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Sample records for cilnidipine suppresses podocyte

  1. Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel.

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    Shimizu, Hideo; Nakagami, Hironori; Yasumasa, Natsuki; Mariana, Osako Kiomy; Kyutoku, Mariko; Koriyama, Hiroshi; Nakagami, Futoshi; Shimamura, Munehisa; Rakugi, Hiromi; Morishita, Ryuichi

    2012-01-01

    Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a β-blocker) because β-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.

  2. Preparation and evaluation of cilnidipine microemulsion

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    Hemal Tandel

    2012-01-01

    Full Text Available Cilnidipine, a calcium channel blocker having neuroprotective action and BCS Class II drug, hence formulating in Microemulsion will increase solubility, absorption and bioavailability. The formulation was prepared using titration method by tocotrienol, tween 20 and transcutol HP as oil, surfactant and co-surfactant and characterized for dilutability, dye solubility, assay (98.39±0.06, pH (6.6±1.5, Viscosity (98±1.0 cps and Conductivity (0.2±0.09 μS/cm. The formulation was optimized on basis of percentage transmittance (99.269±0.23 at 700 nm, Globule size (13.31±4.3 nm and zeta potential (-11.4±2.3 mV. Cilnidipine microemulsion was found to be stable for 3 months.

  3. Stressed podocytes

    DEFF Research Database (Denmark)

    Svenningsen, Per

    2015-01-01

    predictor of the progression kidney disease (Ruggenenti et al., 2001). Within the last decades, the importance of podocytes for a functional glomerular filtration barrier has emerged. Podocytes are terminally differentiated epithelial cells with a highly organized structure, and injury to the podocyte...

  4. [Podocyte dysfunction and proteinuria

    NARCIS (Netherlands)

    Vogtländer, N.P.J.; Rietjens, S.J.; Vlag, J. van der; Berden, J.H.M.

    2004-01-01

    Podocytes play a central role in the pathogenesis of several glomerular diseases. In recent years, this has been revealed by molecular analysis of a number of rare hereditary renal diseases. Podocytes contain three domains: the domain bound to the glomerular basement membrane (GBM), the domain of th

  5. Antihypertensive Efficiency and Safety of L- & N- type Ca2+ Antagonists -cilnidipine

    Institute of Scientific and Technical Information of China (English)

    张向阳; 刘国树

    2003-01-01

    Objectives To evaluate antihypertensive efficiency and safety of a new domesticof L - & N - type Ca2+ antagonist - cilnidipine withimidapril as a positive control. Methods After 2weeks' placebo washingout, 22 patients were treatedwith cilnidipine 5 mg daily and 27 patients were treatedwith imidapril 5 mg daily. 4 weeks later, if patient'ssitting diastolic blood pressure is over 90 mmHg, his/her dosage was doubled for another 4 weeks, the othersmeasuring up remained their dosage unchanged foranother 4 weeks. Blood pressure, heart rate, blood andurine routine examination, serum glucose, serumchemical examination including total cholesterol,triglyceride, HDL, LDL, transaminase, creatine etcand side reactions were recorded before and after thetrial. Data were analyzed statistically. Results After8 weeks' treatment, blood pressure was significantlydecreased (P < 0.05) in both groups, and the twomedicines had similar antihypertensive effects. Fur-thermore, the reducing of heart rate was statisticallysignificant compared with baseline ( P < 0.01 ) in thecilnidipine group, but not in the imidapril group. Thenegative chronotropic effect of cilnidipine had little ef-fect on continuing the therapy. There were no changeson blood and urine routine examination and serumlipid, serum glucose, creatine, transaminase and etcin both groups. Their side reactions were mild and well-tolerated. Conclusions Cilnidipine has a con-vincing antihypertensive effect similar to that of imi-dapril. Especially cilnidipine may be administered topatients with relatively mild tachycardia.

  6. DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR ESTIMATION OF CILNIDIPINE AND METOPROLOL SUCCINATE

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    Mo.Salauddin A Shaikh

    2015-07-01

    Full Text Available A simple, specific, accurate and precise reversed phase high performance liquid chromatographic method was developed and validated for the simultaneous estimation of Cilnidipine and Metoprolol Succinate, using a Cosmosil C18 (250 х 4.6 mm i.d. column and a mobile phase composed of 0.05M potassium dihydrogen phosphate buffer: Methanol (70:30 pH 3.5 adjusted with ophosphoric acid and at flow rate of 1.0 ml/min. The retention times of Cilnidipine and Metoprolol Succinate were found to be 3.493 min and 5.960 min, respectively. Linearity was established for Cilnidipine and Metoprolol Succinate in the range of 12.5-37.5 μg/ml and 2.5-7.5 μg/ml, respectively. The percentage recoveries of Cilnidipine and Metoprolol Succinate were found to be in the range of 100.13-100.40 % and 99.24-100.29 %, respectively. The correlation coefficients for both components were found to be 0.999. The developed methods were validated according to ICH guidelines and values of linearity, accuracy, precision and other analysis were found to be in good accordance with the prescribed values. This method can be successfully employed for simultaneous quantitative analysis of Cilnidipine and Metoprolol Succinate in its dosage form. The developed HPLC method was subjected to stability indicating studies for marketed formulation. Interfering peak from degraded products or solvent did not interfere with estimation of drugs and the developed method was found to be specific for estimation of Cilnidipine and Metoprolol Succinate.

  7. Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro.

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    Jiang, Xu-Shun; Chen, Xue-Mei; Wan, Jiang-Min; Gui, Hai-Bo; Ruan, Xiong-Zhong; Du, Xiao-Gang

    2017-02-22

    Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis.

  8. Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro

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    Jiang, Xu-shun; Chen, Xue-mei; Wan, Jiang-min; Gui, Hai-bo; Ruan, Xiong-zhong; Du, Xiao-gang

    2017-01-01

    Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis. PMID:28225005

  9. Podocyte Pathology and Nephropathy

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    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  10. Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro

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    Ying Xu

    2016-04-01

    Full Text Available It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN. Here we used shRNA transfection to knockdown the insulin receptor (IR gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation. The present study deepens our understanding of the role of autophagy in the pathogenesis of DN.

  11. Silencing of Histone Deacetylase 9 Expression in Podocytes Attenuates Kidney Injury in Diabetic Nephropathy

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    Liu, Feng; Zong, Ming; Wen, Xiaofei; Li, Xuezhu; Wang, Jun; Wang, Yi; Jiang, Wei; Li, Xiaojun; Guo, Zhongliang; Qi, Hualin

    2016-01-01

    Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN. Secondly, knockdown of HDAC9 in mouse podocytes significantly suppressed HG-induced reactive oxygen species (ROS) generation, cell apoptosis and inflammation through JAK2/STAT3 pathway and reduced the podocytes injury by decreasing the expression levels of Nephrin and Podocin. Moreover, in diabetic db/db mice, silencing of HDAC9 attenuated the glomerulosclerosis, inflammatory cytokine release, podocyte apoptosis and renal injury. Collectively, these data indicate that HDAC9 may be involved in the process of DN, especially podocyte injury. Our study suggest that inhibition of HDAC9 may have a therapeutic potential in DN treatment. PMID:27633396

  12. Comparison of amlodipine with cilnidipine on antihypertensive efficacy and incidence of pedal edema in mild to moderate hypertensive individuals: A prospective study

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    Prabhakar Adake

    2015-01-01

    Full Text Available To compare amlodipine with cilnidipine on antihypertensive efficacy and incidence of pedal edema in hypertensive individuals. This was a three months prospective, observational study done at the tertiary care center of Karnataka, India. A total number of 60 (n = 60 newly diagnosed hypertensives (≥140/90 of either gender, attending outpatient department of medicine, were included in the study. Out of 60 patients, 30 patients who have been prescribed tablet amlodipine 5-10 mg/day and the other 30 who have been prescribed tablet cilnidipine 10-20 mg/day orally by the consulting physician, depending upon the severity of hypertension were followed every fortnight, screened for the presence of pedal edema and blood pressure control over a period of 3 months. Antihypertensive efficacy between two groups was compared by unpaired t-test and incidence of pedal edema was compared by Fisher′s exact test. Of 30 patients in the amlodipine group, 19 patients presented with pedal edema (63.3% and 2 patients (6.66% in cilnidipine group presented with pedal edema during the study period. There was a significant difference in the incidence of pedal edema between amlodipine and cilnidipine group (P 0.05. Both amlodipine and cilnidipine have shown equal efficacy in reducing blood pressure in hypertensive individuals. But cilnidipine being N-type and L-type calcium channel blocker, associated with lower incidence of pedal edema compared to only L-type channel blocked by amlodipine.

  13. The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1.

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    Masahiko Itoh

    Full Text Available Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecular mechanisms that organize the podocyte filtration barrier are not fully understood. In this study, we suggest that tight junction protein 1 (Tjp1 or ZO-1, which is encoded by Tjp1 gene, plays an essential role in establishing the podocyte filtration barrier. The podocyte-specific deletion of Tjp1 down-regulated the expression of podocyte membrane proteins, impaired the interdigitation of the foot processes and the formation of the slit diaphragm, resulting in glomerular dysfunction. We found the possibility that podocyte filtration barrier requires the integration of two independent units, the pre-existing epithelial junction components and the newly synthesized podocyte-specific components, at the final stage in glomerular morphogenesis, for which Tjp1 is indispensable. Together with previous findings that Tjp1 expression was decreased in glomerular diseases in human and animal models, our results indicate that the suppression of Tjp1 could directly aggravate glomerular disorders, highlights Tjp1 as a potential therapeutic target.

  14. The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1.

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    Itoh, Masahiko; Nakadate, Kazuhiko; Horibata, Yasuhiro; Matsusaka, Taiji; Xu, Jianliang; Hunziker, Walter; Sugimoto, Hiroyuki

    2014-01-01

    Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecular mechanisms that organize the podocyte filtration barrier are not fully understood. In this study, we suggest that tight junction protein 1 (Tjp1 or ZO-1), which is encoded by Tjp1 gene, plays an essential role in establishing the podocyte filtration barrier. The podocyte-specific deletion of Tjp1 down-regulated the expression of podocyte membrane proteins, impaired the interdigitation of the foot processes and the formation of the slit diaphragm, resulting in glomerular dysfunction. We found the possibility that podocyte filtration barrier requires the integration of two independent units, the pre-existing epithelial junction components and the newly synthesized podocyte-specific components, at the final stage in glomerular morphogenesis, for which Tjp1 is indispensable. Together with previous findings that Tjp1 expression was decreased in glomerular diseases in human and animal models, our results indicate that the suppression of Tjp1 could directly aggravate glomerular disorders, highlights Tjp1 as a potential therapeutic target.

  15. The Structural and Functional Organization of the Podocyte Filtration Slits Is Regulated by Tjp1/ZO-1

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    Itoh, Masahiko; Nakadate, Kazuhiko; Horibata, Yasuhiro; Matsusaka, Taiji; Xu, Jianliang; Hunziker, Walter; Sugimoto, Hiroyuki

    2014-01-01

    Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecular mechanisms that organize the podocyte filtration barrier are not fully understood. In this study, we suggest that tight junction protein 1 (Tjp1 or ZO-1), which is encoded by Tjp1 gene, plays an essential role in establishing the podocyte filtration barrier. The podocyte-specific deletion of Tjp1 down-regulated the expression of podocyte membrane proteins, impaired the interdigitation of the foot processes and the formation of the slit diaphragm, resulting in glomerular dysfunction. We found the possibility that podocyte filtration barrier requires the integration of two independent units, the pre-existing epithelial junction components and the newly synthesized podocyte-specific components, at the final stage in glomerular morphogenesis, for which Tjp1 is indispensable. Together with previous findings that Tjp1 expression was decreased in glomerular diseases in human and animal models, our results indicate that the suppression of Tjp1 could directly aggravate glomerular disorders, highlights Tjp1 as a potential therapeutic target. PMID:25184792

  16. 西尼地平在人肝微粒体内代谢及代谢抑制%Metabolism and metabolic inhibition of cilnidipine in human liver microsomes

    Institute of Scientific and Technical Information of China (English)

    柳晓泉; 赵阳; 李丹; 钱之玉; 王广基

    2003-01-01

    目的:在体外研究西尼地平在人肝微粒体内的代谢及选择性细胞色素P-450(CYP450)酶抑制剂对其代谢的影响.方法:在体外用人肝微粒体研究西尼地平的代谢,并用CYP450酶的选择性抑制剂探讨其对西尼地平代谢的影响及人肝微粒体中参与西尼地平二氢吡啶环脱氢代谢的CYP450酶.结果:西尼地平在人肝微粒体内被迅速代谢为三个代谢物,分别是西尼地平二氢吡啶环脱氢代谢物M1,二氢吡啶环侧链脱甲基代谢物M2,二氢吡啶环脱氢及其侧链脱甲基代谢物M3.酮康唑竞争性地抑制西尼地平二氢吡啶环的脱氢代谢,同时降低西尼地平的代谢速率.而其它抑制剂,奎尼丁,α-Naphthoflavone,diethyldithiocarbamate,sulfaphenazole和tra-nylcypromine对西尼地平二氢吡啶环的脱氢代谢没有明显的影响.结论:西尼地平在人肝微粒体内被迅速代谢,其二氢吡啶环的脱氢代谢是其代谢的关键性的步骤.CYP3A作为主要的CYP酶参与了西尼地平二氢吡啶环的脱氢代谢,CYP3A的抑制剂可能会与西尼地平发生代谢相互作用.%AIM: To study the metabolism of cilnidipine and the effects of selective cytochrome P-450 (CYP450) inhibitors onthe metabolism of cilnidipine in human liver microsomes in vitro. METHODS: Human liver microsomes were usedto perform metabolism studies. Various selective CYP450 inhibitors were used to investigate their effects on themetabolism of cilnidipine and the principal CYP450 isoform involved in dehydrogenation of dihydropyridine ring ofcilnidipine in human liver microsomes. RESULTS: Cilnidipine was rapidly metabolized to three metabolites. Theyare dehydrogenated metabolite of dihydropyridine ring of cilnidipine (M1), demethylation metabolite of lateral chainof dihydropyridine ring of cilnidipine (M2), and the dehydrogenation and demethylation metabolite of cilnidipine(M3). Ketoconazole (Ket) competitively inhibited the dehydrogenation of dihydropyridine ring

  17. Reduction of microalbuminuria in type-2 diabetes mellitus with angiotensin-converting enzyme inhibitor alone and with cilnidipine.

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    Singh, V K; Mishra, A; Gupta, K K; Misra, R; Patel, M L; Shilpa

    2015-01-01

    The aim of our study was to find out the antiproteinuric effect of enalapril angiotensin-converting enzyme (ACE inhibitor) alone or in combination with cilnidipine in patients with type-2 diabetes mellitus. The study was conducted on 71 patients with type-2 diabetes mellitus patients with hypertension and microalbuminuria. They were divided into two groups randomly as follows: Group I (enalaprilalone, n = 36) and Group II (enalapril with cilnidipine, n = 35). In both the groups, baseline 24 h urinary albumin was estimated and was repeated every 3 months upto 1-year. After 1-year follow-up, reduction in microalbuminuria was found to be greater in Group II. In Group I microalbuminuria came down by 25.68 ± 21.40 while in Group II it reduced by 54.88 ± 13.84 (P microalbuminuria reduction over and above the well-proven effect of ACE inhibitors.

  18. SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis

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    Shi, Jian-Xia; Wang, Qi-Jin; Li, Hui; Huang, Qin

    2017-01-01

    Diabetic nephropathy is a diabetic complication associated with capillary damage and increased mortality. Sirtuin 4 (SIRT4) plays an important role in mitochondrial function and the pathogenesis of metabolic diseases, including aging kidneys. The aim of the present study was to investigate the association between SIRT4 and diabetic nephropathy in a glucose-induced mouse podocyte model. A CCK-8 assay showed that glucose simulation significantly inhibited podocyte proliferation in a time- and concentration-dependent manner. Reverse transcription-quantitative polymerase chain reaction and western blot analysis showed that the mRNA and protein levels of SIRT4 were notably decreased in a concentration-dependent manner in glucose-simulated podocytes. However, SIRT4 overexpression increased proliferation and suppressed apoptosis, which was accompanied by increases in mitochondrial membrane potential and reduced production of reactive oxygen species (ROS). Notably, SIRT4 overexpression downregulated the expression of apoptosis-related proteins NOX1, Bax and phosphorylated p38 and upregulated the expression of Bcl-2 in glucose-simulated podocytes. In addition, SIRT4 overexpression significantly attenuated the inflammatory response, indicated by reductions in the levels of TNF-α, IL-1β and IL-6. These results demonstrate for the first time that the overexpression of SIRT4 prevents glucose-induced podocyte apoptosis and ROS production and suggest that podocyte apoptosis represents an early pathological mechanism leading to diabetic nephropathy. PMID:28123512

  19. Innate Immune Activity in Glomerular Podocytes

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    Xia, Hong; Bao, Wenduona; Shi, Shaolin

    2017-01-01

    Glomerular podocytes are specialized in structure and play an essential role in glomerular filtration. In addition, podocyte stress can initiate glomerular damage by inducing the injury of other glomerular cell types. Studies have shown that podocytes possess the property of immune cells and may be involved in adaptive immunity. Emerging studies have also shown that podocytes possess signaling pathways of innate immune responses and that innate immune responses often result in podocyte injury. More recently, mitochondrial-derived damage-associated molecular patterns (mtDAMPs) have been shown to play a critical role in a variety of pathological processes in cells. In the present mini-review, we summarize the recent advances in the studies of innate immunity and its pathogenic role in podocytes, particularly, from the perspective of mtDAMPs. PMID:28228761

  20. Activation of peroxisome proliferator-activated receptor-γ coactivator 1α ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury.

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    Yuan, Yanggang; Huang, Songming; Wang, Wenyan; Wang, Yingying; Zhang, Ping; Zhu, Chunhua; Ding, Guixia; Liu, Bicheng; Yang, Tianxin; Zhang, Aihua

    2012-10-01

    Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity.

  1. Development and Validation of Stability-Indicating HPTLC Method for Simultaneous Determination of Telmisartan and Cilnidipine in Combined Tablet Dosage Form

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    Santosh R. Butle

    2015-11-01

    Full Text Available A new simple, accurate, precise and selective stability-indicating high performance thin layer chromatographic (HPTLC method has been developed and validated for simultaneous estimation of Telmisartan and Cilnidipine in combined tablet dosage form. The mobile phase selected was Toluene: Methanol: Glacial acetic acid (8: 2: 1, v/v/v with UV detection at 260 nm. The retention factor for Telmisartan and Cilnidipine were found to be 0.38 ± 0.004 and 0.62 ± 0.007. The method was validated with respect to linearity, accuracy, precision and robustness. The drugs were subjected to stress condition of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. Results found to be linear in the concentration range of 200-1400ng band-1 and 50-600ng band-1 for Telmisartan and Cilnidipine, respectively. The method has been successfully applied for the analysis of drugs in pharmaceutical formulation. The % assay (Mean ± S.D. was found to be 100.79 ± 1.38 for Telmisartan and 99.55 ± 1.13 for Cilnidipine. The developed and validated stability indicating method can be used for assessing the stability of Telmisartan and Cilnidipine in bulk drug and pharmaceutical dosage form.

  2. Relationship between urinary podocytes and kidney diseases.

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    Sun, Dong; Zhao, Xudong; Meng, Li

    2012-01-01

    Podocyte loss is an important component of disease progression in glomerular diseases. To some extent, the loss of podocytes can predict the degree of damage and the advancement of renal disease. Detecting the loss of podocytes in the urine could be a valuable, noninvasive method for obtaining information about the activity of the disease or the disease type, allowing the early diagnosis of glomerular diseases. One of the most robust markers that has been successfully used for urinary podocyte diagnostics is podocalyxin (PDX). PDX is a sialoprotein that is expressed on podocytes and on a variety of nonrenal cells as well as on glomerular endothelial and parietal epithelial cells. Therefore, podocyte loss can be detected by the amount of PDX in the urine. The relationship between urinary podocytes and renal diseases is supported by the detection of podocytes in patients with immunoglobulin A (IgA) nephropathy, Henoch-Schönlein purpura nephritis, lupus nephritis, diabetic nephropathy, and focal segmental glomerulosclerosis. The use of technology for detecting podocytes in the urine would have broad implications for the evaluation of disease activity, the degree of dedifferentiation, and the possibility of regeneration.

  3. A novel source of cultured podocytes.

    Science.gov (United States)

    Da Sacco, Stefano; Lemley, Kevin V; Sedrakyan, Sargis; Zanusso, Ilenia; Petrosyan, Astgik; Peti-Peterdi, Janos; Burford, James; De Filippo, Roger E; Perin, Laura

    2013-01-01

    Amniotic fluid is in continuity with multiple developing organ systems, including the kidney. Committed, but still stem-like cells from these organs may thus appear in amniotic fluid. We report having established for the first time a stem-like cell population derived from human amniotic fluid and possessing characteristics of podocyte precursors. Using a method of triple positive selection we obtained a population of cells (hAKPC-P) that can be propagated in vitro for many passages without immortalization or genetic manipulation. Under specific culture conditions, these cells can be differentiated to mature podocytes. In this work we compared these cells with conditionally immortalized podocytes, the current gold standard for in vitro studies. After in vitro differentiation, both cell lines have similar expression of the major podocyte proteins, such as nephrin and type IV collagen, that are characteristic of mature functional podocytes. In addition, differentiated hAKPC-P respond to angiotensin II and the podocyte toxin, puromycin aminonucleoside, in a way typical of podocytes. In contrast to immortalized cells, hAKPC-P have a more nearly normal cell cycle regulation and a pronounced developmental pattern of specific protein expression, suggesting their suitability for studies of podocyte development for the first time in vitro. These novel progenitor cells appear to have several distinct advantages for studies of podocyte cell biology and potentially for translational therapies.

  4. A novel source of cultured podocytes.

    Directory of Open Access Journals (Sweden)

    Stefano Da Sacco

    Full Text Available Amniotic fluid is in continuity with multiple developing organ systems, including the kidney. Committed, but still stem-like cells from these organs may thus appear in amniotic fluid. We report having established for the first time a stem-like cell population derived from human amniotic fluid and possessing characteristics of podocyte precursors. Using a method of triple positive selection we obtained a population of cells (hAKPC-P that can be propagated in vitro for many passages without immortalization or genetic manipulation. Under specific culture conditions, these cells can be differentiated to mature podocytes. In this work we compared these cells with conditionally immortalized podocytes, the current gold standard for in vitro studies. After in vitro differentiation, both cell lines have similar expression of the major podocyte proteins, such as nephrin and type IV collagen, that are characteristic of mature functional podocytes. In addition, differentiated hAKPC-P respond to angiotensin II and the podocyte toxin, puromycin aminonucleoside, in a way typical of podocytes. In contrast to immortalized cells, hAKPC-P have a more nearly normal cell cycle regulation and a pronounced developmental pattern of specific protein expression, suggesting their suitability for studies of podocyte development for the first time in vitro. These novel progenitor cells appear to have several distinct advantages for studies of podocyte cell biology and potentially for translational therapies.

  5. Podocytes [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jochen Reiser

    2016-01-01

    Full Text Available Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman’s capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction, a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.

  6. Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes.

    Science.gov (United States)

    Li, Yanjiao; Shen, Yachen; Li, Min; Su, Dongming; Xu, Weifeng; Liang, Xiubin; Li, Rongshan

    2015-07-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have beneficial effects on the kidney diseases through preventing microalbuminuria and glomerulosclerosis. However, the mechanisms underlying these effects remain to be fully understood. In this study, we investigate the effects of PPAR-γ agonist, rosiglitazone (Rosi) and pioglitazone (Pio), on collagen IV production in mouse podocytes. The endogenous expression of PPAR-γ was found in the primary podocytes and can be upregulated by Rosi and Pio, respectively, detected by RT-PCR and Western blot. PPAR-γ agonist markedly blunted the increasing of collagen IV expression and extraction in podocytes induced by TGF-β. In contrast, adding PPAR-γ antagonist, GW9662, to podocytes largely prevented the inhibition of collagen IV expression from Pio treatment. Our data also showed that phosphorylation of Smad2/3 enhanced by TGF-β in a time-dependent manner was significantly attenuated by adding Pio. The promoter region of collagen IV gene contains one putative consensus sequence of Smad-binding element (SBE) by promoter analysis, Rosi and Pio significantly ameliorated TGF-β-induced SBE4-luciferase activity. In conclusion, PPAR-γ activation by its agonist, Rosi or Pio, in vitro directly inhibits collagen IV expression and synthesis in primary mouse podocytes. The suppression of collagen IV production was related to the inhibition of TGF-β-driven phosphorylation of Smad2/3 and decreased response activity of SBEs of collagen IV in PPAR-γ agonist-treated mouse podocytes. This represents a novel mechanistic support regarding PPAR-γ agonists as podocyte protective agents.

  7. Nuclear hormone receptors in podocytes

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    Khurana Simran

    2012-09-01

    Full Text Available Abstract Nuclear receptors are a family of ligand-activated, DNA sequence-specific transcription factors that regulate various aspects of animal development, cell proliferation, differentiation, and homeostasis. The physiological roles of nuclear receptors and their ligands have been intensively studied in cancer and metabolic syndrome. However, their role in kidney diseases is still evolving, despite their ligands being used clinically to treat renal diseases for decades. This review will discuss the progress of our understanding of the role of nuclear receptors and their ligands in kidney physiology with emphasis on their roles in treating glomerular disorders and podocyte injury repair responses.

  8. VEGF regulates TRPC6 channels in podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Loddenkemper, Christoph;

    2012-01-01

    BACKGROUND: Both, increased plasma concentrations of vascular endothelial growth factor (VEGF) and increased expression of transient receptor potential canonical type 6 (TRPC6) channels in podocytes have been associated with proteinuric kidney diseases. Now, we investigated the hypothesis that VE...

  9. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chenglong [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zheng, Haining [Department of Hyperbaric Oxygen, Nanjing General Hospital of Nanjing Military Command, Nanjing (China); Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Ding, Dafa, E-mail: dingdafa2004@aliyun.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Lu, Yibing, E-mail: luyibing2004@126.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  10. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

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    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  11. Direct Action of Endothelin-1 on Podocytes Promotes Diabetic Glomerulosclerosis

    OpenAIRE

    Lenoir, Olivia; Milon, Marine; Virsolvy, Anne; Hénique, Carole; Schmitt, Alain; Massé, Jean-Marc; Kotelevtsev, Yuri; Yanagisawa, Masashi; Webb, David J; Richard, Sylvain; Tharaux, Pierre-Louis

    2014-01-01

    The endothelin system has emerged as a novel target for the treatment of diabetic nephropathy. Endothelin-1 promotes mesangial cell proliferation and sclerosis. However, no direct pathogenic effect of endothelin-1 on podocytes has been shown in vivo and endothelin-1 signaling in podocytes has not been investigated. This study investigated endothelin effects in podocytes during experimental diabetic nephropathy. Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium tr...

  12. Early autophagy activation inhibits podocytes from apoptosis induced by aldosterone

    Institute of Scientific and Technical Information of China (English)

    王文琰

    2013-01-01

    Objective To explore the protection of early autoph-agy activation on podocyte injury induced by aldosterone.Methods In vitro cultured mouse podocyte clones(MPC5) were treated with aldosterone for 6,12,24,48 hrespectively. Apoptosis of podocytes was detected by

  13. Intrinsic proinflammatory signaling in podocytes contributes to podocyte damage and prolonged proteinuria.

    Science.gov (United States)

    Brähler, Sebastian; Ising, Christina; Hagmann, Henning; Rasmus, Melanie; Hoehne, Martin; Kurschat, Christine; Kisner, Tuelay; Goebel, Heike; Shankland, Stuart; Addicks, Klaus; Thaiss, Friedrich; Schermer, Bernhard; Pasparakis, Manolis; Benzing, Thomas; Brinkkoetter, Paul Thomas

    2012-11-15

    Inflammation conveys the development of glomerular injury and is a major cause of progressive kidney disease. NF-κB signaling is among the most important regulators of proinflammatory signaling. Its role in podocytes, the epithelial cells at the kidney filtration barrier, is poorly understood. Here, we inhibited NF-κB signaling in podocytes by specific ablation of the NF-κB essential modulator (NEMO, IKKγ). Podocyte-specific NEMO-deficient mice (NEMO(pko)) were viable and did not show proteinuria or overt changes in kidney morphology. After induction of glomerulonephritis, both NEMO(pko) and control mice developed significant proteinuria. However, NEMO(pko) mice recovered much faster, showing rapid remission of proteinuria and restoration of podocyte morphology. Interestingly, quantification of infiltrating macrophages, T-lymphocytes, and granulocytes at day 7 revealed no significant difference between wild-type and NEMO(pko). To further investigate the underlying mechanisms, we created a stable NEMO knockdown mouse podocyte cell line. Again, no overt changes in morphology were observed. Translocation of NF-κB to the nucleus after stimulation with TNFα or IL-1 was sufficiently inhibited. Moreover, secretion of proinflammatory chemokines from podocytes after stimulation with TNFα or IL-1 was significantly reduced in NEMO-deficient podocytes and in glomerular samples obtained at day 7 after induction of nephrotoxic nephritis. Collectively, these results show that proinflammatory activity of NF-κB in podocytes aggravates proteinuria in experimental glomerulonephritis in mice. Based on these data, it may be speculated that immunosuppressive drugs may not only target professional immune cells but also podocytes directly to convey their beneficial effects in various types of glomerulonephritis.

  14. Podocyte biology and pathogenesis of kidney disease.

    Science.gov (United States)

    Reiser, Jochen; Sever, Sanja

    2013-01-01

    Proteinuric chronic kidney disease (CKD), once a rare affliction believed to be mainly caused by genetic mutations, has become a global pandemic that severely diminishes the quality of life for millions. Despite the changing face of CKD, treatment options and resources remain woefully antiquated and have failed to arrest or reverse the effects of kidney-related diseases. Histological and genetic data strongly implicate one promising target: the podocyte. Podocytes are terminally differentiated cells of the kidney glomerulus that are essential for the integrity of the kidney filter. Their function is primarily based on their intricate structure, which includes foot processes. Loss of these actin-driven membrane extensions is tightly connected to the presence of protein in the urine, podocyte loss, development of CKD, and ultimately renal failure.

  15. Metadherin facilitates podocyte apoptosis in diabetic nephropathy

    Science.gov (United States)

    Liu, Wen-Ting; Peng, Fen-Fen; Li, Hong-Yu; Chen, Xiao-Wen; Gong, Wang-Qiu; Chen, Wen-Jing; Chen, Yi-Hua; Li, Pei-Lin; Li, Shu-Ting; Xu, Zhao-Zhong; Long, Hai-Bo

    2016-01-01

    Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5). These levels are positively correlated with podocyte apoptosis rate. The inhibition of Mtdh expression, using small interfering RNA, but not Mtdh overexpression, was shown to inhibit HG-induced MPC5 apoptosis and p38 MAPK pathway, and Bax and cleaved caspase 3 expression. This was shown to be similar to the effects of p38 MAPK inhibitor (SB203580). Furthermore, luciferase assay results demonstrated that Mtdh represents the target of miR-30s. Transient transfection experiments, using miR-30 microRNA (miRNA) inhibitors, led to the increase in Mtdh expression and induced the apoptosis of MPC5, whereas the treatment with miR-30 miRNA mimics led to the reduction in Mtdh expression and apoptosis of HG-induced MPC5 cells in comparison with their respective controls. Our results demonstrate that Mtdh is a potent modulator of podocyte apoptosis, and that it represents the target of miR-30 miRNAs, facilitating podocyte apoptosis through the activation of HG-induced p38 MAPK-dependent pathway. PMID:27882943

  16. The Expression Profile of Complement Components in Podocytes.

    Science.gov (United States)

    Li, Xuejuan; Ding, Fangrui; Zhang, Xiaoyan; Li, Baihong; Ding, Jie

    2016-03-30

    Podocytes are critical for maintaining the glomerular filtration barrier and are injured in many renal diseases, especially proteinuric kidney diseases. Recently, reports suggested that podocytes are among the renal cells that synthesize complement components that mediate glomerular diseases. Nevertheless, the profile and extent of complement component expression in podocytes remain unclear. This study examined the expression profile of complement in podocytes under physiological conditions and in abnormal podocytes induced by multiple stimuli. In total, 23/32 complement component components were detected in podocyte by conventional RT-PCR. Both primary cultured podocytes and immortalized podocytes expressed the complement factors C1q, C1r, C2, C3, C7, MASP, CFI, DAF, CD59, C4bp, CD46, Protein S, CR2, C1qR, C3aR, C5aR, and Crry (17/32), whereas C4, CFB, CFD, C5, C6, C8, C9, MBL1, and MBL2 (9/32) complement factors were not expressed. C3, Crry, and C1q-binding protein were detected by tandem mass spectrometry. Podocyte complement gene expression was affected by several factors (puromycin aminonucleoside (PAN), angiotensin II (Ang II), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β)). Representative complement components were detected using fluorescence confocal microscopy. In conclusion, primary podocytes express various complement components at the mRNA and protein levels. The complement gene expressions were affected by several podocyte injury factors.

  17. Acute podocyte injury is not a stimulus for podocytes to migrate along the glomerular basement membrane in zebrafish larvae

    Science.gov (United States)

    Siegerist, Florian; Blumenthal, Antje; Zhou, Weibin; Endlich, Karlhans; Endlich, Nicole

    2017-01-01

    Podocytes have a unique 3D structure of major and interdigitating foot processes which is the prerequisite for renal blood filtration. Loss of podocytes leads to chronic kidney disease ending in end stage renal disease. Until now, the question if podocytes can be replaced by immigration of cells along the glomerular basement membrane (GBM) is under debate. We recently showed that in contrast to former theories, podocytes are stationary in the zebrafish pronephros and neither migrate nor change their branching pattern of major processes over 23 hours. However, it was still unclear whether podocytes are able to migrate during acute injury. To investigate this, we applied the nitroreductase/metronidazole zebrafish model of podocyte injury to in vivo two-photon microscopy. The application of metronidazole led to retractions of major processes associated with a reduced expression of podocyte-specific proteins and a formation of subpodocyte pseudocyst. Electron microscopy showed that broad areas of the capillaries became denuded. By 4D in vivo observation of single podocytes, we could show that the remaining podocytes did not walk along GBM during 24 h. This in vivo study reveals that podocytes are very stationary cells making regenerative processes by podocyte walking along the GBM very unlikely. PMID:28252672

  18. Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy.

    Science.gov (United States)

    Tagawa, Atsuko; Yasuda, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-Ichi; Koya, Daisuke; Asanuma, Katsuhiko; Kim, Eun-Hee; Haneda, Masakazu; Kajiwara, Nobuyuki; Hayashi, Kazuyuki; Ohashi, Hiroshi; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2016-03-01

    Overcoming refractory massive proteinuria remains a clinical and research issue in diabetic nephropathy. This study was designed to investigate the pathogenesis of massive proteinuria in diabetic nephropathy, with a special focus on podocyte autophagy, a system of intracellular degradation that maintains cell and organelle homeostasis, using human tissue samples and animal models. Insufficient podocyte autophagy was observed histologically in patients and rats with diabetes and massive proteinuria accompanied by podocyte loss, but not in those with no or minimal proteinuria. Podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in a high-fat diet (HFD)-induced diabetic model for inducing minimal proteinuria. Interestingly, huge damaged lysosomes were found in the podocytes of diabetic rats with massive proteinuria and HFD-fed, podocyte-specific autophagy-deficient mice. Furthermore, stimulation of cultured podocytes with sera from patients and rats with diabetes and massive proteinuria impaired autophagy, resulting in lysosome dysfunction and apoptosis. These results suggest that autophagy plays a pivotal role in maintaining lysosome homeostasis in podocytes under diabetic conditions, and that its impairment is involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy. These results may contribute to the development of a new therapeutic strategy for advanced diabetic nephropathy.

  19. Emerging role of podocyte autophagy in the progression of diabetic nephropathy.

    Science.gov (United States)

    Yasuda-Yamahara, Mako; Kume, Shinji; Tagawa, Atsuko; Maegawa, Hiroshi; Uzu, Takashi

    2015-01-01

    Glomerular podocytes are pivotal in maintaining glomerular filtration barrier function. As severe podocyte injury results in proteinuria in patients with diabetic nephropathy, determining the pathogenesis of podocyte injury may contribute to the development of new treatments. We recently showed that autophagy is involved in the pathogenesis of diabetes-related podocyte injury. Insufficient podocyte autophagy and podocyte loss are observed in diabetic patients with massive proteinuria. Podocyte loss and massive proteinuria occur in high-fat diet-induced diabetic mice with podocyte-specific autophagy deficiency, with podocytes of these mice and of diabetic rats having huge damaged lysosomes. Sera from diabetic patients and from rodents with massive proteinuria cause autophagy insufficiency, resulting in lysosome dysfunction and apoptosis of cultured podocytes. These findings suggest the importance of autophagy in maintaining lysosome homeostasis in podocytes under diabetic conditions. Impaired autophagy may be involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy.

  20. Mammalian target of rapamycin complex 2 signaling pathway regulates transient receptor potential cation channel 6 in podocytes.

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    Fangrui Ding

    Full Text Available Transient receptor potential cation channel 6 (TRPC6 is a nonselective cation channel, and abnormal expression and gain of function of TRPC6 are involved in the pathogenesis of hereditary and nonhereditary forms of renal disease. Although the molecular mechanisms underlying these diseases remain poorly understood, recent investigations revealed that many signaling pathways are involved in regulating TRPC6. We aimed to examine the effect of the mammalian target of rapamycin (mTOR complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2] signaling pathways on TRPC6 in podocytes, which are highly terminally differentiated renal epithelial cells that are critically required for the maintenance of the glomerular filtration barrier. We applied both pharmacological inhibitors of mTOR and specific siRNAs against mTOR components to explore which mTOR signaling pathway is involved in the regulation of TRPC6 in podocytes. The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2. In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed. The TRPC6 mRNA and protein expression levels were examined via real-time quantitative PCR and Western blot, respectively. Additionally, fluorescence calcium imaging was performed to evaluate the function of TRPC6 in podocytes. Rapamycin displayed no effect on the TRPC6 mRNA or protein expression levels or TRPC6-dependent calcium influx in podocytes. However, ku0063794 down-regulated the TRPC6 mRNA and protein levels and suppressed TRPC6-dependent calcium influx in podocytes. Furthermore, knockdown of raptor did not affect TRPC6 expression or function, whereas rictor knockdown suppressed TRPC6 protein expression and TRPC6-dependent calcium influx in podocytes. These findings indicate that the mTORC2 signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling pathway does not appear

  1. Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources.

    Science.gov (United States)

    Kaverina, Natalya V; Eng, Diana G; Schneider, Remington R S; Pippin, Jeffrey W; Shankland, Stuart J

    2016-06-01

    The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the podocyte markers p57, synaptopodin, and podocin were markedly decreased by 44%, and this was accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker staining, which is consistent with podocyte depletion. Staining for p57, synaptopodin, podocin, and DAPI increased at FSGS day 28 and was augmented by the ACE inhibitor enalapril, which is consistent with a partial replenishment of podocytes. In contrast, ZsGreen fluorescence did not return and remained significantly low at day 28, indicating replenishment was from a nonpodocyte origin. Despite administration of bromodeoxyuridine (BrdU) thrice weekly throughout the course of disease, BrdU staining was not detected in podocytes, which is consistent with an absence of proliferation. Although ZsGreen reporting was reduced in the tuft at FSGS day 28, labeled podocytes were detected along the Bowman's capsule in a subset of glomeruli, which is consistent with migration from the tuft. Moreover, more than half of the migrated podocytes coexpressed the parietal epithelial cell (PEC) proteins claudin-1, SSeCKS, and PAX8. These results show that although podocytes can be partially replenished following abrupt depletion, a process augmented by ACE inhibition, the source or sources are nonpodocyte in origin and are independent of proliferation. Furthermore, a subset of podocytes migrate to the Bowman's capsule and begin to coexpress PEC markers.

  2. Intravital imaging of podocyte calcium in glomerular injury and disease.

    Science.gov (United States)

    Burford, James L; Villanueva, Karie; Lam, Lisa; Riquier-Brison, Anne; Hackl, Matthias J; Pippin, Jeffrey; Shankland, Stuart J; Peti-Peterdi, János

    2014-05-01

    Intracellular calcium ([Ca²⁺]i) signaling mediates physiological and pathological processes in multiple organs, including the renal podocyte; however, in vivo podocyte [Ca²⁺]i dynamics are not fully understood. Here we developed an imaging approach that uses multiphoton microscopy (MPM) to directly visualize podocyte [Ca²⁺]i dynamics within the intact kidneys of live mice expressing a fluorescent calcium indicator only in these cells. [Ca²⁺]i was at a low steady-state level in control podocytes, while Ang II infusion caused a minor elevation. Experimental focal podocyte injury triggered a robust and sustained elevation of podocyte [Ca²⁺]i around the injury site and promoted cell-to-cell propagating podocyte [Ca²⁺]i waves along capillary loops. [Ca²⁺]i wave propagation was ameliorated by inhibitors of purinergic [Ca²⁺]i signaling as well as in animals lacking the P2Y2 purinergic receptor. Increased podocyte [Ca²⁺]i resulted in contraction of the glomerular tuft and increased capillary albumin permeability. In preclinical models of renal fibrosis and glomerulosclerosis, high podocyte [Ca²⁺]i correlated with increased cell motility. Our findings provide a visual demonstration of the in vivo importance of podocyte [Ca²⁺]i in glomerular pathology and suggest that purinergic [Ca²⁺]i signaling is a robust and key pathogenic mechanism in podocyte injury. This in vivo imaging approach will allow future detailed investigation of the molecular and cellular mechanisms of glomerular disease in the intact living kidney.

  3. Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice.

    Science.gov (United States)

    Liu, Ye; Zhao, Huichen; Qiang, Ye; Qian, Guanfang; Lu, Shengxia; Chen, Jicui; Wang, Xiangdong; Guan, Qingbo; Liu, Yuantao; Fu, Yuqin

    2015-01-01

    The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated β-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased β-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced β-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher β-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/β-catenin pathway.

  4. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  5. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  6. Loss of the Podocyte-Expressed Transcription Factor Tcf21/Pod1 Results in Podocyte Differentiation Defects and FSGS

    DEFF Research Database (Denmark)

    Maezawa, Yoshiro; Onay, Tuncer; Scott, Rizaldy P;

    2014-01-01

    Podocytes are terminally differentiated cells with an elaborate cytoskeleton and are critical components of the glomerular barrier. We identified a bHLH transcription factor, Tcf21, that is highly expressed in developing and mature podocytes. Because conventional Tcf21 knockout mice die in the pe...

  7. Activation of podocytes by mesangial-derived TNF-alpha: glomerulo-podocytic communication in IgA nephropathy.

    Science.gov (United States)

    Lai, Kar Neng; Leung, Joseph C K; Chan, Loretta Y Y; Saleem, Moin A; Mathieson, Peter W; Lai, Fernand M; Tang, Sydney C W

    2008-04-01

    We have previously documented that human mesangial cell (HMC)-derived TNF-alpha is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the role of mesangial cells in the activation of podocytes in IgAN. There was no binding of IgA from patients with IgAN to podocytes. Podocytes cultured with IgA from patients with IgAN did not induce the release of growth factors or cytokines. Furthermore, podocytes did not express mRNA of known IgA receptors. In contrast, IgA-conditioned medium (IgA-HMC medium) prepared by culturing HMC with IgA from patients with IgAN for 48 h significantly increased the gene expression and protein synthesis of TNF-alpha by podocytes with a 17-fold concentration above that of IgA-HMC medium. The upregulation of TNF-alpha expression by podocyte was only abolished by a neutralizing antibody against TNF-alpha but not by other antibodies. Exogenous TNF-alpha upregulated the synthesis of TNF-alpha by podocytes in an autocrine fashion. IgA-HMC medium prepared with IgA from patients with IgAN also significantly upregulated the expression of both TNF-alpha receptor 1 and 2 in podocytes. Our in vitro finding suggests podocytes may play a contributory role in the development of interstitial damage in IgAN by amplifying the activation of tubular epithelial cells with enhanced TNF-alpha synthesis after inflammatory changes of HMC.

  8. Generation of functional podocytes from human induced pluripotent stem cells

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    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  9. Adriamycin increases podocyte permeability: evidence and molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    李晓忠; 袁海涛; 张学光

    2003-01-01

    Objective To investigate the increased podocyte permeability by evidence of adriamycin (AD) and its molecular mechanism.Methods In this study, we explored the direct effects of AD on cultured mouse podocytes and the potential protection effects of Dexamethasome (Dex).Results After 24-hour AD (5×10-7 mol/L) treatment, albumin passage through podocyte monolayers was increased by 2.27-fold (P<0.01). AD caused a 62% decrease in Zonula Occluden -1 (ZO-1) protein (P<0.05), suggesting that AD might increase podocyte permeability by disrupting tight junctions. Dex (1×10-6 mol/L), co-administered with AD, protected podocytes from AD-induced increased albumin passage. This may be linked with an increased P-cadherin protein level to 1.93 fold of control (P<0.01).Conclusions AD has a direct, detrimental effect on podocyte permeability, probably through disrupting tight junctions; Dex could protect against AD-induced high podocyte permeability by upregulating adherent protein P-cadherin.

  10. The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes.

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    Yao, Min; Wang, Xiaomei; Wang, Xiaomeng; Zhang, Tao; Chi, Yanqing; Gao, Feng

    2015-07-01

    The Notch pathway is known to contribute to the development of glomerular disease. Angiotensin II (Ang II), an important member of the renin-angiotensin system, stimulates the accumulation of extracellular matrix components in glomerular disease; however, the exact mechanisms involved remain to be elucidated. In the present study, we aimed to investigate the effects of the Notch pathway on the synthesis of extracellular matrix components in Ang II-stimulated podocytes. Mouse podocytes were stimulated with Ang II (10-6 mol/l). The activation of the Notch pathway was inhibited by a vector carrying short hairpin RNA (shRNA) targeting Notch1 (sh-Notch1) or by γ-secretase inhibitor (GSI). The protein levels of Notch1, Notch intracellular domain 1 (NICD1), hairy and enhancer of split-1 (Hes1), matrix metalloproteinase (MMP)-2, MMP-9, transforming growth factor-β1 (TGF-β1), type IV collagen and laminin were determined by western blot analysis. The Notch1, Hes1, MMP-2, MMP-9, TGF-β1, type IV collagen and laminin mRNA levels were detected by RT-PCR. The MMP-2 and MMP-9 activity was measured using a cell active fluorescence assay kit. The levels of TGF-β1, type IV collagen and laminin were determined in the culture medium of the podocytes by enzyme-linked immunosorbent assay (ELISA). Our results revealed that Ang II upregulated Notch1, NICD1, Hes1, TGF-β1, type IV collagen and laminin expression and downregulated MMP-2 and MMP-9 expression in the cultured podocytes. The inhibition of the Notch pathway by sh-Notch1 or GSI increased MMP-2 and MMP-9 expression, decreased the TGF-β1 level and suppressed type IV collagen and laminin expression. The inhibition of the Notch pathway by sh-Notch1 or GSI also increased MMP-2 and MMP-9 activity, and decreased TGF-β1 levels, type IV collagen levels and laminin secretion. These findings indicate that the Notch pathway potentially mediates the Ang II-induced synthesis of extracellular matrix components in podocytes through the

  11. Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome?

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    Zea, Arnold H.; Stewart, Tyrus; Ascani, Jeannine; Tate, David J.; Finkel-Jimenez, Beatriz; Wilk, Anna; Reiss, Krzysztof; Smoyer, William E.; Aviles, Diego H.

    2016-01-01

    The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS) have increased IL-2 production. We hypothesized that podocytes express an IL-2 receptor (IL-2R) and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were stimulated with IL-2 in vitro, to study signaling events via the JAK/STAT pathway. The results showed that stimulation with IL-2 resulted in increased mRNA and protein expression of STAT 5a, phosphorylated STAT 5, JAK 3, and phosphorylated JAK 3. We then investigated for signs of cellular injury and the data showed that pro-apoptotic markers Bax and cFLIP were significantly increased following IL-2 exposure, whereas LC3 II was decreased. Furthermore, mitochondrial depolarization and apoptosis were both significantly increased following activation of the IL-2R. We used a paracellular permeability assay to monitor the structural integrity of a podocyte monolayer following IL-2 exposure. The results showed that podocytes exposed to IL-2 have increased albumin leakage across the monolayer. We conclude that murine podocytes express the IL-2R, and that activation through the IL-2R results in podocyte injury. PMID:27389192

  12. Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome?

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    Arnold H Zea

    Full Text Available The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS have increased IL-2 production. We hypothesized that podocytes express an IL-2 receptor (IL-2R and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were stimulated with IL-2 in vitro, to study signaling events via the JAK/STAT pathway. The results showed that stimulation with IL-2 resulted in increased mRNA and protein expression of STAT 5a, phosphorylated STAT 5, JAK 3, and phosphorylated JAK 3. We then investigated for signs of cellular injury and the data showed that pro-apoptotic markers Bax and cFLIP were significantly increased following IL-2 exposure, whereas LC3 II was decreased. Furthermore, mitochondrial depolarization and apoptosis were both significantly increased following activation of the IL-2R. We used a paracellular permeability assay to monitor the structural integrity of a podocyte monolayer following IL-2 exposure. The results showed that podocytes exposed to IL-2 have increased albumin leakage across the monolayer. We conclude that murine podocytes express the IL-2R, and that activation through the IL-2R results in podocyte injury.

  13. The directed differentiation of human iPS cells into kidney podocytes.

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    Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

    2012-01-01

    The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

  14. Expression of phospholipase A2 receptor in primary cultured podocytes derived from dog kidneys.

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    Sugahara, Go; Kamiie, Junichi; Kobayashi, Ryosuke; Mineshige, Takayuki; Shirota, Kinji

    2016-06-01

    Phospholipase A2 receptor (PLA2R) expressed in human podocytes has been highlighted as a causative autoantigen of human idiopathic membranous nephropathy. However, its expression was found to be minimal or absent in murine and rat podocytes. In this study, immunofluorescence revealed the expression of PLA2R in the glomerular podocytes in the kidney tissue sections of dogs. We then attempted to culture canine podocytes and investigate the expression of PLA2R in these cells. Glomeruli were isolated from dog kidneys and cultured to obtain podocytes using nylon mesh-based isolation method as followed for isolating rat podocytes. The cultured cells expressed PLA2R mRNA and protein in addition to other podocyte markers (synaptopodin, podocin and nephrin). These results indicate that the canine podocytes express PLA2R.

  15. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

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    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  16. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion

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    Fan, Xueping; Yang, Hongying; Kumar, Sudhir; Tumelty, Kathleen E.; Pisarek-Horowitz, Anna; Sharma, Richa; Chan, Stefanie; Tyminski, Edyta; Shamashkin, Michael; Belghasem, Mostafa; Henderson, Joel M.; Coyle, Anthony J.; Berasi, Stephen P.

    2016-01-01

    The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development and podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating podocyte function is not known. Here we report that a potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with ROBO2/SRGAP1/NMIIA in the presence of SLIT2. Immunostaining demonstrated that SRGAP1 is a podocyte protein and is colocalized with ROBO2 on the basal surface of podocytes. In addition, SLIT2 stimulation inhibits NMIIA activity, decreases focal adhesion formation, and reduces podocyte attachment to collagen. In vivo studies further showed that podocyte-specific knockout of Robo2 protects mice from hypertension-induced podocyte detachment and albuminuria and also partially rescues the podocyte-loss phenotype in Myh9 knockout mice. Thus, we have identified SLIT2/ROBO2/SRGAP1/NMIIA as a potentially novel signaling pathway in kidney podocytes, which may play a role in regulating podocyte adhesion and attachment. Our findings also suggest that SLIT2/ROBO2 signaling might be a therapeutic target for kidney diseases associated with podocyte detachment and loss. PMID:27882344

  17. Podocyte Injury and Albuminuria in Experimental Hyperuricemic Model Rats

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    Asakawa, Shinichiro; Morimoto, Chikayuki; Shiraishi, Takeshi; Nakamura, Takashi; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto

    2017-01-01

    Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries. Notably, hyperuricemic rats showed significant albuminuria, and the podocyte injury marker, desmin, was upregulated in the glomeruli. Conversely, podocin, the key component of podocyte slit diaphragm, was downregulated. Structural analysis using transmission electron microscopy confirmed podocyte injury in this model. We found that urinary 8-hydroxy-2′-deoxyguanosine levels were significantly increased and correlated with albuminuria and podocytopathy. Interestingly, although the superoxide dismutase mimetic, tempol, ameliorated the vascular changes and the hypertension, it failed to reduce albuminuria, suggesting that vascular remodeling and podocyte injury in this model are mediated through different mechanisms. In conclusion, vasculopathy and podocytopathy may distinctly contribute to the kidney injury in a hyperuricemic state. PMID:28337250

  18. Overexpression of Mafb in podocytes protects against diabetic nephropathy.

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    Morito, Naoki; Yoh, Keigyou; Ojima, Masami; Okamura, Midori; Nakamura, Megumi; Hamada, Michito; Shimohata, Homare; Moriguchi, Takashi; Yamagata, Kunihiro; Takahashi, Satoru

    2014-11-01

    We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target.

  19. Secondary Focal Segmental Glomerulosclerosis: From Podocyte Injury to Glomerulosclerosis

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    Jae Seok Kim

    2016-01-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is a common cause of proteinuria and nephrotic syndrome leading to end stage renal disease (ESRD. There are two types of FSGS, primary (idiopathic and secondary forms. Secondary FSGS shows less severe clinical features compared to those of the primary one. However, secondary FSGS has an important clinical significance because a variety of renal diseases progress to ESRD thorough the form of secondary FSGS. The defining feature of FSGS is proteinuria. The key event of FSGS is podocyte injury which is caused by multiple factors. Unanswered questions about how these factors act on podocytes to cause secondary FSGS are various and ill-defined. In this review, we provide brief overview and new insights into FSGS, podocyte injury, and their potential linkage suggesting clues to answer for treatment of the disease.

  20. HIV-1 expression induces cyclin D1 expression and pRb phosphorylation in infected podocytes: cell-cycle mechanisms contributing to the proliferative phenotype in HIV-associated nephropathy

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    Husain Mohammad

    2002-09-01

    Full Text Available Abstract Background The aberrant cell-cycle progression of HIV-1-infected kidney cells plays a major role in the pathogenesis of HIV-associated nephropathy, however the mechanisms whereby HIV-1 induces infected glomerular podocytes or infected tubular epithelium to exit quiescence are largely unknown. Here, we ask whether the expression of HIV-1 genes in infected podocytes induces cyclin D1 and phospho-pRb (Ser780 expression, hallmarks of cyclin D1-mediated G1 → S phase progression. Results We assessed cyclin D1 and phospho-pRb (Ser780 expression in two well-characterized models of HIV-associated nephropathy pathogenesis: HIV-1 infection of cultured podocytes and HIV-1 transgenic mice (Tg26. Compared to controls, cultured podocytes expressing HIV-1 genes, and podocytes and tubular epithelium from hyperplastic nephrons in Tg26 kidneys, had increased levels of phospho-pRb (Ser780, a target of active cyclin D1/cyclin-dependent kinase-4/6 known to promote G1 → S phase progression. HIV-1-infected podocytes showed markedly elevated cyclin D1 mRNA and cyclin D1 protein, the latter of which did not down-regulate during cell-cell contact or differentiation, suggesting post-transcriptional stabilization of cyclin D1 protein levels by HIV-1. The selective suppression of HIV-1 transcription by the cyclin-dependent kinase inhibitor, flavopiridol, abrogated cyclin D1 expression, underlying the requirement for HIV-1 encoded products to induce cyclin D1. Indeed, HIV-1 virus deleted of nef failed to induce cyclin D1 mRNA to the level of other single gene mutant viruses. Conclusions HIV-1 expression induces cyclin D1 and phospho-pRb (Ser780 expression in infected podocytes, suggesting that HIV-1 activates cyclin D1-dependent cell-cycle mechanisms to promote proliferation of infected renal epithelium.

  1. Effects of mycophenolate mofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan; CHEN Bing; HOU Xiang-hua; GUAN Guang-ju; LIU Gang; LIU Hai-ying; LI Xue-gang

    2007-01-01

    Background Podocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin Ⅱ receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats.Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1.Results Compared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P<0.01), and the nephrin mRNA level in DM group was significantly lower (P<0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P<0.05) and no significant differences were found among the three treatment groups (P>0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and

  2. The role of Notch signaling in kidney podocytes.

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    Asanuma, Katsuhiko; Oliva Trejo, Juan Alejandro; Tanaka, Eriko

    2017-02-01

    The Notch signaling pathway is a basic cell-to-cell communication mechanism. This pathway is activated by the interaction between Notch receptors and the ligands of adjacent cells. Once activated, Notch receptors are cleaved and the intracellular domains translocate into the nucleus, where the transcription of target genes starts. In the mammalian kidney, Notch receptors are activated during nephrogenesis. Afterwards, in the mature glomeruli, the Notch pathway becomes silent. However, many researchers have reported the activation of Notch receptors in mature podocytes under pathological conditions. In this review, we discuss the role of Notch signaling in podocytes.

  3. Autophagy is involved in mouse kidney development and podocyte differentiation regulated by Notch signalling.

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    Zhang, Chuyue; Li, Wen; Wen, Junkai; Yang, Zhuo

    2017-02-03

    Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down-regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT-treated cells, and as a result, nephrin was recovered and DAPT-induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.

  4. Planar cell polarity pathway regulates nephrin endocytosis in developing podocytes.

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    Babayeva, Sima; Rocque, Brittany; Aoudjit, Lamine; Zilber, Yulia; Li, Jane; Baldwin, Cindy; Kawachi, Hiroshi; Takano, Tomoko; Torban, Elena

    2013-08-16

    The noncanonical Wnt/planar cell polarity (PCP) pathway controls a variety of cell behaviors such as polarized protrusive cell activity, directional cell movement, and oriented cell division and is crucial for the normal development of many tissues. Mutations in the PCP genes cause malformation in multiple organs. Recently, the PCP pathway was shown to control endocytosis of PCP and non-PCP proteins necessary for cell shape remodeling and formation of specific junctional protein complexes. During formation of the renal glomerulus, the glomerular capillary becomes enveloped by highly specialized epithelial cells, podocytes, that display unique architecture and are connected via specialized cell-cell junctions (slit diaphragms) that restrict passage of protein into the urine; podocyte differentiation requires active remodeling of cytoskeleton and junctional protein complexes. We report here that in cultured human podocytes, activation of the PCP pathway significantly stimulates endocytosis of the core slit diaphragm protein, nephrin, via a clathrin/β-arrestin-dependent endocytic route. In contrast, depletion of the PCP protein Vangl2 leads to an increase of nephrin at the cell surface; loss of Vangl2 functions in Looptail mice results in disturbed glomerular maturation. We propose that the PCP pathway contributes to podocyte development by regulating nephrin turnover during junctional remodeling as the cells differentiate.

  5. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

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    Xiaoying Li

    Full Text Available Our previous in vitro studies suggested that cyclic AMP (cAMP signaling prevents adriamycin (ADR and puromycin aminonucleoside (PAN-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA or exchange protein directly activated by cAMP (Epac pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator, PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  6. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

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    Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Chuang, Peter Y; He, John Cijiang; Gu, Leyi

    2014-01-01

    Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  7. UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation.

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    Lohmann, Frithjof; Sachs, Marlies; Meyer, Tobias N; Sievert, Henning; Lindenmeyer, Maja T; Wiech, Thorsten; Cohen, Clemens D; Balabanov, Stefan; Stahl, R A K; Meyer-Schwesinger, Catherine

    2014-07-01

    Podocytes are terminally differentiated cells of the glomerular filtration barrier that react with hypertrophy in the course of injury such as in membranous nephropathy (MGN). The neuronal deubiquitinase ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed and activated in podocytes of human and rodent MGN. UCH-L1 regulates the mono-ubiquitin pool and induces accumulation of poly-ubiquitinated proteins in affected podocytes. Here, we investigated the role of UCH-L1 in podocyte hypertrophy and in the homeostasis of the hypertrophy associated "model protein" p27(Kip1). A better understanding of the basic mechanisms leading to podocyte hypertrophy is crucial for the development of specific therapies in MGN. In human and rat MGN, hypertrophic podocytes exhibited a simultaneous up-regulation of UCH-L1 and of cytoplasmic p27(Kip1) content. Functionally, inhibition of UCH-L1 activity and knockdown or inhibition of UCH-L1 attenuated podocyte hypertrophy by decreasing the total protein content in isolated glomeruli and in cultured podocytes. In contrast, UCH-L1 levels and activity increased podocyte hypertrophy and total protein content in culture, specifically of cytoplasmic p27(Kip1). UCH-L1 enhanced cytoplasmic p27(Kip1) levels by nuclear export and decreased poly-ubiquitination and proteasomal degradation of p27(Kip1). In parallel, UCH-L1 increased podocyte turnover, migration and cytoskeletal rearrangement, which are associated with known oncogenic functions of cytoplasmic p27(Kip1) in cancer. We propose that UCH-L1 induces podocyte hypertrophy in MGN by increasing the total protein content through altered degradation and accumulation of proteins such as p27(Kip1) in the cytoplasm of podocytes. Modification of both UCH-L1 activity and levels could be a new therapeutic avenue to podocyte hypertrophy in MGN.

  8. Effect of benfotiamine in podocyte damage induced by peritoneal dialysis fluid

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    Sandra eMüller-Krebs

    2015-03-01

    Full Text Available Background:In peritoneal dialysis (PD residual renal function (RRF fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE mediated toxicity by blocking hyperglycemia associated podocyte damage via the pentose phosphate pathway.Methods: A human differentiated podocyte cell line was incubated with control solution (Control, 2.5% glucose solution (Glucose and 2.5% PD fluid (PDF for 48 h either ± 50 μM benfotiamine.Podocyte damage and potential benefit of benfotiamine were analyzed using immunofluorescence, western blot analysis, and a functional migration assay. For quantitation, a semiquantitative score was used. Results:When incubating podocytes with benfotiamine, Glucose and PDF mediated damage was reduced resulting in lower expression of AGE and intact podocin and ZO-1 localization. The reorganization of the actin cytoskeleton was restored in the presence of benfotiamine as functional podocyte motility reached Control level. Decreased level of inflammation could be shown as well as reduced podocyte apoptosis.Conclusions:These data suggest that benfotiamine protects podocytes from Glucose and PDF mediated dysfunction and damage, in particular with regard to cytoskeletal reorganization, motility, inflammation and podocyte survival.

  9. Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression

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    Emese Bányai

    2014-01-01

    Full Text Available Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.

  10. Fluvastatin attenuates the down-regulation of β1 integrin expression in PAN-treated podocytes by inhibiting ROS

    Institute of Scientific and Technical Information of China (English)

    刘佳

    2013-01-01

    Objective To investigate the effect of fluvastatin(FLV) on the expression of β1 integrin in puromycin aminonucleoside(PAN)-treated podocytes and its mechanism. Methods Cultured human podocytes were divided into PAN,different concentrations of

  11. Defective glycosylation of α-dystroglycan contributes to podocyte flattening.

    Science.gov (United States)

    Kojima, Kenichiro; Nosaka, Hitonari; Kishimoto, Yuki; Nishiyama, Yuri; Fukuda, Seiichi; Shimada, Masaru; Kodaka, Kenzo; Saito, Fumiaki; Matsumura, Kiichiro; Shimizu, Teruo; Toda, Tatsushi; Takeda, Satoshi; Kawachi, Hiroshi; Uchida, Shunya

    2011-02-01

    In addition to skeletal muscle and the nervous system, α-dystroglycan is found in the podocyte basal membrane, stabilizing these cells on the glomerular basement membrane. Fukutin, named after the gene responsible for Fukuyama-type congenital muscular dystrophy, is a putative glycosyltransferase required for the post-translational modification of α-dystroglycan. Chimeric mice targeted for both alleles of fukutin develop severe muscular dystrophy; however, these mice do not have proteinuria. Despite the lack of a functional renal defect, we evaluated glomerular structure and found minor abnormalities in the chimeric mice by light microscopy. Electron microscopy revealed flattening of podocyte foot processes, the number of which was significantly lower in the chimeric compared to wild-type mice. A monoclonal antibody against the laminin-binding carbohydrate residues of α-dystroglycan did not detect α-dystroglycan glycosylation in the glomeruli by immunoblotting or immunohistochemistry. In contrast, expression of the core α-dystroglycan protein was preserved. There was no statistical difference in dystroglycan mRNA expression or in the amount of nephrin and α3-integrin protein in the chimeric compared to the wild-type mice as judged by immunohistochemistry and real-time RT-PCR. Thus, our results indicate that appropriate glycosylation of α-dystroglycan has an important role in the maintenance of podocyte architecture.

  12. Influence of dexamethasone on the expression and distribution of transient receptor potential cation channel 6 in glomerular podocytes

    Institute of Scientific and Technical Information of China (English)

    王辉阳

    2014-01-01

    Objective To observe the changes of foot processes,expression and distribution of transient receptor potential cation channel 6(TRPC6)in podocytes by puromycin aminonucleoside(PAN)and dexamethasone(DEX)intervention,then to investigate the function of TRPC6 in podocytes and its relation to proteinuria in kidney diseases.Methods Podocytes cultured in vitro were divided into three group:control group,PAN stimulation group and DEX intervention group.Mouse podocyte cell line

  13. Insulin Increases Expression of TRPC6 Channels in Podocytes by a Calcineurin-Dependent Pathway

    DEFF Research Database (Denmark)

    Xia, Shengqiang; Liu, Ying; Li, Xinming

    2016-01-01

    BACKGROUND/AIMS: Insulin signaling to podocytes is relevant for the function of the glomerulus. Now, we tested the hypothesis that insulin increases the surface expression of canonical transient receptor potential canonical type 6 (TRPC6) channels in podocytes by a calcineurin-dependent pathway. ...

  14. Podocyte expression of membrane transporters involved in puromycin aminonucleoside-mediated injury.

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    Zennaro, Cristina; Rastaldi, Maria Pia; Pascolo, Lorella; Stebel, Marco; Trevisan, Elisa; Artero, Mary; Tiribelli, Claudio; Di Maso, Vittorio; Carraro, Michele

    2013-01-01

    Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA). We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp) family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR) efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury.

  15. Fluid flow shear stress upregulates prostanoid receptor EP2 but not EP4 in murine podocytes.

    Science.gov (United States)

    Srivastava, Tarak; McCarthy, Ellen T; Sharma, Ram; Kats, Alexander; Carlton, Carol G; Alon, Uri S; Cudmore, Patricia A; El-Meanawy, Ashraf; Sharma, Mukut

    2013-01-01

    Podocytes in the glomerular filtration barrier regulate the passage of plasma proteins into urine. Capillary pressure and ultrafiltration impact the structure and function of podocytes. The mechanism of podocyte injury by fluid flow shear stress (FFSS) from hyperfiltration in chronic kidney disease (CKD) is not completely understood. Recently, we demonstrated increased synthesis of prostaglandin E2 in podocytes exposed to FFSS. Here, we determine the effect of FFSS on prostanoid receptors EP1-EP4 in cultured podocytes and in Os/+ mouse kidney, a model of hyperfiltration. Results of RT-PCR, qRT-PCR, immunoblotting and immunofluorescence studies indicate that cultured podocytes express EP1, EP2 and EP4 but not EP3. FFSS resulted in upregulated expression of only EP2 in podocytes. Kidney immunostaining showed significantly increased expression of EP2 in Os/+ mice compared with littermate controls. These novel results suggest that EP2 may be responsible for mediating podocyte injury from hyperfiltration-induced augmented FFSS in CKD.

  16. Inhibition of p53 deSUMOylation Exacerbates Puromycin Aminonucleoside-Induced Apoptosis in Podocytes

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    Lingyu Wang

    2014-11-01

    Full Text Available Apoptosis is a major cause of reduced podocyte numbers, which leads to proteinuria and/or glomerulosclerosis. Emerging evidence has indicated that deSUMOylation, a dynamic post-translational modification that reverses SUMOylation, is involved in the apoptosis of Burkitt’s lymphoma cells and cardiomyocytes; however, the impact of deSUMOylation on podocyte apoptosis remains unexplored. The p53 protein plays a major role in the pathogenesis of podocyte apoptosis, and p53 can be SUMOylated. Therefore, in the present study, we evaluated the effect of p53 deSUMOylation, which is regulated by sentrin/SUMO-specific protease 1 (SENP1, on podocyte apoptosis. Our results showed that SENP1 deficiency significantly increases puromycin aminonucleoside (PAN-induced podocyte apoptosis. Moreover, SENP1 knockdown results in the accumulation of SUMOylated p53 protein and the increased expression of the p53 target pro-apoptotic genes, BAX, Noxa and PUMA, in podocytes during PAN stimulation. Thus, SENP1 may be essential for preventing podocyte apoptosis, at least partly through regulating the functions of p53 protein via deSUMOylation. The regulation of deSUMOylation may provide a novel strategy for the treatment of glomerular disorders that involve podocyte apoptosis.

  17. The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy

    NARCIS (Netherlands)

    Andeen, Nicole K; Nguyen, Tri Q; Steegh, Floor; Hudkins, Kelly L; Najafian, Behzad; Alpers, Charles E

    2015-01-01

    Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells th

  18. Microarray analyses of glucocorticoid and vitamin D3 target genes in differentiating cultured human podocytes.

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    Xiwen Cheng

    Full Text Available Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor and vitamin D3 (ligand for vitamin D receptor protect or promote repair of podocytes from injury. In order to elucidate the mechanisms underlying hormone-mediated podocyte-protecting activity from injury, we carried out microarray gene expression studies to identify the target genes and corresponding pathways in response to these hormones during podocyte differentiation. We used immortalized human cultured podocytes (HPCs as a model system and carried out in vitro differentiation assays followed by dexamethasone (Dex or vitamin D3 (VD3 treatment. Upon the induction of differentiation, multiple functional categories including cell cycle, organelle dynamics, mitochondrion, apoptosis and cytoskeleton organization were among the most significantly affected. Interestingly, while Dex and VD3 are capable of protecting podocytes from injury, they only share limited target genes and affected pathways. Compared to VD3 treatment, Dex had a broader and greater impact on gene expression profiles. In-depth analyses of Dex altered genes indicate that Dex crosstalks with a broad spectrum of signaling pathways, of which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ pathways are predominantly altered. Together, our study provides new information and identifies several new avenues for future investigation of hormone signaling in podocytes.

  19. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

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    Li, Ruizhao, E-mail: liruizhao1979@126.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Li, E-mail: Zhanglichangde@163.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Southern Medical University, Guangzhou, Guangdong (China); Shi, Wei, E-mail: shiwei.gd@139.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Bin, E-mail: zhangbinyes@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liang, Xinling, E-mail: xinlingliang@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liu, Shuangxin, E-mail: mplsxi@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Wang, Wenjian, E-mail: wwjph@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China)

    2013-04-15

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

  20. Abnormality of Renin-Angiotensin System in Podocyte Dysfunction in Diabetic Kidney Disease%肾素-血管紧张素系统在糖尿病肾病肾脏足细胞损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    邵德翠; 陆利民

    2011-01-01

    糖尿病肾病(diabetic kidney disease,DKD)作为诱发终末期肾脏病(end-stage renal disease,ESRD)的主要原因,至今其病理机制仍不十分清楚.DKD病程中蛋白尿持续增多并伴随肾素-血管紧张素系统(renin-angiotensin system,RAS)过度激活.阻断RAS能改善蛋白尿,有良好的临床肾脏保护作用.足细胞表达RAS的各成员,作为肾小球滤过的最后屏障,其损伤与蛋白尿的发生关系密切.本文就RAS与足细胞损伤在DKD病理中作用作一简单综述.%Diabetic kidney disease (DKD) is currently the leading cause of end-stage renal disease (ESRD). DKD is stamped by proteinuria and progressive renal dysfunction. Excessive activation of RAS under hyperglycemic condition is associated with the development of DKD. Suppression of RAS markedly reduces proteinuria and retards progression of DKD in clinic. Podocyte forms the final barrier to protein in glomerular filtration. Podocyte injury leads to abnormality in glomerular filtration permeability, results in proteinuria. Various components of RAS have been identified to be expressed in podocyte. Here we reviewed the progress on RAS in regulating the function of podocyte and progress of DKD.

  1. Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress

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    Wilhelm eKriz

    2014-12-01

    Full Text Available Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE. This occurred in microdomains within the same podocyte; thus features of detachment and of reinforced attachment may simultaneously be found in the same podocyte.(1 Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e. expansions of the subpodocyte space.(2 Podocytes entered the process of FPE starting with the retraction of foot processes and the replacement of the slit diaphragm by occluding junctions thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3 Failure of sealing the slits led to gaps of varying width between retracting foot processes facilitating the outflow of the filtrate from the GBM.(4 Since those gaps are frequently overarched by broadened primary processes the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM.(5 The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment.(6 Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7 Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

  2. Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress.

    Science.gov (United States)

    Kriz, Wilhelm; Hähnel, Brunhilde; Hosser, Hiltraud; Rösener, Sigrid; Waldherr, Rüdiger

    2014-01-01

    Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE). This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment. (6) Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7) Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

  3. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    Science.gov (United States)

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  4. Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury.

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    Lingling Wu

    Full Text Available The podocyte functions as a glomerular filtration barrier. Autophagy of postmitotic cells is an important protective mechanism that is essential for maintaining the homeostasis of podocytes. Exploring an in vivo rat model of passive Heymann nephritis and an in vitro model of puromycin amino nucleotide (PAN-cultured podocytes, we examined the specific mechanisms underlying changing autophagy levels and podocyte injury. In the passive Heymann nephritis model rats, the mammalian target-of-rapamycin (mTOR levels were upregulated in injured podocytes while autophagy was inhibited. In PAN-treated podocytes, mTOR lowered the level of autophagy through the mTOR-ULK1 pathway resulting in damaged podocytes. Rapamycin treatment of these cells reduced podocyte injury by raising the levels of autophagy. These in vivo and in vitro experiments demonstrate that podocyte injury is associated with changes in autophagy levels, and that rapamycin can reduce podocyte injury by increasing autophagy levels via inhibition of the mTOR-ULK1 pathway. These results provide an important theoretical basis for future treatment of diseases involving podocyte injury.

  5. Wnt/β-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy

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    Zhang, Hongxia; Luo, Weili; Sun, Yonghong; Qiao, Yanchun; Zhang, Liying; Zhao, Zhilian; Lv, Shijun

    2016-01-01

    Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR. Kidney biopsies of DN patients and health individuals were stained by immunofluorescence (IF) method. The morphological and functional changes of podocytes were tested by F-actin staining and cell migration assay. Results demonstrated that HG induced upregulation of UCH-L1 and activation of the Wnt/β-catenin signaling pathway in podocytes. However, blocking of the Wnt pathway by dickkopf related protein 1 (DKK1) eliminated the above changes. Furthermore, IF staining confirmed that, compared with healthy individuals, the expression of UCH-L1 and β-catenin were obviously increased in kidney biopsy of DN patients. Overexpression of UCH-L1 remodeled its actin cytoskeleton, increased its cell migration and impacted its important proteins. All the findings manifested that Wnt/β-catenin/UCH-L1 may be a new potential therapy method in the treatment of DN in future. PMID:27571062

  6. Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions.

    Science.gov (United States)

    Paeng, Jisun; Chang, Jae Hyun; Lee, Sun Ha; Nam, Bo Young; Kang, Hye-Young; Kim, Seonghun; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2014-12-01

    Glycogen synthase kinase-3β (GSK-3β) is involved in the pathogenesis of various kidney diseases. This study was undertaken to examine the changes in GSK-3β activity in podocytes under diabetic conditions and to elucidate the functional role of GSK-3β in podocyte apoptosis. In vivo, 32 rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with 6-bromoindirubin-3'-oxime (BIO) for 3 months. In vitro, immortalized mouse podocytes were exposed to 5.6 mM glucose or 30 mM glucose (HG) with or without 10 μM BIO. Western blot analysis and TUNEL or Hoechst 33342 staining were performed to identify apoptosis. Urinary albumin excretion was significantly higher in DM rats, and this increase was significantly abrogated in DM rats by BIO treatment. The protein expression of Tyr216-phospho-GSK-3β was significantly increased in DM glomeruli and in cultured podocytes exposed to HG. Western blot analysis revealed that the protein expression of Bax and active fragments of caspase-3 were significantly increased, whereas phospho-Akt, β-catenin, and Bcl-2 protein expression were significantly decreased in DM glomeruli and HG-stimulated podocytes. Apoptosis, determined by TUNEL assay and Hoechst 33342 staining, was also significantly increased in podocytes under diabetic conditions. The changes in the expression of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG-stimulated podocytes were significantly ameliorated by BIO. These findings suggest that enhanced GSK-3β activity within podocytes under diabetic conditions is associated with podocyte loss in diabetic nephropathy.

  7. Defining the molecular character of the developing and adult kidney podocyte.

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    Eric W Brunskill

    Full Text Available BACKGROUND: The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. METHODOLOGY/PRINCIPAL FINDINGS: In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. CONCLUSIONS/SIGNIFICANCE: The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells.

  8. Role of Protein Kinase C (PKC in Podocytes and Development of Glomerular Damage in Diabetic Nephropathy

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    Beina eTeng

    2014-11-01

    Full Text Available The early glomerular changes in diabetes include a podocyte phenotype with loss of slit diaphragm proteins, changes in the actin cytoskeleton and foot process architecture. This review focusses on the role of the Protein Kinase C family in podocytes and points out the differential roles of classical, novel and atypical PKCs in podocytes. Some PKC-isoforms are indispensable for proper glomerular development and slit diaphragm maintenance whereas others might be harmful when activated in the diabetic milieu. Therefore some might be interesting treatment targets in the early phase of diabetes.

  9. Effects of artificial cordyceps sinensis on epithelial-mesenchymal transition in the podocytes of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    蔡芸莹

    2013-01-01

    Objective To assess the effects of artificial cordyceps sinensis(Jin shuibao) on the numbers of podocytes and epithelial-mesenchymal transition in diabetic rats. Methods Diabetes was induced by intraperitoneal injection of low dose streptozocin.

  10. Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand.

    Directory of Open Access Journals (Sweden)

    Osamu Ichii

    Full Text Available Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR, a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while more severely affected mice showed increased mesangial matrix, segmental solidification, and mesangiolysis. In normal mouse kidneys, AhR was predominantly localized to the podocyte nuclei. In mice exposed to indoxyl sulfate for 2 h, isolated glomeruli manifested increased Cyp1a1 expression, indicating AhR activation. After 8 w of indoxyl sulfate, podocytes showed foot process effacement, cytoplasmic vacuoles, and a focal granular and wrinkled pattern of podocin and synaptopodin expression. Furthermore, vimentin and AhR expression in the glomerulus was increased in the indoxyl sulfate-exposed glomeruli compared to controls. Glomerular expression of characteristic podocyte mRNAs was decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, and Wt1. In vitro, immortalized-mouse podocytes exhibited AhR nuclear translocation beginning 30 min after 1 mM indoxyl sulfate exposure, and there was increased phospho-Rac1/Cdc42 at 2 h. After exposure to indoxyl sulfate for 24 h, mouse podocytes exhibited a pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased expression of podocyte-specific genes, and decreased cell viability. In immortalized human podocytes, indoxyl sulfate treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, as well as integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. We propose that basal levels of AhR activity regulate

  11. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy

    OpenAIRE

    Weil, E. Jennifer; Lemley, Kevin V; Mason, Clinton C; Yee, Berne; Jones, Lois I.; Blouch, Kristina; Lovato, Tracy; Richardson, Meghan; Myers, Bryan D.; Nelson, Robert G.

    2012-01-01

    Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from ten kidney donors (not Americans Indians) showed almost undetectable (0.03%) podocyte detachment a...

  12. Podocyte expression of membrane transporters involved in puromycin aminonucleoside-mediated injury.

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    Cristina Zennaro

    Full Text Available Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA. We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury.

  13. Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli.

    Science.gov (United States)

    Ilatovskaya, Daria V; Palygin, Oleg; Levchenko, Vladislav; Staruschenko, Alexander

    2015-06-27

    Podocytes (renal glomerular epithelial cells) are known to regulate glomerular permeability and maintain glomerular structure; a key role for these cells in the pathogenesis of various renal diseases has been established since podocyte injury leads to proteinuria and foot process effacement. It was previously reported that various endogenous agents may cause a dramatic overload in intracellular Ca(2+) concentration in podocytes, presumably leading to albuminuria, and this likely occurs via calcium-conducting ion channels. Therefore, it appeared important to study calcium handling in the podocytes both under normal conditions and in various pathological states. However, available experimental approaches have remained somewhat limited to cultured and transfected cells. Although they represent a good basic model for such studies, they are essentially extracted from the native environment of the glomerulus. Here we describe the methodology of studying podocytes as a part of the freshly isolated whole glomerulus. This preparation retains the functional potential of the podocytes, which are still attached to the capillaries; therefore, podocytes remain in the environment that conserves the major parts of the glomeruli filtration apparatus. The present manuscript elaborates on two experimental approaches that allow 1) real-time detection of calcium concentration changes with the help of ratiometric confocal fluorescence microscopy, and 2) the recording of the single ion channels activity in the podocytes of the freshly isolated glomeruli. These methodologies utilize the advantages of the native environment of the glomerulus that enable researchers to resolve acute changes in the intracellular calcium handling in response to applications of various agents, measure basal concentration of calcium within the cells (for instance, to evaluate disease progression), and assess and manipulate calcium conductance at the level of single ion channels.

  14. Podocyte EphB4 signaling helps recovery from glomerular injury.

    Science.gov (United States)

    Wnuk, Monika; Hlushchuk, Ruslan; Janot, Mathilde; Tuffin, Gérald; Martiny-Baron, Georg; Holzer, Philipp; Imbach-Weese, Patricia; Djonov, Valentin; Huynh-Do, Uyen

    2012-06-01

    Eph receptor tyrosine kinases and their ligands (ephrins) have a pivotal role in the homeostasis of many adult organs and are widely expressed in the kidney. Glomerular diseases beginning with mesangiolysis can recover, with podocytes having a critical role in this healing process. We studied here the role of Eph signaling in glomerular disease recovery following mesangiolytic Thy1.1 nephritis in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and were upregulated during Thy1.1 nephritis, with EphB4 strongly phosphorylated around day 9. Treatment with NPV-BHG712, an inhibitor of EphB4 phosphorylation, did not cause glomerular changes in control animals. Nephritic animals treated with vehicle did not have morphological evidence of podocyte injury or loss; however, application of this inhibitor to nephritic rats induced glomerular microaneurysms, podocyte damage, and loss. Prolonged NPV-BHG712 treatment resulted in increased albuminuria and dysregulated mesangial recovery. Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive angiogenesis (an alternative to sprouting angiogenesis), indicating a previously unrecognized role of podocytes in regulating intussusceptive vessel splitting. Thus, our results identify EphB4 signaling as a pathway allowing podocytes to survive transient capillary collapse during glomerular disease.

  15. Pathogenesis of common glomerular diseases – role of the podocyte cytoskeleton

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    Kumagai T

    2012-10-01

    Full Text Available Takanori Kumagai, Flaviana Mouawad, Tomoko TakanoDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaAbstract: Glomerulus is the filtration unit of the kidney where the first step of urine formation takes place. In the glomerulus, water and small molecules including waste products of the body are filtered into the urine, while large molecules essential for body function such as albumin are retained. When this barrier function of the kidney is impaired, protein leakage into the urine (proteinuria occurs. Proteinuria is not only a hallmark of many glomerular diseases but also a prognostic marker of kidney disease progression. Visceral glomerular epithelial cells (commonly called podocytes are known to have an important role in the maintenance of glomerular barrier function. In the last decade, remarkable progress has been made in podocyte biology, mainly led by the discoveries of important proteins that work together to maintain the intricate morphology and function of podocytes. Most of these so-called podocyte proteins modulate the actin cytoskeleton either directly or indirectly. The aim of the current review is to discuss the pathogenesis of common glomerular diseases with a particular focus on the role of the actin cytoskeleton in podocytes. The diseases covered include minimal change disease, focal segmental glomerulosclerosis (idiopathic and hereditary, membranous nephropathy, hypertensive glomerulosclerosis, and diabetic nephropathy.Keywords: glomerular disease, podocyte, cytoskeleton, proteinuria

  16. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases.

    Science.gov (United States)

    Ilatovskaya, Daria V; Staruschenko, Alexander

    2015-09-01

    Podocytes (terminally differentiated epithelial cells of the glomeruli) play a key role in the maintenance of glomerular structure and permeability and in the incipiency of various renal abnormalities. Injury to podocytes is considered a major contributor to the development of kidney disease as their loss causes proteinuria and progressive glomerulosclerosis. The physiological function of podocytes is critically dependent on proper intracellular calcium handling; excessive calcium influx in these cells may result in the effacement of foot processes, apoptosis, and subsequent glomeruli damage. One of the key proteins responsible for calcium flux in the podocytes is transient receptor potential cation channel, subfamily C, member 6 (TRPC6); a gain-of-function mutation in TRPC6 has been associated with the onset of the familial forms of focal segmental glomerulosclerosis (FSGS). Recent data also revealed a critical role of this channel in the onset of diabetic nephropathy. Therefore, major efforts of the research community have been recently dedicated to unraveling the TRPC6-dependent effects in the initiation of podocyte injury. This mini-review focuses on the TRPC6 channel in podocytes and colligates recent data in an attempt to shed some light on the mechanisms underlying the pathogenesis of TRPC6-mediated glomeruli damage and its potential role as a therapeutic target for the treatment of chronic kidney diseases.

  17. Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes.

    Science.gov (United States)

    Tolvanen, Tuomas A; Dash, Surjya Narayan; Polianskyte-Prause, Zydrune; Dumont, Vincent; Lehtonen, Sanna

    2015-12-15

    The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin-dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes.

  18. Angiopoietin-Like-4, a Potential Target of Tacrolimus, Predicts Earlier Podocyte Injury in Minimal Change Disease.

    Science.gov (United States)

    Li, Jian-Si; Chen, Xiao; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Diao, Tian-Tian; He, Yi-Xin; Liu, Fang; Wei, Qiu-Ju; Zhang, Qing-Fang; Li, Bing

    2015-01-01

    Podocyte injury plays central roles in proteinuria and kidney dysfunction, therefore, identifying specific biomarker to evaluate earlier podocyte injury is highly desirable. Podocyte-secreted angiopoietin-like-4 (Angptl4) mediates proteinuria in different types of podocytopathy. In the present study, we established an experimental minimal change disease (MCD) rat model, induced by adriamycin (ADR) and resulted in definite podocyte injury, to identify the dynamic changes in Angptl4 expression. We also investigated the direct effects of tacrolimus on Angptl4 and podocyte repair. We determined that the glomerular Angptl4 expression was rapidly upregulated and reached a peak earlier than desmin, an injured podocyte marker, in the ADR rats. Furthermore, this upregulation occurred prior to heavy proteinuria and was accompanied by increased urinary Angptl4. We observed that the Angptl4 upregulation occurred only when podocyte was mainly damaged since we didn't observe little Angptl4 upregulation in MsPGN patients. In addition, we observed the glomerular Angptl4 mainly located in injured podocytes rather than normal podocytes. Moreover, we found that tacrolimus treatment significantly promoted podocyte repair and reduced glomerular and urinary Angptl4 expression at an earlier stage with a significant serum Angptl4 upregulation. And similar results were confirmed in MCD patients. In conclusion, this study represents the first investigation to demonstrate that Angptl4 can predict podocyte injury at earlier stages in MCD and the identification of earlier podocyte injury biomarkers could facilitate the prompt diagnosis and treatment of patients with podocytopathy, as well as determination of the prognosis and treatment efficacy in these diseases.

  19. Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl-2 and p53 pathways.

    Science.gov (United States)

    Gao, Feng; Yao, Min; Shi, Yonghong; Hao, Jun; Ren, Yunzhuo; Liu, Qingjuan; Wang, Xiaomeng; Duan, Huijun

    2013-05-01

    Recent studies have shown that Notch pathway plays a key role in the pathogenesis of diabetic nephropathy (DN), however, the exact mechanisms remain elusive. Here we demonstrated that high glucose (HG) upregulated Notch pathway in podocytes accompanied with the alteration of Bcl-2 and p53 pathways, subsequently leading to podocytes apoptosis. Inhibition of Notch pathway by chemical inhibitor or specific short hairpin RNA (shRNA) vector in podocytes prevented Bcl-2- and p53-dependent cell apoptosis. These findings suggest that Notch pathway mediates HG-induced podocytes apoptosis via Bcl-2 and p53 pathways.

  20. Combined blockade of angiotensin II and prorenin receptors ameliorates podocytic apoptosis induced by IgA-activated mesangial cells.

    Science.gov (United States)

    Leung, Joseph C K; Chan, Loretta Y Y; Saleem, M A; Mathieson, P W; Tang, Sydney C W; Lai, Kar Neng

    2015-07-01

    Glomerulo-podocytic communication plays an important role in the podocytic injury in IgA nephropathy (IgAN). In this study, we examine the role of podocytic angiotensin II receptor subtype 1 (AT1R) and prorenin receptor (PRR) in podocytic apoptosis in IgAN. Polymeric IgA (pIgA) was isolated from patients with IgAN and healthy controls. Conditioned media were prepared from growth arrested human mesangial cells (HMC) incubated with pIgA from patients with IgAN (IgA-HMC media) or healthy controls (Ctl-HMC media). A human podocyte cell line was used as a model to examine the regulation of the expression of AT1R, PRR, TNF-α and CTGF by IgA-HMC media. Podocytic nephrin expression, annexin V binding and caspase 3 activity were used as the functional readout of podocytic apoptosis. IgA-HMC media had no effect on AngII release by podocytes. IgA-HMC media significantly up-regulated the expression of AT1R and PRR, down-regulated nephrin expression and induced apoptosis in podocytes. Mono-blockade of AT1R, PRR, TNF-α or CTGF partially reduced podocytic apoptosis. IgA-HMC media activated NFκB, notch1 and HEY1 expression by podocytes and dual blockade of AT1R with PRR, or anti-TNF-α with anti-CTGF, effectively rescued the podocytic apoptosis induced by IgA-HMC media. Our data suggests that pIgA-activated HMC up-regulates the expression of AT1R and PRR expression by podocytes and the associated activation of NFκB and notch signalling pathways play an essential role in the podocytic apoptosis induced by glomerulo-podocytic communication in IgAN. Simultaneously targeting the AT1R and PRR could be a potential therapeutic option to reduce the podocytic injury in IgAN.

  1. Astragaloside IV, a novel antioxidant, prevents glucose-induced podocyte apoptosis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Dingkun Gui

    Full Text Available Glucose-induced reactive oxygen species (ROS production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN. Here, we tested the hypothesis that Astragaloside IV(AS-IV exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg(-1·d(-1 for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation.

  2. Assessment of Urinary Osteopontin in Association with Podocyte for Early Predication of Nephropathy in Diabetic Patients

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    Abdulrahman L. Al-Malki

    2014-01-01

    Full Text Available Objectives. Microalbuminuria has been clinically used for noninvasive evaluation of renal dysfunctions. However, it is a nonspecific marker of diabetic nephropathy (DN. Methods. This study was conducted from March 2012 to April 2013 at Biochemistry Unit, King Fahd Medical Research Center (KFMRC. In this study, urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM were determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria, and nephritic syndrome compared with healthy subjects. Results. It was found that in diabetic microalbuminuria patients have a highly significant increase in urinary IgM, osteopontin, and podocyte levels as compared to other groups. Nephrotic syndrome patients showed a moderate significant elevation of these parameters compared to control subjects. At a given specificity of 97%, podocytes yielded the highest sensitivity of all markers, 95.5%. The sensitivity was considerably higher compared to IgM and osteopontin. Podocyte number was positively correlated with serum IgM and osteopontin (r=0.63 and 0.56, respectively. Its cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of DN. Conclusion. Monitoring urinary podocyte may provide a noninvasive tool that is a sensitive, accurate, and specific biomarker of glomerular injury and can be used in combination with osteopontin and IgM to more reliably detect and monitor prognosis.

