TP53 codon 72 polymorphism and type 2 diabetes: a case–control study in South Indian population

Molecular Biology Reports - TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor...     

Evaluation of DNA Methylation Changes by CRED–RA Analysis Following Prednisone Treatment of Endophyte,Fusarium oxysporum

Endophytes that represent a sub-set of plant resident microbes are a reservoir of bioactive metabolites. Many of the secondary metabolite biosynthetic gene clusters of endophytes are silent under axenic culture conditions. Epigenetic reprogramming of such cryptic pathways is possible by use of small molecule modulators like prednisone. Methylation changes induced by prednisone, a hypomethylating epigenetic modulator were studied in endophytic Fusarium oxysporum. CRED–RA analysis following exposure to non-cytotoxic dose (300 µM) revealed prednisone as effective in inducing non-methylation and semi-methylation pattern while inhibiting full-methylation of the genome. Effectiveness of prednisone as a DNA methyl transferase inhibitor can be explored in future to study alterations in secondary metabolite gene expression profile in endophytic F. oxysporum.     

Mitochondrial Dysfunction in Aging Rat Brain Regions upon Chlorpyrifos Toxicity and Cold Stress: An Interactive Study

Mitochondrial dysfunction and consequent energy depletion are the major causes of oxidative stress resulting to bring alterations in the ionic homeostasis causing loss of cellular integrity. Our previous studies have shown the age-associated interactive effects in rat central nervous system (CNS) upon co-exposure to chlorpyrifos (CPF) and cold stress leading to macromolecular oxidative damage. The present study elucidates a possible mechanism by which CPF and cold stress interaction cause(s) mitochondrial dysfunction in an age-related manner. In this study, the activity levels of Krebs cycle enzymes and electron transport chain (ETC) protein complexes were assessed in the isolated fraction of mitochondria. CPF and cold stress (15 and 20 °C) exposure either individually or in combination decreased the activity level of Krebs cycle enzymes and ETC protein complexes in discrete regions of rat CNS. The findings confirm that cold stress produces significant synergistic effect in CPF intoxicated aging rats. The synergism between CPF and cold stress at 15 °C caused a higher depletion of respiratory enzymes in comparison with CPF and cold stress alone and together at 20 °C indicating the extent of deleterious functional alterations in discrete regions of brain and spinal cord (SC) which may result in neurodegeneration and loss in neuronal metabolic control. Hence, co-exposure of CPF and cold stress is more dangerous than exposure of either alone. Among the discrete regions studied, the cerebellum and medulla oblongata appears to be the most susceptible regions when compared to cortex and SC. Furthermore, the study reveals a gradual decrease in sensitivity to CPF toxicity as the rat matures.     

Chlorpyrifos Induced Region Specific Vulnerability in Rat CNS and Modulation by Age and Cold Stress: An Interactive Study

Chlorpyrifos (CPF), an organophosphorus insecticide is known to cause ill health in non-target animals by inducing oxidative stress. In this study influence of cold stress (15°C and 20°C) and age as modulating factors on CPF induced oxidative stress was addressed to assess age-related differences and vulnerability in central nervous system of rats. The results indicated an interaction with age and cold exposure resulting in marked decreased activity levels of SOD (P < 0.05), CAT (P < 0.05), GPx (P < 0.05), GST (P < 0.05) followed by increased MDA (P < 0.05) and decreased GSH levels (P < 0.05). The ANOVA and Post-hoc analysis showed that antioxidant enzymes decreased significantly (P < 0.05) on CPF exposure. Moreover synergistic action of CPF and cold stress at 15°C caused higher inhibition on comparison with CPF and cold stress alone and together at 20°C indicating the extent of peroxidative damage in discrete regions of CNS. Further this study showed young individuals to be more sensitive than adults.     

