TOTAL PHENOLIC CONTENT AND FREE RADICAL SCAVENGING ACTIVITY OF MIMUSOPS ELENGI L. LEAVES

Objective: The motive of the current study was to find out the total phenolic content (TPC) and free radical scavenging (FRS) activity of various solvent extracts of leaves. Methods: Leaves powder was subjected to extraction with different solvents, namely methanol, methanol 80%, ethanol, ethanol 80%, chloroform, acetone, aqueous, and ethyl acetate. Different concentrations of extracts were evaluated for FRS activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and TPC spectrophotometrically by Folin–Ciocalteu method. Results: The results clearly indicate that inhibition concentration of DPPH by leaf extracts was higher in methanol (inhibitory concentration 50=8.74) followed by ethanol >ethanol 80% >methanol 80% > acetone > aqueous > chloroform > ethyl acetate. TPC was higher in methanol (6.2±0.01 mg gallic acid equivalent/g) followed by ethanol > methanol 80% > acetone > aqueous >ethyl acetate > ethanol 80% > chloroform. A significant correlation (y=0.6265x +42.91 R2=0.9756) exists between TPC and FRS activity of methanolic extract. Conclusion: The finding revealed that methanolic extract of leaves contains a significant amount of FRS activity and phenolic compounds compared to other extracts

Oxidative stress in patients with laryngeal carcinoma

Background : Cancer is a multifactorial disease. Repetitive cumulative damage of cellular organelles by oxy-free radicals are few of the important causative factors. Aim : To assess the role of oxidative stress in the laryngeal cancer patients in Indian population. Setting and Design : Case control study. Materials and Methods : Level of malondialdehyde (MDA) as a marker of oxidative stress was examined in large cohort of control (50) and laryngeal carcinoma patients (155) from North India. Both the controls and laryngeal carcinoma patients were smokers. Results : In control healthy subjects MDA levels were 0.102±0.07 (0.080- 0.303, 95% CI) n mol/ml, as compared to 0.329±0.16 (0.124-0.354, 95% CI) n mol/ml in the cases of laryngeal carcinoma patients. Three times higher serum MDA levels indicated that there was significant oxidative stress in the subjects having laryngeal carcinoma lesions. In addition patients with secondaries were having MDA levels of 0.4±0.02 (0.391-0.408 95% CI) n mol/ml, as compared to 0.57±0.03 (0.558-0.582 95% CI)n mol/ml in group of patients without secondaries. These two values were statistically significant as compared to control values (P< 0.01). Conclusion : These findings suggest that in case of laryngeal carcinoma patients, there is increase in the level of oxidative enzyme MDA. The oxidative stress might be due to the modulation of pro-oxidant or anti-oxidant systems in laryngeal carcinoma

Oxidative stress in patients with laryngeal carcinoma

Background : Cancer is a multifactorial disease. Repetitive cumulative damage of cellular organelles by oxy-free radicals are few of the important causative factors. Aim : To assess the role of oxidative stress in the laryngeal cancer patients in Indian population. Setting and Design : Case control study. Materials and Methods : Level of malondialdehyde (MDA) as a marker of oxidative stress was examined in large cohort of control (50) and laryngeal carcinoma patients (155) from North India. Both the controls and laryngeal carcinoma patients were smokers. Results : In control healthy subjects MDA levels were 0.102\ub10.07 (0.080- 0.303, 95% CI) n mol/ml, as compared to 0.329\ub10.16 (0.124-0.354, 95% CI) n mol/ml in the cases of laryngeal carcinoma patients. Three times higher serum MDA levels indicated that there was significant oxidative stress in the subjects having laryngeal carcinoma lesions. In addition patients with secondaries were having MDA levels of 0.4\ub10.02 (0.391-0.408 95% CI) n mol/ml, as compared to 0.57\ub10.03 (0.558-0.582 95% CI)n mol/ml in group of patients without secondaries. These two values were statistically significant as compared to control values (P&lt; 0.01). Conclusion : These findings suggest that in case of laryngeal carcinoma patients, there is increase in the level of oxidative enzyme MDA. The oxidative stress might be due to the modulation of pro-oxidant or anti-oxidant systems in laryngeal carcinoma

BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells

Women who carry a germline mutation in BRCA1 gene typically develop triple negative breast cancers (TNBC) and high grade serous ovarian cancers (HGSOC). Previously, we reported that wild type BRCA1 proteins, unlike the disease-associated mutant BRCA1 proteins to bind the sole sumo E2-conjugating enzyme Ubc9. In this study, we have used clinically relevant cell lines with known BRCA1 mutations and report the in-vivo association of BRCA1 and Ubc9 in normal mammary epithelial cells but not in BRCA1 mutant HGSOC and TNBC cells by immunofluorescence analysis. BRCA1-mutant HGSOC / TNBC cells and ovarian tumor tissues showed increased expression of Ubc9 compared to BRCA1 reconstituted HGSOC, normal mammary epithelial cells and matched normal ovarian tissues. Knockdown of Ubc9 expression resulted in decreased proliferation and migration of BRCA1 mutant TNBC and HGSOC cells. This is the first study demonstrating the functional link between BRCA1 mutation, high Ubc9 expression and increased migration of HGSOC and TNBC cells. High Ubc9 expression due to BRCA1 mutation may trigger an early growth and transformation advantage to normal breast and ovarian epithelial cells resulting in aggressive cancers. Future work will focus on studying whether Ubc9 expression could show a positive correlation with BRCA1 linked HGSOC and basal like TNBC phenotype

Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation

Mutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy – tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient-derived cells carrying the most prevalent disease related mtDNA mutation, the m.3243 A &gt; G. These studies reveal that the mutation promotes changes in metabolites which are associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 reduced mtDNA mutant load and partially rescued cellular bioenergetic function. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243 A &gt; G mutation

Quantifying uncertainty in the measurement of arsenic in suspended particulate matter by Atomic Absorption Spectrometry with hydride generator

Arsenic is the toxic element, which creates several problems in human being specially when inhaled through air. So the accurate and precise measurement of arsenic in suspended particulate matter (SPM) is of prime importance as it gives information about the level of toxicity in the environment, and preventive measures could be taken in the effective areas. Quality assurance is equally important in the measurement of arsenic in SPM samples before making any decision. The quality and reliability of the data of such volatile elements depends upon the measurement of uncertainty of each step involved from sampling to analysis. The analytical results quantifying uncertainty gives a measure of the confidence level of the concerned laboratory. So the main objective of this study was to determine arsenic content in SPM samples with uncertainty budget and to find out various potential sources of uncertainty, which affects the results. Keeping these facts, we have selected seven diverse sites of Delhi (National Capital of India) for quantification of arsenic content in SPM samples with uncertainty budget following sampling by HVS to analysis by Atomic Absorption Spectrometer-Hydride Generator (AAS-HG). In the measurement of arsenic in SPM samples so many steps are involved from sampling to final result and we have considered various potential sources of uncertainties. The calculation of uncertainty is based on ISO/IEC17025: 2005 document and EURACHEM guideline. It has been found that the final results mostly depend on the uncertainty in measurement mainly due to repeatability, final volume prepared for analysis, weighing balance and sampling by HVS. After the analysis of data of seven diverse sites of Delhi, it has been concluded that during the period from 31st Jan. 2008 to 7th Feb. 2008 the arsenic concentration varies from 1.44 ± 0.25 to 5.58 ± 0.55 ng/m3 with 95% confidence level (k = 2)

