Direct mapping of the spin-filtered surface bands of a three-dimensional quantum spin Hall insulator

Spin-polarized band structure of the three-dimensional quantum spin Hall insulator $\rm Bi_{1-x}Sb_{x}$ (x=0.12-0.13) was fully elucidated by spin-polarized angle-resolved photoemission spectroscopy using a high-yield spin polarimeter equipped with a high-resolution electron spectrometer. Between the two time-reversal-invariant points, $\bar{\varGamma}$ and $\bar{M}$, of the (111) surface Brillouin zone, a spin-up band ($\Sigma_3$ band) was found to cross the Fermi energy only once, providing unambiguous evidence for the strong topological insulator phase. The observed spin-polarized band dispersions determine the "mirror chirality" to be -1, which agrees with the theoretical prediction based on first-principles calculations

Characterization of galactose-dependent promoters from an oleaginous fungus Mortierella alpina 1S-4.

An inducible promoter is a useful tool for the controlled expression of a given gene. In this report, we describe galactose-dependent promoters for potential use in an oleaginous fungus Mortierella alpina. We cloned the putative promoter regions of two genes encoding galactose metabolic enzymes, GAL1 and GAL10, from the genome of M. alpina 1S-4. The β-glucuronidase (GUS) reporter gene assay in M. alpina 1S-4 revealed that regulation of these promoters was dependent on the presence of galactose in the medium both with and without other sugars. With the GAL10 promoter, an approximately 50-fold increase of GUS activity was demonstrated by addition of galactose into the culture media at any cultivation phase. The 5' deletion analysis of the GAL10 promoter revealed that a promoter region of over 2, 000 bp length was required for its high-level activity and sufficient inducible response. Significantly, this is the first report of inducible promoters of zygomycetes. The GAL10 promoter will be a valuable tool for gene manipulation in M. alpina 1S-4

Selection and characterization of promoters based on genomic approach for the molecular breeding of oleaginous fungus Mortierella alpina 1S-4.

To express a foreign gene effectively, a good expression system is required. In this study, we investigated various promoters as useful tools for gene manipulation in oleaginous fungus Mortierella alpina 1S-4. We selected and cloned the promoter regions of 28 genes in M. alpina 1S-4 on the basis of expression sequence tag abundance data. The activity of each promoter was evaluated using the β-glucuronidase (GUS) reporter gene. Eight of these promoters were shown to enhance GUS expression more efficiently than a histone promoter, which is conventionally used for the gene manipulation in M. alpina. Especially, the predicted protein 3 and the predicted protein 6 promoters demonstrated approximately fivefold higher activity than the histone promoter. The activity of some promoters changed along with the cultivation phase of M. alpina 1S-4. Seven promoters with constitutive or time-dependent, high-level expression activity were selected, and deletion analysis was carried out to determine the promoter regions required to retain activity. This is the first report of comprehensive promoter analysis based on a genomic approach for M. alpina. The promoters described here will be useful tools for gene manipulation in this strain

DRU classificationに基づく特発性側弯症の適切な観察間隔の設定 多施設研究

Purpose: To determine the capability of the distal radius and ulna (DRU) classification for predicting the scoliosis progression risk within 1 year in patients with adolescent idiopathic scoliosis (AIS) and to develop simple recommendations for follow-up durations. Methods: Medical records of patients with AIS at two tertiary scoliosis referral centers were retrospectively reviewed for their DRU classification and major curve Cobb angles. Baseline DRU grades and Cobb angles with subsequent 1-year follow-up curve magnitudes were studied for scoliosis progression, which was defined as exacerbation of the Cobb angle by ≥ 6°. The relationship between DRU classification and scoliosis progression risk within 1 year was investigated. Patients were divided into three groups according to the Cobb angle (10°-19°, 20°-29°, ≥ 30°). Results: Of the 205 patients with 283 follow-up visits, scoliosis progression occurred in 86 patients (90 follow-up visits). Radius and ulna grades were significantly related to scoliosis progression (p 80% of patients within 1 year. Curve progression was less likely for grades R9 and U7. Most patients with more mature DRU grades did not experience progression, even with Cobb angles ≥ 30°. Conclusion: With R6, R7, and U5, scoliosis may progress within a short period; therefore, careful follow-up with short intervals within 6 months is necessary. R9 and U7 may allow longer 1-year follow-up intervals due to the lower progression risk.博士（医学）・甲第771号・令和3年3月15日© Springer-Verlag GmbH Germany, part of Springer Nature 2020This is a post-peer-review, pre-copyedit version of an article published in European spine journal. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00586-020-06441-4

頚椎症性脊髄症症例における頚椎アライメント評価 : 坐位頚椎レントゲンと立位全脊椎レントゲンは等しく有用か?

