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In the Sea of Japan, the mature red snow crab Chionoecetes japonicus is distributed at a depth of 500���2,700 m. However, its planktonic larvae occur at depths shallower than 300 m. To better understand the factors influencing larval dispersal and settlement of the red snow crab in its natural habitat, we tested the effects of temperatures ranging from 1��C to 18��C on the survival, developmental period, and growth of red snow crab zoeal and megalopal larvae. The mean number of days from hatching to second zoeae and megalopae and from megalopae to the first crab instar was significantly shorter at warmer temperatures. Moreover, the relationships between mean temperatures and larval periods were well described by heat summation theory equations and a nonlinear thermodynamic Sharpe-Schoolfield-Ikemoto (SSI) model. The higher survival rate, intrinsic optimum temperatures in the SSI model, and larger carapace width suggested that the optimum temperatures for the development of zoeal and megalopal stages of the red snow crab are 9���10��C and 7���8��C, respectively. A lower optimum temperature in the megalopal stage than in the zoeal stages was considered an adaptation to facilitate deeper vertical distributions in the megalopal stage.

The population structure and demographic history of a pelagic lumpsucker, Aptocyclus ventricosus, were investigated on the basis of sequence variation in the mitochondrial cytochrome b gene (1038 bp). The haplotype network clearly recovered two haplotype groups, consisting of western and eastern North Pacific individuals, except for some specimens collected from offshore of Tohoku, northern Japan. The geographic distribution of haplotypes suggests that the ocean currents in the North Pacific have shaped the population structure of the species after historical vicariant events between the Kuril Islands and Kamchatka Peninsula. In addition, the demographic histories of the two haplotype groups were quite different, suggesting that the western North Pacific group experienced a population expansion starting around 10,000 years ago, while the population size of the eastern North Pacific group has remained more stable.

Background: CCL2 (also known as monocyte chemoattractant protein 1) and CX3CR1 (also known as Fractalkine receptor)-deficient mice have damaged photoreceptors. Objectives: We examined the interaction of SDF1 and CXCR4 on the differentiation of retinal progenitors into rhodopsin-positive photoreceptors. Methods: Cloned retinal progenitors were obtained by Pax6 gene transfection of mouse iPS cells followed by serial dilution. Clones were selected by expression of nestin, Musashi1, Six3, and Chx10 mRNA. Cell surface protein expression was analyzed by flow cytometry. The levels of mRNA and intracellular protein were examined by real-time PCR and immunochemistry, respectively. Transient transfection experiments of retinal progenitors were conducted using a human rhodopsin promoter luciferase plasmid. Results: We selected 10 clones that expressed Six3, Chx10, Crx, Rx1, Nrl, CD73, and rhodopsin mRNA, which, except for rhodopsin, are photoreceptor precursor markers. Clones expressed both CD73 and CXCR4 on the cell surface and differentiated into rhodopsin-positive photoreceptors, which was reinforced by the addition of exogenous SDF1. A CXCR4 inhibitor AMD3100 blocked SDF1-mediated differentiation of progenitors into photoreceptors. SDF1 enhanced human rhodopsin promoter transcription activity, possibly via the NFκB pathway. Addition of SDF1 to the cell culture induced nuclear translocation of NFκB on retinal progenitor cell clones. Neonatal and newborn mouse retinas expressed SDF1 and CXCR4. Cells in the outer nuclear layer where photoreceptors are located expressed CXCR4 at P14 and P56. Cells in the inner nuclear layer expressed SDF1. Conclusions: These findings suggest that retinal progenitor cell differentiation was at least partly regulated by SDF1 and CXCR4 via upregulation of NFκB activity.

