Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate–ubiquinone oxidoreductase

AbstractWe have mapped large (cybL) and small (cybS) subunits of cytochrome b in the succinate–ubiquinone oxidoreductase (complex II) of human mitochondria to chromosome 1q21 and 11q23, respectively (H. Hirawake et al., Cytogenet. Cell Genet. 79 (1997) 132–138). In the present study, the human SDHD gene encoding cybS was cloned and characterized. The gene comprises four exons and three introns extending over 19 kb. Sequence analysis of the 5′ promoter region showed several motifs for the binding of transcription factors including nuclear respiratory factors NRF-1 and NRF-2 at positions −137 and −104, respectively. In addition to this gene, six pseudogenes of cybS were isolated and mapped on the chromosome

Usefulness and Problems of Endoscopic Ultrasonography in Prediction of the Depth of Tumor Invasion in Early Gastric Cancer

The objectives of this study were to evaluate the accuracy of endoscopic ultrasonography (EUS) in local and regional staging of early gastric cancer, to analyze the factors influencing the accuracy of EUS, and to reveal the usefulness and problems of EUS in pre-treatment staging of gastric cancer. We examined 105 lesions in 104 patients with histologically confirmed gastric cancer and retrospectively evaluated them with EUS. The diagnostic accuracy, sensitivity, and specificity of EUS were determined by comparing the pre-treatment EUS with the postoperative histopathological findings. The overall diagnostic accuracy of EUS for the depth of cancer invasion was 86%. The overall sensitivity and specificity were 60% and 96%, respectively. The accuracy significantly declined in lesions located in the upper-third of the stomach (70%). Type 0-I lesions tended to be over-staged (12&), and the upper-third lesions tended to be under-staged (23%). The accuracy significantly declined in differentiated adenocarcinoma with massive submucosal invasion (56.5%). EUS is useful for evaluating the depth of gastric cancer invasion which determines the feasibility of endoscopic treatment. However, it is noteworthy that the diagnostic accuracy of the invasion depth diminished for lesions in the upper third of the stomach

Involvement of peripheral ionotropic glutamate receptors in orofacial thermal hyperalgesia in rats

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to elucidate the mechanisms that may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) neurons to heat or cold stimulation of the orofacial region following glutamate (Glu) injection.</p> <p>Results</p> <p>Glu application to the tongue or whisker pad skin caused an enhancement of head-withdrawal reflex and extracellular signal-regulated kinase (ERK) phosphorylation in Vc-C2 neurons. Head-withdrawal reflex and ERK phosphorylation were also enhanced following cold stimulation of the tongue but not whisker pad skin in Glu-injected rats, and the head-withdrawal reflex and ERK phosphorylation were enhanced following heat stimulation of the tongue or whisker pad skin. The enhanced head-withdrawal reflex and ERK phosphorylation after heat stimulation of the tongue or whisker pad skin, and those following cold stimulation of the tongue but not whisker pad skin were suppressed following ionotropic glutamate receptor antagonists administration into the tongue or whisker pad skin. Furthermore, intrathecal administration of MEK1/2 inhibitor PD98059 caused significant suppression of enhanced head-withdrawal reflex in Glu-injected rats, heat head-withdrawal reflex in the rats with Glu injection into the tongue or whisker pad skin and cold head-withdrawal reflex in the rats with Glu injection into the tongue.</p> <p>Conclusions</p> <p>The present findings suggest that peripheral Glu receptor mechanisms may contribute to cold hyperalgesia in the tongue but not in the facial skin, and also contribute to heat hyperalgesia in the tongue and facial skin, and that the mitogen-activated protein kinase cascade in Vc-C2 neurons may be involved in these Glu-evoked hyperalgesic effects.</p

