The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA

This research was originally published in Journal of Biological Chemistry. Ahmet Can Berkyurek, Isao Suetake, Kyohei Arita, Kohei Takeshita, Atsushi Nakagawa, Masahiro Shirakawa and Shoji Tajima. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. Journal of Biological Chemistry. 2014; 289, 379-386. © the American Society for Biochemistry and Molecular Biology

miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells

Dental pulp cells (DPCs) are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs) have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP) cells from human DPCs and periodontal ligament cells (PDLCs), and performed a locked nucleic acid (LNA)-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP) cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs), which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs

miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells

Dental pulp cells (DPCs) are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs) have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP) cells from human DPCs and periodontal ligament cells (PDLCs), and performed a locked nucleic acid (LNA)-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP) cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs), which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs

NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP

Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.009855

NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP

Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.009855

Efficient method to perform quantum number projection and configuration mixing for most general mean-field states

Combining several techniques, we propose an efficient and numerically reliable method to perform the quantum number projection and configuration mixing for most general mean-field states, i.e., the Hartree-Fock-Bogoliubov (HFB) type product states without symmetry restrictions. As for example of calculations, we show the results of the simultaneous parity, number and angular-momentum projection from HFB type states generated from the cranked Woods-Saxon mean-field with a very large basis that is composed of Nmax=20 spherical harmonic oscillator shells

Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus.

DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation

First measurements of p11B fusion in a magnetically confined plasma

Proton-boron (p11B) fusion is an attractive potential energy source but technically challenging to implement. Developing techniques to realize its potential requires first developing the experimental capability to produce p11B fusion in the magnetically-confined, thermonuclear plasma environment. Here we report clear experimental measurements supported by simulation of p11B fusion with high-energy neutral beams and boron powder injection in a high-temperature fusion plasma (the Large Helical Device) that have resulted in diagnostically significant levels of alpha particle emission. The injection of boron powder into the plasma edge results in boron accumulation in the core. Three 2 MW, 160 kV hydrogen neutral beam injectors create a large population of well-confined, high -energy protons to react with the boron plasma. The fusion products, MeV alpha particles, are measured with a custom designed particle detector which gives a fusion rate in very good relative agreement with calculations of the global rate. This is the first such realization of p11B fusion in a magnetically confined plasma