Free Cysteine Modulates the Conformation of Human C/EBP Homologous Protein

The C/EBP Homologous Protein (CHOP) is a nuclear protein that is integral to the unfolded protein response culminating from endoplasmic reticulum stress. Previously, CHOP was shown to comprise extensive disordered regions and to self-associate in solution. In the current study, the intrinsically disordered nature of this protein was characterized further by comprehensive in silico analyses. Using circular dichroism, differential scanning calorimetry and nuclear magnetic resonance, we investigated the global conformation and secondary structure of CHOP and demonstrated, for the first time, that conformational changes in this protein can be induced by the free amino acid l-cysteine. Addition of l-cysteine caused a significant dose-dependent decrease in the protein helicity – dropping from 69.1% to 23.8% in the presence of 1 mM of l-cysteine – and a sequential transition to a more disordered state, unlike that caused by thermal denaturation. Furthermore, the presence of small amounts of free amino acid (80 µM, an 8∶1 cysteine∶CHOP ratio) during CHOP thermal denaturation altered the molecular mechanism of its melting process, leading to a complex, multi-step transition. On the other hand, high levels (4 mM) of free l-cysteine seemed to cause a complete loss of rigid cooperatively melting structure. These results suggested a potential regulatory function of l-cysteine which may lead to changes in global conformation of CHOP in response to the cellular redox state and/or endoplasmic reticulum stress

The Shapes of Cooperatively Rearranging Regions in Glass Forming Liquids

The shapes of cooperatively rearranging regions in glassy liquids change from being compact at low temperatures to fractal or ``stringy'' as the dynamical crossover temperature from activated to collisional transport is approached from below. We present a quantitative microscopic treatment of this change of morphology within the framework of the random first order transition theory of glasses. We predict a correlation of the ratio of the dynamical crossover temperature to the laboratory glass transition temperature, and the heat capacity discontinuity at the glass transition, Delta C_p. The predicted correlation agrees with experimental results for the 21 materials compiled by Novikov and Sokolov.Comment: 9 pages, 6 figure

Fluorescence Quantum Yield of Thioflavin T in Rigid Isotropic Solution and Incorporated into the Amyloid Fibrils

In this work, the fluorescence of thioflavin T (ThT) was studied in a wide range of viscosity and temperature. It was shown that ThT fluorescence quantum yield varies from 0.0001 in water at room temperature to 0.28 in rigid isotropic solution (T/η→0). The deviation of the fluorescence quantum yield from unity in rigid isotropic solution suggests that fluorescence quantum yield depends not only on the ultra-fast oscillation of ThT fragments relative to each other in an excited state as was suggested earlier, but also depends on the molecular configuration in the ground state. This means that the fluorescence quantum yield of the dye incorporated into amyloid fibrils must depend on its conformation, which, in turn, depends on the ThT environment. Therefore, the fluorescence quantum yield of ThT incorporated into amyloid fibrils can differ from that in the rigid isotropic solution. In particular, the fluorescence quantum yield of ThT incorporated into insulin fibrils was determined to be 0.43. Consequently, the ThT fluorescence quantum yield could be used to characterize the peculiarities of the fibrillar structure, which opens some new possibilities in the ThT use for structural characterization of the amyloid fibrils

ARPES: A probe of electronic correlations

Angle-resolved photoemission spectroscopy (ARPES) is one of the most direct methods of studying the electronic structure of solids. By measuring the kinetic energy and angular distribution of the electrons photoemitted from a sample illuminated with sufficiently high-energy radiation, one can gain information on both the energy and momentum of the electrons propagating inside a material. This is of vital importance in elucidating the connection between electronic, magnetic, and chemical structure of solids, in particular for those complex systems which cannot be appropriately described within the independent-particle picture. Among the various classes of complex systems, of great interest are the transition metal oxides, which have been at the center stage in condensed matter physics for the last four decades. Following a general introduction to the topic, we will lay the theoretical basis needed to understand the pivotal role of ARPES in the study of such systems. After a brief overview on the state-of-the-art capabilities of the technique, we will review some of the most interesting and relevant case studies of the novel physics revealed by ARPES in 3d-, 4d- and 5d-based oxides.Comment: Chapter to appear in "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancini, Springer Series in Solid-State Sciences (2013). A high-resolution version can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Reviews/ARPES_Springer.pdf. arXiv admin note: text overlap with arXiv:cond-mat/0307085, arXiv:cond-mat/020850