NMDA Receptors as Potential Therapeutic Targets in Diabetic Nephropathy: Increased Renal NMDA Receptor Subunit Expression in Akita Mice and Reduced Nephropathy Following Sustained Treatment With Memantine or MK-801.

PubMed

Roshanravan, Hila; Kim, Eun Young; Dryer, Stuart E

2016-10-01

N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice. Sustained continuous treatment with the strong NMDA receptor antagonist dizocilpine (MK-801) for 28 days starting at 8 weeks of age reduced 24-h albumin excretion and mesangial matrix expansion and improved glomerular ultrastructure in Akita mice. MK-801 did not alleviate reduced Akita mouse body weight and had no effect on kidney histology or ultrastructure in DBA/2J controls. The structurally dissimilar NMDA antagonist memantine also reduced diabetic nephropathy, although it was less effective than MK-801. Inhibition of NMDA receptors may represent a valid therapeutic approach to reduce renal complications of diabetes, and it is possible to develop well-tolerated agents with minimal central nervous system effects. Two such agents, memantine and dextromethorphan, are already in widespread clinical use. © 2016 by the American Diabetes Association.

Pathology of whooper swans (Cygnus cygnus) infected with H5N1 avian influenza virus in Akita, Japan, in 2008.

PubMed

Ogawa, Shuji; Yamamoto, Yu; Yamada, Manabu; Mase, Masaji; Nakamura, Kikuyasu

2009-10-01

Two (1 adult and 1 young bird) of 4 H5N1-highly-pathogenic-avian-influenza (HPAI)-virus-infected whooper swans in Akita, Japan, in 2008 were investigated pathologically. Macroscopically, white spots with hemorrhages were scattered in the pancreas in the adult bird. Histologically, the adult bird had severe necrotizing pancreatitis and mild nonpurulent encephalitis. The young bird had severe nonpurulent encephalitis and nonpurulent enteric ganglionitis, and intestinal venous wall thickening. Virus antigens were detected in the lesions of pancreatitis in the adult bird and of encephalitis in adult and young birds. These findings suggest that the swans died or became moribund due to neurological disorders and necrotizing pancreatitis caused by H5N1 HPAI virus infection.

Basic investigation of vascular interventional radiology (IR) using large rabbits.

PubMed

Nitta, Norihisa; Sonoda, Akinaga; Nitta-Seko, Ayumi; Ohta, Shinichi; Tsuchiya, Keiko; Tanaka, Toyohiko; Kanasaki, Shuzo; Mukaisho, Kenichi; Takahashi, Masashi; Murata, Kiyoshi

2009-10-01

The purpose of this study was to determine the usefulness of large rabbits for basic vascular interventional radiology (IR) experiments. We used 5 Akita large rabbits (Akita) and 5 Japanese white rabbits (JW). We conducted measurements of vessel diameters such as the aorta, and the iliac, renal, superior mesenteric, celiac, and proper hepatic arteries, and of the growth rates of VX2 liver tumors. There were significant differences between Akita and JW in the diameters of the thoracic aorta, lower abdominal aorta, and celiac artery. In other blood vessels, no significant differences were found. There was no difference in the growth rates of the VX2 tumors between Akita and JW. The possibility that Akita large rabbits could be utilized for vascular IR was demonstrated.

Late-intervention study with ebselen in an experimental model of type 1 diabetic nephropathy.

PubMed

Tan, S M; Sharma, A; Stefanovic, N; de Haan, J B

2015-03-01

Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is lacking. Thus, we aimed to investigate the effects of ebselen in attenuating established renal injury in type 1 diabetic nephropathy using the Akita mouse model. Baseline blood glucose and albumin-to-creatinine ratio (ACR) were measured in wild-type (WT) and heterozygous Akita mice at 9 weeks of age. At 10 weeks of age, WT and Akita mice were randomized to receive either vehicle (5% carboxymethyl cellulose) or ebselen by oral gavage at 10mg/kg twice daily. Kidney and urine were collected after 16 weeks of treatment with ebselen for histological and functional analyses. At 9 weeks of age, Akita mice displayed well-established renal dysfunction with significant increases in ACR and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels when compared with WT controls. After 16 weeks of treatment with ebselen, oxidative stress, as measured by nitrotyrosine immunostaining and urinary 8-OHdG levels, was significantly reduced in the Akita mice. Furthermore, gene expression of the major reactive oxygen species-producing nicotinamide adenine dinucleotide phosphate enzyme, Nox4, was also reduced by ebselen. However, ebselen had no effect on ACR and glomerulosclerosis. Chronic treatment with ebselen significantly reduced oxidative stress in the Akita mice. However, ebselen failed to attenuate functional or structural kidney damage in this late-intervention study using the Akita mouse model.

3D numerical modelling of negative apparent conductivity anomalies in loop-loop electromagnetic measurements: a case study at a dacite intrusion in Sugisawa, Akita Prefecture, Japan

NASA Astrophysics Data System (ADS)

Selepeng, Ame Thato; Sakanaka, Shin'ya; Nishitani, Tadashi

2017-04-01

Under certain geological conditions, low induction number electromagnetic (LIN-EM) instruments are known to produce negative apparent conductivity (σa) responses. This is particularly the case when the shallow subsurface is characterised by highly conductive bodies, however little attention has been given to this issue in the research literature. To analyse negative σa anomalies and their causative structures, we make use of a 3D integral equation forward modelling technique based on a 3D weighting function. We present 3D numerical modelling results over a volcanic tuff body intruded by several dacite dikes, in Sugisawa, Akita Prefecture, Japan. Apparent conductivity data were acquired using a Geonics EM-34-3 system in the horizontal magnetic dipole (HMD) and vertical magnetic dipole (VMD) operating modes. Our 3D model resolved the horizontal and vertical extent of the dacite dikes and also delineated a high conductive zone between the volcanic tuff and the intrusive dacite dikes. This zone is the causative structure for negative σa responses in the VMD data, and is interpreted to be an alteration zone. Interestingly, the negative σa response was absent when the instrument alignment azimuth was changed, implying an anisotropic effect on the EM signature in the study area. The true conductivity model achieved by 3D forward modelling is shown to compare favourably with the DC resistivity data acquired in the same area.

QRS/T-wave and calcium alternans in a type I diabetic mouse model for spontaneous postmyocardial infarction ventricular tachycardia: A mechanism for the antiarrhythmic effect of statins.

PubMed

Jin, Hongwei; Welzig, Charles M; Aronovitz, Mark; Noubary, Farzad; Blanton, Robert; Wang, Bo; Rajab, Mohammad; Albano, Alfred; Link, Mark S; Noujaim, Sami F; Park, Ho-Jin; Galper, Jonas B

2017-09-01

The incidence of sudden arrhythmic death is markedly increased in diabetics. The purpose of this study was to develop a mouse model for postmyocardial infarction (post-MI) ventricular tachycardia (VT) in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. ECG transmitters were implanted in wild-type (WT), placebo, and pravastatin-treated type I diabetic Akita mice. MIs were induced by coronary ligation, and Ca 2+ transients were studied by optical mapping, and Ca 2+ transients and sparks in left ventricular myocytes (VM) by the Ionoptix system and confocal microscopy. Burst pacing of Akita mouse hearts resulted in rate-related QRS/T-wave alternans, which was attenuated in pravastatin-treated mice. Post-MI Akita mice developed QRS/T-wave alternans and VT at 2820 ± 879 beats per mouse, which decreased to 343 ± 115 in pravastatin-treated mice (n = 13, P <.05). Optical mapping demonstrated pacing-induced VT originating in the peri-infarction zone and Ca 2+ alternans, both attenuated in hearts of statin-treated mice. Akita VM displayed Ca 2+ alternans, and triggered activity as well as increased Ca 2+ transient decay time (Tau), Ca 2+ sparks, and cytosolic Ca 2+ and decreased SR Ca 2+ stores all of which were in part reversed in cells from statin treated mice. Homogenates of Akita ventricles demonstrated decreased SERCA2a/PLB ratio and increased ratio of protein phosphatase (PP-1) to the PP-1 inhibitor PPI-1 which were reversed in homogenates of pravastatin-treated Akita mice. Pravastatin decreased the incidence of post-MI VT and Ca 2+ alternans in Akita mouse hearts in part by revering abnormalities of Ca 2+ handling via the PP-1/PPI-1 pathway. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

In Vivo Protection against Retinal Neurodegeneration by Sigma Receptor 1 Ligand (+)-Pentazocine

PubMed Central

Smith, Sylvia B.; Duplantier, Jennifer; Dun, Ying; Mysona, Barbara; Roon, Penny; Martin, Pamela M.; Ganapathy, Vadivel

2008-01-01

Purpose To evaluate the neuroprotective properties of the sigma receptor 1 (σR1) ligand, (+)-pentazocine in an in vivo model of retinal neurodegeneration. Methods Spontaneously diabetic Ins2Akita/+ and wild-type mice received intraperitoneal injections of (+)-pentazocine for 22 weeks beginning at diabetes onset. Retinal mRNA and protein were analyzed by RT-PCR and Western blot analysis. Retinal histologic sections were measured to determine total retinal thickness, thicknesses of inner-outer nuclear and plexiform layers (INL, ONL, IPL, INL), and the number of cell bodies in the ganglion cell layer (GCL). Immunolabeling experiments were performed using antibodies specific for 4-hydroxynonenal and nitrotyrosine, markers of lipid peroxidation, and reactive nitrogen species, respectively, and an antibody specific for vimentin to view radial Müller fibers. Results σR1 mRNA and protein levels in the Ins2Akita/+ retina were comparable to those in the wild-type, indicating that σR1 is an available target during the disease process. Histologic evaluation of eyes of Ins2Akita/+ mice showed disruption of retinal architecture. By 17 to 25 weeks after birth, Ins2Akita/+ mice demonstrated ∼30% and 25% decreases in IPL and INL thicknesses, respectively, and a 30% reduction in ganglion cells. In the (+)-pentazocine-treated group, retinas of Ins2Akita/+ mice showed remarkable preservation of retinal architecture; IPL and INL thicknesses of (+)-pentazocinetreated Ins2Akita/+ mouse retinas were within normal limits. The number of ganglion cells was 15.6 ± 1.5 versus 10.4 ± 1.2 cells/100 μm retinal length in (+)-pentazocine-treated versus nontreated mutant mice. Levels of nitrotyrosine and 4-hydroxynonenal increased in Ins2Akita/+ retinas, but were reduced in (+)-pentazocine-treated mice. Retinas of Ins2Akita/+ mice showed loss of the uniform organization of radial Müller fibers. Retinas of (+)-pentazocine-treated mice maintained the radial organization of glial processes

Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes.

PubMed

Lo, Chao-Sheng; Shi, Yixuan; Chang, Shiao-Ying; Abdo, Shaaban; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao-Ling; Chan, John S D

2015-10-01

We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied. Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1-7 receptor [MasR]) expression, and normalised urinary Ang 1-7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-β1 and Tgf-βrII gene expression. Furthermore, hnRNP F overexpression prevented TGF-β1 signalling and TGF-β1 inhibition of Ace-2 gene expression. These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-β1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.

Copy number variations in the amylase gene (AMY2B) in Japanese native dog breeds.

PubMed

Tonoike, A; Hori, Y; Inoue-Murayama, M; Konno, A; Fujita, K; Miyado, M; Fukami, M; Nagasawa, M; Mogi, K; Kikusui, T

2015-10-01

A recent study suggested that increased copy numbers of the AMY2B gene might be a crucial genetic change that occurred during the domestication of dogs. To investigate AMY2B expansion in ancient breeds, which are highly divergent from modern breeds of presumed European origins, we analysed copy numbers in native Japanese dog breeds. Copy numbers in the Akita and Shiba, two ancient breeds in Japan, were higher than those in wolves. However, compared to a group of various modern breeds, Akitas had fewer copy numbers, whereas Shibas exhibited the same level of expansion as modern breeds. Interestingly, average AMY2B copy numbers in the Jomon-Shiba, a unique line of the Shiba that has been bred to maintain their appearance resembling ancestors of native Japanese dogs and that originated in the same region as the Akita, were lower than those in the Shiba. These differences may have arisen from the earlier introduction of rice farming to the region in which the Shiba originated compared to the region in which the Akita and the Jomon-Shiba originated. Thus, our data provide insights into the relationship between the introduction of agriculture and AMY2B expansion in dogs. © 2015 Stichting International Foundation for Animal Genetics.

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction.

PubMed

Duan, Yaqian; Beli, Eleni; Li Calzi, Sergio; Quigley, Judith L; Miller, Rehae C; Moldovan, Leni; Feng, Dongni; Salazar, Tatiana E; Hazra, Sugata; Al-Sabah, Jude; Chalam, Kakarla V; Le Phuong Trinh, Thao; Meroueh, Marya; Markel, Troy A; Murray, Matthew C; Vyas, Ruchi J; Boulton, Michael E; Parsons-Wingerter, Patricia; Oudit, Gavin Y; Obukhov, Alexander G; Grant, Maria B

2018-05-15

Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2 -/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2 -/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis towards myelopoiesis, and an impairment of lineage - c-kit + hematopoietic stem/progenitor cell (HS/PC) migration and proliferation. Migratory and proliferative dysfunction of these cells was corrected by exposure to angiotensin-1-7 (Ang-1-7), the protective peptide generated by ACE2. Over the duration of diabetes examined, ACE2 deficiency led to progressive reduction in electrical responses assessed by electroretinography and to increases in neural infarcts observed by fundus photography. Compared to Akita mice, ACE2 -/y -Akita at 9-months of diabetes showed an increased number of acellular capillaries indicative of more severe diabetic retinopathy. In diabetic and control human subjects, CD34 + cells, a key bone marrow HS/PC population, were assessed for changes in mRNA levels for MAS, the receptor for Ang-1-7. Levels were highest in CD34 + cells from diabetics without retinopathy. Higher serum Ang-1-7 levels predicted protection from development of retinopathy in diabetics. Treatment with Ang-1-7 or alamandine restored the impaired migration function of CD34 + cells from subjects with retinopathy. These data support that activation of the protective RAS within HS/PCs may represent a therapeutic strategy for prevention of diabetic retinopathy. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

Evaluating the oxidation of shale during hydraulic fracturing using SEM-EDS and spectrocolorimetry

NASA Astrophysics Data System (ADS)

Tan, X. Y.; Nakashima, S.

2017-12-01

During hydraulic fracturing (fracking) for shale gas/oil extraction, oxygen is introduced into deep oxygen-poor environments, and Fe2+-bearing minerals in rocks can be oxidized thus leading to the degradation of rock quality. Akita diatomaceous shale is considered to be one of the source rocks for oil and gas fields in northwestern Japan. Outcrops of Akita shale often show presence of jarosite (Fe sulfate: yellow) and/or goethite (Fe hydroxide: brown to orange) as oxidation products of pyrite (FeS2). Several series of oxidation experiments of Akita shale under dry, humid, and wet conditions were conducted at temperatures of around 30 oC and 50oC for 30-40 days. Portable color spectro-colorimeters were used to monitor color changes of the rock surfaces every hour. SEM-EDS, UV-Vis, and Raman spectroscopic analyses were performed on the rock sample surface to examine the chemical and mineralogical compositions of Akita shale before and after the dry, humid, and wet experiments. In SEM-EDS analyses before the humid experiment, Fe and S containing phases show their atomic ratio close to 1:2 indicating that this is pyrite (FeS2). After the experiment, the ratio changed to around 1:1 suggesting a conversion from pyrite (FeS2) to mackinawite-like mineral (FeS). In addition, the formation of Ca sulfate (possibly gypsum: CaSO4.2H2O) and goethite-like Fe hydroxide were identified which were not present initially. Therefore, oxidation pathways of iron sulfide (pyrite: FeS2) via FeS to sulfate is confirmed by our humid experiments around 30oC on Akita shale. These oxidation processes might occur during the fracking of shale within relatively short time periods associated with precipitation of sulfates and hydroxides. Therefore, further studies are needed for their effects on rock properties and gas/oil production.

The influence of changes in soil moisture in association with geomorphic change on the formation of a subalpine coniferous forest on Mt. Akita-Komagatake, northern Japan

NASA Astrophysics Data System (ADS)

Konno, A.

2015-12-01

The coniferous forest (largely composed of Abies mariesii) is presently the typical vegetation of the subalpine zone in Japan. Pollen analysis revealed that few A. mariesii were present during the last glacial period, and the species began to expand to the subalpine zone during the Holocene (Morita, 1992). However, on Mt. Akita-Komagatake in northern Japan, the expected predominance of A. mariesii is not extensively observed, and the predominant vegetation is instead the dwarf bamboo (Sasa kurilensis). It is unknown why the area under coniferous forest is small in this region. Therefore, I examined this issue from the perspectives of (1) distribution of vegetation, (2) geomorphology, (3) soil moisture, and (4) vegetation history. (1) Precise digital elevation model data and photographic interpretation showed that this coniferous forest was densely distributed in a flat segment considered to be formed by a landslide; (2) this landslide is thought to have occurred up to 3,699 ± 26 yr BP because a boring-core specimen from the landslide included the AK-3 tephra layer (2,300-2,800 yr BP: Wachi et al, 1997) and the radiocarbon date of the lowermost humic soil layer was 3,699 ± 26 yr BP; (3) the soil in the forest area had higher volumetric water content than that in the non-forest area; and (4) phytolith analysis revealed that the main species in the study site was initially dwarf bamboo, but coniferous forest replaced it after the Towada-a tephra (1035 cal. BP, Machida and Arai, 1992) layer fell. These results suggest that soil water conditions changed because of the formation of the flat segment by the landslide, and the coniferous forest was consequently established. However, the landslide only indirectly affected the formation of the coniferous forest, because the forest developed over several thousand years after the landslide occurred. In other words, more direct reasons for the establishment of the coniferous forest may involve changes in soil moisture. This

A Novel Quantitative Method for Diabetic Cardiac Autonomic Neuropathy Assessment in Type 1 Diabetic Mice

PubMed Central

Yang, Bufan; Posada-Quintero, Hugo F.; Siu, Kin L.; Rolle, Marsha; Brink, Peter; Birzgalis, Aija; Moore, Leon C.

2014-01-01

In this work, we used a sensitive and noninvasive computational method to assess diabetic cardiovascular autonomic neuropathy (DCAN) from pulse oximeter (photoplethysmographic; PPG) recordings from mice. The method, which could be easily applied to humans, is based on principal dynamic mode (PDM) analysis of heart rate variability (HRV). Unlike the power spectral density, PDM has been shown to be able to separately identify the activities of the parasympathetic and sympathetic nervous systems without pharmacological intervention. HRV parameters were measured by processing PPG signals from conscious 1.5- to 5-month-old C57/BL6 control mice and in Akita mice, a model of insulin-dependent type 1 diabetes, and compared with the gold-standard Western blot and immunohistochemical analyses. The PDM results indicate significant cardiac autonomic impairment in the diabetic mice in comparison to the controls. When tail-cuff PPG recordings were collected and analyzed starting from 1.5 months of age in both C57/Bl6 controls and Akita mice, onset of DCAN was seen at 3 months in the Akita mice, which persisted up to the termination of the recording at 5 months. Western blot and immunohistochemical analyses also showed a reduction in nerve density in Akita mice at 3 and 4 months as compared to the control mice, thus, corroborating our PDM data analysis of HRV records. Western blot analysis of autonomic nerve proteins corroborated the PPG-based HRV analysis via the PDM approach. In contrast, traditional HRV analysis (based on either the power spectral density or time-domain measures) failed to detect the nerve rarefaction. PMID:25097056

Decreased Mitochondrial Pyruvate Transport Activity in the Diabetic Heart

PubMed Central

Vadvalkar, Shraddha S.; Matsuzaki, Satoshi; Eyster, Craig A.; Giorgione, Jennifer R.; Bockus, Lee B.; Kinter, Caroline S.; Kinter, Michael

2017-01-01

Alterations in mitochondrial function contribute to diabetic cardiomyopathy. We have previously shown that heart mitochondrial proteins are hyperacetylated in OVE26 mice, a transgenic model of type 1 diabetes. However, the universality of this modification and its functional consequences are not well established. In this study, we demonstrate that Akita type 1 diabetic mice exhibit hyperacetylation. Functionally, isolated Akita heart mitochondria have significantly impaired maximal (state 3) respiration with physiological pyruvate (0.1 mm) but not with 1.0 mm pyruvate. In contrast, pyruvate dehydrogenase activity is significantly decreased regardless of the pyruvate concentration. We found that there is a 70% decrease in the rate of pyruvate transport in Akita heart mitochondria but no decrease in the mitochondrial pyruvate carriers 1 and 2 (MPC1 and MPC2). The potential role of hyperacetylation in mediating this impaired pyruvate uptake was examined. The treatment of control mitochondria with the acetylating agent acetic anhydride inhibits pyruvate uptake and pyruvate-supported respiration in a similar manner to the pyruvate transport inhibitor α-cyano-4-hydroxycinnamate. A mass spectrometry selective reactive monitoring assay was developed and used to determine that acetylation of lysines 19 and 26 of MPC2 is enhanced in Akita heart mitochondria. Expression of a double acetylation mimic of MPC2 (K19Q/K26Q) in H9c2 cells was sufficient to decrease the maximal cellular oxygen consumption rate. This study supports the conclusion that deficient pyruvate transport activity, mediated in part by acetylation of MPC2, is a contributor to metabolic inflexibility in the diabetic heart. PMID:28154187

Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in {beta}-cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jie, E-mail: jie.wang2@osumc.edu; Osei, Kwame

2011-07-22

Highlights: {yields} Primary proinsulin maturation disorder is inherent in Ins2{sup +/Akita} islets/{beta}-cells. {yields} A consequence is the inefficient conversion of proinsulin to insulin. {yields} Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. {yields} Proinsulin maturation chaos results in defects in the following conversion process. {yields} A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested. -- Abstract: Disproportionate hyperproinsulinemia is an indicator of {beta}-cell dysfunction in diabetes and the basis underlying this abnormality remains obscure. Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostaticmore » balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in normal {beta}-cells as a result of the integration of maturation and disposal processes. PIHO is susceptible to environmental and genetic influences. Perturbation of PIHO produces a number of toxic consequences with known association to {beta}-cell failure in diabetes. To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2{sup +/Akita} islets/{beta}-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic-labeling studies found an increased ratio of proinsulin to insulin in the cellular or released proteins of Ins2{sup +/Akita} islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the {beta}-cells of Ins2{sup +/Akita} islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2{sup +/Akita} {beta}-cells further confirmed the increased ratio of

Evaluation of serum cobalamin concentrations in dogs of 164 dog breeds (2006-2010).