An 86-year-old woman’s stool sample was positive for blood. Computed tomography (CT) showed wall thickening of the ascending colon at the hepatic flexure. Colonoscopy showed near-complete obturation by colon cancer. Since she was asymptomatic, elective surgery was planned. Laparoscopic right hemicolectomy was performed. Histopathological examination showed poorly differentiated carcinoma cells proliferating in a solid pattern with marked lymphocyte infiltration. The diagnosis was lymphoepithelioma-like carcinoma (LELC) associated with Epstein-Barr virus (EBV) infection; however, EBV-encoded small RNA–in situ hybridization was negative. Microsatellite instability was not assessed. The postoperative course was uneventful and she was discharged on the 15th postoperative day. She remains recurrence-free at 2 years after surgery. Past reports note that colorectal carcinomas with dense lymphoid stroma may be related to LELC or medullary carcinoma (MC). Gastrointestinal LELC is rare, with some reports on LELC of the esophagus and stomach. Reports on LELC of the large intestine are very rare. MC of the large intestine is relatively new concept, firstly described in the WHO Classification of Tumours of the Digestive System 3rd Edition in 2000. We herein present a case of lymphoepithelioma-like carcinoma of the ascending colon and relevant case reports about LELC and MC of the large intestine.

// Yuji Ueda 1 , 2 , 3 , Koichi Kawamoto 1 , 2 , 3 , Masamitsu Konno 2 , 3 , Kozo Noguchi 1 , 2 , Satoru Kaifuchi 4 , Taroh Satoh 3 , Hidetoshi Eguchi 1 , Yuichiro Doki 1 , Takaaki Hirotsu 4 , 5 , Masaki Mori 1 and Hideshi Ishii 2 , 3 1 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan 2 Department of Medical Data Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan 3 Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan 4 Hirotsu Bioscience Co., Ltd., Tokyo 107-0062, Japan 5 Department of Biology, Graduate School of Science, Kyushu University, Fukuoka 819-0395, Japan Correspondence to: Hideshi Ishii, email: hishii@gesurg.med.osaka-u.ac.jp Keywords: early detection; pancreatic cancer; C. elegans; genetically-engineered mice Abbreviations: PDAC: pancreatic ductal adenocarcinoma; C.elegans: Caenorhabditis elegans Received: July 02, 2019 Accepted: July 17, 2019 Published: September 10, 2019 ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) exhibits a very early onset of metastasis. Thus, early detection and treatment are pivotal to successful eradication of pancreatic cancers. Economical and non-invasive cancer screening systems is indispensable for this purpose. Previously our group developed a novel method to detect various kinds of human cancer using nematode Caenorhabditis elegans (C. elegans) that respond to cancer odor in urine; however, whether this method is useful for non-human species remains to be understood. In this study, we examined its effectiveness in the detection of murine pancreatic tumor spontaneously generated in genetically-engineered mice. We generated pancreas-specific Kras G12D and/or c-Met deletion mutant mice and measured the probability of spontaneous tumor generation in these mice. The chemotactic indexes of C. elegans to the urine samples of these mutant mice were measured. As previously described, oncogenic Kras G12D was necessary to induce pancreatic intraepithelial neoplasia in this mouse model, while c -Met mutation did not show further effect. The chemotactic analysis indicated that C. elegans avoids urine of healthy recipient mice, while they tended to be attracted to urine of mice with Kras G12D . Our study demonstrated that C. elegans can recognize the odor of pancreatic cancer in urine of Kras G12D model mouse, suggesting the similarity of cancer odor between species. Our result facilitates further studies on mechanism of cancer detection by C. elegans .

An 80-year-old women admitted to our hospital with jaundice. Abdominal contrast-enhanced CT scan revealed an enhanced tumor, measuring 10 mm, at the duodenal ampulla. Upper endoscopy showed a submucosal tumor-like lesion at the duodenal ampulla. Immunohistochemical findings showed positive for chromogranin A and synaptophysin, and neuroendocrine carcinoma was diagnosed. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed. The final diagnosis was large cell neuroendocrine carcinoma(LCNEC). Multiple metastases of liver, lung and bone were occurred 14 months after the surgery, and she died 21 months after the surgery. LCNEC of the duodenal ampulla is very rare, and its prognosis is poor.

