Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers

BACKGROUND: Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown. RESULTS: Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs. CONCLUSIONS: DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-868) contains supplementary material, which is available to authorized users

Python Implementation of intelligent system for Quality Control of Argo Floats using Alpha Convex Hull

In each research field, quality control is the crucial part in order to ensure that the data collected is trustworthy. Quality control management helps in detecting abnormal behavior, monitor the health of detecting instruments. Argo Float is an ocean instrument which gives a lot of information regarding the conditions of the ocean. The information obtained has its value only if the quality of the parameter measuring procedure involves good quality tools. So, maintaining the quality of the procedure is as important as analyzing the obtained data. The  salinity and the temperature data from Argo floats which collect data from in situ regions of ocean need to be scrutinized for anomalous values and examined to find out the reason behind the abnormal values recorded using a new method  proposed by using Alpha convex hull. The data collected is used to construct an alpha shape polygon which is fine tuned to obtain best possible results. This method segregates by representing good data inside the polygon and the bad data outside the polygon. The proposed intelligent system is observed to detect the anomalous data occurring due to various problems such as sensor corrosion, bias ,spikes etc. This method aims to perform quality control for oceanographic data of argos at present but aims to work on different sources. The main advantages of the proposed system can be seen as the ability to identify anomalous data from in situ bulk data in minimal steps and to be applicable for cumulative data of various depths together

EPIDEMIOLOGY, PATHOPHYSIOLOGY, AND HINDRANCE OF UREA CYCLE ERROR OF METABOLISM

Inborn errors of metabolism (IEMs) are a class of genetic disorders that are rare individually, but collectively they occur in common terms exhibiting an average prevalence of 1 in 1000 individuals. One of the most commonly occurring IEMs is the urea cycle disorders (UCDs), which are a group of unusual disorders that have an effect on the urea cycle, a sequence of metabolic processes through which nitrogen is transformed into urea and expelled from the body by the urine. These diseases are the primary cause of hereditary hyperammonemia, and they can result in developmental disabilities, epilepsy, loss of psychomotor control, and death. UCDs are most commonly diagnosed during infancy, although certain infants do not exhibit symptoms until they are in their early childhood. IEMs are precisely diagnosed and recorded through tandem mass spectroscopy-based newborn screening. Recent advances in IEMs include new therapies based on dietary modification, enzyme replacement therapy, development of novel compounds, and diagnosis involving untargeted metabolomics and whole-exome sequencing are also widely being used in new disease discovery. Modern improvements in diagnosis and care have increased the prognosis significantly for a lot of children with IEM. It has been suggested that expanded access to awareness of IEMs is the most significant change leading to better treatment. The purpose of this review is to provide an overview on IEM and present in-depth knowledge about the UCDs including their subtypes

PHENYL ALANINE AMMONIA LYASE (PAL) ACTIVITY AND ARTEMISININ CONTENTS OF ARTEMISIA ANNUA L., DURING CALLUS GROWTH

The relationship between the level of phenyl alanine ammonia lyase and the concentration of artemisinin produced in the callus cultures of Artemisia annua. L was studied. TLC and high performance liquid chromatographic analysis indicated the presence of maximum artemisinin production was associated with the higher level of PAL activity at the 4th week of callus growth. Both artemisinin and level of enzyme activity declined subsequently by 5th week. Protein and nucleic acid contents of the callus during the growth showed an inverse relationship with the level of phenyl alanine ammonia lyase. The enzyme appears to play a cardinal role in the production of artemisinin during the callus growth

MOLECULAR DOCKING STUDIES ON FLAVONOID COMPOUNDS: AN INSIGHT INTO AROMATASE INHIBITORS

Objective: Aromatase is a key enzyme that plays a crucial role in the synthesis of estrogen and has a major effect in pathogenesis of estrogen‑dependent disease, including breast cancer, endometrial cancer, and endometriosis. The abnormal over expression of aromatase can be inhibited by aromatase inhibitors. The objective of the present study is to evaluate the binding interaction of flavonoid compounds with cytochrome P450 enzyme aromatase, which is involved in the metabolism of estrogens and considered as a powerful target for treatment of estrogen-dependent breast cancers. Methods: To understand the mechanisms involved in the binding of flavonoid compounds and their interactions with the binding site of aromatase, molecular docking studies were carried using Autodock 4.2. Results: The docking results revealed that, benzoflavanones showed higher binding affinity compared to other class of compounds. The presence of hydrogen bond interaction and cation–π interaction contributed to their higher binding affinity. The flavonoid compounds with unsubstituted or less substituted rings showed higher binding affinity than those with substituted rings. The hydrogen bonding interactions were predominant in all the classes of compounds considered for the study and were found to be important for inhibition. The docking studies showed that the binding energies mainly depend on aromatic properties like cation–π and π–π interactions. These properties play a key role in determining the biological activity of flavonoid compounds. Conclusion: The present findings provided valuable information on the binding process of flavonoid compounds to the binding site of aromatase and revealed the structural requirement needed for binding

