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\"Ninja Attack! introduces dozens of unforgettable real-life ninja straight out of the annals of Japanese history--many of whom are all but unknown outside their home country. Ninja masters. Solo assassins and operatives. Femme fatales as deadly as they were sexy. Swordfighters out of legend. And the Shogun and warlords who commanded them. Each individual is profiled with a full-page manga-style drawing and a dossier brimming with top-secret information, including photos, anecdotes, and dramatic stories of the individuals in action. The book covers ninja clothing styles, the types of weapons that were used, ninja tools, ninja tricks of the trade, and the basics of the ninja diet. It also includes a do-it-yourself tour of ninja related spots in modern Tokyo. Ninja Attack! is the product of years of research, and the result is engaging and fun for all. It's everything you always wanted to know about ninja but were too afraid you'd get a shuriken in the eye to ask\"-- Provided by publisher.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer . However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

Spatial transcriptomics is useful for understanding the molecular organization of a tissue and providing insights into cellular function in a morphological context. In order to obtain reproducible results in spatial transcriptomics, we have to maintain tissue morphology and RNA molecule stability during the image acquisition and biomolecule collection processes. Here, we developed a tissue processing method for robust and reproducible RNA-seq from tissue microdissection samples. In this method, we suppressed RNA degradation in fresh-frozen tissue specimens by dehydration fixation and effectively collected a small amount of RNA molecules from microdissection samples by magnetic beads. We demonstrated the spatial transcriptome analysis of the mouse liver and brain in serial microdissection samples (100 μm in a diameter and 10 μm in thickness) produced by a microdissection punching system. Using our method, we could prevent RNA degradation at room temperature and effectively produce a sequencing library with Smart-seq2. This resulted in reproducible sequence read mapping in exon regions and the detection of more than 2000 genes compared to non-fixed samples in the RNA-seq analysis. Our method would be applied to various transcriptome analyses, providing the information for region specific gene expression in tissue specimens.

Gene expression analysis at the single-cell level by next generation sequencing has revealed the existence of clonal dissemination and microheterogeneity in cancer metastasis. The current spatial analysis technologies can elucidate the heterogeneity of cell-cell interactions in situ. To reveal the regional and expressional heterogeneity in primary tumors and metastases, we performed transcriptomic analysis of microtissues dissected from a triple-negative breast cancer (TNBC) cell line MDA-MB-231 xenograft model with our automated tissue microdissection punching technology. This multiple-microtissue transcriptome analysis revealed three cancer cell-type clusters in the primary tumor and axillary lymph node metastasis, two of which were cancer stem cell (CSC)-like clusters (CD44/MYC-high, HMGA1-high). Reanalysis of public single-cell RNA-seq (scRNA-seq) datasets confirmed that the two CSC-like populations existed both in TNBC xenograft models and TNBC patients. The diversity of these multiple CSC-like populations may cause differential anticancer drug resistance, increasing the difficulty of curing this cancer.

In invertebrates inhabiting hydrothermal vent areas, hypotaurine, a precursor of taurine, is thought to mitigate the toxicity of hydrogen sulfide in vent fluids. Information about hypotaurine synthesis pathways in invertebrates is limited, although two pathways, the cysteamine [2-aminoethanethiol (AET)] pathway and the cysteine sulfinate (CSA) pathway are known in mammals. In this study, we cloned a cDNA encoding AET dioxygenase (ADO), the central enzyme of the AET pathway, from the vent mussel Bathymodiolus septemdierum . In the encoded protein ( Bs ADO), functionally important residues, including metal-binding histidines, are conserved. In maximum likelihood phylogenetic analysis, Bs ADO clustered with ADOs of other invertebrates. By reverse transcription PCR, BsADO mRNA was detected in all tissues examined at similar levels, suggesting that its function is distinct from that of the CSA pathway, predominantly expressed in the gill. Bs ADO with a His tag, expressed in Escherichia coli in the presence of Fe 2+ , converted AET to hypotaurine, but Bs ADO expressed in the absence of iron exhibited lower activity. Bs ADO was active from pH 8 to 11, and from 0 °C to 37 °C, with a peak at 20 °C. This is the first functional characterization of ADO in marine invertebrates.