We previously demonstrated that rapid posthypothermic rewarming in noninjured animals was capable of damaging cerebral arterioles both at endothelial and smooth muscle levels. Such adverse consequences could be prevented with antioxidants, suggesting the involvement of free radicals. In this study, we further investigate the mechanisms associated with free radicals production by using two radical scavengers, superoxide dismutase (SOD) and catalase. Employing rats, the cerebral vascular response was evaluated at 2, 3, and 4 hours after onset of hypothermia. Before rapid rewarming, SOD treatment, but not catalase, preserved the NO-mediated dilation induced by acetylcholine (ACh). On the contrary, catalase preserved the hypercapnia-induced relaxation of the smooth muscle cells, whereas SOD offered only partial protection. Adding SOD to catalase treatment offered no additional benefit. These results suggest that rapid posthypothermic rewarming impairs ACh- and hypercapnia-induced vasodilation through different subcellular mechanisms. In the case of diminished vascular response to ACh, it appears to act on the endothelial front primarily by superoxide anions, as evidenced by its full preservation after SOD treatment. In terms of impaired dilation to hypercapnia, hydrogen peroxide and/or its derivatives are the likely candidates in targeting the smooth muscle cells. The partial protection of SOD to hypercapnia-induced dilation is believed to be the reduced amount of superoxide that would otherwise spontaneously dismutate to produce hydrogen peroxide. Although SOD exerts some indirect influence on the hydrogen peroxide production downstream, catalase apparently has no influence on upstream superoxide production.

A new species of softnose skate (Arhynchobatidae), Bathyraja sexoculata Misawa, Orlov, Orlova, Gordeev and Ishihara is described on the basis of five specimens collected from off the east coast of Simushir Island, Kuril Islands, located in the western North Pacific. The specimens conformed to the genus Bathyraja by having the anteriormost pectoral-fin skeleton almost reaching the snout tip, and a slender unsegmented rostral cartilage. Within Bathyraja, the new species belongs to the subgenus Arctoraja (currently with four valid species) due to the relatively short tail (79–86% of disc width), high count of predorsal caudal vertebrae (more than 86), and large strong nuchal and scapular thorns. It is most similar to Bathyraja (Arctoraja) smirnovi, distributed in the Seas of Japan and Okhotsk, in having tail thorns not extending to the nuchal area, median thorns discontinuous from the nape to the tail, and no mid-dorsal thorns. However, B. sexoculata can be distinguished from B. smirnovi by the following characters: three pairs of white blotches on the dorsal disc surface (vs. blotches absent, or a pair of white or dark blotches in B. smirnovi), dark blotch around cloaca, dark bands along mid ventral line of tail (vs. dark blotch and band usually absent ventral disc surface in B. smirnovi), 86–93 predorsal caudal vertebrae (vs. 80–87 in B. smirnovi), and a unique mitochondrial DNA cytochrome c oxidase subunit I sequence. Proportional measurements, including disc width, disc length, head length, preoral length, prenarial length, internarial distance, eye diameter, and tail length, also differ between the two species. For the referential purpose, geographical variations of B. smirnovi distributed in the Seas of Japan and Okhotsk are analyzed and clarified based on morphological and genetic data. Significant morphological and genetic differences were found between local populations in the Seas of Japan and Okhotsk.

An intra-abdominaldesmoid tumor, especially omentaldesmoid tumor, is rare. Here, we report a case of omentaldesmoid tumor after a smallbowelresection for gastrointestinalstromaltumor (GIST). A 73-year-old man underwent a partial resection of smallbowelfor GIST. He received adjuvant therapy with imatinib due to high risk of recurrence. After 2.5 years of treatment, a follow-up CT showed a 15mm nodule in the omentum near the splenic flexure. We considered the possibility of recurrence and imatinib failure, and laparoscopic tumor resection was performed for differential diagnosis. Immunohistochemicalstaining showed negative for c-kit, CD34, desmin, and S100. However, it was diagnosed as desmoid tumor because of positive b-catenin. Intra-abdominal desmoid tumor should be a differential diagnosis for a new single lesion in patients with GIST.

Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1–associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear. We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016. Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT. Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation. In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.

Growth and moulting of male adolescent snow crabs were investigated in a laboratory culture experiment. The moulting season of adolescents was separated into two groups of earlier and later, and they were regarded as normal and skip moulters, respectively. The existence of male snow crab skip moulters was first demonstrated in the Sea of Japan. Although the precise moulting season of the earlier moulter could not be revealed owing to the captive method, the later moulter is suspected to moult approximately 1 year after the earlier moulter. Earlier and later moulters were not different in growth of carapace width or chela height during the pubertal and terminal moult. Our moult and growth results of earlier and later moulters will be useful for predicting recruitment to legally fishable (>90 mm carapace width) or valuable (hard-shelled adult) populations of male snow crab in the Sea of Japan.

Gastrointestinal stromal tumors (GISTs) are a type of sarcoma, and the most common mesenchymal tumor of the gastrointestinal tract. Systemic chemotherapy is recommended for unresectable or metastatic GISTs. Imatinib is an oral multitargeted receptor tyrosine kinase inhibitor that is effective as adjuvant chemotherapy for primary high-risk cases, and as palliative chemotherapy for unresectable or metastatic cases. For imatinib-resistant cases, second-line chemotherapy with sunitinib is recommended due to significantly longer median progression-free survival and higher response rates compared with a placebo. A 54-year-old woman presented with persistent upper abdominal pain and anorexia. An upper gastrointestinal endoscopy and computed tomography revealed a submucosal tumor of the stomach with no apparent metastases. The patient underwent total radical gastrectomy, and was diagnosed histologically with high-risk GIST for recurrence, therefore, the patient received adjuvant chemotherapy with imatinib. However, multiple liver and lymph node metastases were detected, and the patient received sunitinib therapy. After four cycles of sunitinib, the liver and lymph node metastases disappeared, and a complete response (CR) was achieved. To date, there have been no cases of CR in the prospective clinical trials examining the effects of sunitinib, or in case reports worldwide. Therefore, this is a very rare case report of a patient with metastatic GISTs who achieved CR with sunitinib as second-line chemotherapy.

The purpose of this study is to investigate damage process of concrete of the footing supporting steel pier subjected to bi-directional force. A model which can reproduce complicated behavior caused by separation/contact between baseplate and anchor bolt and those between baseplate and footing concrete, was set up for three-dimensional nonlinear FE analysis. The model was verified by comparison of the relation between the bending moment and rotation angle of static loading and for cyclic loading analysis. Furthermore, analysis of the damage process inside footing concrete was performed under bi-directional loading as well as single-directional loading.

Detecting drivers of population divergence across phylogeographic breaks is a major challenge in marine population genetics, partly due to uncertainties in molecular dating. Although the calibration of demographic transition (CDT) method is the most promising rate calibration technique for population-level events, there is a risk of making the false assumption that post-glacial population expansions coincided with global temperature rise. Further generalization of the technique is required to evaluate population histories of marine species whose abundance may be independent of changes in temperature. We explored the population history of a dwarf eelpout Petroschmidtia teraoi on Japanese continental slopes in the Sea of Japan and Sea of Okhotsk as a model organism for phylogeographic study. For rate calibration, we estimated historical stock sizes from a species distribution model and incorporated this data into the CDT method as a proxy for demographic transition (we term this combined method extended CDT, or eCDT). Our species distribution model showed that the range of P. teraoi is mainly determined by water depth and locality (i.e., latitude and longitude). Reconstructed historical stock sizes revealed contrasting demographic trends in the northern and western Sea of Japan on either side of the Noto peninsula, located at the midpoint of the Japanese mainland. We also found a sharp genetic break in the same location, and inferred contrasting demographic histories of local populations from the molecular data. The striking differences in the demographic histories of local populations even on apparently continuous continental slopes are most likely due to differences in available habitat area. eCDT appeared to work well as a rate calibration method for our temperature-independent study species, and our species distribution model revealed that local populations could have diverged due to discontinuities in available habitat. Finally, we assessed the strengths and weakness of the novel calibration method by analyzing simulated sequences.