Marriage and the crisis of peasant society in Gujarat, India

This contribution takes marriage as the example of a crisis of production and reproduction in rural India. Through the juxtaposition of ethnography separated by six decades, we detail a shift away from land and agriculture as the primary markers of status among the Patidars of central Gujarat, western India, in favour of a hierarchical understanding of international migration. The paper discusses the disconnect between a cultural revolution in favour of migration, and the failure of many to live up to their own cultural standards. More broadly, we reflect on the forces that simultaneously strengthen and dissolve caste inequality in the context of India's uneven growth

Exploring the Therapeutic Potential of Rosemary: An In-depth Review of its Pharmacological Properties

The pharmacological effects of rosemary plant period a wide range and include anti-inflammatory and antioxidant properties. Rosemary is shown to have its potential on Ischemic stroke because of its Anti-oxidant and Anti-inflammatory properties. It contains strong antioxidants such carnosol, which has anti-inflammatory properties, and Rosmarinus acid, which fights oxidative stress. Rosemary is an attractive possibility for treating disorders like oxidative-related diseases because of its dual activity. Additionally, Rosemary has shown neuroprotective qualities that aid in maintaining brain health and cognitive function. The aromatic components in its essential oil may improve concentration and memory. Rosemary has also been investigated for its potential in hair care, with research indicating that it can encourage hair growth. These rosemary Officinalis also have different chemical substances and compounds like Terpenes, Essential oils, Bicyclic monoterpenes, Monoterpenoids, Ester and also, we have different pharmacological activates they are Anti-oxidative, Anti-inflammatory, Anti-microbial, Anti-obesity, Anti-fungal, Anti-cancer, Anti-diabetic, Cardiovascular activity, Skin health, Neuroprotective, Gastrointestinal, Sperm motility, Anti-depressant, Anti-viral activity

<i>In Silico</i>Molecular Docking and<i>In Vitro</i>Antidiabetic Studies of Dihydropyrimido[4,5-<i>a</i>]acridin-2-amines

Anin vitroantidiabetic activity onα-amylase andα–glucosidase activity of novel 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amines (3a–3f) were evaluated. Structures of the synthesized molecules were studied by FT-IR,1H NMR,13C NMR, EI-MS, and single crystal X-ray structural analysis data. Anin silicomolecular docking was performed on synthesized molecules (3a–3f). Overall studies indicate that compound3eis a promising compound leading to the development of selective inhibition ofα-amylase andα-glucosidase.</jats:p

Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, Platelet Factor-4

<p>Abstract</p> <p>Background</p> <p>Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer <it>in vivo</it>.</p> <p>Methods</p> <p>The <it>Lady </it>transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry.</p> <p>Results</p> <p>Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025). This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P < 0.0001). While prostates of mice receiving standard chow were enlarged and burdened with poorly differentiated carcinoma, those of mice on the supplemented diet appeared normal. Immunohistochemical analysis revealed marked amplifications of both platelet binding and platelet factor-4 within the blood vessels of prostates from mice receiving micronutrients only.</p> <p>Conclusion</p> <p>We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding.</p

Relational approaches to poverty in rural India: social, ecological and technical dynamics

Poverty is now widely recognised as multidimensional, with indicators including healthcare, housing and sanitation. Yet, relational approaches that foreground political-cultural processes remain marginalised in policy discourses. Focusing on India, we review a wide range of relational approaches to rural poverty. Beginning with early approaches that focus on structural reproduction of class, caste and to a lesser extent gender inequality, we examine new relational approaches developed in the last two decades. The new approaches examine diverse ways in which poverty is experienced and shapes mobilisations against deprivation. They draw attention to poor people’s own articulations of deprivation and alternate conceptions of well-being. They also show how intersecting inequalities of class, caste and gender shape governance practices and political movements. Despite these important contributions, the new relational approaches pay limited attention to technologies and ecologies in shaping the experience of poverty. Reviewing studies on the Green Revolution and wider agrarian transformations in India, we then sketch the outlines of a hybrid relational approach to poverty that combines socio-technical and -ecological dynamics. We argue that such an approach is crucial to challenge narrow economising discourses on poverty and to bridge the policy silos of poverty alleviation and (environmentally) sustainable development