Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling

<p>Abstract</p> <p>Background</p> <p><it>O</it>-fucosyltransferase1 (OFUT1) is a conserved ER protein essential for Notch signaling. OFUT1 glycosylates EGF domains, which can then be further modified by the <it>N</it>-acetylglucosaminyltransferase Fringe. OFUT1 also possesses a chaperone activity that promotes the folding and secretion of Notch. Here, we investigate the respective contributions of these activities to Notch signaling in <it>Drosophila</it>.</p> <p>Results</p> <p>We show that expression of an isoform lacking fucosyltransferase activity, <it>Ofut1</it>^{<it>R</it>245<it>A</it>}, rescues the requirement for <it>Ofut1 </it>in embryonic neurogenesis. Lack of requirement for <it>O</it>-fucosylation is further supported by the absence of embryonic phenotypes in <it>Gmd </it>mutants, which lack all forms of fucosylation. Requirements for <it>O</it>-fucose during imaginal development were evaluated by characterizing clones of cells expressing only <it>Ofut1</it>^{<it>R</it>245<it>A</it>}. These clones phenocopy <it>fringe </it>mutant clones, indicating that the absence of <it>O</it>-fucose is functionally equivalent to the absence of elongated <it>O</it>-fucose.</p> <p>Conclusion</p> <p>Our results establish that Notch does not need to be <it>O</it>-fucosylated for <it>fringe</it>-independent Notch signaling in <it>Drosophila</it>; the chaperone activity of OFUT1 is sufficient for the generation of functional Notch.</p

Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study.

INTRODUCTION/OBJECTIVES: To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA). METHODS: We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted. RESULTS: Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15-5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32-3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13-10.19 points). CONCLUSIONS: Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA. Key Points • Higher extracellular-to-intracellular water (ECW/ICW) ratios are associated with greater functional disability levels in patients with knee osteoarthritis (OA). • ECW/ICW ratios are useful clinical signs as a biomarker for poor functional abilities in patients with knee OA

大腿骨頭靭帯の組織学的および分子学的特性に関する研究

The ligamentum capitis femoris (LCF) has increased in clinical significance through the development of hip arthroscopy. The histological pathologies and molecular composition of the femoral attachment of the LCF and the degeneration caused by LCF disruption were investigated in the human hip joint. Twenty-four LCFs were retrieved at surgery for femoral neck fracture (age range: 63–87 years). In the “intact” (i.e., intact throughout its length, n = 12) group, the attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in the midsubstance. In contrast, the construction of the attachment in the “disrupted” (i.e., ligament no longer attached to the femoral head, n = 12) group had disappeared. The attachment in the disrupted group was not labeled for type II collagen or aggrecan, while that in the intact group was labeled for types I, II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and versican. The percentage of single-stranded DNA-positive chondrocytes was significantly higher in the disrupted group than in the intact group. We conclude that the femoral attachment of the LCF has a characteristic fibrocartilaginous structure that is likely to adjust to the mechanical load, and suggest that its degeneration is advanced by disruption and should be regarded as a clinical pathology.博士（医学）・乙第1353号・平成27年3月16日© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

A Tutoring for Behavior-Based Recursive Programming

プログラミングを行うためには,プログラムは少なくとも,プログラムの動作について明確に理解しておく必要がある.しかしながら初心者の場合プログラムの個々の命令の振舞いを理解できても,プログラム全体の動作を正しく理解できなかったり,プログラム仕様から動作を想定できない場合がよく見られる.このような初心者を対象とする場合,動作とプログラムコード,動作とプログラム仕様の対応関係について説明することが重要となる.本論文では動作の理解が特に難しい再帰プログラムを対象に,プログラムの動作を介したプログラミングを支援する知的教育システムについて述べる.筆者らは再帰プログラミングのモデルを想定した上で,学習者にとって理解が容易となるようにプログラムの動作を表現し,これをプログラムの振舞いと呼んでいる.本論文ではこの振舞い表現を用いて,再帰プログラムの設計過程および理解過程を支援する方法について論じる.特に,雛形を用いた解法による設計過程の支援ならびに,振舞い表現の可視化による理解過程の支援について述べる.更に振舞い表現の評価実験についても述べる