PubMed

Grützner, Niels; Cranford, Shannon M; Norby, Bo; Suchodolski, Jan S; Steiner, Jörg M

2012-11-01

Altered serum cobalamin concentrations have been observed in dogs with gastrointestinal disorders such as exocrine pancreatic insufficiency (EPI) or gastrointestinal inflammation. The aims of the current study were 1) to identify breeds with a higher proportion of dogs with a decreased serum cobalamin concentration, 2) to determine whether dogs with such decreased concentrations tend to have serum canine trypsin-like immunoreactivity (cTLI) concentrations diagnostic for EPI, and 3) to compare the number of submissions for serum cobalamin analysis by breed to the American Kennel Club (AKC) breed ranking list of 2009. In this retrospective study, results of 28,675 cobalamin tests were reviewed. Akitas, Chinese Shar-Peis, German Shepherd Dogs, Greyhounds, and Labrador Retrievers had increased proportions of serum cobalamin concentrations below the lower limit of the reference interval (<251 ng/l; all P < 0.0001). Akitas, Chinese Shar-Peis, German Shepherd Dogs, and Border Collies had increased proportions of serum cobalamin concentrations below the detection limit of the assay (<150 ng/l; all P < 0.0001). Akitas, Border Collies, and German Shepherd Dogs with serum cobalamin concentrations <150 ng/l were more likely to have a serum cTLI concentration considered diagnostic for EPI (≤2.5 µg/l; all P ≤ 0.001). The breed with the highest proportion of samples submitted for serum cobalamin analysis in comparison with the AKC ranking list was the Greyhound (odds ratio: 84.6; P < 0.0001). In Akitas and Border Collies, further investigations are warranted to clarify if a potentially breed-specific gastrointestinal disorder is responsible for the increased frequency of decreased serum cobalamin and cTLI concentrations.

Decreased Mitochondrial Pyruvate Transport Activity in the Diabetic Heart: ROLE OF MITOCHONDRIAL PYRUVATE CARRIER 2 (MPC2) ACETYLATION.

PubMed

Vadvalkar, Shraddha S; Matsuzaki, Satoshi; Eyster, Craig A; Giorgione, Jennifer R; Bockus, Lee B; Kinter, Caroline S; Kinter, Michael; Humphries, Kenneth M

2017-03-17

Alterations in mitochondrial function contribute to diabetic cardiomyopathy. We have previously shown that heart mitochondrial proteins are hyperacetylated in OVE26 mice, a transgenic model of type 1 diabetes. However, the universality of this modification and its functional consequences are not well established. In this study, we demonstrate that Akita type 1 diabetic mice exhibit hyperacetylation. Functionally, isolated Akita heart mitochondria have significantly impaired maximal (state 3) respiration with physiological pyruvate (0.1 mm) but not with 1.0 mm pyruvate. In contrast, pyruvate dehydrogenase activity is significantly decreased regardless of the pyruvate concentration. We found that there is a 70% decrease in the rate of pyruvate transport in Akita heart mitochondria but no decrease in the mitochondrial pyruvate carriers 1 and 2 (MPC1 and MPC2). The potential role of hyperacetylation in mediating this impaired pyruvate uptake was examined. The treatment of control mitochondria with the acetylating agent acetic anhydride inhibits pyruvate uptake and pyruvate-supported respiration in a similar manner to the pyruvate transport inhibitor α-cyano-4-hydroxycinnamate. A mass spectrometry selective reactive monitoring assay was developed and used to determine that acetylation of lysines 19 and 26 of MPC2 is enhanced in Akita heart mitochondria. Expression of a double acetylation mimic of MPC2 (K19Q/K26Q) in H9c2 cells was sufficient to decrease the maximal cellular oxygen consumption rate. This study supports the conclusion that deficient pyruvate transport activity, mediated in part by acetylation of MPC2, is a contributor to metabolic inflexibility in the diabetic heart. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

MicroRNA-200b Downregulates Oxidation Resistance 1 (Oxr1) Expression in the Retina of Type 1 Diabetes Model

PubMed Central

Murray, Anne R.; Chen, Qian; Takahashi, Yusuke; Zhou, Kevin K.; Park, Kyoungmin; Ma, Jian-xing

2013-01-01

Purpose. MicroRNAs (miRNAs) are known to participate in post-transcriptional regulation of gene expression and are involved in multiple pathogenic processes. Here, we identified miRNA expression changes in the retinas of Akita mice, a genetic model of type 1 diabetes, and investigated the potential role of miRNA in diabetic retinopathy. Methods. Visual function of Akita and control mice was evaluated by electroretinography. MiRNA expression changes in the retinas of Akita mice were identified by miRNA-specific microarray and confirmed by quantitative RT-PCR (qRT-PCR). The potential downstream targets of identified miRNAs were predicted by bioinformatic analysis using web-based applications and confirmed by dual luciferase assay. The mRNA and protein changes of identified downstream targets were examined by qRT-PCR and Western blot analysis. Results. MiRNA-specific microarray and qRT-PCR showed that miR-200b was upregulated significantly in the Akita mouse retina. Sequence analysis and luciferase assay identified oxidation resistance 1 (Oxr1) as a downstream target gene regulated by miR-200b. In a human Müller cell line, MIO-M1, transfection of a miR-200b mimic downregulated Oxr1 expression. Conversely, transfection of MIO-M1 with a miR-200b inhibitor resulted in upregulated Oxr1. Furthermore, overexpression of recombinant Oxr1 attenuated oxidative stress marker, nitration of cellular proteins, and ameliorated apoptosis induced by 4-hydroxynonenal (4-HNE), an oxidative stressor. Similarly, transfection of a miR-200b inhibitor decreased, whereas transfection of miR-200b mimic increased the number of apoptotic cells following 4-HNE treatment. Conclusions. These results suggested that miR-200b–regulated Oxr1 potentially has a protective role in diabetic retinopathy. PMID:23404117

Sigma Receptor 1 Modulates Endoplasmic Reticulum Stress in Retinal Neurons

PubMed Central

Ha, Yonju; Dun, Ying; Thangaraju, Muthusamy; Duplantier, Jennifer; Dong, Zheng; Liu, Kebin; Ganapathy, Vadivel

2011-01-01

Purpose. To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons. Methods. Oxidative stress, which is implicated in diabetic retinopathy, was induced in mouse primary ganglion cells (GCs) and RGC-5 cells, and the effect of the σR1 ligand (+)-pentazocine on pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was examined. Binding of σR1 to BiP, an ER chaperone protein, and σR1 phosphorylation status were examined by immunoprecipitation. Retinas were harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the expression of ER stress genes and of the retinal transcriptome was evaluated. Results. Oxidative stress induced the death of primary GCs and RGC-5 cells. The effect was decreased by the application of (+)-pentazocine. Stress increased σR1 binding to BiP and enhanced σR1 phosphorylation in RGC-5 cells. BiP binding was prevented, and σR1 phosphorylation decreased in the presence of (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1α, and CHOP were upregulated in RGC-5 cells during oxidative stress, but decreased in the presence of (+)-pentazocine. A similar phenomenon was observed in retinas of Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice compared with wild-type revealed differential expression of the genes critically involved in oxidative stress, differentiation, and cell death. The expression profile of those genes was reversed when the Ins2Akita/+ mice were treated with (+)-pentazocine. Conclusions. In retinal neurons, the molecular chaperone σR1 binds BiP under stressful conditions; (+)-pentazocine may exert its effects by dissociating σR1 from BiP. As stress in retinal cells increases, phosphorylation of σR1 is increased, which is attenuated when agonists bind to the receptor. PMID:20811050

Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons.

PubMed

Ha, Yonju; Dun, Ying; Thangaraju, Muthusamy; Duplantier, Jennifer; Dong, Zheng; Liu, Kebin; Ganapathy, Vadivel; Smith, Sylvia B

2011-01-01

To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons. Oxidative stress, which is implicated in diabetic retinopathy, was induced in mouse primary ganglion cells (GCs) and RGC-5 cells, and the effect of the σR1 ligand (+)-pentazocine on pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was examined. Binding of σR1 to BiP, an ER chaperone protein, and σR1 phosphorylation status were examined by immunoprecipitation. Retinas were harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the expression of ER stress genes and of the retinal transcriptome was evaluated. Oxidative stress induced the death of primary GCs and RGC-5 cells. The effect was decreased by the application of (+)-pentazocine. Stress increased σR1 binding to BiP and enhanced σR1 phosphorylation in RGC-5 cells. BiP binding was prevented, and σR1 phosphorylation decreased in the presence of (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1α, and CHOP were upregulated in RGC-5 cells during oxidative stress, but decreased in the presence of (+)-pentazocine. A similar phenomenon was observed in retinas of Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice compared with wild-type revealed differential expression of the genes critically involved in oxidative stress, differentiation, and cell death. The expression profile of those genes was reversed when the Ins2Akita/+ mice were treated with (+)-pentazocine. In retinal neurons, the molecular chaperone σR1 binds BiP under stressful conditions; (+)-pentazocine may exert its effects by dissociating σR1 from BiP. As stress in retinal cells increases, phosphorylation of σR1 is increased, which is attenuated when agonists bind to the receptor.

Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice.

PubMed

McLenachan, Samuel; Magno, Aaron Len; Ramos, David; Catita, Joana; McMenamin, Paul G; Chen, Fred Kuanfu; Rakoczy, Elizabeth Piroska; Ruberte, Jesus

2015-09-01

The mouse retina is a commonly used animal model for the study of pathogenesis and treatment of blinding retinal vascular diseases such as diabetic retinopathy. In this study, we aimed to characterize normal and pathological variations in vascular anatomy in the mouse retina using fluorescein angiography visualized with scanning laser ophthalmoscopy and optical coherence tomography (SLO-OCT). We examined eyes from C57BL/6J wild type mice as well as the Ins2(Akita) and Akimba mouse models of diabetic retinopathy using the Heidelberg Retinal Angiography (HRA) and OCT system. Angiography was performed on three focal planes to examine distinct vascular layers. For comparison with angiographic data, ex vivo analyses, including Indian ink angiography, histology and 3D confocal scanning laser microscopy were performed in parallel. All layers of the mouse retinal vasculature could be readily visualized during fluorescein angiography by SLO-OCT. Blood vessel density was increased in the deep vascular plexus (DVP) compared with the superficial vascular plexus (SVP). Arteriolar and venular typologies were established and structural differences were observed between venular types. Unexpectedly, the hyaloid artery was found to persist in 15% of C57BL/6 mice, forming anastomoses with peripheral retinal capillaries. Fluorescein leakage was easily detected in Akimba retinae by angiography, but was not observed in Ins2(Akita) mice. Blood vessel density was increased in the DVP of 6 month old Ins2(Akita) mice, while the SVP displayed reduced branching in precapillary arterioles. In summary, we present the first comprehensive characterization of the mouse retinal vasculature by SLO-OCT fluorescein angiography. Using this clinical imaging technique, we report previously unrecognized variations in C57BL/6J vascular anatomy and novel features of vascular retinopathy in the Ins2(Akita) mouse model of diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults.

PubMed

Shiina, Yumi; Funabashi, Nobusada; Lee, Kwangho; Murayama, Taichi; Nakamura, Koki; Wakatsuki, Yu; Daimon, Masao; Komuro, Issei

2009-01-24

To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects. The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range 23-40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress. Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake; p=0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)-0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake, X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR). Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.

Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice.

PubMed

Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; Macdougall, Mary; Abboud-Werner, Sherry

2012-06-01

Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita ⁻/⁻ mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita ⁻/⁻ and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita ⁻/⁻ mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita ⁻/⁻ teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

PubMed

Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

2016-09-01

Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice

PubMed Central

Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; MacDougall, Mary; Abboud-Werner, Sherry

2012-01-01

Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita −/− mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita −/− and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita −/− mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita −/− teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

Origin of three Red-crowned Cranes Grus japonensis found in northeast Honshu and west Hokkaido, Japan, from 2008 to 2012.

PubMed

Miura, Yoshiaki; Shiraishi, Junya; Shiomi, Akira; Kitazawa, Takio; Hiraga, Takeo; Matsumoto, Fumio; Teraoka, Hiroki; Masatomi, Hiroyuki

2013-01-01

The Red-crowned Crane Grus japonensis is an endangered species that has two separate breeding populations, one in the Amur River basin and the other in north and east Hokkaido, Japan. So far, only two (Gj1 and Gj2) and seven (Gj3-Gj9) haplotypes in D-loop of mtDNA were identified in Japan and in the continent, respectively. We obtained feathers from three cranes found in northeast Honshu. The crane in Akita in 2008, which also arrived at west Hokkaido, had a novel haplotype (Gj10). Another crane in Akita in 2009 showed a heteroplasmy (Gj7 and a novel type, Gj12). The third crane in Miyagi in 2010 also showed another type, Gj11. These results suggest that three Red-crowned Cranes appeared in Honshu and west Hokkaido were from the continent.

The 1998 World Solar Rallye: Akita, Japan

NASA Astrophysics Data System (ADS)

Shacklock, Andy; Duke, Mike; Burgess, Nigel

In early August 1998, 81 solar/electric vehicles participated in a three day endurance race in Japan. The objective was to complete as many laps of the 31 km circuit as possible. Some of the cars used state-of-the-art motors, batteries, chassis, solar cells and tyres to produce vehicles which could travel at speeds of 70-80 km/h on about 1 kW of input power. With only 20 kg of battery, some solar cars were travelling around 450 km a day. This paper tells the story of the race and the technological developments behind the successful vehicles.

The photosensitizer talaporfinum caused microvascular embolization for photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Liming; Aizawa, Katsuo

2005-07-01

Photodynamic therapy (PDT) has been evolving rapidly in the recent years. A second-generation Photosensitizer mono-1-aspartyl chlorine 6 (Talaporfin / Npe6 / ME2906, Japan Meiji Seika, Ltd.) has been sanctified for the lung cancer clinical PDT by the Japan Ministry of Health, Labor and Welfare. In this paper, Talaporfin was injected to the implant cancer of a mouse a Talaporfin dose of 5mg/kg through intravenous. After 6 hours, the fluorescence images of the mouse were observed with a microscope and a 664 nm diode laser. Effects of therapy were clarified using the different irradiation energies of the laser (50, 100, 200 J/cm2). Both in plasma and in cancer, the concentrations of Talaporfin were analyzed using High Performance Liquid Chromatography (HPLC). Authors find that the higher concentrations of Talaporfin in plasma, the better PDD effect. It is experimentally verified that local microvascular embolisms in the cancer are formed for photodynamic therapy after the Talaporfin injection and the laser irradiation.

Immunohistochemical Characterization of Connexin43 Expression in a Mouse Model of Diabetic Retinopathy and in Human Donor Retinas

PubMed Central

Mugisho, Odunayo O.; Green, Colin R.; Zhang, Jie; Binz, Nicolette; Acosta, Monica L.; Rakoczy, Elizabeth

2017-01-01

Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced vascular disruptions in the retina with connexin43 expression patterns in the disease still debated. Here, the effects of hyperglycemia and inflammation on connexin43 expression in vitro in a mouse model of DR and in human donor tissues were evaluated. Primary human retinal microvascular endothelial cells (hRMECs) were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1β and TNF-α (10 ng/mL each) or both before assessing connexin43 expression. Additionally, connexin43, glial fibrillary acidic protein (GFAP), and plasmalemma vesicular associated protein (PLVAP) were labeled in wild-type (C57BL/6), Akita (diabetic), and Akimba (DR) mouse retinas. Finally, connexin43 and GFAP expression in donor retinas with confirmed DR was compared to age-matched controls. Co-application of HG and cytokines increased connexin43 expression in hRMECs in line with results seen in mice, with no significant difference in connexin43 or GFAP expression in Akita but higher expression in Akimba compared to wild-type mice. On PLVAP-positive vessels, connexin43 was higher in Akimba but unchanged in Akita compared to wild-type mice. Connexin43 expression appeared higher in donor retinas with confirmed DR compared to age-matched controls, similar to the distribution seen in Akimba mice and correlating with the in vitro results. Although connexin43 expression seems reduced in diabetes, hyperglycemia and inflammation present in the pathology of DR seem to increase connexin43 expression, suggesting a causal role of connexin43 channels in the disease progression. PMID:29186067

A Decrease in Suicide Rates in Japanese Rural Towns after Community-Based Intervention by the Health Promotion Approach

ERIC Educational Resources Information Center

Motohashi, Yutaka; Kaneko, Yoshihiro; Sasaki, Hisanaga

2007-01-01

A community-based intervention study for suicide prevention was conducted in six towns (total population 43,964) in Akita Prefecture of Japan according to a quasi-experimental design to reduce suicide rates in rural towns. Public awareness raising activities using a health promotion approach emphasizing the empowerment of residents and civic…

Highly pathogenic avian influenza virus (H5N1) isolated from whooper swans, Japan.

PubMed

Uchida, Yuko; Mase, Masaji; Yoneda, Kumiko; Kimura, Atsumu; Obara, Tsuyoshi; Kumagai, Seikou; Saito, Takehiko; Yamamoto, Yu; Nakamura, Kikuyasu; Tsukamoto, Kenji; Yamaguchi, Shigeo

2008-09-01

On April 21, 2008, four whooper swans were found dead at Lake Towada, Akita prefecture, Japan. Highly pathogenic avian influenza virus of the H5N1 subtype was isolated from specimens of the affected birds. The hemagglutinin (HA) gene of the isolate belongs to clade 2.3.2 in the HA phylogenetic tree.

Massilia sp. BS-1, a novel violacein-producing bacterium isolated from soil.

PubMed

Agematu, Hitosi; Suzuki, Kazuya; Tsuya, Hiroaki

2011-01-01

A novel bacterium, Massilia sp. BS-1, producing violacein and deoxyviolacein was isolated from a soil sample collected from Akita Prefecture, Japan. The 16S ribosomal DNA of strain BS-1 displayed 93% homology with its nearest violacein-producing neighbor, Janthinobacterium lividum. Strain BS-1 grew well in a synthetic medium, but required both L-tryptophan and a small amount of L-histidine to produce violacein.

Nrdp1-Mediated ErbB3 Increase During Androgen Ablation and Its Contribution to Androgen-Independence

DTIC Science & Technology

2011-09-01

after the first day. Cell lysates were immunoblotted with anti-Nrdp1 and anti-tubulin antibodies. 7 Differential regulation of Nrdp1 by...Prostate Cancer PDGFR Platelet -derived growth factor receptor PI3K Phosphatidylinositol 3-kinase PKC Protein Kinase C pRB Retinoblastoma gene product PSA... glioma . Cancer Res. 2007; 67(17):7960–7965. [PubMed: 17804702] 131. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D

The administrative project of Helicobacter pylori infection screening among junior high school students in an area of Japan with a high incidence of gastric cancer.

PubMed

Kusano, Chika; Gotoda, Takuji; Ishikawa, Hideki; Moriyama, Mitsuhiko

2017-03-01

Helicobacter pylori infection is a common chronic infection that is closely associated with gastric cancer, known to be decreasing worldwide. We set up an administrative project of screening examination for H. pylori infection in junior high school students in Akita Prefecture to investigate the current prevalence of H. pylori infection in childhood in an area where the incidence of gastric cancer is particularly high. All students in their second or third year of junior high school (13 to 15 years old) in two cities in Akita Prefecture were recruited. First, a urine-based enzyme-linked immunosorbent assay for detection of H. pylori antibody was performed. Then, a 13 C-urea breath test ( 13 C-UBT) was carried out in students who tested positive on the urinary test. Written informed consent was obtained from all participants and their parents. A total of 1813 students were recruited in this study; 1765 (97.3%) students agreed to participate in this project and underwent a screening examination. Among 96 students (5.4%) testing positive for H. pylori on the initial screening examination, 90 (93.7%, 90/96) underwent a subsequent 13 C-UBT, and 85 (4.8%, 85/1765) were diagnosed as positive for H. pylori. The current prevalence of H. pylori infection among students was low even in an area of Japan with a high incidence of gastric cancer.

Heterogeneous Nuclear Ribonucleoprotein F Suppresses Angiotensinogen Gene Expression and Attenuates Hypertension and Kidney Injury in Diabetic Mice

PubMed Central

Lo, Chao-Sheng; Chang, Shiao-Ying; Chenier, Isabelle; Filep, Janos G.; Ingelfinger, Julie R.; Zhang, Shao Ling; Chan, John S.D.

2012-01-01

We investigated the impact of heterogeneous nuclear ribonucleoprotein F (hnRNP F) overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs were created, and the effects on systemic hypertension, Agt gene expression, renal hypertrophy, and interstitial fibrosis were studied. We also examined immortalized rat RPTCs stably transfected with control plasmid or plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F overexpression attenuated systemic hypertension, suppressed Agt and transforming growth factor-β1 (TGF-β1) gene expression, and reduced urinary Agt and angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose stimulation of Agt and TGF-β1 mRNA expression and cellular hypertrophy in RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes. PMID:22664958

Urinary Podocyte Microparticles Identify Prealbuminuric Diabetic Glomerular Injury

PubMed Central

Burger, Dylan; Thibodeau, Jean-Francois; Holterman, Chet E.; Burns, Kevin D.; Touyz, Rhian M.

