A cornerstone of the antiviral interferon response is phosphorylation of eukaryotic initiation factor (eIF)2␣. This limits the availability of eIF2⅐GTP⅐Met-tRNA i Met ternary complexes, reduces formation of 43S preinitiation complexes, and blocks viral (and most cellular) mRNA translation. However, many viruses have developed counterstrategies that circumvent this cellular response. Herein, we characterize a novel class of translation initiation inhibitors that block ternary complex formation and prevent the assembly of 43S preinitiation complexes. We find that translation driven by the HCV IRES is refractory to inhibition by these compounds at concentrations that effectively block cap-dependent translation in vitro and in vivo. Analysis of initiation complexes formed on the HCV IRES in the presence of inhibitor indicates that eIF2␣ and Met-tRNA i Met are present, defining a tactic used by HCV to evade part of the antiviral interferon response.

The National Cancer Institute (NCI) Human Tumor Cell Line Anti-Cancer Drug Screen has evaluated the cytotoxicity profiles of a large number of synthetic compounds, natural products, and plant extracts on 60 different cell lines. The data for each compound/extract can be assessed for similarity of cytotoxicity pattern, relative to a given test compound, using an algorithm called COMPARE. In applying a chemical biology approach to better understand the mechanism of eukaryotic protein synthesis, we used these resources to search for novel inhibitors of translation. The cytotoxicity profiles of 31 known protein synthesis inhibitors were used to identify compounds from the NCI database with similar activity profiles. Using this approach, two natural products, phyllanthoside and nagilactone C, were identified and characterized as novel protein synthesis inhibitors. Both compounds are specific for the eukaryotic translation apparatus, function in vivo and in vitro, and interfere with translation elongation. Our results demonstrate the feasibility of utilizing cytotoxicity profiles to identify new inhibitors of translation.

Bacillus thuringiensis (Bt) biopesticides, a recognized eco-friendly pest control agent, can be used to reduce many problems associated with indiscriminate use of chemical pesticides such as environmental pollutions, public health problems, emergence of resistance among pests in many developing countries etc. Bt strains were, therefore, isolated from different ecosystems of Bangladesh and characterized based on biochemical typing, 16S rRNA gene analysis, plasmid and cry genes profiles. Bt index was calculated 0.86 in this study and variations in abundance and distribution pattern of 16 different biotypes were demonstrated within 316 indigenous Bt strains which was compared to the other parts of the world. Bt indiana (17.8%), Bt kurstaki (16.7%), and Bt thuringiensis (12.7%) were found to be the most prevalent in Bangladesh among other biotypes. Hemolytic activity was variable among the biotypes and it was maximum for Bt biotype 10 (100%). Plasmids in the biotypes indiana, kurstaki, thuringiensis, and israelensis were observed to occupy a wider range than other biotypes. The screening for insecticidal genes viz. cry1, cry2, cry3, cry4A, cry8, cry9, cry10, and cry11 in the native Bt strains revealed their presence in varied proportion rendering cry1, cry2, and cry3 the most abundant. The abundance of Bt strains, their diversities and the cry genes profile were thus analyzed in this study which will be the basis for further research development with Bt biopesticide in Bangladesh.

The use of small molecule inhibitors in the study of cellular processes is a powerful approach to understanding gene function. During the course of a high throughput screen for novel inhibitors of eukaryotic translation, we identified a number of nucleic acid binding ligands that showed activity in our assay. When tested on a panel of mRNA transcripts displaying different modes of translation initiation, these ligands showed a range of biological activities -with some inhibiting both cap-dependent and internal initiation and others preferentially blocking internal initiation. We used this information to identify a novel threading intercalator that inhibits Hepatitis C virus internal initiation.