Study Design: Retrospective review of medical charts and radiographic data. Objectives: We aimed to clarify the differences in cervical alignment findings between sitting cervical lateral radiographs and standing whole-spine lateral radiographs with clavicle positioning in cervical spondylotic myelopathy (CSM) patients. Methods: We retrospectively evaluated the radiographs of 50 consecutive patients who underwent cervical surgery for CSM in our hospital. Cervical sagittal alignment was evaluated based on the C0-2 angles and C2-7 Gore and Cobb angles. Head position was evaluated in terms of the center of gravity of the head to C7 (CGH-C7) angle and the McGregor angle (ie, the angle between the McGregor line and a horizontal line). The T1-slope was also evaluated. Results: The mean values of the CGH-C7 angle and T1-slope were significantly lower, while the mean value of the McGregor angle was significantly higher on whole-spine lateral radiographs with clavicle positioning than on sitting cervical lateral radiographs. The mean values of the C0-2 and C2-7 angles did not differ significantly between the 2 radiographic positioning approaches. Conclusions: Using whole-spine lateral radiographs with clavicle positioning may result in a significantly lower T1-slope and a posterior tilt of the head. In the absence of a compensatory change in cervical alignment, clavicle positioning may force patients to adopt an upward gazing position of the head. These compensatory mechanisms should be considered while evaluating cervical alignment on whole-spine lateral radiographs with clavicle positioning. Surgical planning should take into account the effect of posture on the radiographic appearance of cervical alignment.博士（医学）・甲第702号・平成31年3月15日© The Author(s) 2018. Creative Commons Non Commercial No Derivs CC BY-NC-ND: This article is distributed under the terms of the Creative Commons Attribution-Non Commercial-NoDerivs 4.0 License (http://www.creativecommons.org/licenses/by-nc-nd/4.0/) which permits non-commercial use, reproduction and distribution of the work as published without adaptation or alteration, without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage)

外側環軸関節の関節症性変化のリスク増加に関連する要因; 後ろ向き研究

Purpose Atlantodens osteoarthritis and atlantoaxial osteoarthritis cause neck pain and suboccipital headaches. Currently, knowledge on the risk factors for atlantoaxial osteoarthritis is lacking. This study aimed to investigate the factors related to the increased risk of atlantoaxial osteoarthritis. Methods We analyzed computed tomography (CT) images of the upper cervical spine of 1266 adult trauma patients for whom upper cervical spine CT was performed at our hospital between 2014 and 2019. The degree of atlantoaxial osteoarthritis was quantified as none-to-mild (not having osteoarthritis) or moderateto- severe (having osteoarthritis). Risk factors associated with atlantoaxial osteoarthritis were identified using univariate and multivariable logistic regression analyses. Results The study group included 69.4% men, and the overall average age of the study population was 54.9 ± 20.4 years. The following factors were independently and significantly associated with atlantoaxial osteoarthritis in the multivariable logistic regression analysis: age in the sixth decade or older (odds ratio [OR], 20.5; 95% confidence interval [CI], 6.2‒67.2, p < 0.001), having calcific synovitis (OR, 4.9; 95% CI, 2.4‒9.9, p < 0.001), women sex (OR, 3.3; 95% CI, 1.9‒5.7, p = 0.002), and not having atlantodens osteoarthritis (OR, 2.1; 95% CI, 1.2‒3.8, p = 0.014). Conclusion In the multivariable logistic regression analysis, age in the sixth decade or older, calcification of the transverse ligament, being women, and not having atlantodens osteoarthritis were found to be significantly associated with atlantoaxial osteoarthritis. Delayed diagnosis and treatment can be avoided by focusing on these risk factors.博士（医学）・甲第873号・令和5年3月15

HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis

白血病を引き起こすタンパク質間相互作用の発見. 京都大学プレスリリース. 2021-08-31.Leukemic oncoproteins cause uncontrolled self-renewal of hematopoietic progenitors by aberrant gene activation, eventually causing leukemia. However, the molecular mechanism underlying aberrant gene activation remains elusive. Here, we showed that leukemic MLL fusion proteins associate with the HBO1 histone acetyltransferase (HAT) complex through their trithorax homology domain 2 (THD2) in various human cell lines. MLL proteins associated with the HBO1 complex through multiple contacts mediated mainly by the ING4/5 and PHF16 subunits in a chromatin-bound context where histone H3 lysine 4 tri-methylation marks were present. Of the many MLL fusions, MLL-ELL particularly depended on the THD2-mediated association with the HBO1 complex for leukemic transformation. The C-terminal portion of ELL provided a binding platform for multiple factors including AF4, EAF1, and p53. MLL-ELL activated gene expression in murine hematopoietic progenitors by loading an AF4/ENL/P-TEFb (AEP) complex onto the target promoters wherein the HBO1 complex promoted the association with AEP complex over EAF1 and p53. Moreover, the NUP98-HBO1 fusion protein exerted its oncogenic properties via interaction with MLL but not its intrinsic HAT activity. Thus, the interaction between the HBO1 complex and MLL is an important nexus in leukemic transformation, which may serve as a therapeutic target for drug development

Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia

The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4-ENL-P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia

骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.博士（医学）・甲第656号・平成28年11月24日© Copyright 2016 American Association of Neurological SurgeonsThe definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250