2014-01-01

Microparticles (MPs) are small (0.1–1.0 µm) vesicles shed from the surface of cells in response to stress. Whether podocytes produce MPs and whether this production reflects glomerular injury are unclear. We examined MP formation in cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-β. Urinary podocyte MPs were assessed in three mouse models of diabetic nephropathy: streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG increased MP release as assessed by flow cytometry (P<0.01 and P<0.05, respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited increased urinary podocyte MPs compared with age-matched nondiabetic mice. Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs compared with wild-type littermates (P<0.01). In 1 week post-STZ–treated and 6- and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our results indicate that podocytes produce MPs that are released into urine. Podocyte-derived MPs are generated by exposure to mechanical stretch and high glucose in vitro and could represent early markers of glomerular injury in diabetic nephropathy. PMID:24676640

The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activator dh404 protects against diabetes-induced endothelial dysfunction.

PubMed

Sharma, Arpeeta; Rizky, Luddwi; Stefanovic, Nada; Tate, Mitchel; Ritchie, Rebecca H; Ward, Keith W; de Haan, Judy B

2017-03-03

Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to vascular dysfunction. Nrf2, a master regulator of several anti-oxidant genes and a suppressor of inflammatory NF-κB, has potential as a target to combat oxidative stress and inflammation. The aim of this study was to investigate the effects of a novel Nrf2 activator, the bardoxolone methyl derivative dh404, on endothelial function in vitro and in vivo. dh404 at 3 mg/kg was administered to male Akita mice, an established diabetic mouse model of insulin insufficiency and hyperglycemia, from 6 weeks of age. At 26 weeks of age, vascular reactivity was assessed by wire myography, pro-inflammatory expression was assessed in the aortas by qRT-PCR and immunohistochemistry, and systemic and vascular oxidative stress measurements were determined. Additionally, studies in human aortic endothelial cells (HAECs) derived from normal and diabetic patients in the presence or absence of dh404 included assessment of pro-inflammatory genes by qRT-PCR and western blotting. Oxidative stress was assessed by three methods; L-012, DCFDA and amplex red. Static adhesion assays were performed to determine the leukocyte-endothelial interaction in the presence or absence of dh404. Dh404 significantly attenuated endothelial dysfunction in diabetic Akita mice characterized by reduced contraction in response to phenylephrine and the downregulation of inflammatory genes (VCAM-1, ICAM-1, p65, IL-1β) and pro-oxidant genes (Nox1 and Nox2). Furthermore, reduced systemic and vascular oxidative stress levels were observed in diabetic Akita mice. dh404 exhibited cytoprotective effects in diabetic HAECs in vitro, reflected by significant upregulation of Nrf2-responsive genes, NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), reduction of oxidative stress markers (O 2 ·- and H 2 O 2 ), inhibition of inflammatory

Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes

PubMed Central

Maher, Pamela; Dargusch, Richard; Ehren, Jennifer L.; Okada, Shinichi; Sharma, Kumar; Schubert, David

2011-01-01

The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications. PMID:21738623

The relationship between pollen count levels and prevalence of Japanese cedar pollinosis in Northeast Japan.

PubMed

Honda, Kohei; Saito, Hidekazu; Fukui, Naoko; Ito, Eiko; Ishikawa, Kazuo

2013-09-01

The prevalence of Japanese cedar (JC) pollinosis in Japanese children is increasing. However, few studies have reported the relationship between pollen count levels and the prevalence of pollinosis. To evaluate the relationship between JC pollen count levels and the prevalence of pollinosis in children, we investigated the sensitization and development of symptoms for JC pollen in two areas of Akita in northeast Japan with contrasting levels of exposure to JC pollen. The study population consisted of 339 elementary school students (10-11 years of age) from the coastal and mountainous areas of Akita in 2005-2006. A questionnaire about symptoms of allergic rhinitis was filled out by the students' parents. A blood sample was taken to determine specific IgE antibodies against five common aeroallergens. The mean pollen count in the mountainous areas was two times higher than that in the coastal areas in 1996-2006. The prevalence rates of nasal allergy symptoms and sensitization for mites were almost the same in both areas. On the other hand, the rates of nasal allergy symptoms and sensitization for JC pollen were significantly higher in the mountainous areas than in the coastal areas. The rate of the development of symptoms among children sensitized for JC pollen was almost the same in both areas. These results suggest that pollen count levels may correlate with the rate of sensitization for JC pollinosis, but may not affect the rate of onset among sensitized children in northeast Japan.

Time-dependent changes in the plasma amino acid concentration in diabetes mellitus.

PubMed

Mochida, Taiga; Tanaka, Takayuki; Shiraki, Yasuko; Tajiri, Hiroko; Matsumoto, Shirou; Shimbo, Kazutaka; Ando, Toshihiko; Nakamura, Kimitoshi; Okamoto, Masahiro; Endo, Fumio

2011-08-01

We investigated longitudinal change in the amino acid (AA) profile in type 1 diabetes mellitus (DM) using AKITA mice, which develop DM as a result of insulin deficiency. The plasma concentrations of valine, leucine, isoleucine, as well as the total branched chain amino acids, alanine, citrulline and proline, were significantly higher in the diabetic mice. We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM. Copyright © 2011 Elsevier Inc. All rights reserved.

Fractalkine Signaling Attenuates Perivascular Clustering of Microglia and Fibrinogen Leakage during Systemic Inflammation in Mouse Models of Diabetic Retinopathy

PubMed Central

Mendiola, Andrew S.; Garza, Rolando; Cardona, Sandra M.; Mythen, Shannon A.; Lira, Sergio A.; Akassoglou, Katerina; Cardona, Astrid E.

2017-01-01

Fractalkine (FKN) is a chemokine expressed constitutively by healthy neurons and signals to microglia upon interaction with the FKN receptor, CX3CR1. Signaling between FKN and CX3CR1 transduces inhibitory signals that ameliorate microglial activation and proinflammatory cytokine release in neuroinflammatory conditions. The aim of this study is to determine the mechanisms associated with microglial activation and vascular leakage during diabetic retinopathy (DR) and under conditions of low-level endotoxemia, common in diabetic patients. Utilizing the Ins2Akita strain (Akita), a mouse model of type 1 diabetes, our results show that leakage of the blood-protein fibrin(ogen) into the retina occurs as a result of chronic (4 months) but not acute (1.5 months) hyperglycemia. Conversely, inducing endotoxin-mediated systemic inflammation during acute diabetes resulted in fibrinogen deposition in the retina, a phenotype that was exacerbated in mice lacking CX3CR1 signaling. Systemic inflammation in Cx3cr1−/− mice led to robust perivascular clustering of proliferating microglia in areas of fibrinogen extravasation, and induced IL-1β expression in microglia and astrocytes. Lastly, we determined a protective effect of modulating FKN/CX3CR1 signaling in the diabetic retina. We show that intravitreal (iv) administration of recombinant FKN into diabetic FKN-KO mice, reduced fibrinogen deposition and perivascular clustering of microglia in the retina during systemic inflammation. These data suggest that dysregulated microglial activation via loss of FKN/CX3CR1 signaling disrupts the vascular integrity in retina during systemic inflammation. PMID:28119571

Biomedical Applications of Mid-Infrared Spectroscopic Imaging and Multivariate Data Analysis: Contribution to the Understanding of Diabetes Pathogenesis

NASA Astrophysics Data System (ADS)

Aboualizadeh, Ebrahim

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of adult vision loss. Although a great deal of progress has been made in ophthalmological examinations and clinical approaches to detect the signs of retinopathy in patients with diabetes, there still remain outstanding questions regarding the molecular and biochemical changes involved. To discover the biochemical mechanisms underlying the development and progression of changes in the retina as a result of diabetes, a more comprehensive understanding of the bio-molecular processes, in individual retinal cells subjected to hyperglycemia, is required. Animal models provide a suitable resource for temporal detection of the underlying pathophysiological and biochemical changes associated with DR, which is not fully attainable in human studies. In the present study, I aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the retinal tissue from Ins2Akita/+ (Akita/+; a model of Type I diabetes) male mice with different duration of diabetes. Employing label-free, spatially resolved Fourier transform infrared (FT-IR) imaging engaged with chemometric tools enabled me to identify temporal-dependent reproducible biomarkers of the diabetic retinal tissue from mice with 6 or 12 weeks, and 6 or 10 months of diabetes. I report, for the first time, the origin of molecular changes in the biochemistry of individual retinal layers with different duration of diabetes. A robust classification between distinctive retinal layers - namely photoreceptor layer (PRL), outer plexiform layer (OPL), inner nuclear layer (INL), and inner plexiform layer (IPL) - and associated temporal-dependent spectral biomarkers, were delineated. Spatially-resolved super resolution chemical images revealed oxidative stress-induced structural and morphological alterations within the nucleus of the photoreceptors. Comparison among the PRL, OPL, INL, and IPL suggested that the

Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

PubMed

Levis, Brooke; Benedetti, Andrea; Riehm, Kira E; Saadat, Nazanin; Levis, Alexander W; Azar, Marleine; Rice, Danielle B; Chiovitti, Matthew J; Sanchez, Tatiana A; Cuijpers, Pim; Gilbody, Simon; Ioannidis, John P A; Kloda, Lorie A; McMillan, Dean; Patten, Scott B; Shrier, Ian; Steele, Russell J; Ziegelstein, Roy C; Akena, Dickens H; Arroll, Bruce; Ayalon, Liat; Baradaran, Hamid R; Baron, Murray; Beraldi, Anna; Bombardier, Charles H; Butterworth, Peter; Carter, Gregory; Chagas, Marcos H; Chan, Juliana C N; Cholera, Rushina; Chowdhary, Neerja; Clover, Kerrie; Conwell, Yeates; de Man-van Ginkel, Janneke M; Delgadillo, Jaime; Fann, Jesse R; Fischer, Felix H; Fischler, Benjamin; Fung, Daniel; Gelaye, Bizu; Goodyear-Smith, Felicity; Greeno, Catherine G; Hall, Brian J; Hambridge, John; Harrison, Patricia A; Hegerl, Ulrich; Hides, Leanne; Hobfoll, Stevan E; Hudson, Marie; Hyphantis, Thomas; Inagaki, Masatoshi; Ismail, Khalida; Jetté, Nathalie; Khamseh, Mohammad E; Kiely, Kim M; Lamers, Femke; Liu, Shen-Ing; Lotrakul, Manote; Loureiro, Sonia R; Löwe, Bernd; Marsh, Laura; McGuire, Anthony; Mohd Sidik, Sherina; Munhoz, Tiago N; Muramatsu, Kumiko; Osório, Flávia L; Patel, Vikram; Pence, Brian W; Persoons, Philippe; Picardi, Angelo; Rooney, Alasdair G; Santos, Iná S; Shaaban, Juwita; Sidebottom, Abbey; Simning, Adam; Stafford, Lesley; Sung, Sharon; Tan, Pei Lin Lynnette; Turner, Alyna; van der Feltz-Cornelis, Christina M; van Weert, Henk C; Vöhringer, Paul A; White, Jennifer; Whooley, Mary A; Winkley, Kirsty; Yamada, Mitsuhiko; Zhang, Yuying; Thombs, Brett D

2018-06-01

original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Low-frequency source parameters of twelve large earthquakes. M.S. Thesis

NASA Technical Reports Server (NTRS)

Harabaglia, Paolo

1993-01-01

A global survey of the low-frequency (1-21 mHz) source characteristics of large events are studied. We are particularly interested in events unusually enriched in low-frequency and in events with a short-term precursor. We model the source time function of 12 large earthquakes using teleseismic data at low frequency. For each event we retrieve the source amplitude spectrum in the frequency range between 1 and 21 mHz with the Silver and Jordan method and the phase-shift spectrum in the frequency range between 1 and 11 mHz with the Riedesel and Jordan method. We then model the source time function by fitting the two spectra. Two of these events, the 1980 Irpinia, Italy, and the 1983 Akita-Oki, Japan, are shallow-depth complex events that took place on multiple faults. In both cases the source time function has a length of about 100 seconds. By comparison Westaway and Jackson find 45 seconds for the Irpinia event and Houston and Kanamori about 50 seconds for the Akita-Oki earthquake. The three deep events and four of the seven intermediate-depth events are fast rupturing earthquakes. A single pulse is sufficient to model the source spectra in the frequency range of our interest. Two other intermediate-depth events have slower rupturing processes, characterized by a continuous energy release lasting for about 40 seconds. The last event is the intermediate-depth 1983 Peru-Ecuador earthquake. It was first recognized as a precursive event by Jordan. We model it with a smooth rupturing process starting about 2 minutes before the high frequency origin time superimposed to an impulsive source.

Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumonia liver translocation

PubMed Central

Wu, Ying-Ying; Fung, Chang-Phone; Hsu, Ching-Mei

2017-01-01

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1β and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. L-NAME treatment decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. Dead E.coli (2×108 CFU/ml) feeding for one week induced iNOS and TLR4 expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL-1β and TNF-α expression of Kupffer cells in GF mice but not in GF TLR4-/- mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases diabetes-induced intestinal iNOS expression and KP liver translocation. Diabetes induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production. PMID:28493939

Comparison of strong-motion spectra with teleseismic spectra for three magnitude 8 subduction-zone earthquakes

NASA Astrophysics Data System (ADS)

Houston, Heidi; Kanamori, Hiroo

1990-08-01

A comparison of strong-motion spectra and teleseismic spectra was made for three Mw 7.8 to 8.0 earthquakes: the 1985 Michoacan (Mexico) earthquake, the 1985 Valparaiso (Chile) earthquake, and the 1983 Akita-Oki (Japan) earthquake. The decay of spectral amplitude with the distance from the station was determined, considering different measures of distance from a finite fault, and it was found to be different for these three events. The results can be used to establish empirical relations between the observed spectra and the half-space responses depending on the distance and the site condition, making it possible to estimate strong motions from source spectra determined from teleseismic records.

Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs.

PubMed

Dierks, C; Mömke, S; Philipp, U; Distl, O

2013-08-01

Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Generating double knockout mice to model genetic intervention for diabetic cardiomyopathy in humans.

PubMed

Chavali, Vishalakshi; Nandi, Shyam Sundar; Singh, Shree Ram; Mishra, Paras Kumar

2014-01-01

Diabetes is a rapidly increasing disease that enhances the chances of heart failure twofold to fourfold (as compared to age and sex matched nondiabetics) and becomes a leading cause of morbidity and mortality. There are two broad classifications of diabetes: type1 diabetes (T1D) and type2 diabetes (T2D). Several mice models mimic both T1D and T2D in humans. However, the genetic intervention to ameliorate diabetic cardiomyopathy in these mice often requires creating double knockout (DKO). In order to assess the therapeutic potential of a gene, that specific gene is either overexpressed (transgenic expression) or abrogated (knockout) in the diabetic mice. If the genetic mice model for diabetes is used, it is necessary to create DKO with transgenic/knockout of the target gene to investigate the specific role of that gene in pathological cardiac remodeling in diabetics. One of the important genes involved in extracellular matrix (ECM) remodeling in diabetes is matrix metalloproteinase-9 (Mmp9). Mmp9 is a collagenase that remains latent in healthy hearts but induced in diabetic hearts. Activated Mmp9 degrades extracellular matrix (ECM) and increases matrix turnover causing cardiac fibrosis that leads to heart failure. Insulin2 mutant (Ins2+/-) Akita is a genetic model for T1D that becomes diabetic spontaneously at the age of 3-4 weeks and show robust hyperglycemia at the age of 10-12 weeks. It is a chronic model of T1D. In Ins2+/- Akita, Mmp9 is induced. To investigate the specific role of Mmp9 in diabetic hearts, it is necessary to create diabetic mice where Mmp9 gene is deleted. Here, we describe the method to generate Ins2+/-/Mmp9-/- (DKO) mice to determine whether the abrogation of Mmp9 ameliorates diabetic cardiomyopathy.

Incidence of disability and its associated factors in Japanese men and women: the Longitudinal Cohorts of Motor System Organ (LOCOMO) study.

PubMed

Yoshimura, Noriko; Akune, Toru; Fujiwara, Saeko; Shimizu, Yoko; Yoshida, Hideyo; Nishiwaki, Yuji; Sudo, Akihiro; Omori, Go; Yoshida, Munehito; Shimokata, Hiroshi; Suzuki, Takao; Muraki, Shigeyuki; Oka, Hiroyuki; Nakamura, Kozo

2015-03-01

We investigated the incidence of disability and its risk factors in older Japanese adults to establish an evidence-based disability prevention strategy for this population. For this purpose, we used data from the Longitudinal Cohorts of Motor System Organ (LOCOMO) study, initiated in 2008 to integrate information from cohorts in nine communities across Japan: Tokyo (two regions), Wakayama (two regions), Hiroshima, Niigata, Mie, Akita, and Gunma prefectures. We examined the annual occurrence of disability from 8,454 individuals (2,705 men and 5,749 women) aged ≥65 years. The estimated incidence of disability was 3.58/100 person-years (p-y) (men: 3.17/100 p-y; women: 3.78/100 p-y). To determine factors associated with disability, Cox's proportional hazard model was used, with the occurrence of disability as an objective variable and age (+1 year), gender (vs. women), body build (0: normal/overweight range, BMI 18.5-27.5 kg/m(2); 1: emaciation, BMI <18.5 kg/m(2); 2: obesity, BMI >27.5 kg/m(2)), and regional differences (0: rural areas including Wakayama, Niigata, Mie, Akita, and Gunma vs. 1: urban areas including Tokyo and Hiroshima) as explanatory variables. Age, body build, and regional difference significantly influenced the occurrence of disability (age, +1 year: hazard ratio 1.13, 95% confidence interval 1.12-1.15, p < 0.001; body build, vs. emaciation: 1.24, 1.01-1.53, p = 0.041; body build, vs. obesity: 1.36, 1.08-1.71, p = 0.009; residence, vs. living in rural areas: 1.59, 1.37-1.85, p < 0.001). We concluded that higher age, both emaciation and obesity, and living in rural areas would be risk factors for the occurrence of disability.

Cytometric analysis of retinopathies in retinal trypsin digests

NASA Astrophysics Data System (ADS)

Ghanian, Zahra; Staniszewski, Kevin; Sorenson, Christine M.; Sheibani, Nader; Ranji, Mahsa

2014-03-01

The objective of this work was to design an automated image cytometry tool for determination of various retinal vascular parameters including extraction of features that are relevant to postnatal retinal vascular development, and the progression of diabetic retinopathy. To confirm the utility and accuracy of the software, retinal trypsin digest from TSP1-/- and diabetic Akita/+; TSP1-/- mice were analyzed. TSP1 is a critical inhibitor of development of retinopathies and lack of TSP1 exacerbates progression of early diabetic retinopathies. Loss of vascular cells of and gain more acellular capillaries as two major signs of diabetic retinopathies were used to classify a retina as normal or injured. This software allows quantification and high throughput assessment of retinopathy changes associated with diabetes.

Knowing the people who come to public astronomical observatories: The case of Akita prefecture, Japan

NASA Astrophysics Data System (ADS)

Kawamura, N.

2015-03-01

The purpose of this research is to know and gain a better understanding of people who come to astronomical observatories and to find out more about their experiences and thoughts on astronomy. To find some of the issues about science communication in astronomy, the author carried out questionnaire research studies involving high school students and junior high school and elementary school teachers.

Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy

PubMed Central

Sieg, Kelsey M.; Shallow, Keegan D.; Sorenson, Christine M.; Sheibani, Nader

2013-01-01

Purpose Hyperglycemia activates several metabolic pathways, including the hexosamine biosynthetic pathway. Uridine diphosphate N-acetylglucosamine (GlcNAc) is the product of the hexosamine biosynthetic pathway and the substrate for O-linked GlcNAc (O-GlcNAc) modification. This modification affects a wide range of proteins by altering their activity, cellular localization, and/or protein interactions. However, the role O-GlcNAcylation may play in normal postnatal retinal vascular development and in the ocular complications of diabetes, including diabetic retinopathy, requires further investigation. Methods The total levels of O-GlcNAc-modified proteins were evaluated by western blot analysis of lysates prepared from retinas obtained at different days during postnatal retinal vascularization and oxygen-induced ischemic retinopathy. Similar experiments were performed with retinal lysate prepared from diabetic Ins2Akita/+ mice with different durations of diabetes and retinal vascular cells cultured under various glucose conditions. The localization of O-GlcNAc-modified proteins in the retinal vasculature was confirmed by immunofluorescence staining. The impact of altered O-GlcNAcylation on the migration of retinal vascular cells was determined using scratch wound and transwell migration assays. Results We detected an increase in protein O-GlcNAcylation during mouse postnatal retinal vascularization and aging, in part through the regulation of the enzymes that control this modification. The study of the diabetic Ins2Akita/+ mouse retina showed an increase in the O-GlcNAc modification of retinal proteins. We also observed an increase in retinal O-GlcNAcylated protein levels during the neovascularization phase of oxygen-induced ischemic retinopathy. Our fluorescence microscopy data confirmed that the alterations in retinal O-GlcNAcylation are similarly represented in the retinal vasculature and in retinal pericytes and endothelial cells. Particularly, the migration of

Social and Geographical Inequalities in Suicide in Japan from 1975 through 2005: A Census-Based Longitudinal Analysis

PubMed Central

Suzuki, Etsuji; Kashima, Saori; Kawachi, Ichiro; Subramanian, S. V.

2013-01-01

Background Despite advances in our understanding of the countercyclical association between economic contraction and suicide, less is known about the levels of and changes in inequalities in suicide. The authors examined social and geographical inequalities in suicide in Japan from 1975 through 2005. Methods Based on quinquennial vital statistics and census data, the authors analyzed the entire population aged 25–64 years. The total number of suicides was 75,840 men and 30,487 women. For each sex, the authors estimated odds ratios (ORs) and 95% credible intervals (CIs) for suicide using multilevel logistic regression models with “cells” (cross-tabulated by age and occupation) at level 1, seven different years at level 2, and 47 prefectures at level 3. Prefecture-level variance was used as an estimate of geographical inequalities in suicide. Results Adjusting for age and time-trends, the lowest odds for suicide was observed among production process and related workers (the reference group) in both sexes. The highest OR for men was 2.52 (95% CI: 2.43, 2.61) among service workers, whereas the highest OR for women was 9.24 (95% CI: 7.03, 12.13) among security workers. The degree of occupational inequalities increased among men with a striking change in the pattern. Among women, we observed a steady decline in suicide risk across all occupations, except for administrative and managerial workers and transport and communication workers. After adjusting for individual age, occupation, and time-trends, prefecture-specific ORs ranged from 0.76 (Nara Prefecture) to 1.36 (Akita Prefecture) for men and from 0.79 (Kanagawa Prefecture) to 1.22 (Akita Prefecture) for women. Geographical inequalities have increased primarily among men since 1995. Conclusions The present findings demonstrate a striking temporal change in the pattern of social inequalities in suicide among men. Further, geographical inequalities in suicide have considerably increased across 47 prefectures

[Acute encephalopathy caused by cyanogenic fungi in 2004, and magic mushroom regulation in Japan].

