Computer Aided Drug Design and Studies of Antiviral Drug against H3N2 Influenza Virus

The worldwide prevalence of H3N2 influenza virus and its increasing resistance to the existing drugs necessitates for the development of an improved/better targeting anti-influenza drug. H3N2 influenza neuraminidase is one of the two membrane-bound proteins belonging to group-2 neuraminidases. It acts as key player involved in viral pathogenicity and hence, is an important target of anti-influenza drugs. Oseltamivir is one of the potent drugs targeting this neuraminidase. In the present work, we have taken subtype N2 neuraminidase as the receptor and probable analogs of oseltamivir as drug molecules to study the protein-drug interaction in anticipation of finding efficient modified candidate compound. Oseltamivir analogs were made by modifying the functional groups using Marvin Sketch software and were docked using Schrodinger-s Glide. Oseltamivir analog 10 was detected to have significant energy value (16% less compared to Oseltamivir) and could be the probable lead molecule. It infers that some of the modified compounds can interact in a novel manner with increased hydrogen bonding at the active site of neuraminidase and it might be better than the original drug. Further work can be carried out such as enzymatic inhibition studies; synthesis and crystallizing the drug-target complex to analyze the interactions biologically.

Proteomic Analysis of Tumor Tissue after Treatment with Ascorbic Acid

Tumor cells have an invasive and metastatic phenotype that is the main cause of death for cancer patients. Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression. In this study, intraperitoneal administration of a high concentration of ascorbic acid inhibited tumor establishment and decreased tumor mass in BALB/C mice implanted with S-180 sarcoma cancer cells. To identify proteins involved in the ascorbic acid-mediated inhibition of tumor progression, changes in the tumor proteome associated with ascorbic acid treatment of BALB/C mice implanted with S-180 were investigated using two-dimensional gel electrophoresis and mass spectrometry. Twenty protein spots were identified whose expression was different between control and ascorbic acid treatment groups.

Extraction Condition of Phaseolus vulgaris

Theoptimal extraction condition of dried Phaseolus vulgaris powderwas studied. The three independent variables are raw material concentration, shaking and centrifugaltime. The dependent variables are both yield percentage of crude extract and alphaamylase enzyme inhibition activity. The experimental design was based on box-behnkendesign. Highest yield percentage of crude extract could get from extraction condition at concentration of 1, 0,1, concentration of 0.15 M ,extraction time for 2hour, and separationtime for60 min. Moreover, the crude extract with highest alpha-amylase enzyme inhibition activityoccurred by extraction condition at concentration of 0.10 M, extraction time for 2 min, and separation time for 45 min

Inhibition of the Growth of Pathogenic Candida spp. by Salicylhydroxamic Acid

Candida spp. are common and aggressive pathogens. Because of the growing resistance of Candida spp. to current antifungals, novel targets, found in Candida spp. but not in humans or other flora, have to be identified. The alternative oxidase (AOX) is one such possibility. This enzyme is insensitive to cyanide, but is sensitive to compounds such as salicylhydroxamic acid (SHAM), disulfiram and n-alkyl gallates. The growth each of six Candida spp. was inhibited significantly by ~13 mM SHAM or 2 mM cyanide, albeit to differing extents. In C. dubliniensis, C. krusei and C. tropicalis the rate of O2 uptake was inhibited by 18-36% by 25 mM SHAM, but this had little or no effect on C. glabrata, C. guilliermondii or C. parapsilosis. Although SHAM substantially inhibited the growth of Candida spp., it is unlikely that the inhibition of AOX was the cause. Salicylhydroxamic acid is used therapeutically in the treatment of urinary tract infections and urolithiasis, but it also has some potential in the treatment of Candida spp. infection.

