Hiroyuki Awano

Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center

Recent developments in molecular therapies for Duchenne muscular dystrophy (DMD) demand accurate genetic diagnosis, because therapies are mutation specific. The KUCG (Kobe University Clinical Genetics) database for DMD and Becker muscular dystrophy is a hospital-based database comprising 442 cases. Using a combination of complementary DNA (cDNA) and chromosome analysis in addition to conventional genomic DNA-based method, mutation detection was successfully accomplished in all cases, and the largest mutation database of Japanese dystrophinopathy was established. Among 442 cases, deletions and duplications encompassing one or more exons were identified in 270 (61%) and 38 (9%) cases, respectively. Nucleotide changes leading to nonsense mutations or disrupting a splice site were identified in 69 (16%) or 24 (5%) cases, respectively. Small deletion/insertion mutations were identified in 34 (8%) cases. Remarkably, two retrotransposon insertion events were also identified. Dystrophin cDNA analysis successfully revealed novel transcripts with a pseudoexon created by a single-nucleotide change deep within an intron in four cases. X-chromosome abnormalities were identified in two cases. The reading frame rule was upheld for 93% of deletion and 66% of duplication mutation cases. For the application of molecular therapies, induction of exon skipping was deemed the first priority for dystrophinopathy treatment. At one Japanese referral center, the hospital-based mutation database of the dystrophin gene was for the first time established with the highest levels of quality and patients number.

Mirror-symmetric magneto-optical Kerr rotation using visible light in [(GeTe)2(Sb2Te3)1]n topological superlattices.

Interfacial phase change memory (iPCM), that has a structure of a superlattice made of alternating atomically thin GeTe and Sb2Te3 layers, has recently attracted attention not only due to its superior performance compared to the alloy of the same average composition in terms of energy consumption but also due to its strong response to an external magnetic field (giant magnetoresistance) that has been speculated to arise from switching between topological insulator (RESET) and normal insulator (SET) phases. Here we report magneto-optical Kerr rotation loops in the visible range, that have mirror symmetric resonances with respect to the magnetic field polarity at temperatures above 380 K when the material is in the SET phase that has Kramers-pairs in spin-split bands. We further found that this threshold temperature may be controlled if the sample was cooled in a magnetic field. The observed results open new possibilities for use of iPCM beyond phase-change memory applications.

Direct Observation of Domain Wall Motion Induced by Low-Current Density in TbFeCo Wires

The motion of magnetic domain walls (DWs) in TbFeCo wires induced by low-current density up to 4.97×1010 A/m2 has been directly observed by Kerr polarized optical microscopy. The critical current density slightly increases with wire width, from 4.97×1010 A/m2 for 800-nm-width wires to 6.16×1010 A/m2 for 1500-nm-width wires. DW velocity is estimated to be 28±2 m/s, and mostly independent on the wire width. Increasing current density results in an increase of the wall velocity up to 59±4 m/s. These findings indicate that TbFeCo nanowire is an excellent candidate for low-energy, fast accessing DW-controlled devices.

Current-Induced Domain Wall Motion in Perpendicular Magnetized Tb?Fe?Co Wire with Different Interface Structures

Current-induced domain wall motion has been investigated in perpendicular magnetic anisotropy SiO2/TbFeCo/Pt (asymmetric interface) and Pt/TbFeCo/Pt (symmetric interface) wires. The domain wall is found to be moved in opposite to the electron-flow direction in the asymmetric interface wire whereas it is kept same direction in the symmetric one at room temperature. As an alternative to the conventional spin-transfer torque, the Rashba field at the TbFeCo/Pt interface and the spin Hall current injected from the Pt layer are possibilities of the reversed domain wall motion in an ultrathin magnetic film sandwiched by dissimilar materials.

Small Mutations Detected by Multiplex Ligation–Dependent Probe Amplification of the Dystrophin Gene

Currently, multiplex ligation-dependent probe amplification (MLPA) has been recognized as the most powerful and convenient method to identify exon deletions or duplications in the dystrophin gene, the mutation of which causes Duchenne and Becker muscular dystrophies (DMD/BMD). The mutation diagnosis is easily done by assessing the amounts amplified by MLPA (loss, single, or double). However, an ambiguous amount of amplified product has never been reported. When 77 Japanese DMD/BMD patients were examined by MLPA from MRC-Holland (Amsterdam, The Netherlands), deletions/duplications in the dystrophin gene were identified in 64.8%. Ten male patients showed loss of a single exon by MLPA, but one of them was found to have not an exon deletion, but a four-nucleotide deletion (c.3347-3350delAGAA) within the exon. Remarkably, two patients showed ambiguous amounts of product with less than half of that of a single copy, making the genetic diagnosis impossible. In one patient, a novel single-nucleotide change (c.4303G>T) leading to a nonsense mutation was identified. In another patient, a novel five-nucleotide deletion (c.4536-4540delGAGTG) was identified. It was considered that these two mutations partially disturbed MLPA amplification, resulting in ambiguous amplification. These results show that MLPA can serve as a tool for screening small mutations, as well as for detecting exon deletions or duplications.