In this study, commercially available γ -type manganese dioxide, namely electrolytic manganese dioxide (EMD), was transformed to a bifunctional catalyst that exhibits activity not only for the oxygen reduction reaction (ORR) but also for the oxygen evolution reaction (OER), by the doping of cobalt into EMD without changing its framework structure. The use of EMD, which has long been proven in the primary battery industry, would be advantageous in terms of manufacturing, supply, and quality control. The process involves a simple wet treatment of EMD in the presence of N2H4 and Co2+. EMD is intrinsically active for the ORR, more than chemically-synthesized MnO2, but inactive for the inverse reaction, the OER. Here, the extremely high mass activity of a small amount of Co that was introduced into the framework of γ -MnO2 boosted its OER activity, while did not offset the ORR activity. As a result, the overpotential at 10 mA cm−2 in the OER was measured to be 440 mV, while that at −1 mA cm−2 in the ORR was 447 mV. Their sum (ηOER+ηORR) of 887 mV was much smaller than that (1040 mV) of pristine EMD and differed from that of Pt/C by only 26 mV.

Reelin is a large glycoprotein which regulates central nervous system (CNS) development. Dysfunctions of Reelin were reported on certain neuropsychiatric diseases. We examined involvement of Reelin pathway in functional recovery of hemiplegic mice after neural transplantation. Reelin was expressed 1 day after cryogenic injury of right motor cortex. We transplanted neural stem/progenitor cells (NSPCs) from wild-type mice into ipsilateral striatum of hemiplegic mice. The grafts migrated from the striatum and reached the injured cortex 14 days after transplantation. The transplantation significantly improved their motor functions (P The NSPCs migrating toward the cortex expressed Reelin receptors, Apoer and Vldlr, and phosphorylated Disabled1 (Dab1), a downstream signaling molecule of Reelin. The grafts expressed Ncadherin and active form of Integrin β1, both of which were known to become active with Reelin stimulation. At day 28, the grafts expressed Ctip2, Crim1, Foxp2, and Fezf2, all of which were forebrain motoneuron associated markers, and Nfm and Synapsin1 on the damaged cortex. We then transplanted NSPCs of yotari mice (yot/yot genotype) having nonfunctional Dab1 by a mutation of its gene. Majority of the grafts from yotari mice (>80%) did not migrate and thus remained at the striatum. The grafts did not express the forebrain motoneuron associated markers nor the cell adhesion molecules including Ncadherin and active Integrin β1. Reelin pathway was involved in graft migration by regulating certain adhesion molecules and in their differentiation to functional motoneurons accompanying synapse formation. We suggested involvement of Reelin pathway for neural regeneration and functional recovery of hemiplegic mice in adulthood after neural transplantation.

Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently, researchers have reported that, in mouse experiments, altered gut microbe-dependent T cell differentiation occurred in gut associated lymphoid tissues. Here, we investigated whether gut microbe alteration existed, and if so, the alteration affected peripheral T cell differentiation in patients with RP. In an analysis of gut microbiota, we found increased annotated species numbers in RP patients compared with normal individuals. In the RP gut microbiota, we observed several predominant species, namely Veillonella parvula, Bacteroides eggerthii, Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species of which were reported to associate with propionate production in human intestine. Propionate is a short-chain fatty acid and is suggested to associate with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut associated lymphoid tissues. IL10 gene expressions were moderately higher in freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than those of normal individuals. Six hours after the initiation of the cell culture, regardless of the presence and absence of mitogen stimulation, IL10 gene expressions were significantly lower in RP patients than those in normal individuals. It is well known that PBMC of patients with autoimmune and inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest that, in RP patients, continuous stimulation of intestinal T cells by excessive propionate leads to the spontaneous IL10 production and a subsequent refractory period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon activation may associate with inflammatory cytokine production of PBMC and subsequently relate to chondritis in RP patients.