Oxidative Macromolecular Alterations in the Rat Central Nervous System in Response to Experimentally Co-Induced Chlorpyrifos and Cold Stress: A Comparative Assessment in Aging Rats

Reactive oxygen species are generated as a result of a number of physiological and pathological processes which can promote multiple forms of oxidative damage including protein oxidation, and thereby influence the function of a diverse array of cellular processes. In our previous study we have reported that co-exposure to chlorpyrifos and cold stress in aging rats markedly influence the toxic outcome as a result of oxidative stress. In the present study, key neurochemical/enzymes were measured in order to evaluate the macromolecular alterations in response to experimentally co-induced chlorpyrifos and cold stress (15 and 20°C) either concurrently or individually in vivo for 48 h in discrete regions of brain and spinal cord of different age group rats. CPF and cold stress exposure either individually or in combination substantially increased the activity/levels of protein carbonyls, AST, ALT and decreased protein thiols, DNA, RNA and total proteins in discrete regions of CNS. Overall, the effects of co-exposure were appreciably different from either of the exposures. However, synergistic-action of CPF and cold stress at 15°C showed higher dyshomeostasis in comparison with CPF and cold stress alone and together at 20°C indicating the extent of oxidative macromolecular damage in discrete regions of brain and spinal cord. Furthermore, the present study demonstrates that macromolecular oxidative damage is highly pronounced in neonates and juveniles than the young adults.     

Cold stress interaction on organophosphate insecticide poisoning: age-related assessment in rat cerebral cortex

The present study was undertaken to identify the nature of the interactive effects of chlorpyrifos (CPF) and cold stress (15 degrees and 20 degrees C) on the activities of acetyl cholinesterase (AChE), choline acetyl transferase (ChAT), Na+, K(+)-ATPase and malondialdehyde (MDA) level in the cerebral cortex of 1 week, 3 weeks and 3 months of age. The results indicated an interaction of CPF with age of animal and cold exposure resulting in marked decrease in the activity levels of AChE, ChAT, Na+, K(+)-ATPase, followed by increased MDA levels. Overall, the effects of co-exposure of cold stress and CPF were appreciably different from either of the exposures. However, synergistic-action of CPF and cold stress at 15 degrees C showed a greater inhibition of AChE, ChAT, and Na+, K(+)-ATPase in comparison with CPF or cold stress alone and together at 20 degrees C. The results reveal that young animals are markedly more sensitive to interactive effects of CPF and cold stress than adults.     

Profiling antibiotic resistance in Escherichia coli strains displaying differential antibiotic susceptibilities using Raman spectroscopy

The rapid identification of antibiotic resistant bacteria is important for public health. In the environment, bacteria are exposed to sub-inhibitory antibiotic concentrations which has implications in the generation of multi-drug resistant strains. To better understand these issues, Raman spectroscopy was employed coupled with partial least squares-discriminant analysis to profile Escherichia coli strains treated with sub-inhibitory concentrations of antibiotics. Clear differences were observed between cells treated with bacteriostatic (tetracycline and rifampicin) and bactericidal (ampicillin, ciprofloxacin, and ceftriaxone) antibiotics for 6 hr: First, atomic force microscopy revealed that bactericidal antibiotics cause extensive cell elongation whereas short filaments are observed with bacteriostatic antibiotics. Second, Raman spectral analysis revealed that bactericidal antibiotics lower nucleic acid to protein (I₈₁₂/I₈₃₀) and nucleic acid to lipid ratios (I₁₄₈₃/I₁₄₅₂) whereas the opposite is seen with bacteriostatic antibiotics. Third, the protein to lipid ratio (I₂₉₃₆/I₂₈₈₅ and I₂₉₃₆/I₂₈₅₀) is a Raman stress signature common to both the classes. These signatures were validated using two mutants, Δlon and ΔacrB, that exhibit relatively high and low resistance towards antibiotics, respectively. In addition, these spectral markers correlated with the emergence of phenotypic antibiotic resistance. Overall, this study demonstrates the efficacy of Raman spectroscopy to identify resistance in bacteria to sub-lethal concentrations of antibiotics.