An extension of the graph theoretical approach to predict the secondary structure of large RNAs: the complex of 16S and 23S rRNAs from E.coli as a case study

An algorithm using the graph theoretical approach to predictsecondary structures of large nucleic acids is discussed. Reliabilityof prediction can be improved by incorporating available experimentaldata and sequence homology information. As a case study, thisalgorithm is applied to predict the secondary structure of the16S–23S rRNA complex from E. coli. It was found that severalstructures of the complex can coexist. The computer programdeveloped to predict the secondary structure of large RNAs canbe run on IBM PC/AT compatible systems. Received on November 20, 1988; accepted on April 15, 1989     

Genome sequencing of <Emphasis Type="Italic">Pediococcus acidilactici</Emphasis> (NRCC1), a novel isolate from dromedary camel (<Emphasis Type="Italic">Camelus dromedarius</Emphasis>) rumen fluid

The lactic acid bacterium Pediococcus acidilactici has recently been reported to help in treating constipation, diarrhea, relieving stress, and enhancing growth rate and immune response in humans, birds, fishes, and small animals. In the present study, we sequenced and analyzed the whole genome of P. acidilactici NRCC1, a novel isolate from rumen fluid of dromedary camel (Camelus dromedarius). The genome of P. acidilactici NRCC1 was assembled into 60 contigs, comprising 1,785,679 bp and 42.5% GC content. The 1705 CDS were predicted and annotated using the RAST server. The genome encodes numerous enzymes for utilization of different carbohydrates. It also harbors genes for antibiotic biosynthesis and many others which might confer probiotic properties. The comparative genome analysis with P. acidilactici DSM 20284 revealed some unique features in P. acidilactici NRCC1. Thus, the genome sequencing of P. acidilactici NRCC1 has opened up new horizons for further research in animal probiotics and feed supplements.     

Evolutionary correlation between floral monosymmetry and corolla pigmentation patterns in <Emphasis Type="Italic">Rhododendron</Emphasis>

Floral symmetry and pigmentation are features of flowers that are believed to be associated due to their shared influence on pollinator behaviour. However, the evolution of such associations has so far not been examined. We analysed variation in Rhododendron flowers, in a phylogenetic context, to test whether the evolution of floral symmetry types and pigment patterns are correlated. Variation in floral symmetry due to variation in corolla form, stamen flexion, stamen arrangement, pistil flexion, as well as corolla pigment patterns was documented in 98 species of Rhododendron. Phylogenetic relations among these species were estimated using maximum likelihood (ML) and Bayesian methods, building on a published molecular dataset of sequences of RNA Polymerase II subunit (RPB2-I). Evolution of the floral traits was studied using phylogenetic correlation tests and ancestral state reconstructions (maximum parsimony, MP and ML methods). Significant correlations were found between corolla pigment pattern and type of floral symmetry at the level of corolla form, stamen flexion or arrangement, and pistil flexion. As expected from their similar roles in enhancing attractability to pollinator, monosymmetric corollas and presence of pigment pattern are correlated; in addition, monosymmetry involving other whorls too shows such a relationship with pigment patterns, and with each other. Multiple evolutionary shifts were detected between monosymmetry and polysymmetry of floral traits in Rhododendron. The relationship between floral monosymmetry attributes and presence of corolla pigment patterns, and additionally, frequent evolutionary shifts in these traits suggest pollinator-mediated selective pressures in Rhododendron.     

Rapid ecosystem service assessment of the impact of Koshi Tappu Wildlife Reserve on wetland benefits to local communities

Wetlands are important for biodiversity and are critical for human livelihoods, providing ecosystem services such as clean water, food and global climate regulation. Many wetlands are threatened by land-use conversion, but creating protected areas to conserve them can benefit both biodiversity and people. However, protected areas can also have socio-economic costs for local communities. At Koshi Tappu Wildlife Reserve in Nepal, there has been historical conflict over the creation of the reserve. In light of a recent proposal to expand the protected area, we explored the use of a rapid ecosystem service assessment tool (TESSA) to assess the impact of the reserve on some of the key ecosystem services the site provides. Based on the ecosystem services assessed we estimated that the economic value of KTWR as a protected area is $350,000 y^?1 ($20 ha^?1y^?1) less than the value of the wetland in an unprotected state. However, this difference is relatively small and is affected by the limitations of the approach and sensitivity of the values to market prices and the assumptions made, so we cannot draw clear conclusions on the overall impact of the reserve in relation to local livelihoods. However, we found TESSA to be a useful tool for engaging with the stakeholder community and for highlighting the potential impacts that land use decisions can have on key ecosystem services. In the context of informing the potential expansion of the reserve, it is clear that further intensive socio-economic assessment of the potential costs and benefits is necessary.     

Synthesis and structure based optimization of novel Akt inhibitors

Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).     

Design, synthesis, and studies of small molecule STAT3 inhibitors

A series of small molecule STAT3 inhibitors originally derived from our lead compound STA 21 were synthesized and evaluated. The most potent compound in this series, compound 1, exhibited the same anti-proliferative activities as STA 21 against prostate cancer cell lines that express constitutively active STAT3. Molecular docking showed compound 1 bound to the STAT3beta SH2 domain in a similar manner as STA 21.     

Structure–activity relationship studies of curcumin analogues

Two series of curcumin analogues, a total of twenty-four compounds, were synthesized and evaluated. The most potent compound, compound 23, showed potent growth inhibitory activities on both prostate and breast cancer lines with IC₅₀ values in sub-micromolar range, fifty times more potent than curcumin. Curcumin analogues might be potential anti-tumor agents for breast and prostate cancers.