  3. Small Molecule Membrane Transporters in the Mammalian Podocyte: A Pathogenic and Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Cristina Zennaro

    2014-11-01

    Full Text Available The intriguingly complex glomerular podocyte has been a recent object of intense study. Researchers have sought to understand its role in the pathogenesis of common proteinuric diseases such as minimal change disease and focal segmental glomerular sclerosis. In particular, considerable effort has been directed towards the anatomic and functional barrier to macromolecular filtration provided by the secondary foot processes, but little attention has been paid to the potential of podocytes to handle plasma proteins beyond the specialization of the slit diaphragm. Renal membrane transporters in the proximal tubule have been extensively studied for decades, particularly in relation to drug metabolism and elimination. Recently, uptake and efflux transporters for small organic molecules have also been found in the glomerular podocyte, and we and others have found that these transporters can engage not only common pharmaceuticals but also injurious endogenous and exogenous agents. We have also found that the activity of podocyte transporters can be manipulated to inhibit pathogen uptake and efflux. It is conceivable that podocyte transporters may play a role in disease pathogenesis and may be a target for future drug development.

  4. High glucose induces podocyte injury via enhanced (prorenin receptor-Wnt-β-catenin-snail signaling pathway.

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    Caixia Li

    Full Text Available (Prorenin receptor (PRR expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-β-catenin-snail signaling pathway. Mouse podocytes were cultured in normal (5 mM or high (25 mM D-glucose for 3 days. Compared to normal glucose, high glucose significantly decreased mRNA and protein expressions of podocin and nephrin, and increased mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail, respectively. Confocal microscopy studies showed significant reduction in expression and reorganization of podocyte cytoskeleton protein, F-actin, in response to high glucose. Transwell functional permeability studies demonstrated significant increase in albumin flux through podocytes monolayer with high glucose. Cells treated with high glucose and PRR siRNA demonstrated significantly attenuated mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail; enhanced expressions of podocin mRNA and protein, improved expression and reorganization of F-actin, and reduced transwell albumin flux. We conclude that high glucose induces podocyte injury via PRR-Wnt-β-catenin-snail signaling pathway.

  5. High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Lee, Marlene; Xia, Shengqiang

    2014-01-01

    Transient receptor potential canonical (TRPC) channels type 6 play an important role in the function of human podocytes. Diabetic nephropathy is characterized by altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxid...

  6. Tracking the stochastic fate of cells of the renin lineage after podocyte depletion using multicolor reporters and intravital imaging.

    Science.gov (United States)

    Kaverina, Natalya V; Kadoya, Hiroyuki; Eng, Diana G; Rusiniak, Michael E; Sequeira-Lopez, Maria Luisa S; Gomez, R Ariel; Pippin, Jeffrey W; Gross, Kenneth W; Peti-Peterdi, Janos; Shankland, Stuart J

    2017-01-01

    Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS). Because cells of the renin lineage (CoRL) serve as adult podocyte and parietal epithelial cell (PEC) progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP) were restricted to cells in the juxtaglomerular compartment (JGC) at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57) and two glomerular parietal epithelial cell (PEC) proteins (claudin-1, PAX8). To monitor the precise migration of a subset of CoRL over a 2w period following podocyte depletion, intravital multiphoton microscopy was used. Our findings demonstrate direct visual support for the migration of single CoRL from the JGC to the parietal Bowman's capsule, early proximal tubule, mesangium and glomerular tuft. In summary, these results suggest that following podocyte depletion, multi-clonal CoRL migrate to the glomerulus and replace podocyte and PECs in experimental FSGS.

  7. The Protective Effects of Erythropoietin on Rat Glomerular Podocytes in Culture are Modulated by Extracellular Matrix Proteins

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    Jan Krtil

    2014-03-01

    Full Text Available Background/Aims: Podocytes are typically cultured on collagen I; however, collagen I is absent from healthy glomerular basement membranes. Erythropoietin (EPO is thought to protect podocytes in vivo. Here, we studied how various types of extracellular matrix (ECM proteins and EPO affect podocytes in culture. Methods: Primary rat podocytes were replated on collagen I, collagen IV, whole ECM extract, laminin, or bare plastic. Cellular adhesion (8 hours after plating, proliferation (5 days, 10 % serum, and resistance to serum deprivation (3 days, 0.5 % serum were assessed. BrdU incorporation and expression of podocyte-specific markers were employed as measures of cellular proliferation and differentiation, respectively. qPCR was used to verify expression of EPO receptor in cultured podocytes. Results: Cellular adhesion was similar on all ECM proteins and unaffected by EPO. Proliferation was accelerated by laminin and the ECM extract, but the final cell density was similar on all ECM surfaces. Collagen IV supported the serum-deprived cells better than the other ECM proteins. EPO (2-20 ng/ml improved viability of serum-deprived podocytes on collagen I, collagen IV, and ECM, but not on laminin or bare plastic. The cells expressed mRNA for EPO receptor. Conclusion: The physiological ECM proteins are more supportive of primary podocytic cultures compared with collagen I. The protective effects of EPO during serum deprivation are modulated by the cultivation surface.

  8. Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis.

    LENUS (Irish Health Repository)

    Akilesh, Shreeram

    2011-10-01

    The specialized epithelial cell of the kidney, the podocyte, has a complex actin-based cytoskeleton. Dynamic regulation of this cytoskeleton is required for efficient barrier function of the kidney. Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because disruption of components of the cytoskeleton results in podocyte damage, cell loss, and a prototypic injury response called focal segmental glomerulosclerosis (FSGS). Searching for actin regulatory proteins that are expressed in podocytes, we identified a RhoA-activated Rac1 GTPase-activating protein (Rac1-GAP), Arhgap24, that was upregulated in podocytes as they differentiated, both in vitro and in vivo. Increased levels of active Rac1 and Cdc42 were measured in Arhgap24 knockdown experiments, which influenced podocyte cell shape and membrane dynamics. Consistent with a role for Arhgap24 in normal podocyte functioning in vivo, sequencing of the ARHGAP24 gene in patients with FSGS identified a mutation that impaired its Rac1-GAP activity and was associated with disease in a family with FSGS. Thus, Arhgap24 contributes to the careful balancing of RhoA and Rac1 signaling in podocytes, the disruption of which may lead to kidney disease.

  9. Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells.

    Science.gov (United States)

    Puelles, Victor G; Douglas-Denton, Rebecca N; Cullen-McEwen, Luise A; Li, Jinhua; Hughson, Michael D; Hoy, Wendy E; Kerr, Peter G; Bertram, John F

    2015-09-01

    Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335-502), 389 NECs (IQR=265-498), and 146 PECs (IQR=111-206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431-746; Pnumber of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology.

  10. Podocytes in urine, a novel biomarker of preeclampsia?

    Science.gov (United States)

    Konieczny, Andrzej; Ryba, Monika; Wartacz, Justyna; Czyżewska-Buczyńska, Agnieszka; Hruby, Zbigniew; Witkiewicz, Wojciech

    2013-01-01

    Preeclampsia is a disorder occurring during pregnancy typically after 20 weeks of gestation. It affects both mother and unborn baby in at least 5-8% of all pregnancies. It is a rapidly progressive condition characterized by high blood pressure and the presence of protein in the urine. The symptoms, such as swelling, sudden weight gain, headaches and vision disturbances, are important signs of preeclampsia which can lead to maternal and infant illness and death. It is estimated that this disorder is responsible for 76,000 maternal and 500,000 infant deaths each year. The main hypothesis explaining the development of preeclampsia is the theory of placental hypoxia/ischemia. An imbalance between vascular endothelial growth factor (VEGF) and soluble fms-like tyro-sine kinase-1 (sFlt-1) seems to play a crucial role. Currently there is no way to predict, with certainty whether preeclampsia will develop during a given pregnancy. There is a need for a diagnostic tool which can help to identify and monitor women at risk. There is growing evidence that podocyturia - urinary excretion of viable podocytes may be a useful predictor of preeclampsia. This paper presents facts supporting such a hypothesis.

  11. Intraglomerular crosstalk elaborately regulates podocyte injury and repair in diabetic patients: insights from a 3D multiscale modeling study

    Science.gov (United States)

    Tan, Hua; Yi, Hualin; Zhao, Weiling; Ma, Jian-Xing; Zhang, Yuanyuan; Zhou, Xiaobo

    2016-01-01

    Podocytes are mainly involved in the regulation of glomerular filtration rate (GFR) under physiological condition. Podocyte depletion is a crucial pathological alteration in diabetic nephropathy (DN) and results in a broad spectrum of clinical syndromes such as protein urine and renal insufficiency. Recent studies indicate that depleted podocytes can be regenerated via differentiation of the parietal epithelial cells (PECs), which serve as the local progenitors of podocytes. However, the podocyte regeneration process is regulated by a complicated mechanism of cell-cell interactions and cytokine stimulations, which has been studied in a piecemeal manner rather than systematically. To address this gap, we developed a high-resolution multi-scale multi-agent mathematical model in 3D, mimicking the in situ glomerulus anatomical structure and micro-environment, to simulate the podocyte regeneration process under various cytokine perturbations in healthy and diabetic conditions. Our model showed that, treatment with pigment epithelium derived factor (PEDF) or insulin-like growth factor-1 (IGF-1) alone merely ameliorated the glomerulus injury, while co-treatment with both cytokines replenished the damaged podocyte population gradually. In addition, our model suggested that continuous administration of PEDF instead of a bolus injection sustained the regeneration process of podocytes. Part of the results has been validated by our in vivo experiments. These results indicated that amelioration of the glomerular stress by PEDF and promotion of PEC differentiation by IGF-1 are equivalently critical for podocyte regeneration. Our 3D multi-scale model represents a powerful tool for understanding the signaling regulation and guiding the design of cytokine therapies in promoting podocyte regeneration. PMID:27683034

  12. sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor.

    Science.gov (United States)

    Pan, Yangbin; Wan, Jianxin; Liu, Yipeng; Yang, Qian; Liang, Wei; Singhal, Pravin C; Saleem, Moin A; Ding, Guohua

    2014-01-01

    The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with the PLA2R, sPLA2 IB induced podocyte apoptosis in a time- and concentration-dependent manner. sPLA2 IB-induced podocyte PLA2R upregulation was not only associated with increased ERK1/2 and cPLA2α phosphorylation but also displayed enhanced apoptosis. In contrast, PLA2R-silenced human podocytes displayed attenuated apoptosis. sPLA2 IB enhanced podocyte arachidonic acid (AA) content in a dose-dependent manner. These data indicate that sPLA2 IB has the potential to induce human podocyte apoptosis via binding to the PLA2R. The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2α and through increasing the podocyte AA content.

  13. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

    Science.gov (United States)

    Imasawa, Toshiyuki; Obre, Emilie; Bellance, Nadège; Lavie, Julie; Imasawa, Tomoko; Rigothier, Claire; Delmas, Yahsou; Combe, Christian; Lacombe, Didier; Benard, Giovanni; Claverol, Stéphane; Bonneu, Marc; Rossignol, Rodrigue

    2017-01-01

    Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy

  14. Effect of Cordyceps sinensis and Tripterygium wilfordii polyglycosidium on podocytes in rats with diabetic nephropathy

    Science.gov (United States)

    HAO, LI; PAN, MENG-SHU; ZHENG, YUN; WANG, RUI-FENG

    2014-01-01

    The aim of the present study was to investigate the effects of Cordyceps sinensis (CS) and Tripterygium wilfordii polyglycosidium (TWP) on podocytes in rats with diabetic nephropathy (DN). DN rat models were established and divided randomly into normal control (group A), DN (group B), CS (group C), TWP (group D) and CS and TWP groups (group E). After 12 weeks, levels of 24-h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), white blood cells, blood glucose (GLU), aspartate aminotransferase, alanine aminotransferase and kidney weight (KW)/body weight (BW) were determined. Renal pathological changes were evaluated using hematoxylin and eosin staining, whereas the structural changes in the podocytes were observed under a transmission electron microscope. The expression levels of nephrin and podocin were evaluated using immunofluorescence staining. Compared with group A, the SCR and BUN levels in group B were higher (P<0.05) and the GLU, KW/BW and the 24-h urine protein were markedly higher (P<0.01). Moreover, incidences of glomerular disorders, chronic tubulointerstitial damage and glomerular podocyte lesions in groups B, C, D and E were observed, compared with group A. The high cortical expression of nephrin and podocin protein decreased. Compared with group B, the KW/BW and 24-h urinary protein level in groups C, D and E were lower (P<0.01). The glomeruli, tubules and podocytes exhibited pathomorphological improvements and the nephrin and podocin protein expression levels were higher in the nephridial tissue. A decrease in KW/BW and the 24-h urinary protein level, as well as improvements in glomerular disorder, chronic tubulointerstitial damage and glomerular podocyte lesions, were observed in groups C, D and E. Therefore, the results demonstrated that CS and TWP exhibited a protective effect on the podocytes of rats with DN. Moreover, CS combined with TWP increased this protective effect. PMID:24926327

  15. DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis.

    Science.gov (United States)

    Cai, Minchao; Zhou, Tong; Wang, Xuan; Shang, Minghua; Zhang, Yueyue; Luo, Maocai; Xu, Chundi; Yuan, Weijie

    2016-03-01

    Podocytes, the main target of immune complex, participate actively in the development of glomerular injury as immune cells. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune molecular that has an immune recognition function, and is involved in mediation of cell adhesion and immunoregulation. Here we explored the expression of DC-SIGN on podocytes and its role in immune and inflammatory responses in lupus nephritis (LN). Expression of DC-SIGN and immunoglobulin (Ig)G1 was observed in glomeruli of LN patients. DC-SIGN was co-expressed with nephrin on podocytes. Accompanied by increased proteinuria of LN mice, DC-SIGN and IgG1 expressions were observed in the glomeruli from 20 weeks, and the renal function deteriorated up to 24 weeks. Mice with anti-DC-SIGN antibody showed reduced proteinuria and remission of renal function. After the podocytes were stimulated by serum of LN mice in vitro, the expression of DC-SIGN, major histocompatibility complex (MHC) class II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced and the interferon (IFN)-γ/interleukin (IL)-4 ratio increased. However, anti-DC-SIGN antibody treatment reversed these events. These results suggested that podocytes in LN can exert DC-like function through their expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissues. However, blockage of DC-SIGN can inhibit immune functions of podocytes, which may have preventive and therapeutic effects.

  16. Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι.

    Science.gov (United States)

    Worthmann, Kirstin; Leitges, Michael; Teng, Beina; Sestu, Marcello; Tossidou, Irini; Samson, Thomas; Haller, Hermann; Huber, Tobias B; Schiffer, Mario

    2013-12-01

    The atypical protein kinase C (aPKC) isotypes PKCλ/ι and PKCζ are both expressed in podocytes; however, little is known about differences in their function. Previous studies in mice have demonstrated that podocyte-specific loss of PKCλ/ι leads to a severe glomerular phenotype, whereas mice deficient in PKCζ develop no renal phenotype. We analyzed various effects caused by PKCλ/ι and PKCζ deficiency in cultured murine podocytes. In contrast to PKCζ-deficient podocytes, PKCλ/ι-deficient podocytes exhibited a severe actin cytoskeletal phenotype, reduced cell size, decreased number of focal adhesions, and increased activation of small GTPases. Comparative microarray analysis revealed that the guanine nucleotide exchange factor Def-6 was specifically up-regulated in PKCλ/ι-deficient podocytes. In vivo Def-6 expression is significantly increased in podocytes of PKCλ/ι-deficient mice. Cultured PKCλ/ι-deficient podocytes exhibited an enhanced membrane association of Def-6, indicating enhanced activation. Overexpression of aPKCλ/ι in PKCλ/ι-deficient podocytes could reduce the membrane-associated expression of Def-6 and rescue the actin phenotype. In the present study, PKCλ/ι was identified as an important factor for actin cytoskeletal regulation in podocytes and Def-6 as a specific downstream target of PKCλ/ι that regulates the activity of small GTPases and subsequently the actin cytoskeleton of podocytes.

  17. High glucose increases Cdk5 activity in podocytes via transforming growth factor-β1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yue [Department of Diagnostics, Hebei Medical University, Shijiazhuang 050017 (China); Li, Hongbo; Hao, Jun [Department of Pathology, Hebei Medical University, Shijiazhuang 050017 (China); Zhou, Yi [Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000 (China); Liu, Wei, E-mail: lwei929@126.com [Department of Pathology, Hebei Medical University, Shijiazhuang 050017 (China)

    2014-08-15

    Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in the development and progression of diabetic nephropathy (DN). Cyclin-dependent kinase 5 (Cdk5), who is an atypical but essential member of the Cdk family of proline-directed serine/threonine kinases, has been shown as a key regulator of podocyte differentiation, proliferation and morphology. Our previous studies demonstrated that the expression of Cdk5 was significantly increased in podocytes of diabetic rats, and was closely related with podocyte injury of DN. However, the mechanisms of how expression and activity of Cdk5 are regulated under the high glucose environment have not yet been fully elucidated. In this study, we showed that high glucose up-regulated the expression of Cdk5 and its co-activator p35 with a concomitant increase in Cdk5 kinase activity in conditionally immortalized mouse podocytes in vitro. When exposed to 30 mM glucose, transforming growth factor-β1 (TGF-β1) was activated. Most importantly, we found that SB431542, the Tgfbr1 inhibitor, significantly decreased the expression of Cdk5 and p35 and Cdk5 kinase activity in high glucose-treated podocytes. Moreover, high glucose increased the expression of early growth response-1 (Egr-1) via TGF-β1-ERK1/2 pathway in podocytes and inhibition of Egr-1 by siRNA decreased p35 expression and Cdk5 kinase activity. Furthermore, inhibition of Cdk5 kinase activity effectively alleviated podocyte apoptosis induced by high glucose or TGF-β1. Thus, the TGF-β1-ERK1/2-Egr-1 signaling pathway may regulate the p35 expression and Cdk5 kinase activity in high glucose-treated podocytes, which contributes to podocyte injury of DN. - Highlights: • HG up-regulated the expression of Cdk5 and p35, and Cdk5 activity in podocytes. • HG activated TGF-β1 pathway and SB431542 inhibited Cdk5 expression and activity. • HG increased the expression of Egr-1 via TGF-β1-ERK1/2 pathway. • Inhibition of Egr-1

  18. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Il; Park, Soo Hyun, E-mail: parksh@chonnam.ac.kr

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  19. Expression and significance of Pdlim2 in the glomerular podocyte of hyperlipidemic rate

    Institute of Scientific and Technical Information of China (English)

    彭兰

    2014-01-01

    Objective To investigate the expression changes and significance of Pdlim2 in the glomerular podocyte of hyperlipidemic rats.Methods Forty-five individuals of SD rats were divided randomly into 3 groups(n=15 in each group).The control group was fed with normal diet.The high fat group was fed with high fat diet.The simvastatin

  20. Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

    DEFF Research Database (Denmark)

    Blattner, Simone M; Hodgin, Jeffrey B; Nishio, Masashi

    2013-01-01

    Podocytes are highly specialized epithelial cells with complex actin cytoskeletal architecture crucial for maintenance of the glomerular filtration barrier. The mammalian Rho GTPases Rac1 and Cdc42 are molecular switches that control many cellular processes, but are best known for their roles in ...

  1. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Haiyan Xu

    2017-01-01

    Full Text Available This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

  2. Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway.

    Science.gov (United States)

    Gao, Feng; Yao, Min; Cao, Yanping; Liu, Shuxia; Liu, Qingjuan; Duan, Huijun

    2016-05-01

    The Notch pathway is known to be linked to diabetic nephropathy (DN); however, its underlying mechanism was poorly understood. In the present study, we examined the effect of Valsartan, an angiotensin II type 1 receptor antagonist, on the Notch pathway and podocyte loss in DN. Diabetes was induced in mice by an intraperitoneal injection of streptozotocin and and this was followed by treatment with Valsartan. Levels of blood glucose, kidney weight and body weight, as well as proteinuria were measured. Samples of the kidneys were also histologically examined. The relative levels of Jagged1, Notch1, Notch intracellular domain 1 (NICD1), Hes family BHLH transcription factor 1 (Hes1) and Hes-related family BHLH transcription factor with YRPW motif 1 expression (Hey1) in the glomeruli were determined by immunohistochemical analysis, western blot analysis and RT-qPCR. The B-Cell CLL/Lymphoma 2 (Bcl-2) and p53 pathways were examined by western blot analysis. Apoptosis and detachment of podocytes from the glomerular basement membrane were examined using a TUNEL assay, flow cytometric analysis and ELISA. The number of podocytes was quantified by measuring Wilms tumor-1 (WT-1) staining. We noted that the expression of Jagged1, Notch1, NICD1, Hes1 and Hey1 was increased in a time-dependent manner in the glomeruli of mice with streptozotocin (STZ)-induced diabetes. Moreover, in diabetic mice, Valsartan significantly reduced kidney weight and proteinuria, and mitigated the pathogenic processes in the kidneys. Valsartan also inhibited the activation of Notch, Bcl-2 and p53 pathways and ameliorated podocyte loss in the glomeruli of mice with STZ-induced diabetes. Taken together, these findings indicated that Valsartan exerted a beneficial effect on reducing podocyte loss, which is associated with inhibition of Notch pathway activation in the glomeruli of diabetic mice.

  3. Calcium Uptake via Mitochondrial Uniporter Contributes to Palmitic Acid-induced Apoptosis in Mouse Podocytes.

    Science.gov (United States)

    Yuan, Zeting; Cao, Aili; Liu, Hua; Guo, Henjiang; Zang, Yingjun; Wang, Yi; Wang, Yunman; Wang, Hao; Yin, Peihao; Peng, Wen

    2017-02-09

    Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner. Palmitic acid induces apoptosis in podocytes through up-regulation of cytosolic and mitochondrial Ca(2+) , mitochondrial membrane potential (MMP), cytochrome c release and depletion of endoplasmic reticulum (ER) Ca(2+) , The intracellular calcium chelator, 1,2-bis (2-aminophenoxy) ethane-N,N,N, N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM), partially prevented this up-regulation whereas 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-triphosphate receptor (IP3R) inhibitor; dantrolene, a ryanodine receptor (RyR) inhibitor; and 4,4'-diisothiocyanatostibene-2,2'-disulfonic acid (DIDS), an anion exchange inhibitor, had no effect. Interestingly, ruthenium red and Ru360, both inhibitors of the mitochondrial Ca(2+) uniporter (MCU), blocked palmitic acid-induced mitochondrial Ca(2+) elevation, cytochrome c release from mitochondria to cytosol, and apoptosis. siRNA to MCU markedly reduced curcumin-induced apoptosis. These data indicate that Ca(2+) uptake via mitochondrial uniporter contributes to palmitic acid-induced apoptosis in mouse podocytes. This article is protected by copyright. All rights reserved.

  4. The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm.

    Science.gov (United States)

    Weavers, Helen; Prieto-Sánchez, Silvia; Grawe, Ferdinand; Garcia-López, Amparo; Artero, Ruben; Wilsch-Bräuninger, Michaela; Ruiz-Gómez, Mar; Skaer, Helen; Denholm, Barry

    2009-01-15

    The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation, 'nephron-like' features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity to the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialized filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly (Drosophila melanogaster) orthologues of the major constituents of the slit diaphragm, including nephrin, NEPH1 (also known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find that the nephrocyte diaphragm is completely lost in flies lacking the orthologues of nephrin or NEPH1-a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in human congenital nephrotic syndrome of the Finnish type, NPHS1) or NEPH1. These changes markedly impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting that the two cell types are evolutionarily related, and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases.

  5. The Structural and Functional Organization of the Podocyte Filtration Slits Is Regulated by Tjp1/ZO-1

    OpenAIRE

    Itoh, Masahiko; Nakadate, Kazuhiko; Horibata, Yasuhiro; Matsusaka, Taiji; Xu, Jianliang; Hunziker, Walter; Sugimoto, Hiroyuki

    2014-01-01

    Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecu...

  6. Pharmacological characterization of the P2 receptors profile in the podocytes of the freshly isolated rat glomeruli.

    Science.gov (United States)

    Ilatovskaya, Daria V; Palygin, Oleg; Levchenko, Vladislav; Staruschenko, Alexander

    2013-11-15

    Calcium flux in the podocytes is critical for normal and pathophysiological regulation of these types of cells, and excessive calcium signaling results in podocytes damage and improper glomeruli function. Purinergic activation of P2 receptors is a powerful and rapid signaling process; however, the exact physiological identity of P2 receptors subtypes in podocytes remains essentially unknown. The goal of this study was to determine the P2 receptor profile in podocytes of the intact Sprague-Dawley rat glomeruli using available pharmacological tools. Glomeruli were isolated by differential sieving and loaded with Fluo-4/Fura Red cell permeable calcium indicators, and the purinergic response in the podocytes was analyzed with ratiometric confocal fluorescence measurements. Various P2 receptors activators were tested and compared with the effect of ATP, specifically, UDP, MRS 2365, bzATP, αβ-methylene, 2-meSADP, MRS 4062, and MRS 2768, were analyzed. Antagonists (MRS 2500, 5-BDBD, A438079, and NF 449) were tested when 10 μM ATP was applied as the EC50 for ATP activation of the calcium influx in the podocytes was determined to be 10.7 ± 1.5 μM. Several agonists including MRS 2365 and 2-meSADP caused calcium flux. Importantly, only the P2Y1-specific antagonist MRS 2500 (1 nM) precluded the effects of ATP concentrations of the physiological range. Immunohistochemical analysis confirmed that P2Y1 receptors are highly expressed in the podocytes. We conclude that P2Y1 receptor signaling is the predominant P2Y purinergic pathway in the glomeruli podocytes and P2Y1 might be involved in the pathogenesis of glomerular injury and could be a target for treatment of kidney diseases.

  7. The chloride intracellular channel 5A stimulates podocyte Rac1, protecting against hypertension-induced glomerular injury.

    Science.gov (United States)

    Tavasoli, Mahtab; Li, Laiji; Al-Momany, Abass; Zhu, Lin-Fu; Adam, Benjamin A; Wang, Zhixiang; Ballermann, Barbara J

    2016-04-01

    Glomerular capillary hypertension elicits podocyte remodeling and is a risk factor for the progression of glomerular disease. Ezrin, which links podocalyxin to actin in podocytes, is activated through the chloride intracellular channel 5A (CLIC5A)-dependent phosphatidylinositol 4,5 bisphosphate (PI[4,5]P2) accumulation. Because Rac1 is involved in podocyte actin remodeling and can promote PI[4,5]P2 production we determined whether CLIC5A-dependent PI[4,5]P2 generation and ezrin activation are mediated by Rac1. In COS7 cells, CLIC5A expression stimulated Rac1 but not Cdc42 or Rho activity. CLIC5A also stimulated phosphorylation of the Rac1 effector Pak1 in COS7 cells and in cultured mouse podocytes. CLIC5A-induced PI[4,5]P2 accumulation and Pak1 and ezrin phosphorylation were all Rac1 dependent. In DOCA/Salt hypertension, phosphorylated Pak increased in podocytes of wild-type, but not CLIC5-deficient mice. In DOCA/salt hypertensive mice lacking CLIC5, glomerular capillary microaneurysms were more frequent and albuminuria was greater than in wild-type mice. Thus, augmented hypertension-induced glomerular capillary injury in mice lacking CLIC5 results from abrogation of Rac1-dependent Pak and ezrin activation, perhaps reducing the tensile strength of the podocyte actin cytoskeleton.

  8. Deficiency of the planar cell polarity protein Vangl2 in podocytes affects glomerular morphogenesis and increases susceptibility to injury.

    Science.gov (United States)

    Rocque, Brittany L; Babayeva, Sima; Li, Jane; Leung, Vicki; Nezvitsky, Lisa; Cybulsky, Andrey V; Gros, Philippe; Torban, Elena

    2015-03-01

    The planar cell polarity (PCP) signaling pathway is crucial for tissue morphogenesis. Van Gogh-like protein 2 (Vangl2) is central in the PCP pathway; in mice, Vangl2 loss is embryonically lethal because of neural tube defects, and mutations in Vangl2 are associated with human neural tube defects. In the kidney, PCP signaling may be important for tubular morphogenesis and organization of glomerular epithelial cells (podocytes) along the glomerular basement membrane. Podocyte cell protrusions (foot processes) are critical for glomerular permselectivity; loss of foot process architecture results in proteinuria and FSGS. Previously, we showed a profound effect of PCP signaling on podocyte shape, actin rearrangement, cell motility, and nephrin endocytosis. To test our hypothesis that the PCP pathway is involved in glomerular development and function and circumvent lethality of the ubiquitous Vangl2 mutation in the Looptail mouse, we generated a mouse model with a podocyte-specific ablation of the Vangl2 gene. We report here that podocyte-specific deletion of Vangl2 leads to glomerular maturation defects in fetal kidneys. In adult mice, we detected significantly smaller glomeruli, but it did not affect glomerular permselectivity in aging animals. However, in the context of glomerular injury induced by injection of antiglomerular basement membrane antibody, deletion of Vangl2 resulted in exacerbation of injury and accelerated progression to chronic segmental and global glomerular sclerosis. Our results indicate that Vangl2 function in podocytes is important for glomerular development and protects against glomerular injury in adult animals.

  9. Endoplasmic reticulum stress is involved in podocyte apoptosis induced by saturated fatty acid palmitate

    Institute of Scientific and Technical Information of China (English)

    TAO Jian-ling; WEN Yu-bing; SHI Bing-yang; ZHANG Hong; RUAN Xiong-zhong; LI Hang; LI Xue-mei; DONG Wen-ji; LI Xue-wang

    2012-01-01

    Background Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy.Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis,contributing to the onset of diabetes.We hypothesized that palmitate could induce podocyte apoptosis via ER stress,which initiates or aggravates proteinuria in diabetic nephropathy.Methods Podocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain.The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78),indicators of ER-associated apoptosis C/EBP homologous protein (CHOP),and Bcl-2 were assayed by Western blotting and real-time PCR.GRP78 and synaptopodin were co-localized by immunofluorescence stain.Results Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours,13 hours,and 15 hours compared with 0 hour,P <0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control,P <0.001).Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP,and decreased that of Bcl-2.Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP,and decreased that of Bcl-2 compared to control (P <0.001),with the maximum concentration being 0.75 mmol/L.Palmitate 0.5 mmol/L loading for 3 hours,8 hours,and 12 hours significantly increased mRNA of GRP78 and CHOP,and decreased that of Bcl-2 compared to 0 hour (P <0.001),with the maximum effect at 3 hours.Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.Conclusion Palmitate could induce podocyte apoptosis via ER stress,suggesting podocyte apoptosis and consequent proteinuria caused

  10. Cyclin-dependent kinase 5 contributes to endoplasmic reticulum stress induced podocyte apoptosis via promoting MEKK1 phosphorylation at Ser280 in diabetic nephropathy.

