Sequences Sufficient for Programming Imprinted Germline DNA Methylation Defined

Epigenetic marks are fundamental to normal development, but little is known about signals that dictate their placement. Insights have been provided by studies of imprinted loci in mammals, where monoallelic expression is epigenetically controlled. Imprinted expression is regulated by DNA methylation programmed during gametogenesis in a sex-specific manner and maintained after fertilization. At Rasgrf1 in mouse, paternal-specific DNA methylation on a differential methylation domain (DMD) requires downstream tandem repeats. The DMD and repeats constitute a binary switch regulating paternal-specific expression. Here, we define sequences sufficient for imprinted methylation using two transgenic mouse lines: One carries the entire Rasgrf1 cluster (RC); the second carries only the DMD and repeats (DR) from Rasgrf1. The RC transgene recapitulated all aspects of imprinting seen at the endogenous locus. DR underwent proper DNA methylation establishment in sperm and erasure in oocytes, indicating the DMD and repeats are sufficient to program imprinted DNA methylation in germlines. Both transgenes produce a DMD-spanning pit-RNA, previously shown to be necessary for imprinted DNA methylation at the endogenous locus. We show that when pit-RNA expression is controlled by the repeats, it regulates DNA methylation in cis only and not in trans. Interestingly, pedigree history dictated whether established DR methylation patterns were maintained after fertilization. When DR was paternally transmitted followed by maternal transmission, the unmethylated state that was properly established in the female germlines could not be maintained. This provides a model for transgenerational epigenetic inheritance in mice

Basal Jawed Vertebrate Phylogenomics Using Transcriptomic Data from Solexa Sequencing

The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi) and an African lungfish (Protopterus sp.) we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values). Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0). The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences

How 'universal' is the United Nations' Universal Periodic Review process? An examination of the discussions held on polygamy

In 2006, United Nations Human Rights Council was tasked to establish a new human rights monitoring mechanism: Universal Periodic Review process. The primary aim of this process is to promote and protect the universality of all human rights issues and concerns via a dialogical peer review process. The aim of this investigation isto ask the following question: has this claim of promoting and protecting the universality of the human rights been met, or challenged, during state reviews in the UPR process? The issue of polygamy has been selected as the focus for this investigation to be used, primarily, as a tool to undertake an in-depth analysis of the discussions held during state reviews in the review process. In addition, this paper will employ scholarly debates between universalism and cultural relativism, as well as the sophisticated and nuanced approaches that fall in between the polarised opposites, to analyse the discussions held on human rights during state reviews. Ultimately, the findings and discussion of this investigation will provide a unique and valuable insight to the work and operation of the UPR process, so far

On the use of parataxonomy in biodiversity monitoring: a case study on wild flora

International audienceMonitoring programs that assess species-richness and turnover are now regarded as essential to document biodiversity loss worldwide. Implementation of such programs is impeded by a general decrease in the number of skilled naturalists. Here we studied how morphotypes, instead of species, might be used by unskilled participants (referred to as “volunteers”) to survey common plant communities. Our main questions were: (1) Can morphotypes be used as a robust estimator of species-richness (alpha-diversity) and assemblage turnover (Beta-diversity)? and (2) What is the robustness (reproducibility and repeatability) of such methods? Double inventories were performed on 150 plots in arable Weld margins, one by a non-expert using morphotypes, the other by a taxonomist using species. To test the robustness of morphotype identiWcation among participants, 20 additional plots were surveyed by eight volunteers using the same protocol. We showed that (1) the number of morphotypes identiWed by unskilled volunteers in a plot was always strongly correlated with species-richness. (2) Morphotypes were sensitive to diVerences among habitats but were less accurate than species to detect these diVerences. (3) Morphotype identiWcation varied signiWcantly within and between volunteers. Due to this lack of repeatability and reproducibility, parataxonomy cannot be considered a good surrogate for taxonomy. Nevertheless, assuming that morphotypes are identiWed with standardized methods, and that results are used only to evaluate gross species-richness but not species turnover, parataxonomy might be a valuable tool for rapid biodiversity assessment of common wild flora

Islet transplantation from a nationally funded UK centre reaches socially deprived groups and improves metabolic outcomes

Acknowledgements We thank the transplant nurses involved with the Scottish Islet Transplant Programme (T. McGilvray, J. Davidson, M. Phillips and C. Jansen) for help with participant assessment. We thank the Scottish National Blood Transfusion Services including the Histocompatibility and Immunogenetics Team for HLA typing and antibody screening, and the Tissue and Cells Team (A. Timpson, L. Fraser, L. Irvine and P. Henry) for islet isolation and product release testing. We acknowledge the Departments of Transplantation, Diabetes and Interventional Radiology at NHS Lothian for all aspects of patient care and the organ procurement programme. We thank J. Shaw and A. Brooks from the Department of Regenerative Medicine for Diabetes at the University of Newcastle for advice regarding CGMS. C-peptide assays were performed by the NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory. Funding: The Scottish Islet Transplant Programme is funded by the National Services Division. This research was funded by Diabetes UK (Biomedical and Psychosocial Outcomes of Islet Transplantation; Grant no. BDA 06/0003362), Diabetes Research and Wellness Foundation, Diabetes Foundation, Juvenile Diabetes Research Foundation and the Royal Infirmary Diabetes Treatment Trust Fund. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPublisher PD