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

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

High-throughput low-cost nl-qPCR for enteropathogen detection: A proof-of-concept among hospitalized patients in Bangladesh.

BACKGROUND: Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients. METHODS: A census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome. RESULTS: A total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals." CONCLUSIONS: This study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients

Pervasive lesion segregation shapes cancer genome evolution

Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion. Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multi-allelic and combinatorial genetic diversity. The phasing of lesions enables the accurate measurement of strand biased repair processes, quantification of oncogenic selection, and fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.This work was supported by: Cancer Research UK (20412, 22398), the European Research Council (615584, 682398), the Wellcome Trust (WT108749/Z/15/Z, WT106563/Z/14/A, WT202878/B/16/Z), the European Molecular Biology Laboratory, the MRC Human Genetics Unit core funding programme grants (MC_UU_00007/11, MC_UU_00007/16), and the ERDF/Spanish Ministry of Science, Innovation and Universities-Spanish State Research Agency/DamReMap Project (RTI2018-094095-B-I00)

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

Control, care, and conviviality in the politics of technology for sustainability

This article discusses currently neglected distinctions between control, care, and conviviality in the politics of technology for sustainability. We conceptualize control as the ambition to maintain fictitious borders between hierarchically ordered categories such as subjects and objects. This ambition is materialized into a wide range of Modern technological innovations, including genome editing and deep sea mining. Contrasting with control, we conceptualize values of care that constitute socio-technical practices where connections are prioritized over categories and hierarchy is countered with egalitarian commitment. In caring practices, objects are thus treated as subjects, often within political contexts that are dominated by ambitions to control. Building on care, we explore hopes for conviviality as mutualistic autonomy and decolonial self-realization to orient plural socio-technical pathways for moving beyond Modernity. We argue that such pathways are crucial for democratic transformations to sustainability. We illustrate our concepts using two brief case studies of agricultural developments. The first case discusses the politics of control in agricultural biotechnologies in Belgium. The second case reports on care within rural people's coping strategies in a south Indian "green revolution" landscape laden with control. In conclusion, we emphasize the need to situate attempted materializations of control, care, and conviviality in specific historical junctures. Situated understandings of the interplay between control, care, and conviviality can help realize sustainability that does not reproduce the centralizing, control-driven logic of Modern technocratic development

Information Retrieval Based Solutions for Software Engineering Tasks Using C Codebases

Comments are descriptions of laws that a human can understand fluently. It’s easier to identify important law blocks with comments. But, not everyone can write the comments duly. They aren’t streamlined along with the law. Having outdated comments in the law can affect confusion rather than explanation. This paper aims at removing comments which aren’t related to code and not useful using Natural Language Processing( NLP). NLP has come one of the most habituated ways in the analysis of textbooks. In NLP, comments are written from the surrounding code given, and Machine Learning algorithms are applied. A semantic analysis frame for comments using textual and structural features grounded on comment orders and code–comment correlation. A machine learning approach is used to determine whether comments are also consistent and not superfluous based on code and comment correlation