Search

The Cancer Genome Atlas (TCGA) project described a robust gene expression-based molecular classification of glioblastoma (GBM), but the functional and biological significance of the subclasses has not been determined. The present comprehensive analysis of 25 glioma-initiating cell (GIC) lines classifies GIC lines into four subtypes (classical, mesenchymal, proneural, and neural) that are closely related to the TCGA GBM subclasses and display distinct lineage characteristics and differentiation behavior that recapitulate neural development. More importantly, the GIC subtypes exhibit distinct biological phenotypes in relation to self-renewal capacity, proliferation, invasiveness, and angiogenic potential in vitro and in vivo. In addition, the GIC subtypes exhibit divergent patterns of signaling pathway activation and deactivation of the Wnt, Notch, and TGF-&beta, pathways. These results will improve drug discovery targeting certain genetic mutation in glioblastoma and improve the development of precision medicine.

Background The signal transducer and activator of transcription (STAT) 3 plays a critical role in the regulation of cell growth, metastasis, and survival. STAT3 signaling is constitutively activated in various cancers including gynecological cancers. We evaluated the efficacy of a novel selective STAT3 inhibitor, YHO-1701, ex vivo and in vivo for ovarian and endometrial cancer. Methods An expression profile of YHO-1701 treated cells was compared with that of other STAT3 inhibitors or its upstream Janus kinase inhibitor by RNA sequencing. The downstream signaling of YHO-1701 was investigated by western blot. Patients derived primary cancer cells (PDCs) were isolated from surgical specimens or ascites cells from ovarian or endometrial cancer patients, and the growth inhibitory effect of YHO-1701 on PDCs was evaluated by standard colorimetric assays. Antitumor activity of YHO-1701 was assessed using an SKOV3 abdominal dissemination xenograft model. Results We investigated the specificity of YHO-1701 by pathway analysis using RNA sequencing results of the cells treated with or without each inhibitor and found YHO-1701 regulated STAT3 signaling more tightly than others did. We confirmed decreased levels of pSTAT3 S727, Survivin, and c-Myc in the cells treated with YHO-1701. A total of 41 PDCs were treated with YHO-1701 and showed a remarkable growth inhibition compared with the control group (P Conclusions Our results demonstrated the efficacy of YHO-1701 for ovarian and endometrial cancer both ex vivo and in vivo through STAT3 signaling. Legal entity responsible for the study The authors. Funding Yakult Honsha. Disclosure K. Hasegawa: Research grant / Funding (self): Yakult. K. Taniguchi: Full / Part-time employment: Yakult. A. Yoshinaga: Full / Part-time employment: Yakult. M. Tsugane: Full / Part-time employment: Yakut. All other authors have declared no conflicts of interest.

ObjectiveTo evaluate the Sex differences in Sport-related Concussion in Japan.BackgroundWe dont't have the knowledge about the sex differences in SRC in Japan.Design/MethodsThe study design was retrospective study. Facility is Toho University Ohashi Medical Center Neurosurgery Sports-related head injury clinic. The search period is April 2017 to February 2018. Inclusion criteria were as follows: 1) Sports-related head injury cases, 2) Physician-diagnosed Sports-related concussion, 3) Underwent evaluation by the same neurosurgeon, 4) More than 28 days continued follow-up. The following items were compared male and female. The examination items were as follows: 1) Age/sex, 2) competition item, 3) prior concussion, 4) Migraine history, 5) persistent post concussive symptoms. Statistical analysis used t test.ResultsThe 140 selected cases were 114 male (Group M: GM) and 26 female (Group F: GF). The mean Age of both GM and GF was 20 years. The most majority competition item of GM was Rugby football. On the other hand, GF was lacrosse. 42 cases of GM and 9 cases of GF suffered prior concussion (p > 0.05, no significant). 19 cases of GM and 6 cases of GF had migraine history (p > 0.05, no significant). 37 cases of GM and 16 cases of GF had PPCS (p < 0.05).ConclusionsOur result suggests that female players explain the significant difference in the prevalence of PPCS in Japan.