Extracts in organic solvents (namely methanol, ethanol, ethyl acetate and chloroform) of two medicinal plants -Achyranthes aspera and Cassia alata were evaluated for their antibacterial activities against Escherichia coli, Bacillus subtilis, Vibrio cholerae, Salmonella typhi and Staphylococcus aureus. These were carried out by taking the organic extracts of both the leaf and stem parts of the plants at a concentration of 5 mg/ml and their activities were recorded by estimating zones of inhibition as produced by disc-diffusion method on Mueller-Hinton agar media. While neither the leaf nor stem parts of A. aspera in any organic extractions showed antibacterial activity, the methanolic extracts of both the leaf and stem parts of C. alata exhibited antibacterial activity, but only to B. subtilis and S. typhi, and the corresponding MIC values of the leaf extracts were estimated as 1.25 and 1.5 mg/ml respectively. However, the ethanolic extracts of both the stem and leaf parts were found equally effective only to S. aureus (MIC= 1.25 mg/ml). The corresponding MBC values are reported.

Cancer treatment remains as an expensive process due to the cost of sophisticated infrastructure development as well as its maintenance with skilled personnel. At the same time, the success rate is not very inspiring since non-specific target oriented medication could cause other health complexities leading to death. Research for alternative therapies aimed at minimizing the side effects of treatments and increasing the survival rates of patients includes routine explorations for anticancer agents from numerous sources (e.g. microbes, plants and nanoparticles). Anticancer activities of several bacterial components especially from Bacillus spp. were reported in many scientific reports. For economic production of these agents, potential strains from this genus could be feasible and sustainable for their long and successful utilization in industries. The review is therefore, focused on describing the available anticancer and anti-proliferative agents reported worldwide from Bacillus spp.

Aims: Bacillus licheniformis MZK-05 is a keratinolytic bacterium having potential in dehairing of leather and feather hydrolysis. The present study aimed at to improving the production level of keratinase through gene cloning and expression of recombinant keratinase. Methodology and results: Bacillus licheniformis MZK-05 produced an amplicon of 1,156 bp in a polymerase chain reaction while targeting the gene, kerA, responsible for the enzyme keratinase. The amplicon was subsequently cloned into the plasmid vector pGEX-6p-2 for expression in Escherichia coli BL21. A 58 kD GST-KerA fusion protein was expressed upon IPTG induction which was eventually cleaved by PreScission protease that produced a 39 kD protein.A corresponding increase in proteolytic (312 U/mL) and keratinolytic (196 U/mL) activity were observed with the expressed keratinase. Specific enzyme activities for protease and keratinase, an indication of efficiency of the enzyme, were 2621.84 U/mg and 1647 U/mg, respectively and the specific keratinase activity was the highest activity ever reported by any recombinant bacterial strain. Conclusion, significance and impact study: Since the production of keratinase by wild type strain is limited to a certain level, the industrial need could be met by improving the production level through gene cloning and expression of recombinant keratinase. In this connection, the cloning of kerA gene from B. licheniformis MZK-05 into pGEX-6p-2 vector, its expression in Escherichia coli BL21 host and prediction of 3-D model of the expressed protein were performed which will be the basis for industrial production of keratinase in Bangladesh.

Bactrocera cucurbitae melon fruit fly is one of the most detrimental vegetable-damaging pests in Bangladesh. The toxicity of Bacillus thuringiensis Bt has been reported against a few genera of Bactrocera in addition to numerous other insect species. Bt strains, harbouring cry1A-type genes were, therefore, assayed in vivo against the 3 rd instar larvae of B. cucurbitae in this study. The biotype-based prevalence of cry1 and cry1A genes was calculated to be 30.8% and 11.16%, respectively, of the test strains n=224 while their prevalence was greatest in biotype kurstaki. Though three indigenous Bt strains from biotype kurstaki with close genetic relationship exhibited higher toxicity, maximum mortalities were recorded for Btk HD-73 96% and the indigenous Bt JSc1 93% . LC 50 and LC 99 values were determined to be 6.81 and 8.32 for Bt JSc1, 7.30 and 7.92 for Bt SSc2, and 6.99 and 7.67 for Btk HD-73, respectively. The cause of toxicity and its variation among the strains was found to be correlated with the synergistic toxic effects of cry1, cry2, cry3 and cry9 gene products, i.e. relevant Cry proteins. The novel toxicity of the B. thuringiensis strains against B. cucurbitae revealed in the present study thus will help in developing efficient and eco-friendly control measures such as Bt biopesticides and transgenic Bt cucurbits.