Mössbauer Spectroscopic Study on Hofmann-like Coordination Polymer Fe(4-Clpy)2[Ni(CN)4]

57Fe Mössbauer spectroscopic results on the 2D Hofmann-like coordination polymer Fe(4-Clpy)2Ni(CN)4 (sample 1) indicate that iron(II) ions are in a high spin state both at R.T. and T = 80 K, showing that the compound exhibits no spin crossover (SCO) behavior. Mössbauer spectra at R.T. and T = 80 K show one major doublet which corresponds to the HS1 is due to high spin iron(II) sites coordinated by four N atoms of cyano groups and two N atoms of 4-Clpy ligand in the sample 1. Two minor doublets coexisted in sample 1. One minor doublet with a large quadrupole splitting can be explained by the presence of defects in the coordination polymer frameworks. Another minor doublet is with a small quadrupole splitting, indicating the presence of iron(III) high spin species or iron(II) low spin species. This work is licensed under a Creative Commons Attribution 4.0 International License

Examining the Validity of Efforts of the Muscular Dystrophy Medical Network in Nagano : A Questionnaire Study

Article信州医学雑誌 66(3): 205-212(2018)journal articl

Inhibition of EP2/EP4 signaling abrogates IGF-1R-mediated cancer cell growth : Involvement of protein kinase C-θ activation

Associations between growth factor receptor-mediated cell signaling and cancer cell growth have been previously characterized. Receptors for prostaglandin E2, such as EP2, and EP4, play roles in cancer growth, progression and invasion. Thus, we examined the interactions between EP2/EP4- and IGF-1R-mediated cellular signaling in human pancreatic cancer cells. Selective antagonists against EP2 and EP4 abrogated IGF-1-stimulated cell growth and suppressed MEK/ERK phosphorylation. In subsequent experiments, phospho-antibody arrays indicated increased phosphorylation levels of protein kinase C-θ (PKC-θ) at the Thr538 position following the inhibition of EP2/EP4-mediated signaling. Inhibition of PKC-θ activity impaired cell viability compared with EP2/EP4-antagonized IGF-1-stimulated cells. PKC-θ kinase MAP4K3, which plays a pivotal role in PKC-θ activation, also affected growth signaling in the presence of EP2/EP4 antagonists. Administration of EP2 and EP4 antagonists significantly inhibited the growth of an orthotopic xenograft of IGF-1-secreting pancreatic cancer cells, with increased phospho-PKC-θ and decreased phospho-ERK. Clinico-pathological analyses showed that 17.4% of surgical pancreatic cancer specimens were quadruple-positive for IGF-1R, EP2 (or EP4), MAP4K3, and PKC-θ. These results indicate a novel signaling crosstalk between EP2/EP4 and IGF-1R in cancer cells, and suggest that the MAP4K3-PKC-θ axis is central and could be exploited as a molecular target for cancer therapy

Selective loss of GABAB receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture

We generated mice with a selective loss of GABAB receptors in orexin neurons. Orexin neurons in these GABAB1<sup>-/-(orexin)</sup> mice showed reduced responsiveness to GABA<sub>A</sub> receptor agonists due to a compensatory increase in GABAA receptor-mediated inhibition. This increased GABA<sub>A</sub> receptor-mediated inhibition of orexin neurons is due to orexin-1 receptor-mediated activation of local GABAergic interneurons. Surprisingly, orexin neurons were also less responsive to glutamate, apparently because the augmented GABA<sub>A</sub> receptor-mediated inhibition increases the membrane conductance and shunts excitatory currents. These observations indicate that absence of GABA<sub>B</sub> receptors decreases the sensitivity of orexin neurons to both excitatory and inhibitory inputs. GABAB1<sup>-/-(orexin)</sup>mice exhibited severe fragmentation of sleep/wake states during both the light and dark periods without affecting total sleep time or inducing cataplexy, indicating that GABA<sub>B</sub> receptors are crucial regulators of orexin neurons and that "fine tuning" of orexin neurons by inhibitory and excitatory inputs is important for the stability of sleep/waking states

