Mutagens in commercial food processing and its microbial transformation.

Mutagens are chemical molecules that have the ability to damage DNA. Mutagens can enter into our body upon consumption of improperly cooked or processed food products such as high temperature or prolonged cooking duration. Mutagens are found in the food products can be classified into N-nitroso derivatives, polycyclic aromatic hydrocarbons, and heterocyclic aromatic amines. Food products with high fat and protein content are more prone to mutagenic formation. Microorganisms were found to be a potent weapon in the fight against various mutagens through biotransformation. Therefore, searching for the microorganisms which have the ability to transform mutagens and the development of techniques for the identification as well as detection of mutagens in food products is much needed. In the future, methods for the identification and detection of these mutagens as well as the identification of new and more potent microorganisms which can transform mutagens into non-mutagens are much needed.

Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis.

Depletion of glutathione (GSH) is considered a critical pathogenic event promoting alcohol-induced lipotoxicity. We recently show that systemic GSH deficiency in mice harboring a global disruption of the glutamate-cysteine ligase modifier subunit (Gclm) gene confers protection against alcohol-induced steatosis. While several molecular pathways have been linked to the observed hepatic protection, including nuclear factor erythroid 2-related factor 2 and AMP-activated protein kinase pathways, the precise mechanisms are yet to be defined. In this study, to gain insights into the molecular mechanisms underpinning the protective effects of loss of GCLM, global profiling of hepatic polar metabolites combined with liver microarray analysis was carried out. These inter-omics analyses revealed both low GSH- and alcohol-driven changes in multiple cellular pathways involving the metabolism of amino acids, fatty acid, glucose and nucleic acids. Notably, several metabolic changes were uniquely present in alcohol-treated Gclm-null mouse livers, including acetyl-CoA enrichment and diversion of acetyl-CoA flux from lipogenesis to alterative metabolic pathways, elevation in glutamate concentration, and induction of the glucuronate pathway and nucleotide biosynthesis. These metabolic features reflect low GSH-elicited cellular response to chronic alcohol exposure, which is beneficial for the maintenance of hepatic redox and metabolic homeostasis. The current study indicates that fine-tuning of hepatic GSH pool may evoke metabolic reprogramming to cope with alcohol-induced cellular stress.

Mass Spectrometry-Based Profiling of Metabolites in Human Biofluids.

Cancer poses a daunting challenge to researchers and clinicians alike. Early diagnosis, accurate prognosis, and prediction of therapeutic response remain elusive in most types of cancer. In addition, lacunae in our understanding of cancer biology continue to hinder advancement of therapeutic strategies. Metabolic reprogramming has been identified as integral to pathogenesis and progression of the disease. Consequently, analysis of biofluid metabolome has emerged as a promising approach to further our understanding of disease biology as well as to identify cancer biomarkers. However, unbiased identification of robust and meaningful differences in metabolic signatures remains a non-trivial task. This chapter describes a generalized strategy for global metabolic profiling of human biofluids using ultra-performance liquid chromatography (UPLC) and mass spectrometry, which together offer a sensitive, high-throughput, and versatile platform. A step-by-step protocol for performing untargeted metabolic profiling of urine and serum (or plasma), using hydrophilic interaction liquid chromatography (HILIC) or reverse-phase (RP) chromatography coupled with electrospray ionization mass spectrometry (ESI-MS) to multivariate data analysis and identification of metabolites of interest has been detailed.

Investigating the development of spurious magnetism in single crystalline BaTi0.95Fe0.05O3-δ with high δ by local structural probes.

BaTi0.95Fe0.05O3-δ has been suggested to be an intrinsic dilute magnetic oxide with a clear dependence of magnetism on oxygen vacancy concentration. However, it has also been shown that the dopant Fe ions distribute themselves rather inhomogeneously within the lattice, though without disrupting the crystal phase of the parent BaTiO3. With the help of x-ray absorption spectroscopy (XAS), here we find that the incorporation of a larger amount of anion vacancy pushes this inhomogeneity to the extreme, leading to the precipitation of Fe metal clusters. It is also observed that the residual solid, without the Fe-metal cluster, undergoes massive structural and compositional reorganization.

Microscopic distribution of metal dopants and anion vacancies in Fe-doped BaTiO(3-δ) single crystals.