    Science.gov (United States)

    Zhang, Yue; Gao, Xiang; Chen, Shuanggang; Zhao, Min; Chen, Jing; Liu, Rui; Cheng, Shengyang; Qi, Mengyuan; Wang, Shuo; Liu, Wei

    2017-02-01

    Endoplasmic reticulum (ER) stress has been reported to be associated with podocyte apoptosis in diabetic nephropathy, but the mechanism of ER signaling in podocyte apoptosis hasn't been fully understood. Our previous studies have demonstrated that Cyclin-dependent kinase 5 (Cdk5) was associated with podocyte apoptosis in diabetic nephropathy. The present study was designed to examine whether and how Cdk5 activity plays a role in ER stress induced podocyte apoptosis in diabetic nephropathy. The results showed that along with induction of Cdk5 and apoptosis, GRP78 and its two sensors as well as CHOP and cleaved caspase-12 were induced in high glucose treated podocytes. These responses were attenuated by treated salubrinal. The ER stress inducer, tunicamycin, also up-regulated the kinase activity and protein expression of Cdk5 in podocytes accompanied with the increasing of GRP78. On the other hand, Cdk5 phosphorylates MEKK1 at Ser280 in tunicamycin treated podocytes, and together, they increase the JNK phosphorylation. Moreover, disruption of this pathway can decrease the podocyte apoptosis induced by tunicamycin. Therefore, our study proved that Cdk5 may play an important role in ER stress induced podocyte apoptosis through MEKK1/JNK pathway in diabetic nephropathy.

  11. 20-Hydroxyeicosatetraenoic acid (20-HETE Modulates Canonical Transient Receptor Potential-6 (TRPC6 Channels in Podocytes

    Directory of Open Access Journals (Sweden)

    Hila Roshanravan

    2016-08-01

    Full Text Available The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF. This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La3+, and which are attenuated after siRNA knockdown of TRPC6 subunits. Similar currents are evoked by a membrane-permeable analog of diacylgycerol (OAG, but OAG does not occlude responses to maximally-activating concentrations of 20-HETE (20 μM. Exposure to 20-HETE also increased steady-state surface abundance of TRPC6 subunits in podocytes as assessed by cell-surface biotinylation assays, and increased cytosolic concentrations of reactive oxygen species (ROS. TRPC6 activation by 20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable superoxide dismutase mimic. Activation of TRPC6 by 20-HETE was also blocked when whole-cell recording pipettes contained GDP-βS, indicating a role for either small or heterotrimeric G proteins in the transduction cascade. Responses to 20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes NADPH oxidase complexes with TRPC6 subunits in this cell type. In summary, modulation of ionic channels in podocytes may contribute to glomerular actions of 20-HETE.

  12. Persistent urinary podocyte loss following preeclampsia may reflect subclinical renal injury.

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    Wendy M White

    Full Text Available OBJECTIVE: Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells, is associated with proteinuria in preeclampsia. We postulated that urinary podocyte loss may persist after preeclamptic pregnancies, thus resulting in renal injury. This may lead to future chronic renal injury. In addition, we compared the postpartum levels of the angiogenic factors, which previously have been associated with preeclampsia, between normotensive versus preeclamptic pregnancies. STUDY DESIGN: The diagnosis of preeclampsia was confirmed using standard clinical criteria. Random blood and urine samples were obtained within 24 hours prior to delivery and 5 to 8 weeks postpartum. Urine sediments were cultured for 24 hours to select for viable cells and staining for podocin was used to identify podocytes. Serum samples were analyzed for the levels of angiogenic markers using ELISA (enzyme-linked immunosorbent assay methodology. RESULTS: At delivery, preeclamptic patients (n = 10 had significantly higher proteinuria (p = 0.006 and podocyturia (p<0.001 than normotensive pregnant patients (n = 18. Postpartum proteinuria was similar between these two groups (p = 0.37, while podocyturia was present in 3 of 10 women with preeclampsia and in none of the normotensive controls (p = 0.037. Angiogenic marker levels, including placental growth factor, soluble vascular endothelial growth factor receptor fms-like tyrosine kinase receptor-1 and endoglin, were not significantly different between women with preeclampsia and women with a normotensive pregnancy, either at delivery or postpartum. CONCLUSION: Persistent urinary podocyte loss after preeclamptic pregnancies may constitute a marker of ongoing, subclinical renal injury.

  13. Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes.

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    Maezawa, Yoshiro; Takemoto, Minoru; Yokote, Koutaro

    2015-01-01

    Diabetic nephropathy is the major cause of end-stage renal failure throughout the world in both developed and developing countries. Diabetes affects all cell types of the kidney, including endothelial cells, tubulointerstitial cells, podocytes and mesangial cells. During the past decade, the importance of podocyte injury in the formation and progression of diabetic nephropathy has been established and emphasized. However, recent findings provide additional perspectives on pathogenesis of diabetic nephropathy. Glomerular endothelial damage is already present in the normoalbuminuric stage of the disease when podocyte injury starts. Genetic targeting of mice that cause endothelial injury leads to accelerated diabetic nephropathy. Tubulointerstitial damage, previously considered to be a secondary effect of glomerular protein leakage, was shown to have a primary significance in the progression of diabetic nephropathy. Emerging evidence suggests that the glomerular filtration barrier and tubulointerstitial compartment is a composite, dynamic entity where any injury of one cell type spreads to other cell types, and leads to the dysfunction of the whole apparatus. Accumulation of novel knowledge would provide a better understanding of the pathogenesis of diabetic nephropathy, and might lead to a development of a new therapeutic strategy for the disease.

  14. Reactive oxygen species are involved in insulin-dependent regulation of autophagy in primary rat podocytes.

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    Audzeyenka, Irena; Rogacka, Dorota; Piwkowska, Agnieszka; Rychlowski, Michal; Bierla, Joanna Beata; Czarnowska, Elżbieta; Angielski, Stefan; Jankowski, Maciej

    2016-06-01

    Autophagy is an intracellular defense mechanism responsible for the turnover of damaged or non-functional cellular constituents. This process provides cells with energy and essential compounds under unfavorable environmental conditions-such as oxidative stress and hyperglycemia, which are both observed in diabetes. The most common diabetes complication is diabetic nephropathy (DN), which can lead to renal failure. This condition often includes impaired podocyte function. Here we investigated autophagic activity in rat podocytes cultured with a high insulin concentration (300nM). Autophagy was activated after 60min of insulin stimulation. Moreover, this effect was abolished following pharmacological (apocynin) or genetic (siRNA) inhibition of NAD(P)H oxidase activity, indicating that insulin-dependent autophagy stimulation involved reactive oxygen species (ROS). We also observed a continuous and time-dependent increase of podocyte albumin permeability in response to insulin, and this process was slightly improved by autophagy inhibition following short-term insulin exposure. Our results suggest that insulin may be a factor affecting the development of diabetic nephropathy.

  15. [New insight in pathogenesis of podocyte disfunction in minimal change disease].

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    Liu, Shanshan; Chen, Jianghua

    2016-03-01

    Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.

  16. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

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    Jiang, Lulu; Hindmarch, Charles C. T.; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W.; Welsh, Gavin I.

    2016-01-01

    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes. PMID:27774996

  17. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy.

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    Jin Ma

    Full Text Available Toll like receptor (TLR 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ diabetes. Subsequently, we demonstrated that TLR4-/- mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA and expression of fibrogenic genes (TGF-β and fibronectin were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.

  18. Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

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    Yanbo Liu

    2015-07-01

    Full Text Available Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

  19. Decreased miR-26a expression correlates with the progression of podocyte injury in autoimmune glomerulonephritis.

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    Osamu Ichii

    Full Text Available MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6.MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6.MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6.MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6.MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.

  20. Estrogen receptor alpha expression in podocytes mediates protection against apoptosis in-vitro and in-vivo.

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    Sebastian Kummer

    Full Text Available CONTEXT/OBJECTIVE: Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes. METHODS: Expression of estrogen receptor alpha (ERα was examined in podocytes in vitro and in vivo. Receptor localization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycin aminonucleoside (PAN, apoptosis induction, estradiol, or both in combination. Apoptotic cells were detected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM. Estradiol-induced phosphorylation of ERK1/2 and p38 MAPK was examined by Western blot. Glomeruli of ERα knock-out mice and wild-type controls were analysed by histomorphometry and immunohistochemistry. RESULTS: ERα was consistently expressed in human and murine podocytes. Estradiol stimulated ERα protein expression, reduced PAN-induced apoptosis in vitro by 26.5±24.6% or 56.6±5.9% (flow cytometry or Hoechst-staining, respectively; both p<0.05, and restored PAN-induced mitochondrial membrane potential depolarization. Estradiol enhanced ERK1/2 phosphorylation. In ERα knockout mice, podocyte number was reduced compared to controls (female/male: 80/86 vs. 132/135 podocytes per glomerulus, p<0.05. Podocyte volume was enhanced in ERα knockout mice (female/male: 429/371 µm(3 vs. 264/223 µm(3 in controls, p<0.05. Tgfβ1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage. CONCLUSIONS: Podocytes express ERα, whose activation leads to a significant protection against experimentally induced apoptosis. Possible underlying

  1. Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure

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    Xueping Fan

    2012-07-01

    Full Text Available Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.

  2. Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro

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    Zhimei Lv

    2016-01-01

    Full Text Available Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.

  3. Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes

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    Huang, Chunfa, E-mail: chunfa.huang@case.edu [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Bruggeman, Leslie A. [Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Hydo, Lindsey M. [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Miller, R. Tyler [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States)

    2012-06-10

    The glomerular capillary wall, composed of endothelial cells, the glomerular basement membrane and the podocytes, is continually subjected to hemodynamic force arising from tractional stress due to blood pressure and shear stress due to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as hyperfiltration is associated with glomerular injury and progressive renal disease, and the conversion of mechanical stimuli to chemical signals in the regulation of the process is poorly understood in podocytes. By examining DNA fragmentation, apoptotic nuclear changes and cytochrome c release, we found that shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes exposed to shear stress also stimulated c-Src phosphorylation, phospholipase D (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the antibodies against c-Src, PLD{sub 1}, and PLD{sub 2} to perform reciprocal co-immunoprecipitations and in vitro PLD activity assay, our data indicated that c-Src interacted with and activated PLD{sub 1} but not PLD{sub 2}. The inhibition of shear stress-induced c-Src phosphorylation by PP{sub 2} (a specific inhibitor of c-Src kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte hypertrophy and apoptosis.

  4. Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2.

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    Sieber, Jonas; Weins, Astrid; Kampe, Kapil; Gruber, Stefan; Lindenmeyer, Maja T; Cohen, Clemens D; Orellana, Jana M; Mundel, Peter; Jehle, Andreas W

    2013-09-01

    Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of TO901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. TO901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death.

  5. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.

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    Paola Krall

    Full Text Available Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6 gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.

  6. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

    NARCIS (Netherlands)

    Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

    2016-01-01

    Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen m

  7. MiR-124 is Related to Podocytic Adhesive Capacity Damage in STZ-Induced Uninephrectomized Diabetic Rats

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    Dong Li

    2013-10-01

    Full Text Available Background: Diabetic nephropathy (DN is the leading cause of end-stage renal disease. Podocyte plays a key role in the pathogenesis of DN. Adhesive capacity damage of podocytes is characteristic in DN. Emerging evidence suggests that microRNAs (miRNAs play crucial roles in controlling many cell adhesion molecules thus contribute to normal cell adhesion. The roles of miRNA in podocytic adhesive capacity damage in diabetic conditions remain largely unknown. Methods: Diabetes was induced by tail vein injection of streptozotocin (STZ into uninephrectomized male Wistar rats. Comparative miRNA expression array and real-time PCR analyses were conducted in sham group at week 0 (W0, n = 3 and STZ-induced uninephrectomized diabetic rats at week 1 (W1, n = 3 and week 2 (W2, n = 3 to demonstrate the greatest increased miRNA in renal cortex. At week 2, STZ-induced uninephrectomized diabetic rats were treated with vehicle (Group U, n = 9, chemically modified antisense RNA oligonucleotide (ASO complementary to the mature miR-124 (Group O, n = 8, miR-124 mismatch control sequence (Group M, n = 8. Urine specimens were obtained for measurement of urine albumin concentration and urinary podocyte specific protein (nephrin and podocin quantitation. Expression of integrin α3 were detected by immunohistochemistry and western blotting. Results: MiRNAs are differentially regulated in renal cortex of STZ-induced uninephrectomized diabetic rats relative to sham rats. Among the up-regulated miRNAs, miR-124 expression demonstrated the greatest increase. Administration of miR-124 ASO for two weeks significantly reduced urinary podocytic nephrin, podocin and albumin excretion and up-regulate integrin α3 expression. Conclusion: MiR-124 is related to podocytic adhesive capacity damage and may be implicated in the pathogenesis of DN.

  8. Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

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    Piwkowska, Agnieszka, E-mail: apiwkowska@cmdik.pan.pl [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Rogacka, Dorota; Angielski, Stefan [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Jankowski, Maciej [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Medical University of Gdansk, Department of Therapy Monitoring and Pharmacogenetics (Poland)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} activates the insulin signaling pathway and glucose uptake in podocytes. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} induces time-dependent changes in AMPK phosphorylation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} enhances insulin signaling pathways via AMPK activation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H{sub 2}O{sub 2}) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H{sub 2}O{sub 2}-induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H{sub 2}O{sub 2} (100 {mu}M) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min ({Delta} 183%, P < 0.05), 3 min ({Delta} 414%, P < 0.05), and 10 min ({Delta} 35%, P < 0.05), respectively. Immunostaining cells with an Akt-specific antibody showed increased intensity at the plasma membrane after treatment with H{sub 2}O{sub 2}>. Furthermore, H{sub 2}O{sub 2} inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; {Delta} -32%, P < 0.05) and stimulated phosphorylation of the AMP-dependent kinase alpha subunit (AMPK{alpha}; 78% at 3 min and 244% at 10 min). The stimulation of AMPK was abolished with an AMPK inhibitor, Compound C (100 {mu}M, 2 h). Moreover, Compound C significantly reduced the effect of H{sub 2}O{sub 2} on IR phosphorylation by about 40% (from 2.07 {+-} 0.28 to 1.28 {+-} 0.12, P < 0.05). In addition, H{sub 2}O{sub 2} increased glucose uptake in podocytes

  9. Urokinase, urokinase receptor, and plasminogen activator inhibitor-1 expression on podocytes in immunoglobulin A glomerulonephritis

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    Lee, Ji-Hye; Oh, Mee-Hye; Park, Jae-seok; Na, Gyoung-Jae; Gil, Hye-Wook; Yang, Jong-Oh; Lee, Eun-Young; Hong, Sae-Yong

    2014-01-01

    Background/Aims The purpose of this study was to investigate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 on podocytes in immunoglobulin A (IgA) glomerulonephritis (GN). Methods Renal biopsy specimens from 52 IgA GN patients were deparaffinized and subjected to immunohistochemical staining for uPA, PAI-1, and uPAR. The biopsies were classified into three groups according to the expression of uPA and uPAR on podo...

  10. MicroRNA-498 Inhibition Enhances the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Podocyte-Like Cells.

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    Zhang, Lina; Li, Kanghua; Yan, Xi; Liang, Xiaolei; Wang, Shihua; Han, Qin; Zhao, Robert Chunhua

    2015-12-15

    Podocyte depletion is a key event in the progression of end-stage kidney disease (ESKD) resulting in nephrotic proteinuria and renal failure, but the treatment options are limited to dialysis and renal transplantation. So there is an urgent need for renal regenerative therapies. Generation of podocytes from human stem cells is regarded as a promising therapeutic strategy to repair or regenerate the damaged kidneys; however, the reliable induction system remains a challenge. In this study, we established a two-stage induction protocol for podocyte generation from human adipose-derived mesenchymal stem cells (hAD-MSCs). We initially established a condition that induces hAD-MSCs toward intermediate mesoderm cells with activin A and high concentration of retinoic acid (RA). Subsequently, by using the combination of activin A and low concentration of RA and BMP7, we generated podocyte-like cells expressing multiple podocyte-specific markers and able to integrate into a developing nephron of embryonic kidney explant culture and ameliorate proteinuria and kidney injure in adriamycin-treated mice. Furthermore, we identified that miRNA-498 inhibitor has potential to improve the differentiation of hAD-MSCs into podocyte-like cells and established a robust induction protocol. Thereby, our study advocated an efficient method for the induction of kidney podocyte-like (iPod) cells from hAD-MSCs and provided an ideal candidate for regenerative therapies of the kidney.

  11. PODOCYTE-SPECIFIC OVEREXPRESSION OF SIRT-1 INCREASES NEPHRIN IN OBESE MICE FED A HIGH-FAT DIET

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    Han Byoung-Geun

    2012-06-01

    Taken together the results, deterioration of the kidney disease caused by obesity and hyperglycemia could be prevented by increasing the level of the nephrin expression through SIRT-1 activation. SIRT-1 may have the ability to protect the podocyte from injuries caused by obesity and hyperglycemia.

  12. An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms.

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    Tomonori Hirose

    Full Text Available Glomerular visceral epithelial cells (podocytes contain interdigitated processes that form specialized intercellular junctions, termed slit diaphragms, which provide a selective filtration barrier in the renal glomerulus. Analyses of disease-causing mutations in familial nephrotic syndromes and targeted mutagenesis in mice have revealed critical roles of several proteins in the assembly of slit diaphragms. The nephrin-podocin complex is the main constituent of slit diaphragms. However, the molecular mechanisms regulating these proteins to maintain the slit diaphragms are still largely unknown. Here, we demonstrate that the PAR3-atypical protein kinase C (aPKC-PAR6beta cell polarity proteins co-localize to the slit diaphragms with nephrin. Furthermore, selective depletion of aPKClambda in mouse podocytes results in the disassembly of slit diaphragms, a disturbance in apico-basal cell polarity, and focal segmental glomerulosclerosis (FSGS. The aPKC-PAR3 complex associates with the nephrin-podocin complex in podocytes through direct interaction between PAR3 and nephrin, and the kinase activity of aPKC is required for the appropriate distribution of nephrin and podocin in podocytes. These observations not only establish a critical function of the polarity proteins in the maintenance of slit diaphragms, but also imply their potential involvement in renal failure in FSGS.

  13. The effects and mechanism of tripterygium wilfordii Hook Fcombination with irbesartan on urinary podocyte excretion in diabetic nephropathy patients

    Institute of Scientific and Technical Information of China (English)

    马瑞霞

    2013-01-01

    Objective To investigate the effects of the combination of tripterygium wilfordii Hook F (TwHF) and irbesartan on urinary podocytes in diabetic kidney disease (DKD) patients,and to discuss the mechanism of protective effect of TwHF on DKD.Methods A total of 45

  14. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

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    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  15. Susceptibility of podocytes to palmitic acid is regulated by fatty acid oxidation and inversely depends on acetyl-CoA carboxylases 1 and 2.

    Science.gov (United States)

    Kampe, Kapil; Sieber, Jonas; Orellana, Jana Marina; Mundel, Peter; Jehle, Andreas Werner

    2014-02-15

    Type 2 diabetes is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are susceptible to saturated FFAs, which induce endoplasmic reticulum (ER) stress and podocyte death. Genome-wide association studies indicate that expression of acetyl-CoA carboxylase (ACC) 2, a key enzyme of fatty acid oxidation (FAO), is associated with proteinuria in type 2 diabetes. Here, we show that stimulation of FAO by aminoimidazole-4-carboxamide-1β-D-ribofuranoside (AICAR) or by adiponectin, activators of the low-energy sensor AMP-activated protein kinase (AMPK), protects from palmitic acid-induced podocyte death. Conversely, inhibition of carnitine palmitoyltransferase (CPT-1), the rate-limiting enzyme of FAO and downstream target of AMPK, augments palmitic acid toxicity and impedes the protective AICAR effect. Etomoxir blocked the AICAR-induced FAO measured with tritium-labeled palmitic acid. The beneficial effect of AICAR was associated with a reduction of ER stress, and it was markedly reduced in ACC-1/-2 double-silenced podocytes. In conclusion, the stimulation of FAO by modulating the AMPK-ACC-CPT-1 pathway may be part of a protective mechanism against saturated FFAs that drive podocyte death. Further studies are needed to investigate the potentially novel therapeutic implications of these findings.

  16. The Protective Effects of Curcumin on Obesity-Related Glomerulopathy Are Associated with Inhibition of Wnt/β-Catenin Signaling Activation in Podocytes

    Directory of Open Access Journals (Sweden)

    Bao-li Liu

    2015-01-01

    Full Text Available The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injury in vitro and obesity-related glomerulopathy (ORG in vivo. Cellular experiments in vitro showed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experiments in vivo showed that curcumin significantly reduced the body weight, Lee’s index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experiments in vitro and in vivo both displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, and β-catenin and upregulate the phosphorylation level of β-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/β-catenin signaling activation in podocytes.

  17. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  18. Minimal change disease in graft versus host disease: a podocyte response to the graft?

    Science.gov (United States)

    Huskey, Janna; Rivard, Chris; Myint, Han; Lucia, Scott; Smith, Maxwell; Shimada, Michiko; Ishimoto, Takuji; Araya, Carlos; Garin, Eduardo H; Johnson, Richard J

    2013-12-01

    Nephrotic syndrome is a rare complication of hematopoietic cell transplantation. It has been suggested that nephrotic syndrome may represent a limited form of graft-versus-host disease although the pathological link between these two entities remains unclear. In this paper, we report a case of a 61-year-old female who underwent nonmyeloablative allogenic stem cell transplantation for T-cell prolymphocytic leukemia and subsequently developed biopsy proven minimal change disease shortly after cessation of her immunosuppression therapy. Urinary CD80 was markedly elevated during active disease and disappeared following corticosteroid-induced remission. We hypothesize that alloreactive donor T cells target the kidney and induce podocyte expression of CD80 that results in proteinuria from limited 'graft versus host' disease.

  19. Correlation study of podocyte injur y and kidney function in patients with acute kidney injur y

    Directory of Open Access Journals (Sweden)

    You-Gang Feng

    2016-11-01

    Full Text Available Objective: To investigate the correlation between the podocyte injury indexes in urine such as nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2-associated protein (CD2AP and the kidney function in patients with acute kidney injury (AKI. Methods: A total of 120 severe postsurgical patients treated in the Intensive Care Unit of our hospital from May 2012 to October 2015 were selected and divided into AKI group (n = 38 and non-AKI group (n = 82 according to the diagnostic criteria of AKI. After admission to the Intensive Care Unit for 24 h, their blood samples were collected to detect the contents of serum creatinine (Scr, serum urea (SUrea, b2-microglobulin (b2-MG and cystatin C (Cys-C, and urine samples were collected to detect the contents of kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, Netrin-1, nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP. Results: For patients in AKI group, the contents of Scr, SUrea, b2-MG and Cys-C in their blood samples and the contents of KIM-1, L-FABP, Netrin-1, nephrin, desmin, Pcadherin, podocin, podocalyxin and CD2AP in their urine samples were both significantly higher than those in non-AKI group. The contents of nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP in urine samples and contents of Scr, SUrea, b2-MG, Cys-C and neutrophil gelatinase associated lipocalin in blood samples were positively correlated with the contents of KIM-1, L-FABP, and Netrin-1 in urine. Conclusions: Contents of podocyte injury molecules in urine of patients with acute kidney injury such as nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP raised remarkably and the changes were consistent with the changes of kidney function indexes in the blood and urine samples.

  20. Active vitamin D prevents podocyte injury via regulation of macrophage M1 and M2 phenotype in diabetic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    郭银凤

    2014-01-01

    Objective To investigate the effect of active vitamin D(VD)on macrophage M1 and M2 phenotype and its role in protecting podocyte impairment in diabetic nephropathy(DN).Methods Diabetes mellitus rats were established by intraperitoneal injection with streptozocin.Rats were randomly divided into four groups:normal-1(NC-1,n=8),normal-2(NC-2,n=8,normal rats treated with calcitriol 0.1μg·kg-1·d-1by gavages),

  1. Disruption of low-density lipoprotein receptor pathway induced by inflammation contributes to podocyte injury in diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    张洋

    2014-01-01

    Objective To investigate the effects of low density lipoprotein receptor(LDLr)pathway on podocyte injury in diabetic nephropathy(DN)under inflammatory stress.Methods Male db/db mice and db/m mice were randomly divided into four groups(8 mice in each group):db/m group(control),casein injected db/m group(db/m+casein),db/db group(db/db),and casein injected

  2. Effects of Tumor Necrosis Factor-α on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Choon Hee Chung

    2015-02-01

    Full Text Available Background/Aims: Tumor necrosis factor (TNF-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1 by enzyme-linked immunosorbent assay (ELISA. TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-κB, phosphatidylinositol 3-kinase (PI3K or Akt. In vivo studies were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-α and MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and correlated with albuminuria. Results: Podocytes treated with TNF-α showed a robust increase (∼900% in the secretion of MCP-1, induced in a dose- and time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, which was inducible by TNF-α ligand, but did not depend on TNFR1. TNF-α then proceeded via the NF-κB and the PI3K/Akt systems, based on the effectiveness of the inhibitors of those pathways. For in vivo relevance to diabetic kidney disease, TNF-α and MCP-1 levels were found to be elevated in the urine of db/db mice but not in the plasma. Conclusion: TNF-α potently stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF-κB and PI3K/Akt pathways. Both TNF-α and MCP-1 levels were increased in the urine of diabetic db/db mice, correlating with the severity of diabetic albuminuria.

  3. Administration of Recombinant Soluble Urokinase Receptor Per Se Is Not Sufficient to Induce Podocyte Alterations and Proteinuria in Mice

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Placier, Sandrine; Ploug, Michael

    2014-01-01

    Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increa...... in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria....

  4. Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2 diabetic nephropathy of db/db mice.

    Science.gov (United States)

    Zhou, Guangyu; Wang, Yanqiu; He, Ping; Li, Detian

    2013-01-01

    The present study was conducted to investigate the effects of probucol on the progression of diabetic nephropathy and the underlying mechanism in type 2 diabetic db/db mice. Eight weeks db/db mice were treated with regular diet or probucol-containing diet (1%) for 12 weeks. Non-diabetic db/m mice were used as controls. We examined body weight, blood glucose, and urinary albumin. At 20 weeks, experimental mice were sacrificed and their blood and kidneys were extracted for the analysis of blood chemistry, kidney histology, oxidative stress marker, and podocyte marker. As a result, 24 h urinary albumin excretions were reduced after probucol treatment. There were improvements of extracellular matrix accumulation and fibronectin and collagen IV deposition in glomeruli in the probucol-treated db/db mice. The reduction of nephrin and the loss of podocytes were effectively prevented by probucol in db/db mice. Furthermore, probucol significantly decreased the production of thiobarbituric acid-reactive substances (TBARS), an index of reactive oxygen species (ROS) generation and down-regulated the expression of Nox2. Taken together, our findings support that probucol may have the potential to protect against type 2 diabetic nephropathy via amelioration of podocyte injury and reduction of oxidative stress.

  5. Following specific podocyte injury captopril protects against progressive long term renal damage [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Yu S Zhou

    2015-06-01

    Full Text Available Background: Angiotensin converting enzyme inhibitors (ACEi reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. Methods: We created transgenic (Podo-DTR mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. Results: After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring. Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05. Conclusions: Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury.

  6. Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes.

    Science.gov (United States)

    Koehler, Sybille; Brähler, Sebastian; Braun, Fabian; Hagmann, Henning; Rinschen, Markus M; Späth, Martin R; Höhne, Martin; Wunderlich, F Thomas; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

    2017-02-07

    Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides. Independent expression of endogenous podocin, codon improved Cre, and mTomato was confirmed by immunofluorescence, fluorescent activated cell sorting and protein analyses. Nphs2(pod.T2A.ciCre.T2A.mTomato/wild-type) mice developed normally and did not show any signs of glomerular disease or off-target effects under basal conditions and in states of disease. Nphs2(pod.T2A.ciCre.T2A.mTomato/wild-type)-mediated gene recombination was superior to conventional hNphs2.Cre mice-mediated gene recombination. Last, we compared Cre efficiency in a disease model by mating Nphs2(pod.T2A.ciCre.T2A.mTomato/wild-type) and hNphs2.Cre mice to Phb2(fl/fl) mice. The podocyte-specific Phb2 knockout by Nphs2(pod.T2A.ciCre.T2A.mTomato/wild-type) mice resulted in an aggravated glomerular injury as compared to a podocyte-specific Phb2 gene deletion triggered by hNphs2.Cre. Thus, we generated the first tricistronic podocyte mouse model combining enhanced Cre recombinase efficiency and fluorescent labeling in podocytes without the need for additional matings with conventional reporter mouse lines.

  7. Glycogen synthase kinase 3β dictates podocyte motility and focal adhesion turnover by modulating paxillin activity: implications for the protective effect of low-dose lithium in podocytopathy.

    Science.gov (United States)

    Xu, Weiwei; Ge, Yan; Liu, Zhihong; Gong, Rujun

    2014-10-01

    Aberrant focal adhesion turnover is centrally involved in podocyte actin cytoskeleton disorganization and foot process effacement. The structural and dynamic integrity of focal adhesions is orchestrated by multiple cell signaling molecules, including glycogen synthase kinase 3β (GSK3β), a multitasking kinase lately identified as a mediator of kidney injury. However, the role of GSK3β in podocytopathy remains obscure. In doxorubicin (Adriamycin)-injured podocytes, lithium, a GSK3β inhibitor and neuroprotective mood stabilizer, obliterated the accelerated focal adhesion turnover, rectified podocyte hypermotility, and restored actin cytoskeleton integrity. Mechanistically, lithium counteracted the doxorubicin-elicited GSK3β overactivity and the hyperphosphorylation and overactivation of paxillin, a focal adhesion-associated adaptor protein. Moreover, forced expression of a dominant negative kinase dead mutant of GSK3β highly mimicked, whereas ectopic expression of a constitutively active GSK3β mutant abolished, the effect of lithium in doxorubicin-injured podocytes, suggesting that the effect of lithium is mediated, at least in part, through inhibition of GSK3β. Furthermore, paxillin interacted with GSK3β and served as its substrate. In mice with doxorubicin nephropathy, a single low dose of lithium ameliorated proteinuria and glomerulosclerosis. Consistently, lithium therapy abrogated GSK3β overactivity, blunted paxillin hyperphosphorylation, and reinstated actin cytoskeleton integrity in glomeruli associated with an early attenuation of podocyte foot process effacement. Thus, GSK3β-modulated focal adhesion dynamics might serve as a novel therapeutic target for podocytopathy.