We have previously demonstrated that the phylum Actinobacteria, the family Lactobacillaceae, and the genus Bifidobacterium increased in relative abundance of gut microbiota in patients with Behcet’s disease (BD). The phylum Firmicutes and the class Clostridia were predominant in the feces of normal individuals. The class Clostridia includes short-chain fatty acid–producing bacteria, important for the balance between regulatory T cells and helper T type 17 (Th17) cells. It is possible that the bacterial compositional alteration causes low intestinal short-chain fatty acid concentrations, leading to skewed immune functions in patients with BD. To test the hypothesis, we examined species composition and gene functions from the 16S rRNA data by utilizing PICRUSt software. We have shown that relative abundance of Eggerthella lenta, Acidaminococcus species, Lactobacillus mucosae, Bifidobacterium bifidum, Lactobacillus iners, Streptococcus species, and Lactobacillus salivarius increased significantly in patients with BD. Relative abundance of Megamonas hypermegale, Butyrivibrio species, Streptococcus infantis, and Filifactor species increased significantly in normal individuals compared with BD patients. In the functional annotation analysis by PICRUSt, we found prevalent gene functions of the pentose phosphate pathway and the inosine monophosphate biosynthesis in patients with BD. The data suggested that BD gut microbes altered nucleic acid and fatty acid synthesis. These compositional and functional alterations of gut microbes may accompany unfavorable molecular exchanges between intestinal immunocompetent cells and gut microbes, and these interactions may have an association with the immune aberration in patients with BD.

Genetic divergence between two color (yellow and red) morphotypes and among regional populations of the liparid Crystallichthys matsushimae were investigated using AFLP and mitochondrial DNA (mtDNA) sequence variations on the partial COI and Cyt-b genes. A principal coordinate analysis (PCoA) based on AFLP data showed a rough separation of the yellow morphotype, distributed in the southern Sea of Japan, from the red morphotype, distributed in the Sea of Okhotsk, northern Sea of Japan and Pacific coast of northern Japan. In addition, both PCoA and the Bayesian-based individual assignment test indicated an extensive population structure among the Sea of Japan, Sea of Okhotsk and Pacific Ocean. In contrast, the mtDNA sequence variations disclosed two haplotype groups, partly corresponding to either the two color morphotypes or the regional populations. However, gene flow restrictions were indicated between both the morphotypes and among the regional populations. Genetic divergence in the mtDNA within C. matsushimae suggested that the color morphotypes and/or regional populations were isolated by sea-level oscillations during the glacial periods. In addition, the discrepancy between the results of AFLP and mtDNA sequencing may be due to the complex history of the species, including introgressive hybridization and gene flow between regional populations as well as a sudden population expansion.

We have reported that helper T type 17 (Th17) cells increased in patients with Behcet's disease (BD). It remains obscure how Th17 cells increase in the patients. We here analyzed whether T cells preferentially differentiate into Th17 cells in response to various inflammatory cytokines in patients with BD. Exogenous interleukin (IL)23 sustained the higher Th17 cell frequencies of CD4+CD45RO+ T cells after a 2-day culture in vitro in patients with BD, whereas the T cell subpopulation of normal individuals did not respond to IL23 to sustain/increase Th17 cell frequencies. IL23 receptor positive cell frequencies in freshly isolated BD CD4+CD45RO+ T cells correlated with Th17 cell frequencies assessed by intracellular cytokine staining. After a 2-day culture with IL23, BD CD4+ T cells retained the correlation between IL23 receptor expression level and extent of IL17 secretion (as indicated by Th17 cell frequencies), whereas such correlation was not noted in normal individuals. IL23 signals with its receptor were thus suggested to induce IL17 secretion (Th17 cell frequencies) in a short-time culture in patients with BD. We cultured CD4+CD45RO- T cells for 11 days with various inflammatory cytokines to study which cytokine associated with the enhanced Th17 frequencies in the patients. IL17 production by CD4+CD45RO- T cells of BD patients increased significantly by the supplementation of IL1β and tumor necrosis factor (TNF)α, in addition to IL23, compared with that of normal individuals. These results suggest that proinflammatory cytokines, such as IL1β, TNFα, and IL23, may associate with the expansion of Th17 cells in patients with BD. This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000003806).

