Genome-scale network model of metabolism and histone acetylation reveals metabolic dependencies of histone deacetylase inhibitors

Abstract Histone acetylation plays a central role in gene regulation and is sensitive to the levels of metabolic intermediates. However, predicting the impact of metabolic alterations on acetylation in pathological conditions is a significant challenge. Here, we present a genome-scale network model that predicts the impact of nutritional environment and genetic alterations on histone acetylation. It identifies cell types that are sensitive to histone deacetylase inhibitors based on their metabolic state, and we validate metabolites that alter drug sensitivity. Our model provides a mechanistic framework for predicting how metabolic perturbations contribute to epigenetic changes and sensitivity to deacetylase inhibitors.https://deepblue.lib.umich.edu/bitstream/2027.42/148146/1/13059_2019_Article_1661.pd

EVALUATION OF DRUG YIELDING POTENTIAL OF MICROPROPAGATED CURCUMA AROMATICA

Objective: GC MS analysis and antioxidant activity of micropropagated and conventionally grown Curcuma aromatica essential oil and extract was done for their large scale commercial cultivation. Molecular marker based studies were performed to know their genetic fidelity as well as to trace any somaclonal variation existing between the regenerants.Methods: In vitro regeneration and multiplication were done using Murashige and Skoog media with various combinations of growth regulators. Component identification was done by GC MS analysis. Random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) markers were used for molecular profiling. Antioxidant activity was performed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH).Results: Molecular marker-based analysis revealed uniform banding patterns similar to those of the mother plants. Gas chromatography and mass spectroscopy (GC MS) analysis showed the presence of 10 major components accounted for 95.5% of the total compounds. The major components in micropropagated and field grown mother plants were found to be alpha phellandrene (41% and 38%), 4-carene (23% and 25%) and terpeneol etc. Antioxidant activity of leaf oil (IC50-29.3 µg/ml) and methanolic extract (IC50-101.25 µg/ml) of in vitro grown plants showed increased free-radical scavenging activity. Conclusion: Absence of any type of remarkable polymorphism in the essential oil quality and antioxidant activity the present protocol could be used commercially for large scale propagation of C. aromatica. The present report bears immense potential for the future improvement, conservation and domestication of C. aromatica to explore its high prized secondary metabolites.Â

CHEMICAL COMPOSITION, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF ESSENTIAL OIL FROM LIME BASIL (OCIMUM AMERICANUM): A POTENT SOURCE FOR NATURAL ANTIOXIDANT

Objective: GC and GC MS based analysis of the essential oil from leaf samples of Ocimum americanum were done. The essential oil composition, In vitro antioxidant and antimicrobial activity of the essential oil of O. americanum were evaluated in this research to explore its potential for future use. Methods: The component identification was achieved by the GC–MS analysis. Radical-scavenging activities of the plant essential oil were determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) activity. Antimicrobial activity of the essential oil was done using standard pathogenic strains in disc diffusion method. Results: GC and GC/MS analysis of the plant essential oil resulted in the identification of 19 compounds representing 100% of the oil. Citral (47.18%) and β - citral (36.57%) were the two major constituents. The essential oil subjected to analysis of its antioxidant activity using 2, 2- diphenyl-1-1picrylhydrazyl (DPPH) showed higher activity as compared to the standard. The oil was also screened for its antimicrobial activity and the inhibition was recorded against pathogenic microorganisms. Conclusion: Both the antimicrobial and anti oxidant activity of Ocimum americanum showed its potential for further use as natural antioxidant and preservative. Essential oil from the medicinal plants is one of the promising natural compounds for preparation of safer antimicrobial and antioxidant agent. Antioxidants conventionally used in food industries are obtained by chemical synthesis, but their use, reserved for certain categories of food is regulated by dose limits. Leaves of Ocimum americanum L. contain citral rich essential oil which is a potent source for natural antioxidants and biologically active compounds

GC-MS ANALYSIS OF ESSENTIAL OIL OF SOME HIGH DRUG YIELDING GENOTYPES OF TURMERIC (CURCUMA LONGA L.)

Objective: The aim of this investigation was to carry out the qualitative evaluation of selected high drug yielding elite genotypes of turmeric to add to their eliteness.Methods: 131 turmeric genotypes collected from 10 different agroclimatic zones were analysed for curcumin content. Leaves and rhizomes of these plants were collected for extraction of essential oil. Curcumin percentage of the sample was estimated according to the ASTA method. Essential oil was extracted by hydro-distillation of fresh leaves and rhizomes following the method of Guenther (1972). Initial screening of elite genotypes was done on the basis of curcumin content (≥5%), rhizome oil content (≥1.5%) and leaf oil content (≥0.5%). Selected elite genotypes were subjected to qualitative evaluation of essential oil through GC-MS analysis.Results: The five high rhizome oil yielding genotypes, TR1, TR2, TR3 and TR5 containing high rhizome oil yield of 2.1%, 1.7%, 1.6% and 1.5% respectively were considered to be elite clones containing tumerone as the major constituent of rhizome essential oil along with all desirable constituents. On the basis of leaf oil yield, genotypes TL1 and TL2 with 1.9% and 1.1% leaf oil were proved as elite clones with α–phellandrene as the major constituent along with other desirable constituents. GC-MS analysis of 3 selected high curcumin yielding genotypes TC1, TC2 and TC3 with curcumin content 7.3, 7.2 and 7.0% respectively revealed TC1 and TC2 as elite genotypes containing high quality rhizome and leaf oil.Conclusion: The present investigation reveals that eight genotypes of turmeric selected with high drug yield and high quality essential oil would have enough significance for boosting the production and export of value added products in the national and international market.Â

Culture-level dimensions of social axioms and their correlates across 41 cultures

Leung and colleagues have revealed a five-dimensional structure of social axioms across individuals from five cultural groups. The present research was designed to reveal the culture level factor structure of social axioms and its correlates across 41 nations. An ecological factor analysis on the 60 items of the Social Axioms Survey extracted two factors: Dynamic Externality correlates with value measures tapping collectivism, hierarchy, and conservatism and with national indices indicative of lower social development. Societal Cynicism is less strongly and broadly correlated with previous values measures or other national indices and seems to define a novel cultural syndrome. Its national correlates suggest that it taps the cognitive component of a cultural constellation labeled maleficence, a cultural syndrome associated with a general mistrust of social systems and other people. Discussion focused on the meaning of these national level factors of beliefs and on their relationships with individual level factors of belief derived from the same data set.(undefined

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe