Heterologous and High Production of Ergothioneine in Escherichia coli

Ergothioneine (ERG) is a histidine-derived thiol compound suggested to function as an antioxidant and cytoprotectant in humans. Therefore, experimental trials have been conducted applying ERG from mushrooms in dietary supplements and as a cosmetic additive. However, this method of producing ERG is expensive; therefore, alternative methods for ERG supply are required. Five Mycobacterium smegmatis genes, egtABCDE, have been confirmed to be responsible for ERG biosynthesis. This enabled us to develop practical fermentative ERG production by microorganisms. In this study, we carried out heterologous and high-level production of ERG in Escherichia coli using the egt genes from M. smegmatis. By high production of each of the Egt enzymes and elimination of bottlenecks in the substrate supply, we succeeded in constructing a production system that yielded 24 mg/L (104 μM) secreted ERG

内視鏡的ドレナージが有効であった胃壁膿瘍を合併した胃迷入膵の１例

　症例は30歳代女性．３日前から心窩部痛が出現し，徐々に増悪してきたため当院を受診した．血液検査でWBC 15,120/μl，CRP 2.95mg/dl と炎症反応上昇を認め，腹部超音波検査で胃幽門前庭部前壁に約3.5cm の粘膜下腫瘍様隆起を認めた．腫瘍内部はechogenic particles の混在する液体の貯留を認めた．腹部造影CT 検査では，胃前庭部から胃体部前壁にリング状の造影効果を伴う著明な壁肥厚を認めた．以上より胃壁膿瘍と診断した．胃前庭部前壁の弾性硬のやや発赤した粘膜下腫瘍様隆起に対して，超音波内視鏡下穿刺術（EUS-FNA）を行った．粘稠な白色液体の流出を認め，膿瘍を示唆する所見であった．絶食・点滴・抗生剤投与による保存的加療を施行後，速やかに腹部症状は消失し，EUS-FNA 施行後５日目に退院した．４か月後，病変は上部内視鏡検査で頂部に陥凹を有する腫瘍に形態変化を認め，さらに縮小傾向であった．また，腹部超音波検査では粘膜下層内に約５mm 大の嚢胞性領域とそれに接する約４mm 大の境界不明瞭な低エコー域，不整な固有筋層の肥厚を認め，胃迷入膵の所見であった．以上より，胃壁膿瘍を合併した胃迷入膵と診断した．現在，再発なく当科で経過観察中である．胃壁膿瘍を合併した胃迷入膵の報告は非常に稀であり，貴重な症例と考えられた．　Here, we report a case of gastric wall abscess in aberrant pancreas. A 30-yearold woman visited our hospital for epigastric pain. Routine hematological examination showed increased white blood cell count and biochemical tests revealed elevated C reactive protein levels. Abdominal ultrasound revealed a submucosal tumor that appeared as a hypoechoic heterogenous mass in the stomach. Abdominal computed tomography revealed a thickened gastric wall with a low-density area. This mass was diagnosed as a gastric wall abscess, which was treated with endoscopic ultrasound-guided fine needle aspiration and conservative therapy with antibiotics. The patient’s pain resolved after the treatment. Four months after the episode, follow-up examinations showed that the submucosal tumor had changed to a small submucosal mass with depression. This lesion was diagnosed as an aberrant pancreas. Thus, the final diagnosis was a gastric wall abscess in the aberrant pancreas. This patient was followed up for one year following this episode with no incidence of recurrence

アブラナゾク フクニバイタイ シヨクブツ ノ ジユフン セイブツガクテキ ケンキユウ

筑波大学農学博士学位論文・昭和63年3月25日授与 (甲第513号

Abstract Puzzle Generators and Symmetric Puzzle Layout 1

We present two abstract models of puzzles, permutation puzzles and cyclic puzzles, which can be modelled as puzzle graphs. Based on these models, we implement two puzzle generators and produce various layouts of the puzzles using graph drawing algorithms. Using these puzzle generators we can create new puzzles. Further, we can create new user interfaces of a puzzle by applying different layout algorithms. We implement a method for constructing symmetric layouts of puzzles, as symmetry is the most important aesthetic criteria for the puzzle layout

Reduction of butyric acid-producing bacteria in the ileal mucosa-associated microbiota is associated with the history of abdominal surgery in patients with Crohn’s disease

ABSTRACTFecal microbiota is a significant factor determining the cause, course, and prognosis of Crohn’s disease (CD). However, the factors affecting mucosa-associated microbiota (MAM) remain unclear. This retrospective study examined the differences in ileal MAM between CD patients and healthy controls and investigated the factors affecting MAM in CD patients to clarify potential therapeutic targets. Ileal MAM was obtained using brush forceps during endoscopic examination from 23 healthy controls and 32 CD patients (most were in remission). The samples’ microbiota was profiled using the Illumina MiSeq platform. Compared to controls, CD patients had significantly reduced α-diversity in the ileum and a difference in β-diversity. The abundance of butyric acid-producing bacteria in the ileal MAM was significantly lower in CD patients with a history of abdominal surgery than in those without. Because butyric acid is a major energy source in the intestinal epithelium, its metabolism via β-oxidation increases oxygen consumption in epithelial cells, reducing oxygen concentration in the intestinal lumen and increasing the abundance of obligate anaerobic bacteria. The suppression of obligate anaerobes in CD patients caused an overgrowth of facultative anaerobes. Summarily, reducing the abundance of butyric acid-producing bacteria in the ileal MAM may play an important role in CD pathophysiology

Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression

Summary: Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification. : Kondo et al. find that extracellular acidic pH induces different cellular responses than hypoxia and nutrient starvation. SREBP2 is a key transcriptional regulator of cholesterol biosynthetic genes and ACSS2 in response to extracellular acidification. SREBP2 target genes increase tumor growth in low pH and correlate with decreased survival in patients. Keywords: epigenetics, extracellular low pH, sterol regulatory element-binding protein 2, acyl-CoA synthetase short-chain family member 2, cancer metabolism, tumor microenvironment, nutrient starvation, hypoxia, lacat