Genetic Variation in the Gene Encoding Adiponectin Is Associated With an Increased Risk of Type 2 Diabetes in the Japanese Population Kazuo Hara 1 2 3 , Philippe Boutin 4 , Yasumichi Mori 1 4 , Kazuyuki Tobe 1 2 , Christian Dina 4 , Kazuki Yasuda 5 , Toshimasa Yamauchi 1 2 , Shuichi Otabe 6 , Terumasa Okada 1 5 , Kazuhiro Eto 1 2 , Hiroko Kadowaki 4 , Ryoko Hagura 4 , Yasuo Akanuma 2 4 , Yoshio Yazaki 5 , Ryozo Nagai 7 , Matsuo Taniyama 8 , Koichi Matsubara 9 , Madoka Yoda 10 , Yasuko Nakano 10 , Satoshi Kimura 1 , Motowo Tomita 10 , Satoshi Kimura 1 , Chikako Ito 11 , Philippe Froguel 4 and Takashi Kadowaki 1 2 1 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 2 CREST, Japan Science and Technology Corporation (JST), Tokyo, Japan 3 Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan 4 Institute of Biology-Centre National de la Recherche Scientifique (CNRS) 8090, Institute Pasteur de Lille, Lille, France 5 Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo, Japan 6 Department of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, Japan 7 Department of Cardiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 8 3rd Department of Internal Medicine, Showa University, Tokyo, Japan 9 Chugai Diagnostics Science, Tokyo, Japan 10 Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan 11 Hiroshima Atomic Bomb Casualty Council Health Management Center, Hiroshima, Japan Abstract An adipocyte-derived peptide, adiponectin (also known as GBP28), is decreased in subjects with type 2 diabetes. Recent genome-wide scans have mapped a diabetes susceptibility locus to chromosome 3q27 , where the adiponectin gene ( APM1 ) is located. Herein, we present evidence of an association between frequent single nucleotide polymorphisms at positions 45 and 276 in the adiponectin gene and type 2 diabetes ( P = 0.003 and P = 0.002, respectively). Subjects with the G/G genotype at position 45 or the G/G genotype at position 276 had a significantly increased risk of type 2 diabetes (odds ratio 1.70 [95% CI 1.09–2.65] and 2.16 [1.22–3.95], respectively) compared with those having the T/T genotype at positions 45 and 276, respectively. In addition, the subjects with the G/G genotype at position 276 had a higher insulin resistance index than those with the T/T genotype (1.61 ± 0.05 vs. 1.19 ± 0.12, P = 0.001). The G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 ± 0.85 μg/ml, G/T: 13.7 ± 0.87 μg/ml, T/T: 16.6 ± 2.24 μg/ml, P = 0.01) in subjects with higher BMIs. Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes. Footnotes Address correspondence and reprint requests to Takashi Kadowaki, Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: kadowaki-3im{at}h.u-tokyo.ac.jp . Received for publication 16 February 2001 and accepted in revised form 26 October 2001. Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org . EH, Estimation Haplotype; HOMA, homeostasis model assessment; HOMA-IR, HOMA of insulin resistance; OR, odds ratio; SNP, single nucleotide polymorphism.

Slow-motion training, an exercise marked by extremely slow movements, yields a training effect like that of a highly intense training, even when the applied load is small. This study evaluated the effects of low-intensity bodyweight training with slow movement on motor function in frail, elderly patients. Ninety-seven elderly men and women aged 65 years or older, whose level of nursing care was classified as either support required (1 and 2) or long-term care required (care level 1 and 2), volunteered to participate. Two facilities were used. Participants in the first facility used low-intensity bodyweight training with slow movement (the LST group, n = 65), and participants in another facility used machine training (the control group, n = 31). Exercises were conducted for 3 months, once or twice a week, depending on the required level of nursing care. Changes in motor function were examined. Post-exercise measurements showed significant improvements from the pre-exercise levels after 3 months, based on the results of the Timed Up and Go test (p = 0.0263) and chair-stand test (p = 0.0016) in the low-intensity exercise with slow movement and tonic force generation (LST) group. Although the ability to stand on one leg with eyes open tended to improve, no significant change was found (p = 0.0964). We confirmed that carrying out LST bodyweight training for 3 months led to improvements in ambulatory function and lower-limb muscle strength. In this way, it is possible that LST training performed by holding a bar or by staying seated on a chair contributes to improved motor function in elderly patients within a short time. UMIN000030853 . Registered 17 January 2018. (retrospectively registered).