酢酸摂取と運動が脂肪代謝と運動耐久性に及ぼす影響

Previously, we found that acetic acid had effects on lipid metabolism in skeletal muscles and has functions that work against obesity and obesity-linked type 2 diabetes through the activation of AMPactivated protein kinase (AMPK). During exercise, AMPK is activated in skeletal muscle according to exercise intensity and it increases fatty acid oxidation. The purpose of this study was to investigate the interactive effects of chronic intake of acetic acid and exercise training on lipid metabolism and endurance performance. Six-week-old SD rats were randomly assigned to four groups: water-injected (rest-water), acetic acid-injected (rest-ace), exercise-trained after injection of water (water-ex), and exercise-trained after injection of acetic acid (ace-ex) for 4 weeks. Body weight (BW) in rest-ace and ace-ex groups was significantly lower than rest-water group. Exercise-training groups showed an increase of exercise capacity, by the addition of intake of acetic acid, lipid oxidation was promoted during exercise tolerance test. Skeletal muscle of rats treated with acetic acid and exercise training led to higher expressions of cytochrome c (cycs), and tended to stimulate expressions of peroxisome proliferator-activated receptor coactivator 1-α (PGC1-α ) and MHC1 genes than those of rest-water group. Those results indicate that treatments both of exercise training and intake of acetic acid contribute to enhancement of lipid metabolism and improvement of exercise capacity.これまで我々は、酢酸の摂取が骨格筋内のAMP活性化プロテインキナーゼ（AMPK）の活性化を介して脂質代謝と肥満、肥満に関連した2型糖尿病の予防に効果があることを示唆してきた。AMPKは運動によって骨格筋で活性化し、脂肪酸酸化を促進する。この研究は、4週間の継続的な酢酸摂取と運動トレーニングが運動中の脂肪代謝と運動耐久性に及ぼす影響について調べることを目的とした。　6週齢のSD系雄ラットを安静期に水を摂取するrest-water群、酢酸を摂取するrest-ace群、運動前に水を摂取するwater-ex群、運動前に酢酸を摂取するace-ex群に無作為に分け実験を行った。酢酸を継続的に摂取すると水摂取に比較して腹腔内脂肪量の減少と体重増加の抑制がみられた。また継続的な酢酸摂取および運動トレーニングにより、耐久性運動下でのグルコース利用の抑制および脂肪酸酸化の促進が見られた。酢酸摂取および運動トレーニング群の腓腹筋では、MHCIおよびcytochrome c等の遅筋線維マーカー遺伝子が増加していた。継続的な酢酸摂取と運動トレーニングにより、脂肪代謝と運動耐久性の向上が示唆された

琉球大学学術リポジトリの可視性戦略

DRFIC2008 Poster Session No.14DRFIC2008 ポスターセッション資料 14

Electroneurography in the acute stage of facial palsy as a predictive factor for the development of facial synkinesis sequela

Objective We investigated whether the value of ENoG is a predictive factor for the development of facial synkinesis in patients with facial palsy. Methods The degree of oral-ocular synkinesis was evaluated quantitatively by an asymmetry of the interpalpebral space width during the mouth movement (% eye opening). Twenty healthy volunteers without a history of facial palsy (12 men and 8 women; 25-65 years old; mean age: 42.3 ± 9.7 years) were included in the study to examine the normal range of % eye opening. Fifty-one patients with facial palsy including 38 with Bell palsy and 15 with herpes zoster oticus (28 men and 25 women; 11-86 years old; mean age: 54 ± 19 years) were enrolled to examine the relationship between the ENoG value 10-14 days after the onset of facial palsy, and the % eye opening 12 months later. Receiver operating characteristic (ROC) curve for the ENoG value was then used to decide the optimum cut-off value as a predictor of the development of oral-ocular synkinesis. Results We defined a % eye opening inferior to 85% as an index of the development of oral-ocular synkinesis. There was a significant correlation between the values of ENoG 10-14 days after the onset of facial palsy and those of % eye opening 12 months later (ρ=0.81, p<0.001). The area under the ROC curve for the ENoG value was the predictor for the development of oral-ocular synkinesis at 0.913 (95%CI: 0.831-0.996, p<.001). The optimum cut-off value of ENoG 10-14 days after the onset of facial palsy was 46.5% to predict the development of oral-ocular synkinesis 12 months after the onset of facial palsy (sensitivity 97.1% and specificity 77.5%). Conclusion The value of ENoG 10-14 days after the onset of facial palsy is a predictive factor for the development of facial synkinesis 12 months later. Since facial palsy patients with a ENoG value inferior to 46.5% have a high risk of developing synkinesis, they should receive the facial biofeedback rehabilitation with a mirror as a preventive therapy

CFTR associated diarrhea in VP-infection

Vibrio parahaemolyticus is a foodborne bacterium that causes acute gastroenteritis through the consumption of contaminated, raw, or undercooked seafood. Cystic fibrosis transmembrane conductance regulator (CFTR) is a well-characterized chloride channel that regulates several other ion channels and transporters to maintain water homeostasis in the gut lumen. Also, CFTR is a main target of bacterial infection-associated diarrhea. Hence, the aim of this study was to clarify the contribution of CFTR in V. parahaemolyticus-induced diarrhea in a mouse model of intestinal loop fluid accumulation, with CFTR inhibitors and a CFTR knockout model. The results indicated that CFTR plays a critical role in fluid accumulation in response to V. parahaemolyticus infection. We also investigated the inflammatory association in CFTR-mediated V. parahaemolyticus-induced fluid secretion with cyclooxygenase inhibitors and found that fluid accumulation was decreased by inhibition of cyclooxygenase 2 produced by neutrophils. These findings suggest that V. parahaemolyticus-inducing infiltration and activation of neutrophils also participated in CFTR mediated fluid secretion. This study reveals an important relationship between V. parahaemolyticus-induced diarrhea and inflammation in a mouse model