H3K18 lactylation marks tissue-specific active enhancers

Background: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation. Results: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue. Conclusions: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers. Keywords: Adipocyte; CUT&Tag; ChromHMM; Embryonic stem cell; Enhancer; Epigenetics; H3K18la; Histone post-translational modification; Lactate; Lactylation; Macrophage; Muscle; Promoter

Slowing and cooling molecules and neutral atoms by time-varying electric field gradients

A method of slowing, accelerating, cooling, and bunching molecules and neutral atoms using time-varying electric field gradients is demonstrated with cesium atoms in a fountain. The effects are measured and found to be in agreement with calculation. Time-varying electric field gradient slowing and cooling is applicable to atoms that have large dipole polarizabilities, including atoms that are not amenable to laser slowing and cooling, to Rydberg atoms, and to molecules, especially polar molecules with large electric dipole moments. The possible applications of this method include slowing and cooling thermal beams of atoms and molecules, launching cold atoms from a trap into a fountain, and measuring atomic dipole polarizabilities.Comment: 13 pages, 10 figures. Scheduled for publication in Nov. 1 Phys. Rev.

Efficient precision quantization in AdS/CFT

Understanding finite-size effects is one of the key open questions in solving planar AdS/CFT. In this paper we discuss these effects in the AdS_5xS^5 string theory at one-loop in the world-sheet coupling. First we provide a very general, efficient way to compute the fluctuation frequencies, which allows to determine the energy shift for very general multi-cut solutions. Then we apply this to two-cut solutions, in particular the giant magnon and determine the finite-size corrections at subleading order. The latter are then compared to the finite-size corrections from Luscher-Klassen-Melzer formulas and found to be in perfect agreement.Comment: 32 pages, 5 figures; v2: typos corrected, refs adde

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Gender and programming: What's going on?

The learning (and teaching) of programming in Higher Education is a perennial problem, and is the subject of much attention and innovation. One way in which the problem can be addressed is for instructors to investigate and thus better understand the ways in Which students learn to program. We present the results of investigations carried out at the Universities of Bent and Leeds into the ways in which gender influences the learning approach of students in programming. The research shows that gender is a significant factor in determining the way in which students approach learning to program. A better understanding of the issues raised would lead to more effective teaching and thus better learning