Lineshape of the Lambda(1405) Hyperon Measured Through its Sigma0 pion0 Decay

The pp -> p K+ Y0 reaction has been studied for hyperon masses m(Y0)<1540 MeV/c2 at COSY-Juelich by using a 3.65 GeV/c circulating proton beam incident on an internal hydrogen target. Final states comprising two protons, one positively charged kaon and one negatively charged pion have been identified with the ANKE spectrometer. Such configurations are sensitive to the production of the ground state Lambda and Sigma0 hyperons as well as the Sigma0(1385) and Lambda(1405) resonances. Applying invariant- and missing-mass techniques, the two overlapping excited states could be well separated, though with limited statistics. The shape and position of the Lambda(1405) distribution, reconstructed cleanly in the Sigma0 pion0 channel, are similar to those found from other decay modes and there is no obvious mass shift. This finding constitutes a challenging test for models that predict Lambda(1405) to be a two-state resonance.Comment: 10 pages, 4 figures, accepted for publication in Phys. Lett.

bFGF徐放性材料を用いた骨再生モデルにおける骨再生と血管新生の検討

骨欠損に対して再生医学的アプローチをする上で,骨再生組織への新生血管による血液の供給や循環は,安定した骨の形成や感染防御の面において重要であると考えられる.本研究は,bFGF徐放システムによる骨再生モデルを用いて,マイクロフォーカスCTにより同一個体の経時的な骨再生の経過を観察し,連続組織標本を作製することで,骨再生と血管新生の関係を明らかにすることを目的とした.実験方法は,10週齢のWistar系ラットの頭頂骨に直径7mmの骨欠損を形成し,実験群にはbFGF 10μg含有酸性ゼラチンディスクを埋入した.また,対照群には同ディスクに生理食塩液を含浸させたものを埋入した.埋入後2日,1週,2週,4週に同一ラットをマイクロフォーカスCTにて撮影し,三次元画像解析ソフトにて三次元的に骨再生の経過を観察した.また,埋入後1週と4週に連続組織標本をFilm-transfer法にて作製し,H-E染色を行った後,冷却3CCDカメラ装着光学顕微鏡にて二次元コンピューター画像に入力し,再生骨と新生血管の同定を行った.実験の結果,マイクロフォーカスCT所見では,実験群は埋入後2日で再生現象を確認することができなかったが,埋入後1週,2週になると軽度の骨再生が認められ,4週まで継続していた.骨体積計測の結果,埋入後2日,1週,2週では実験群と対照群との間に有意差は認められなかったが,4週には対照群に対し実験群では有意に体積が増加していた(P<0.05).このことから,bFGFによる骨再生誘導は埋入後1週から2週の時期から行われ,4週には骨再生が行われていることが示唆された.組織学的評価では,埋入後1週において,新生血管は,対照群に対し実験群は有意に多く観察された(P<0.001).また,埋入後4週においても実験群は有意に多くの新生血管が観察された(P<0.001).これにより実験群は多数の新生血管により継続的に栄養供給が十分に行われていることが示唆された.以上のことから,骨欠損部へのbFGF含有のAGD埋入によりbFGFが徐放され,血管新生により血液循環と骨断端部への栄養供給が行われ,骨再生誘導に効果を現していることが考えられた.In devising regenerative medical approaches to bone defects, the blood supply to, and perfusion of, regenerated bone tissue by angiogenesis is considered important to ensure stable bone formation and the prevention of infection. This study was conducted to clarify the relationship between bone regeneration and the angiogenesis bFGF sustained release system by serially observing the process of bone regeneration in the same rats, employing microfocus X-ray CT and preparing serial tissue sections. A bone defect of 7mm in diameter was prepared in the parietal region of 10-week-old Wistar rats, and an acidity gelatin disc (AGD) containing 10μg of bFGF was embedded in the study group. In the control group, the same disc saturated with physiologic saline was embedded. The rats were scanned by microfocus X-ray CT 2 days, 1 week, 2 weeks, and 4 weeks after disc embedding, and the process of bone regeneration was three-dimensionally observed using 3D visualization software. Also, 1 and 4 weeks after disc embedding, serial tissue sections were prepared using the film-transfer method, H-E staining was performed, their 2-dimensional images were input into a computer via an optical microscope with a color-chilled 3CCD camera, and regenerated bone and newly-formed vessels were identified. By microfocus X-ray CT, bone regeneration could not be confirmed 2 days after disc embedding in the study group, but slight bone regeneration was noted 1 and 2 weeks after disc embedding, and bone regeneration continued until after 4 weeks. As a result of measurement of the bone volume, no significant difference was noted between the study and control groups 2 days, 1 week, or 2 weeks after disc embedding, but the bone volume had increased in the study group compared with the control group after 4 weeks (p<0.05). This suggests that bFGF began to induce bone regeneration 1 or 2 weeks after disc embedding and continued to promote bone regeneration until after 4 weeks. Histological evaluation showed that the number of newly-formed vessels was significantly higher in the study group than in the control group 1 week (p<0.001) and 4 weeks (p<0.001) after disc embedding. This suggests that the regenerated bone was sufficiently and continuously supplied blood by many newly formed vessels in the study group. These results suggest that bFGF is slowly released from the AGD containing bFGF embedded at the site of the bone defect, that blood and nutrients are supplied by angiogenesis, and that the treatment is effective for inducing bone regeneration