Error Visualization for Pencil Drawing with Three-Dimensional Model

初心者のための鉛筆デッサンの基礎は，対象を見えたまま正確に描きとる写実であり，獲得が難しい技能である．初心者は自己の写実の誤りに気づくことができない，あるいはデッサン画全体に漠然とした違和感を感じることができても，具体的に写実の何が誤りかを判断できず，同じ誤りを繰り返す．反復練習を指導する教師は，写実の誤りを理解させるため，描く対象と異なった立体物をイメージさせるたとえ（比喩）を用いる．学習者は比喩説明を聞く過程で徐々に，明らかに異なるイメージの写実と感じるようになり，ついに自己の写実の誤りに気づくと考えられる．本論文は学習者の鉛筆デッサン画像に含まれる写実の誤りを顕在化した三次元モデルを構築する手法を検討する．本手法は誤った写実による1 枚の画像から，誤りを映し出し，かつ直感的に不自然さを感じさせる三次元モデルを構築する．写実の8 種の誤りを対象に，デッサン画像の誤りを特徴づける15個の特徴量を用いて三次元モデルのスケーリング変換を定義した．三次元モデルを表示する顕在化ツールを実装した．学習者が本ツールを用いることで，鉛筆デッサンに含まれる写実の誤りに気づきやすくなると期待できる．本研究の一部は文部科学省科学研究補助金基盤研究（B）（2）（課題番号：163000369）による

Hemangiopericytoma in the sacrococcygeal space: a case report

<p>Abstract</p> <p>Introduction</p> <p>A hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.</p> <p>Case presentation</p> <p>We describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.</p> <p>Conclusion</p> <p>A complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.</p

Moderately differentiated colorectal adenocarcinoma as a lymph node metastatic phenotype: comparison with well differentiated counterparts

<p>Abstract</p> <p>Background</p> <p>The differences between the metastatic property of moderately (Mod) and well (Wel) differentiated colorectal adenocarcinoma remain unclear. Since Mod is unable to form complete acini, therefore an epithelial-mesenchymal transition (EMT) can occur in that structure. Herein, we hypothesized that Mod metastasizes more easily than the Wel counterparts.</p> <p>Methods</p> <p>The medical records of 283 consecutive patients with Mod (n = 71) or Wel (n = 212) who underwent surgery were reviewed between January 1, 2001, and December 31, 2003, for actual 5-year overall survival. We examined the differences between the clinicopathological characteristics of the Mod and the Wel groups.</p> <p>Results</p> <p>The lymph node involvement (<it>p </it>< 0.0001), lymphatic permeation, venous permeation, depth of invasion, liver metastasis, and carcinomatous peritonitis were significantly higher in the Mod group in comparison to the Wel group. The independent risk factors by a logistic regression analysis for lymph node involvement were as follows: lymphatic permeation, liver metastasis, and Mod (<it>p </it>= 0.0291, Relative Risk of 1.991: 95% Confidence Interval: 1.073-3.697). A Kaplan-Meier survival curve showed that Mod had a trend towards a poor survival (<it>p </it>= 0.0517).</p> <p>Conclusion</p> <p>Mod metastasizes to the lymph nodes more easily in comparison to Wel. Therefore, patients with Mod may be considered the existence of lymph node involvement.</p

Newly Diagnosed Atrial Fibrillation in Acute Myocardial Infarction

[Background] It remains controversial whether long‐term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. [Methods and Results] The current study population from the CREDO‐Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave‐2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long‐term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow‐up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5‐year incidence of all‐cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P<0.001). The adjusted hazard ratios (HRs) for mortality of newly diagnosed AF and prior AF relative to no AF remained significant with similar magnitude (HR, 1.31; 95% CI, 1.12–1.54; P<0.001, and HR, 1.32; 95% CI, 1.14–1.52; P<0.001, respectively). The cumulative 5‐year incidence of stroke decreased in the order of newly diagnosed AF, prior AF and no AF (15.5%, 12.9%, and 6.3%, respectively, P<0.001). The higher adjusted HRs of both newly diagnosed AF and prior AF relative to no AF were significant for stroke, with a greater risk of newly diagnosed AF than that of prior AF (HR, 2.05; 95% CI, 1.56–2.69; P<0.001, and HR, 1.33; 95% CI, 1.00–1.78; P=0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35–2.22; P<0.001, and HR, 2.23; 95% CI, 1.82–2.74; P<0.001, respectively) and major bleeding (HR, 1.46; 95% CI, 1.23–1.73; P<0.001, and HR, 1.36; 95% CI, 1.15–1.60; P<0.001, respectively). [Conclusions] Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF