Influence of stereoisomer of dispiro-1,2,4,5-tetraoxanes on their binding mode with heme and on antimalarial activity: molecular docking studies

Based on the fact that different isomers may exhibit substantial distinct activities, quantum chemical calculations and automated molecular docking simulations were carried out for 13 dispiro-1,2,4,5-tetraoxane compounds, which experimentally exist as a mixture of several isomers, to elucidate the most probable isomer(s) responsible for their antimalarial activity. The results indicate significant effects of stereoisomer on the binding mode and the activity. Moreover, the antimalarial potency of each compound can be described by the docking results. Compounds 1, 2, 4, 5, 7, and 9 have the most probable isomers coordinate suitably with heme iron and hence they have high activities while the most probable isomer in compounds 3 and 8 could not bind appropriately to heme yielding only moderate activities. On the other hand, the steric hindrance in compounds 11-13 prevents an approach of heme iron to peroxide bonds resulting in a devoid of antimalarial activity. However, compounds 6 and 10 with isopropyl substituents exhibit a different docking character, which is possibly caused by a limitation in molecular flexibility of the available docking technique. Our results can be used as a guideline for stereochemical control in synthesis process to improve drug's potency.     

Identification of regulatory regions and regulatory protein complexes of the Spirulina desD gene under temperature stress conditions: Role of thioredoxin as an inactivator of a transcriptional repressor GntR under low-temperature stress

In the present study, electrophoretic mobility shift assays were used to identify temperature responsive elements in the 5' upstream region (5' UTR) of the Spirulina desD gene. Overlapping, synthetic oligonucleotides of both sense and anti-sense strands that spanned the entire 5' UTR of the gene were analyzed. The responsive DNA-binding protein complexes were identified using liquid chromatography-tandem mass spectrometry. The results indicated that the cold-responsive elements were located at -453 to -247, -197 to -151, -105 to -76, and -50 to -1, whereas the low-temperature specific regulatory regions were located at -372 to -352. Moreover, the heat-responsive elements were located at -347 to -243, -197 to -151, and -124 to -1, whereas the high-temperature specific elements were located between -130 to -101 and -30 to -1. In terms of regulatory protein complexes under the two stress conditions, Trx was only detected in the low-temperature responsive protein complex, and divalent cations were essential for the binding of the protein complex to the regulatory elements. Furthermore, Trx was shown to play a critical role as a reducing agent that inactivates the Spirulina desD repressor, GntR. Consequently, the desD gene expression is induced under the low-temperature condition.     

Rediocides A and G as Potential Antitoxins Against Cobra Venom

Rediocides A and G, the principle components of Trigonostemon reidioides (Kurz ) Craib , which is known as Lotthanong in Thai, were investigated for a detoxification mechanism against Naja kaouthia venom by in silico, in vitro, and in vivo methods. Molecular dockings of α‐cobratoxin with rediocides A and G were performed, and the binding energies were found to be ?14.17 and ?14.14 kcal/mol, respectively. Rediocides bind to α‐cobratoxin at the same location as α‐cobratoxin binds to the nicotinic acetylcholine receptor (nAChR), i.e., at the Asp27, Phe29, Arg33, Gly34, Lys35, and Val37 residues. α‐Cobratoxin cannot bind to nAChR, because some of its binding sites are occupied with rediocides. From in vitro SDS‐PAGE, it was found that rediocides can diminish the bands of α‐cobratoxin. In the presence of acetylcholine‐binding protein (AChBP), it was apparent that rediocides can bind both α‐cobratoxin and AChBP. From an in vivo test, it was found that injection of rediocides at 0.5 mg/kg immediately after an α‐cobratoxin dose of three times LD₅₀ cannot prolong the survival time of mice. However, rediocide can prolong the survival time, if it is injected 30 min before the injection of α‐cobratoxin. The in vitro SDS‐PAGE and the in vivo results support the in silico detoxification mechanism of rediocides against cobra venom at a molecular level.     

Culicoides Latreille (Diptera: Ceratopogonidae) as potential vectors for Leishmania martiniquensis and Trypanosoma sp. in northern Thailand

Biting midges of genus Culicoides (Diptera: Ceratopogonidae) are the vectors of several pathogenic arboviruses and parasites of humans and animals. Several reports have suggested that biting midges might be a potential vector of Leishmania parasites. In this study, we screened for Leishmania and Trypanosoma DNA in biting midges collected from near the home of a leishmaniasis patient in Lamphun province, northern Thailand by using UV-CDC light traps. The identification of biting midge species was based on morphological characters and confirmed using the Cytochrome C oxidase subunit I (COI) gene. The detection of Leishmania and Trypanosoma DNA was performed by amplifying the internal transcribed spacer 1 (ITS1) and small subunit ribosomal RNA (SSU rRNA) genes, respectively. All the amplified PCR amplicons were cloned and sequenced. The collected 223 biting midges belonged to seven species (Culicoides mahasarakhamense, C. guttifer, C. innoxius, C. sumatrae, C. huffi, C. oxystoma, and C. palpifer). The dominant species found in this study was C. mahasarakhamense (47.53%). Leishmania martiniquensis DNA was detected in three samples of 106 specimens of C. mahasarakhamense tested indicating a field infection rate of 2.83%, which is comparable to reported rates in local phlebotomines. Moreover, we also detected Trypanosoma sp. DNA in one sample of C. huffi. To our knowledge, this is the first molecular detection of L. martiniquensis in C. mahasarakhamense as well as the first detection of avian Trypanosoma in C. huffi. Blood meal analysis of engorged specimens of C. mahasarakhamense, C. guttifer, and C. huffi revealed that all specimens had fed on avian, however, further studies of the host ranges of Culicoides are needed to gain a better insight of potential vectors of emerging leishmaniasis. Clarification of the vectors of these parasites is also important to provide tools to establish effective disease prevention and control programs in Thailand.     

Morbidity Rate Prediction of Dengue Hemorrhagic Fever (DHF) Using the Support Vector Machine and the Aedes aegypti Infection Rate in Similar Climates and Geographical Areas

BackgroundIn the past few decades, several researchers have proposed highly accurate prediction models that have typically relied on climate parameters. However, climate factors can be unreliable and can lower the effectiveness of prediction when they are applied in locations where climate factors do not differ significantly. The purpose of this study was to improve a dengue surveillance system in areas with similar climate by exploiting the infection rate in the Aedes aegypti mosquito and using the support vector machine (SVM) technique for forecasting the dengue morbidity rate.ConclusionsThe infection rates of the Ae. aegypti female mosquitoes and larvae improved the morbidity rate forecasting efficiency better than the climate parameters used in classical frameworks. We demonstrated that the SVM-R-based model has high generalization performance and obtained the highest prediction performance compared to classical models as measured by the accuracy, sensitivity, specificity, and mean absolute error (MAE).     

Enhancement of carotenoids and lipids production by oleaginous red yeast Sporidiobolus pararoseus KM281507

Bioconversion of biodiesel-derived crude glycerol into carotenoids and lipids was investigated by a microbial conversion of an oleaginous red yeast Sporidiobolus pararoseus KM281507. The methanol content in crude glycerol (0.5%, w/v) did not show a significant effect on biomass production by strain KM281507. However, demethanolized crude glycerol significantly supported the production of biomass (8.64?±?0.13?g/L), lipids (2.92?±?0.03?g/L), β-carotene (15.76?±?0.85?mg/L), and total carotenoids (33.67?±?1.28?mg/L). The optimal conditions suggested by central composite design were crude glycerol concentration (55.04?g/L), initial pH of medium (pH 5.63) and cultivation temperature (24.01°C). Under these conditions, the production of biomass, lipids, β-carotene, and total carotenoids were elevated up to 8.83?±?0.05, 4.00?±?0.06?g/L, 27.41?±?0.20, and 53.70?±?0.48?mg/L, respectively. Moreover, an addition of olive oil (0.5???2.0%) dramatically increased the production of biomass (14.47?±?0.15?g/L), lipids (6.40?±?0.09?g/L), β-carotene (54.43?±?0.95?mg/L), and total carotenoids (70.92?±?0.51?mg/L). The oleic acid content in lipids was also increased to 75.1% (w/w) of total fatty acids, indicating a good potential to be an alternative biodiesel feedstock. Meanwhile, the β-carotene content in total carotenoids was increased to 76.7% (w/w). Hence, strain KM281507 could be a good potential source of renewable biodiesel feedstock and natural carotenoids.     

<Emphasis Type="Italic">Arundinella kokutensis</Emphasis> (Poaceae,Arundinelleae), a new species from south-eastern Thailand

Arundinella kokutensis Teerawat. & Sungkaew is described and illustrated here as a new species from Kut Island, Trat Province, Thailand.