  8. 3,5-二羟基苯甘氨酸对体外氨基核苷嘌呤霉素诱导的足细胞凋亡的影响%Effect of (S)-3, 5-dihydroxyphenylglycine on puromycin aminonucleosideinduced apoptosis of podocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    李肖瑛; 顾乐怡; 倪兆慧; 梁馨月; 严玉澄; 钱家麒

    2013-01-01

    Objective To investigate the effect of ( S)-3, 5-dihydroxyphenylglycine ( DHPG), a selective metabotropic glutamate receptors (mGluR) 1 and 5 agonist, on aminonucleoside puromycin ( PAN) -induced podocyte apoptosis in vitro, and explore the possible mechanism. Methods Conditional immortalized mouse podocytes 5P12 were cultured in vitro, and were grouped based on different interventions. CCK-8, Western blotting, EIA, JC-1 staining and flow cytometry, immunofluorescence staining, TUNEL staining and confocal laser scanning microscopy were employed to examine the cell viability, expression of mGluR1/5 and activated cleaved caspase-3, cyclic adenosine monophosphate ( cAMP) level, mitochondrial membrane potential, cAMP responsive element binding protein ( CREB) and apoptosis of podocytes. Results Podocytes treated with DHPG generated cAMP and activated expression of CREB. DHPG inhibited PAN-induced podocyte loss, cleaved caspase-3 upregulation, decrease of mitochondrial membrane potential and advanced apoptosis, which could be suppressed by selective antagonist of mGluRl/5 ( AIDA), adenylate cyclase inhibitor ( SQ22536) and RNA interference-mediated knockdown of mGluRl or mGluR5. Conclusion DHPG can protect against PAN-induced apoptosis of podocytes, which may be associated with mGluR/cAMP signalling pathway.%目的 研究代谢型谷氨酸受体1(mGluR1)和mGluR5的激动剂3,5-二羟基苯甘氨酸(DHPG)在体外对由氨基核苷嘌呤霉素(PAN)诱导的足细胞凋亡的影响,探讨可能的作用途径.方法 体外培养小鼠条件永生型足细胞株5P12,根据添加干预药物的不同进行分组.采用CCK-8法、Western blotting 、EIA法、JC-1单标法流式细胞术、免疫荧光法和TUNEL染色激光共聚焦显微镜观察等方法,对足细胞的细胞活力、mGluR1/5和活化的胱冬肽酶-3(cleaved caspase-3)的表达、环磷酸腺苷(cAMP)水平、线粒体膜电位变化、磷酸化cAMP反应元件结合蛋白(CREB)及细胞凋

  9. Quarkonium suppression

    Indian Academy of Sciences (India)

    P Petreczky

    2003-04-01

    I discuss quarkonium suppression in equilibrated strongly interacting matter. After a brief review of basic features of quarkonium production I discuss the application of recent lattice data on the heavy quark potential to the problem of quarkonium dissociation as well as the problem of direct lattice determination of quarkonium properties in finite temperature lattice QCD.

  10. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-01-01

    Full Text Available This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation, and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators. Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  11. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.

    Science.gov (United States)

    Manda, Gina; Checherita, Alexandru-Ionel; Comanescu, Maria Victoria; Hinescu, Mihail Eugen

    2015-01-01

    This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  12. The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

    Energy Technology Data Exchange (ETDEWEB)

    Pawluczyk, I.Z.A., E-mail: izap1@le.ac.uk [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); John Walls Renal Unit, Leicester General Hospital Leicester (United Kingdom); Pervez, A.; Ghaderi Najafabadi, M. [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); Saleem, M.A. [Academic and Children' s Renal Unit, University of Bristol, Southmead Hospital, Bristol (United Kingdom); Topham, P.S. [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); John Walls Renal Unit, Leicester General Hospital Leicester (United Kingdom)

    2014-08-15

    Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA{sub +FA}) or depleted of them (HSA{sub −FA}). Receptor-mediated endocytosis of FITC-HSA{sub +FA} over 60 min was 5 times greater than that of FITC-HSA{sub −FA}. 24 h exposure of podocytes to albumin up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA{sub −FA.} Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes.

  13. Renal Light Chain Deposition Associated with the Formation of Intracellular Crystalline Inclusion Bodies in Podocytes: A Rare Case Report.

    Science.gov (United States)

    Wang, Yuan-da; Dong, Zhe-yi; Zhang, Xue-guang; Zhang, Wei; Yin, Zhong; Qiu, Qiang; Chen, Xiang-mei

    2016-01-01

    We herein report the case of an elderly woman with bone pain and proteinuria as the main clinical manifestations. The patient was diagnosed with the IgG κ type of multiple myeloma. Her renal pathology consisted of widespread κ light chain protein deposition associated with the formation of large quantities of rod-like crystals in podocytes. This phenomenon is very rare. We explored the significance of this crystal formation via a detailed and descriptive analysis and also performed a literature review, thus providing data to increase the available information about this type of disease.

  14. Microtubule Associated Protein 1b (MAP1B Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

    Directory of Open Access Journals (Sweden)

    Markus Gödel

    Full Text Available Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps, a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.

  15. [Ultrastructure of glomerular podocyts in the incipient phase of minimal change nephrotic syndrome with thin basement membrane disease].

    Science.gov (United States)

    Ogawa, Ryo; Miyoshi, Ken-ichi; Nagao, Tomoaki; Jotoku, Masanori; Irita, Jun; Okura, Takafumi; Higaki, Jitsuo

    2012-01-01

    An 80-year-old woman was referred to the Division of Nephrology at Ehime University Hospital because of leg edema in December 2010. She had been treated with 300 mg of tocopherol for scleroderma since 2007 and treated with 9 mg of prednisolone (PSL) for autoimmune hearing loss since 2010. Due to the occurrence of mild hematuria (5-9/HPF), proteinuria (0.9 g/day) and an increased serum creatinine level (1.31 mg/dL), a renal biopsy was performed. Light microscopy (LM) showed minor abnormality in the glomeruli, and immunohistology showed the absence of deposits of immunoglobulins and complements. Electron microscopy (EM) showed a thin glomerular basement membrane with a limited level of podocyte abnormalities. Due to the findings of intimal thickening of interlobular arteries and subcapsular accumulation of global sclerosis on LM, she was diagnosed with nephrosclerosis and thin basement membrane disease. Four weeks later, her leg edema had increased considerably and urinary protein had increased to 12.4 g/day. The second biopsy showed similar findings in LM and IF as the first biopsy, but EM revealed diffuse foot process effacement. She was diagnosed with minimal change nephrotic syndrome (MCNS) and treated with methylprednisolone pulse therapy followed by 40 mg of oral PSL. Her urinary protein had completely disappeared 6 weeks later. Complete remission with PSL treatment indicates that urinary protein at first renal biopsy was due to MCNS. Our case exhibited podocyte features in the incipient phase of human MCNS.

  16. HLA-DR, and not PLA2R, is expressed on the podocytes in kidney allografts in de novo membranous nephropathy.

    Science.gov (United States)

    Wen, Jiqiu; Xie, Kenan; Zhang, Mingchao; Chen, Jinsong; Zhang, Jiong; Cheng, Dongrui; Li, Xue; Ji, Shuming; Liu, Zhihong

    2016-09-01

    Idiopathic membranous nephropathy (IMN) is known to be associated with antibodies acting on the M-type phospholipase A2 receptor (PLA2R) of the podocyte. However, the mechanism underlying de novo membranous nephropathy (dn MN) posttransplantation remains unclear. In this study, we aimed to elucidate the mechanism underlying dn MN.We selected 8 cases with dn MN and compared them to 20 IMN cases. Fifteen cases of stable grafts were selected as controls.Several differences between the dn MN group and the IMN group were detected. IgG4 showed negligible positive staining in patients with dn MN, while it was predominant in the IMN group (1/8 vs 20/20, P PLA2R antibodies and anti-PLA2R antibodies of the podocyte were very few in the dn MN patients; however, these antibodies were detected in most of the IMN patients (serum anti-PLA2R antibodies: 1/8 vs 16/20, P = 0.002, anti-PLA2R antibodies of the podocyte: 0/8 vs 17/20, P PLA2R pathway, which is known to play a role in IMN, was not involved in the mechanism underlying dn MN. On the contrary, dn MN might be associated with the alloimmune response directed against the podocyte.

  17. DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

    Science.gov (United States)

    Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

    2016-05-01

    Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

  18. Expression of TM4SF10, a Claudin/EMP/PMP22 family cell junction protein, during mouse kidney development and podocyte differentiation.

    Science.gov (United States)

    Bruggeman, Leslie A; Martinka, Scott; Simske, Jeffrey S

    2007-02-01

    Cell junctions in the nephron are highly specialized to perform specific and distinct filtration and reabsorption functions. The mature kidney forms complex cell junctions including slit diaphragms that prevent the passage of serum proteins into the filtrate, and tubule cell junctions that regulate specific paracellular ion reuptake. We have investigated the expression of TM4SF10 (Trans-Membrane tetra(4)-Span Family 10) in mouse kidneys. TM4SF10 is the vertebrate orthologue of Caenorhabditis elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. We found that TM4SF10 localizes at the basal-most region of podocyte precursors before the capillary loop stage, at some tubule precursors, and at the ureteric bud junction with S-shaped bodies. Overall expression of TM4SF10 peaked at postnatal day 4 and was virtually absent in adult kidneys. The very limited expression of TM4SF10 protein that persisted into adulthood was restricted to a few tubule segments but remained localized to the basal region of lateral membranes. In undifferentiated cultured podocytes, TM4SF10 localized to the perinuclear region and translocated to the cell membrane after Cadherin appearance at cell-cell contacts. TM4SF10 colocalized with ZO1 and p120ctn in undifferentiated confluent podocytes and also colocalized with the tips of actin filaments at cell contacts. Upon differentiation of cultured podocytes, TM4SF10 protein disappeared from cell contacts and expression ceased. These results suggest that TM4SF10 functions during differentiation of podocytes and may participate in the maturation of cell junctions from simple adherens junctions to elaborate slit diaphragms. TM4SF10 may define a new class of Claudin-like proteins that function during junctional development.

  19. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

  20. Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia.

    Science.gov (United States)

    Wang, Yuping; Gu, Yang; Loyd, Susan; Jia, Xiuyue; Groome, Lynn J

    2015-12-15

    To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe

  1. Levamisole in steroid-sensitive nephrotic syndrome: usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte.

    Science.gov (United States)

    Jiang, Lulu; Dasgupta, Ishita; Hurcombe, Jenny A; Colyer, Heather F; Mathieson, Peter W; Welsh, Gavin I

    2015-06-01

    Minimal change nephropathy (MCN) is the third most common cause of primary nephrotic syndrome in adults. Most patients with MCN respond to corticosteroid therapy, but relapse is common. In children, steroid-dependent patients are often given alternative agents to spare the use of steroids and to avoid the cumulative steroid toxicity. In this respect, levamisole has shown promise due to its ability to effectively maintain remission in children with steroid-sensitive or steroid-dependent nephrotic syndrome. Despite clinical effectiveness, there is a complete lack of molecular evidence to explain its mode of action and there are no published reports on the use of this compound in adult patients. We studied the effectiveness of levamisole in a small cohort of adult patients and also tested the hypothesis that levamisole's mode of action is attributable to its direct effects on podocytes. In the clinic, we demonstrate that in our adult patients, cohort levamisole is generally well tolerated and clinically useful. Using conditionally immortalized human podocytes, we show that levamisole is able to induce expression of glucocorticoid receptor (GR) and to activate GR signalling. Furthermore, levamisole is able to protect against podocyte injury in a puromycin aminonucleoside (PAN)-treated cell model. In this model the effects of levamisole are blocked by the GR antagonist mifepristone (RU486), suggesting that GR signalling is a critical target of levamisole's action. These results indicate that levamisole is effective in nephrotic syndrome in adults, as well as in children, and point to molecular mechanisms for this drug's actions in podocyte diseases.

  2. Class III PI 3-kinase is the main source of PtdIns3P substrate and membrane recruitment signal for PIKfyve constitutive function in podocyte endomembrane homeostasis.

    Science.gov (United States)

    Ikonomov, Ognian C; Sbrissa, Diego; Venkatareddy, Madhusudan; Tisdale, Ellen; Garg, Puneet; Shisheva, Assia

    2015-05-01

    The evolutionarily conserved PIKfyve, which synthesizes PtdIns5P from PtdIns, and PtdIns(3,5)P2 from PtdIns3P, requires PtdIns3P as both an enzyme substrate and a membrane recruitment signal. Whereas the PtdIns3P source is undetermined, class III PI3K (Vps34), the only evolutionarily conserved of the eight mammalian PI3Ks, is presumed as a main candidate. A hallmark of PIKfyve deficiency is formation of multiple translucent cytoplasmic vacuoles seen by light microscopy in cells cultured in complete media. Such an aberrant phenotype is often observed in cells from conditional Vps34 knockout (KO) mice. To clarify the mechanism of Vps34 KO-triggered vacuolation and the PtdIns3P source for PIKfyve functionality, here we have characterized a podocyte cell type derived from Vps34fl/fl mice, which, upon Cre-mediated gene KO, robustly formed cytoplasmic vacuoles resembling those in PikfyveKO MEFs. Vps34wt, expressed in Vps34KO podocytes restored the normal morphology, but only if the endogenous PIKfyve activity was intact. Conversely, expressed PIKfyvewt rescued completely the vacuolation only in PikfyveKO MEFs but not in Vps34KO podocytes. Analyses of phosphoinositide profiles by HPLC and localization patterns by a PtdIns3P biosensor revealed that Vps34 is the main supplier of localized PtdIns3P not only for PIKfyve activity but also for membrane recruitment. Concordantly, Vps34KO podocytes had severely reduced steady-state levels of both PtdIns(3,5)P2 and PtdIns5P, along with PtdIns3P. We further revealed a plausible physiologically-relevant Vps34-independent PtdIns3P supply for PIKfyve, operating through activated class I PI3Ks. Our data provide the first evidence that the vacuolation phenotype in Vps34KO podocytes is due to PIKfyve dysfunction and that Vps34 is a main PtdIns3P source for constitutive PIKfyve functionality.

  3. Growth hormone suppression test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  4. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  5. 足细胞骨架稳定性的调控%Regulation on the stability of podocyte cytoskeleton

    Institute of Scientific and Technical Information of China (English)

    康郁林; 朱光华; 何威逊; 吴滢

    2008-01-01

    足细胞骨架(the cytoskeleton of podocyte)遍及足细胞体和足突,其中足突骨架是足细胞形态结构功能中心,它与部分裂孔隔膜蛋白、足突顶端膜蛋白,黏附分子等相连,涉及的蛋白质分子有α-acti-nin-4、CD2AP、α3β1整合素等,正常足细胞骨架可通过自身调控机制抵抗外力干扰,维护骨架的结构稳定,但当足细胞骨架发生严重病理改变时,足细胞则将变形,消失,进而产生大量的蛋白尿.本文将以足突骨架稳定性相关蛋白如α-actinin-4、CD2AP和α3β1整合素为基点,对足突骨架结构稳定性的维护与调控作一综述.

  6. Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis.

    Science.gov (United States)

    Goto, Kei; Kaneko, Yoshikatsu; Sato, Yuya; Otsuka, Tadashi; Yamamoto, Suguru; Goto, Shin; Yamamoto, Keiko; Yamamoto, Tadashi; Kawachi, Hiroshi; Madaio, Michael P; Narita, Ichiei

    2016-04-01

    Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob(FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/obmice 7 days after NTS injection. The Th17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/obmice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and Th17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

  7. Effects of low protein diet supplemented with ketoacids on local renin-angiotensin system enzyme activities and podocytes loss in patients with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    谷立杰

    2014-01-01

    Objective To explore the effects of low-protein diet supplemented with ketoacids on podocytes as well as local RAS in the kidney of patients with diabetic nephropathy.Methods A total of 61 patients with T2DN and CKD stages 3-4 were included.All the patients were randomly divided into two groups:low protein group(0.6g·kg BW-1·d-1and 30 kcal·kg BW-1·d-1,LPD)

  8. Primary culture and identification of human glomerular podocytes%成人肾脏足细胞的原代培养和鉴定

    Institute of Scientific and Technical Information of China (English)

    张伟伟; 秦贵军; 赵亚兵

    2013-01-01

    Objective To establish a repeatable and feasible method for culturing human glomerular podocytes in vitro.Methods The renal epithelial tissues were obtained from the tumor-free pole of adults' kidneys after kidney tumor resection.Decapsulated human cortical slices were pressed through a series of stainless steel sieves (sieving method) with increasing pore sizes of 220 to 450 μm in a sterile,clean environment; as a final step,the glomeruli were collected on a 125 μm sieve and then cultured in 25 cm2 flasks of which bottoms were soaked by RPMI 1640 medium with 10% fetal bovine serum (FBS) in advance.Made the flasks upside down (explant method) ; 4 hours later,added medium and normally placed them.Cells were kept at 37 ℃ in a humid atmosphere under 5% CO2.Glomerular podocytes cellular markers as nephrin,Wilms tumor protein (WT-1),factor Ⅷ,vimentin and cytokeratin were analyzed by morphology and indirect immunofluorescence staining method,respectively.The purity of podocytes were determine by flow cytometry technology.Results Most of the glomeruli adhered to the wall of culture dish on the 3 rd day.Almost all glomeruli adhered on the 5 th day with a few climbed out polygonal cells which lost both primary and foot processes and appeared as cobblestones.A larger number of cobblestone-like cells which exhibited strong proliferative activity outgrowth from nearly every glomerular around from 7 th to 10 th day.Then the cells were digested by trypsin differences digestion method to remove fibroblast and subcultured.In subculturing,podocytes differentiate into other phenotypes which were large,branched,binucleated and exhibited no proliferative activity.It was observed by immunofluorescent staining that the cells were in line with characteristics of podocytes and expressed WT-1 and nephrin,but not the factor Ⅷ,vimentin and cytokeratin with no pollution of endothelial cells,mesangial cells and parietal epithelial cells.Furthermore,purity of podocytes was 98.3

  9. 马钱苷对糖基化终末产物诱导足细胞损伤的保护作用%Protective effect of loganin on podocyte injury induced by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    吴云皓; 陈玉萍; 吕兴; 周芷若; 沈红胜; 戴国英; 许惠琴

    2016-01-01

    Aim To explore the protective effect of lo-ganin ( an active component in Cornus officinalis ) on podocyte injury induced by advanced glycation end products ( AGEs) and its possible mechanism. Meth-ods Mouse podocytes were cultured in vitro and di-vided into Normal group, model group ( AGEs group) , loganin group and aminoguanidine group ( set as posi-tive control) . After being incubated with loganin( final concentrations are 0. 1, 1, 10 μmol · L-1 ) for 1 h, podocytes were stimulated by AGEs of 100 mg · L-1 for 24 h. Then, the cell viability was measured by u-sing MTT method. Podocytes apoptosis was evaluated by Hoechst33342/PI staining and flow cytometry. Re-ceptors of advanced glycation end products ( RAGE ) ,desmin and apoptosis-related protein like Bax, Bcl-2, cleaved caspase-3 in podocytes were detected by Western blot. Results Loganin ameliorated podocyte injury induced by AGEs, down-regulated the expression of desmin and RAGE. Loganin also reduced the apoptotic rate of podocytes and decreased the ratio of Bax/ Bcl-2 and the expression of pro-apoptotic protein cleaved caspase-3 in podocytes. Conclusion Loganin could ameliorate podocyte injury, and its mechanism may be related to the decrease of the expression of RAGE and inhibition of the apoptotic pathway.%目的:探讨山茱萸环烯醚萜苷特征性成分马钱苷对糖基化终末产物( AGEs)诱导肾脏足细胞损伤的保护作用及其机制。方法体外培养小鼠肾小球足细胞,分为空白对照组、模型组( AGEs组)、马钱苷组,并设氨基胍组作为阳性对照。 MTT法检测马钱苷对足细胞存活率的影响;Hoechst 33342/PI双染观察足细胞凋亡情况,流式细胞仪检测细胞凋亡率;Western blot法检测足细胞AGEs受体( RAGE )、足细胞损伤标志蛋白 desmin 以及凋亡相关蛋白 bax、bcl-2、cleaved caspase-3的表达。结果马钱苷能够抑制AGEs导致的足细胞损伤,下调足细胞Desmin、RAGE蛋白的表达,明显降

  10. Advanced oxidation protein products decrease expression of nephrin and podocin in podocytes via ROS-dependent activation of p38 MAPK

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin.The expression of glomerular podocyte slit diaphragm(PSD)-associated proteins,nephrin and podocin,was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs.Chronic inhibi-tion of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats.This suggested that accumulation of AOPPs promotes proteinuria,possibly via down-regulating the expression of PSD-associated proteins.

  11. Explosion suppression system

    Science.gov (United States)

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  12. Relationship between renal pathology and glomerular podocyte injury in childhood Henoch-Sch(o)nlein purpura nephritis%紫癜性肾炎患儿肾脏病理与足细胞损伤的关系

    Institute of Scientific and Technical Information of China (English)

    任献国; 何旭; 杜丽芳; 高远赋; 樊忠民; 高春林; 茅松; 张沛; 夏正坤

    2013-01-01

    Objective To explore the relationship between renal pathology and glomerular podocyte injury in childhood Henoch-Sch(o)nlein purpura nephritis (HSPN).Methods Renal pathological types of 72 children suffering from HSPN were reviewed during the period of Jan.2008 to Jan.2011 from Nanjing General Hospital of Nanjing Command.In those cases,grade in pathology and immunofluorescence types were acquired.Podocyte injury was classified by electron microscope.The relationship between podocyte injury and grade in pathology was analyzed.Results Pathological findings were classified,grade Ⅱ in 34 cases(47.2%) and grade m in 38 cases(52.8%).Glomerular podocyte injury was classified by electron microscope as food processes of podocyte fused extensively in 21 cases;food processes of podocyte fused segmental in 35 cases,food processes of podocyte without fusion in 11 cases.There was without renal glamorous in nephridial tissue by electron microscope in 5 cases.Cases with foot process of podocyte fused extensively were more grade Ⅲ1 than those cases with foot process fused segmental and without fusion.According to renal immunofluorescence pathology,IgA + IgM + IgG type was mostly in cases with foot process of podocyte fused extensively,IgA +IgG type was mostly in cases with food processes of podocyte fused segmental and IgA type was mostly in cases with food processes of podocyte without fusion.Conclusions In childhood HSPN,renal pathology changed not only expressing on mesangial cell hyperplasia but also podocyte injury.The more seriously on the degree of podocyte injury,more obviously in pathologic change.%目的 探讨儿童紫癜性肾炎(HSPN)肾脏病理分级、免疫荧光分型和肾小球足细胞损伤的关系.方法 回顾性分析2008年1月至201 1年1月南京军区南京总医院儿科肾活检病理检查诊断为HSPN的住院病例72例,对其进行病理分级和免疫荧光分型,并在电镜下观察足细胞损伤情况;分析足细胞损伤

  13. Assessment of the degree of oxidative stress injury, renin-angiotensin system activity and podocyte loss after combined treatment of keto acid with low protein diet for patients with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Yuan-Hua Xu; Mei Wang

    2016-01-01

    Objective:To analyze the degree of oxidative stress injury, RAS activity and podocyte loss after patients with diabetic nephropathy received keto acid combined with low protein diet. Methods:A total of 106 cases of patients with diabetic nephropathy who received hospital treatment in our hospital from September 2012 to July 2015 were selected as research subjects and randomly divided into observation group and control group according to different treatment, each group with 53 cases. Control group received low protein diet treatment alone, observation group received keto acid combined with low protein diet treatment, and then the degree of oxidative stress injury, RAS activity and podocyte loss of two groups were compared. Results:Serum MDA and AOPP levels of observation group after treatment were lower than those of control group, and levels of SOD and T-AOC were higher than those of control group;PRA, AngⅡand Aldosterone levels of observation group after treatment were lower than those of control group;mRNA expression levels of podocin and synaptopodin in urine sediment of observation group after treatment were lower than those of control group. Conclusion:Keto acid combined with low protein diet treatment for patients with diabetic nephropathy can reduce the degree of oxidative stress injury and RAS activity, decrease podocyte loss and optimize patients’ condition.

  14. Proximal tubule dysfunction is associated with podocyte damage biomarkers nephrin and vascular endothelial growth factor in type 2 diabetes mellitus patients: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Ligia Petrica

    Full Text Available There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor.Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried.Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p < 0.001; R2 = 0.125; p < 0.001, nephrinuria (R2 = 0.529; p<0.001; R2 = 0.203; p < 0.001, urinary vascular endothelial growth factor (R2 = 0.709; p < 0.001; R2 = 0.360; p < 0.001, urinary advanced glycation end-products (R2 = 0.578; p < 0.001; R2 = 0.405; p < 0.001, serum cystatin C (R2 = 0.130; p < 0.001; R2 = 0.128; p<0.001, and glomerular filtration rate (R2 = 0.167; p < 0.001; R2 = 0.166; p < 0.001; nephrinuria and urinary vascular endothelial growth factor correlated with urinary albumin:creatinine ratio (R2 = 0.498; p < 0.001; R2 = 0.227; p<0.001, urinary advanced glycation end-products (R2 = 0.251; p < 0.001; R2 = 0.308; p < 0.001, serum cystatin C (R2 = 0.157; p < 0.001; R2 = 0.226; p < 0.001, and glomerular filtration rate (R2 = 0.087; p = 0.007; R2 = 0.218; p < 0.001.In Type 2 diabetes mellitus there is an association of proximal tubule dysfunction with podocyte damage biomarkers, even in the normoalbuminuria stage. This observation suggests a potential role of the proximal tubule in urinary nephrin and urinary vascular endothelial

  15. Suppression subtractive hybridization.

    Science.gov (United States)

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  16. 雷公藤多苷对糖尿病肾病大鼠足细胞的保护作用%Protective effect of TWP on the podocytes of diabetes nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    郑云; 郝丽; 潘梦舒; 丁楠

    2011-01-01

    Objective To explore the protective effect of triptergium wilfordii polyglucoside( TWP ) on the podocytes of diabetes nephropathy ( DN ) rats. Methods Sixty SD rats were randomly divided into normal control group( group A ), DN group( group B ) , TWP group ( group C ). Rats in group B and C were given streptozotocin( STZ ) by intraperitoneal injection to establish animal model of diabetes. After 12 weeks . we observed UAER , kidney organization of pathological changes by HE staining, and ultrastructure changes of podocytes by TEM , and expression of the Nephrin and Podocin protein by immunofluorescence staining. Results Compared with group A, UAER were obviously higher (P<0. 01 ); Nephrin and Podocin protein expressions in nephridial tissue were lower; Pathomorphological change in glomerulus, tubules and podocytes were observed in group B and C. Compared with group B, UAER were obviously lower( P < 0. 01 ) ; Nephrin and Podocin protein expressions in nephridial tissue were higher; Pathomorphologica change in glomerulus, tubules and podocytes showed a better improvement in group C. Conclusion The protective effect of TWP on the podocyte of DN rats may be partly referred with up-regulation of Nephrin andPodocin expressions and improved glomerular podocyte lesion.%目的 探讨雷公藤多苷(TWP)对糖尿病肾病(DN)大鼠足细胞的保护作用.方法 SD大鼠60只,随机分为正常组(A组)、DN组(B组)与TWP治疗组(C组).B、C组分别给予链脲佐菌素(STZ)一次性腹腔注射建立糖尿病大鼠模型.12周后观察24 h尿蛋白排泄量(UAER);HE染色观察肾组织病理变化;透射电镜检查足细胞超微结构变化;免疫荧光方法检测肾皮质Nephrin和Podocin蛋白表达.结果 与A组比较,B、C组UAER明显增高(P<0.01),肾脏皮质Nephrin和Podocin蛋白表达减少,肾小球、小管间质、足细胞病变明显.与B组比较,C组UAER明显减少(P<0.01);肾脏皮质Nephrin和 Podocin蛋白表达增高,肾小球、小管

  17. Accentuation-suppression and scaling

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik; Bundesen, Claus

    2012-01-01

    a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...

  18. Visual surround suppression in schizophrenia

    Directory of Open Access Journals (Sweden)

    Marc Samuel Tibber

    2013-02-01

    Full Text Available Compared to unaffected observers patients with schizophrenia show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgements of contrast - a manifestation of weaker surround suppression. To examine the generality of this phenomenon we measured the ability of 24 individuals with schizophrenia to judge the luminance, contrast, orientation and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with schizophrenia demonstrated weaker surround suppression compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation surround suppression in schizophrenia may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.

  19. Effect of astragaloside IV on diabetic nephropathy rat podocytes and its mechanism%黄芪甲苷对糖尿病肾病大鼠足细胞的影响及其机制研究

    Institute of Scientific and Technical Information of China (English)

    罗蕴龄; 陈宜方; 何东元; 陈建国

    2014-01-01

    Objective To investigate the protect effects of astragaloside IV(AS- IV) on diabetic nephropathy rat podocytes and explore its mechanism. Methods Healthy male Sprague- Dawley (SD) rats of 180~200g were randomly divided into normal control group(NC), diabetic nephropathy group(DN) and diabetic nephropathy with AS- IV treatment group(DN+AS- IV). DN was induced by intraperitoneal injection of streptozotocin. AS- IV treatment was started 2 weeks before STZ injection and lasted 14 weeks. 24 hour urine were col ected and 24 hour urinary protein were measured at the end of the 6th,12th week after STZ injec-tion. At the end of 6th and 12th week after STZ injection, rats were sacrificed and the blood samples were col ected for measuring biochemical parameters. The kidneys were harvested for histopathology, immunohistochemistry, electron microscopy and West-ern blot examinations, and the renal pathology, morphological changes of podocytes, podocyte density changes and expression ofα3β1 integrin protein were analyzed. Results In STZ- induced DN rats severe hyperglycemia and proteinuria were devel-oped. Mesangial expansion, increased podocyte loss and decreased integrin α3 and β1 expression were detected in DN rats. Treatment with AS- IV10mg/ (kg·d) for 14 weeks ameliorated proteinuria and podocyte foot process effacement, attenuated the loss of podocytes in glomerules and up- regulated the expression of integrinα3 andβ1 in podocytes. Conclusion AS- IV may protect podocyte and ameliorate diabetic nephropathy by restoring the expression ofα3β1 integrin in diabetic rats.%目的:探讨黄芪甲苷(AS- IV)对糖尿病肾病(DN)大鼠足细胞的保护作用及其机制,为DN早期防治开辟一条新途径。方法体重180~200g健康雄性SD大鼠45只按配伍法分为正常对照组(NC组)、DN组和AS- IV治疗组(DN+AS- IV组),链脲佐菌素腹腔注射建立大鼠早期DN模型。DN+AS- IV组大鼠在造模前2周予AS- IV 10mg/(kg·d)

  20. 高糖和LY294002干预影响足细胞内Ⅳ型胶原表达%Effects of High Glucose and LY294002 on the Expression of Collagen IV in Mouse Podocyte

    Institute of Scientific and Technical Information of China (English)

    邢玲玲; 刘青娟; 傅淑霞; 曹延萍; 刘巍; 段惠军

    2011-01-01

    探讨高糖和PI3K/Akt通路对足细胞内Ⅳ型胶原(Col Ⅳ)表达的影响.体外培养小鼠足细胞,给予高糖(30 mmol/L)处理后,分别于0,12,24,48 h收集细胞,采用免疫细胞化学染色法和Western blot技术检测Col Ⅳ的表达:Western blot技术检测Akt的活化及LY294002对Col Ⅳ表达的抑制效应.结果表明,高糖诱导足细胞内Col Ⅳ蛋白表达增多,24h明显,各时间点与高糖刺激前相比均有统计学差异(P<0.05);高糖激活Akt蛋-白磷酸化,p-Akt随刺激时间延长表达增多.PI3K/Akt通路抑制剂LY294002孵育细胞24 h后,可减弱高糖诱导的足细胞内Col Ⅳ的表达(P<0.05).因此,高糖可能通过激活PI3K/Akt通路上调足细胞内Ⅳ型胶原表达.%To investigate effects of high glucose and phosphoinositide 3 kinese/protein kinase B (PI3K/Akt) pathway on the expression of collagen IV (Col IV) in mouse podocyte, we divided cultured mouse podocytes into high glucose (30 mmol/L, HG) group and normal glucose (5 mmol/L, NG) group. Cells were collected respectively at 0, 12, 24, 48 h after stimulation. The expression of collogen IV was detected by immunocytochemistry and Western blot analysis. The expression of phospho-Akt and the inhibition of LY294002 on collogen IV were analized by Western blot. Compared with control group, the level of Col IV in mouse podocytes treated by high glucose was significantly increased (P<0.05), with reaching the peak at 24 h. The phosphorylation of Akt was observed in mouse podocytes induced by high glucose. The level of phospho-Akt was increased in a time-dependent manner. However, inhibition of activation of Akt with LY294002, a specific PI3K/Akt pathway inhibitor, attenuated the high glucose-induced expression of Col IV at 24 h after intervention. We conclude that high glucose maybe up-regulate the expression of Col IV in mouse podocytes by activating PI3K/Akt pathway.

