CO(2) Fluxes Measured by Eddy Correlation and Aerodynamic Techniques

To elucidate the seasonal and inter-annual variation of CO(2) exchanges between the atmosphere and cultivated field in Japan, the CO(2) flux has been measured by the eddy correlation technique at the experimental farm of Agricultural Faculty, Okayama University since December in 1998. The CO(2) sensor, however, does not work under rainy conditions. The improved aerodynamic technique was developed and used to cover CO(2) flux data which were not collected. This technique gives reasonable CO(2) fluxes even in rainy days. The reliability of the technique was also confirmed by comparing CO(2) fluxes with those measured by the eddy correlation technique using data in fine weather conditions

Regulation of TGF-β1-Induced Pro-Apoptotic Signaling by Growth Factor Receptors and Extracellular Matrix Receptor Integrins in the Liver

Hepatocellular carcinoma (HCC) often arises from chronically diseased livers. Persistent liver inflammation causes the accumulation of excessive extracellular matrix (ECM) proteins and impairs the liver function, finally leading to the development of HCC. A pleiotropic cytokine, transforming growth factor (TGF)-β1, plays critical roles throughout the process of fibrogenesis and hepatocarcinogenesis. In the liver, TGF-β1 inhibits the proliferation of hepatocytes and stimulates the production of ECM from hepatic stellate cells (HSCs) to maintain tissue homeostasis. During disease progression, both growth factors/cytokines and the ECM alter the TGF-β1 signals by modifying the phosphorylation of Smad proteins at their C-terminal and linker regions. TGF-β1 stimulates the expression of integrins, cellular receptors for ECM, along with an increase in ECM accumulation. The activation of integrins by the ECM modulates the response to TGF-β1 in hepatic cells, resulting in their resistance to TGF-β1-induced growth suppression in hepatocytes and the sustained production of ECM proteins in activated HSCs/myofibroblasts. Both growth factor receptors and integrins modify the expression and/or functions of the downstream effectors of TGF-β1, resulting in the escape of hepatocytes from TGF-β1-induced apoptosis. Recent studies have revealed that the alterations of Smad phosphorylation that occur as the results of the crosstalk between TGF-β1, growth factors and integrins could change the nature of TGF-β1 signals from tumor suppression to promotion. Therefore, the modification of Smad phosphorylation could be an attractive target for the prevention and/or treatment of HCC

Intrauterine growth and the maturation process of adrenal function

Backgrounds Environmental factors during early life alter the hypothalamus-pituitary-adrenal (HPA) axis regulation and increase the risk of diseases in later life. However, adrenal function at each developmental stage has not fully been investigated in relation to pathological antenatal conditions. Cortisol levels of newborns with intrauterine growth restriction (IUGR) are elevated during the neonatal period; however, when studied during early childhood, cortisol levels are reduced compared with their peers, suggesting that the HPA axis regulation might be altered from activation to suppression, the timing of which remains uncertain. Aim The aim of this study was to assess the presence of an interaction between intrauterine growth and postnatal age on cortisol levels in newborns hospitalised at a neonatal intensive care unit. Methods We performed a secondary analysis using a dataset from saliva samples of 62 newborns collected between 30 and 40 weeks corrected age. Interactions between postnatal age and clinical variables with regard to cortisol levels were assessed. Results The z-score of the birth weight and IUGR showed significant interactions with postnatal age on cortisol levels; cortisol levels were higher ≤5 days of birth and lower >14 days of birth than those in their peers without IUGR. Conclusion The adrenal function of newborns with IUGR might be altered from activation to suppression within the first several weeks of life. Longitudinal studies need to address when/how IUGR alters adrenal functions, and how these responses are associated with diseases during adulthood

