Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Xu, X., Li, G., Li, C., Zhang, J., Wang, Q., Simmons, D. K., Chen, X., Wijesena, N., Zhu, W., Wang, Z., Wang, Z., Ju, B., Ci, W., Lu, X., Yu, D., Wang, Q., Aluru, N., Oliveri, P., Zhang, Y. E., Martindale, M. Q., & Liu, J. Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis. National Science Review, 6(5), (2019):993-1003, doi:10.1093/nsr/nwz064.Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular innovations. To search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans. We focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and mammals. Here, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in vertebrates. Functional association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for invertebrates. Interestingly, the single HOX cluster of invertebrates maintains unmethylated status in all stages examined. In contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis. Notably, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals. Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.This work was supported by the National Key Research and Development Program of China (2018YFC1003303), the Strategic Priority Research Program of the CAS (XDB13040200), the National Natural Science Foundation of China (91519306, 31425015), the Youth Innovation Promotion Association of the CAS and the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC016)

Alterations in microRNA expression profiles in inflamed and non-inflamed ascending colon mucosae of patients with active Crohn's disease

Background and aims The miRNA expression profiles of the terminal ileum, sigmoid colon, and rectal mucosa of adult patients with active Crohn';s disease (CD) have been previously reported. The purpose of this study was to identify dysregulated miRNAs in the mucosa of the ascending colon. Methods Biopsy tissue samples were taken from the mucosae of inflammatory (iCD) or non-inflammatory (niCD) areas of the ascending colons of adult patients with active CD. miRNA and mRNA expression profiles were detected using microarray analyses. miRNAs and mRNAs demonstrating significant differences were validated via quantitative real-time PCR (qRT-PCR). Luciferase reporter genes were used to measure two miRNAs inhibition of potential target genes in human 293T cells in vitro. Results Compared with the HC group, the ascending colon miRNA expression profiles revealed that 43 miRNAs were significantly up-regulated and 35 were down-regulated in the iCD group. The mRNA expression profiles indicated that 3,370 transcripts were significantly differentially expressed in the ascending colon, with 2169 up-regulated and 1201 down-regulated mRNAs in the iCD group, and only 20 miRNAs demonstrated significant differential expression in the niCD group. In contrast, nearly 100 miRNAs significantly varied between the iCD and niCD groups. Finally, luciferase reporter gene assays showed that hsa-miR-16-1 directly regulated the human C10orf54 gene and that they were negatively correlated. Conclusions Our results indicated that the differentially expressed miRNAs and mRNAs were related to immune inflammation and intestinal flora. The data provide preliminary evidence that the occurrence of CD involves the inhibition of C10orf54 expression by hsa-miR-16-1

Innovating corporate share listing frameworks: a comparative study of SPAC regulatory regimes in the United Kingdom, Singapore, and Hong Kong

In the 2020s, special purpose acquisition companies (SPACs) have swiftly emerged as an alternative vehicle for global corporations that seek a public listing. This article aims to critically analyse the regulatory frameworks governing SPAC listings in three prominent common law jurisdictions: the United Kingdom, Singapore, and Hong Kong. It evaluates the latest corporate share listing reforms from a comparative perspective, shedding light on how each jurisdiction adapts to the dynamic nature of SPACs and addresses rising challenges regarding investor protection under their new listing regimes. The discussion focuses on the influence of international best practices and the cooperation among global regulatory authorities. By providing an in-depth comparative analysis of SPAC listing rules in London, Singapore, and Hong Kong, this article offers valuable insights for researchers, legal practitioners, policymakers, public companies, and their investors who seek to understand the regulatory landscape for SPACs and innovative corporate regimes in leading financial centres. The findings enhance our understanding of the strengths and weaknesses of the SPAC regulatory frameworks in each of the three jurisdictions, thus assisting stakeholders in making informed decisions in the rapidly evolving global financial landscape

Remarks on quiver gauge theories from open topological string theory

We study effective quiver gauge theories arising from a stack of D3-branes on certain Calabi-Yau singularities. Our point of view is a first principle approach via open topological string theory. This means that we construct the natural A-infinity-structure of open string amplitudes in the associated D-brane category. Then we show that it precisely reproduces the results of the method of brane tilings, without having to resort to any effective field theory computations. In particular, we prove a general and simple formula for effective superpotentials

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification