Molecular geometry,vibrations and electrode potentials of 2-(4,5-dihydroxy-2-methylphenyl)-2-phenyl-2H-indene-1,3-dione; experimental and theoretical attempts

The electrode potential of 2-(4,5-dihydroxy-2-methylphenyl)-2-phenyl-2H-indene-1,3-dione (DMPID) in acetonitrile has been calculated. The calculations were performed using ab initio molecular orbital calculations (HF), and density functional theory (DFT) with the inclusion of entropic and thermochemical corrections to yield free energies of redox reactions. The electrode potential of DMPID was also obtained experimentally with the aid of an electrochemical technique (cyclic voltammetry). The values for geometric parameters and the vibrational frequencies of DMPID and 2-(6-methyl-3,4-dioxocyclohexa-1,5-dienyl)-2-phenyl-2H-indene-1,3-dione (MDPID) were also computed using the same levels with the basis set of 6-31G(d). The calculated IR spectrum of DMPID used for the assignment of IR frequencies was observed in the experimental FT-IR spectrum and the calculated IR and FT-IR observed spectra of DMPID were compared with correlation factor of 0.996. It should be mentioned that the present work is the first research on coagulant derivative molecules in which the electrode potential of a molecule is calculated. Optimized structures of 2-(6-methyl-3,4-dioxocyclohexa-1,5-dienyl)-2-phenyl-2H-indene-1,3-dione (MDPID)     

HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway

Human heat-shock protein (HSP)70 activates innate immune cells and hence requires no additional adjuvants to render bound peptides immunogenic. Here we tested the assumption that endogenous HSP70 activates the Toll/IL-1 receptor signal pathway similar to HSP60 and pathogen-derived molecular patterns. We show that HSP70 induces interleukin-12 (IL-12) and endothelial cell-leukocyte adhesion molecule-1 (ELAM-1) promoters in macrophages and that this is controlled by MyD88 and TRAF6. Furthermore, HSP70 causes MyD88 relocalization and MyD88-deficient dendritic cells do not respond to HSP70 with proinflammatory cytokine production. Using the system of genetic complementation with Toll-like receptors (TLR) we found that TLR2 and TLR4 confer responsiveness to HSP70 in 293T fibroblasts. The expanding list of endogenous ligands able to activate the ancient Toll/IL-1 receptor signal pathway is in line with the "danger hypothesis" proposing that the innate immune system senses danger signals even if they originate from self.     

Accelerated design of bioconversion processes using automated microscale processing techniques

Microscale processing techniques are rapidly emerging as a means to increase the speed of bioprocess design and reduce material requirements. Automation of these techniques can reduce labour intensity and enable a wider range of process variables to be examined. This article examines recent research on various individual microscale unit operations including microbial fermentation, bioconversion and product recovery techniques. It also explores the potential of automated whole process sequences operated in microwell formats. The power of the whole process approach is illustrated by reference to a particular bioconversion, namely the Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-one for the production of optically pure lactones.     

Successful adoptive immunotherapy with vaccine-sensitized T cells,despite no effect with vaccination alone in a weakly immunogenic tumor model

Tumor cell vaccines have been successful at inducing immunity in naïve mice, but only in a few reports has vaccination alone induced regression of established tumors and, generally, only when they are very small. Clinically, vaccinations alone may not be able to cause regression of established human cancers, which tend to be weakly immunogenic. We hypothesized that pharmacologic ex vivo amplification of a vaccination-induced immune response with subsequent adoptive immunotherapy (AIT) to tumor-bearing animals would be more effective in treatment of these animals than vaccination alone. The 4T1 and 4T07 mammary carcinomas are derived from the same parental cell line, but 4T1 is much less immunogenic and more aggressive than 4T07. Vaccination with either 4T1, 4T1-IL-2, or 4T07-IL-2 was not effective as treatment for established 4T1 tumors. However, 4T1 or 4T07-IL-2-vaccine-sensitized draining lymph node (DLN) cells, activated ex vivo with bryostatin 1 and ionomycin and expanded in culture, induced complete tumor regressions when adoptively transferred to 4T1 tumor-bearing animals. This was effective against small tumors as well as more advanced tumors, 10 days after tumor cell inoculation. Furthermore, as would be required for this approach to be used clinically, vaccine-DLN cells obtained from mice with established progressive 4T1 tumors (inoculated 10 days before vaccination) also induced regression of 4T1 tumors in an adoptive host. In none of these experiments was exogenous IL-2 required to induce tumor regression. The response to tumor cell vaccine can be amplified by ex vivo pharmacologic activation of sensitized T cells, which can then cure an established, weakly immunogenic and highly aggressive tumor that was resistant to vaccination alone.     