脊椎手術中のMonophasic刺激下での経頭蓋刺激筋誘発電位における定電流刺激と定電圧刺激での比較検討

Constant-voltage and constant-current stimulators may be used for transcranial electrical stimulation of motor evoked potentials (TES-MEP). However, no previous report has determined whether the two monophasic stimulation methods lead to similar responses during intra-operative monitoring. We studied differences in the lateralities of compound muscle action potentials (CMAPs) during intra-operative spinal cord monitoring via TES-MEP using monophasic constant-current and constant-voltage stimulations. CMAPs were bilaterally recorded from the upper and lower limb muscles in 95 patients who underwent elective spine and spinal cord surgery. We used two monophasic stimulation patterns: pattern 1, right anode and left cathode; pattern 2, right cathode and left anode. There were no statistically significant differences between the right and left sides with respect to success rates, wave amplitudes, and efficiencies, with constant-voltage stimulation, however, there were statistically significant differences between the right and left sides with constant-current stimulation. In case of our stimulation condition, there were no statistically significant differences between the right and left sides with respect to CMAPs with constant-voltage stimulation; constant-current stimulation was influenced by the type of monophasic stimulation, which necessitates the switch the polarity of the stimulation to bilaterally record CMAPs.博士（医学）・甲第725号・令和元年12月5日© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Regulation of tumor suppressor PDCD4 by novel protein kinase C isoforms

AbstractTransforming growth factor-β1 (TGF-β1) induces apoptosis in normal hepatocytes and hepatoma cells. PDCD4 is involved in TGF-β1-induced apoptosis via the Smad pathway. The tumor promoter 12-O-tetradecanoylphorbor-13-acetate (TPA), a protein kinase C stimulator, inhibits TGF-β1-induced apoptosis. However, the mechanisms of TPA action on PDCD4 expression remain to be elucidated. Therefore. the regulatory mechanism of PDCD4 expression by PKC was investigated. The treatment of the human hepatoma cell line, Huh7 with TPA suppressed PDCD4 protein expression and TGF-β1 failed to increase the PDCD4 protein expression. PKC inhibitors Ro-31-8425 or bisindolylmaleimide-1-hydrocholoride (pan-PKC inhibitors) and rottlerin (PKCδ inhibitor), but not Go6976 (PKCα inhibitor), enhanced the induction of PDCD4 protein by TGF-β1. Furthermore, siRNA-mediated knockdown of PKCδ and ε, but not PKCα, augmented the TGF-β1-stimulated PDCD4 protein expression. However, TPA or pan-PKC inhibitor did not alter the PDCD4 mRNA expression either under basal- and TGF-β1-treated conditions. The down-regulation of PDCD4 by TPA was restored by treatment with the proteasome inhibitor MG132. These data suggest that two isoforms of PKCs are involved in the regulation of the PDCD4 protein expression related to the proteasomal degradation pathway

PDCD4 Knockdown Induces Senescence in Hepatoma Cells by Up-Regulating the p21 Expression

While the over-expression of tumor suppressor programmed cell death 4 (PDCD4) induces apoptosis, it was recently shown that PDCD4 knockdown also induced apoptosis. In this study, we examined the cell cycle regulators whose activation is affected by PDCD4 knockdown to investigate the contribution of PDCD4 to cell cycle regulation in three types of hepatoma cells: HepG2, Huh7 (mutant p53 and p16-deficient), and Hep3B (p53- and Rb-deficient). PDCD4 knockdown suppressed cell growth in all three cell lines by inhibiting Rb phosphorylation via down-regulating the expression of Rb itself and CDKs, which phosphorylate Rb, and up-regulating the expression of the CDK inhibitor p21 through a p53-independent pathway. We also found that apoptosis was induced in a p53-dependent manner in PDCD4 knockdown HepG2 cells (p53+), although the mechanism of cell death in PDCD4 knockdown Hep3B cells (p53-) was different. Furthermore, PDCD4 knockdown induced cellular senescence characterized by β-galactosidase staining, and p21 knockdown rescued the senescence and cell death as well as the inhibition of Rb phosphorylation induced by PDCD4 knockdown. Thus, PDCD4 is an important cell cycle regulator of hepatoma cells and may be a promising therapeutic target for the treatment of hepatocellular carcinoma