Electrochemical power sources that use oxygen as a reactant may play an essential role in the future energy needs of the society. Fuel cells, aqueous metal-air batteries, and metal hydride (MH)/air batteries hold promise as the power sources. Especially, for rechargeable batteries, an oxygen reduction reaction (ORR) and an oxygen evolution reaction (OER) are the cathode reactions during charge and discharge. Therefore, the development of highly active catalysts (i.e., low activation overpotential) for the reactions is required and remains challenging. Then, we attempted to develop the electrode catalysts which decrease in the overpotential for ORR and OER in an alkaline aqueous solution. Especially, we focus on the pyrochlore type metal oxide including bismuth and ruthenium ions as Bi2Ru2O7 (BRO) and evaluated the overpotential and Tafel slopes for both ORR and OER by using the rotating ring-disk electrode (RRDE) technique as well as a half-cell test. We also have investigated the effect of aluminum ion addition to BRO, which is called as ABRO, by the addition of aluminium nitrate [Al(NO3)3] during the synthesis of BRO. BRO and ABRO were prepared by a precipitation method. In order to prepare BRO, the method is denoted bellow. At first, Bi(NO3)3 and RuCl3 aqueous solutions were separately prepared and well mixed in a 1 : 1 molar ratio. The mixture solution was heated up to 75 oC and stirred for 1 hour. Then, NaOH aqueous solution was added to the mixed solution to produce a precipitate and stirred for 72 hour. After that, the precipitate was made for calcination under atmospheric air at 500 and 600oC for 3 hours and then it was washed with pure water and dried at 120 oC for 3 hours. On the other hand, Al(NO3)3 was also added to the mixture solution during the synthesis to investigate an effect of aluminum ion on the ORR and OER of BRO. These products were obtained after the calcination at the desired temperatures as 500 and 600oC in air. X-ray diffraction (XRD) and Field emission scanning electron microscope (FE-SEM) observation were performed for characterization. The catalytic behavior was investigated by a RRDE. The disk and ring electrodes were made by titanium (Ti) and Pt, respectively. BRO or ABRO powder was loaded on Ti disk. Hg|HgO reference electrode and a Ni mesh counter electrode were used. The electrochemical cell was made of polytetrafluoroethylene (PFA). The electrolyte was 0.1 mol dm-3 KOH aqueous solution. We also measured constant current charge-discharge measurements to evaluate BRO as the cathode catalyst for the air-battery. In this test, 6.0 mol dm-3 KOH aqueous solution was used as the electrolyte. The peaks in the XRD patterns of BRO were assigned to Bi2Ru2O7, when the calcination temperature was 500oC; on the other hand, the peaks were assigned to Bi1.87Ru2O6.903 when the calcination temperature was 600oC. In addition to these, tiny diffraction peaks of Bi2O3 were also confirmed. These results indicated that both of oxygen and bismuth were decreased between 500oC and 600oC due to the elimination of oxygen from BRO. In the case of ABRO, the peaks were assigned to Bi1.87Ru2O6.903 at 500oC and to Bi1.88Ru2O6.906 at 600oC and simultaneously, Al2O3 was also confirmed in both cases. Table 1 shows the overpotentials and Tafel slopes for ORR and OER of BRO and ABRO. The overpotentials and Tafel slopes for OER of BRO@500oC were around 0.14 V and 70 mV dec.-1, respectively. The overpotential was increased when the calcination temperature was at 600oC, but the Tafel slope was unchanged. The overpotential of ABRO for OER was estimated at 0.11 V, which shows that the aluminium nitrate addition would be effective to decrease in the overpotential. In this presentation, we will report the catalyst performances during the constant current charge-discharge measurements as the air-battery. This work was supported by “Development of Hydrogen|Air battery”, “Advanced Low Carbon Technology Research and Development Program (ALCA)” of Japan Science and Technology Agency (JST). Table 1 The overpotentials and Tafel slopes for ORR and OER of BRO and ABRO. Sample Overpotential / V Tafel slope / mV dec.-1 ORR OER ORR OER BRO@500 0.34 0.14 -69 71 BRO@600 0.33 0.19 -64 74 ABRO@500 0.37 0.11 -51 62 ABRO@600 0.35 011 -41 41

In order to make a direct link between the morphological and functional study of the nervous system, we established an experimental protocol for labeling individual neurons persistently without microscopic guidance by injecting a plasmid encoding fluorescent protein electroporatively after recording their activity extracellularly. Using a glass pipette filled with electrolyte solution containing a plasmid encoding green fluorescent protein (GFP), single-neuron recording and electroporation were performed on anesthetized rats. When performing the electroporation at the completion of recording, the degree of contact between the target neuron and the electrode tip was adjusted by monitoring the change of the trace of recorded action potentials and the increase of electrode resistance. The expression of GFP and its immunostaining with a polyclonal antibody enabled us to clearly see the basic structural components such as cell bodies, axons, dendrites, and even smaller components such as spines. Identification of the morphological subtypes of neurons was possible with every labeled neuron. The optimum condition for labeling was a 30% increase of the electrode resistance, and the labeling success rate evaluated 3 days after labeling was 40%. The rate evaluated one month after labeling was only slightly lower (33%). We also confirmed experimentally that this recording and labeling procedure can be similarly successful in head-fixed behaving rats. This new experimental protocol will be a breakthrough in systems neuroscience because it makes a direct link between the morphology and behavior-related activity of single neurons.

Recently, we identified the structurally related homeoproteins EGAM1, EGAM1N, and EGAM1C in both preimplantation mouse embryos and mouse embryonic stem (ES) cells. These EGAM1 homeoproteins act as positive or negative regulators of differentiation and cell growth in mouse ES cells, such that these proteins are considered transcriptional regulators. In this study, we investigated their nuclear localization and identified the amino acid residues crucial for the nuclear translocation of EGAM1 and EGAM1C. When expressed exogenously in pluripotent ES cells and somatic NIH3T3 cells, all EGAM1 homeoproteins localized to the nucleus. Analysis using the web-based tool PSORTII predicted a potential nuclear localization signal (NLS) motif, RKDLIRSWFITQRHR, in the homeodomain shared by EGAM1 and EGAM1C. The introduction of mutations, such as mutations from K or R, both basic amino acid residues, to A, in this potential NLS resulted in significant impairment of the nuclear localization of both EGAM1 and EGAM1C. In contrast, GFP fusion proteins of all the full-length EGAM1 homeoproteins failed to localize to the nucleus. These results, when taken together, suggest that basic amino acid residues in the common homeodomain of EGAM1 and EGAM1C and the intact structures of the EGAM1 homeoproteins contribute, at least in part, to the nuclear localization of these proteins in mouse ES cells.

Many breast cancer cells express aberrantly activated receptor tyrosine kinases and are associated with deregulated phosphorylation of Akt (PKB). They are also often associated with a high level of free monounsaturated (MUFA) and saturated (SFA) fatty acids. We studied the effect of DHA and other polyunsaturated fatty acids (PUFAs) on these anomalies in a human breast cancer cell line, MDA-MB-453. Inhibitors of the Akt T308 kinase (PDK1) or S473 kinase (mTORC2, DNA-dependent protein kinase and integrin-linked kinase) and combinations of two of them incompletely inhibited, or even enhanced, the phosphorylation in this cell line. In contrast, it was found that DHA as well as other PUFAs inhibited Akt phosphorylation on T308 after 24h. These PUFAs also blocked phosphorylation of S473, although certain omega-6 PUFAs were ineffective. After 48h, only DHA inhibited Akt phosphorylation on the both residues. DHA, and other PUFAs though less efficiently, also elevated the expression of a mitochondrial enzyme, 2,4-dienoyl-CoA reductase, which catalyzes process necessary for β-oxidation of PUFAs. These PUFAs were present in the cells at high concentrations and reduced the amount of free and phospholipid-bound MUFAs. DHA most efficiently blocked deregulated cell proliferation while the effects of other PUFAs were moderate. These results suggest that DHA suppressed the growth of the cancer cell through its specifically persistent block of Akt phosphorylation in conjunction with modulation of fatty acid metabolism.

Fibroblast growth factor 4 (FGF4) is considered a crucial gene in the proper development of bovine embryos. We recently determined the FGF4 gene sequence in eight cattle derived from three breeds and revealed a common nucleotide sequence of the structural gene encoding FGF4, which leads to the deletion and mutation of amino acid sequences in the mature FGF4 (Pro(32) -Leu(206) ) compared with the sequence previously reported. In the present study, HisbFGF4, a 6× histidine-tagged bovine FGF4 (Pro(32) -Leu(206) ), was produced in Escherichia coli based on the validated nucleotide sequence and purified by heparin column chromatography. In primary bovine fibroblasts, HisbFGF4 showed significant mitogenic activity, whereas, intriguingly, the activity of a commercially available recombinant human FGF4 (Gly(25) -Leu(206) ) produced in E. coli was weaker than that of HisbFGF4. In conclusion, the present study provides a simple method for the production of a bioactive bovine FGF4 derivative in E. coli utilizing its structural gene elucidated by us.