Autobiographical Memory and Flexible Remembering: Gender Differences

In this study, we examined gender differences in: (1) a flexible remembering task, that asked for episodic memory decisions at an item-specific versus category-based level, and (2) the retrieval specificity of autobiographical memory during free recall. Differences favouring women were found on both measures. Furthermore, a significant association was observed, across gender groups, between level of specificity in the autobiographical memory interview and sensitivity to gist on the flexible remembering task. These results suggest that similar cognitive processes may partially contribute to both the ability for specific autobiographical recall and the capacity for inhibition of gist-information on the flexible remembering task.

The Effect of Hylocereus polyrhizus and Hylocereus undatus on Physicochemical, Proteolysis, and Antioxidant Activity in Yogurt

Yogurt is a coagulated milk product obtained from the lactic acid fermentation by the action of Lactobacillus bulgaricus and Streptococcus thermophilus. The additions of fruits into milk may enhance the taste and the therapeutical values of milk products. However fruits also may change the fermentation behaviour. In this present study, the changes in physicochemical, the peptide concentration, total phenolics content and the antioxidant potential of yogurt upon the addition of Hylocereus polyrhizus and Hylocereus undatus (white and red dragon fruit) were investigated. Fruits enriched yogurt (10%, 20%, 30% w/w) were prepared and the pH, TTA, syneresis measurement, peptide concentration, total phenolics content and DPPH antioxidant inhibition percentage were determined. Milk fermentation rate was enhanced in red dragon fruit yogurt for all doses (-0.3606 - -0.4126 pH/h) while only white dragon fruit yogurt with 20% and 30% (w/w) composition showed increment in fermentation rate (-0.3471 - -0.3609 pH/h) compared to plain yogurt (-0.3369pH/h). All dragon fruit enriched yogurts generally showed lower pH readings (pH 3.95 - 4.03) compared to plain yogurt (pH 4.05). Both fruit yogurts showed a higher lactic acid percentage (1.14-1.23%) compared to plain yogurt (1.08%). Significantly higher syneresis percentage (57.19 - 70.32%) compared to plain yogurt (52.93%) were seen in all fruit enriched yogurts. The antioxidant activity of plain yogurt (19.16%) was enhanced by the presence of white and red dragon fruit (24.97- 45.74%). All fruit enriched yogurt showed an increment in total phenolic content (36.44 - 64.43mg/ml) compared to plain yogurt (20.25mg/ml). However, the addition of white and red dragon fruit did not enhance the proteolysis of milk during fermentation. Therefore, it could be concluded that the addition of white and red dragon fruit into yogurt enhanced the milk fermentation rate, lactic acid content, syneresis percentage, antioxidant activity, and total phenolics content in yogurt.

Antifungal Activity of Silver Colloidal Nanoparticles against Phytopathogenic Fungus (Phomopsis sp.) in Soybean Seeds

Among the many promising nanomaterials with antifungal properties, metal nanoparticles (silver nanoparticles) stand out due to their high chemical activity. Therefore, the aim of this study was to evaluate the effect of silver nanoparticles (AgNPs) against Phomopsis sp. AgNPs were synthesized by silver nitrate reduction with sodium citrate and stabilized with ammonia. The synthesized AgNPs have further been characterized by UV/Visible spectroscopy, Biophysical techniques like Dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM). The average diameter of the prepared silver colloidal nanoparticles was about 52 nm. Absolute inhibitions (100%) were observed on treated with a 270 and 540 µg ml-1 concentration of AgNPs. The results from the study of the AgNPs antifungal effect are significant and suggest that the synthesized silver nanoparticles may have an advantage compared with conventional fungicides.

