Tohoku University

About: Tohoku University is a education organization based out in Sendai, Japan. It is known for research contribution in the topics: Magnetization & Alloy. The organization has 72116 authors who have published 170791 publications receiving 3941714 citations. The organization is also known as: Tōhoku daigaku.

The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA

Abstract: DNA methyltransferase (cytosine-5) 1 (Dnmt1) is the principal enzyme responsible for maintenance of CpG methylation and is essential for the regulation of gene expression, silencing of parasitic DNA elements, genomic imprinting and embryogenesis. Dnmt1 is needed in S phase to methylate newly replicated CpGs occurring opposite methylated ones on the mother strand of the DNA, which is essential for the epigenetic inheritance of methylation patterns in the genome. Despite an intrinsic affinity of Dnmt1 for such hemi-methylated DNA, the molecular mechanisms that ensure the correct loading of Dnmt1 onto newly replicated DNA in vivo are not understood. The Np95 (also known as Uhrf1 and ICBP90) protein binds methylated CpG through its SET and RING finger-associated (SRA) domain. Here we show that localization of mouse Np95 to replicating heterochromatin is dependent on the presence of hemi-methylated DNA. Np95 forms complexes with Dnmt1 and mediates the loading of Dnmt1 to replicating heterochromatic regions. By using Np95-deficient embryonic stem cells and embryos, we show that Np95 is essential in vivo to maintain global and local DNA methylation and to repress transcription of retrotransposons and imprinted genes. The link between hemi-methylated DNA, Np95 and Dnmt1 thus establishes key steps of the mechanism for epigenetic inheritance of DNA methylation.

Mutations of optineurin in amyotrophic lateral sclerosis

Abstract: Amyotrophic lateral sclerosis (ALS) has its onset in middle age and is a progressive disorder characterized by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord. Most cases of ALS are sporadic, but about 10% are familial. Genes known to cause classic familial ALS (FALS) are superoxide dismutase 1 (SOD1), ANG encoding angiogenin, TARDP encoding transactive response (TAR) DNA-binding protein TDP-43 (ref. 4) and fused in sarcoma/translated in liposarcoma (FUS, also known as TLS). However, these genetic defects occur in only about 20-30% of cases of FALS, and most genes causing FALS are unknown. Here we show that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma (POAG), in patients with ALS. We found three types of mutation of OPTN: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Analysis of cell transfection showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B (NF-kappaB), and the E478G mutation revealed a cytoplasmic distribution different from that of the wild type or a POAG mutation. A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic inclusions. Furthermore, TDP-43- or SOD1-positive inclusions of sporadic and SOD1 cases of ALS were also noticeably immunolabelled by anti-OPTN antibodies. Our findings strongly suggest that OPTN is involved in the pathogenesis of ALS. They also indicate that NF-kappaB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder.

Shear bands in metallic glasses

Abstract: Shear-banding is a ubiquitous plastic-deformation mode in materials. In metallic glasses, shear bands are particularly important as they play the decisive role in controlling plasticity and failure at room temperature. While there have been several reviews on the general mechanical properties of metallic glasses, a pressing need remains for an overview focused exclusively on shear bands, which have received tremendous attention in the past several years. This article attempts to provide a comprehensive and up-to-date review on the rapid progress achieved very recently on this subject. We describe the shear bands from the inside out, and treat key materials-science issues of general interest, including the initiation of shear localization starting from shear transformations, the temperature and velocity reached in the propagating or sliding band, the structural evolution inside the shear-band material, and the parameters that strongly influence shear-banding. Several new discoveries and concepts, such as stick-slip cold shear-banding and strength/plasticity enhancement at sub-micrometer sample sizes, will also be highlighted. The understanding built-up from these accounts will be used to explain the successful control of shear bands achieved so far in the laboratory. The review also identifies a number of key remaining questions to be answered, and presents an outlook for the field.

High Efficiency of Dye-Sensitized Solar Cells Based on Metal-Free Indoline Dyes

Abstract: We now report metal-free organic dyes having a new type of indoline structure, which exhibits high efficiencies in dye-sensitized solar cells. The solar energy to current conversion efficiencies with the new indoline dye was 6.51%. Under the same conditions, the N3 dye was 7.89% and the N719 dye was 8.26%. The new indoline dye was optimized for the amount of 4-tert-butyl pyridine in the electrolyte and cholic acid as a coadsorbent. Subsequently, the solar energy to current conversion efficiencies reached 8.00%. This value was the highest obtained efficiency for dye-sensitized solar cells based on metal-free organic dyes without an antireflection layer.