An in silico structural insights into Plasmodium LytB protein and its inhibition

In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new anti-malarial compounds or inhibitors. Here a systematic in silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three-dimensional (3D) structure of Plasmodium LytB taking Escherichia coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand data-set containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG: -20.9734 kcal/mol). Among them, five were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any “drug like” molecule and the knowledge of Plasmodium LytB-inhibitory mechanism which can provide valuable support for the anti-malarial-inhibitor design in future.     

Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders

Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down''s syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down''s syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction network were constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only – CBL, EGFR genes were commonly present, which makes the allelic variants of these genes – good candidates for future studies regarding the familial link between DS and NTDs.

Abbreviations

NTD - Neural Tube Disorders, DS - Down''s Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR– 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.     

Bioemulsifier production by Streptomyces sp. S22 isolated from garden soil

Out of 45 actinomycetes isolated from garden soil, pond water and air; fifteen showed good emulsification activity. Streptomyces sp. S22 isolated from garden soil produced maximum bioemulsifier with 0.5% (v/v) sunflower oil during stationary phase at 37 degrees C, pH 6 and 250 rev/min. Emulsification activity was maximum (320 EU/ml) with sunflower oil as substrate. Partially purified bioemulsifier from Streptomyces sp. S22 was a peptidoglycolipid containing lipid (51.25%), protein (30%), non-reducing sugar (17.75%) and reducing sugar (1%). The yield of partially purified bioemulsifier was 1.6 g/l and reduced the surface tension of water by 23.09 mN/m. The bioemulsifier produced by Streptomyces sp. S22 was stable at room temperature for seven days.     

Targeting Glycinebetaine for Abiotic Stress Tolerance in Crop Plants: Physiological Mechanism,Molecular Interaction and Signaling

In the era of climate change, abiotic stresses (e.g., salinity, drought, extreme temperature, flooding, metal/metalloid(s), UV radiation, ozone, etc.) are considered as one of the most complex environmental constraints that restricts crop production worldwide. Introduction of stress-tolerant crop cultivars is the most auspicious way of surviving this constraint, and to produce these types of tolerant crops. Several bioengineering mechanisms involved in stress signaling are being adopted in this regard. One example of this kind of manipulation is the osmotic adjustment. The quarternary ammonium compound glycinebetaine (GB), also originally referred to as betaine is a methylated glycine derivative. Among the betaines, GB is the most abundant one in plants, which is mostly produced in response to dehydration caused by different abiotic stresses like drought, salinity, and extreme temperature. Glycinebetaine helps in decreased accumulation and detoxification of ROS, thereby restoring photosynthesis and reducing oxidative stress. It takes part in stabilizing membranes and macromolecules. It is also involved in the stabilization and protection of photosynthetic components, such as ribulose-1, 5-bisphosphate carboxylase/oxygenase, photosystem II and quarternary enzyme and protein complex structures under environmental stresses. Glycinebetaine was found to perform in chaperone-induced protein disaggregation. In addition, GB can confer stress tolerance in very low concentrations, and it acts in activating defense responsive genes with stress protection. Recently, field application of GB has also shown protective effects against environmental adversities increasing crop yield and quality. In this review, we will focus on the role of GB in conferring abiotic stress tolerance and the possible ways to engineer GB biosynthesis in plants.     

Privacy preserving sub-feature selection based on fuzzy probabilities

The feature selection addresses the issue of developing accurate models for classification in data mining. The aggregated data collection from distributed environment for feature selection makes the problem of accessing the relevant inputs of individual data records. Preserving the privacy of individual data is often critical issue in distributed data mining. In this paper, it proposes the privacy preservation of individual data for both feature and sub-feature selection based on data mining techniques and fuzzy probabilities. For privacy purpose, each party maintains their privacy as the instruction of data miner with the help of fuzzy probabilities as alias values. The techniques have developed for own database of data miner in distributed network with fuzzy system and also evaluation of sub-feature value included for the processing of data mining task. The feature selection has been explained by existing data mining techniques i.e., gain ratio using fuzzy optimization. The estimation of gain ratio based on the relevant inputs for the feature selection has been evaluated within the expected upper and lower bound of fuzzy data set. It mainly focuses on sub-feature selection with privacy algorithm using fuzzy random variables among different parties in distributed environment. The sub-feature selection is uniquely identified for better class prediction. The algorithm provides the idea of selecting sub-feature using fuzzy probabilities with fuzzy frequency data from data miner’s database. The experimental result shows performance of our findings based on real world data set.     