Fibroblast growth factor 4 (FGF4) is considered a crucial gene in the development of mammalian embryos. Here we identified common amino acid sequences predicted from coding exons of the FGF4 gene in five pigs of two breeds, and HispFGF4, a 6× histidine-tagged porcine FGF4, was produced in Escherichia coli. HispFGF4 was purified efficiently from the supernatant of cell lysate by heparin column chromatography. In a porcine embryonic fibroblast cell line, HispFGF4 showed significant mitogenic activities at concentrations as low as 0.001 nM (p

Background/Aims: Osteoporosis is found to have high prevalence after gastrectomy and therefore, it is important to prevent this condition by means of effective medication, such as alendronate sodium hydrate. Methods: A total number of 48 gastric cancer patients diagnosed with osteoporosis after R0 gastrectomy was registered in this study between December 2013 and August 2014. Twenty-three patients received intravenous (i.v.) alendronate sodium hydrate and 25 patients received the drug in an oral jelly form. Serological and urinary examinations related to bone metabolism and bone mineral density (BMD) were performed periodically and the results obtained from the 2 groups were compared. Results: BMD increased, serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b, and the urine level of urine N-terminal telopeptide decreased with time in both groups. However, the serum Ca level did not change. Two-way analysis of variance revealed no significant differences in these factors between the 2 groups. Conclusion: It is essential to prevent both forms of osteoporosis by using alendronate sodium hydrate after gastrectomy for gastric cancer. A prospective, randomized, controlled trial in many patients following long duration should be conducted to clarify the benefits of i.v. alendronate sodium hydrate.

This paper proposes a face verification system that runs on Android mobile devices. In this system, facial image is captured by a built-in camera on the Android device firstly, and then face detection is implemented using Haar-like features and AdaBoost learning algorithm. The proposed system verify the detected face using histogram based features, which are generated by binary Vector Quantization (VQ) histogram using DCT coefficients in low frequency domains, as well as Improved Local Binary Pattern (Improved LBP) histogram in spatial domain. Verification results with different type of histogram based features are first obtained separately and then combined by weighted averaging. We evaluate our proposed algorithm by using publicly available ORL database and facial images captured by an Android tablet.

Chronic pancreatitis is a significant risk factor for pancreatic cancer. Previously, we demonstrated that the pancreatic cancer cells show enhanced expression of collapsin response mediator protein 4 (CRMP4) that strongly correlates with severe venous invasion, liver metastasis, and poor prognosis. However, involvement of CRMP4 in acute or chronic pancreatitis remains unknown.Acute and chronic pancreatitis mice models were developed by periodic injection of caerulein. The expression levels of CRMP4 and its phosphorylation were examined.Elevated CRMP4 levels were observed in the infiltrated lymphocytes as well as in the pancreas parenchyma of both acute and chronic pancreatitis. The expression pattern of phosphorylated CRMP4 was similar to that of CRMP4. Cdk5 partially co-localized with the phosphorylated CRMP4.Pancreatitis induces CRMP4 expression in the pancreas parenchyma and in the infiltrated lymphocytes. Overlapping expression of CRMP4 and Cdk5 may suggest that the Cdk5 is at least, in part, responsible for the phosphorylation of CRMP4. The results suggest that CRMP4 is involved in the inflammatory response in pancreatitis. Understanding the mechanisms of CRMP4 would help us to develop novel therapeutic strategies against acute or chronic pancreatitis, and pancreatic cancer.

Embryonic stem (ES) cells have been considered as a valuable renewable source of materials in regenerative medicine. Recently, we identified the homeoprotein EGAM1 both in preimplantation mouse embryos and mouse ES cells. Expression of the Egam1 transcript and its encoded protein was detectable in differentiating mouse ES cells, while it was almost undetectable in undifferentiated cells. In the present study, in order to clarify the effect of forced expression of EGAM1 on the differentiation of mouse ES cells in vitro, transfectants expressing exogenous EGAM1 were generated. Egam1 transfectants promoted differentiation into cell types expressing Gata6, Gata4, Afp, or Plat, genes associated with emergence of the extra-embryonic endoderm lineages. On the other hand, Egam1 transfectants inhibited the expression of specific genes for the embryonic lineages, including Fgf5 (epiblast) and T (mesoderm), in addition to Cdx2, a specific gene for the extra-embryonic trophectoderm lineages. Changes in the percentage of cells recognizing by antibodies against specific marker proteins closely correlated with the expression patterns of their transcripts. Taken together, the results obtained in this study suggested that mouse ES cells expressing exogenous EGAM1 preferentially differentiate into extra-embryonic primitive endoderm lineages, rather than embryonic lineages or extra-embryonic trophectoderm lineages.