Hypoglycemic Activity of Water Soluble Polysaccharides of Yam (Dioscorea hispida Dents) Prepared by Aqueous, Papain, and Tempeh Inoculum Assisted Extractions

This research studied the hypoglycemic effect of water soluble polysaccharide (WSP) extracted from yam (Dioscorea hispida) tuber by three different methods: aqueous extraction, papain assisted extraction, and tempeh inoculums assisted extraction. The two later extraction methods were aimed to remove WSP binding protein to have more pure WSP. The hypoglycemic activities were evaluated by means in vivo test on alloxan induced hyperglycemic rats, glucose response test (GRT), in situ glucose absorption test using everted sac, and short chain fatty acids (SCFAs) analysis. All yam WSP extracts exhibited ability to decrease blood glucose level in hyperglycemia condition as well as inhibited glucose absorption and SCFA formation. The order of hypoglycemic activity was tempeh inoculums assisted- >papain assisted- >aqueous WSP extracts. GRT and in situ glucose absorption test showed that order of inhibition was papain assisted- >tempeh inoculums assisted- >aqueous WSP extracts. Digesta of caecum of yam WSP extracts oral fed rats had more SCFA than control. Tempeh inoculums assisted WSP extract exhibited the most significant hypoglycemic activity.

The Effect of Sodium Chloride and pH on the Antimicrobial Effectiveness of Essential Oils Against Pathogenic and Food Spoilage Bacteria:Implications in Food Safety

The purpose of this study was to elucidate the factors affecting antimicrobial effectiveness of essential oils against food spoilage and pathogenic bacteria. The minimum inhibition concentrations (MIC) of the essential oils, were determined by turbidimetric technique using Biocreen C, analyzer. The effects of pH ranging from 7.3 to 5.5 in absence and presence of essential oils and/or NaCl on the lag time and mean generation time of the bacteria at 370C, were carried out and results were determined showed that, combination of low pH and essential oil at 370C had additive effects against the test micro-organisms. The combination of 1.2 % (w/v) of NaCl and clove essential oil at 0.0325% (v/v) was effective against E. coli. The use of concentrations less than MIC in combination with low pH and or NaCl has the potential of being used as an alternative to “traditional food preservatives".

Inhibition Effect of Brazilin to Human Bladder Cancer Cell Line T24

The inhibition effect of brazilin to human bladder tumor cell line T24 in vitro and in vivo was studied. The results of the in vitro experiments showed that brazilin has strong inhibition activity on the target cells. The inhibition ratio of 100 μg/mL brazilin and 100 μg/mL mitomycin to the target cells was 90.90 % and 63.24 % respectively, which showed that brazilin has higher inhibition activity than mitomycin under the same concentration. Brazilin could induce cell apoptosis in T24 cells. Significant antitumor activity of brazilin was also showed in the animals experiments. The life extention rate of 200 mg/mL, 300 mg/kg, and 400 mg/kg brazilin intraperitoneally injected into Balb/c-nu-nu nude mice that with human bladder cancer were 51.50 %, 56.90 %, and 58.42 %(P

The Influence of Some Polyphenols on Human Erythrocytes Glutathione S-Transferase Activity

Glutathione S-transferase was purified from human erythrocytes and effects of some polyphenols were investigated on the enzyme activity. The purification procedure was performed on Glutathione-Agarose affinity chromatography after preparation of erythrocytes hemolysate with a yield of 81%. The purified enzyme showed a single band on the SDS-PAGE. The effects of some poliphenolic compounds such as catechin, dopa, dopamine, progallol and catechol were examined on the in vitro GST activity. Catechin was determined to be inhibitor for the enzyme, but others were not effective on the enzyme as inhibitors or activators. IC50 value -the concentration of inhibitor which reduces enzyme activity by 50%- was estimated to be 10 mM. Ki constants were also calculated as 6.38 ± 0,70 mM with GSH substrate, and 3.86 ± 0,78 mM with CDNB substrate using the equations of graphs for the inhibitor, and its inhibition type was determined as non-competitive.