The effect of water temperature on the growth of juvenile snow crabs Chionoecetes opilio (Fabricius, 1788) was investigated in laboratory culture experiments. Laboratory-born juveniles were cultured from instar I to VIII at four temperatures (approximately 1, 3, 5 and 8°C). The growth indices (size increments at moulting in mm and in % of premoult carapace width) were significantly higher in crabs reared at 5°C than in those reared at other temperatures. The relationship between the mean temperature (T) and intermoult period (D) of each instar was described by the heat summation theory equation: D=K∕(T−α). The thermal constant K is the summation of the effective temperature for development (above the threshold temperature, α) up to a selected biological end point. The thermal constant tended to increase and the threshold temperature tended to decrease with increasing mean premoult carapace width of each instar, reaching asymptotes of 1573 day-degrees and −4.7°C, respectively. Size- and temperature-dependent growth models were developed for snow crab juveniles.

Ontogenetic growth functions provide basic information in biological and ecological studies. Various growth functions classified into the Pütter model have been used historically, regardless of controversies over their appropriateness. Here, we present a novel growth function for fish and aquatic organisms (generalised q-VBGF) by considering an allocation schedule of allometrically produced surplus energy between somatic growth and reproduction. The generalised q-VBGF can track growth trajectories in different life history strategies from determinate to indeterminate growth by adjusting the value of the 'growth indeterminacy exponent' q. The timing of maturation and attainable body size can be adjusted by the 'maturation timing parameter' τ while maintaining a common growth trajectory before maturation. The generalised q-VBGF is a comprehensive growth function in which exponentials in the traditional monomolecular, von Bertalanffy, Gompertz, logistic, and Richards functions are replaced with q-exponentials defined in the non-extensive Tsallis statistics, and it fits to actual data more adequately than these conventional functions. The relationship between the estimated parameter values τ and rq forms a unique hyperbola, which provides a new insight into the continuum of life history strategies of organisms.

Malignant lymphomas of the duodenum and small intestine are relatively rare, but are clinically important, as they may result in perforation peritonitis. Here, we report a case of perforation peritonitis caused by multiple duodenal and small intestinal malignant lymphomas. An 84-year-old man was diagnosed with malignant lymphoma of the duodenum. Although chemotherapy was planned, emergency surgery was performed to treat perforation peritonitis. Laparoscopic observation revealed that the perforation was not in the duodenum, but in the ileum. In addition, numerous lymphoma lesions were revealed throughout the small intestine. Partial resection of the small intestine including the perforation was performed. Primary gastrointestinal malignant lymphoma may exist over multiple digestive tracts and it is necessary to carefully diagnose and treat, even in emergency surgery.

The patient was 69-year-old man. For the remnant gastric cancer, partial resection of the remnant stomach with combined resection of mesentery of transverse colon was performed. Pathological diagnosis was adenocarcinoma(tub2tub1), M, B- 50-AJ, type 3, pT4b(mesentery of transverse colon), pN0, CY0. A CT scan of 6 months after the surgery showed a tumor on the left side abdomen and diagnosed as peritoneal recurrence. Chemotherapy consisted of 1 course of TS-1(100mg/body) plus cisplatin(70mg/body), 4 courses(2 weeks administration and 1 week break)of TS-1(100mg/body), 8 courses of docetaxel(80mg/body). Tumor shrinkage and internal necrosis were observed. Peritoneal tumor was resected 19 months after the first surgery, and partial resection of the invaded transverse colon and jejunum was performed. Pathological diagnosis was metastasis of remnant gastric cancer. After that, it is 61 months since the first surgery and 42 months from the recurrence surgery without relapse.