Background The baseline data obtained in the CKD-JAC demonstrated that insufficient treatment was being provided for renal anemia by institutions specializing in renal disease. The objective of this study was to investigate the status of treatment for renal anemia, including renal/cardiovascular outcomes and mortality, at regional medical facilities since the development of long-acting erythropoiesis-stimulating agents (LA-ESA). Methods Non-dialysis outpatients with chronic kidney disease and renal anemia were eligible. Anemia was treated based on the clinical condition of each patient and targeted hemoglobin (Hb) levels. Results A total of 283 patients from 21 institutions were enrolled and followed up for a maximum of 3 years. A doubling of the serum creatinine level was observed in 89 patients, and renal replacement therapy was initiated in 57 patients. Multivariate Cox regression analysis revealed that a lower mean Hb level (mHb) and receiving fewer frequency of ESA during the follow-up period were independent determinants of the composite renal outcome and overall mortality. During the follow-up period, the percentages of patients with mHb of 10–10.9 g/dL and ≥ 11 g/dL were increased. Similar trends were seen regardless of whether the patients were treated by nephrologists or non-nephrologists. The frequency of ESA treatment was increased among the patients treated by non-nephrologists; however, it was much lower than nephrologists. Conclusion This study demonstrated that, in the era of LA-ESA treatment, higher Hb levels are associated with reduced composite renal outcomes at regional medical facilities. The importance of renal anemia management should be highlighted, even among non-nephrologists.

Gene expression analysis at the single-cell level by next generation sequencing has revealed the existence of clonal dissemination and microheterogeneity in cancer metastasis. The current spatial analysis technologies can elucidate the heterogeneity of cell-cell interactions in situ. To reveal the regional and expressional heterogeneity in primary tumors and metastases, we performed transcriptomic analysis of microtissues dissected from a triple-negative breast cancer (TNBC) cell line MDA-MB-231 xenograft model with our automated tissue microdissection punching technology. This multiple-microtissue transcriptome analysis revealed three cancer cell-type clusters in the primary tumor and axillary lymph node metastasis, two of which were cancer stem cell (CSC)-like clusters (CD44/MYC-high, HMGA1-high). Reanalysis of public single-cell RNA-seq (scRNA-seq) datasets confirmed that the two CSC-like populations existed both in TNBC xenograft models and TNBC patients. In addition, the gene signature of the HMGA1-high CSC-like cluster has the potential to serve as a novel biomarker for diagnosis. The diversity of these multiple CSC-like populations may cause differential anticancer drug resistance, increasing the difficulty of curing this cancer. Competing Interest Statement The authors have declared no competing interest. Footnotes * In this revision, we focused on the existence of two cancer stem cell-like populations in TNBC xenografts and patients. Following the comments, we performed the extraction of DEGs with significant threshold; therefore, we revised the results of enrichment analysis but it did not influence our main findings.To validate the existence of two types of cancer stem-like cells in TNBC tumors, we performed the additional analyses (reanalysis of public scRNA-seq datasets and immuno-staining of MDA-MB-231 primary tumor). These results verified two cancer stem cell-like populations (HMGA1-high, CD44-high) in MDA-MB-231 xenograft and TNBC patients. We believe that our findings are solid results because the findings were also validated by other methods. * https://github.com/JunNakayama/Spatial-Transcriptomics-of-MDA-MB-231-xenografts