Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitory activities

6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2-12) were synthesized and evaluated for their cytotoxic and topoisomerase IIα inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising in vitro cytotoxic activities against four cancer cell lines, with IC₅₀ values ranging from 0.38 to 0.73 μM. These three compounds also strongly inhibited topoisomerase II activity at 68.3-93.5% and showed a moderately high DNA intercalating property.     

Simplified approaches for the development of an ELISA to detect circulating autoantibodies to p53 in cancer patients

Background  

The recognition that human tumors stimulate the production of autoantibodies has initiated the use of this immune response as serological markers for the early diagnosis and management of cancer. The enzyme-linked immunosorbent assay (ELISA) is the most common method used in detecting autoantibodies, which involves coating the microtiter plate with the tumor associated antigen (TAA) of interest and allowing serum antibodies to bind. The patient's sample is directly in contact with the coating antigen so the protein used for coating must be pure to avoid non-specific binding. In this study, a simplified method to selectively and specifically immobilize TAAs onto microtiter plates in order to detect circulating autoantibodies in cancer patients without prior purification process was described. Wild type full-length p53 protein was produced in fusion with biotin carboxyl carrier peptide (BCCP) or hexahistidine [(His)6] using pAK400 and pET15b(+) vectors, respectively. The recombinant p53 fusion protein produced was then subjected to react with either a commercial p53 monoclonal antibody (mAb) or sera from lung cancer patients and healthy volunteers in an enzyme-linked immunosorbent assay (ELISA) format.     

Distribution and diversity of palms in a tropical biodiversity hotspot (Thailand) assessed by species distribution modeling

Species distribution modeling has been widely used to address questions related to ecology, biogeography and species conservation on global and regional scales. Here, we study palms (Arecaceae) in a tropical biodiversity hotspot (Thailand) using species distribution modeling to assess range‐limiting factors and estimate distribution and diversity patterns based on a comprehensive compilation of occurrence records. We focused on palms as a model group due to their key‐stone importance for ecosystem functioning and socio‐economics. Different combinations of climatic, non‐climatic environmental and spatial predictors were used. The most accurate models as indicated by the ‘area under the receiver operating characteristic curve’ (AUC) statistic were those that combined all predictors. The four strongest single predictors of palm species distributions were, in decreasing order of importance, 1) latitude, 2) precipitation of driest quarter, 3) annual precipitation, and 4) minimum temperature of the coldest month, suggesting rainfall patterns and latitudinal spatial constraints as the main range determinants. Overlaying the predicted distributions revealed that potential palm hotspots are situated in the provinces of Satun and Yala in southern Thailand where vast areas remain relatively open to the discovery of new palm records and perhaps even new species.     

Is Zinc Concentration in Toxic Phase Plasma Related to Dengue Severity and Level of Transaminases?

Objective

To determine the relationship between plasma zinc values and the severity of dengue viral infection (DVI) and DVI-caused hepatitis.

Methods

A prospective cohort study was conducted during 2008–2010 in hospitalized children aged <15 years confirmed with DVI. Complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and zinc values (mcg/dL) were determined twice: first during the toxic phase (Zn1) and secondly two weeks after recovery (Zn2).

Results

39 patients were enrolled with a mean age of 9.7±3.7 years, and 15/39 diagnosed with dengue shock syndrome (DSS). Zn1 values were lower than Zn2 values [median (IQR): 46.0 (37.0, 58.0) vs 65.0 (58.0, 81.0) mcg/dL, respectively, p <0.01]. Zn1 but not Zn2 values had a negative correlation with AST and ALT (r_s = −0.33, p = 0.04 and r_s = −0.31, p = 0.05, respectively). Patients with DSS had lower Zn1 but not Zn2 values compared with non-DSS patients [median (IQR) Zn1, 38.0 (30.0, 48.0) vs 52.5 (41.2, 58.7), p = 0.02; Zn2, 61.0 (56.0, 88.0) vs 65.0 (59.5, 77.5), respectively, p = 0.76]. Zn1 values showed a decreasing trend across increasing dengue severity groups (p = 0.02). Age <5 years and DVI-associated diarrhea were associated with low Zn1.

Conclusion

Children who had a higher grade of dengue disease severity and liver cell injury had lower Zn1 values. Low Zn1 values were probably caused by loss from diarrhea and from zinc translocating to liver cells.     