PubMed

Gonmori, Kunio; Yokoyama, Kazumasa

2009-03-01

Two topics, related to mushroom poisoning of recent interest in Japan, have been presented. In autumn 2004, 59 cases of acute encephalopathy were reported across 9 prefectures in Japan (24 from Akita Prefecture with 8 deaths; age 48-93, average 70; female 14, male 10). Of 24 cases, 20 had kidney dysfunction. Four poisoned subjects showed no kidney trouble. Of the 24 poisoning cases, 23 people ate Pleurocybella porrigens, and one ate Grifola frondosa. The latter subject (female, late 40's) was receiving dialysis for more than 35 years. In August, she felt dizziness, headache and tinnitus. She visited hospital and asked to stay there. In the hospital she ate 5g of stewed G. frondosa and 10g of the same fungus boiled with chicken and taro on different days. Fourteen to 18 days after the eatings, she developed cramps and lost consciousness, and fell into a coma. Her cramp and coma continued for about 10 days almost until her death. Her symptoms caused by G. frondosa were similar to those observed for the above 23 cases of P. porrigens ingestion. Therefore, we concluded that encephalopathy experienced in Akita Prefecture caused by was the cyanogenic fungi such as P. porrigens , G. frondosa, Pleurotus eringii etc. Although the amounts of mushrooms eaten by poisoned subjects were not so clear, we estimated that the amounts of hydrogen cyanide (HCN) taken into human bodies exceeded the detoxication limit of HCN, resulting in HCN poisoning. However, it has not been proved that the encephalopathy is directly or indirectly caused by the HCN poisoning. Many typhoons came across Japan and landed 10 times in 2004, and mushroom size was larger than usual one, and HCN contents in fruit-bodies seemed to be increased especially in the late-stage of their growth. Thirteen species of magic mushrooms were prohibited by the law from 2002 in Japan. They include Copelandia (Panaeolus) cyanescens, Panaeolus papilionaceus, Panaeolus sphinctrinus, Panaeolus subbalteatus, Psilocybe argentipes

Policies and Practices of School Leaderships in Japan: A Case of Leadership Development Strategies in Akita

ERIC Educational Resources Information Center

Yamamoto, Yukiko; Enomoto, Naoko; Yamaguchi, Shinobu

2016-01-01

Reflecting the social and economic change, Japanese education has shifted to decentralization since the 1980s. With an increased autonomy and responsibility, the local government plays an important role to develop competent school leaders. This descriptive study employs case study approach to illustrate current status of leadership development at…

Effect of climate change on annual fluctuations in the population density of the brown marmorated stink bug (Hemiptera: Pentatomidae) in northern Japan.

PubMed

Funayama, Ken

2013-10-01

The relationship between the population density of overwintering adults of the brown marmorated stink bug and the temperatures of each month during the preceding November to April was investigated in Akita Prefecture, northern Japan, from 1999 to 2012. The number of adults entering traps for overwintering at the monitored hibernation site differed considerably among years. There was a significant negative correlation between the increase ratio (the ratio of the number collected in the current year to the number collected in the previous year) and the mean daily maximum temperature of the preceding March and April. These results suggest that the proportion of surviving adult brown marmorated stink bug may be higher when temperatures in early spring (March and April) are lower, as the postoverwintering adults may need to survive without food for a shorter period of time.

PREFACE Preface

NASA Astrophysics Data System (ADS)

Takahashi, Migaku; Saito, Hitoshi; Yoshimura, Satoru; Takanashi, Koki; Sahashi, Masashi; Tsunoda, Masakiyo

2011-01-01

23 countries, with about 40 percent of participants attending from overseas (see figure). The program involved 4 plenary talks (45 minutes each), 37 invited talks (30 minutes), 85 contributed talks (15 minutes), and 352 posters. Pie chart Organizing Committee of ISAMMA 2010 M TakahashiTohoku Univ., Japan, Chairman K TakanashiTohoku Univ., Japan, Chair of the Program Committee H SaitoAkita Univ., Japan, Chair of the Publication Committee M SahashiTohoku Univ., Japan, Chair of the Treasury Committee M TsunodaTohoku Univ., Japan, General Secretary H AkinagaAIST, Japan H FukunagaNagasaki Univ., Japan K HonoNIMS, Japan S IshioAkita Univ., Japan S IwataNagoya Univ., Japan K NakagawaNihon Univ., Japan S NakagawaTokyo Inst. of Tech., Japan T OnoKyoto Univ., Japan Y SuzukiOsaka Univ., Japan M TanakaEhime Univ., Japan T Tanaka Univ. of Tokyo, Japan Program Committee of ISAMMA 2010 K TakanashiTohoku Univ., Japan, ChairS MizukamiTohoku Univ., Japan M MizuguchiTohoku Univ., Japan, Vice-chairH NaganumaTohoku Univ., Japan M DoiTohoku Univ., JapanS NakagawaTokyo Inst. of Tech., Japan A FujitaTohoku Univ., JapanK NakamuraTohoku Univ., Japan K IshiyamaTohoku Univ., JapanK OnoKEK, Japan T KatoNagoya Univ., JapanT OnoKyoto Univ., Japan T KawagoeOsaka Pref. Univ.of Edu., JapanF SatoTohoku Univ., Japan O KitakamiTohoku Univ., JapanM ShiraiTohoku Univ., Japan Y KitamotoTokyo Inst. of Tech., JapanS SugimotoTohoku Univ., Japan F MatsukuraTohoku Univ., JapanM YamaguchiTohoku Univ., Japan C MitsumataHitachi Metals, Japan Publication Committee of ISAMMA 2010 H SaitoAkita Univ., Japan, ChairS MitaniNIMS, Japan S YoshimuraAkita Univ., Japan, Vice-chairH MuraokaTohoku, Japan Y AndoTohoku Univ., JapanM NakanoNagasaki Univ., Japan J AriakeAIT, JapanR NakataniOsaka Univ., Japan H AsanoNagoya Univ., JapanK O'GradyUniv. of York, UK M FutamotoChuo Univ., JapanA SakumaTohoku Univ., Japan J HayakawaHitachi, ARL, JapanT SatoKeio Univ., Japan T HondaKyushu Inst. of Tech., JapanT SatoShinshu Univ., Japan M

Prevalence of psychological distress, as measured by the Kessler 6 (K6), and related factors in Japanese employees.

PubMed

Fushimi, Masahito; Saito, Seiji; Shimizu, Tetsuo; Kudo, Yasutsugu; Seki, Masayuki; Murata, Katsuyuki

2012-06-01

The aim of this study was to examine the prevalence of and related factors for psychological distress among employees. The employees in Akita prefecture, Japan, were invited to complete the Kessler 6 (K6). A value of 13 or higher on the K6 scale indicated high psychological distress. Furthermore, we identified the relationships among the prevalence of high psychological distress, socio-demographic status, and employment-related variables. The data of 1,709 employees indicated that 10.8% of the employees had high psychological distress; the proportion of psychological distress found in the present study was high compared to that found in previous studies. The identified socio-demographic and occupation-related factors included young age groups associated with a high risk and clerical or administrative tasks associated with a low risk of psychological distress. The data of this study can be used as K6 benchmark values, which enhance the significance of future corporate health risk appraisal surveys.

Quantitative Assessment of Retinopathy Using Multi-parameter Image Analysis

PubMed Central

Ghanian, Zahra; Staniszewski, Kevin; Jamali, Nasim; Sepehr, Reyhaneh; Wang, Shoujian; Sorenson, Christine M.; Sheibani, Nader; Ranji, Mahsa

2016-01-01

A multi-parameter quantification method was implemented to quantify retinal vascular injuries in microscopic images of clinically relevant eye diseases. This method was applied to wholemount retinal trypsin digest images of diabetic Akita/+, and bcl-2 knocked out mice models. Five unique features of retinal vasculature were extracted to monitor early structural changes and retinopathy, as well as quantifying the disease progression. Our approach was validated through simulations of retinal images. Results showed fewer number of cells (P = 5.1205e-05), greater population ratios of endothelial cells to pericytes (PCs) (P = 5.1772e-04; an indicator of PC loss), higher fractal dimension (P = 8.2202e-05), smaller vessel coverage (P = 1.4214e-05), and greater number of acellular capillaries (P = 7.0414e-04) for diabetic retina as compared to normal retina. Quantification using the present method would be helpful in evaluating physiological and pathological retinopathy in a high-throughput and reproducible manner. PMID:27186534

Retrospective study on temporal and regional variations of methylmercury concentrations in preserved umbilical cords collected from inhabitants of the Minamata area, Japan.

PubMed

Sakamoto, Mineshi; Murata, Katsuyuki; Tsuruta, Kazuhito; Miyamoto, Kenichiro; Akagi, Hirokatsu

2010-09-01

The present study was conducted to investigate the historical time-course changes and regional distribution of methylmercury concentrations in preserved umbilical cords collected from Minamata-area inhabitants born between 1947 and 1989. The data from Miyazaki, Tottori, Akita, Tsushima (Nagasaki), Fukuoka and Tokyo were used as controls. A total of 325 data were analyzed to estimate the temporal and spatial distribution of methylmercury among inhabitants born in the Minamata area. Elevated methylmercury concentrations (>or=1 microg/g) were mainly observed in inhabitants born between 1947 and 1968. That peak coincided with the peak of acetaldehyde production in Minamata. The methylmercury concentrations started to decrease in keeping with the decline of acetaldehyde production, which ceased in 1968, and thereafter the methylmercury levels gradually decreased to the control levels. Elevated methylmercury concentrations were first observed in the districts of Minamata, followed by Izumi, Tsunagi and Ashikita, indicating the time-course-dependent regional distributions of methylmercury pollution. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Application of a multilocus variable number of tandem repeats analysis to regional outbreak surveillance of Enterohemorrhagic Escherichia coli O157:H7 infections.

PubMed

Konno, Takayuki; Yatsuyanagi, Jun; Saito, Shioko

2011-01-01

A total of 18 strains of EHEC O157:H7 were isolated from distinct cases in Akita Prefecture, Japan from July to September 2007. The genetic relatedness of these isolates was investigated by performing a multilocus variable number of tandem repeats analysis (MLVA) and a pulsed-field gel electrophoresis (PFGE) analysis using XbaI. The PFGE analyses allowed us to group these 18 isolates into three major clusters. The MLVA results correlated closely with those obtained by PFGE, although some variants were found within the clusters obtained by PFGE, thus highlighting the utility of this technique for determining a precise classification when it is difficult to differentiate between isolates with indistinguishable or very similar PFGE patterns. In addition, MLVA is a much easier and more rapid method than PFGE for analysis of the genetic relatedness of strains. Thus, as a second molecular epidemiological subtyping method, MLVA is useful for the regional outbreak surveillance of EHEC O157:H7 infections.

Glucose 6-phosphate dehydrogenase variants in Japan.

PubMed

Miwa, S

1980-01-01

Fifty-four cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency have so far been reported in Japan. Among them, 21 G6PD variants have been characterized. Nineteen out of the 21 variants were characterized in our laboratory and G6PD Heian and "Kyoto" by others. G6PD Tokyo, Tokushima, Ogikubo, Kurume, Fukushima, Yokohama, Yamaguchi, Wakayama, Akita, Heian and "Kyoto" were classified as Class 1, because all these cases showed chronic hemolytic anemia and severe enzyme deficiency. All these variants showed thermal instability. G6PD Mediterranean-like, Ogori, Gifu and Fukuoka were classified as Class 2, whereas G6PD Hofu, B(-) Chinese, Ube, Konan, Kamiube and Kiwa belonged to Class 3. All the 6 Class 3 variants were found as the results of the screening tests. The incidence of the deficiency in Japanese seems to be 0.1-0.5% but that of the cases which may slow drug-induced hemolysis would be much less. G6PD Ube and Konan appear to be relatively common in Japan.

Identification of crude-oil components and microorganisms that cause souring under anaerobic conditions.

PubMed

Hasegawa, R; Toyama, K; Miyanaga, K; Tanji, Y

2014-02-01

Oil souring has important implications with respect to energy resources. Understanding the physiology of the microorganisms that play a role and the biological mechanisms are both important for the maintenance of infrastructure and mitigation of corrosion processes. The objective of this study was to identify crude-oil components and microorganisms in oil-field water that contribute to crude-oil souring. To identify the crude-oil components and microorganisms that are responsible for anaerobic souring in oil reservoirs, biological conversion of crude-oil components under anaerobic conditions was investigated. Microorganisms in oil field water in Akita, Japan degraded alkanes and aromatics to volatile fatty acids (VFAs) under anaerobic conditions, and fermenting bacteria such as Fusibacter sp. were involved in VFA production. Aromatics such as toluene and ethylbenzene were degraded by sulfate-reducing bacteria (Desulfotignum sp.) via the fumarate-addition pathway and not only degradation of VFA but also degradation of aromatics by sulfate-reducing bacteria was the cause of souring. Naphthenic acid and 2,4-xylenol were not converted.

Evolutionary genetics of highly pathogenic H5N1 avian influenza viruses isolated from whooper swans in northern Japan in 2008.

PubMed

Usui, Tatsufumi; Yamaguchi, Tsuyoshi; Ito, Hiroshi; Ozaki, Hiroichi; Murase, Toshiyuki; Ito, Toshihiro

2009-12-01

In April and May 2008, highly pathogenic avian influenza viruses subtype H5N1 were isolated from dead or moribund whooper swans in Aomori, Akita and Hokkaido prefectures in northern Japan. To trace the genetic lineage of the isolates, the nucleotide sequences of all eight genes were determined and phylogenetically analyzed. The Japanese strains were nearly identical to chicken viruses isolated in Russia in April 2008 and closely related to viruses isolated from dead wild birds in Hong Kong in 2007-2008. Their HA genes clustered in clade 2.3.2. On the other hand, NA and the other internal genes were closely related to those of clade 2.3.4 viruses (genotype V) whose NP genes originated from an HA clade 2.3.2 virus. In conclusion, the H5N1 viruses isolated in Japan, Russia and Hong Kong were derived from a common ancestor virus belonging to genotype V that was generated from genetic reassortment events between viruses of HA clades 2.3.2 and 2.3.4.

Possible Short-Term Precursors of Strong Crustal Earthquakes in Japan based on Data from the Ground Stations of Vertical Ionospheric Sounding

NASA Astrophysics Data System (ADS)

Korsunova, L. P.; Khegai, V. V.

2018-01-01

We have studied changes in the ionosphere prior to strong crustal earthquakes with magnitudes of M ≥ 6.5 based on the data from the ground-based stations of vertical ionospheric sounding Kokobunji, Akita, and Wakkanai for the period 1968-2004. The data are analyzed based on hourly measurements of the virtual height and frequency parameters of the sporadic E layer and critical frequency of the regular F2 layer over the course of three days prior to the earthquakes. In the studied intervals of time before all earthquakes, anomalous changes were discovered both in the frequency parameters of the Es and F2 ionospheric layers and in the virtual height of the sporadic E layer; the changes were observed on the same day at stations spaced apart by several hundred kilometers. A high degree of correlation is found between the lead-time of these ionospheric anomalies preceding the seismic impact and the magnitude of the subsequent earthquakes. It is concluded that such ionospheric disturbances can be short-term ionospheric precursors of earthquakes.

Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

PubMed Central

Colombo, Carlo; Porzio, Ottavia; Liu, Ming; Massa, Ornella; Vasta, Mario; Salardi, Silvana; Beccaria, Luciano; Monciotti, Carla; Toni, Sonia; Pedersen, Oluf; Hansen, Torben; Federici, Luca; Pesavento, Roberta; Cadario, Francesco; Federici, Giorgio; Ghirri, Paolo; Arvan, Peter; Iafusco, Dario; Barbetti, Fabrizio

2008-01-01

Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic β cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM. PMID:18451997

Reversal of Diabetic Nephropathy by a Ketogenic Diet

PubMed Central

Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.

2011-01-01

Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091

Risk factors for acquired myasthenia gravis in dogs: 1,154 cases (1991-1995).

PubMed

Shelton, G D; Schule, A; Kass, P H

1997-12-01

To determine frequency of initial clinical signs and risk factors for acquired myasthenia gravis (MG) in dogs. Retrospective study. 1,154 dogs residing within the United States from 1991 to 1995 with a confirmed diagnosis of acquired MG and 7,176 dogs with other neuromuscular disorders, including generalized weakness, megaesophagus, and dysphagia (control group). Records were retrieved from a database containing results of serum samples tested for acetylcholine receptor antibodies. Signalment, breed, age, state of origin, and month of onset of clinical signs were obtained. An antibody titer > 0.6 nmol/L was diagnostic for acquired MG. Unconditional logistic regression was used for statistical analysis. In comparison with mixed-breed dogs, dogs with the highest risk of acquired MG were Akitas, terrier group, Scottish Terriers, German Shorthaired Pointers, and Chihuahuas. Rottweilers, Doberman Pinschers, Dalmatians, and Jack Russell Terriers had low relative risks. Sexually intact males and dogs less than 1 year old had some protection from risk. Generalized weakness with megaesophagus and megaesophagus alone were the most common initial clinical signs. Breed predispositions for acquired MG were demonstrated. Age and sex were contributing factors. Although most dogs had generalized clinical signs, a substantial proportion of dogs had focal signs.

First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil.

PubMed

Maldonado, Arnaldo; Simões, Raquel O; Oliveira, Ana Paula M; Motta, Esther M; Fernandez, Mônica A; Pereira, Zilene M; Monteiro, Simone S; Torres, Eduardo J Lopes; Thiengo, Silvana Carvalho

2010-11-01

The rat lungworm Angiostrongylus cantonensis is a worldwide-distributed zoonotic nematode that can cause human eosinophilic meningoencephalitis. Here, for the first time, we report the isolation of A. cantonensis from Achatina fulica from two Brazilian states: Rio de Janeiro (specifically the municipalities of Barra do Piraí, situated at the Paraiba River Valley region and São Gonçalo, situated at the edge of Guanabara Bay) and Santa Catarina (in municipality of Joinville). The lungworms were identified by comparing morphological and morphometrical data obtained from adult worms to values obtained from experimental infections of A. cantonensis from Pernambuco, Brazil, and Akita, Japan. Only a few minor morphological differences that were determined to represent intra-specific variation were observed. This report of A. cantonensis in South and Southeast Brazil, together with the recent report of the zoonosis and parasite-infected molluscs in Northeast Brazil, provide evidence of the wide distribution of A. cantonensis in the country. The need for efforts to better understand the role of A. fulica in the transmission of meningoencephalitis in Brazil and the surveillance of molluscs and rodents, particularly in ports, is emphasized.

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

PubMed Central

Losiewicz, Mandy K.; Pennathur, Subramaniam; Jefferson, Leonard S.; Kimball, Scot R.; Abcouwer, Steven F.; Gardner, Thomas W.

2014-01-01

Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2Akita diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. PMID:24740573

Population data of six STR loci using hexaplex PCR amplification and typing system, "Midi-6" in four regional populations in Japan.

PubMed

Uchihi, Rieko; Yamamoto, Toshimichi; Yoshimoto, Takashi; Inoue, Chikako; Kishida, Tetsuko; Yoshioka, Naofumi; Katsumata, Yoshinao

2007-07-04

The genetic differences of the allele frequency distributions for six STR loci (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290) among regions in Japan were examined using our recently designed hexaplex amplification and typing system, "Midi-6" newly named, to construct a database in the Japanese population. Genotypes at six loci were analyzed in 198, 200, 175, and 196 individuals from the area of Akita, Nagoya, Oita, and Okinawa, respectively, in Japan. The allele frequency distributions were significantly different (p<0.05) at from one to five loci among the four populations when compared pairwise. Significant differences were also observed at two or three loci between Oita- or Okinawa-Japanese and the "pooled" population (n=769), respectively. However, since F(ST) (theta) values were extremely low (<0.05), ranging from 0.0020 to 0.0118 for six loci, genetic differentiation within the pooled Japanese population was negligible. Therefore, it suggested that the data of the allele frequencies at six loci in the pooled population would be employed as the base of calculation for statistical probabilities.

The prevalence of ABCB1:c.227_230delATAG mutation in affected dog breeds from European countries.

PubMed

Firdova, Zuzana; Turnova, Evelina; Bielikova, Marcela; Turna, Jan; Dudas, Andrej

2016-06-01

Deletion of 4-base pairs in the canine ABCB1 (MDR1) gene, responsible for encoding P-glycoprotein, leads to nonsense frame-shift mutation, which causes hypersensitivity to macrocyclic lactones drugs (e.g. ivermectin). To date, at least 12 purebred dog breeds have been found to be affected by this mutation. The aim of this study was to update information about the prevalence of ABCB1 mutation (c.227_230delATAG) in predisposed breeds in multiple European countries. This large scale survey also includes countries which were not involved in previous studies. The samples were collected in the period from 2012 to 2014. The overview is based on genotyping data of 4729 individuals. The observed mutant allele frequencies were 58.5% (Smooth Collie), 48.3% (Rough Collie), 35% (Australian Shepherd), 30.3% (Shetland Sheepdog), 28.1% (Silken Windhound), 26.1% (Miniature Australian Shepherd), 24.3% (Longhaired Whippet), 16.2% (White Swiss Shepherd) and 0% (Border Collie). The possible presence of an ABCB1 mutant allele in Akita-Inu breed has been investigated with negative results. This information could be helpful for breeders in optimization of their breeding strategy and for veterinarians when prescribing drug therapy for dogs of predisposed breeds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental Diabetes Mellitus in Different Animal Models

PubMed Central

Al-awar, Amin; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

2016-01-01

Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. PMID:27595114

The relationship between suicide and five climate issues in a large-scale and long-term study in Japan.

