ANALYSIS OF EPIGENETIC MODIFICATIONS IN NEURAL STEM CELLS OF MOUSE EMBRYOS FROM DIABETIC PREGNANCY

Ph.DDOCTOR OF PHILOSOPHY (SOM

Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development

Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis. To address this, high throughput miRNA expression profiling in neural stem cells (NSCs) isolated from the forebrain of embryos from normal or streptozotocin-induced diabetic pregnancy was carried out. It is known that maternal diabetes results in fetal hypoglycemia/hyperglycemia or hypoxia. Hence, NSCs from embryos of control pregnant mice were exposed to low or high glucose or hypoxia in vitro. miRNA pathway analysis revealed distinct deregulation of several biological pathways, including axon guidance pathway, which are critical for brain development in NSCs exposed to different treatments. Among the differentially expressed miRNAs, the miRNA-30 family members which are predicted to target genes involved in brain development was upregulated in NSCs from embryos of diabetic pregnancy when compared to control. miRNA-30b was found to be upregulated while its target gene Sirtuin 1 (Sirt1), as revealed by luciferase assay, was down regulated in NSCs from embryos of diabetic pregnancy. Further, overexpression of miRNA-30b in NSCs, resulted in decreased expression of Sirt1 protein, and altered the neuron/glia ratio. On the other hand, siRNA mediated knockdown of Sirt1 in NSCs promoted astrogenesis, indicating that miRNA-30b alters lineage specification via Sirt1. Overall, these results suggest that maternal diabetes alters the genes involved in neural tube formation via regulating miRNAs

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down’s syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature

Greenhouse gas emission from wastewater irrigated soils

With increasing demand for world water supply, wastewater reuse is a great opportunity to meet the water need, especially for agricultural and industrial development. Wastewater originates from many sources and hence its composition differs from origin and treatment processes. Wastewater rich in organic matter acts as a soil conditioner, thereby enhancing soil health. Wastewater also acts as a source of nutrient input in agriculture whichin turn can reduce, or even eliminate the need for commercial fertilisers. However, wastewater usage in agriculture poses several threats like eutrophication, salinity, toxic chemicals (heavy metal(loids), pesticides), pathogen contamination, and most notably, nutrient leaching, and greenhouse gas (GHG) emission. These threats affect public health, soil and ground water resources, environment, crop quality, ecological, and property values. Biological degradation of the organic matter present in wastewater is considered one of the anthropogenic sources of major GHGs (carbon dioxide (CO,), nitrous oxide (N,O), and methane (CH4) , In this paper, an overview of various sources of wastewater, effects of wastewater application on GHG emission from soil, and the strategies to mitigate wastewater-induced GHG emission from soils is presented.

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

10.3390/genes8060150GENES8

Knockout of the Erythromycin Biosynthetic Cluster Gene, eryBI, Blocks Isoflavone Glucoside Bioconversion during Erythromycin Fermentations in Aeromicrobium erythreum but Not in Saccharopolyspora erythraea▿

Isoflavone glucosides are valuable nutraceutical compounds and are present in commercial fermentations, such as the erythromycin fermentation, as constituents of the soy flour in the growth medium. The purpose of this study was to develop a method for recovery of the isoflavone glucosides as value-added coproducts at the end of either Saccharopolyspora erythraea or Aeromicrobium erythreum fermentation. Because the first step in isoflavone metabolism was known to be the conversion of isoflavone glucosides to aglycones by a β-glucosidase, we chose to knock out the only β-glucosidase gene known at the start of the study, eryBI, to see what effect this had on metabolism of isoflavone glucosides in each organism. In the unicellular erythromycin producer A. erythreum, knockout of eryBI was sufficient to block the conversion of isoflavone glucosides to aglycones. In S. erythraea, knockout of eryBI had no effect on this reaction, suggesting that other β-glucosidases are present. Erythromycin production was not significantly affected in either strain as a result of the eryBI knockout. This study showed that isoflavone metabolism could be blocked in A. erythreum by eryBI knockout but that eryBI knockout was not sufficient to block isoflavone metabolism in S. erythraea