Overcoming doxorubicin-resistance in the NCI/ADR-RES model cancer cell line by novel anthracene-9,10-dione derivatives

Overcoming drug resistance with remarkable cytotoxic activity by anthracene-9,10-dione derivatives would offer a potential therapeutic strategy. In this study, we report the synthesis and the cytotoxicity of a novel set of anthraquninones. (4-(4-Aminobenzylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl-4-methylbenzenesulfonate) (3) has excellent in vitro cytotoxicity against doxorubicin-resistant cancer cell line (IC₅₀ = 0.8 μM), 20-fold higher than doxorubicin. The cytotoxic effect via G2/M arrest does not appear to be ROS.     

Changes in physicochemical properties of waxy corn starches at different stages of harvesting

Starches were isolated from immature waxy corn kernels harvested at 0, 2, 4 and 6 days after optimum stage (DAO) and from mature kernels at 16 DAO. The starch contents showed varied according to genotypes and harvesting stages. The accumulation of starches showed an increasing trend in relation to delayed harvesting time, from the optimum stage until the physiological maturity stage. Among all harvesting stages, medium granules had the highest contribution to the total starch volume (60.8–81.5%), followed by large (5.7–30.1%), and small granules (9.1–15.3%). Average chain length distribution of amylopectin ranged from DP 14.7 to 16.9 for KKU–UB, DP 16.9 to 17.4 for KKU–JD, and DP 5.7 to 30.1 for Violet white. The pasting behaviors of starches were greatly affected by harvesting times. The peak viscosity of starches increased with delayed harvesting until physiological maturity and then decreased until dried kernels at 35 days after pollination.     

Distributed control for recruitment, scanning and subunit joining steps of translation initiation

Protein synthesis utilizes a large proportion of the available free energy in the eukaryotic cell and must be precisely controlled, yet up to now there has been no systematic rate control analysis of the in vivo process. We now present a novel study of rate control by eukaryotic translation initiation factors (eIFs) using yeast strains in which chromosomal eIF genes have been placed under the control of the tetO7 promoter system. The results reveal that, contrary to previously published reports, control of the initiation pathway is distributed over all of the eIFs, whereby rate control (the magnitude of their respective component control coefficients) follows the order: eIF4G>eIF1A>eIF4E>eIF5B. The apparent rate control effects of eIFs observed in standard cell-free extract experiments, on the other hand, do not accurately reflect the steady state in vivo data. Overall, this work establishes the first quantitative control framework for the study of in vivo eukaryotic translation.     

The complete mitochondrial DNA sequence of the Mekong giant catfish (Pangasianodon gigas), and the phylogenetic relationships among Siluriformes

The Mekong giant catfish (Pangasianodon gigas) is the largest scale-less freshwater fish of the world, and a critically endangered species. We determined the complete nucleotide sequence (16,533 bp) of the mitochondrial genome of the Mekong giant catfish, and conducted phylogenetic analyses based on mitochondrial protein (the combined amino acid sequences of all 13 mitochondrial protein coding genes) and rRNA (the combined nucleotide sequences of mitochondrial 12S and 16S rRNA genes) data sets in order to further clarify the relative phylogenetic position of P. gigas, and to recover phylogenetic relationships among 15 out of the 33 families of Siluriformes. Phylogenetic analyses (maximum parsimony, minimum evolution, maximum likelihood, Bayesian inference) of the protein data set were congruent with a basal split of the order into Loricarioidei and Siluroidei, and supported a closer relationship of the Mekong giant catfish (family Pangasiidae) to Siluridae than to Bagridae. The rRNA-based Bayesian phylogeny recovered Callichthyidae as the sister group of all other analyzed non-diplomystid catfish families, rendering Loricarioidei paraphyletic. In addition, Loricariidae were recovered as paraphyletic due to the inclusion of Astroblepidae. However, none of the two relationships received bootstrap support in the maximum parsimony, minimum evolution, and maximum likelihood analyses, and should be interpreted with caution. The derived position of Cetopsidae within Siluroidei, the sister group relationship of Pseudopimelodidae and Pimelodidae, and a close relationship of Doradidae and Auchenipteridae to the exclusion of Mochokidae were strongly supported. Pangasiidae was placed as a single lineage without clear affinities.