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Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered “housekeeping” genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa. We performed RNA Sequencing on paired metastatic/non‐metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient‐derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing. Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non‐metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse‐free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro‐inflammatory cytokine expression in PCa. Our results demonstrate that SNORA55 up‐regulation predicts PCa progression and that silencing this non‐coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target., Highlights The role of small nucleolar RNAs (SnoRNAs) in prostate cancer progression has been scarcely investigated.We analyzed the transcriptome of patient‐derived prostate cancer xenografts.Our analysis revealed that SNORA55 is up‐regulated in prostate cancer and associated with worse prognosis.SNORA55 inhibition impaired prostate cancer cell growth and metastatic potential.Pathway analysis revealed that SNORA55 interacts with pro‐oncogenic and inflammatory pathways.

Detection of Shiga toxins (Stx) is important for accurate diagnosis of Enterohemorrhagic Escherichia coli infection. In this study, we quantitatively analyzed Stx protein in nine patients’ stool during an outbreak that occurred in Japan. Highly sensitive immunoassay (bead enzyme-linked immunosorbent assay (bead-ELISA)) revealed that the concentrations of toxins in stool of patients ranged from 0.71 to 10.44 ng/mL for Stx1 and 2.75 to 51.61 ng/mL for Stx2. To our knowledge, this is the first report that reveals the range of Stx protein concentrations in human stools.

Plants have evolved various mechanisms that protect against the harmful effects of UV-B radiation (280–315 nm) on growth and development. Cyclobutane pyrimidine dimer (CPD) photolyase, the repair enzyme for UV-B-induced CPDs, is essential for protecting cells from UV-B radiation. Expression of the CPD photolyase gene (PHR) is controlled by light with various wavelengths including UV-B, but the mechanisms of this regulation remain poorly understood. In this study, we investigated the regulation of PHR expression by light with various wavelengths, in particular low-fluence UV-B radiation (280 nm, 0.2 µmol m–2 s –1), in Arabidopsis thaliana seedlings grown under light–dark cycles for 7 d and then adapted to the dark for 3 d. Low-fluence UV-B radiation induced CPDs but not reactive oxygen species. AtPHR expression was effectively induced by UV-B, UV-A (375 nm) and blue light. Expression induced by UV-A and blue light was predominantly regulated by the cryptochrome-dependent pathway, whereas phytochromes A and B played a minor but noticeable role. Expression induced by UV-B was predominantly regulated by the UVR8-dependent pathway. AtPHR expression was also mediated by a UVR8-independent pathway, which is correlated with CPD accumulation induced by UV-B radiation. These results indicate that Arabidopsis has evolved diverse mechanisms to regulate CPD photolyase expression by multiple photoreceptor signaling pathways, including UVR8-dependent and -independent pathways, as protection against harmful effects of UV-B radiation.

Six types of poly(2-methoxyethyl acrylate) (PMEA) analogues were synthesized and the water structure in the hydrated polymers was characterized using differential scanning calorimetry (DSC). The hydrated PMEA analogues exhibited the different amounts of intermediate water. Non-thrombogenicity evaluation was performed on PMEA analogues for platelet adhesion and protein adsorption. Platelet adhesion was suppressed on PMEA analogues. In addition, the protein adsorption and deformation were suppressed by increasing the amount of intermediate water. This study demonstrates that the amount of intermediate water might play a key role in expressing the blood compatibility of polymeric materials.

The purpose of this study is to virtualize draping which is one of the methods to design paper patterns for clothing. It takes time and costs to make made-to-order clothing by draping method. If draping is virtualized, the processes to make made-to-order clothing become much more efficient. In our study, the components of the method such as cloth, hand and dress form are modeled. The cloth is modeled mechanically, and its dynamic shape is numerically calculated. Hand, also modeled, a sensor detects the motion of the hand or fingers in the real world, the data of the motion is transferred to a computer and the motion is reflected to the hand model. The dress form is also modeled as the basis to apply the cloth model to the surface of the dress form model. The intrusions of an element into another element are prevented by the detection and reaction of the collisions between those elements. The user of the system can manipulate the cloth model in the virtual world by moving hand or fingers in the real world. We are constructing a system in virtual environment. In the environment, the image of the real world is also projected. We are trying to superimpose virtual object on real object to improve the workability of the system.