PubMed

Inoue, K; Nishimura, Y; Fujita, Y; Ono, Y; Fukunaga, T

2012-08-01

Suicide rates in Japan were high in 1998 and have remained high since then. Many researchers have discussed the current state of suicide in Japan and the world; however, there are various opinions about the relationship between suicide and climate. In the present study, we report on long-term data of suicide and examine five climatic issues in Japan as a whole and in 10 selected prefectures: the five with the highest suicide rates in 2006 (Akita, Iwate, Shimane, Yamagata and Miyazaki Prefectures) and the five with the lowest (Nara, Tokushima, Okayama, Kanagawa and Kyoto Prefectures). Annual age-adjusted suicide rates were found to have a significant inverse correlation with annual mean air temperature in the five prefectures with the highest suicide rates and in the three prefectures with the lowest suicide rates among women. Annual age-adjusted suicide rates were significantly correlated with annual mean relative humidity in the three prefectures with the highest suicide rates among women and with the annual total sunshine duration in the three prefectures with the highest suicide rates among women. It is important that these associations between suicide and climatic factors be discussed further from various viewpoints, including those of many researchers and relevant organizations.

Collaborative Sounding Rocket launch in Alaska and Development of Hybrid Rockets

NASA Astrophysics Data System (ADS)

Ono, Tomohisa; Tsutsumi, Akimasa; Ito, Toshiyuki; Kan, Yuji; Tohyama, Fumio; Nakashino, Kyouichi; Hawkins, Joseph

Tokai University student rocket project (TSRP) was established in 1995 for a purpose of the space science and engineering hands-on education, consisting of two space programs; the one is sounding rocket experiment collaboration with University of Alaska Fairbanks and the other is development and launch of small hybrid rockets. In January of 2000 and March 2002, two collaborative sounding rockets were successfully launched at Poker Flat Research Range in Alaska. In 2001, the first Tokai hybrid rocket was successfully launched at Alaska. After that, 11 hybrid rockets were launched to the level of 180-1,000 m high at Hokkaido and Akita in Japan. Currently, Tokai students design and build all parts of the rockets. In addition, they are running the organization and development of the project under the tight budget control. This program has proven to be very effective in providing students with practical, real-engineering design experience and this program also allows students to participate in all phases of a sounding rocket mission. Also students learn scientific, engineering subjects, public affairs and system management through experiences of cooperative teamwork. In this report, we summarize the TSRP's hybrid rocket program and discuss the effectiveness of the program in terms of educational aspects.

Natural lactic acid bacteria population of tropical grasses and their fermentation factor analysis of silage prepared with cellulase and inoculant.

PubMed

Khota, Waroon; Pholsen, Suradej; Higgs, David; Cai, Yimin

2016-12-01

Natural lactic acid bacteria (LAB) populations in tropical grasses and their fermentation characteristics on silage prepared with cellulase enzyme and LAB inoculants were studied. A commercial inoculant Lactobacillus plantarum Chikuso 1 (CH), a local selected strain Lactobacillus casei TH14 (TH14), and 2 cellulases, Acremonium cellulase (AC) and Maicelase (MC; Meiji Seika Pharma Co. Ltd., Tokyo, Japan), were used as additives to silage preparation with fresh and wilted (6 h) Guinea grass and Napier grass. Silage was prepared using a laboratory-scale fermentation system. Treatments were CH, TH14, AC at 0.01% fresh matter, AC 0.1%, MC 0.01%, MC 0.1%, CH+AC 0.01%, CH+AC 0.1%, CH+MC 0.01%, CH+MC 0.1%, TH14+AC 0.1%, TH14+AC 0.01%, TH14+MC 0.1%, and TH14+MC 0.01%. Microorganism counts of Guinea grass and Napier grass before ensiling were 10 2 LAB and 10 6 aerobic bacteria; these increased during wilting. Based on morphological and biochemical characteristics, and 16S rRNA gene sequence analysis, natural strains from both grasses were identified as L. plantarum, L. casei, Lactobacillus acidipiscis, Leuconostoc pseudomesenteroides, Leuconostoc garlicum, Weissella confusa, and Lactococcus lactis. Lactobacillus plantarum and L. casei are the dominant species and could grow at lower pH and produce more lactic acid than the other isolates. Crude protein and neutral detergent fiber were 5.8 and 83.7% of dry matter (DM) for Guinea grass, and 7.5 and 77.1% of DM for Napier grass. Guinea grass had a low level of water-soluble carbohydrates (0.39% of DM). Guinea grass silage treated with cellulase had a lower pH and higher lactic acid content than control and LAB treatments. The 0.1% AC and MC treatments had the best result for fermentation quality. All high water-soluble carbohydrate (2.38% DM) Napier grass silages showed good fermentation quality. Compared with control and LAB-inoculated silage, the cellulase-treated silages had significantly higher crude protein content and

Non-dietary risk factors for gastric dilatation-volvulus in large and giant breed dogs.

PubMed

Glickman, L T; Glickman, N W; Schellenberg, D B; Raghavan, M; Lee, T

2000-11-15

To identify non-dietary risk factors for gastric dilatation-volvulus (GDV) in large breed and giant breed dogs. Prospective cohort study. 1,637 dogs > or = 6 months old of the following breeds: Akita, Bloodhound, Collie, Great Dane, Irish Setter, Irish Wolfhound, Newfoundland, Rottweiler, Saint Bernard, Standard Poodle, and Weimaraner. Owners of dogs that did not have a history of GDV were recruited at dog shows, and the dog's length and height and the depth and width of its thorax and abdomen were measured. Information concerning the dog's medical history, genetic background, personality, and diet was obtained from the owners, and owners were contacted by mail and telephone at approximately 1-year intervals to determine whether dogs had developed GDV or died. Incidence of GDV, calculated on the basis of dog-years at risk for dogs that were or were not exposed to potential risk factors, was used to calculate the relative risk of GDV. Cumulative incidence of GDV during the study was 6% for large breed and giant breed dogs. Factors significantly associated with an increased risk of GDV were increasing age, having a first-degree relative with a history of GDV, having a faster speed of eating, and having a raised feeding bowl. Approximately 20 and 52% of cases of GDV among the large breed and giant breed dogs, respectively, were attributed to having a raised feed bowl.

Incidence of and breed-related risk factors for gastric dilatation-volvulus in dogs.

PubMed

Glickman, L T; Glickman, N W; Schellenberg, D B; Raghavan, M; Lee, T L

2000-01-01

To compare incidence of and breed-related risk factors for gastric dilatation-volvulus (GDV) among 11 dog breeds (Akita, Bloodhound, Collie, Great Dane, Irish Setter, Irish Wolfhound, Newfoundland, Rottweiler, Saint Bernard, Standard Poodle, and Weimaraner). Prospective cohort study. 1,914 dogs. Owners of dogs that did not have a history of GDV were recruited at dog shows, and the dog's length and height and depth and width of the thorax and abdomen were measured. Information concerning the dogs' medical history, genetic background, personality, and diet was obtained from owners, and owners were contacted by mail and telephone at approximately 1-year intervals to determine whether dogs had developed GDV or died. Incidence of GDV based on the number of dog-years at risk was calculated for each breed, and breed-related risk factors were identified. Incidence of GDV for the 7 large (23 to 45 kg [50 to 99 lb]) and 4 giant (> 45 kg [> 99 lb]) breeds was 23 and 26 cases/1,000 dog-years at risk, respectively. Of the 105 dogs that developed GDV, 30 (28.6%) died. Incidence of GDV increased with increasing age. Cumulative incidence of GDV was 5.7% for all breeds. The only breed-specific characteristic significantly associated with a decreased incidence of GDV was an owner-perceived personality trait of happiness.

Japanese Wolves are Genetically Divided into Two Groups Based on an 8-Nucleotide Insertion/Deletion within the mtDNA Control Region.

PubMed

Ishiguro, Naotaka; Inoshima, Yasuo; Yanai, Tokuma; Sasaki, Motoki; Matsui, Akira; Kikuchi, Hiroki; Maruyama, Masashi; Hongo, Hitomi; Vostretsov, Yuri E; Gasilin, Viatcheslav; Kosintsev, Pavel A; Quanjia, Chen; Chunxue, Wang

2016-02-01

The mitochondrial DNA (mtDNA) control region (198- to 598-bp) of four ancient Canis specimens (two Canis mandibles, a cranium, and a first phalanx) was examined, and each specimen was genetically identified as Japanese wolf. Two unique nucleotide substitutions, the 78-C insertion and the 482-G deletion, both of which are specific for Japanese wolf, were observed in each sample. Based on the mtDNA sequences analyzed, these four specimens and 10 additional Japanese wolf samples could be classified into two groups- Group A (10 samples) and Group B (4 samples)-which contain or lack an 8-bp insertion/deletion (indel), respectively. Interestingly, three dogs (Akita-b, Kishu 25, and S-husky 102) that each contained Japanese wolf-specific features were also classified into Group A or B based on the 8-bp indel. To determine the origin or ancestor of the Japanese wolf, mtDNA control regions of ancient continental Canis specimens were examined; 84 specimens were from Russia, and 29 were from China. However, none of these 113 specimens contained Japanese wolf-specific sequences. Moreover, none of 426 Japanese modern hunting dogs examined contained these Japanese wolf-specific mtDNA sequences. The mtDNA control region sequences of Groups A and B appeared to be unique to grey wolf and dog populations.

Myostatin inhibition therapy for insulin-deficient type 1 diabetes.

PubMed

Coleman, Samantha K; Rebalka, Irena A; D'Souza, Donna M; Deodhare, Namita; Desjardins, Eric M; Hawke, Thomas J

2016-09-01

While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with Myostatin(Ln/Ln) mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management.

Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models

PubMed Central

Chen, Ying; Hu, Yang; Lin, Mingkai; Jenkins, Alicia J.; Keech, Anthony C.; Mott, Robert; Lyons, Timothy J.; Ma, Jian-xing

2013-01-01

Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism. PMID:23043158

Determinants of platelet aggregation in 50-70-year-old men from three Japanese communities.

PubMed

Imano, Hironori; Iso, Hiroyasu; Sato, Shinichi; Kitamura, Akihiko; Okamura, Tomonori; Tanigawa, Takeshi; Ohira, Tetsuya; Kudo, Minako; Naito, Yoshihiko; Iida, Minoru; Shimamoto, Takashi

2002-12-01

To investigate the association of lifestyle and constitutional variables with platelet aggregation, we examined the platelet aggregation, serum fatty acid composition, alcohol intake, smoking, and dietary intake of seafood and soybean estimated by a 1-week dietary record in 448 males aged 50-70 in three rural Japanese communities: Ikawa, Akita prefecture (northeast coast), Noichi, Kochi prefecture (southwest coast), and Kyowa, Ibaraki prefecture (central inland). Platelet aggregatory threshold index (PATI) was used to determine the minimum concentration of adenosine 5'-diphosphate (ADP) that caused a non-reversible aggregation of platelets. Intake of seafood and n3-polyunsaturated fatty acid and ingestion of ethanol were higher in the northeast coastal community than in the other two communities. Mean platelet and white blood cell counts were lower in northeast coastal community than in the other two communities. The geometric mean PATI was higher (i.e. platelet aggregation was lower) in the northeast coastal community than the other two communities. Within the entire sample, platelet aggregation correlated inversely with serum level of n3-polyunsaturated fatty acids and gamma-glutamyl transpeptidase, an index of alcohol consumption, and positively with platelet and white blood cell counts. Platelet aggregation tended to correlate positively with serum arachidonic acid. There was no correlation between smoking and platelet aggregation. Our results suggest that seafood intake and moderate alcohol consumption reduce platelet aggregation.

Genetic variation analysis of the Bali street dog using microsatellites

PubMed Central

Irion, Dawn N; Schaffer, Alison L; Grant, Sherry; Wilton, Alan N; Pedersen, Niels C

2005-01-01

Background Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships. Results The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis. Conclusions This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time. PMID:15701179

Antioxidants Complement the Requirement for Protein Chaperone Function to Maintain β-Cell Function and Glucose Homeostasis

PubMed Central

Han, Jaeseok; Song, Benbo; Kim, Jiun; Kodali, Vamsi K.; Pottekat, Anita; Wang, Miao; Hassler, Justin; Wang, Shiyu; Pennathur, Subramaniam; Back, Sung Hoon; Katze, Michael G.

2015-01-01

Proinsulin misfolding in the endoplasmic reticulum (ER) initiates a cell death response, although the mechanism(s) remains unknown. To provide insight into how protein misfolding may cause β-cell failure, we analyzed mice with the deletion of P58IPK/DnajC3, an ER luminal co-chaperone. P58IPK−/− mice become diabetic as a result of decreased β-cell function and mass accompanied by induction of oxidative stress and cell death. Treatment with a chemical chaperone, as well as deletion of Chop, improved β-cell function and ameliorated the diabetic phenotype in P58IPK−/− mice, suggesting P58IPK deletion causes β-cell death through ER stress. Significantly, a diet of chow supplemented with antioxidant dramatically and rapidly restored β-cell function in P58IPK−/− mice and corrected abnormal localization of MafA, a critical transcription factor for β-cell function. Antioxidant feeding also preserved β-cell function in Akita mice that express mutant misfolded proinsulin. Therefore defective protein folding in the β-cell causes oxidative stress as an essential proximal signal required for apoptosis in response to ER stress. Remarkably, these findings demonstrate that antioxidant feeding restores cell function upon deletion of an ER molecular chaperone. Therefore antioxidant or chemical chaperone treatment may be a promising therapeutic approach for type 2 diabetes. PMID:25795214

mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.

PubMed

Fort, Patrice E; Losiewicz, Mandy K; Pennathur, Subramaniam; Jefferson, Leonard S; Kimball, Scot R; Abcouwer, Steven F; Gardner, Thomas W

2014-09-01

Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2(Akita) diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Cost-effectiveness and budget impact analyses of a long-term hypertension detection and control program for stroke prevention.

PubMed

Yamagishi, Kazumasa; Sato, Shinichi; Kitamura, Akihiko; Kiyama, Masahiko; Okada, Takeo; Tanigawa, Takeshi; Ohira, Tetsuya; Imano, Hironori; Kondo, Masahide; Okubo, Ichiro; Ishikawa, Yoshinori; Shimamoto, Takashi; Iso, Hiroyasu

2012-09-01

The nation-wide, community-based intensive hypertension detection and control program, as well as universal health insurance coverage, may well be contributing factors for helping Japan rank near the top among countries with the longest life expectancy. We sought to examine the cost-effectiveness of such a community-based intervention program, as no evidence has been available for this issue. The hypertension detection and control program was initiated in 1963 in full intervention and minimal intervention communities in Akita, Japan. We performed comparative cost-effectiveness and budget-impact analyses for the period 1964-1987 of the costs of public health services and treatment of patients with hypertension and stroke on the one hand, and incidence of stroke on the other in the full intervention and minimal intervention communities. The program provided in the full intervention community was found to be cost saving 13 years after the beginning of program in addition to the fact of effectiveness that; the prevalence and incidence of stroke were consistently lower in the full intervention community than in the minimal intervention community throughout the same period. The incremental cost was minus 28,358 yen per capita over 24 years. The community-based intensive hypertension detection and control program was found to be both effective and cost saving. The national government's policy to support this program may have contributed in part to the substantial decline in stroke incidence and mortality, which was largely responsible for the increase in Japanese life expectancy.

Origin of methane-rich natural gas at the West Pacific convergent plate boundary.

PubMed

Sano, Yuji; Kinoshita, Naoya; Kagoshima, Takanori; Takahata, Naoto; Sakata, Susumu; Toki, Tomohiro; Kawagucci, Shinsuke; Waseda, Amane; Lan, Tefang; Wen, Hsinyi; Chen, Ai-Ti; Lee, Hsiaofen; Yang, Tsanyao F; Zheng, Guodong; Tomonaga, Yama; Roulleau, Emilie; Pinti, Daniele L

2017-11-15

Methane emission from the geosphere is generally characterized by a radiocarbon-free signature and might preserve information on the deep carbon cycle on Earth. Here we report a clear relationship between the origin of methane-rich natural gases and the geodynamic setting of the West Pacific convergent plate boundary. Natural gases in the frontal arc basin (South Kanto gas fields, Northeast Japan) show a typical microbial signature with light carbon isotopes, high CH 4 /C 2 H 6 and CH 4 / 3 He ratios. In the Akita-Niigata region - which corresponds to the slope stretching from the volcanic-arc to the back-arc -a thermogenic signature characterize the gases, with prevalence of heavy carbon isotopes, low CH 4 /C 2 H 6 and CH 4 / 3 He ratios. Natural gases from mud volcanoes in South Taiwan at the collision zone show heavy carbon isotopes, middle CH 4 /C 2 H 6 ratios and low CH 4 / 3 He ratios. On the other hand, those from the Tokara Islands situated on the volcanic front of Southwest Japan show the heaviest carbon isotopes, middle CH 4 /C 2 H 6 ratios and the lowest CH 4 / 3 He ratios. The observed geochemical signatures of natural gases are clearly explained by a mixing of microbial, thermogenic and abiotic methane. An increasing contribution of abiotic methane towards more tectonically active regions of the plate boundary is suggested.

Insulin Inhibits Nrf2 Gene Expression via Heterogeneous Nuclear Ribonucleoprotein F/K in Diabetic Mice

PubMed Central

Ghosh, Anindya; Abdo, Shaaban; Zhao, Shuiling; Wu, Chin-Han; Shi, Yixuan; Lo, Chao-Sheng; Chenier, Isabelle; Alquier, Thierry; Filep, Janos G.; Ingelfinger, Julie R.; Zhang, Shao-Ling

2017-01-01

Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2–related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress, and renal injury; inhibited renal Nrf2 and angiotensinogen (Agt) gene expression; and upregulated heterogeneous nuclear ribonucleoprotein F and K (hnRNP F and hnRNP K) expression in Akita mice with T1D. In immortalized rat renal proximal tubular cells, insulin suppressed Nrf2 and Agt but stimulated hnRNP F and hnRNP K gene transcription in high glucose via p44/42 mitogen-activated protein kinase signaling. Transfection with small interfering RNAs of p44/42 MAPK, hnRNP F, or hnRNP K blocked insulin inhibition of Nrf2 gene transcription. Insulin curbed Nrf2 promoter activity via a specific DNA-responsive element that binds hnRNP F/K, and hnRNP F/K overexpression curtailed Nrf2 promoter activity. In hyperinsulinemic-euglycemic mice, renal Nrf2 and Agt expression was downregulated, whereas hnRNP F/K expression was upregulated. Thus, the beneficial actions of insulin in diabetic nephropathy appear to be mediated, in part, by suppressing renal Nrf2 and Agt gene transcription and preventing Nrf2 stimulation of Agt expression via hnRNP F/K. These findings identify hnRNP F/K and Nrf2 as potential therapeutic targets in diabetes. PMID:28324005

Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

PubMed

Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

2012-01-01

This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD.

Rapid genetic diversification within dog breeds as evidenced by a case study on Schnauzers.

PubMed

Streitberger, K; Schweizer, M; Kropatsch, R; Dekomien, G; Distl, O; Fischer, M S; Epplen, J T; Hertwig, S T

2012-10-01

As a result of strong artificial selection, the domesticated dog has arguably become one of the most morphologically diverse vertebrate species, which is mirrored in the classification of around 400 different breeds. To test the influence of breeding history on the genetic structure and variability of today's dog breeds, we investigated 12 dog breeds using a set of 19 microsatellite markers from a total of 597 individuals with about 50 individuals analysed per breed. High genetic diversity was noted over all breeds, with the ancient Asian breeds (Akita, Chow Chow, Shar Pei) exhibiting the highest variability, as was indicated chiefly by an extraordinarily high number of rare and private alleles. Using a Bayesian clustering method, we detected significant genetic stratification within the closely related Schnauzer breeds. The individuals of these three recently differentiated breeds (Miniature, Standard and Giant Schnauzer) could not be assigned to a single cluster each. This hidden genetic structure was probably caused by assortative mating owing to breeders' preferences regarding coat colour types and the underlying practice of breeding in separate lineages. Such processes of strong artificial disruptive selection for different morphological traits in isolated and relatively small lineages can result in the rapid creation of new dog types and potentially new breeds and represent a unique opportunity to study the evolution of genetic and morphological differences in recently diverged populations. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

PubMed

Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

2016-03-01

Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

Spatial data analysis for exploration of regional scale geothermal resources

NASA Astrophysics Data System (ADS)

Moghaddam, Majid Kiavarz; Noorollahi, Younes; Samadzadegan, Farhad; Sharifi, Mohammad Ali; Itoi, Ryuichi

2013-10-01

Defining a comprehensive conceptual model of the resources sought is one of the most important steps in geothermal potential mapping. In this study, Fry analysis as a spatial distribution method and 5% well existence, distance distribution, weights of evidence (WofE), and evidential belief function (EBFs) methods as spatial association methods were applied comparatively to known geothermal occurrences, and to publicly-available regional-scale geoscience data in Akita and Iwate provinces within the Tohoku volcanic arc, in northern Japan. Fry analysis and rose diagrams revealed similar directional patterns of geothermal wells and volcanoes, NNW-, NNE-, NE-trending faults, hotsprings and fumaroles. Among the spatial association methods, WofE defined a conceptual model correspondent with the real world situations, approved with the aid of expert opinion. The results of the spatial association analyses quantitatively indicated that the known geothermal occurrences are strongly spatially-associated with geological features such as volcanoes, craters, NNW-, NNE-, NE-direction faults and geochemical features such as hotsprings, hydrothermal alteration zones and fumaroles. Geophysical data contains temperature gradients over 100 °C/km and heat flow over 100 mW/m2. In general, geochemical and geophysical data were better evidence layers than geological data for exploring geothermal resources. The spatial analyses of the case study area suggested that quantitative knowledge from hydrothermal geothermal resources was significantly useful for further exploration and for geothermal potential mapping in the case study region. The results can also be extended to the regions with nearly similar characteristics.

Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in the winter season of 2016-2017 in Northern Japan.

PubMed

Hiono, Takahiro; Okamatsu, Masatoshi; Matsuno, Keita; Haga, Atsushi; Iwata, Ritsuko; Nguyen, Lam Thanh; Suzuki, Mizuho; Kikutani, Yuto; Kida, Hiroshi; Onuma, Manabu; Sakoda, Yoshihiro

2017-09-01

On 15 November 2016, a black swan that had died in a zoo in Akita prefecture, northern Japan, was strongly suspected to have highly pathogenic avian influenza (HPAI); an HPAI virus (HPAIV) belonging to the H5N6 subtype was isolated from specimens taken from the bird. After the initial report, 230 cases of HPAI caused by H5N6 viruses from wild birds, captive birds, and domestic poultry farms were reported throughout the country during the winter season. In the present study, 66 H5N6 HPAIVs isolated from northern Japan were further characterized. Phylogenetic analysis of the hemagglutinin gene showed that the H5N6 viruses isolated in northern Japan clustered into Group C of Clade 2.3.4.4 together with other isolates collected in Japan, Korea and Taiwan during the winter season of 2016-2017. The antigenicity of the Japanese H5N6 isolate differed slightly from that of HPAIVs isolated previously in Japan and China. The virus exhibited high pathogenicity and a high replication capacity in chickens, whereas virus growth was slightly lower in ducks compared with that of an H5N8 HPAIV isolate collected in Japan in 2014. Comprehensive analyses of Japanese isolates, including those from central, western, and southern Japan, as well as rapid publication of this information are essential for facilitating greater control of HPAIVs. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

The origin of chow chows in the light of the East Asian breeds.

PubMed

Yang, Hechuan; Wang, Guodong; Wang, Meng; Ma, Yaping; Yin, Tingting; Fan, Ruoxi; Wu, Hong; Zhong, Li; Irwin, David M; Zhai, Weiwei; Zhang, Yaping

2017-02-16

East Asian dog breeds are one of the most ancient groups of dogs that radiated after the domestication of the dog and represent the most basal lineages of dog evolution. Among these, the Chow Chow is an ancient breed that embodies very distinct morphological and physiological features, such as sturdy build, dense coat, and blue/purple tongue. Using a Restricted site Associated DNA (RAD) sequencing approach, we sequenced the genomes of nine Chow Chows from China. Combined with a dataset of 37 canid whole genome sequencing (WGS) from several published works, we found that the Chow Chow is one of the most basal lineages, which originated together with other East Asian breeds, such as the Shar-Pei and Akita. Demographic analysis found that Chow Chows originated from the Chinese indigenous dog about 8300 years ago. The bottleneck leading to Chow Chows was not strong and genetic migration between Chow Chows and other populations is low. Two classes of genes show strong evidence of positive selection along the Chow Chow lineage, namely genes related to metabolism and digestion as well as muscle/heart development and differentiation. Dog breeds from East Asia, including the Chow Chow, originated from Chinese indigenous dogs very early in time. The genetic bottleneck leading to Chow Chows and migrations with other populations are found to be quite mild. Our current study represents an early endeavor to characterize the origin of East Asian dog breeds and establishes an important reference point for understanding the origin of ancient breeds in Asia.

Identifying a breeding habitat of a critically endangered fish, Acheilognathus typus, in a natural river in Japan

NASA Astrophysics Data System (ADS)

Sakata, Masayuki K.; Maki, Nobutaka; Sugiyama, Hideki; Minamoto, Toshifumi

2017-12-01

Freshwater biodiversity has been severely threatened in recent years, and to conserve endangered species, their distribution and breeding habitats need to be clarified. However, identifying breeding sites in a large area is generally difficult. Here, by combining the emerging environmental DNA (eDNA) analysis with subsequent traditional collection surveys, we successfully identified a breeding habitat for the critically endangered freshwater fish Acheilognathus typus in the mainstream of Omono River in Akita Prefecture, Japan, which is one of the original habitats of this species. Based on DNA cytochrome B sequences of A. typus and closely related species, we developed species-specific primers and a probe that were used in real-time PCR for detecting A. typus eDNA. After verifying the specificity and applicability of the primers and probe on water samples from known artificial habitats, eDNA analysis was applied to water samples collected at 99 sites along Omono River. Two of the samples were positive for A. typus eDNA, and thus, small fixed nets and bottle traps were set out to capture adult fish and verify egg deposition in bivalves (the preferred breeding substrate for A. typus) in the corresponding regions. Mature female and male individuals and bivalves containing laid eggs were collected at one of the eDNA-positive sites. This was the first record of adult A. typus in Omono River in 11 years. This study highlights the value of eDNA analysis to guide conventional monitoring surveys and shows that combining both methods can provide important information on breeding sites that is essential for species' conservation.

Identifying a breeding habitat of a critically endangered fish, Acheilognathus typus, in a natural river in Japan.

PubMed

Sakata, Masayuki K; Maki, Nobutaka; Sugiyama, Hideki; Minamoto, Toshifumi

2017-11-14

Freshwater biodiversity has been severely threatened in recent years, and to conserve endangered species, their distribution and breeding habitats need to be clarified. However, identifying breeding sites in a large area is generally difficult. Here, by combining the emerging environmental DNA (eDNA) analysis with subsequent traditional collection surveys, we successfully identified a breeding habitat for the critically endangered freshwater fish Acheilognathus typus in the mainstream of Omono River in Akita Prefecture, Japan, which is one of the original habitats of this species. Based on DNA cytochrome B sequences of A. typus and closely related species, we developed species-specific primers and a probe that were used in real-time PCR for detecting A. typus eDNA. After verifying the specificity and applicability of the primers and probe on water samples from known artificial habitats, eDNA analysis was applied to water samples collected at 99 sites along Omono River. Two of the samples were positive for A. typus eDNA, and thus, small fixed nets and bottle traps were set out to capture adult fish and verify egg deposition in bivalves (the preferred breeding substrate for A. typus) in the corresponding regions. Mature female and male individuals and bivalves containing laid eggs were collected at one of the eDNA-positive sites. This was the first record of adult A. typus in Omono River in 11 years. This study highlights the value of eDNA analysis to guide conventional monitoring surveys and shows that combining both methods can provide important information on breeding sites that is essential for species' conservation.

Sleep/awake status throughout the night and circadian motor activity patterns in older nursing-home residents with or without dementia, and older community-dwelling people without dementia.

PubMed

Kume, Yu; Kodama, Ayuto; Sato, Kotaro; Kurosawa, Satoko; Ishikawa, Takashi; Ishikawa, Sachiko

2016-12-01

Sleep disturbances are commonly observed in older nursing home residents, mainly in combination with dementia. However, sleep-associated circadian motor activity patterns have not been thoroughly investigated in Japanese nursing homes. The present study aimed to respectively clarify the effect of community living and the presence of dementia on sleep disturbances and interrupted activity rhythm of older nursing-home residents with or without dementia and older community-dwelling people without dementia. Actigraph devices worn on the participants' non-dominant wrists for seven days were used to collect objective measurements of the sleep/awake status throughout the night and the circadian motor activity patterns. The presence of dementia was assessed by a trained medical doctor using the residents' records and the Clinical Dementia Rating (CDR). The functional capacity of the participants was determined using the Barthel Index (BI). Fifty-one older people in Akita prefecture were included in the current study, consisting of 17 residents with dementia (mean age: 82.2 years), 17 residents without dementia (84.5 years), and 17 community-dwelling people (83.6 years). The results showed that older nursing-home residents with dementia had significantly a lower rate of sleep efficiency and a longer awake time throughout the night than the other groups. Older nursing-home residents with and without dementia had more fragmented rhythm than community-dwelling people without dementia. These results provide evidence of poor sleep/awake status throughout the night and interrupted circadian activity rhythms in nursing-home residents with and without dementia. However, further studies performed according to dementia classifications are needed.

First reported case of Haemoglobin-M Hyde Park in a Malay family living in Malaysia.

PubMed

Loong, Tang Yee; Chong, Doris Lau Sie; Jamal, A Rahman A; Murad, Nor Azian Abdul; Sabudin, Raja Zahratul Azma Raja; Fun, Leong Chooi

2016-01-01

Haemoglobin (Hb)-M Hyde Park, also known as Hb-M Akita is a rare type of hereditary Hb M due to autosomal dominant mutation of CAC>TAC on codon 92 of β globin gene resulting in the replacement of histidine by tyrosine on β globin chain. This variant Hb has a tendency to form methaemoglobin (metHb). The iron ion in metHb is oxidized to ferric (Fe3+) which is unable to carry oxygen and the patients manifest as cyanosis clinically. A 9-year-old Malay girl was incidentally found to be cyanotic when she presented to a health clinic. Laboratory investigations revealed raised methaemoglobin levels and Hb analysis findings were consistent with Hb-M Hyde Park. β gene sequencing confirmed a point mutation of CAC>TAC on codon 92 in one of the β genes. The family study done on the individuals with cyanosis showed similar findings. A diagnosis of heterozygous Hb-M Hyde Park was made. Patients with this variant Hb usually presented with cyanosis with mild haemolysis and maybe misdiagnosed as congenital heart disease. No further treatment is needed as patients are relatively asymptomatic. Although the disease is harmless in the heterozygous carriers but the offspring of the carriers may suffer severe haemolytic anaemia when the offspring also inherit other β haemoglobinopathies/thalassemia. This can happen due to high prevalence of β thalassemia carrier (3.5-4 %) found in Malaysia. At the time of writing, this is the first case of hereditary Hb-M Hyde Park diagnosed in a Malay family living in Malaysia.

Changes in suicide rates in disaster-stricken areas following the Great East Japan Earthquake and their effect on economic factors: an ecological study.

PubMed

Orui, Masatsugu; Harada, Shuichiro; Hayashi, Mizuho

2014-11-01

Devastating disasters may increase suicide rates due to mental distress. Previous domestic studies have reported decreased suicide rates among men following disasters. Few reports are available regarding factors associated with disasters, making it difficult to discuss how these events affect suicide rates. This study aimed to observe changes in suicide rates in disaster-stricken and neighboring areas following the Great East Japan Earthquake, and examine associations between suicide rates and economic factors. Monthly suicide rates were observed from March 2009 to February 2013, during which time the earthquake occurred on March, 2011. Data were included from disaster-stricken (Iwate, Miyagi, and Fukushima Prefectures) and neighboring (control: Aomori, Akita, and Yamagata Prefectures) areas. The association between changes in suicide rates and economic variables was evaluated based on the number of bankruptcy cases and ratio of effective job offers. In disaster-stricken areas, post-disaster male suicide rates decreased during the 24 months following the earthquake. This trend differed relative to control areas. Female suicide rates increased during the first seven months. Multiple regression analysis showed that bankruptcy cases (β = 0.386, p = 0.038) and ratio of effective job offers (β = -0.445, p = 0.018) were only significantly associated with male post-disaster suicide rates in control areas. Post-disaster suicide rates differed by gender following the earthquake. Our findings suggest that considering gender differences might be important for developing future post-disaster suicide prevention measures. This ecological study revealed that increasing effective job offers and decreasing bankruptcy cases can affect protectively male suicide rates in control areas.

Pemphigus foliaceus in dogs: a review of 37 cases.

PubMed

Ihrke, P J; Stannard, A A; Ardans, A A; Griffin, C E

1985-01-01

Thirty-seven dogs with pemphigus foliaceus were seen over a span of 9 years in a veterinary medical teaching hospital. Four breeds of dogs (Bearded Collie, Akita, Newfoundland, Schipperke) were at significant elevated risk when compared with both the dermatology canine case population and the hospital canine population. The mean age of onset was 4.2 years. The dorsal part of the muzzle was the most common site of initial involvement in over 50% of the dogs, and lesions of the head were seen first in 81% of the dogs. Disease progression was gradual (greater than 3 months) in 73% of the dogs. Somewhat bilaterally symmetric scaling, crusting, and alopecia were seen in all of the dogs. Vesicles, pustules, and bullae were not seen commonly, but target lesions with peripheral collarettes were seen frequently. Most dogs had characteristic footpad lesions, with erythematous swelling at the pad margins, cracking, and villous hypertrophy. Generalized exfoliative dermatitis was seen in dogs with widespread disease. Pruritus was noted in less than one half of the dogs. Typical histopathologic findings included subcorneal and intragranular cell layer epidermal pustules, or intrafollicular pustules with prominent acantholysis. Direct immunofluorescence in an intercellular pattern was noted in 76% of the dogs tested and indirect immunofluorescence was noted in 75% of a much smaller sample. Thirty-nine percent of the dogs responded to corticosteroid therapy alone, and 50% and 55% responded, respectively, to prednisone and cytotoxic drugs, and to prednisone with aurothioglucose. Aurothioglucose was successful alone in 27% of the dogs. One-year survival was achieved in 53% of the dogs.

Induction of atherosclerosis in mice and hamsters without germline genetic engineering.

PubMed

Bjørklund, Martin Maeng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup; Dagnaes-Hansen, Frederik; Christoffersen, Christina; Mikkelsen, Jacob Giehm; Bentzon, Jacob Fog

2014-05-23

Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. To develop a method for induction of atherosclerosis without germline genetic engineering. Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions to the fibroatheromatous stage. To demonstrate the applicability of this method for rapid analysis of the atherosclerosis susceptibility of a mouse strain and for providing temporal control over disease induction, we demonstrated the accelerated atherosclerosis of mature diabetic Akita mice. Furthermore, the versatility of this approach for creating atherosclerosis models also in nonmurine species was demonstrated by inducing hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters. Single injections of proprotein convertase subtilisin/kexin type 9-encoding recombinant adeno-associated viral vectors are a rapid and versatile method to induce atherosclerosis in animals. This method should prove useful for experiments that are high-throughput or involve genetic techniques, strains, or species that do not combine well with current genetically engineered models. © 2014 American Heart Association, Inc.

[Disease mongering and bipolar disorder in Japan].

PubMed

Ihara, Hiroshi

2011-01-01

Frequently used in a pejorative sense, "disease mongering" connotes a widening of the diagnostic boundaries of illness. Pharmaceutical companies conduct disease awareness campaigns on the pretext of educating the public about the prevention of illness or the promotion of health. Encouraged by disease awareness advertisements, people gradually become filled with concern that they are ill and need medical treatment. As a result, pharmacotherapy is increasingly being applied to ever-milder conditions, leading to potentially unnecessary medication, wasted resources, and even adverse side effects. Among all fields of clinical medicine, psychiatry is undoubtedly the most vulnerable to the danger of disease mongering. In Japan, depression provides the most drastic example of the impact of disease awareness campaigns on the number of patients seeking treatment. Until the late 1990s, Japanese psychiatrists focused almost exclusively on psychosis and endogenous depression, the latter being severe enough to require conventional forms of antidepressants, known as tricyclic antidepressants, and even hospitalization. At this time, people's attitude toward depression was generally unfavorable. Indeed, the Japanese word for clinical depression, utubyo, has a negative connotation, implying severe mental illness. This situation, however, changed immediately after fluvoxiamine (Luvox-Fujisawa, Depromel-Meiji Seika), the first selective serotonin re-uptake inhibitor (SSRI) to receive approval in Japan, was introduced in 1999. In order to aid the drug's acceptance by the Japanese public, pharmaceutical companies began using the catchphrase kokoro no kaze, which literally means "a cold of the soul". Thus armed with this phrase, the pharmaceutical industry embarked on a campaign to lessen the stigma surrounding depression. According to national data from the Ministry of Health and Welfare, the number of patients with a diagnosis of mood disorder increased from 327,000 in 1999 to 591

Increased SHP-1 Protein Expression by High Glucose Levels Reduces Nephrin Phosphorylation in Podocytes*

PubMed Central

Denhez, Benoit; Lizotte, Farah; Guimond, Marie-Odile; Jones, Nina; Takano, Tomoko; Geraldes, Pedro

2015-01-01

Nephrin, a critical podocyte membrane component that is reduced in diabetic nephropathy, has been shown to activate phosphotyrosine signaling pathways in human podocytes. Nephrin signaling is important to reduce cell death induced by apoptotic stimuli. We have shown previously that high glucose level exposure and diabetes increased the expression of SHP-1, causing podocyte apoptosis. SHP-1 possesses two Src homology 2 domains that serve as docking elements to dephosphorylate tyrosine residues of target proteins. However, it remains unknown whether SHP-1 interacts with nephrin and whether its elevated expression affects the nephrin phosphorylation state in diabetes. Here we show that human podocytes exposed to high glucose levels exhibited elevated expression of SHP-1, which was associated with nephrin. Coexpression of nephrin-CD16 and SHP-1 reduced nephrin tyrosine phosphorylation in transfected human embryonic kidney 293 cells. A single tyrosine-to-phenylalanine mutation revealed that rat nephrin Tyr1127 and Tyr1152 are required to allow SHP-1 interaction with nephrin. Overexpression of dominant negative SHP-1 in human podocytes prevented high glucose-induced reduction of nephrin phosphorylation. In vivo, immunoblot analysis demonstrated that nephrin expression and phosphorylation were decreased in glomeruli of type 1 diabetic Akita mice (Ins2+/C96Y) compared with control littermate mice (Ins2+/+), and this was associated with elevated SHP-1 and cleaved caspase-3 expression. Furthermore, immunofluorescence analysis indicated increased colocalization of SHP-1 with nephrin in diabetic mice compared with control littermates. In conclusion, our results demonstrate that high glucose exposure increases SHP-1 interaction with nephrin, causing decreased nephrin phosphorylation, which may, in turn, contribute to diabetic nephropathy. PMID:25404734

Gastric dilation-volvulus in dogs attending UK emergency-care veterinary practices: prevalence, risk factors and survival.

PubMed

O'Neill, D G; Case, J; Boag, A K; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2017-11-01

To report prevalence, risk factors and clinical outcomes for presumptive gastric dilation-volvulus diagnosed among an emergency-care population of UK dogs. The study used a cross-sectional design using emergency-care veterinary clinical records from the VetCompass Programme spanning September 1, 2012 to February 28, 2014 and risk factor analysis using multivariable logistic regression modelling. The study population comprised 77,088 dogs attending 50 Vets Now clinics. Overall, 492 dogs had presumptive gastric dilation-volvulus diagnoses, giving a prevalence of 0·64% (95% Confidence interval: 0·58 to 0·70%). Compared with cross-bred dogs, breeds with the highest odds ratios for the diagnosis of presumptive gastric dilation-volvulus were the great Dane (odds ratio: 114·3, 95% Confidence interval 55·1 to 237·1, P<0·001), akita (odds ratio: 84·4, 95% Confidence interval 33·6 to 211·9, P<0·001) and dogue de Bordeaux (odds ratio: 82·9, 95% Confidence interval 39·0 to 176·3, P<0·001). Odds increased as dogs aged up to 12 years and neutered male dogs had 1·3 (95% Confidence interval 1·0 to 1·8, P=0·041) times the odds compared with entire females. Of the cases that were presented alive, 49·7% survived to discharge overall, but 79·3% of surgical cases survived to discharge. Approximately 80% of surgically managed cases survived to discharge. Certain large breeds were highly predisposed. © 2017 British Small Animal Veterinary Association.

Design of the health examination survey on early childhood physical growth in the Great East Japan Earthquake affected areas.

PubMed

Matsubara, Hiroko; Ishikuro, Mami; Kikuya, Masahiro; Chida, Shoichi; Hosoya, Mitsuaki; Ono, Atsushi; Kato, Noriko; Yokoya, Susumu; Tanaka, Toshiaki; Isojima, Tsuyoshi; Yamagata, Zentaro; Tanaka, Soichiro; Kuriyama, Shinichi; Kure, Shigeo

2017-03-01

To investigate the impact of the Great East Japan Earthquake on preschool children's physical growth in the disaster-affected areas, the three medical universities in Iwate, Miyagi, and Fukushima Prefectures conducted a health examination survey on early childhood physical growth. The survey was conducted over a 3-year period to acquire data on children who were born in different years. Our targets were as follows: 1) children who were born between March 1, 2007 and August 31, 2007 and experienced the disaster at 43-48 months of age, 2) children who were born between March 1, 2009 and August 31, 2009 and experienced the disaster at 19-24 months of age, and 3) children who were born between June 1, 2010 and April 30, 2011 and were under 10 months of age or not born yet when the disaster occurred. We collected their health examination data from local governments in Iwate, Miyagi, and Fukushima Prefectures. We also collected data from Aomori, Akita, and Yamagata Prefectures to use as a control group. The survey items included birth information, anthropometric measurements, and methods of nutrition during infancy. Eighty municipalities from Iwate, Miyagi, and Fukushima Prefectures and 21 from the control prefectures participated in the survey. As a result, we established three retrospective cohorts consisting of 13,886, 15,474, and 32,202 preschool children. The large datasets acquired for the present survey will provide valuable epidemiological evidence that should shed light on preschool children's physical growth in relation to the disaster. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Iron Corrosion Induced by Nonhydrogenotrophic Nitrate-Reducing Prolixibacter sp. Strain MIC1-1

PubMed Central

Ito, Kimio; Wakai, Satoshi; Tsurumaru, Hirohito; Ohkuma, Moriya; Harayama, Shigeaki

2014-01-01

Microbiologically influenced corrosion (MIC) of metallic materials imposes a heavy economic burden. The mechanism of MIC of metallic iron (Fe0) under anaerobic conditions is usually explained as the consumption of cathodic hydrogen by hydrogenotrophic microorganisms that accelerates anodic Fe0 oxidation. In this study, we describe Fe0 corrosion induced by a nonhydrogenotrophic nitrate-reducing bacterium called MIC1-1, which was isolated from a crude-oil sample collected at an oil well in Akita, Japan. This strain requires specific electron donor-acceptor combinations and an organic carbon source to grow. For example, the strain grew anaerobically on nitrate as a sole electron acceptor with pyruvate as a carbon source and Fe0 as the sole electron donor. In addition, ferrous ion and l-cysteine served as electron donors, whereas molecular hydrogen did not. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MIC1-1 was a member of the genus Prolixibacter in the order Bacteroidales. Thus, Prolixibacter sp. strain MIC1-1 is the first Fe0-corroding representative belonging to the phylum Bacteroidetes. Under anaerobic conditions, Prolixibacter sp. MIC1-1 corroded Fe0 concomitantly with nitrate reduction, and the amount of iron dissolved by the strain was six times higher than that in an aseptic control. Scanning electron microscopy analyses revealed that microscopic crystals of FePO4 developed on the surface of the Fe0 foils, and a layer of FeCO3 covered the FePO4 crystals. We propose that cells of Prolixibacter sp. MIC1-1 accept electrons directly from Fe0 to reduce nitrate. PMID:25548048

Incidence of hypophosphatemia in advanced cancer patients: a recent report from a single institution.