  1. Cryogenic Acoustic Suppression Testing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will explore and test the feasibility and effectiveness of using a cryogenic fluid (liquid nitrogen) to facilitate acoustic suppression in a...

  2. Simple suppression of radiation damping.

    Science.gov (United States)

    Khitrin, A K; Jerschow, Alexej

    2012-12-01

    Radiation damping is known to cause line-broadening and frequency shifts of strong resonances in NMR spectra. While several techniques exist for the suppression of these effects, many require specialized hardware, or are only compatible with the presence of few strong resonances. We describe a simple pulse sequence for radiation damping suppression in spectra with many strong resonances. The sequence can be used as-is to generate simple spectra or as a signal excitation part in more advanced experiments.

  3. Suppressed Charmed B Decay

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, Hella Leonie [Vrije Univ., Amsterdam (Netherlands)

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  4. 不同饱和度脂肪酸与足细胞损伤关系及损伤机制%Relationship between different saturated fatty acids and podocyte injury and its mechanism

    Institute of Scientific and Technical Information of China (English)

    丁晓华; 聂晓晶; 李莉; 马雷; 杨勇辉; 赵锋; 谢婷婷; 张勇

    2016-01-01

    目的:探讨不同饱和度脂肪酸与足细胞损伤的关系及相应的损伤机制。方法不同饱和度脂肪酸(棕榈酸、油酸、20碳5烯酸)分别干预足细胞,MTT法测足细胞存活率、免疫荧光检测足细胞骨架,从而判断足细胞是否损伤;Western印迹检测p38、细胞外信号调节激酶(ERK)1/2和氨基末端激酶(JNK)变化,RT⁃PCR检测COX⁃2和TNF⁃α,探讨相应损伤机制。结果经脂肪酸处理10 h,饱和脂肪酸棕榈酸组和对照组的细胞存活率分别为(66.96±2.41)%和(90.95±5.37)%(P<0.05);棕榈酸组丝状肌动蛋白(F⁃actin)较其他实验组减少;棕榈酸组p38、ERK1/2和JNK磷酸化水平升高,棕榈酸组与对照组的p⁃p38/p38、p⁃ERK/ERK和p⁃JNK/JNK差异均存在统计学意义(P<0.05);棕榈酸组COX⁃2和TNF⁃α表达升高,与对照组比较差异有统计学意义(P<0.05)。4~8 h期间,单不饱和脂肪酸油酸可提高足细胞存活率。结论饱和脂肪酸棕榈酸可损伤足细胞,MAPK信号通路介导该损伤过程, MAPK信号通路中的p38、ERK1/2和JNK出现活化,并介导炎症因子COX⁃2和TNF⁃α产生;不饱和脂肪酸油酸可短期提高足细胞活力。%Objective To investigate the relationship between different saturated fatty acids and podocyte injury and the corresponding injury mechanism. Methods The podocytes were intervened by different saturated fatty acids(palmitate,oleate and eicosapentaenoic acid),respectively. The viability and cytoskeleton of podocytes were determined by MTT method and immunofluorescence to determine whether the podocytes were injured. The changes of MAPK signaling pathways(p38,ERK1/2 and JNK)were determined by Western blot. RT⁃PCR was used to determine COX⁃2 and TNF⁃α,and the corresponding injury mechanism was investigated. Results After 10h of fatty acid treatment,the cell viability in the palmitate (saturated fatty acid)group and the

  5. 来氟米特对高糖环境下足细胞表达的影响及其机制%Effects of leflunomide on podocytes exposed to high glucose condition and its mechanism

    Institute of Scientific and Technical Information of China (English)

    赵星; 于为民; 李荣山; 任小军

    2013-01-01

    目的 探讨高糖环境下来氟米特(A771726)对人足细胞Podocalyxin(PCX)、核因子(NF)-κB和基质金属蛋白酶9(MMP-9)表达的影响及其机制.方法 在高糖环境下培养足细胞,Western印迹法检测不同时间点足细胞特征蛋白PCX表达的变化;再将足细胞分为正常糖组、来氟米特组、高糖组、高渗对照组进行培养,用Western印迹法检测各组足细胞PCX蛋白的表达.Western印迹法检测不同时间点高糖培养足细胞NF-κB p65及磷酸化NF-κB p65(P-NF-κBp65)活性;再将足细胞分为正常糖组、甘露醇高渗对照组、高糖组、来氟米特组和NF-κB阻断剂(PDTC)组,用Western印迹法检测各组足细胞MMP-9蛋白的表达.结果 在高糖环境下,足细胞特征蛋白PCX的表达随时间持续下降;来氟米特组PCX蛋白表达明显高于高糖组(0.46±0.04比0.13±0.03,P<0.05).在高糖刺激足细胞在30 min时,NF-κB的活化开始,P-NF-κBp65蛋白表达上升,60 min达高峰,6h后接近基础水平;而在同一时点NF-κB阻断剂PDTC组和来氟米特组足细胞MMP-9蛋白表达明显低于高糖组,差异均有统计学意义(0.71 ±0.01、0.64±0.03比1.64±-0.03,均P<0.05).结论 来氟米特(A771726)对高糖环境下的足细胞有保护作用,其机制可能是通过抑制NF-κB活化而减少足细胞表达MMP-9.%Objective To explore the protective effects of leflunomide (A771726) on the expression of podocalyxin,NF-κB and matrix metalloproteinase-9 (MMP-9) in podocytes exposed to high glucose environment and elucidate its mechanism.Methods Podocytes were cultured in high glucose.And the altered expressions of podocyte protein podocalyxin were detected by Western blotting at different timepoints.Then podocytes were divided into 4 groups of normal glucose control,leflunomide,high glucose and hypertonic control.The expression level of podocalyxin protein in each group was detected by Western blotting.And NF-κB p65 and phosphorylation of NF

  6. 亚麻木酚素提取物对糖尿病大鼠肾脏足细胞的影响%Effect of flaxseed lignan extract on podocytes in diabetic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    徐海娥; 张慧; 王孙璟; 顾呈华; 李莉

    2013-01-01

    目的:观察亚麻木酚素提取物对糖尿病大鼠肾脏足细胞损伤的影响.方法:将未造模大鼠作为正常对照组;成模大鼠随机分为3组(模型组、实验组、药物对照组).实验12周末检测24h尿白蛋白排泄率、肾重系数等变化,透射电镜观察肾脏足细胞超微病理结构变化.结果:与糖尿病模型组比较,实验组降低肾重、24h尿白蛋白排泄率、Scr、BUN (P <0.05).实验组和药物对照组病理改变均较糖尿病模型组明显减轻,足突部分融合,系膜基质轻度增多,肾小球基底膜增厚减轻.结论:亚麻木酚素提取物可减轻糖尿病大鼠肾脏足细胞病理损伤,改善肾功能.%Objective: To explore the effect of Flaxseed Lignan Extract on the podocytes of rats with diabetes nephropathy. Methods; Fifty Wistar rats were randomly divided into normal control group, DN model group (model group) .Enalapril treatment group, Flaxseed Lignan Extract treatment group. After 12 weeks, 24 h urinary protein excretion rate, BUN, Scr and kidney weight/body weight were determined. The renal pathology and the changes of podocytes were observed under light microscope and transmission electron microscope. Results: After treatment of Flaxseed Lignan Extract and Enalapril, urinary protein quantity in 24 h, SCr, BUN were reduced ( respectively P < 0.05) compared with the DN model group. Flaxseed Lignan Extract and Enalapril can improve ultrastructure in kidney of diabetic rats, lessen the fusion of foot process, ameliorate the renal pathomorphology change. Conclusion: Flaxseed Lignan Extract can rescue the podocyte injury and provide protective effects on renal fuction of diabetic nephropathy rats.

  7. Soft substrates suppress droplet splashing

    CERN Document Server

    Howland, Christopher J; Style, Robert W; Castrejón-Pita, A A

    2015-01-01

    Droplets splash when they impact dry, flat substrates above a critical velocity that depends on parameters such as droplet size, viscosity and air pressure. We show that substrate stiffness also impacts the splashing threshold by imaging ethanol drops impacting silicone gels of different stiffnesses. Splashing is significantly suppressed: droplets on the softest substrates need over 70% more kinetic energy to splash than they do on rigid substrates. We show that splash suppression is likely to be due to energy losses caused by deformations of soft substrates during the first few microseconds of impact. We find that solids with Youngs modulus $\\lesssim O(10^5)$Pa suppress splashing, in agreement with simple scaling arguments. Thus materials like soft gels and elastomers can be used as simple coatings for effective splash prevention.

  8. Visual Surround Suppression in Schizophrenia

    Science.gov (United States)

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  9. Intercropping leeks to suppress weeds

    NARCIS (Netherlands)

    Baumann, D.T.; Kropff, M.J.; Bastiaans, L.

    2000-01-01

    Many field vegetables such as leek are weak competitors against weeds, causing high costs for weed management practice. Using celery as a companion cash crop was suggested to improve the weed suppression of leek. Three field experiments were carried out to study the intra- and interspecific competit

  10. Polypyrrole Actuators for Tremor Suppression

    DEFF Research Database (Denmark)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse

    2003-01-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers...

  11. High temperature suppression of dioxins.

    Science.gov (United States)

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants.

  12. CD2相关蛋白在肾病综合征中的表达及意义%Expression of CD2AP on podocytes with different pathological types of nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    史秀岩; 张春; 付应峰; 朱忠华; 朱红艳; 易丽霞; 付玲

    2012-01-01

    目的 观察不同病理类型的原发性肾病综合征(nephrotic syndrome,NS)患者肾小球足细胞中CD2相关蛋白(CD2AP)的表达,探讨其与足细胞损伤的关系.方法 选取原发性NS患者54例,10例同期肾肿瘤切除患者正常肾组织作为对照.肾活检后常规染色观察肾脏组织病理改变,肾组织行免疫荧光法CD2AP和肾小球上皮细胞蛋白-1(GLEPP1)双重标记,对肾小球CD2AP的表达进行定位;分别用real time PCR和免疫组化SP法检测组织中CD2AP的表达,采用real time PCR检测nephrin的表达,透射电镜观察足细胞的结构变化,并定量测量足突密度.结果 (1)NS患者肾小球中CD2AP的表达及nephrin的表达下调,足细胞足突不同程度融合,足突密度降低.(2)病理表现为微小病变性肾病(minimal change disease,MCD)、局灶性节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)和膜性肾病(membranous nephropathy,MN)的NS患者CD2AP表达及nephrin表达较对照组明显降低,且CD2AP与nephrin表达呈正相关,病理表现为MCD和FSGS的NS患者CD2AP表达与足突密度呈正相关.结论 本研究首次发现原发性NS患者肾小球足细胞中CD2AP的表达降低,且在MCD和FSGS中与足细胞病变程度相关,提示CD2AP低表达在足细胞病变为主的肾小球疾病中发挥重要作用.CD2AP有利于诊断足细胞病变的早期检测,对CD2AP表达减低进行早期干预可能有助于延缓疾病进展.%Purpose To investigate the CD2AP expression of the renal podocytes in patients with nephrotic syndrome, and to study the association between expression of CD2AP and podocyte injury. Methods 54 patients with nephrotic syndrome ( NS ) were studied, and 10 patients with renal tumor undergone nephrectomy were enrolled as control. Renal pathological change after renal biopsy was bserved. CD2AP and GLEPP1 by immunofluorescence double staining were performed. The renal CD2AP was detected by immunohis-tochemistry and quantitive real

  13. Effect of advanced glycation end products on renin-angiotensin system in podocytes%晚期糖基化终产物对足细胞内肾素-血管紧张素系统的影响

    Institute of Scientific and Technical Information of China (English)

    成彩联; 郑振达; 石成钢; 叶增纯; 刘迅; 娄探奇

    2013-01-01

    Objective To investigate the effect and mechanism of advanced glycation end products (AGEs) on the components of renin-angiotensin system (RAS) in the podocytes.Methods Immortalized mouse podocytes were exposed to various concentrations of AGEs for 24 h.The expression levels of renin,angiotensinogen (AGT) and angiotensin Ⅱ type 1 and 2 receptors (AT1R and AT2R),the level of angiotensin Ⅱ (Ang Ⅱ),and the activity of angiotensin-converting enzyme (ACE) were assayed.The levels of Akt and phosphorylated Akt were examined by Western blotting.Cell adhesion was measured in the podocytes pretreated with phosphoinositide 3-kinase (PI3-K) inhibitor LY294002,losartan,captopril and chymostatin,respectively.Results Treatment with AGEs resulted in significant increase in the expression of AGT and AT1R.Moreover,ACE activity and Ang Ⅱ level increased significantly.However,there was no significant change in renin and AT2R expression.AGEs increased the phosphorylation of Akt by 100%.When the podocytes were pretreated with LY294002 (10 μmol/L),the AGEs-induced increase in AGT and AT1R expression reduced remarkably.Likewise,ACE activity and Ang Ⅱ level decreased significantly,and the reduced podocyte adhesive capacity induced by AGEs was improved significantly.Conclusions AGEs activate the RAS via PI3-K/Akt-dependent pathway,and lead to a decrease in podocyte adhesion.%目的 观察晚期糖基化终产物(advanced glycation end products,AGEs)对足细胞内肾素-血管紧张素系统(renin-angiotensin system,RAS)的影响及作用机制.方法 不同浓度的AGEs干预小鼠足细胞24h,分别检测肾素(renin)、血管紧张素原(renin-angiotensin system,AGT)、血管紧张素Ⅱ1型、2型受体(AT1R、AT2R)的表达,血管紧张素转换酶(angiotensin-converting enzyme,ACE)的活性和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)的浓度,观察蛋白激酶B(Akt)的磷酸化,然后分别加入磷酸肌醇3激酶抑制剂LY294002、Iosartan、captopril和chymastatin,

  14. Protective Effect of Candesartan on Podocyte Damage in Rats with Diabetic Nephropathy%坎地沙坦对糖尿病肾病大鼠足细胞保护作用的研究

    Institute of Scientific and Technical Information of China (English)

    李桂霞; 周静; 李秋月; 吕金雷; 李六生

    2011-01-01

    Objective To investigate the changes in podocyte ultrastructure and nephrin expression in rats with diabetic nephropathy(DN) ,and to observe the effect of candesartan on podocyte damage. Methods Thirty-six Sprague-Dawley rats were randomly divided into normal control group(group A),DN model group(group B),and candesartan treatment group (group C),with 12 rats in each group. DN was induced by intravenous injection of streptozotocin (30 mg · kg-1) and rats in group C were intragastricly given candesartan (5 mg · kg-1 · d-1) 1 week after induction of DN. Rats in group A and group B were given the same amount of normal saline. Blood glucose levels, body weight, 24-hour urinary protein excretion and endogenous creatinine clearance(Ccr) were measured at 4 and 7 weeks after treatment. Pathological changes in renal tissues were evaluated by HE staining and podocyte ultrastructure was observed using electron microscop. The expression of nephrin was detected by RT-PCR. Results Compared with group A, 24-hour urinary protein excretion and serum creatinine increased, Ccr decreased at 7 weeks, and nephrin expression reduced in group B(all P<0. 05). Compared with group B, 24-hour urinary protein excretion,serum creatinine,foot process width and glomerular basement membrane thickness decreased,and Ccr and nephrin expression increased in group C (all P<0.05). Conclusion DN patients have abnormal podocyte ultrastructure and nephrin expression. Candesartan can protect podocyte damage through up-regulating nephrin expression and improving podocyte ultrastructure.%目的 探讨糖尿病肾病(diabetic nephropathy,DN)大鼠足细胞超微结构及其相关分子nephrin表达的变化,以及坎地沙坦对其干预的影响,为DN的防治提供理论依据.方法 选择健康雄性SD大鼠36只,按随机数字表法分为A组(正常对照组)、B组(DN组)和C组(DN+坎地沙坦组),每组12只.B、C组尾静脉注射链脲佐菌素(30 mg·kg-1)制

  15. 自噬减轻造影剂诱导足细胞氧化应激损伤%Autophagy alleviate podocytes injury induced by contrast media via oxidative stress

    Institute of Scientific and Technical Information of China (English)

    汪雄攀; 杨定平; 杨定位; 贾汝汉; 丁国华; 朱吉莉; 简永红

    2014-01-01

    Objective To evaluate the effects of autophagy on oxidative stress induced by contrast media in podocytes.Methods The differentiated mouse podocytes were exposed to contrast media (Iopromide,50 mg/L)、rapamycin (Rap,autophagy enhancer,1 ng/L),3-methyladenine (3-MA,autophagy inhibitor,2 mmol/L) for 2 hours.The expression of autophagy protein LC3-Ⅱ and Beclin-1 as well as oxidative stress-related proteins Catalase,MnSOD were detected by Western blot.The formations of autophagy were observed by MDC staining,and the levels of reactive oxygen species (ROS) by CM-H2DCFDA staining.Cell activity was evaluated by CCK8 assay.Results Both the levels of oxidative stress and autophagy in podocytes increased when stimulated by contrast media,the expression of LC3-Ⅱ and Beclin-1 were enhanced,Catalase and MnSOD were inhibited (all P < 0.05).Rapamycin increased the expression of Catalase,MnSOD and cell activity of podocytes,reduced the generation of ROS (all P < 0.05),but in Rap group,cell activity showed no significant difference (P > 0.05).3-MA decreased the expression of Catalase 、MnSOD and inhibited the cell activity of podocyte,increased the generation of ROS (all P < 0.05).Conclusion Autophagy protects podocyte from contrast media by the means of reducing oxidative stress.%目的 研究自噬在造影剂诱导足细胞氧化应激损伤中的作用.方法 培养的小鼠永生化足细胞共分为6组:(1)正常对照(Con)组;(2)造影剂(CM)组;(3)雷帕霉素(Rap)组;(4)造影剂加雷帕霉素(CM+Rap)组;(5)3-甲基腺嘌呤(3-MA)组;(6)造影剂加3-甲基腺嘌呤(CM+3-MA)组,予以相应的刺激2h.观察自噬增强剂雷帕霉素与自噬抑制剂3-甲基腺嘌呤对造影剂诱导的足细胞氧化应激及细胞活性的影响.Western印迹检测各组足细胞内自噬相关蛋白LC3-Ⅱ、Beclin-1及氧化应激相关蛋白Catalase、MnSOD的表达,丹酰戊二胺(MDC)染色检测足细胞内自噬体变化,采用氯甲基-2',7'-二氯

  16. Burst Suppression: A Review and New Insights

    Directory of Open Access Journals (Sweden)

    Jonathan Dillon Kenny

    2014-12-01

    Full Text Available Burst suppression is a pattern of brain electrical activity characterized by alternating periods of high-amplitude bursts and electrical silence. Burst suppression can arise from several different pathological conditions, as well as from general anesthesia. Here we review current algorithms that are used to quantify burst suppression, its various etiologies, and possible underlying mechanisms. We then review clinical applications of anesthetic-induced burst suppression. Finally, we report the results of our new study showing clear electrophysiological differences in burst suppression patterns induced by two common general anesthetics, sevoflurane and propofol. Our data suggest that the circuit mechanisms that generate burst suppression activity may differ between different general anesthetics.

  17. Suppression of stratified explosive interactions

    Energy Technology Data Exchange (ETDEWEB)

    Meeks, M.K.; Shamoun, B.I.; Bonazza, R.; Corradini, M.L. [Wisconsin Univ., Madison, WI (United States). Dept. of Nuclear Engineering and Engineering Physics

    1998-01-01

    Stratified Fuel-Coolant Interaction (FCI) experiments with Refrigerant-134a and water were performed in a large-scale system. Air was uniformly injected into the coolant pool to establish a pre-existing void which could suppress the explosion. Two competing effects due to the variation of the air flow rate seem to influence the intensity of the explosion in this geometrical configuration. At low flow rates, although the injected air increases the void fraction, the concurrent agitation and mixing increases the intensity of the interaction. At higher flow rates, the increase in void fraction tends to attenuate the propagated pressure wave generated by the explosion. Experimental results show a complete suppression of the vapor explosion at high rates of air injection, corresponding to an average void fraction of larger than 30%. (author)

  18. 儿童紫癜性肾炎足突融合与肾脏病理分级相关性研究%Discussion of relationship between renal pathology and glomerular podocyte injury in childhood Henoch-Sch(o)nlein purpura nephritis.

    Institute of Scientific and Technical Information of China (English)

    任献国; 张沛; 杜丽芳; 高远赋; 樊忠民; 高春林; 茅松; 何旭; 夏正坤

    2013-01-01

    Objective To analyze relationship between renal pathology and glomerular podocyte food processes fused in childhood Henoch-Sch(o)nlein purpura nephritis.Methods Renal pathological types of 72 children suffering from HSPN were reviewed during the period from January 1st 2008 to January 1st 2011 from Nanjing Command of Jingling Hospital.Pathological grading and immunofluorescence typing were analyzed.The information of podocyte food processes fused was showed by electron microscopy.Results Pathological findings were classified as ISKDC (the International Society of Kidney Disease in Children) grade Ⅱ in 34 (47.2%) and grade Ⅲ in 38 (52.8%).Glomerular podocyte injury was classified by electron microscope as food processes of podocyte fused extensively in 21 cases,food processes of podocyte fused segmentally in 35 cases,food processes of podocyte without fusion in 1 lcases.There was no renal glamorous in nephridial tissue by electron microscope in five cases.Conclusion The childhood HSPN is expressed with foot process of podocytes fused more extensively on electron microscope besides glomerular pathologic change.The more serious the degree of podocyte injury is,the more obvious the pathologic changeis.%目的 探讨儿童紫癜性肾炎(Henoch-Sch(o)nlein purpura nephritis,HSPN)足突融合与肾脏病理分级的相关性.方法 回顾性分析2008年1月1日至2011年1月1日南京军区南京总医院儿科肾活检病理检查诊断为过敏性紫癜性肾炎的住院病例72例,对其进行病理分级和免疫荧光分型,并在电镜下观察足细胞足突融合情况.结果 病理分级按照国际儿童肾脏病学会(ISKDC)分类集中在Ⅱ级和Ⅲ级,其中病理分级为Ⅱ级的患儿34例(47.2%),病理分级为Ⅲ级38例(52.8%).电镜下观察肾小球足细胞损伤情况:足突广泛融合21例,足突节段融合35例和无足突融合11例;5例电镜下未见肾小球.足突广泛融合患儿病理分级为Ⅲ级者较足突节段融

  19. Chk1 suppressed cell death

    Directory of Open Access Journals (Sweden)

    Meuth Mark

    2010-09-01

    Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

  20. EMP and HPM Suppression Techniques

    Science.gov (United States)

    2007-11-02

    power lines from external sources. Lightning is in the induced category. It is unlikely that any transient suppression device will survive or protect...from a direct lightning hit; however, direct hits are extremely rare. Most damage to electronic circuits caused by lightning is the result of the...tested by Littelfuse, Inc. in accordance with IEC 801-2 ESD test specifications. Taking into account the relative energies associated with ESD and

  1. Jet Suppression Measured in ATLAS

    CERN Document Server

    Citron, Zvi Hirsh; The ATLAS collaboration

    2015-01-01

    In relativistic heavy ion collisions, a hot medium with a high density of unscreened color charges is produced, and jets propagating through this medium are known to suffer energy loss. This results in a lower yield of jets emerging from the medium than expected in the absence of medium effects, and thus modifications of the jet yield are directly sensitive to the energy loss mechanism. Furthermore, jets with different flavor content are expected to be affected by the medium in different ways. Parton showers initiated by quarks tend to have fewer fragments carrying a larger fraction of the total jet energy than those resulting from gluons. In this talk, the latest ATLAS results on single jet suppression will be presented. Measurements of the nuclear modification factor, RAA, for fully reconstructed jets are shown. The rapidity dependence of jet suppression is discussed, which is sensitive to the relative energy loss between quark and gluon jets. New measurements of single hadron suppression out to pT~150 GeV ...

  2. FLUTTER SUPPRESSION USING DISTRIBUTEDPIEZOELECTRIC ACTUATORS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A piezoelectric actuator has the benefits of flexibility of its position, without time lag and wide bandpass characteristics. The early results of the wind tunnel flutter suppression test using the piezoeletric actuator were presented in Ref.[1]. A rigid rectangular wing model is constrained by a plunge spring and a pitch spring, and a pair of piezoelectric actuators is bonded on both sides of the plunge spring so as to carry out the active control. Refs.[2,3] reported two flutter suppression wind tunnel tests where the distributed piezoelectric actuators were used. In Ref.[2] low speed wind tunnel tests were conducted with aluminum and composite plate-like rectangular models fully covered by piezoelectric actuators. Flutter speed is increased by 11%. In Ref.[3] a composite plate-like swept back model with piezoceramic actuators bonded on the inboard surface was tested in a transonic wind tunnel and a 12% increment of flutter dynamic pressure was achieved.  In the present investigation, an aluminum plate-like rectangular model with inboard bonded piezoceramic actuators is adopted. Active flutter suppression control law has been designed. A series of analyses and ground tests and, finally, low-speed wind tunnel tests with the active control system opened and closed are conducted. Reasonable results have been obtained.

  3. Adaptive Filtering for Aeroservoelastic Response Suppression Project

    Data.gov (United States)

    National Aeronautics and Space Administration — CSA Engineering proposes the design of an adaptive aeroelastic mode suppression for advanced fly-by-wire aircraft, which will partition the modal suppression...

  4. Effect of triperygium wilfordii polyglucoside on the podocytes of diabetic nephropathy rats%雷公藤多苷对糖尿病肾病大鼠足细胞病变的影响

    Institute of Scientific and Technical Information of China (English)

    郑云; 郝丽; 潘梦舒; 丁楠

    2011-01-01

    目的 探讨雷公藤多苷(TWP)对糖尿病肾病大鼠足细胞病变的影响.方法 SD大鼠100只,按随机数字表法分为正常对照组(A组)、糖尿病组(B组)与TWP治疗组(C 组).并将C组按4、8、16 mg·kg-1·d-1不同给药剂量分为3组(Ca、Cb、Cc).糖尿病组与TWP 治疗组大鼠分别给予链脲菌素(STZ)一次性腹腔注射建立糖尿病大鼠模型.12周后检测24 h 尿蛋白量、血肌酐(Scr)、尿素氮(BUN)、外周血白细胞(WBC)、血糖(Glu)、肾质量/体质量(KW/BW)的变化;HE染色检测肾组织病理变化;透射电镜测量足细胞超微结构变化;免疫荧光法检测肾皮质nephrin和podocin蛋白表达.结果 (1)与A组比较,B组及C组Scr、BUN 增高(P<0.05);Glu、KW/BW和24 h尿蛋白量显著增高(P<0.01),除Cc组(3/20)出现肝酶(ALT、AST)增高及WBC下降外,各组ALT、AST、WBC差异无统计学意义;肾且庠皮质nephrin 和podocin蛋白表达减少,肾小球、小管间质及足细胞病变明显.(2)与B组比较,C组KW/BW 和24 h尿蛋白量降低(P<0.01),肾脏皮质nephrin和podocin蛋白表达增高(均P<0.01),肾小球、小管间质及足细胞病变明显减轻,并随雷公藤多苷剂量的增加而越加明显.结论 TWP对糖尿病大鼠足细胞病变具有保护作用,并与剂量相关.其部分机制可能与上调nephrin 和podocin蛋白表达有关.%Objective To explore the effect of triperygium wilfordii polyglucoside(TWP) on the podocytes of rats with diabetes nephropathy(DN). Methods One hundred SD rats were randomly divided into normal control group (Group A),DN group (Group B),TWP group(Group C).TWP group was divided into 3 subgroups(Ca,Cb,Cc)according to the different doses 4,8,16mg·kg-1·d-1,respectively.Rats in DN group and TWp group were given streptozocin(STZ)by intraperitoneal injection to establish animal model of diabetes.After 12 weeks,24 h urinary protein excretion rate(UAER),BUN,Scr,white blood cell(WBC),blood glucose(Glu),and kidney weight (KW

  5. Menstrual suppression in special circumstances.

    Science.gov (United States)

    Kirkham, Yolanda A; Ornstein, Melanie P; Aggarwal, Anjali; McQuillan, Sarah; Allen, Lisa; Millar, Debra; Dalziel, Nancy; Gascon, Suzy; Hakim, Julie; Ryckman, Julie; Spitzer, Rachel; Van Eyk, Nancy

    2014-10-01

    Objectif : Offrir, aux fournisseurs de soins de santé, un document de consensus canadien comptant des recommandations pour ce qui est de la suppression menstruelle chez les patientes qui font face à des obstacles physiques et/ou cognitifs ou chez les patientes qui font l’objet d’un traitement contre le cancer et pour lesquelles les règles pourraient exercer un effet délétère sur la santé. Options : Le présent document analyse les options disponibles aux fins de la suppression menstruelle, les indications, les contre-indications et les effets indésirables (tant immédiats qu’à long terme) propres à cette dernière, et les explorations et le monitorage nécessaires tout au long de la suppression. Issues : Les cliniciens seront mieux renseignés au sujet des options et des indications propres à la suppression menstruelle chez les patientes qui présentent des déficiences cognitives et/ou physiques et chez les patientes qui font l’objet d’une chimiothérapie, d’une radiothérapie ou d’autres traitements contre le cancer. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, EMBASE, OVID et The Cochrane Library au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « heavy menstrual bleeding », « menstrual suppression », « chemotherapy/radiation », « cognitive disability », « physical disability », « learning disability »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés, aux études observationnelles et aux études pilotes. Aucune restriction n’a été imposée en matière de langue ou de date. Les recherches ont été mises à jour de façon régulière et du nouveau matériel a été intégré à la directive clinique jusqu’en septembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d

  6. How to suppress undesired synchronization

    CERN Document Server

    Louzada, V H P; Andrade, J S; Herrmann, H J

    2012-01-01

    It is delightful to observe the emergence of synchronization in the blinking of fireflies to attract partners and preys. Other charming examples of synchronization can also be found in a wide range of phenomena such as, e.g., neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in communication networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge of the system, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement in mitigation is observed when contrarians sit at the highly connected ele...