In this study, we found that phospholipids containing an eicosapentaenyl group form a novel membrane microdomain at the cell division site of a Gram-negative bacterium, Shewanella livingstonensis Ac10, using chemically synthesized fluorescent probes. The occurrence of membrane microdomains in eukaryotes and prokaryotes has been demonstrated with various imaging tools for phospholipids with different polar headgroups. However, few studies have focused on the hydrocarbon chain-dependent localization of membrane-resident phospholipids in vivo. We previously found that lack of eicosapentaenoic acid (EPA), a polyunsaturated fatty acid found at the sn-2 position of glycerophospholipids, causes a defect in cell division after DNA replication of S. livingstonensis Ac10. Here, we synthesized phospholipid probes labeled with a fluorescent 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD) group to study the localization of EPA-containing phospholipids by fluorescence microscopy. A fluorescent probe in which EPA was bound to the glycerol backbone via an ester bond was found to be unsuitable for imaging because EPA was released from the probe by in vivo hydrolysis. To overcome this problem, we synthesized hydrolysis-resistant ether-type phospholipid probes. Using these probes, we found that the fluorescence localized between two nucleoids at the cell center during cell division when the cells were grown in the presence of the eicosapentaenyl group-containing probe (N-NBD-1-oleoyl-2-eicosapentaenyl-sn-glycero-3-phosphoethanolamine), whereas this localization was not observed with the oleyl group-containing control probe (N-NBD-1-oleoyl-2-oleyl-sn-glycero-3-phosphoethanolamine). Thus, phospholipids containing an eicosapentaenyl group are specifically enriched at the cell division site. Formation of a membrane microdomain enriched in EPA-containing phospholipids at the nucleoid occlusion site probably facilitates cell division.

The number of elderly patients who undergo hepatectomy for hepatocellular carcinoma (HCC) has been increasing. Therefore, criteria for selection of an appropriate hepatectomy procedure are required.Two hundred and twenty-nine HCC patients undergoing hepatectomy were enrolled in the present study. Patients were classified into two groups: the elderly group (age ≥75 years, n=34) and the non-elderly group (age75 years, n=195). The hepatectomy procedure was selected based on the prognostic score (PS) formula, that includes patient age as a variable.The incidence of non-anatomical resection was higher (p=0.015) and the weight of resected specimens was lower (p=0.019) in the elderly group than in the non-elderly group. No significant difference was observed in the postoperative complication rate between the two groups. The 5-year survival rates were comparable between the two groups.Favorable short- and long-term outcomes can be obtained based on cautious selection criteria for hepatectomy procedures, while considering patient age, in the treatment of elderly patients with HCC.

The role of the double bonds in docosahexaenoic acid (22:6 Δ4,7,10,13,16,19 ; DHA) in cytotoxic lipid peroxidation was studied in a superoxide dismutase-defective human colorectal tumor cell line, HT-29. In a conventional culture, DHA and other polyunsaturated fatty acids (PUFAs) were found to induce acute lipid peroxidation and subsequent cell death. PUFAs that lack one or both the terminal double bonds (Δ19 and Δ4) but share Δ7,10,13,16 such as 22:5 Δ7,10,13,16,19 , 22:5 Δ4,7,10,13,16 , and 22:4 Δ7,10,13,16 were more effective than DHA. Lipid peroxidation and cell death were completely inhibited, except by 22:4 Δ7,10,13,16 when radical-mediated reactions were suppressed by culturing cells in 2% O 2 in the presence of vitamin E. DHA and C22:5 PUFAs but not 22:4 Δ7,10,13,16 were efficiently incorporated in phosphatidylinositol, regardless of the culturing conditions. These and other results suggested that the internal unsaturations Δ7,10,13,16 were sensitive to lipid peroxidation, whereas the terminal ones Δ19 and Δ4 appeared to be involved in assimilation into phospholipids.

Background The optimal surgical management for adenocarcinoma of the esophagogastric junction, including surgical approach, range of nodal dissection, and type of gastrectomy remains controversial. Methods In our two institutions, from January 2001 to September 2016, we retrospectively analyzed clinicopathological factors and long-term results of 72 patients who underwent radical resection and evaluated the priority of nodal dissection based on the therapeutic value index [ = the frequency of lymph node metastasis (%) x the 5-year survival rate (%)/100] and recurrence pattern. Results Median age:66 (44–94), male/female = 54/18, TG/PG = 60/12, Tumor size Conclusion Our study showed that distal gastric lymph nodes dissection is unnecessary, and gastrectomy with lower mediastinal and proximal gastric lymph node dissection is recommended for the treatment of adenocarcinoma of EGJ. Since diffuse type and pN2–3 were independent prognostic factors even after potentially curative resection, so additional chemotherapy might be required for such cases. Disclosure All authors have declared no conflicts of interest.

Electrochemical power sources that use oxygen as a reactant may play an essential role in the future energy needs of the society. In particular, fuel cells, aqueous metal-air batteries, and metal hydride (MH)/air batteries hold promise as power sources beyond lithium-ion batteries. An alkaline solution is often employed as the electrolyte for such electrochemical power sources, and an oxygen electrode reaction occurs at the cathode. However, the development of highly active catalysts (i.e., with low activation overpotential) for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) remains challenging. We focus on the pyrochlore type metal oxide including bismuth and ruthenium ions as Bi2Ru2O7 (BRO) and have devoted to evaluate the overpotentials and Tafel slopes for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). If the carbonaceous materials are used as the electrode substrate and the additives for the electrochemical measurements, its activity for ORR as well as its oxidation during OER should be concerned. Then, we attempted to evaluate the overpotentials and Tafel slopes by using a titanium substrate. BRO was prepared by a precipitation method. Bi(NO3)3 and RuCl3 aqueous solutions were separately prepared and well mixed in a 1 : 1 molar ratio. The mixed solution was heated up to 75 oC and stirred for 1 hour. Then, NaOH aqueous solution was added to the mixed solution to produce a precipitate and stirred for 72 hour. After that, the precipitate was made for calcination under atmospheric air at 250, 400, 500 and 600 oC for 3 hour. Finally, it was washed with pure water and dried at 120 oC for 3 hour. X-ray diffraction (XRD) was used to characterize the product. The weight change during the calcination was investigated by Thermo-gravimetry. The catalytic behavior for ORR and OER was investigated by a rotating ring disk electrode (RRDE). The disk and ring electrodes were made by titanium (Ti) and Pt, respectively. The product was dispersed on Ti substrate. Hg|HgO reference electrode and a Ni mesh counter electrode were placed in a perfluoroalkoxyalkane beaker cell. The electrolyte was 0.1 mol dm-3 KOH aqueous solution. The XRD patterns of the products were assigned for Bi2Ru2O7 when the calcination temperature was below 500 oC. On the other hand, it was likely to assign to Bi1.9Ru2O6.91 after the calcination at 600 oC. These results indicated that both of oxygen and bismuth were partially decreased between 500 oC and 600 oC. The lattice constant became to be small with raising the calcination temperature; while the crystallite size increased. Figure 1 (a) and (b) shows the hydrodynamic voltammograms for ORR and OER in 0.1 mol dm-3 KOH solution. Here, BRO250 was the product which was obtained at the 250 oC and the others was given by the same manner. The reduction currents originated from ORR were shown below 0.90 V in (a) and therefore the overpotentials were considered to be around 0.3 V. The overpotentials and Tafel slopes for OER were around 0.2 V and 60-70 mV dec-1, respectively. The overpotentials and Tafel slopes for both of ORR and OER were not strongly dependent on the calcination temperature over 250 oC. The addition of aluminum ion to the preparation of BRO will be also discussed. This work was supported by “Advanced Low Carbon Technology Research and Development Program (ALCA)” of Japan Science and Technology Agency (JST). Figure 1

5544Background: With the progress of immune-oncology, the immunological background of epithelial ovarian carcinoma (EOC) is gradually becoming understood. However, most of the studies have been foc...

5562Background: iPocc is a randomized, multicenter international study comparing the efficacy of first line intravenous (IV) dose-dense paclitaxel and intraperitoneal (IP) carboplatin with standard...

application/pdf

An Antarctic psychrotrophic bacterium, Shewanella livingstonensis Ac10, produces cis-5,8,11,14,17-eicosapentaenoic acid (EPA), a long-chain polyunsaturated fatty acid (LPUFA), as a component of membrane phospholipids at low temperatures. The EPA-less mutant generated by disruption of the EPA synthesis gene becomes cold-sensitive. We studied whether the cold sensitivity could be suppressed by supplementation of various LPUFAs. The EPA-less mutant was cultured at 6 degrees C in the presence of synthetic phosphatidylethanolamines (PEs) that contained oleic acid at the sn-1 position and various C20 fatty acids with different numbers of double bonds from zero to five or cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) at the sn-2 position. Mass spectrometric analyses revealed that all these fatty acids became components of various PE and phosphatidylglycerol species together with shorter partner fatty acids, indicating that large-scale remodeling followed the incorporation of synthetic PEs. As the number of double bonds in the sn-2 acyl chain decreased, the growth rate decreased and the cells became filamentous. The growth was restored to the wild-type level only when the medium was supplemented with phospholipids containing EPA or DHA. We found that about a half of DHA was converted into EPA. The results suggest that intact EPA is best required for cold adaptation of this bacterium.