PubMed

Yoshida, Taichi; Taguchi, Daiki; Fukuda, Koji; Shimazu, Kazuhiro; Inoue, Masahiro; Murata, Katsunori; Shibata, Hiroyuki

2017-04-01

Recent approval of molecular-targeted agents has contributed to improving the therapeutic outcomes of advanced cancer patients. However, they result in unusual adverse events that rarely occur with cytotoxic agents, such as hypertension, hypomagnesemia, and an acne-like rash. Although hypophosphatemia can be induced by various agents, some kinds of molecular-targeted agents are known to induce it. In addition, cancer survivors may be at a risk of hypophosphatemia. One hundred and seventy patients, who visited the Department of Clinical Oncology at Akita University from 1 April 2014 to 31 August 2016 were enrolled in this study after providing informed consent. Serum inorganic phosphorus levels were examined along with other routine clinical examinations. Correlation between the serum inorganic phosphorus level and other clinical data were also analyzed. Grade ≥2 severe hypophosphatemia (<2.5 mg/dL of phosphorus) was detected in 49.4% of patients, and grade ≥3 (<2.0 mg/dL of phosphorus) was observed in 22.9% patients. These results indicated that the presence of bone metastasis (p < 0.001), history of bone-modifying agents (p < 0.001) and molecular-targeted drugs (p = 0.001), and time from the date of the first visit to the date of minimum serum phosphorus level (p < 0.001) might correlate with hypophosphatemia. Multivariate logistic regression analysis showed that disease duration might be a risk factor (p = 0.0466). As hypophosphatemia can be induced by various factors in advanced cancer patients, the serum phosphorus level of cancer patients at risk should be cautiously examined.

Rover exploration on the lunar surface; a science proposal for SELENE-B mission

NASA Astrophysics Data System (ADS)

Sasaki, S.; Kubota, T.; Akiyama, H.; Hirata, N.; Kunii, Y.; Matsumoto, K.; Okada, T.; Otake, M.; Saiki, K.; Sugihara, T.

LUNARSURFACE:ASCIENCES. Sasaki (1), T. Kubota (2) , H. Akiyama (1) , N. Hirata (3), Y. Kunii (4), K. Matsumoto (5), T. Okada (2), M. Otake (3), K. Saiki (6), T. Sugihara (3) (1) Department of Earth and Planetary Science, Univ. Tokyo, (2) Institute of Space and Astronautical Sciences, (3) National Space Development Agency of Japan, (4) Department of Electrical and Electronic Engineering, Chuo Univ., (5) National Aerospace Laboratory of Japan, (6) Research Institute of Materials and Resources, Akita Univ. sho@eps.s.u -tokyo.ac.jp/Fax:+81-3-5841-4569 A new lunar landing mission (SELENE-B) is now in consideration in Japan. Scientific investigation plans using a rover are proposed. To clarify the origin and evolution of the moon, the early crustal formation and later mare volcanic processes are still unveiled. We proposed two geological investigation plans: exploration of a crater central peak to discover subsurface materials and exploration of dome-cone structures on young mare region. We propose multi-band macro/micro camera using AOTF, X-ray spectrometer/diffractometer and gamma ray spectrometer. Since observation of rock fragments in brecciaed rocks is necessary, the rover should have cutting or scraping mechanism of rocks. In our current scenario, landing should be performed about 500m from the main target (foot of a crater central peak or a cone/dome). After the spectral survey by multi-band camera on the lander, the rover should be deployed for geological investigation. The rover should make a short (a few tens meter) round trip at first, then it should perform traverse observation toward the main target. Some technological investigations on SELENE-B project will be also presented.

Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy.

PubMed

Mori, Keita P; Yokoi, Hideki; Kasahara, Masato; Imamaki, Hirotaka; Ishii, Akira; Kuwabara, Takashige; Koga, Kenichi; Kato, Yukiko; Toda, Naohiro; Ohno, Shoko; Kuwahara, Koichiro; Endo, Tomomi; Nakao, Kazuwa; Yanagita, Motoko; Mukoyama, Masashi; Mori, Kiyoshi

2017-01-01

The amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin-knockout mouse line, megalin(lox/lox);Ndrg1-CreER T2 (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild-type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol-binding protein. Furthermore, urinary albumin excretion increased to 175 μg/d (0.46 mg albumin/mg creatinine) in Tam-treated iMegKO mice, suggesting that this was the amount of total nephron albumin filtration. By comparing Tam-treated, streptozotocin-induced diabetic iMegKO mice with Tam-treated nondiabetic iMegKO mice, we estimated that the development of diabetes led to a 1.9-fold increase in total nephron albumin filtration, a 1.8-fold increase in reabsorption, and a significant reduction in reabsorption efficiency (86% efficiency versus 96% efficiency in nondiabetic mice). Insulin treatment normalized these abnormalities. Akita;iMegKO mice, another model of type 1 diabetes, showed equivalent results. Finally, nondiabetic iMegKO mice had a glomerular sieving coefficient of albumin of 1.7×10 -5 , which approximately doubled in diabetic iMegKO mice. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy in mice, bringing new insights to our understanding of renal albumin dynamics associated with the hyperfiltration status of diabetic nephropathy. Copyright © 2016 by the American Society of Nephrology.

Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children.

PubMed

Kusano, Chika; Gotoda, Takuji; Suzuki, Sho; Ikehara, Hisatomo; Moriyama, Mitsuhiko

2018-06-01

Helicobacter pylori infection is a risk factor for gastric cancer, and it has been reported that eradication of H. pylori is effective for preventing such cancer. Recently, H. pylori eradication has been performed in children as first-line therapy against gastric cancer. Here, we report use of triple therapy with a potassium-competitive acid blocker (P-CAB) for H. pylori eradication in children. H. pylori infection testing and eradication therapy began in fiscal year 2015 in junior high school students located in Yurihonjo city and Nikaho city, Akita prefecture, Japan. Urine-based immunochromatography, stool antigen enzyme-linked immunosorbent assay tests, and serum antibody tests were performed as the initial screening examination. Those who tested positive on one of the three examinations then underwent a urea breath test ( 13 C-UBT). Those who tested positive on 13 C-UBT and expressed the desire to undergo H. pylori eradication then received eradication therapy comprising 20 mg P-CAB, 750 mg amoxicillin, and 200 mg clarithromycin twice a day for 7 days. At least 8 weeks after treatment, eradication success was evaluated using 13 C-UBT. A total of 118 students received eradication therapy. Eradication rates were 81.3% (95% confidence interval: 74.3-88.4, 96/118) in ITT analysis and 85.7% (95% confidence interval: 79.1-92.9 96/112) in PP analysis. Adverse effects associated with eradication therapy were observed in 25 of 118 subjects (21.1%), seven of whom required hospital treatment (rash in five, vomiting in two). All seven subjects either discontinued therapy or were administered anti-allergy drugs, which resulted in swift alleviation of symptoms. First-line triple therapy with a P-CAB for H. pylori eradication in children was found to be safe.

Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells

PubMed Central

Konopinski, Ryszard; Krishnan, Manickam; Roman, Linda; Bera, Alakesh; Hongying, Zheng; Habib, Samy L.; Mohan, Sumathy

2015-01-01

Endothelial nitric oxide (NO) synthase (eNOS) is the predominant isoform that generates NO in the blood vessels. Many different regulators, including heat shock protein 90 (Hsp90), govern eNOS function. Hsp90-dependent phosphorylation of eNOS is a critical event that determines eNOS activity. In our earlier study we demonstrated an inhibitor-κB kinase-β (IKKβ)-Hsp90 interaction in a high-glucose environment. In the present study we further define the putative binding domain of IKKβ on Hsp90. Interestingly, IKKβ binds to the middle domain of Hsp90, which has been shown to interact with eNOS to stimulate its activity. This new finding suggests a tighter regulation of eNOS activity than was previously assumed. Furthermore, addition of purified recombinant IKKβ to the eNOS-Hsp90 complex reduces the eNOS-Hsp90 interaction and eNOS activity, indicating a competition for Hsp90 between eNOS and IKKβ. The pathophysiological relevance of the IKKβ-Hsp90 interaction has also been demonstrated using in vitro vascular endothelial growth factor-mediated signaling and an Ins2Akita in vivo model. Our study further defines the preferential involvement of α- vs. β-isoforms of Hsp90 in the IKKβ-eNOS-Hsp90 interaction, even though both Hsp90α and Hsp90β stimulate NO production. These studies not only reinforce the significance of maintaining a homeostatic balance of eNOS and IKKβ within the cell system that regulates NO production, but they also confirm that the IKKβ-Hsp90 interaction is favored in a high-glucose environment, leading to impairment of the eNOS-Hsp90 interaction, which contributes to endothelial dysfunction and vascular complications in diabetes. PMID:25652452

Rodent models of diabetic nephropathy: their utility and limitations

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study

PubMed Central

Kusano, Chika; Yamada, Nobuo; Kikuchi, Kenji; Hashimoto, Masaji; Gotoda, Takuji

2016-01-01

Background: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient’s family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients’ families after PEG in Japan. Methods: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient’s families to ask about their satisfaction with and thoughts about PEG. Results: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients’ families. When asked, “Was performing PEG a good decision?”, 57.5% (182/316) of the patients’ families answered yes. Meanwhile, when patients’ family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. Conclusions: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG. PMID:27313796

Petrothermobacter organivorans gen. nov., sp. nov., a thermophilic, strictly anaerobic bacterium of the phylum Deferribacteres isolated from a deep subsurface oil reservoir.

PubMed

Tamazawa, Satoshi; Mayumi, Daisuke; Mochimaru, Hanako; Sakata, Susumu; Maeda, Haruo; Wakayama, Tatsuki; Ikarashi, Masayuki; Kamagata, Yoichi; Tamaki, Hideyuki

2017-10-01

A novel thermophilic, anaerobic, chemoheterotrophic, acetate-oxidizing and iron(III)-, manganese(IV)-, nitrate- and sulfate-reducing bacterium, designated strain ANA T , was isolated from a deep subsurface oil field in Japan (Yabase oil field, Akita Pref.). Cells of strain ANA T were Gram-stain-negative, non-motile, non-spore forming and slightly curved or twisted rods (1.5-5.0 µm long and 0.6-0.7 µm wide). The isolate grew at 25-60 °C (optimum 55 °C) and pH 6.0-8.0 (optimum pH 7.0). The isolate was capable of reducing iron(III), manganese(IV), nitrate and sulfate as an electron acceptor. The isolate utilized a limited range of electron donors such as acetate, lactate, pyruvate and yeast extract for iron reduction. Strain ANA T also used pyruvate, fumarate, succinate, malate, yeast extract and peptone for fermentative growth. The major respiratory quinones were menaquinone-7(H8) and menaquinone-8. The strain contained C18 : 0, iso-C18 : 0 and C16 : 0 as the major cellular fatty acids. The G+C content of the genomic DNA was 34.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain ANA T was closely related to Calditerrivibrio nitroreducens in the phylum Deferribacteres with low sequence similarities (89.5 %), and formed a distinct clade within the family Deferribacteraceae. In addition, the isolate is the first sulfate-reducing member of the phylum Deferribacteres. Based on phenotypic, chemotaxonomic and phylogenetic properties, a novel genus and species, Petrothermobacter organivorans gen. nov., sp. nov., is proposed for the isolate (type strain=ANA T = NBRC 112621 T =DSM 105015 T ).

Raman spectroscopy of triolein under high pressures

NASA Astrophysics Data System (ADS)

Tefelski, D. B.; Jastrzębski, C.; Wierzbicki, M.; Siegoczyński, R. M.; Rostocki, A. J.; Wieja, K.; Kościesza, R.

2010-03-01

This article presents results of the high pressure Raman spectroscopy of triolein. Triolein, a triacylglyceride (TAG) of oleic acid, is an unsaturated fat, present in natural oils such as olive oil. As a basic food component and an energy storage molecule, it has considerable importance for food and fuel industries. To generate pressure in the experiment, we used a high-pressure cylindrical chamber with sapphire windows, presented in (R.M. Siegoczyński, R. Kościesza, D.B. Tefelski, and A. Kos, Molecular collapse - modification of the liquid structure induced by pressure in oleic acid, High Press. Res. 29 (2009), pp. 61-66). Pressure up to 750 MPa was applied. A Raman spectrometer in "macro"-configuration was employed. Raman spectroscopy provides information on changes of vibrational modes related to structural changes of triolein under pressure. Interesting changes in the triglyceride C‒H stretching region at 2650-3100 cm-1 were observed under high-pressures. Changes were also observed in the ester carbonyl (C˭ O) stretching region 1700-1780 cm-1 and the C‒C stretching region at 1050-1150 cm-1. The overall luminescence of the sample decreased under pressure, making it possible to set longer spectrum acquisition time and obtain more details of the spectrum. The registered changes suggest that the high-pressure solid phase of triolein is organized as β-polymorphic, as was reported in (C. Akita, T. Kawaguchi, and F. Kaneko, Structural study on polymorphism of cis-unsaturated triacylglycerol: Triolein, J. Phys. Chem. B 110 (2006), pp. 4346-4353; E. Da Silva and D. Rousseau, Molecular order and thermodynamics of the solid-liquid transition in triglycerides via Raman spectroscopy, Phys. Chem. Chem. Phys. 10 (2008), pp. 4606-4613) (with temperature-induced phase transitions). The research has shown that Raman spectroscopy in TAGs under pressure reveals useful information about its structural changes.

High-resolution past environmental reconstruction in East Asia using annually laminated lake sediments of Lake Megata in northeastern Japan

NASA Astrophysics Data System (ADS)

Yamada, K.; Gotanda, K.; Yonenobu, H.; Shinozuka, Y.; Kitagawa, J.; Makohonienko, M.; Schwab, M.; Haraguchi, T.; Yasuda, Y.

2007-12-01

37 m-long non-glacial varved sequences were taken from Ichi-no-Megata maar in Oga Peninsula, Akita, northern part of Japan. Ichi-no-Megata maar occupies 0.25 km2 with a maximum water depth of ca. 45.1 m. The shape of lake is a kettle-type basin and the deepest bottom basin is very flat. We took core samples (named IMG06 core) at the center of the lake in November to December in 2006. In order to take completely continuous maar sediment, we drilled three holes and take every sample from each hole which apart only few meters. In this drilling campaign, we can 37 m-long continuous maar sediment except thick volcanic deposits from 26.5 to 31.7m in core. The sedimentological feature of IMG06 core is dominated by thin lamination clay/silt from most top part up to 37 m with turbidites characterized upward fining structure. The SEM image observation of lamination reveals that sponge-like lamina consists of diatom assemblage against dark colored lamina consists of mixture of detritus minerals, clay minerals, and diatom. It means sponge-like lamina deposits during spring season, and later one deposits during another three seasons, and then these thin lamination of IMG06 core could be identified as annual lamination (varves). This interpretation is supported by the correlation of historic event as earthquake and tunnel construction. In this IMG06 core, six volcanic ashes are found and we have also analyzed radiocarbon dating from 38 horizons of the core to use leaf and seeds inter-bedded varves. As the results, the IMG06 core covers from 25,000 to 4,000 14C yr BP with stable sedimentation rates (0.71mm/year).

A New Standard Installation Method of the Offline Seismic Observation Station in Heavy Snowfall Area of Tohoku Region

NASA Astrophysics Data System (ADS)

Hirahara, S.; Nakayama, T.; Hori, S.; Sato, T.; Chiba, Y.; Okada, T.; Matsuzawa, T.

2015-12-01

Soon after the 2011 Tohoku earthquake, seismic activity of Tohoku region, NE Japan is induced in the inland area of Akita prefecture and the border area between Fukushima and Yamagata prefectures. We plan to install a total of 80 offline seismic observation stations in these areas for studying the effect of megathrust earthquake on the activities of inland earthquakes. In our project, maintenance will be held twice-a-year for 4 years from 2015 by using 2.0Hz short-period 3-component seismometer, KVS-300 and ultra-low-power data logger, EDR-X7000 (DC12V 0.08W power supply). We installed seismometer on the rock surface or the slope of the natural ground at the possible sites confirmed with low noise level to obtain distinct seismic waveform data. We report an improvement in installation method of the offline seismic observation station in the heavy snowfall area of Tohoku region based on the retrieved data. In the conventional method, seismometer was installed in the hand-dug hole of a slope in case it is not waterproof. Data logger and battery were installed in the box container on the ground surface, and then, GPS antenna was installed on the pole fixed by stepladder. There are risks of the inclination of seismometer and the damage of equipment in heavy snowfall area. In the new method, seismometer is installed in the robust concrete box on the buried basement consists of precast concrete mass to keep its horizontality. Data logger, battery, and GPS antenna are installed on a high place by using a single pole with anchor bolt and a pole mount cabinet to enhance their safety. As a result, total costs of installation are kept down because most of the equipment is reusable. Furthermore, an environmental burden of waste products is reduced.

Microbial diversity and iron oxidation at Okuoku-hachikurou Onsen, a Japanese hot spring analog of Precambrian iron formations.

PubMed

Ward, L M; Idei, A; Terajima, S; Kakegawa, T; Fischer, W W; McGlynn, S E

2017-11-01

Banded iron formations (BIFs) are rock deposits common in the Archean and Paleoproterozoic (and regionally Neoproterozoic) sedimentary successions. Multiple hypotheses for their deposition exist, principally invoking the precipitation of iron via the metabolic activities of oxygenic, photoferrotrophic, and/or aerobic iron-oxidizing bacteria. Some isolated environments support chemistry and mineralogy analogous to processes involved in BIF deposition, and their study can aid in untangling the factors that lead to iron precipitation. One such process analog system occurs at Okuoku-hachikurou (OHK) Onsen in Akita Prefecture, Japan. OHK is an iron- and CO 2 -rich, circumneutral hot spring that produces a range of precipitated mineral textures containing fine laminae of aragonite and iron oxides that resemble BIF fabrics. Here, we have performed 16S rRNA gene amplicon sequencing of microbial communities across the range of microenvironments in OHK to describe the microbial diversity present and to gain insight into the cycling of iron, oxygen, and carbon in this ecosystem. These analyses suggest that productivity at OHK is based on aerobic iron-oxidizing Gallionellaceae. In contrast to other BIF analog sites, Cyanobacteria, anoxygenic phototrophs, and iron-reducing micro-organisms are present at only low abundances. These observations support a hypothesis where low growth yields and the high stoichiometry of iron oxidized per carbon fixed by aerobic iron-oxidizing chemoautotrophs like Gallionellaceae result in accumulation of iron oxide phases without stoichiometric buildup of organic matter. This system supports little dissimilatory iron reduction, further setting OHK apart from other process analog sites where iron oxidation is primarily driven by phototrophic organisms. This positions OHK as a study area where the controls on primary productivity in iron-rich environments can be further elucidated. When compared with geological data, the metabolisms and mineralogy at

Copper Transporter ATP7A Protects Against Endothelial Dysfunction in Type 1 Diabetic Mice by Regulating Extracellular Superoxide Dismutase

PubMed Central

Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; McKinney, Ronald D.; Llanos, Roxana M.; Mercer, Julian F.B.; Ushio-Fukai, Masuko; Fukai, Tohru

2013-01-01

Oxidative stress and endothelial dysfunction contribute to vascular complication in diabetes. Extracellular superoxide dismutase (SOD3) is one of the key antioxidant enzymes that obtains copper via copper transporter ATP7A. SOD3 is secreted from vascular smooth muscles cells (VSMCs) and anchors at the endothelial surface. The role of SOD3 and ATP7A in endothelial dysfunction in type 1 diabetes mellitus (T1DM) is entirely unknown. Here we show that the specific activity of SOD3, but not SOD1, is decreased, which is associated with increased O2•− production in aortas of streptozotocin-induced and genetically induced Ins2Akita T1DM mice. Exogenous copper partially rescued SOD3 activity in isolated T1DM vessels. Functionally, acetylcholine-induced, endothelium-dependent relaxation is impaired in T1DM mesenteric arteries, which is rescued by SOD mimetic tempol or gene transfer of SOD3. Mechanistically, ATP7A expression in T1DM vessels is dramatically decreased whereas other copper transport proteins are not altered. T1DM-induced endothelial dysfunction and decrease of SOD3 activity are rescued in transgenic mice overexpressing ATP7A. Furthermore, SOD3-deficient T1DM mice or ATP7A mutant T1DM mice augment endothelial dysfunction and vascular O2•− production versus T1DM mice. These effects are in part due to hypoinsulinemia in T1DM mice, since insulin treatment, but not high glucose, increases ATP7A expression in VSMCs and restores SOD3 activity in the organoid culture of T1DM vessels. In summary, a decrease in ATP7A protein expression contributes to impaired SOD3 activity, resulting in O2•− overproduction and endothelial dysfunction in blood vessels of T1DM. Thus, restoring copper transporter function is an essential therapeutic approach for oxidant stress–dependent vascular and metabolic diseases. PMID:23884884

Association of Cervical Cancer Screening with Knowledge of Risk Factors, Access to Health Related Information, Health Profiles, and Health Competence Beliefs among Community-Dwelling Women in Japan