SUMMARYA large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157 occurred in Japan in April 2011. We conducted an unmatched case-control study and trace-back investigation to determine the source of EHEC O111 infection and risk factors for severe complications. Pulsed-field gel electrophoresis was performed to help define cases. A total of 86 individuals met the case definition. Of these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute encephalopathy, and 6% died. Illness was significantly associated with eating the raw beef dish yukhoe (odds ratio 19·64, 95% confidence interval 7·03–54·83), the likely food vehicle. EHEC O111 and its closely related stx-negative variants were found in the beef. HUS occurred most frequently in individuals aged 5–9 years, and this age group was significantly associated with acute encephalopathy. The prevalence of HUS and acute encephalopathy was higher than in previous non-O157-related outbreaks, indicating a high risk of severe complications.

We previously developed a multiplex real-time PCR assay (Rapid Foodborne Bacterial Screening 24 ver.5, [RFBS24 ver.5]) for simultaneous detection of 24 foodborne bacterial targets. Here, to overcome the discrepancy of the results from RFBS24 ver.5 and bacterial culture methods (BC), we analyzed 246 human clinical samples from 49 gastroenteritis outbreaks using RFBS24 ver.5 and evaluated the correlation between the cycle threshold (CT) value of RFBS24 ver.5 and the BC results. The results showed that the RFBS24 ver.5 was more sensitive than BC for Campylobacter jejuni and Escherichia coli harboring astA or eae, with positive predictive values (PPV) of 45.5-87.0% and a kappa coefficient (KC) of 0.60-0.92, respectively. The CTs were significantly different between BC-positive and -negative samples (p ＜ 0.01). All RFBS24 ver.5-positive samples were BC-positive under the lower confidence interval (CI) limit of 95% or 99% for the CT of the BC-negative samples. We set the 95% or 99% CI lower limit to the determination CT (d-CT) to discriminate for assured BC-positive results (d-CTs: 27.42-30.86), and subsequently the PPVs (94.7%-100.0%) and KCs (0.89-0.95) of the 3 targets were increased. Together, we concluded that the implication of a d-CT-based approach would be a valuable tool for rapid and accurate diagnoses using the RFBS24 ver.5 system.

Multidrug-resistant (MDR) Acinetobacter spp. have been globally disseminated in association with the successful clonal lineage Acinetobacter baumannii international clone II (IC II). Because the prevalence of MDR Acinetobacter spp. in Japan remains very low, we characterized all Acinetobacter spp. ( n = 866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology of Acinetobacter spp. The most prevalent species was A. baumannii ( n = 645; 74.5%), with A. baumannii IC II ( n = 245) accounting for 28.3% of the total. Meropenem-resistant isolates accounted for 2.0% ( n = 17) and carried IS Aba1-bla OXA-23-like ( n = 10), bla IMP ( n = 4), or IS Aba1-bla OXA-51-like ( n = 3). Multilocus sequence typing of 110 representative A. baumannii isolates revealed the considerable prevalence of domestic sequence types (STs). A. baumannii IC II isolates were divided into the domestic sequence type 469 (ST469) ( n = 18) and the globally disseminated STs ST208 ( n = 14) and ST219 ( n = 4). ST469 isolates were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced the intrinsic AmpC β-lactamase. A. baumannii IC II and some A. baumannii non-IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone resistance. This study revealed that carbapenem-susceptible A. baumannii IC II was moderately disseminated in Japan. The low prevalence of acquired carbapenemase genes and presence of domestic STs could contribute to the low prevalence of MDR A. baumannii . A similar epidemiology might have appeared before the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone resistance associated with A. baumannii IC II may provide insight into the significance of A. baumannii epidemic clones.

Cupriavidus sp. D384 was isolated from forest soil in Japan and is known to utilize caffeine as a sole source of carbon and energy. We report here the 6,835,230-bp genome sequence for this strain, which contains 6,116 predicted coding sequences, including gene operon for alkaloid degradation.

Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation. Mice with osteoclast-specific Fbw7 ablation revealed osteoporotic phenotypes reminiscent of HCS, due to elevated Notch2 signaling. Importantly, administration of Notch inhibitors in Fbw7 conditional knockout mice alleviated progressive bone resorption. These findings highlight the molecular basis of HCS pathogenesis and provide clinical insights into potential targeted therapeutic strategies for skeletal disorders associated with the aberrant FBW7/NOTCH2 pathway as observed in patients with HCS.

東京電力ホールディングス(東京電力)福島第一原子力発電所において採取された汚染水(滞留水, 処理水)、汚染水処理二次廃棄物、瓦礫、土壌が分析され、放射性核種濃度等の分析データが報告されている。そこで、東京電力, 日本原子力研究開発機構, 国際廃炉研究開発機構により2016年3月末までに公開されたデータを収集し、データ集としてとりまとめた。また分析試料についての情報、分析により得られた放射性核種濃度等の値を表としてまとめるとともに、主な放射性核種濃度の時間変化を表す図を作成して収録した。電子情報として英訳と収録した分析データを提供する。, At Fukushima Daiichi Nuclear Power Station owned by Tokyo Electric Power Company Holdings, Incorporated (TEPCO), contaminated water (accumulated, treated) secondary waste from water treatment, rubble and soil were collected and analyzed. The data already opened to public was collected as this report. The analytical data reported by TEPCO, Japan Atomic Energy Agency and International Research Institute for Nuclear Decommissioning until the end of March, 2016, was collected. Information on the samples and values of radioactive nuclide concentration and others were tabulated, besides figures, which show change in radioactive nuclide concentration for major nuclides, are contained. And, English translation and the collected data are provided as electric data.

In April and May 2011, there was a serious food-poisoning outbreak in Japan caused by enterohemorrhagic Escherichia coli (EHEC) strains O111:H8 and O157:H7 from raw beef dishes at branches of a barbecue restaurant. This outbreak involved 181 infected patients, including 34 hemolytic-uremic syndrome (HUS) cases (19%). Among the 34 HUS patients, 21 developed acute encephalopathy (AE) and 5 died. Patient stool specimens yielded E. coli O111 and O157 strains. We also detected both EHEC O111 stx 2 and stx -negative E. coli O111 strains in a stock of meat block from the restaurant. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analysis (MLVA) showed that the stx -negative E. coli O111 isolates were closely related to EHEC O111 stx 2 isolates. Although the EHEC O157 strains had diverse stx gene profiles ( stx 1 , stx 2 , and stx 1 stx 2 ), the PFGE and MLVA analyses indicated that these isolates originated from a single clone. Deletion of the Stx2-converting prophage from the EHEC O111 stx 2 isolates was frequently observed during in vitro growth, suggesting that strain conversion from an EHEC O111 stx 2 to an stx -negative strain may have occurred during infection.

Various research groups have attempted to grow fresh, histologically intact human prostate cancer tissues in immunodeficient mice. Unfortunately, grafting of such tissues to the sub-cutaneous compartment was found to be associated with low engraftment rates. Furthermore, xenografts could only be established using high-grade, advanced stage, but not low- or moderate-grade prostate cancer tissues.This paper describes methods for xenografting both benign and malignant human prostate tissue to severe combined immunodeficient (SCID) mice. We examine the efficiency and histopathologic consequences of grafting to the sub-cutaneous, sub-renal capsule, and prostatic orthotopic sites.Sub-renal capsule grafting was most efficient in terms of take rate (90%) for both benign and malignant tissue. Orthotopic grafts consistently exhibited the best histopathologic differentiation, although good differentiation with continued expression of androgen receptors (AR) and PSA was also seen in the sub-renal capsule site. Sub-cutaneous grafting resulted in low take rates and the lowest level of histodifferentiation in surviving grafts. Grafted benign tissues in all sites appropriately expressed AR, PSA, cytokeratins 8, 18, and 14 as well as p63; carcinoma tissues did not express the basal cell markers. Grafting of tissues to castrated hosts did not affect the graft take rates (but was not practical in the case of the orthotopic site). Grafting followed by host castration resulted in epithelial regression with loss PSA and reduced AR expression at all three sites.These data suggest that sub-renal capsule and orthotopic grafting of human prostate tissue can be used for many basic scientific and translational studies.

Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant