Kardar-Parisi-Zhang universality in a two-component driven diffusive model

We elucidate the universal spatio-temporal scaling properties of the time-dependent correlation functions in a two-component one-dimensional (1D) driven diffusive system that consists of two coupled asymmetric exclusion process. By using a perturbative renormalization group framework, we show that the relevant scaling exponents have values same as those for the 1D Kardar-Parisi-Zhang (KPZ) equation. We thus establish that the model belongs to the 1D KPZ universality class.Comment: 13 pages, 2 figure

Evaluation of Cell Types for Assessment of Cytogenetic Damage in Arsenic Exposed Population

Background: Cytogenetic biomarkers are essential for assessing environmental exposure, and reflect adverse human health effects such as cellular damage. Arsenic is a potential clastogen and aneugen. In general, the majority of the studies on clastogenic effects of arsenic are based on frequency of micronuclei (MN) study in peripheral lymphocytes, urothelial and oral epithelial cells. To find out the most suitable cell type, here, we compared cytogenetic damage through MN assay in (a) various populations exposed to arsenic through drinking water retrieved from literature review, as also (b) arsenic-induced Bowen's patients from our own survey. Results: For literature review, we have searched the Pubmed database for English language journal articles using the following keywords: "arsenic", "micronuclei", "drinking water", and "human" in various combinations. We have selected 13 studies consistent with our inclusion criteria that measured micronuclei in either one or more of the above-mentioned three cell types, in human samples. Compared to urothelial and buccal mucosa cells, the median effect sizes measured by the difference between people with exposed and unexposed, lymphocyte based MN counts were found to be stronger. This general pattern pooled from 10 studies was consistent with our own set of three earlier studies. MN counts were also found to be stronger for lymphocytes even in arsenicinduced Bowen's patients (cases) compared to control individuals having arsenic-induced noncancerous skin lesions. Conclusion: Overall, it can be concluded that MN in lymphocytes may be superior to other epithelial cells for studying arsenic-induced cytogenetic damage

Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes

BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08–2.66] for His20His; OR = 1.66 [95% CI, 1.04–2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05–2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions. KEY WORDS: arsenic, As3MT, GSTO1, GSTO2, PNP, skin lesion, susceptibility. Environ Health Perspect 116:501–505 (2008). doi:10.1289/ehp.10581 available via http://dx.doi.org/ [Online 14 January 2008

Biophysical Studies on the Interaction of the Akaloid Chelerythrine with Nucleic Acids

DNA-deoxyribonucleic acid is the blueprint for life. It is present in organisms ranging from the smallest bacterium to the largest whale. DNA carries most of the genetic instructions used in the development, functioning and reproduction of well known living organisms. James Dewey Watson and Francis Harry Compton Crick had revolutionized the field of molecular biology and medicine by proposing the structure of deoxyribonucleic acid through model building studies in their celebrated paper published in the Nature magazine of April 23 (Watson and Crick, 1953). Although the Watson and Crick was known as father of DNA the preliminary research on DNA was started many decades ago on 1868 by Swiss chemist Friedrich Miescher. Miescher in 1868 detected a phosphorus-containing substance from the nuclei of pus cells obtained from discarded surgical bandages. He named it ‘nuclein’ consisting of an acidic portion which we know today as DNA. In 1878, Albrecht Kossel isolated the nonprotein component of “nuclein”, the nucleic acid, and later isolated its five primary nucleobases (Albrect, 1879). In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit (Levene, 1919). Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. Levene thought the chain was short and the bases repeated in a fixed order. In 1937, William Astbury produced the first X-ray diffraction pattern that showed that DNA had a regular structure (Astbury and Florence, 1938). In 1944 Oswald Avery and his coworkers discovered that DNA carries a cell’s genetic material and can be altered through transformation

Biophysical studies on the interaction of the alkaloid chelerythrine with nucleic acids

DNA-deoxyribonucleic acid is the blueprint for life. It is present in organisms ranging from the smallest bacterium to the largest whale. DNA carries most of the genetic instructions used in the development, functioning and reproduction of well known living organisms. James Dewey Watson and Francis Harry Compton Crick had revolutionized the field of molecular biology and medicine by proposing the structure of deoxyribonucleic acid through model building studies in their celebrated paper published in the Nature magazine of April 23 (Watson and Crick, 1953). Although the Watson and Crick was known as father of DNA the preliminary research on DNA was started many decades ago on 1868 by Swiss chemist Friedrich Miescher. Miescher in 1868 detected a phosphorus-containing substance from the nuclei of pus cells obtained from discarded surgical bandages. He named it ‘nuclein’ consisting of an acidic portion which we know today as DNA. In 1878, Albrecht Kossel isolated the nonprotein component of “nuclein”, the nucleic acid, and later isolated its five primary nucleobases (Albrect, 1879). In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit (Levene, 1919). Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. Levene thought the chain was short and the bases repeated in a fixed order. In 1937, William Astbury produced the first X-ray diffraction pattern that showed that DNA had a regular structure (Astbury and Florence, 1938). In 1944 Oswald Avery and his coworkers discovered that DNA carries a cell’s genetic material and can be altered through transformatio

Elucidation of the DNA binding specificity of the natural plant alkaloid chelerythrine: A biophysical approach

Interaction of the anticancer plant alkaloid chelerythrine with four sequence specific synthetic polynucleotides was studied by spectroscopy and calorimetry experiments. The binding resulted in strong hypochromic and bathochromic effects in the absorption spectrum of the alkaloid, enhancement in the fluorescence with the AT polynucleotides and the homo-GC polynucleotide and quenching with the hetero- GC polynucleotide. Cooperative binding was observed with all the polynucleotides. Fluorescence polarization anisotropy, iodide quenching and viscosity results confirmed intercalative binding of the alkaloid. The binding resulted in the thermal stabilization of the polynucleotides and moderate perturbations in the B-conformation of the DNA. The high binding affinity values (�106 M�1) evaluated from the spectroscopic data was in excellent agreement with those obtained from calorimetry. The binding was exothermic and favoured by negative standard molar enthalpy and positive standard molar entropic contributions in all cases other than homo-AT polynucleotide, where it was endothermic and entropy driven. Salt-dependent calorimetry data revealed that the binding reaction was driven mostly by non-polyelectrolytic forces. The magnitude of the negative heat capacity values confirmed the role of significant hydrophobic effects in the interaction profile of the alkaloid with the polynucleotides. The results revealed the specificity of chelerythrine to follow homo-GC > hetero-GC > hetero-AT = homo-AT polynucleotid

Structural and thermodynamic basis of interaction of the putative anticancer agent chelerythrine with single, double and triple-stranded RNAs

comparative study on the interaction of the natural plant alkaloid chelerythrine with triple helical poly(U)$poly(A)*poly(U), double helical poly(A)$poly(U) and single stranded poly(U) (the dot and star representing the Watson-Crick and Hoogsteen base pairing) has been performed using various biophysical and thermodynamic techniques. Chelerythrine binds to the duplex and triplexes in a cooperative manner with affinity of the order of 106 M�1. A weaker binding (�105 M�1) in a non-cooperative mode occurred with poly(U). Chelerythrine is more selective towards RNA triplex than its parent duplex. The triplex was stabilized specifically without affecting the stability of the duplex. Fluorescence quenching, fluorescence polarization and energy transfer from the nucleotides to the alkaloid, and viscosity results gave convincing evidence for a true intercalative binding of chelerythrine to the triplex and the duplex structures, and partial base stacking with poly(U). The conformations of both double and triple helices were perturbed on binding but no effect occurred to the single strand structure. The binding of the alkaloid to all three RNA helices was found to be exothermic; to the triplex it was entropy driven with favorable enthalpy change, to the duplex enthalpy driven and to the single strand it was enthalpy driven.These results provide new knowledge on the mode, mechanism and specificity, and energetics of binding of the natural alkaloid and putative anticancer agent chelerythrine to different RNA conformation

Entropy driven binding of the alkaloid chelerythrine to polyadenylic acid leads to spontaneous self-assembled structure formation

The binding thermodynamics and interaction of the putative anticancer alkaloid chelerythrine with polyadenylic acid were investigated by isothermal titration calorimetry, absorption and fluorescence spectroscopy, circular dichroism, differential scanning calorimetry and thermal melting experiments. The equilibrium binding constant was evaluated to be of the order of 107 M�1. Strong positive entropic and favorable enthalpic contributions to the binding were revealed. The binding affinity was enhanced within (10 to 100) mM Na+ concentration. Circular dichroism spectra confirmed that the increase in entropy change was caused by a strong conformational change in the RNA polynucleotide. Absorption and circular dichroism melting studies revealed that chelerythrine binding induced self-assembled duplex structure formation in poly(A) molecules resulting in a cooperative melting profile. This was further confirmed from differential scanning calorimetry data. The intercalation binding of the alkaloid involved strong energy transfer from the polynucleotide bases to the bound alkaloid molecules. The remarkably high entropy driven binding of the alkaloid induced spontaneous self-assembled structure formation in poly(A) and the associated binding affinity is the highest so far reported for a small molecule binding to poly(A)