PubMed Central

Oba, Shino; Toyoshima, Masato; Ogata, Hiromitsu

2017-01-01

Objective: The aim of this study was to evaluate the past attendance for cervical cancer screening with knowledge of risk factors, access to health-related information, health profiles and health competence beliefs among Japanese women. Methods: Women ages 25, 30, 35, 40, 45, 50, 55, and 60 were contacted cross-sectionally as part of a project for the Japanese Ministry of Health, Labour and Welfare in Nikaho, Akita prefecture Japan between June 2010 and March 2011, and 249 women were analyzed for the current study. The questionnaire asked about past cervical cancer screening. Knowledge of each cervical cancer risk factor was determined on a four-point scale. A barriers to information access scale was utilized to assess the degree of difficulty in accessing health-related information. Health profiles were measured using the EuroQOL EQ-5D. Perceived health competence was measured using a scale (PHCS). The association was evaluated with odds ratios with 95% confidence interval were calculated from a logistic regression analysis after adjustment for age and potential confounders. The trend across the level was also assessed. Results: Women who knew that sexual intercourse at young age was a risk factor were significantly more likely to have participated in cervical cancer screening sometime in their lives (p for trend =0.02). Women who had pain/discomfort and those who had anxiety/depression were significantly more likely to have participated in cervical screening within the past two years (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.04–3.94; OR: 2.32, 95% CI: 1.05–5.16, respectively). Women with higher PHCS were significantly more likely to have attended for cervical screened at some point in their lives (p=0.04). Conclusion: This study observed that specific knowledge of cervical cancer risk factors, health profiles and PHCS were associated with the past attendance for cervical cancer screening among women in a community. Further researches are

Mt. Kilimanjaro expedition in earth science education

NASA Astrophysics Data System (ADS)

Sparrow, Elena; Yoshikawa, Kenji; Narita, Kenji; Brettenny, Mark; Yule, Sheila; O'Toole, Michael; Brettenny, Rogeline

2010-05-01

Mt. Kilimanjaro, Africa's highest mountain is 5,895 meters above sea level and is located 330 km south of the equator in Tanzania. In 1976 glaciers covered most of Mt. Kilimanjaro's summit; however in 2000, an estimated eighty percent of the ice cap has disappeared since the last thorough survey done in 1912. There is increased scientific interest in Mt. Kilimanjaro with the increase in global and African average temperatures. A team of college and pre-college school students from Tanzania, South Africa and Kenya, teachers from South Africa and the United States, and scientists from the University of Alaska Fairbanks in the United States and Akita University in Japan, climbed to the summit of Mt Kilimanjaro in October 2009. They were accompanied by guides, porters, two expedition guests, and a videographer. This expedition was part of the GLOBE Seasons and Biomes Earth System Science Project and the GLOBE Africa science education initiative, exploring and contributing to climate change studies. Students learned about earth science experientially by observing their physical and biological surroundings, making soil and air temperature measurements, participating in discussions, journaling their experience, and posing research questions. The international trekkers noted the change in the biomes as the altitude, temperature and conditions changed, from cultivated lands, to rain forest, heath zone, moorland, alpine desert, and summit. They also discovered permafrost, but not at the summit as expected. Rather, it was where the mountain was not covered by a glacier and thus more exposed to low extreme temperatures. This was the first report of permafrost on Mt. Kilimanjaro. Classrooms from all over the world participated in the expedition virtually. They followed the trek through the expedition website (http://www.xpeditiononline.com/) where pictures and journals were posted, and posed their own questions which were answered by the expedition and base camp team members

Early Diagenetic Changes of Sediment Pore Properties Beneath the Seafloor and Their Contributions to Gas Hydrate Concentration in the Eastern Margin of Japan Sea

NASA Astrophysics Data System (ADS)

Uchida, T.; Horiuchi, S.; Kato, Y.; Matsumoto, R.

2014-12-01

Recently many of the chimney-shape gas hydrate concentrated beneath the seafloor have been confirmed off Shimane and off Akita as well as off Joetsu in the eastern margin of Japan Sea, which are quite different from the occurrences of pore space hydrate filling the intergranular pore system of sands recognized in Nankai Trough, Mallik and other sites. Sediment samples below the seafloor were retrieved in 2010 up to 40 m long at the Umitaka Spur, Joetsu Channel, Toyama Trough, Japan Basin, Nishi Tsugaru and Okushiri Ridge areas. Small amounts of sandy sediment have been retrieved as thin intercalations in Pleistocene and Holocene muddy layers transported approximately around 3 to 30 ka according to the tephra ages, where supplying sediments might have not been abundant due to sea level fluctuation during the Pleistocene ice age. It is important to clarify the relationship between burial depths and absolute porosities of the argillaceous sediments in relation to early diagenesis. Macroscopic observations and descriptions, measurements of porosity and permeability, SEM (scanning electron microscope) observations, and X-ray diffraction analyses have been performed. They consist of silt- to clay-grained particles, and they sometimes contain very fine- to medium-grained thin sandy layers. Average porosities of these fine-grained sediments are 50 % in all study areas, which quickly reduce from 60% to less than 50% within 10 meters and gradually decrease to the depth. However, mean pore sizes in the Nishi Tsugaru are around 1000 nm while 100 nm in the other areas, which tend to decrease with depth. It is suggested that repacking of the muddy particles gradually advances by mechanical compaction, which may crucially influence permeability. They usually contain much opal-A, quartz, feldspar, illite and smectite that do not change definitely with depth. By optical and microscopic observations, diatom tests, foraminifers and framboidal pyrites are commonly observed, and, in

Early Diagenesis of Subseafloor Sandy Sediments Closely Related to Gas Hydrate Occurrences and Their Provenances in the Eastern Margin of Japan Sea

NASA Astrophysics Data System (ADS)

Uchida, T.; Sakai, H.; Horiuchi, S.; Matsumoto, R.

2015-12-01

A lot of effort have been put into recovering gas hydrate, methane induced carbonate, and associated sediments in order to develop the geologic model of gas hydrate accumulation and evaluate its possible environmental impact for the last glacial-interglacial cycles. Having investigated gas hydrate occurrences in the eastern margin of Japan Sea revealed wide distributions of chimney-shape gas hydrate concentrations beneath the seafloor, confirmed off Shimane and off Akita/Yamagata as well as off Joetsu (Niigata), which are quite different from the occurrences of pore space hydrate filling intergranular pore systems of sands recognized in Nankai Trough, Mallik and other sites. Many sediment samples have been obtained below from the Umitaka Spur, Joetsu Channel, Toyama Trough, Mogami Trough and Okushiri Ridge areas. Small amounts of sandy sediment have been retrieved as thin intercalations in Holocene and Pleistocene silty/muddy layers, where trace fossils and strong bioturbations are commonly observed. Sandy sediments consist of very fine- to fine-grained sand grains, and are sometimes tuffaceous. Pore-size distribution measurements and thin-section observations of these sands were carried out, which indicate that porosities of silty sediments are around 50 % but those of arenites range from 42 to 52 %, of which mean pore sizes and permeabilities are larger than those of silty sediments. These coarser sediments might have been transported approximately around 3 to 30 ka due to the tephra ages, where supplying sediments might be abundant due to sea level fluctuation during the Pleistocene ice age. Sandy sediments contain not only detrital quartz and feldspar but mafic minerals (pyroxene, amphibole and mica), contents of which may indicate their provenances. Silty/muddy sediments usually contain diatom tests, foraminifers and framboidal pyrites, and, in particular, the shapes of diatom are usually various, dominantly fragmental and infrequently preserved. It is

Impurity of Sulfur Layers and Magmatic Gas Scrubbing: Implications for Gas Monitoring

NASA Astrophysics Data System (ADS)

Scolamacchia, T.

2017-12-01

stated above. References Bacon RF, Fanelli R, J Am Chem Soc 65, 639-648 (1943). Christenson BW, Wood CP, Bull Volcan 55, 547-565 (1993). Ohashi R, J. Akita Min. Coll 1, 1-10 (1919) Oppenheimer C, Stevenson D, Nature 342, 790-793 (1989) Symonds RB, Gerlach TM, Reed MH, J. Volc Geot Res 108, 303-341 (2001)

Barite aerosol particles from volcanic plumes and fumaroles - FESEM/EDS analysis

NASA Astrophysics Data System (ADS)

Obenholzner, J. H.; Schroettner, H.; Delgado, H.

2003-04-01

Studies of aerosol particles (AP) contained in volcanic plumes has been enormously benefited by the use of field emission scanning electron microscope (FESEM/EDS; responsability by H. Schroettner) permitting morphological, mineralogical and chemical detailed observations and opening new scientific questions. This work shows the ubiquitous presence of Ba in volcanic emissions. We sampled e.g. a volcanic plume (Popocatepetl v.; 1997, 2002) revealing Ba-S-O particles, interpreteted as barite (BaSO4) and Sr-bearing barite with Fe-rich rim (w=1µm). The ca. 500 nm - 4 µm long crystals are +/- euhedral, anhedral and/or partially etched. The µm-sized crystals had been collected on a Teflon fiber filter (1997), the nm-sized on borosilicate fiber filter (BFF, 2002); one set of crystals (ca. l=500-800 nm) is scattered on Fe-hydr/oxide(?). APs collected from the degassing lava flow of Etna (2001) revealed barite (l= ca. 100 nm) on a rounded NaCl (d= 500 nm) and on Fe-hydr/oxides (?). BFF exposed to the F0 fumarole at Vulcano (2001) showed incrustations of barite (l=ca.200 nm) on fibers indicating barite formation during 5 min sampling. At Solfatra we observed almost euhedral barite particles (l=ca.300 nm) of unusual pseudo-trigonal shape. APs from Alpine air masses (A) did not reveal barite. Sources for barite could be vesicle fillings of lavas (known from continental-crust settings), vapor-phase crystallization of ignimbrites (Bandelier Tuff, USA), Ba-rich fumarolic incrustations, rock coatings in the vicinity of fumaroles (Vulcano, I.), sinter of hot springs (Akita-Yaka-Yama v., J.), barite veins (Milos, Gr.), contact-metamorphosed sedimentary xenoliths (Kloech, A.) or lithics associated with hydrovolcanic eruptions (Alban Hills v., I.). Barite has been observed in many Si-tube experiments. Stratospheric APs (1985) of the El Chichon eruption (1982) revealed barite. Ba is known as a trace element in fumarole gases of Vulcano (F11) and TOF mass spectrometry studies detected

Lateral variation of H2O/K2O ratios in Quaternary Magma of the Northeastern Japan arc

NASA Astrophysics Data System (ADS)

Miyagi, I.

2012-12-01

larger quantity of volcanic products along the frontal side of the NE Japan arc. This research project has been conducted under the research contract with Nuclear and Industrial Safety Agency (NISA). I thank Drs. H. Kawaraya, D. Ishiyama, and O. Matsubaya at Akita univ. for their help in the analysis of hydrogen isotopic ratios.

Novel Chemical Methodology for Identifying Origin of Archeological Bitumen: Chasing the Trade Routes along the Japanese Archipelago and Sakhalin Island in Prehistory

NASA Astrophysics Data System (ADS)

Ogasawara, M.; Kato, K.

2009-04-01

, spread to the north in 2000 BC. It reached a small island near the north end of Hokkaido. Bitumen from Sakhalin reached the central lowland in Hokkaido, but it did not go into Honshu. Bitumen from Akita, another main source in Honshu, was predominated in the northeastern part of Honshu and the Oshima peninsula located at the southeastern end of Hokkaido. The story is consistent with a strong cultural tie between the Oshima peninsula and the northern Honshu throughout the Jomon period, the long lasting cultural period in Japanese prehistory. The long trade route along the coast of the Sea of Japan is being argued due to the recent archaeological findings obtained by excavations. Our results will shed more light on the geopolitical situation in the Jomon period of the area.

How do aquifers respond to volcanic strain changes?

NASA Astrophysics Data System (ADS)

Strehlow, Karen; Gottsmann, Jo; Rust, Alison

2015-04-01

are two of the most important influences on the simulated hydraulic head change. Especially the elastic stratigraphy needs to be carefully considered when inverting signals: In certain elastic settings, the resulting hydraulic head change is of opposite sign than what would be expected from poroelastic theory for a homogeneous earth. The generic setups developed to study poroelastic responses to volcanic strain changes now also provide the platform to study reported real cases in more detail and test hypotheses for the observed changes in hydrological systems. Candidate volcanoes include Souffrière Hills Volcano (Montserrat), Unzen (Japan), Kilauea (Hawaii) and Hekla (Iceland). References: Matsumoto, N., Sato, T., Matsushima, N., Akita, F., Shibata, T., and Suzuki, A. (2002). Hydrological anomalies associated with crustal deformation before the 2000 eruption of Usu volcano, Japan. Geophysical research letters, 29(5):1057. Mogi, K. (1958). Relations between the eruptions of various volcanoes and the deformations of the ground surface around them. Bull. Earthquake Res. Inst. Univ. Tokyo, 36:99-134.

Crustal architecture of the eastern margin of Japan Sea: back-arc basin opening and contraction

NASA Astrophysics Data System (ADS)

No, T.; Sato, T.; Takahashi, N.; Kodaira, S.; Kaneda, Y.; Ishiyama, T.; Sato, H.

2012-12-01

Basin and Japan Basin; however, the development of an asymmetric anticline and its associated reverse fault was observed off Akita prefecture, which could indicate a very recent growth structure. This development is associated with an active structure on the southern extension of the fault that caused the 1983 Nihonkai-Chubu Earthquake. On the other hand, the results from the seismic refraction/wide-angle reflection imaging using OBSs indicated that the area from the basin to the continental shelf, including the source area of the 1964 Niigata Earthquake, and the island arc crust had a large lateral variation in the upper and middle crust. In contrast, beneath the source area of the 1983 Nihonkai-Chubu Earthquake, the crustal structure is interpreted as a transitional crust between oceanic and island arc crusts, with larger variation in the P-wave velocity than those of the surrounding areas. Furthermore, the crust of the Yamato Basin area is thicker than a typical oceanic crust, whereas the crust of the Japan Basin area is similar to a typical oceanic crust.

Aftershocks associated with impaired health caused by the great East Japan disaster among youth across Japan: a national cross-sectional survey.

PubMed

Sugimoto, Takashi; Shinozaki, Tomohiro; Miyamoto, Yuki

2013-12-20

The Great East Japan earthquake, subsequent tsunamis and the Fukushima nuclear incident had a tremendous impact on Japanese society. Although small-scale surveys have been conducted in highly affected areas, few have elucidated the disaster's effect on health from national perspective, which is necessary to prepare national policy and response. The aim of the present study was to describe prefecture-level health status and investigate associations with number of aftershocks, seismic intensity, a closer geographical location to the Fukushima Nuclear Power Plant, or higher reported radiation dose in each prefecture even after adjusting for individual socioeconomic factors, by utilizing individual-level data acquired from a national cross-sectional Internet survey as well as officially reported prefecture-level data. A Japanese government research institute obtained 12,000 participants by quota sampling and 7335 participants were eligible for the analysis in an age range between 17 and 27 years old. We calculated the percentage of people with decreased subjective health in each prefecture after the earthquake. Variability introduced by a small sample size for some prefectures was smoothed using empirical Bayes estimation with a random-intercept logistic model, with and without demographic factors. Multilevel logistic regression was used to calculate adjusted odds ratios (ORs) for change of subjective health associated with prefecture-level and individual-level factors. Adjusted empirical Bayes estimates were higher for respondents commuting in the northeast region (Iwate 14%, Miyagi 19%, and Fukushima 28%), which faces the Pacific Ocean, while the values for Akita (10%) and Yamagata (8%) prefectures, which do not face the Pacific Ocean, were lower than those of Tokyo (12%). The values from the central to the western region were clearly lower. The number of aftershocks was coherently associated with decreased health (OR 1.05 per 100 times, 95% CI 1.04-1.06; P<.001

The Prevalence and Management of Diabetic Nephropathy in Asia

PubMed Central

Tomino, Yasuhiko; Gohda, Tomohito

2015-01-01

Background Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-Ay mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Message It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the

EDITORIAL: Focus on Carbon Nanotubes

NASA Astrophysics Data System (ADS)

2003-09-01

planes to stable loops caused by annealing M Endo, B J Lee, Y A Kim, Y J Kim, H Muramatsu, T Yanagisawa, T Hayashi, M Terrones and M S Dresselhaus Energetics and electronic structure of C70-peapods and one-dimensional chains of C70 Susumu Okada, Minoru Otani and Atsushi Oshiyama Theoretical characterization of several models of nanoporous carbon F Valencia, A H Romero, E Hernández, M Terrones and H Terrones First-principles molecular dynamics study of the stretching frequencies of hydrogen molecules in carbon nanotubes Gabriel Canto, Pablo Ordejón, Cheng Hansong, Alan C Cooper and Guido P Pez The geometry and the radial breathing mode of carbon nanotubes: beyond the ideal behaviour Jeno Kürti, Viktor Zólyomi, Miklos Kertesz and Sun Guangyu Curved nanostructured materials Humberto Terrones and Mauricio Terrones A one-dimensional Ising model for C70 molecular ordering in C70-peapods Yutaka Maniwa, Hiromichi Kataura, Kazuyuki Matsuda and Yutaka Okabe Nanoengineering of carbon nanotubes for nanotools Yoshikazu Nakayama and Seiji Akita Narrow diameter double-wall carbon nanotubes: synthesis, electron microscopy and inelastic light scattering R R Bacsa, E Flahaut, Ch Laurent, A Peigney, S Aloni, P Puech and W S Bacsa Sensitivity of single multiwalled carbon nanotubes to the environment M Krüger, I Widmer, T Nussbaumer, M Buitelaar and C Schönenberger Characterizing carbon nanotube samples with resonance Raman scattering A Jorio, M A Pimenta, A G Souza Filho, R Saito, G Dresselhaus and M S Dresselhaus FTIR-luminescence mapping of dispersed single-walled carbon nanotubes Sergei Lebedkin, Katharina Arnold, Frank Hennrich, Ralph Krupke, Burkhard Renker and Manfred M Kappes Structural properties of Haeckelite nanotubes Ph Lambin and L P Biró Structural changes in single-walled carbon nanotubes under non-hydrostatic pressures: x-ray and Raman studies Sukanta Karmakar, Surinder M Sharma, P V Teredesai, D V S Muthu, A Govindaraj, S K Sikka and A K Sood Novel properties of 0

EDITORIAL: Focus on Carbon Nanotubes

NASA Astrophysics Data System (ADS)

2003-09-01

, P Umek, K Hernadi, P Marcoux, B Lukic, Cs Mikó, M Milas, R Gaál and L Forró Transitional behaviour in the transformation from active end planes to stable loops caused by annealing M Endo, B J Lee, Y A Kim, Y J Kim, H Muramatsu, T Yanagisawa, T Hayashi, M Terrones and M S Dresselhaus Energetics and electronic structure of C70-peapods and one-dimensional chains of C70 Susumu Okada, Minoru Otani and Atsushi Oshiyama Theoretical characterization of several models of nanoporous carbon F Valencia, A H Romero, E Hernández, M Terrones and H Terrones First-principles molecular dynamics study of the stretching frequencies of hydrogen molecules in carbon nanotubes Gabriel Canto, Pablo Ordejón, Cheng Hansong, Alan C Cooper and Guido P Pez The geometry and the radial breathing mode of carbon nanotubes: beyond the ideal behaviour Jeno Kürti, Viktor Zólyomi, Miklos Kertesz and Sun Guangyu Curved nanostructured materials Humberto Terrones and Mauricio Terrones A one-dimensional Ising model for C70 molecular ordering in C70-peapods Yutaka Maniwa, Hiromichi Kataura, Kazuyuki Matsuda and Yutaka Okabe Nanoengineering of carbon nanotubes for nanotools Yoshikazu Nakayama and Seiji Akita Narrow diameter double-wall carbon nanotubes: synthesis, electron microscopy and inelastic light scattering R R Bacsa, E Flahaut, Ch Laurent, A Peigney, S Aloni, P Puech and W S Bacsa Sensitivity of single multiwalled carbon nanotubes to the environment M Krüger, I Widmer, T Nussbaumer, M Buitelaar and C Schönenberger Characterizing carbon nanotube samples with resonance Raman scattering A Jorio, M A Pimenta, A G Souza

[Lessons learned from tuberculosis outbreak cases].

PubMed

Kato, Seiya; Kuwabara, Katsuhiro

2014-02-01

Teishin Hospital), Toru MORI (Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association) The index case was a patient who was admitted to a general hospital where she was treated with pulsed corticosteroid therapy and then put on a respirator. Soon after, she developed tuberculosis (TB) and died. Immediately after her death, the healthcare workers who had close contact with the index case were given the QuantiFERON TB Gold (QFT) test, which indicated that all staff except one were negative. However, a QFT test administered eight weeks later had a positive rate of 18.6%. Subsequently, a total of five workers, including a doctor, nurses, and radiology technicians, developed TB. The bacterial isolates from five of them exhibited an RFLP pattern identical to that of the index case. These secondary cases of TB included a case who had contact of less than 5 minutes, a case whose QFT was negative ("doubtful" in the Japanese criterion of the QFT), and a case who was QFT-positive but declined to be treated for latent TB infection (LTBI). No other workers nor hospitalized patients developed TB. The healthcare worker contacts were further examined with the QFT 6, 9 and 12 months after the contact. The QFT results revealed four additional positive reactors and four "doubtful" reactors who were indicated for LTBI treatment. Among them were seven subjects who turned positive six months after the contact. TB prevention in hospital settings and contact investigations were discussed with the hospital staff, with special reference to the application of QFT. 3. Summary and issues of concern relating to a tuberculosis outbreak in a prison: Mitsunobu HOMMA, Takefumi ITOH (Department of Respiratory Medicine, Akita City Hospital) We report a tuberculosis outbreak that occurred in a prison in the spring of 2011, resulting in 11 cases of active disease and 40 cases of infection. The primary cause of the outbreak is thought to be the delay in identifying the index case, where the