NGCPV: A new generation of concentrator photovoltaic cells, modules and systems

This work introduces the lines of research that the NGCPV project is pursuing and some of the first results obtained. Sponsored by the European Commission under the 7th Framework Program and NEDO (Japan) within the first collaborative call launched by both Bodies in the field of energy, NGCPV project aims at approaching the cost of the photovoltaic kWh to competitive prices in the framework of high concentration photovoltaics (CPV) by exploring the development and assessment of concentrator photovoltaic solar cells and modules, novel materials and new solar cell structures as well as methods and procedures to standardize measurement technology for concentrator photovoltaic cells and modules. More specific objectives we are facing are: (1) to manufacture a cell prototype with an efficiency of at least 45% and to undertake an experimental activity, (2) to manufacture a 35% module prototype and elaborate the roadmap towards the achievement of 40%, (3) to develop reliable characterization techniques for III-V materials and quantum structures, (4) to achieve and agreement within 5% in the characterization of CPV cells and modules in a round robin scheme, and (5) to evaluate the potential of new materials, devices technologies and quantum nanostructures to improve the efficiency of solar cells for CPV

Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects

金沢大学大学院医学系研究科金沢大学医薬保健研究域医学系Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-β, α1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis. © 2008 Elsevier B.V. All rights reserved

Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis

金沢大学医薬保健研究域医学系Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and is one of the most common liver diseases in the developed world. The histological findings of NASH are characterized by hepatic steatosis, inflammation, and fibrosis. However, an optimal treatment for NASH has not been established. Tranilast, N-(3′,4′-dimedioxycinnamoyl)- anthranilic acid, is an antifibrogenic agent that inhibits the action of transforming growth factor beta (TGF-β). This drug is used clinically for fibrogenesis-associated skin disorders including hypertrophic scars and scleroderma. TGF-β plays a central role in the development of hepatic fibrosis, and tranilast may thus ameliorate the pathogenesis of NASH. We investigated the effects of tranilast using an established dietary animal model of NASH, obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats fed a methionine-deficient and choline-deficient diet. Treatment with 2% tranilast (420 mg/kg/day) for 8 weeks prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for TGF-β and TGF-β-target molecules, including α1 procollagen and plasminogen activator-1. In addition, tranilast attenuated hepatic inflammation and Kupffer cell recruitment, and down-regulated the expression of tumor necrosis factor alpha. Unexpectedly, tranilast ameliorated hepatic steatosis and up-regulated the expression of genes involved in beta-oxidation, such as peroxisome proliferator-activated receptor α and carnitine O-palmitoyltransferase-1. Most of these effects were observed in LETO rats and OLETF rats, which suggest that the action of tranilast is mediated through the insulin resistance-independent pathway. Conclusion: Our findings suggest that targeting TGF-β with tranilast represents a new mode of therapy for NASH. Copyright © 2008 by the American Association for the Study of Liver Diseases

NGCPV: a new generation of concentrator photovoltaic cells, modules and systems

Starting on June 2011, NGCPV is the first project funded jointly between the European Commission (EC) and the New Energy and Industrial Technology Development Organization (NEDO) of Japan to research on new generation concentration photovoltaics (CPV). The Project, through a collaborative research between seven European and nine Japanese leading research centers in the field of CPV, aims at lowering the cost of the CPVproduced photovoltaic kWh down to 5 ?cents. The main objective of the project is to improve the present concentrator cell, module and system efficiency, as well as developing advanced characterization tools for CPV components and systems. As particular targets, the project aims at achieving a cell efficiency of at least 45% and a CPV module with an efficiency greater than 35%. This paper describes the R&D activities that are being carried out within the NGCPV project and summarizes some of the most relevant results that have already been attained, for instance: the manufacturing of a 44.4% world record efficiency triple junction solar cell (by Sharp Corp.) and the installation of a 50 kWp experimental CPV plant in Spain, which will be used to obtain accurate forecasts of the energy produced at system level

Metformin Prevents and Reverses Inflammation in a Non-Diabetic Mouse Model of Nonalcoholic Steatohepatitis

Background: Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Methodology/Principal Findings: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. Conclusions/Significance: These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance. © 2012 Kita et al