In vitro anticancer properties of selected <Emphasis Type="Italic">Eucalyptus</Emphasis> species

In spite of the recent advancements in oncology, the overall survival rate for pancreatic cancer has not improved over the last five decades. Eucalypts have been linked with cytotoxic and anticancer properties in various studies; however, there is very little scientific evidence that supports the direct role of eucalypts in the treatment of pancreatic cancer. This study assessed the anticancer properties of aqueous and ethanolic extracts of four Eucalyptus species using an MTT assay. The most promising extracts were further evaluated using a CCK-8 assay. Apoptotic studies were performed using a caspase 3/7 assay in MIA PaCa-2 cells. The aqueous extract of Eucalyptus microcorys leaf and the ethanolic extract of Eucalyptus microcorys fruit inhibited the growth of glioblastoma, neuroblastoma, lung and pancreatic cancer cells by more than 80% at 100 μg/mL. The E. microcorys and Eucalyptus saligna extracts showed lower GI₅₀ values than the ethanolic Eucalyptus robusta extract in MIA PaCa-2 cells. Aqueous E. microcorys leaf and fruit extracts at 100 μg/mL exerted significantly higher cell growth inhibition in MIA PaCa-2 cells than other extracts (p < 0.05). Statistically similar IC₅₀ values (p > 0.05) were observed in aqueous E. microcorys leaf (86.05 ± 4.75 μg/mL) and fruit (64.66 ± 15.97 μg/mL) and ethanolic E. microcorys leaf (79.30 ± 29.45 μg/mL) extracts in MIA PaCa-2 cells using the CCK-8 assay. Caspase 3/7-mediated apoptosis and morphological changes of cells were also witnessed in MIA PaCa-2 cells after 24 h of treatment with the extracts. This study highlighted the significance of E. microcorys as an important source of phytochemicals with efficacy against pancreatic cancer cells. Further studies are warranted to purify and structurally identify individual compounds and elucidate their mechanisms of action for the development of more potent and specific chemotherapeutic agents for pancreatic cancer.     

Lipid peroxidation in cataract of the human

Lipid peroxidation was investigated as one of the possible mechanisms of cataractogenesis in the human. Malondialdehyde (MDA), a major breakdown product of lipid peroxides, was significantly higher in cataractous lenses as compared to that in normal lenses. 2-Thiobarbituric acid-reactive material, isolated from cortical cataracts and purified by Sephadex G-10 column chromatography, was identified as MDA. In cataractous lenses the enzymic defenses against reactive species of O2 were impaired as evidenced by the significant decrease in activities of superoxide dismutase, catalase and glutathione peroxidase. Hydrogen peroxide in aqueous humor and vitreous humor of human eyes associated with cataract was increased 2-3 fold. It is possible that carbonyl groups of MDA could interact with primary amino groups of proteins and phospholipids of lenticular plasmalemmae by a cross-linking reaction forming Schiff-base conjugates and these mechanisms might be involved in the pathogenesis of cataract.     

Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium.

The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.     

The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine

Low concentrations (?20 μg/ml) of 8-azaguanine are 1000 fold more toxic to V79 Chinese hamster cells in medium containing 10% dialyzed fetal calf serum than in medium containing 10% undialyzed serum. Serum enzyme activity that converts AG to nontoxic 8-azaxanthine degrades AG at the same rate, whether or not the serum is dialyzed. However, cytotoxicity results similar to those obtained with US were produced in medium containing DS and 2.5 μg of hypoxanthine (HX)/ml (DSH). Therefore, serum HX is considered to be responsible for the relatively low cytotoxicity of AG in medium containing US. Colonies that arose in medium containing AG were isolated and characterized. Those that remained resistant to AG (40 μg/ml) and sensitive to aminopterin in the presence of HX and thymidine (HAT) were considered mutants; nonmutants were sensitive to AG and resistant to HAT. Colonies isolated from medium containing DSH of US and low concentrations of AG were not mutants, but those from medium containing high concentrations (? μg/l) of AG were mutants. Spontaneous and N-methyl-N′-nitrosoguanidine induced mutants were detectable in medium containing DSH without replating the cells prior to adding AG (?30 μg/ml), but in order to detect MNNG induced mutations in medium containing DS replating was essential. In DS, the mutation frequency increased as an exponential function of the toxicity of MNNG, but remained two orders of magnitude lower than the induced mutation frequencies that occurred in DSH, HX, in DSH or US, produced profound effects, other than interference with AG toxicity, that distort the results of mutagenesis assays. To study mutation using AG resistance as the endpoint, it is essential to use dialyzed serum.     

Catalase Activity in Rice Shoot Apex during Panicle Initiation

There was a gradual increase in the catalase activity in theshoot apices of the two rice varieties—Ratna and BAM 11,till panicle initiation. Peroxide content in the Ratna shootapices decreased with time and was low during and after panicleinitiation. In Ratna plants, exogenous application of cycloheximideand 3-amino-1,2,4-triazole resulted in a delay in panicle initiationwith a corresponding decrease in catalase activity. Exogenousapplication of hydrogen peroxide caused a rise in catalase activityand delayed panicle initiation in both Ratna and BAM 11 varieties.In BAM 11 plants treated with 28 consecutive short photoinductivecycles there was an earliness in flowering accompanied by anearly peak in catalase activity. (Received May 10, 1985; Accepted August 12, 1985)