Distinguishing epigenetic marks of developmental and imprinting regulation.

BACKGROUND: The field of epigenetics is developing rapidly, however we are only beginning to comprehend the complexity of its influence on gene regulation. Using genomic imprinting as a model we examine epigenetic profiles associated with different forms of gene regulation. Imprinting refers to the expression of a gene from only one of the chromosome homologues in a parental-origin-specific manner. This is dependent on heritable germline epigenetic control at a cis-acting imprinting control region that influences local epigenetic states. Epigenetic modifications associated with imprinting regulation can be compared to those associated with the more canonical developmental regulation, important for processes such as differentiation and tissue specificity. Here we test the hypothesis that these two mechanisms are associated with different histone modification enrichment patterns. RESULTS: Using high-throughput data extraction with subsequent analysis, we have found that particular histone modifications are more likely to be associated with either imprinting repression or developmental repression of imprinted genes. H3K9me3 and H4K20me3 are together enriched at imprinted genes with differentially methylated promoters and do not show a correlation with developmental regulation. H3K27me3 and H3K4me3, however, are more often associated with developmental regulation. We find that imprinted genes are subject to developmental regulation through bivalency with H3K4me3 and H3K27me3 enrichment on the same allele. Furthermore, a specific tri-mark signature comprising H3K4me3, H3K9me3 and H4K20me3 has been identified at all imprinting control regions. CONCLUSION: A large amount of data is produced from whole-genome expression and epigenetic profiling studies of cellular material. We have shown that such publicly available data can be mined and analysed in order to generate novel findings for categories of genes or regulatory elements. Comparing two types of gene regulation, imprinting and developmental, our results suggest that different histone modifications associate with these distinct processes. This form of analysis is therefore a useful tool to elucidate the complex epigenetic code associated with genome function and to determine the underlying features conferring epigenetic states.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Sexualisation of children in the contemporary media

In 2006, The Australia Institute published two discussion papers on the issue of the sexualisation of children in the contemporary media: Corporate paedophilia: sexualisation of children in the media1 and Letting children be children: stopping the sexualisation of children in Australia.2 The two papers prompted considerable public debate amongst parents, media and retail industry stakeholders, academics and interested parties more generally, indicating a high level of public interest in the issue. This report examines the sexualisation of children in the contemporary media environment, including radio and television, children\u27s magazines, other print and advertising material and the Internet

Attitudes to E-Cigarettes and Cessation Support for Pregnant Women from English Stop Smoking Services: A Mixed Methods Study

Smoking in pregnancy remains a public health problem. In the UK e-cigarettes are the most popular aid to quitting smoking outside of pregnancy, but we don’t know the extent of e-cigarette use in pregnancy or how English Stop Smoking Services (SSS) respond to pregnant women who vape. In 2015 we surveyed SSS managers about cessation support for pregnant women and responses to clients who vaped. Subsequently we interviewed a sub-sample of managers to seek explanations for the SSS’ position on e-cigarettes; interviews were thematically analysed. Survey response rate was 67.8% (72/106); overall managers reported 2.2% (range 1.4–4.3%) of pregnant clients were using e-cigarettes. Most SSS reported supporting pregnant women who already vaped, but would not recommend e-cigarette use; for women that were still smoking and not using e-cigarettes, 8.3% of SSS were likely/very likely to advise using e-cigarettes, with 56.9% of SSS unlikely/very unlikely to advise using them. Fifteen respondents were interviewed; interviewees were generally positive about the potential of e-cigarettes for cessation in pregnancy although concerns about perceived lack of evidence for safety were expressed and most wanted research on this. Clear guidance on e-cigarette use informed by pregnancy specific research will assist SSS to provide consistent evidence-based support

Reported antimicrobial use and Salmonella resistance on 90 Alberta swine farms

The study objectives were to describe antimicrobial use (AMU) and Salmonella resistance on 90 Alberta swine farms. The vast majority of antimicrobials were used in-feed. In weaners, in-feed use did not vary among farms, suggesting heavy reliance on in-feed antimicrobials. For grow-to-finish production phases, most farms reported heavy reliance on in-feed antimicrobials, but 6 and 14 farms did not report any in-feed AMU in growers and finishers, respectively

Hydrological modelling as a tool for interdisciplinary workshops on future drought

© 2018, © The Author(s) 2018. Transformative interdisciplinary methods and tools are required to address crucial water-related challenges facing societies in the current era of the Anthropocene. In a community-based study in the Limpopo basin of South Africa, physical and social science methods were brought together to run interdisciplinary workshops aimed at enhancing preparedness for possible future drought. To generate storylines for the workshops, relevant scenarios were modelled using a catchment-scale hydrological model, SHETRAN. Set up using freely available data, local knowledge, and narrative-based group interviews on past experiences of drought, the model acted as a locally-relevant tool for prompting discussions about potential future drought impacts, responses and preparedness, and to stimulate the production of community future narratives. In this paper, we discuss the elements involved in the modelling process: the building of the model through an interdisciplinary approach; setting up the model with limited data; and the translation of the model results into storylines for the workshops. We found that by using this methodology scientific grounding was given to the workshop storylines, and that the local context of the model and the engaging approach of creating narratives encouraged participant involvement in discussions about the future. The method of generating these future stories was an important process for the participants in developing their thinking about possible futures, preparedness and adaptation. In this paper we show how this alternative approach of using a hydrological model has benefits and we discuss the limitations and lessons of the approach for future interdisciplinary research

Effect of offering different levels of support and free nicotine replacement therapy via an English national telephone quitline: randomised controlled trial

Objective To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to standard smoking cessation support offered through a telephone quitline

Water governance challenges in rural South Africa: exploring institutional coordination in drought management

Droughts have severe direct impacts on the livelihoods of rural populations. Thus, the management of water for communal agriculture and water supply should be well coordinated to enhance drought resilience. Notwithstanding the interrelations among water management institutions in South Africa, there are complexities in the way these institutions work together, both in preparation for, and during drought times. In this article, we examine the governance of water resources in South Africa with a view to understanding institutional coordination in drought management at different operational scales. Using a qualitative approach, the roles and relationships between water actors at the local and regional level were analyzed for their adequacy in building local level drought resilience in a village in the Limpopo province, South Africa. Key informant interviews conducted revealed operational drought management challenges that emanate from communication barriers, coordination inconsistences, and undefined, unclear actor roles and responsibilities during disasters. The top-down approach to disaster management, while of some value, currently constrains the effectiveness of the local-level institutions implementing local drought risk reduction efforts. Achieving more successful water and drought governance endeavors could be enhanced by greater and wider engagement with community-based actors and water management institutions

Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression.

BACKGROUND: Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence. RESULTS: Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes. CONCLUSIONS: The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.The authors acknowledge support from the Wellcome Trust, BBSRC, and EU FP7 Initial Training Networks INGENIUM (Marie-Curie Action 290123) and EpiHealthNet (Marie Curie Action 317146).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13059-015-0672-

Exploratory analysis of methods for automated classification of laboratory test orders into syndromic groups in veterinary medicine

Background: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes-syndromic surveillance-using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. Methods: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. Results: High performance (F1-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F1-micro score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F1-macro), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F1-micro score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F1-micro = 0.994 and F1-macro =. 955), however the classification process is not transparent to the domain experts. Conclusion: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input

An unbiased assessment of the role of imprinted genes in an intergenerational model of developmental programming.

Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT-PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated