Artificial escape from XCI by DNA methylation editing of the CDKL5 gene.

A significant number of X-linked genes escape from X chromosome inactivation and are associated with a distinct epigenetic signature. One epigenetic modification that strongly correlates with X-escape is reduced DNA methylation in promoter regions. Here, we created an artificial escape by editing DNA methylation on the promoter of CDKL5, a gene causative for an infantile epilepsy, from the silenced X-chromosomal allele in human neuronal-like cells. We identify that a fusion of the catalytic domain of TET1 to dCas9 targeted to the CDKL5 promoter using three guide RNAs causes significant reactivation of the inactive allele in combination with removal of methyl groups from CpG dinucleotides. Strikingly, we demonstrate that co-expression of TET1 and a VP64 transactivator have a synergistic effect on the reactivation of the inactive allele to levels >60% of the active allele. We further used a multi-omics assessment to determine potential off-targets on the transcriptome and methylome. We find that synergistic delivery of dCas9 effectors is highly selective for the target site. Our findings further elucidate a causal role for reduced DNA methylation associated with escape from X chromosome inactivation. Understanding the epigenetics associated with escape from X chromosome inactivation has potential for those suffering from X-linked disorders

Developmental perspectives on Europe

The crisis of 2008–2009 has ended, stockmarkets skyrocketed in 2012–2013, while growth of the real sector remained sluggish in Europe. This article attempts to explain the latter puzzle. Analyzing long term factors, the costs of short-termism in crisis management become obvious. The limitations of EU as a growth engine are highlighted

May Measurement Month 2017: an analysis of blood pressure screening in Hungary—Europe

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Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain

Acknowledgments We thank Szilvia Minorits for technical assistance. I.U. conceived and designed the project and wrote the manuscript. All authors participated in designing and performing the experiments, and analyzing the results. The authors declare no competing financial interests. This work was also supported by a grant from the National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00001. Funding: This work was supported by Hungarian Science Foundation Grant OTKA 109521 and National Research Development and Innovation Office GINOP-2.3.2-15-2016-00001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Image rights: Exploitation and legal control in English and Hungarian law

In the past decades due to changed technical advances, features of the personality have become economically exploitable to an extent not previously known. Pop stars, TV celebrities as well as famous athletes have sought protection against the commercial use of their images, names and likenesses without their consent.1 Despite the economic value of personality and image rights, there is currently no international standard or agreed legal concept for recognising an image right. While many jurisdictions, for example, the US, Germany, France and Hungary offer express statutory protection against the unauthorised commercial use of an individual’s image by a third party in the context of publicity or personality rights, English law provides no cause of action for the infringement of image rights as such. Although a celebrity may currently obtain protection through various statutory and common law rights, such as the developing law of privacy, trade mark law breach of confidence and, in particular, the tort of passing off, none of these rights were designed to protect image or personality rights.2 In this context, this article explores the potentially enforceable rights, their benefits and practical strategies to protect name and image rights in the UK3 and Hungary

Inequities in cancer drug development in terms of unmet medical need

This study measures inequality and inequity in the distribution of clinical trials on cancer drug development between 1996 and 2016, comparing the number of clinical trials with cancer need, proxied by prevalence, incidence, or survival rates for both rare and non-rare cancers. We leverage a unique global database of clinical trials activity and costs between 1996 and 2016, constructed for 227 different cancer types to measure for rare and non-rare cancers: i) inequalities and inequity of clinical trial activity, considering all trials as well as split by R&D stage; ii) inequalities and inequity in R&D investment proxied by trial enrollment and duration; iii) evolution of inequity over time. Inequalities are measured with concentration curves and indices and inequities measured with the health inequity index. We find four important results. First, we show pro-low need inequity across cancer types for both rare and non-rare cancers, for all need proxies. Second, we show inequity differs across R&D stages and between rare and non-rare cancers. The distribution of clinical trials for non-rare cancers disproportionately favors low-need non-rare cancers from earlier to later stages of R&D, whilst for rare cancers this only occurs in Phase 2 trials. Third, inequity analyses in R&D investment show that only trial enrollment for rare cancers and trial duration for non-rare cancers are disproportionately concentrated among low-need cancers. Finally, while pro-low need inequity has persisted between 1996 and 2016 for non-rare cancers, it has faded for rare cancers post-EU orphan drugs’ legislation

Cigarette smoke elicits relaxation of renal arteries

Epidemiological studies suggest that cigarette smoking - probably by eliciting hyperperfusion - increases glomerular filtration rate; thus, we hypothesized that cigarette smoke affects the vasomotor tone of renal arteries