Geranylgeranyl reductase from Sulfolobus acidocaldarius was shown to catalyze the reduction of geranylgeranyl groups in the precursors of archaeal membrane lipids, generally reducing all four double bonds. However, when geranylgeranyl diphosphate was subjected to the reductase reaction, only three of the four double bonds were reduced. Mass spectrometry and acid hydrolysis indicated that the allylic double bond was preserved in the partially reduced product derived from geranylgeranyl diphosphate. Thus, the reaction product was shown to be phytyl diphosphate, which is a substrate for archaeal prenyltransferases, unlike the completely reduced compound phytanyl diphosphate.

In 2014, we published an article titled “Novel uterine sarcoma preoperative diagnosis score predicts the need for surgery in patients presenting with a uterine mass” on the preoperative diagnosis of uterine sarcoma, in the SpringerPlus (Nagai et al. in SpringerPlus 2014, 3:678. doi: 10.1186/2193-1801-3-678 ). Subsequently, we received several suggestions from readers, which were used to modify the statistical analysis methods and create a more precise preoperative diagnostic scoring system, which we present here as a supplemental report. The subjects were 63 patients who underwent surgical therapy for suspected uterine sarcoma (sarcoma group: 15 patients, benign group: 48 patients). Logistic regression analysis using the exact method was performed considering the subjects’ preoperative age, serum lactate dehydrogenase levels, magnetic resonance imaging findings, and endometrial cytology findings. We then used parameter estimates obtained from this analysis to revise the PREoperative Sarcoma Score (PRESS). The revised PRESS (rPRESS) has a maximum score of 10 points and an optimal cut-off value of 4 points, as derived from a receiver operating characteristic curve. Using this, the accuracy, positive predictive value, and negative predictive value were 93.7, 92.3, and 94.0 %, respectively. The diagnostic precision of the rPRESS is better than that of the original PRESS.

The glycoprotein-gene (G gene) -deleted rabies virus (RV) vector is a powerful tool to examine the function and structure of neural circuits. We previously reported that the deletion of the G gene enhances the transgene expression level of the RV vector. However, the mechanism of this enhancement remains to be clarified. We presume that there are two possible factors for this enhancement. The first factor is the glycoprotein of RV, which shows cytotoxicity; thus, may cause a dysfunction in the translation process of infected cells. The second possible factor is the enhanced expression of the L gene, which encodes viral RNA polymerase. In the RV, it is known that the gene expression level is altered depending on the position of the gene. Since G-gene deletion displaces the L gene in the genome, the expression of the L gene and viral transcription may be enhanced. In this study, we compared the transgene expression level and viral transcription of three recombinant RV vectors. The effect of glycoprotein was examined by comparing the viral gene expression of G-gene-intact RV and G-gene-replaced RV. Despite the fact that the L-gene transcription level of these two RV vectors was similar, the G-gene-replaced RV vector showed higher viral transcription and transgene expression level than the G-gene-intact RV vector. To examine the effect of the position of the L gene, we compared the viral gene expression of the G-gene-deleted RV and G-gene-replaced RV. The G-gene-deleted RV vector showed higher L-gene transcription, viral transcription, and transgene expression level than the G-gene-replaced RV vector. These results indicate that G-gene deletion enhances the transgene expression level through at least two factors, the absence of glycoprotein and enhancement of L-gene expression. These findings enable investigators to design a useful viral vector that shows a controlled desirable transgene expression level in applications.

The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.

