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Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.

Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development.sup.1-4. However, these simple culture systems lack the complexity to adequately model the spatiotemporal cellular and molecular dynamics that occur during early embryonic development. Here we describe the reprogramming of fibroblasts into in vitro three-dimensional models of the human blastocyst, termed iBlastoids. Characterization of iBlastoids shows that they model the overall architecture of blastocysts, presenting an inner cell mass-like structure, with epiblast- and primitive endoderm-like cells, a blastocoel-like cavity and a trophectoderm-like outer layer of cells. Single-cell transcriptomics further confirmed the presence of epiblast-, primitive endoderm-, and trophectoderm-like cells. Moreover, iBlastoids can give rise to pluripotent and trophoblast stem cells and are capable of modelling, in vitro, several aspects of the early stage of implantation. In summary, we have developed a scalable and tractable system to model human blastocyst biology; we envision that this will facilitate the study of early human development and the effects of gene mutations and toxins during early embryogenesis, as well as aiding in the development of new therapies associated with in vitro fertilization. Human fibroblasts are reprogrammed to generate blastocyst-like structures called iBlastoids, which recapitulate aspects of embryo implantation., Author(s): Xiaodong Liu [sup.1] [sup.2] [sup.3] , Jia Ping Tan [sup.1] [sup.2] [sup.3] , Jan Schröder [sup.1] [sup.2] [sup.3] , Asma Aberkane [sup.3] , John F. Ouyang [sup.4] , Monika [...]

Machado-Joseph disease (MJD; also called spinocerebellar ataxia type 3) is a dominantly inherited late-onset neurodegenerative disorder caused by expansion of polyglutamine (polyQ)-encoding CAG repeats in the MJD1 gene (also known [...]

Hydrogen safety sensors must meet specific performance requirements, mandated by the U.S. Department of Energy, for hydrogen fueling station monitoring. Here, we describe the long-term performance of two zirconia-based mixed potential electrochemical hydrogen gas sensors, developed specifically with a high sensitivity to hydrogen, low cross-sensitivity, and fast response time. Over a two-year period, sensors with tin-doped indium oxide and strontium doped lanthanum chromite electrodes were deployed at two stations in four field trials tests conducted in Los Angeles. The sensors documented the existence of hydrogen plumes ranging in concentration from 100 to as high as 2700 ppm in the area surrounding the dispenser, consistent with depressurization from 700 bar following vehicle refueling. As expected, the hydrogen concentration reported by the mixed potential sensors was influenced by wind direction. Baseline stability testing at a Chino, CA station showed nomeasureable baseline drift throughout 206 days of uninterrupted data acquisition. The high baseline stability, excellent correlation with logged fueling/depressurization events, and absence of false alarms suggest that the zirconia-based mixed potential sensor platform is a good candidate for protecting hydrogen infrastructure where frequent calibrations or sensor replacement to reduce the false alarm frequency have been shown to be cost prohibitive. [ABSTRACT FROM AUTHOR]