Toxicity Study of Two Different Synthesized Silver Nanoparticles on Bacteria Vibrio Fischeri

A comparative evaluation of acute toxicity of synthesized nano silvers using two different procedures (biological and chemical reduction methods) and silver ions on bacteria Vibrio fischeri was investigated. The bacterial light inhibition test as a toxicological endpoint was used by applying of a homemade luminometer. To compare the toxicity effects as a quantitative parameter, a nominal effective concentrations (EC) of chemicals and a susceptibility constant (Z-value) of bacteria, after 5 min and 30 min exposure times, were calculated. After 5 and 30 min contact times, the EC50 values of two silver nanoparticles and the EC20 values were about similar. It demonstrates that toxicity of silvers was independent of their procedure. The EC values of nanoparticles were larger than those of the silver ions. The susceptibilities(Z- Values) of V.fischeri (L/mg) to the silver ions were greater than those of the nano silvers. According to the EC and Z values, the toxicity of silvers decreased in the following order: Silver ions >> silver nanoparticles from chemical reduction method ~ silver nanoparticles from biological method.

Effect of Anionic and Non-ionic Surfactants on Activated Sludge Oxygen Uptake Rate and Nitrification

A local wastewater treatment plant (WWTP) experiencing poor nitrification tracked down high level of surfactants in the plant-s influent and effluent. The aims of this project were to assess the potential inhibitory effect of surfactants on activated sludge processes. The effect of the presence of TergitolNP-9, TrigetolNP-7, Trigetol15-S-9, dodecylbenzene sulphonate (SDBS) and sodium dodecyl sulfate (SDS) on activated sludge oxygen uptake rate (OUR) and nitrification were assessed. The average concentration of non-ionic and anionic surfactants in the influent to the local WWTP were 7 and 8.7 mg/L, respectively. Removal of 67% to 90% of the non-ionic and 93-99% of the anionic surfactants tested were measured. All surfactants tested showed inhibitory effects both on OUR and nitrification. SDS incurred the lowest inhibition whereas SDBS and NP-9 caused severe inhibition to OUR and Nitrification. Activated sludge flocs sizes slightly decreased after 3 hours contact with the surfactant present in the test. The results obtained indicated that high concentrations of surfactants are likely to have an adverse effect on the performance of WWTPs utilizing activated sludge processes.

SDS-induced Serine Protease Activity of an Antiviral Red Fluorescent Protein

A rare phenomenon of SDS-induced activation of a latent protease activity associated with the purified silkworm excretory red fluorescent protein (SE-RFP) was noticed. SE-RFP aliquots incubated with SDS for different time intervals indicated that the protein undergoes an obligatory breakdown into a number of subunits which exhibit autoproteolytic (acting upon themselves) and/or heteroproteolytic (acting on other proteins) activities. A strong serine protease activity of SE-RFP subunits on Bombyx mori nucleopolyhedrovirus (BmNPV) polyhedral protein was detected by zymography technique. A complete inhibition of BmNPV infection to silkworms was observed by the oral administration assay of the SE-RFP. Here, it is proposed that the SE-RFP prevents the initial infection of BmNPV to silkworms by obliterating the polyhedral protein. This is the first report on a silkworm red fluorescent protein that exhibits a protease activity on exposure to SDS. The present studies would help in understanding the antiviral mechanism of silkworm red fluorescent proteins.

Cohabiting in Multiethnic Community: Forms, Representations and Images of the Diversity

Modern culture, based on disinhibition of cultural trends and on heterodirection, is promoting openmindedness attitudes towards ethnic diversity, but on the other hand also new forms of social representations of the foreigner. Social representation is situated between the psychic field and the social one; it is the representation of oneself and of the other one, hanging between social categories and individual inner world. We will produce the results of a research on the representation of the foreigner, built on the type of prejudice prevailing among middle-low or middle-high educational qualification subjects, in which prejudicial attitudes seem to descend from precise mental images of the foreigner.

Antibacterial Activity of Lactic Acid Bacteria Isolated from Table Olives against Skin Pathogens

The aim of this study was to assess the effect of LAB isolated from Iranian native olives on the opportunistic skin pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Lactic Acid Bacteria were isolated from the brine of each sample in the prior of time. The samples were spread on MRS agar for isolation of lactobacillus and for lactococcus. 28 strains of labs were isolated. The labs were centrifuged, the supernatant was strewed and pellet was used to inoculation in wells or at blank disks. 20μl of each pellet was inoculated to blank disks and 40μl of each pellet was inoculated to each well. The result of disk and well diffusion agar against these pathogens were confirmed each other. The size of inhibition zone was different according to the type of bacteria, the method and the concentrations of labs.