Previous studies highlighted that aminopeptidase N (APN)/CD13 acts as a scavenger in the survival of hepatocellular carcinoma (HCC) stem cells by reducing reactive oxygen species (ROS) levels. Hence, it has been proposed that APN/CD13 inhibition can increase cellular ROS levels and sensitize cells to chemotherapeutic agents. Although ubenimex, also known as bestatin, competitively inhibits proteases such as APN/CD13 on the cellular membrane and it is clinically used for patients with acute myeloid leukemia and lymphedema, research has demonstrated that higher concentrations of the agent induce the death of APN/CD13+ HCC stem cells. In this study, we developed a poly(ethylene glycol)-poly(lysine) block copolymer-ubenimex conjugate (PEG-b-PLys(Ube)) to increase the efficacy of reagents in APN/CD13+ cancer stem cells. Exposure to PEG-b-PLys(Ube) increased the intracellular ROS concentration by inhibiting APN enzyme activity, permitting the induction of apoptosis and attenuation of HCC cell proliferation. In addition, PEG-b-PLys(Ube) exhibited a relatively stronger antitumor effect in mice than PEG-b-PLys alone or phosphate-buffered saline. Moreover, an isobologram analysis revealed that combinations of fluorouracil, cisplatin, or doxorubicin with PEG-b-PLys(Ube) exhibited synergistic effects. This study demonstrated that PEG-b-PLys(Ube) does not impair the properties of ubenimex and exerts a potent antitumor effect.

Growth and moulting of wild-born immature snow crabs (Chionoecetes opilio (Fabricius, 1788)) were investigated by laboratory culture experiments. Crabs with 16.2-42.9 mm carapace width caught from the Sea of Japan were cultured at a temperature of their natural habitat (approximately 1°C). The growth indices (size increments at moulting in mm and in % of premoult carapace width) and intermoult period were significantly affected by premoult carapace width, but sex did not affect these variables. Furthermore, we demonstrated that premoult carapace width and days after moulting significantly affected moulting probability and we developed a moulting probability model based on these variables. From this model, the number of days of intermoult periods when moults occurred in 50% of crabs of instars VI, VII and VIII was estimated at 234, 284 and 346 days, respectively.

The deep-sea crangonid shrimp, Argis lar, is a highly abundant species from the northern Pacific Ocean. We investigated its phylogeographic and demographic structure across the species' extensive range, using mitochondrial DNA sequence variation to evaluate the impact of deep-sea paleoenvironmental dynamics in the Sea of Japan on population histories. The haplotype network detected three distinct lineages with allopatric isolation, which roughly corresponded to the Sea of Japan (Lineage A), the northwestern Pacific off the Japanese Archipelago (Lineage B), and the Bering Sea/Gulf of Alaska (Lineage C). Lineage A showed relatively low haplotype and nucleotide diversity, a significantly negative value of Tajima's D, and a star-shaped network, suggesting that anoxic bottom-water in the Sea of Japan over the last glacial period may have brought about a reduction in the Sea of Japan population. Furthermore, unexpectedly, the distributions of Lineage A and B were closely related to the pathways of the two ocean currents, especially along the Sanriku Coast. This result indicated that A. lar could disperse across shallow straits through the ocean current, despite their deep-sea adult habitat. Bayesian inference of divergence time revealed that A. lar separated into three lineages approximately 1 million years before present (BP) in the Pleistocene, and then had been influenced by deep-sea paleoenvironmental change in the Sea of Japan during the last glacial period, followed by a more recent larval dispersal with the ocean current since ca. 6 kilo years BP.