Inhibition of human hemoglobin autoxidation by sodium n-dodecyl sulphate

The effect of sodium n-dodecyl sulphate (SDS) on hemoglobin autoxidation was studied in the presence of a 100 mM phosphate buffer (pH 7.0) by different methods. These included spectrophotometry, fluorescence technique, cyclic voltametry, differential scanning calorimetry, and densitometry. Spectroscopic studies showed that SDS concentrations up to 1 mM increased deoxy-, decreases oxy-, and had no significant effect on the met- conformation of hemoglobin. Therefore, a SDS concentration up to 1 mM increased the deoxy form of hemoglobin as the folded, compact state and decreases the oxy conformation. The turbidity measurements and differential scanning calorimetry techniques indicated a more stable conformation for hemoglobin in the presence of SDS up to 1 mM. Electrochemical studies also confirmed a more difficult oxidation under these conditions. The induction of the deoxy form in the presence of SDS was confirmed by densitometry techniques. The compact structure of deoxyhemoglobin blocks the formation of met-conformation in low SDS concentrations.     

Silica-encapsulated magnetic nanoparticles: enzyme immobilization and cytotoxic study

Silica-encapsulated magnetic nanoparticles (MNPs) were prepared via microemulsion method. The products were characterized by high resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectrum (EDS). MNPs with no observed cytotoxic activity against human lung carcinoma cell and brine shrimp lethality were used as suitable support for glucose oxidase (GOD) immobilization. Binding of GOD onto the support was confirmed by the FTIR spectra. The amount of immobilized GODs was 95 mg/g. Storage stability study showed that the immobilized GOD retained 98% of its initial activity after 45 days and 90% of the activity was also remained after 12 repeated uses. Considerable enhancements in thermal stabilities were observed for the immobilized GOD at elevated temperatures up to 80°C and the activity of immobilized enzyme was less sensitive to pH changes in solution.     

Anthropometric measures and risk of ovarian cancer among BRCA1 and BRCA2 mutation carriers

Studies conducted among women in the general population suggest that various anthropometric measures, including height and weight, may be associated with the risk of developing ovarian cancer. Whether such an association exists among women who carry a BRCA1 or BRCA2 mutation has not been evaluated. Thus, we investigated the association between height, weight, changes in body weight, and BMI, and the risk of developing ovarian cancer among 938 women carrying a BRCA1 or BRCA2 mutation. A matched case-control study was conducted in 469 pairs of women carrying a deleterious mutation in either BRCA1 (n = 403 pairs) or BRCA2 (n = 66 pairs). Information about height and weight at ages 18, 30, and 40 was collected from a questionnaire routinely administered to women during the course of genetic counseling. Conditional logistic regression was used to estimate the association between these body size measures and the risk of ovarian cancer. Height, weight, and BMI were not associated with the risk of ovarian cancer (P-trend ≥ 0.15). Also, there was no association between changes in body weight between ages 18-30, or ages 30-40, or ages 18-40 and the risk of ovarian cancer (P-trend ≥ 0.28). The results from this study suggest that height, weight, or weight gain do not influence the risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation.     

Impact of Bulk and Nanosized Titanium Dioxide (TiO<Subscript>2</Subscript>) on Wheat Seed Germination and Seedling Growth

The impacts of different concentrations of bulk and nanosized TiO₂ on seed germination and seedling growth of wheat were studied in a randomized completely design with four replications in the College of Agriculture, Ferdowsi University of Mashhad, Iran, in 2011. The experimental treatments included five concentrations of bulk (1, 2, 10, 100, and 500 ppm), five concentrations of nanosized TiO₂ (1, 2, 10, 100, and 500 ppm), and control (without any TiO₂). Results indicated that among the wheat germination indices, only mean germination time was affected by treatments. The lowest and the highest mean germination time (0.89 vs. 1.35 days) were obtained in 10 ppm concentration of nanosized TiO₂ and control treatments, respectively. In addition, shoot length, seedling length, and root dry matters were affected by bulk and nanosized TiO₂ concentrations, significantly. Shoot and seedling lengths at 2 and 10 ppm concentrations of nanosized TiO₂ were higher than those of the untreated control and bulk TiO₂ at 2 and 10 ppm concentrations. Employing nanosized TiO₂ in suitable concentration could promote the seed germination of wheat in comparison to bulk TiO₂ but in high concentrations had inhibitory or any effect on wheat.