Antimicrobial Activity and Phytochemicals Screening of Jojoba (Simmondsia chinensis) Root Extracts and Latex

Plants are rich sources of bioactive compounds. In this study the photochemical screening of hexane, ethanolic and aqueous extracts of roots and latex of jojoba (Simmondsia chinensis) plant revealed the presence of saponins, tannins, alkaloids, steroids and glycosides. Ethanolic extract was found to be richer in these metabolites than hexane, aqueous extracts and latex. The extracts and latex displayed effective antimicrobial activity against Salmonella typhimurium, Bacillus cereus, Clostridium perfringens, Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus flavus. The increase in volume of the extracts and latex caused more activity, as shown by zones of inhibition. Candida albicans growth was inhibited only by hexane extract. Jojoba latex was not effective against Candida albicans at 0.1 and 0.5 ml extracts concentration but showed 5mm zone of inhibition at (1.0 ml). Lower volume (0.1ml) of latex encouraged Aspergillus flavus growth, while at (1.00 ml) reduced its mycelial growth. Thus, jojoba root extracts and latex can be of potential natural antimicrobial agents.

Mathematical modeling of Bi-Substrate Enzymatic Reactions with Ping-Pong Mechanism in the Presence of Competitive Inhibitors

The mathematical modeling of different biological processes is usually used to predict or assess behavior of systems in which these processes take place. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions with ping-pong mechanism, which play an important role in different biochemical pathways. Besides that, three models of competitive inhibition were designed using different software packages. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions with ordered pingpong mechanism in the presence of competitive inhibitors, as well as to describe in details the inhibition effects. The simulation of the models with certain kinetic parameters allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of competitive inhibition. Simultaneous presence of two inhibitors, competitive to the S1 and S2 substrates have been studied. Moreover, we have found the pattern of simultaneous influence of both inhibitors.

Computational Model for Predicting Effective siRNA Sequences Using Whole Stacking Energy (% G) for Gene Silencing

The small interfering RNA (siRNA) alters the regulatory role of mRNA during gene expression by translational inhibition. Recent studies show that upregulation of mRNA because serious diseases like cancer. So designing effective siRNA with good knockdown effects plays an important role in gene silencing. Various siRNA design tools had been developed earlier. In this work, we are trying to analyze the existing good scoring second generation siRNA predicting tools and to optimize the efficiency of siRNA prediction by designing a computational model using Artificial Neural Network and whole stacking energy (%G), which may help in gene silencing and drug design in cancer therapy. Our model is trained and tested against a large data set of siRNA sequences. Validation of our results is done by finding correlation coefficient of experimental versus observed inhibition efficacy of siRNA. We achieved a correlation coefficient of 0.727 in our previous computational model and we could improve the correlation coefficient up to 0.753 when the threshold of whole tacking energy is greater than or equal to -32.5 kcal/mol.

Antimicrobial, Antiplasmid and Cytotoxicity Potentials of Marine Algae Halimeda opuntia and Sarconema filiforme Collected from Red Sea Coast

The antimicrobial, antiplasmid and cytotoxic activities of marine algae Halimeda opuntia and Sarconema filiforme were investigated. Antimicrobial bioassay against some human pathogenic bacteria and yeast were conducted using disc diffusion method. Halimeda extract exhibited antibacterial activity against six species of microrganisms, with significant inhibition against Staphylococcus aureus. While Sarconema extract was better potent as antifungal against Candida albicans. Comparative antibacterial studies showed that Halimeda extract showed equivalent or better activity as compared with commercial antibiotic when tested against Staphylococcus aureus. Further tests conducted using dilution method showed both extracts as having bacteriostatic mode of action against the tested microorganisms. Methanol extract of two species showed significant cytotoxicity (LC50