Therapy for CKD-associated muscle dysfunction

Background Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice. Methods The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups. Results In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level. Conclusions Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance

Pseudopodium-enriched atypical kinase 1 mediates angiogenesis by modulating GATA2-dependent VEGFR2 transcription

PEAK1 is a newly described tyrosine kinase and scaffold protein that transmits integrin-mediated extracellular matrix (ECM) signals to facilitate cell movement and growth. While aberrant expression of PEAK1 has been linked to cancer progression, its normal physiological role in vertebrate biology is not known. Here we provide evidence that PEAK1 plays a central role in orchestrating new vessel formation in vertebrates. Deletion of the PEAK1 gene in zebrafish, mice, and human endothelial cells (ECs) induced severe defects in new blood vessel formation due to deficiencies in EC proliferation, survival, and migration. Gene transcriptional and proteomic analyses of PEAK1-deficient ECs revealed a significant loss of vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression, as well as downstream signaling to its effectors, ERK, Akt, and Src kinase. PEAK1 regulates VEGFR2 expression by binding to and increasing the protein stability of the transcription factor GATA-binding protein 2 (GATA2), which controls VEGFR2 transcription. Importantly, PEAK1-GATA2-dependent VEGFR2 expression is mediated by EC adhesion to the ECM and is required for breast cancer-induced new vessel formation in mice. Also, elevated expression of PEAK1 and VEGFR2 mRNA are highly correlated in many human cancers including breast cancer. Together, our findings reveal a novel PEAK1-GATA2-VEGFR2 signaling axis that integrates cell adhesion and growth factor cues from the extracellular environment necessary for new vessel formation during vertebrate development and cancer.NIHNCIAHANIGMS/NIHRay Thomas Edwards FoundationUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USAUniv Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, La Jolla, CA 92093 USAUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, BrazilUniv Calif San Diego, Sanford Consortium Regenerat Med, La Jolla, CA 92093 USAComenius Univ, Jessenius Fac Med Martin, Dept Mol Med, Biomed Ctr Martin, Martin 03601, SlovakiaUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, BrazilNIH: CA182495NIH: CA184594NIH: CA097022NIH: HL135737NIH: CA050286NCI: CA180374AHA: 16POST27250126NIGMS/NIH: K12GM068524Web of Scienc

Induction and Down-regulation of Sox17 and Its Possible Roles During the Course of Gastrointestinal Tumorigenesis

金沢大学がん研究所がん幹細胞研究センターBackground & Aims: The activation of Wnt/ﾎｲ-catenin signaling causes the development of gastric and colon cancers. Sox17 represses Wnt/ﾎｲ-catenin signaling and is down-regulated in colon cancer. This study was designed to elucidate the role of Sox17 during the course of gastrointestinal tumorigenesis. Methods: Sox17 expression was examined in gastrointestinal tumors of mouse models and humans. The roles of Sox17 in gastric tumorigenesis were examined by cell culture experiments and by construction of Sox17 transgenic mice. Results: Sox17 was induced in K19-Wnt1/C2mE mouse gastric tumors and K19-Wnt1 preneoplastic lesions, where Wnt/ﾎｲ-catenin signaling was activated. Consistently, Wnt activation induced Sox17 expression in gastric cancer cells. In contrast, Sox17 was rarely detected by immunohistochemistry in gastric and colon cancers, whereas strong nuclear staining of Sox17 was found in >70% of benign gastric and intestinal tumors. Treatment with a demethylating agent induced Sox17 expression in gastric cancer cells, thus indicating the down-regulation of Sox17 by methylation. Moreover, transfection of Sox17 in gastric cancer cells suppressed both the Wnt activity and colony formation efficiency. Finally, transgenic expression of Sox17 suppressed dysplastic tumor development in K19-Wnt1/C2mE mouse stomach. Conclusions: Sox17 plays a tumor suppressor role through suppression of Wnt signaling. However, Sox17 is induced by Wnt activation in the early stage of gastrointestinal tumorigenesis, and Sox17 is down-regulated by methylation during malignant progression. It is therefore conceivable that Sox17 protects benign tumors from malignant progression at an early stage of tumorigenesis, and down-regulation of Sox17 contributes to malignant progression through promotion of Wnt activity. © 2009 AGA Institute

Search for Theta+ via K+p -> pi+X reaction with a 1.2 GeV/c K+ beam

The Theta+ was searched for via the K+p -> pi+X reaction using the 1.2 GeV/c K+ beam at the K6 beam line of the KEK-PS 12 GeV Proton Synchrotron. In the missing mass spectrum of the K+p -> pi+X reaction, no clear peak structure was observed. Therefore a 90 % C.L. upper limit of 3.5 ub/sr was derived for the differential cross section averaged over 2degree to 22degree in the laboratory frame of the K+p -> pi+Theta+ reaction. This upper limit is much smaller than the theoretical calculation for the t-channel process where a K0* is exchanged. From the present result, either the t-channel process is excluded or the coupling constant of g_{K*N\Theta} is quite small.Comment: 11pages, 13figure