A detailed microscopic structural study on two single crystalline dilute magnetic oxides, BaTi0.95Fe0.05O(3-δ) with and without perceptible δ, has been carried out. Although it has been reported earlier that varying δ significantly affects high temperature ferromagnetism, the real distribution/redistribution of vacancies and dopant Fe ions inside the 6H hexagonal structure was never probed. This study reveals that oxygen vacancies reduce the dopant Fe(3+) ions to Fe(2+) and mostly accumulate around these Fe(2+) ions. Another distinct trend is the tendency of the dopant Fe ions to get closer instead of being distributed randomly, thereby creating Fe2(2+)O(9-δ') like dimers within the 6H hexagonal unit cell. This experimental observation definitively confirms previous hypotheses based on theoretical models.

Defect controlled room temperature ferromagnetism in Co-doped barium titanate nanocrystals.

Defect mediated high temperature ferromagnetism in oxide nanocrystallites is the central feature of this work. Here, we report the development of room temperature ferromagnetism in nanosized Co-doped barium titanate particles with a size of around 14 nm, synthesized by a solvothermal drying method. A combination of x-ray diffraction with state-of-the-art electron microscopy techniques confirms the intrinsic doping of Co into BaTiO3. The development of the room temperature ferromagnetism was tracked down to the different donor defects, namely hydroxyl groups at the oxygen site (OH·(O) and oxygen vacancies (V··(O), and their relative concentrations at the surface and the core of the nanocrystal, which could be controlled by post-synthesis drying and thermal treatments.

Physicochemical and conformational studies on BSA-surfactant interaction in aqueous medium.

In this paper, results of physicochemical studies on the interaction of bovine serum albumin (BSA) with alkyltrimethylammonium bromide (ATAB), pentaethylene glycol mono-n-dodecyl ether (C12E5), and sodium dodecyl sulfate (SDS) under the experimental conditions of phosphate buffer at pH 7 in the presence of 10 mM sodium bromide (NaBr), maintaining the ionic strength of the overall solution at micro = 0.015 M, have been presented and discussed. Here, BSA-ATAB corresponds to a polyion-surfactant system bearing opposite charges. BSA precipitated out of the solution on addition of ATAB solution over a certain range of ATAB concentration, the concentration range being dependent on the particular member of the ATAB family. In our earlier reports on the precipitation of oppositely charged polymer-surfactant, the tensiometric profile for surfactant addition in polymer solution differed significantly from that expected from addition of surfactant in the dispersion medium. In the present study, the precipitation process could hardly affect the smoothness of the tensiometric profile. This indicates the interaction process is operative in bulk solution. Microcalorimetric profiles also evidenced an extra hump in the interaction profile at lower surfactant concentrations, without much affecting the dilution enthalpograms beyond micellization. This interaction appeared unimodal and the extent of interaction increased with increasing tail length of ATAB, evidencing the hydrophobic effect to be an important factor. Addition of salt (NaBr) also affected the nature of interaction: at lower concentration of NaBr, the interaction was mildly assisted, whereas 50 mM NaBr fairly assisted the interaction. The nonionic surfactant C12E5 modestly interacted with BSA. The anionic amphiphile SDS, on the other hand, interacted with BSA in two distinctly different stages, as evidenced from the tensiometric profile. The complexity of the BSA-SDS tensiometric isotherm compared to that of BSA-ATAB arose from the presence of cationic binding sites adjacent to hydrophobic patches of BSA in its native state, so that electrostatic and hydrophobic interactions can cooperatively operate side by side. The interfacial saturation occurred at a lower concentration in the presence of BSA compared to the normal cmc of SDS under identical solution conditions in the absence of BSA, which was slightly delayed for nonionic C12E5. The multitechnique approach evidenced that different experimental techniques probe different physicochemical phenomena and an attempt to show the concurrence of the break points in different techniques is only diluting the essence of this area.

Mixed micelle formation among anionic gemini surfactant (212) and its monomer (SDMA) with conventional surfactants (C12E5 and C12E8) in brine solution at pH 11.

The micellization of anionic gemini surfactant, N,N'-ethylene(bis(sodium N-dodecanoyl-beta-alaninate)) (212), and its monomer, N-dodecanoyl-N-methyl alaninate (SDMA), and polyethoxylated nonionic surfactants, C(12)E(5) and C(12)E(8), has been studied tensiometrically in pure and mixed states in an aqueous solution of 0.1 M NaCl at pH 11 to determine physicochemical properties such as critical micellar concentration (cmc), surface tension at the cmc (gamma(cmc)), maximum surface excess (Gamma(max)) and minimum area per surfactant molecule at the air/water interface (A(min)). The theories of Rosen, Rubingh, Motomura, Maeda, and Nagarajan have been applied to investigate the interaction between those surfactants at the interface and in the micellar solution, the composition of the aggregates formed, the theoretical cmc in pure and mixed states, and the structural parameters as proposed by Tanford and Israelachvili. Various thermodynamic parameters (free energy of micellization and interfacial adsorption) have been calculated with the help of regular solution theory and the pseudophase model for micellization.

Physicochemical studies on pepsin-CTAB interaction: energetics and structural changes.

The interaction between pepsin and CTAB has been elaborately studied with a number of techniques. The enzyme-induced interaction produced complexes, aggregates, and micelles of CTAB with distinct physicochemical features. It was found that at very low surfactant concentration (much below the critical micellar concentration (cmc) of pure CTAB), the surfactant got adsorbed both in monomeric and lower aggregated forms to the high-energy sites of the native biopolymer, leading to enhanced hydrophobicity of the combine, and hence, lowering of the interfacial (air/solution) tension. This was followed by the formation of a faintly turbid solution of the polymer-surfactant coacervate. The CTAB interacted unfolded pepsin along with the surfactant monomer remained adsorbed at the interface to decrease the interfacial tension (gamma) to a low level to produce a break in the gamma vs log [CTAB] plot prior to the normally observed extended cmc (cmce) in presence of polymers. The cac-like aggregation (as observed in tensiometry and viscometry) was not found in conductometry and microcalorimetry, whereas microcalorimetry evidenced the formation of the cmce of CTAB in the presence of the biopolymer. The CTAB influenced structural features of the pepsin were assessed from spectral, viscometric, and circular dichroism measurements.

Sodium carboxymethylcellulose-CTAB interaction: a detailed thermodynamic study of polymer-surfactant interaction with opposite charges.

Interaction between polymer and surfactant bearing opposite charges is much more complex from a physicochemical point of view as compared to interaction between ionic surfactant and nonionic polymer. Electrostatic and hydrophobic interactions interplay in the former, whereas the hydrophobic effect is the prevailing factor in the latter. We have studied the interaction between a water-soluble polyanion, sodium salt of carboxymethylcellulose (NaCMC), with a cationic amphiphile, CTAB, in aqueous medium. There were manifold discrepancies with the reported works in NaCMC-alkyltrimethylammonium bromide, which is assumed to be an effect of difference in degree of substitution, which in turn affects the charge density of the polymer chain. We have noticed that the bulk complexation and interfacial interaction driven by electrostatic forces operate side by side. Thereafter, there is a wrapping process by the polyanion to the polymer-induced smaller surfactant aggregates driven by increase in entropy of the solution as a result of expulsion of the counterions from the ionic atmosphere around the surfactant aggregate. Because of the electrostatic interaction, hydrophobicity of the polymer-surfactant complex increases, leading to coacervation, and again solubilization in the hydrophobic core of the self-aggregated structure provided by the added excess CTAB. The tensiometric, conductometric, microcalorimetric, and turbidimetric techniques have been applied to address these problems.

Micellization and related behavior of binary and ternary surfactant mixtures in aqueous medium: cetyl pyridinium chloride (CPC), cetyl trimethyl ammonium bromide (CTAB), and polyoxyethylene (10) cetyl ether (Brij-56) derived system.

Mixed micelles formed with cetyl pyridinium chloride (CPC), cetyl trimethylammonium bromide (CTAB), and polyoxyethylene (10) cetyl ether (Brij-56) mixed in different combinations in aqueous medium have been studied in detail by tensiometric, conductometric, calorimetric, spectrophotometric, and fluorimetric techniques. Different physicochemical properties such as critical micellar concentration (cmc), micellar dissociation, energetic parameters (free energy, enthalpy, and entropy) of micellization, interfacial adsorption, and micellar aggregation number have been determined. The results have been analyzed in terms of the equations of Clint, Motomura, Rosen, Rubingh, Blankschtein et al., and Rubingh and Holland for justification of the experimental cmc, determination of micellar composition parameters, quantification of interaction among the mixed micelle components, and estimation of their activity coefficients.