) inhibits the activity of methanogenic bacteria. This explains why gas release studies of mine water treatment wetlands never report methane emissions; CO2 is the only greenhouse gas emitted, and this is clearly not at levels sufficient to undo the benefits of wetlands as net CO2 sinks. While the compete infilling of open pits with organic sediments might take a very long time, only minimal maintenance would be needed, and if carbon trading markets finally mature, a steady income stream could be obtained to cover the costs, thus extending the economic life of the mine site far beyond cessation of mining

Molecular Evolution and Functional Divergence of the Cytochrome P450 3 (CYP3) Family in Actinopterygii (Ray-Finned Fish)

The cytochrome P450 (CYP) superfamily is a multifunctional hemethiolate enzyme that is widely distributed from Bacteria to Eukarya. The CYP3 family contains mainly the four subfamilies CYP3A, CYP3B, CYP3C and CYP3D in vertebrates; however, only the Actinopterygii (ray-finned fish) have all four subfamilies and detailed understanding of the evolutionary relationship of Actinopterygii CYP3 family members would be valuable.Phylogenetic relationships were constructed to trace the evolutionary history of the Actinopterygii CYP3 family genes. Selection analysis, relative rate tests and functional divergence analysis were combined to interpret the relationship of the site-specific evolution and functional divergence in the Actinopterygii CYP3 family. The results showed that the four CYP3 subfamilies in Actinopterygii might be formed by gene duplication. The first gene duplication event was responsible for divergence of the CYP3B/C clusters from ancient CYP3 before the origin of the Actinopterygii, which corresponded to the fish-specific whole genome duplication (WGD). Tandem repeat duplication in each of the homologue clusters produced stable CYP3B, CYP3C, CYP3A and CYP3D subfamilies. Acceleration of asymmetric evolutionary rates and purifying selection together were the main force for the production of new subfamilies and functional divergence in the new subset after gene duplication, whereas positive selection was detected only in the retained CYP3A subfamily. Furthermore, nearly half of the functional divergence sites appear to be related to substrate recognition, which suggests that site-specific evolution is closely related with functional divergence in the Actinopterygii CYP3 family.The split of fish-specific CYP3 subfamilies was related to the fish-specific WGD, and site-specific acceleration of asymmetric evolutionary rates and purifying selection was the main force for the origin of the new subfamilies and functional divergence in the new subset after gene duplication. Site-specific evolution in substrate recognition was related to functional divergence in the Actinopterygii CYP3 family

Coal Mining Machinery Development As An Ecological Factor Of Progressive Technologies Implementation

At present, a significant amount of energy spent for the work of mining machines and coal mining equipment on coal mines and open pits goes to the coal grinding in the process of its extraction in mining faces. Meanwhile, the increase of small fractions in mined coal does not only reduce the profitability of its production, but also causes a further negative impact on the environment and degrades labor conditions for miners. The countermeasure to the specified processes is possible with the help of coal mining equipment development. However, against the background of the technological decrease of coal mine equipment applied in Russia the negative impact on the environment is getting reinforced

Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers

MicroRNAs (miRNAs) are a class of noncoding small RNAs that regulate gene expression by base pairing with target mRNAs at the 3′-terminal untranslated regions (3′-UTRs), leading to mRNA cleavage or translational repression. Single-nucleotide polymorphisms (SNPs) located at miRNA-binding sites (miRNA-binding SNPs) are likely to affect the expression of the miRNA target and may contribute to the susceptibility of humans to common diseases. We herein performed a genome-wide analysis of SNPs located in the miRNA-binding sites of the 3′-UTR of various human genes. We found that miRNA-binding SNPs are negatively selected in respect to SNP distribution between the miRNA-binding ‘seed’ sequence and the entire 3′-UTR sequence. Furthermore, we comprehensively defined the expression of each miRNA-binding SNP in cancers versus normal tissues through mining EST databases. Interestingly, we found that some miRNA-binding SNPs exhibit significant different allele frequencies between the human cancer EST libraries and the dbSNP database. More importantly, using human cancer specimens against the dbSNP database for case-control association studies, we found that twelve miRNA-binding SNPs indeed display an aberrant allele frequency in human cancers. Hence, SNPs located in miRNA-binding sites affect miRNA target expression and function, and are potentially associated with cancers

Genomic, evolutionary, and expression analyses of cee, an ancient gene involved in normal growth and development

AbstractThe cee (conserved edge expressed protein) gene was recently identified in a genome-wide screen to discover genes associated with myotube formation in fast muscle of pufferfish. Comparative genomic analyses indicate that cee arose some 1.6–1.8 billion years ago and is found as a single-copy gene in most eukaryotic genomes examined. The complexity of its structure varies from an intronless gene in yeast and tunicates to nine exons and eight introns in vertebrates. cee is particularly conserved among vertebrates and is located in a syntenic region within tetrapods and between teleosts and invertebrates. Low dN/dS ratios in the cee coding region (0.02–0.09) indicate that the Cee protein is under strong purifying selection. In Atlantic salmon, cee is expressed in the superficial layers of developing organs and tissues. These data, together with functional screens in yeast and Caenorhabditis elegans, indicate that cee has a hitherto uncharacterized role in normal growth and development