Although intraoperative peritoneal lavage is often performed routinely with the aim of reducing peritoneal contamination, little evidence of lavage benefits in elective liver resection without bile duct resection is available. We addressed the issue with a randomized clinical trial.We prospectively and randomly assigned consecutive patients undergoing liver resection to a lavage group or a non-lavage group. Peritoneal lavage was performed at the end of operation for patients in the lavage group. The primary endpoint was the rate of surgical site infection.Ninety-six patients were assigned to the lavage group and 97 to the non-lavage group. When superficial/deep incisional infection and organ/space infection were considered together, no significant difference in surgical site infection rate was evident between lavage (21.9%) and non-lavage groups (13.4%, P = 0.135). However, organ/space infection was significantly more frequent in the lavage group (16.7%) than the non-lavage group (7.2%, P = 0.048). Peritoneal lavage was identified as a risk factor for organ/space infection by multivariate analysis (relative risk, 2.977; confidence interval, 1.094 to 8.100; P = 0.033).Intraoperative peritoneal lavage does not reduce overall incidence of surgical site infection and may increase risk of organ/space infection.

Preoperative diagnosis of uterine sarcoma is very difficult, and currently, its diagnostic accuracy is not satisfactory. It is therefore important to perform surgery and establish the pathological diagnosis if the clinical findings and various examination findings indicate possible uterine sarcoma. We investigated the accuracy of the combination of various types of predictors of uterine sarcoma and the novel PRE operative S arcoma S core (PRESS) for avoiding unnecessary surgery while diagnosing uterine sarcoma. We retrospectively analyzed the clinical findings, blood tests, imaging studies (ultrasonography and magnetic resonance imaging [MRI]), and endometrial cytology of 63 suspected uterine sarcoma cases that underwent surgery from 2006 to 2012. These cases were also scored retrospectively using PRESS. We analyzed the number of unnecessary surgeries that could be avoided using PRESS. Of 63 cases, 15 were diagnosed with uterine sarcoma (sarcoma group), and 48 had benign tumors (benign group). Univariate analysis indicated age, serum lactate dehydrogenase (LDH) values, and MRI and endometrial cytology findings as significant predictors of uterine sarcoma in both groups. In contrast, multivariable analysis identified only age, serum LDH value, and endometrial cytology findings as significant predictors. Accordingly, the latter were placed as 2 points, and the remaining MRI finding as 1 point. The accuracy rate of prediction was 84.1%, and the positive and negative predictive values were 63.2% and 93.2% respectively when the PRESS was interpreted as “positive” when it was 3 points or higher. Using multiple predictors for the preoperative diagnosis of uterine sarcoma, our proposed PRESS score is beneficial in the clinical setting while making treatment decisions in suspected uterine sarcoma cases as well as avoiding unnecessary surgery.

筆者らは、看護技術の修得には不可欠な学生の自己学習を支援する目的で、授業の中のデモンストレーションを撮影・編集し、ビデオ教材を作成している。これまで市販のビデオ教材ではなく自作のビデオ教材にこだわってきた。今回アンケート調査により、学生達は、自主練習の過程で有効にビデオ教材を利用していることが明らかになり、学生の自己学習支援のひとつとして、自作のビデオ教材必要とされていることが分かった。また、今後の課題としては、ビデオ教材だけでなく、他の教材も使い総合的に学生の自己学習支援をしていく必要があることが明らかになった。

学生の基礎看護技術の学習環境を整備し、自己学習を促進するように学内LANを活用し『看護の基礎』ホームページを作成した。その有用性を評価するために、学生にアンケートを実施した。アンケート結果によると、学生は『看護の基礎』のホームページは必要であり、基礎看護技術の学習に役立つと答えている。しかし、改善すべき点があることもわかった。『看護の基礎』のホームページが学生にとってさらに活用され、学生の自己学習支援に役立つためには、「情報の発信と交流」「技術学習支援のための教育環境整備」「エビデンスに基づいた看護技術の知識の学習支援」「自己学習の促進」という課題が明らかになった。

Fibroblast growth factor 4 (FGF4) is considered as a crucial gene for the proper development of bovine embryos. However, the complete nucleotide sequences of the structural genes encoding FGF4 in identified breeds are still unknown. In the present study, direct sequencing of PCR products derived from genomic DNA samples obtained from three Japanese Black, two Japanese Shorthorn and three Holstein cattle, revealed that the nucleotide sequences of the structural gene encoding FGF4 matched completely among these eight cattle. On the other hand, differences in the nucleotide sequences, leading to substitutions, insertions or deletions of amino acid residues were detected when compared with the already reported sequence from unidentified breeds. We cannot rule out a possibility that the structural gene elucidated in the present study is widely distributed in cattle. To the best of our knowledge, this is the first determination of the complete nucleotide sequence of the structural gene encoding bovine FGF4 in identified breeds.