0.04 µm Domain Expansion Readout for the Magnetic Amplifiying Magneto Optical System

Read/write characteristics of the magnetic amplifying magneto optical system (MAMMOS) with alternative readout fields such as carrier to noise ratio (C/N), eye pattern, jitter and bit error rate (BER), are investigated with a 640 nm wavelength laser diode and 0.55 numerical aperture of the objective lens. The C/N value of 0.12 µm is 50 dB and is independent of the mark length. A very clear eye pattern was observed. The results show that the jitter value is less than 3% compared with the window width and it is only dependent on the switching speed of the readout field. The error rate is improved by using a thin recording layer of 50 nm in thickness. The minimum domain length which yields a BER of less than 1×10-4 is 0.045 µm (45 nm); the minimum space length is 0.10 µm (100 nm). These results are confirmed at a track pitch of about 0.40 µm. By using a digital versatile disk (DVD) pickup, the areal density can be estimated to be about 23 Gbit/in2 with the user data capacity of 30 GB/120 mmφ. By using a 400 nm blue laser diode, these values are estimated as 59 Gbit/in2 and 77 GB/120 mmφ.

High efficiency of the spin-orbit torques induced domain wall motion in asymmetric interfacial multilayered Tb/Co wires

We investigated current-induced DW motion in asymmetric interfacial multilayered Tb/Co wires for various thicknesses of magnetic and Pt-capping layers. It is found that the driving mechanism for the DW motion changes from interfacial to bulk effects at much thick magnetic layer (up to 19.8 nm). In thin wires, linearly depinning field dependence of critical current density and in-plane field dependence of DW velocity suggest that the extrinsic pinning governs field-induced DW motion and injecting current can be regarded as an effective field. It is expected that the high efficiency of spin-orbit torques in thick magnetic multilayers would have important implication for future spintronic devices based on in-plane current induced-DW motion or switching.

Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA

Non-autonomous retrotransposon-mediated mobilizations of the Alu family are known pathogenic mechanisms of human disease. Here, we report a pathogenic, contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene. In a Japanese Duchenne muscular dystrophy patient, a 330-bp-long de novo insertion was identified in exon 67 of dystrophin. The insertion induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon. The sequence of the insertion had certain characteristics of retrotransposons: an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication. The insertion site matched the consensus recognition sequence for the L1 endonuclease, indicating a retrotransposon-mediated event, although the inserted sequence did not match any known retrotransposons. The origin of the inserted sequence was mapped to a gene-poor region of chromosome 11. The inserted fragment was expressed in multiple human tissue RNAs, indicating that it is a novel transcript. The full length of the transcript was cloned and showed no meaningful protein coding ability.

Modulation length dependence of magneto-optical Kerr effect in Fe/Cu multilayer films

A relation between modulation length and wavelength dependence of polar magneto-optical Kerr rotation θ K in Fe/Cu compositionally modulated multilayer films has been investigated. A new peak of θ K appears at about λ = 560nm, corresponding to the absorption edge of Cu metal, and becomes large with the increase of modulation length D. The θ K peak moves towards longer wavelength side with increasing thickness ratio of Fe/Cu. There are optimum values of Fe/Cu thickness ratio and modulation length for the enhancement of θ K .

Reversal of Domain Wall Motion in Perpendicularly Magnetized TbFeCo-Based Wires: Size Dependence

Current-induced domain wall (DW) motion has been investigated in interfacial asymmetric SiO2/TbFeCo/Pt wires with different wire widths and thicknesses. The reversed DW motion was observed in these interfacial asymmetric wires at zero field and room temperature. This reversal of DW motion was attributed to the structural inversion asymmetry-induced spin–orbit torques (SOTs) from the Pt/TbFeCo interface and Pt layer of the wire. We found that the reversed DW velocity strongly depends on the size of wires, typically large for thin and narrow wires, suggesting that the SOTs effectively enhance the reversed DW velocity in these asymmetric TbFeCo wires.