  7. How to suppress undesired synchronization.

    Science.gov (United States)

    Louzada, V H P; Araújo, N A M; Andrade, J S; Herrmann, H J

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network.

  8. Tactile stimulation can suppress visual perception.

    Science.gov (United States)

    Ide, Masakazu; Hidaka, Souta

    2013-12-13

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities.

  9. MEK5 suppresses osteoblastic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kaneshiro, Shoichi [Department of Orthopaedic Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka City, Osaka 553-0003 (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Higuchi, Chikahisa, E-mail: c-higuchi@umin.ac.jp [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  10. Tactile stimulation can suppress visual perception

    OpenAIRE

    Masakazu Ide; Souta Hidaka

    2013-01-01

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimul...

  11. NOVEL BIPHASE CODE -INTEGRATED SIDELOBE SUPPRESSION CODE

    Institute of Scientific and Technical Information of China (English)

    Wang Feixue; Ou Gang; Zhuang Zhaowen

    2004-01-01

    A kind of novel binary phase code named sidelobe suppression code is proposed in this paper. It is defined to be the code whose corresponding optimal sidelobe suppression filter outputs the minimum sidelobes. It is shown that there do exist sidelobe suppression codes better than the conventional optimal codes-Barker codes. For example, the sidelobe suppression code of length 11 with filter of length 39 has better sidelobe level up to 17dB than that of Barker code with the same code length and filter length.

  12. Issues in Numerical Simulation of Fire Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  13. 他克莫司通过上调自噬作用保护2型糖尿病大鼠足细胞%Tacrolimus protects podocytes by up-regulating autophagy in type 2 diabetic model rats

    Institute of Scientific and Technical Information of China (English)

    王彤; 马瑞霞; 武国华; 孙益婷

    2016-01-01

    Objective To assess the effects of tacrolimus (FKS06) on podocyte in type 2 diabetic model rats and to explore the potential mechanism.Methods The model rats were fed with high fat and high sugar food and combining with a low-dose of streptozotocin (STZ).They were then randomly divided into a diabetic mellitus group (DM group) and a FK506 group.A normal control group (NC group) was also set.The rats in FK506 group were given with 0.5 mg· kg-1· d-1 FK506 for 8 weeks.The biochemical parameters were measured.The changes of renal pathology and ultrastructure of podocyte were observed by the light and electron microscopy.The expression of nephrin and LC3-Ⅱ was determined by immunohistochemistry and Western blotting.Results (1) Compared with those in NC group,KW/BW,systolic blood pressure (SBP),fasting blood glucose (FBG),triglyceride (TG),total cholesterol (TC),urinary albumin excretion rate (UAE) and creatinine clearance rate (Ccr) in DM group were significantly increased (all P < 0.05).And the KW/BW,UAE and Ccr were decreased in FK506 group compared to those in DM group (all P < 0.05),while other parameters had no significant difference (all P > 0.05).(2) Compared with those in NC group,the glomerular volume,mesangial cell proliferation and accumulation of mesangial matrix were increased,and the foot process became disorder and fusion in DM group,while these changes were significantly reduced in FK506 group.(3) Compared with that in NC group,the expression of nephrin and LC3-Ⅱ was decreased in DM group (all P < 0.05),and both of parameters were higher in FK506 group than those in DM group (all P < 0.05).Conclusion FK506 may enhance podocyte autophagy in type 2 diabetic model rats and attenuate podocyte injury.%目的 探讨他克莫司(FK506)对2型糖尿病(T2DM)大鼠足细胞的保护作用及其可能机制.方法 高糖高脂喂养联合小剂量链佐星(STZ)构建T2DM大鼠模型,模型大鼠随机分为糖尿病组(DM组)和FK506

  14. Impact of interaction of advanced glycation end product and its receptor on podocytes apoptosis%晚期糖基化终末产物与其受体相互作用对足细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    于青; 袁伟杰; 刘智辉; 姚建

    2008-01-01

    目的 探讨可溶性与复合型晚期糖基化终末产物(AGE)与晚期糖基化终末产物受体(RAGE)的相互作用对足细胞凋亡的影响.方法 以可溶性(CML-BSA、AGE-BSA)和复合型(AGE修正胶原IV)AGE刺激小鼠足细胞,并用浓度分别为10、50、100 mg/L的AGE刺激细胞,应用TUNEL染色和荧光激活细胞分类(FACS)法来计数凋亡和坏死的足细胞.用RAGE iRNA转染足细胞后,以同样剂量的可溶性和复合犁AGE刺激足细胞,观察凋亡情况的改变.结果 可溶性和复合型AGE均町诱导小鼠足细胞凋亡,复合型AGE引起的足细胞凋亡是可溶性AGE的2~3倍(均P<0.01).AGE呈剂最依赖性引起足细胞凋亡.用RAGEiRNA转染足细胞,降低60%~70%RAGE基因活性后,可溶性AGE引起的凋亡率明显下降,复合型AGE诱导的凋亡有下降趋势,但不明显.只有在AGE 100 mg/L刺激后才发牛细胞坏死.结论 可溶性AGE主要通过与RAGE相互作用引起足细胞凋亡,复合型AGE部分通过与RAGE相互作用诱导足细胞凋亡.减少AGE生成和RAGE表达可能是预防肾脏病进展的重要途径.%Objective To study the effects of the interaction of advanced glycation end products (AGEs) and the receptor of AGEs (RAGE) on apoptosis of mice podocytes. Methods Podocytes were exposed to soluble AGEs such as bovine serum albumin (BSA), carboxymethyl-lysin (CML)-BSA, AGE-BSA and matrix-bound AGEs (AGE-modified collagen Ⅳ ), and to different concentrations of AGE, such as 10 mg/L, 50 mg/L, 100 mg/L. Apoptosis was assessed by TUNEL staining. Fluorescence-activated cell sorting (FACS) was used for the quantification of apoptotic andnecrotic podocytes after Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling. Apoptosis was described as the ratio of apoptotic cells to the total number cells under the high-power field, siRNA was transfected into podocytes through combining Dharmacon on Targetplus SMART pool siRNA reagents and Amaxa RNAi

  15. Bufalin alleviates adriamycin-induced podocyte injury by up-regulating the expression of vitamin D receptor%蟾蜍灵通过上调维生素D受体表达缓解阿霉素诱导的足细胞损伤

    Institute of Scientific and Technical Information of China (English)

    殷勤; 施会敏; 曲高婷; 张爱青; 甘卫华

    2016-01-01

    Objective To investigate the role of vitamin D receptor (VDR) in the protection of bufalin on podocyte injury induced by adriamycin (ADR).Methods (1) In vitro:the toxic effect of different concentrations of bufalin (10-9,10-8,10-7,104 mol/L) on podocyte was evaluated by lactate dehydrogenase (LDH) test;Annexin V-FITC and RT-PCR were utilized for podocyte apoptosis and VDR mRNA level respectively.Western blotting was used to analyze the protein expression of VDR and nephrin.SiRNA intervene was also applied to evaluate the role of VDR in bufalin's protective effect on podocyte injury induced by ADR.(2) In vitro:24 SD rats were randomly divided into three groups:control group,ADR group and ADR+bufalin group.TUNEL assay was applied to detect the apoptosis of podocytes in the kidney.Immunofluorescence and transmission electron microscope (TEM) were applied to analyze the expression of VDR and the ultrastructure of the glomerulus.Results Bufalin concentration lower than 10-7 mol/L had no toxicity on normal podocyte.Bufalin reduced the urinary protein excretion (P < 0.05),alleviated the removal of podocyte foot processes and attenuated the changes in nephrin expression in the glomerulus of the adriamycin (ADR) rats (P < 0.05).Bufalin notably inhibited the down-regulation of VDR in protein levels on the glomerulus of the ADR rats.Additionally,bufalin inhibited the down-regulation of VDR in both mRNA levels and protein levels (P < 0.05),nephrin protein expression (P< 0.05),and apoptosis induced by ADR in cultured podocytes.Additionally,VDR specific siRNA intervene abolished the protective effect of bufalin in ADR-induced podocyte injury.Conclusion Bufalin can alleviate ADR-induced podocyte injury via enhancing VDR expression.%目的 探讨维生素D受体(vitamin D receptor,VDR)在蟾蜍灵保护阿霉素诱导的足细胞损伤中的作用.方法 (1)体外实验:乳酸脱氢酶(LDH)释放试验观察不同浓度蟾蜍灵(10-9、10-8、10-7、10-6mol/L)对正常足

  16. Attentional selection by distractor suppression.

    Science.gov (United States)

    Caputo, G; Guerra, S

    1998-03-01

    Selective attention was studied in displays containing singletons popping out for their odd form or color. The target was defined as the form-singleton, the distractor as the color-singleton. The task was to discriminate the length of a longer line inside the target. Target-distractor similarity was controlled using a threshold measurement as dependent variable in experiments in which distractor presence vs absence, bottom-up vs top-down selection (through knowledge of target features), and target-distractor distance were manipulated. The results in the bottom-up condition showed that length threshold was elevated when a distractor was present and that this elevation progressively increased as the number of distractors was increased from one to two. This set-size effect was not accounted by the hypothesis that selective attention intervenes only at the stage of decision before response. Selective attention produced a suppressive surround in which discriminability of neighboring objects was strongly reduced, and a larger surround in which discriminability was reduced by an approximately constant amount. Different results were found in the top-down condition in which target discriminability was unaffected by distractor presence and no effect of target-distractor distance was found. On the other hand, response times in both bottom-up and top-down conditions were slower the shorter the target-distractor distance was. On the basis of the experimental results, selective attention is a parallel process of spatial filtering at an intermediate processing level operating after objects have been segmented. This filtering stage explores high level interactions between objects taking control on combinatorial explosion by operating over only a limited spatial extent: it picks out a selected object and inhibits the neighboring objects; then, non-selected objects are suppressed across the overall image. When no feature-based selection is available in the current behavior, this

  17. Atomic clocks with suppressed blackbody radiation shift

    CERN Document Server

    Yudin, V I; Okhapkin, M V; Bagayev, S N; Tamm, Chr; Peik, E; Huntemann, N; Mehlstaubler, T E; Riehle, F

    2011-01-01

    We develop a nonstandard concept of atomic clocks where the blackbody radiation shift (BBRS) and its temperature fluctuations can be dramatically suppressed (by one to three orders of magnitude) independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies $\

  18. Suppressive soils: back on the radar screen

    Science.gov (United States)

    Suppressive soils are those in which a pathogen does not establish or persist, establishes but causes little or no damage, or establishes and causes disease for a while but thereafter the disease is less important, although the pathogen may persist in the soil (Weller, 2002). ‘General suppression,’ ...

  19. Impacts of suppressing guide on information spreading

    Science.gov (United States)

    Xu, Jinghong; Zhang, Lin; Ma, Baojun; Wu, Ye

    2016-02-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  20. Impacts of suppressing guide on information spreading

    CERN Document Server

    Xu, Jinghong; Ma, Baojun; Wu, Ye

    2015-01-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  1. 雷公藤多甙联合厄贝沙坦对糖尿病肾病患者尿足细胞排泄影响及机制探讨%The effects and mechanism of tripterygium wilfordii Hook F combination with irbesartan on urinary podocyte excretion in diabetic nephropathy patients

    Institute of Scientific and Technical Information of China (English)

    马瑞霞; 赵娜; 张伟

    2013-01-01

    Objective To investigate the effects of the combination of tripterygium wilfordii Hook F (TwHF) and irbesartan on urinary podocyte in diabetic kidney disease (DKD) patients,and to discuss the mechanism of protective effect of TwHF on DKD.Methods A total of 45 type 2 diabetic kidney disease patients were enrolled into this prospective study,and were randomly divided into 3 groups:TwHF treatment group (DT,n =15),irbesartan treatment group (DI,n =15),and TwHF combined with irbesartan treatment group (DTI,n =15).After 6 weeks washout,the 3 groups were given TwHF (1-2 mg · kg-1 ·d-1),irbesartan (150-300 mg/d),and TwHF (1-2 mg · kg-1 · d-1) combined with irbesartan (150-300 mg/d) for 12 weeks respectively.Fifteen healthy volunteers served as controls.Urinary podocytes were identified and quantitated by immunofluorescence staining of urinary sediments labeled by monoclonal antibody podocalyxin.In addition,we studied urinary connective tissue growth factor (CTGF),osteopontin (OPN) and transforming growth factor β1 (TGFβ1) concentrations in DKD patients by enzyme-linked immunosorbent assay.Results Urinary detached podocytes were obviously higher in the urine of DKD patients than in healthy controls (P <0.01).Podocyte detection rate was 86.6% in the urine of DKD patients.The protein expressions of CTGF,OPN and TGFβ1 in patients with urinary podocyte were significantly increased than those without urinary podocyte (P < 0.05 or 0.01).Correlation analysis showed that there was positive correlation between urinary protein excretion and urinary podocytes (r =0.79,P < 0.01) and there were positive correlations between the number of urinary podocytes and urinary protein expressions of CTGF,OPN and TGFβ1 (r =0.56,0.41,0.44,respectively,all P values < 0.01).Urinary albumin excretion and urinary podocytes were significantly decreased in all treatment groups (P < 0.01),simultaneously,urinary concentrations of CTGF,OPN and TGFβ1 were reduced in all groups at week 12

  2. Hydrogen suppresses UO 2 corrosion

    Science.gov (United States)

    Carbol, Paul; Fors, Patrik; Gouder, Thomas; Spahiu, Kastriot

    2009-08-01

    Release of long-lived radionuclides such as plutonium and caesium from spent nuclear fuel in deep geological repositories will depend mainly on the dissolution rate of the UO 2 fuel matrix. This dissolution rate will, in turn, depend on the redox conditions at the fuel surface. Under oxidative conditions UO 2 will be oxidised to the 1000 times more soluble UO 2.67. This may occur in a repository as the reducing deep groundwater becomes locally oxidative at the fuel surface under the effect of α-radiolysis, the process by which α-particles emitted from the fuel split water molecules. On the other hand, the groundwater corrodes canister iron generating large amounts of hydrogen. The role of molecular hydrogen as reductant in a deep bedrock repository is questioned. Here we show evidence of a surface-catalysed reaction, taking place in the H 2-UO 2-H 2O system where molecular hydrogen is able to reduce oxidants originating from α-radiolysis. In our experiment the UO 2 surface remained stoichiometric proving that the expected oxidation of UO 2.00 to UO 2.67 due to radiolytic oxidants was absent. As a consequence, the dissolution of UO 2 stopped when equilibrium was reached between the solid phase and U 4+ species in the aqueous phase. The steady-state concentration of uranium in solution was determined to be 9 × 10 -12 M, about 30 times lower than previously reported for reducing conditions. Our findings show that fuel dissolution is suppressed by H 2. Consequently, radiotoxic nuclides in spent nuclear fuel will remain immobilised in the UO 2 matrix. A mechanism for the surface-catalysed reaction between molecular hydrogen and radiolytic oxidants is proposed.

  3. Psychopathology and Thought Suppression: A Quantitative Review

    Science.gov (United States)

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  4. Psychopathology and thought suppression: a quantitative review.

    Science.gov (United States)

    Magee, Joshua C; Harden, K Paige; Teachman, Bethany A

    2012-04-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression.

  5. Effects of tic suppression: ability to suppress, rebound, negative reinforcement, and habituation to the premonitory urge.

    Science.gov (United States)

    Specht, Matt W; Woods, Douglas W; Nicotra, Cassandra M; Kelly, Laura M; Ricketts, Emily J; Conelea, Christine A; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2013-01-01

    The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

  6. The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy O número de podócitos e fendas diafragmáticas estão alterados na nefropatia diabética

    Directory of Open Access Journals (Sweden)

    Mauro Masson Lerco

    2006-04-01

    Full Text Available PURPOSE: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. METHODS: Sixty "Rattus Wistar"of both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. RESULTS: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29µm; semi-interquartile range=0.065µm than in the normal rats (0.23µm; 0.035µm. Diabetic rat podocyte number (8; 1, slit diaphragm number (4; 1, and slit diaphragm extension (0.021µm; 0.00435µm were significantly lower than in normal rats (11; 1 and (7; 1.5, and (0.031µm; 0.0058µm. Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h. CONCLUSION: Experimental diabetes is associated with significant (pOBJETIVO: Determinar o número de podocitos e fendas diafragmáticas, a extensão das fendas diafragmáticas e a espessura da Membrana Basal Glomerular (MBG na nefropatia diabética. MÉTODOS: Sessenta "Rattus Wistar" de ambos os sexos, pesando entre 200-300g, foi dividido em dois grupos experimentais: grupo normal 10 animais, e grupo diabético induzido por aloxana - 50 animais. A Aloxana foi administrada em dose única endovenosa de 42mg/kg de peso. Medimos o peso, ingestão de

  7. 黄蜀葵花对阿霉素肾病大鼠足细胞的保护作用%Protective effect of Sunset Abelmoschus on podocyte injury in adriamycin-induced nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    边琪; 郭志勇; 胡海燕; 李娟

    2012-01-01

    目的 探讨黄蜀葵花(黄葵)治疗阿霉素肾病大鼠的疗效及其对足细胞病变的影响.方法 雄性SD大鼠50只,按随机数字法分为假手术组(n=10)、模型组(n=10)、黄葵低剂量组(0.5 g·kg-1·d-1,n=10)、黄葵中剂量组(1.0 g·kg-1·d-1,n=10)和黄葵高剂量组(2.0 g·kg-1·d-1,n=10).采用单侧肾切除联合两次阿霉素(ADR)注射法,制备阿霉素肾病大鼠模型.黄葵各组于右肾摘除术当天起给予相应剂量黄葵溶液灌胃.分别在术前、术后2、4、6、8周末检测大鼠尿蛋白、尿N-乙酰葡萄糖氨基转移酶(NAG)、血清白蛋白、Scr和血脂.第8周末宰杀大鼠,取肾组织行光镜和电镜检查,并观察肾组织nephrin的分布.结果 与模型组比较,黄葵各组在各时间点的尿蛋白量和尿NAG水平均降低,以高剂量组最显著(P<0.01);且血浆白蛋白增加,血脂紊乱改善,差异均有统计学意义(P<0.05).模型组及黄葵各治疗组Scr自第4周起较假手术组明显升高;第8周末,黄葵高剂量组Scr低于模型组(P<0.05).黄葵各组肾小球球性硬化和节段硬化比例均低于模型组,肾小管间质损害改善,且以高剂量组最显著.与模型组比较,黄葵各组足细胞的足突损伤减轻,足突融合程度和范围均有所改善,以高剂量组最显著.黄葵各组肾组织nephrin表达较模型组增加.结论 黄葵能减少阿霉素肾病大鼠的蛋白尿,减轻肾组织损伤和慢性化,其机制可能与改善足细胞病变有关.%Objective To explore the effect of Sunset Abelmoschus on podocyte injury in adriamycin-induced nephropathy rats.Methods Fifty male SD rats were randomly divided into five groups:sham operation group (n=10),model group (n=10),Sunset Abelmoschus low dose group (0.5 g·kg-1· d-1 n=10),middle dose group (1.0 g· kg-1· d-1,n=10) and high dose group (2.0 g· kg-1· d-1,n=10).Unilateral nephrectomy combined repeated adriamycin injection were performed to establish

  8. The effects of hydrochloride Benazepril on podocyte nephrin protein expression in diabetic rats%盐酸贝那普利对糖尿病大鼠肾脏足细胞及其蛋白nephrin表达的影响

    Institute of Scientific and Technical Information of China (English)

    孔敏; 任伟; 王艳; 陈玉米; 叶山东; 邢燕; 胡闻; 江洁龙

    2012-01-01

    目的 观察盐酸贝那普利对糖尿病大鼠足细胞及其nephrin蛋白表达的影响,初步探讨其对糖尿病大鼠肾脏保护作用及其可能的机制.方法 将健康雄性SD大鼠随机分为正常对照(NC组)和实验组.实验组通过一次性腹腔注射链脲佐菌素建立糖尿病大鼠模型,造模成功后,随机分为糖尿病对照组(DM组)和贝那普利干预组(DT组),DT组予以盐酸贝那普利10 mg·kg-1 ·d-1,混悬液灌胃.NC、DM组予以等量0.9%氯化钠注射溶液相应时间灌胃.每周监测各组大鼠尾外周血血糖.4周后,检测糖化血红蛋白( HbA1c)及尿液中nephrin蛋白、白蛋白(ALB)及视黄醇结合蛋白(RBP).处死大鼠留取肾脏标本,在电镜下观察肾脏组织形态学及足细胞超微结构的变化,采用免疫组织化学方法检测肾组织nephrin蛋白的表达水平.结果 造膜4周后,DM和DT组的HbA1c、肾脏肥大指数、尿nephrin/肌酐(Cr)、尿ALB/Cr、尿RBP/Cr与NC组相比,差异有统计学意义(P<0.05),DM和DT组与NC组nephrin表达水平差异有统计学意义(P<0.05),电镜下糖尿病大鼠组与NC组相比肾组织病变明显.与DM组比较,DT组除血糖和HbA1c水平外,其余各项指标二组之间均差异有统计学意义(P<0.05),肾组织病理改变亦明显减轻.结论 贝那普利通过上调nephrin表达水平改善修复受损足细胞,减少足细胞脱落,从而减少糖尿病大鼠蛋白尿,对糖尿病肾病发挥保护作用.%Objective To observe effects of hydrochloride benazepril on podocyte nephrin protein expression in diabetic rats and investigate its protective effects on the kidney of rats and its possible mechanism. Methods Spra-gue-Dawley (SD) rats were assigned to normal control and model group. The diabetes model was established by a single injection of streptozotoin (STZ) ,randomly divided into diabetic nephropathy (DM group) and benazepril intervention group (DT group). DT group received benazepril hydrochloride

  9. Effect of Yishe Capsule on Podocytes in Renal Tissue of Rats with Diabetic Nephropathy%益肾胶囊对糖尿病肾病模型肾小球足细胞的影响

    Institute of Scientific and Technical Information of China (English)

    许洪燕; 方敬爱; 张晓东; 孙艳艳

    2009-01-01

    Objective:To observe the effect of yishe capsule on pathological changes of renal tissue and podocyte ultrastruc-ture. Method:Totally 60 wistar rats were divided into four groups: normol control group (controf group),DN model group(model group) ,yishe capsule treatment gronp,benazepril treatment group.The rat in group of yishe capsule were garage given 625 mg.kg-1.water was used. AU the mrs received daily gavage for 12 weeks, the urinary protein in 24 h and the level of serum creatinine,urea ni-trogen were measured. The renal pathology and the changes of podocyte ultrastructure were detected under light microscope and transmission electron microscope. Results: In 12 w,urinary protein quantity in 24 h,Scr and BUN of model group rats were higher distinctly than those of control group( respectively, P < 0.05). After treatment of benazepril and yishe capsule, urinary protein quanti-ty in 24 h,Scr,BUN were reduced( respectively P < 0.05). We observed basement membrane thicken,foot process with disorders,foot process fusion,increased mesangial matrix, widened mesangium in model group by light microscope and transmission eletron mi-croscope. Benazepril and yishe capsule can improve ultrastructure in kidney of diabetic rats, lessen the fusion of foot process, ameliorate the renal pathomorphology change. Conclusion: Yishe capsule had a effect on the podocyte of diabetic nephropathy rats by reducing urine protein and improving renal function, thus alleviated the renal damage in diabetic rats.%目的:观察益肾胶囊对糖尿病肾病(DN)大鼠肾组织病理改变及足细胞超微结构的影响.方法:将60只wis-tar大鼠随机分为4组:正常对照组(对照组)、DN模型组(模型组)、苯那普利组、益肾胶囊组.于注射链脲佐菌素(STZ)后3d起,苯那普利组每日每只灌胃苯那普利3.125 mg·kg-1·d-1,益肾胶囊组每日每只灌胃益肾胶囊625 mg·kg-1·d-1,对照组及模型组每日给予等量的蒸镏水.各组分别干预12周,观察24

  10. Suppression factors in diffractive photoproduction of dijets

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, Michael [Joseph Fourier Univ./CNRS-IN2P3/INPG, 38 - Grenoble (France). Lab. de Physique Subatomique et de Cosmologie; Kramer, Gustav [Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik

    2010-06-15

    After new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut. (orig.)

  11. Suppression factors in diffractive photoproduction of dijets

    Science.gov (United States)

    Klasen, Michael; Kramer, Gustav

    2010-11-01

    Now that new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut.

  12. Suppression factors in diffractive photoproduction of dijets

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, Michael [Universite Joseph Fourier/CNRS-IN2P3/INPG, Laboratoire de Physique Subatomique et de Cosmologie, Grenoble (France); Kramer, Gustav [Universitaet Hamburg, II. Institut fuer Theoretische Physik, Hamburg (Germany)

    2010-11-15

    Now that new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut. (orig.)

  13. Suppression factors in diffractive photoproduction of dijets

    CERN Document Server

    Klasen, M

    2010-01-01

    After new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut.

  14. Strangeness suppression in the unquenched quark model

    CERN Document Server

    Bijker, Roelof; Santopinto, Elena

    2016-01-01

    In this contribution, we discuss the strangeness suppression in the proton in the framework of the unquenched quark model. The theoretical results are in good agreement with the values extracted from CERN and JLab experiments.

  15. Quadratic dynamical decoupling with nonuniform error suppression

    Energy Technology Data Exchange (ETDEWEB)

    Quiroz, Gregory; Lidar, Daniel A. [Department of Physics and Center for Quantum Information Science and Technology, University of Southern California, Los Angeles, California 90089 (United States); Departments of Electrical Engineering, Chemistry, and Physics, and Center for Quantum Information Science and Technology, University of Southern California, Los Angeles, California 90089 (United States)

    2011-10-15

    We analyze numerically the performance of the near-optimal quadratic dynamical decoupling (QDD) single-qubit decoherence errors suppression method [J. West et al., Phys. Rev. Lett. 104, 130501 (2010)]. The QDD sequence is formed by nesting two optimal Uhrig dynamical decoupling sequences for two orthogonal axes, comprising N{sub 1} and N{sub 2} pulses, respectively. Varying these numbers, we study the decoherence suppression properties of QDD directly by isolating the errors associated with each system basis operator present in the system-bath interaction Hamiltonian. Each individual error scales with the lowest order of the Dyson series, therefore immediately yielding the order of decoherence suppression. We show that the error suppression properties of QDD are dependent upon the parities of N{sub 1} and N{sub 2}, and near-optimal performance is achieved for general single-qubit interactions when N{sub 1}=N{sub 2}.

  16. Suppression as a stereotype control strategy.

    Science.gov (United States)

    Monteith, M J; Sherman, J W; Devine, P G

    1998-01-01

    Recent research reveals that efforts to suppress stereotypic thoughts can backfire and produce a rebound effect, such that stereotypic thinking increases to a level that is even greater than if no attempt at stereotype control was initially exercised (e.g., Macrae, Bodenhausen, Milne, & Jetten, 1994). The primary goal of this article is to present an in-depth theoretical analysis of stereotype suppression that identifies numerous potential moderators of the effect of stereotype suppression on the likelihood of subsequent rebound. Our analysis of stereotype suppression focuses on two broad issues: the influence of level of prejudice and the influence of processing goals on the activation versus application of stereotypes. Although stereotype rebound occurs under some circumstances, we suggest that a complete understanding of this phenomenon requires consideration of the full array of possible moderating influences.

  17. Measurement of myeloid cell immune suppressive activity.

    Science.gov (United States)

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  18. Flame Suppression Agent, System and Uses

    Science.gov (United States)

    Parrish, Clyde F. (Inventor)

    2013-01-01

    Aqueous droplets encapsulated in a flame retardant polymer are useful in suppressing combustion. Upon exposure to a flame, the encapsulated aqueous droplets rupture and vaporize, removing heat and displacing oxygen to retard the combustion process. The polymer encapsulant, through decomposition, may further add free radicals to the combustion atmosphere, thereby further retarding the combustion process. The encapsulated aqueous droplets may be used as a replacement to halon, water mist and dry powder flame suppression systems.

  19. Noise suppression in surface microseismic data

    Science.gov (United States)

    Forghani-Arani, Farnoush; Batzle, Mike; Behura, Jyoti; Willis, Mark; Haines, Seth S.; Davidson, Michael

    2012-01-01

    We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform. We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform.

  20. Change of podocytes and αvβ3 integrin expression in kidney of diabetic rats%糖尿病大鼠肾组织足细胞数和整合素αvβ3表达的变化

    Institute of Scientific and Technical Information of China (English)

    盛佳曦; 金秀平

    2011-01-01

    目的 观察糖尿病大鼠肾小球足细胞数和整合素αvβ3表达的变化,探讨肾小球足细胞数及整合素αvβ3与糖尿病肾病(DN)的关系.方法 链脲佐菌素(STZ)制备糖尿病大鼠模型,分为对照组(n=10)和实验组(n=14).造模6周后,透射电镜下观察肾脏超微结构变化.采用免疫组化法检测肾脏上皮细胞整合素αvβ3的表达.结果 与对照组比较,实验组大鼠足细胞数减少.实验组大鼠24 h尿蛋白量明显增多(P<0.05).肾脏上皮细胞整合素αvβ3表达明显增强(P<0.01).尿清蛋白与足细胞数呈负相关,与整合素αvβ3表达呈正相关.结论 糖尿病大鼠肾组织整合素αvβ3表达增强和足细胞数减少是DN发生的重要环节.%Objective To observe the changes of podocyte and αvβ3 integrin expression in kidney of type 1 diabetic rats and to inquire into the correlation between podocyte and αvβ3 integrin with diabetic nephropathy(DN). Methods The animal model of DN was induced by intraperitoneal injection of strep tozotocin. The rats were randomized into diabetic model group with rats without STZ injection as the normal control group. After 6 weeks, the rats were sacrificed and renal tissue pathology was observed under light microscope. In addition,the ultrastructure of glomeruli was observed by electron microscope. Integrin αvβ3 expression localized to epithelical cells was detected by immunohistochemistry. Results Comparcd with the control group, podocytes of the diabetic modle group significantly decreased,the 24 h urine microalbumin increased significantly. The expression of αvβ3 integrin expression localized to epithelical was increased. Urine microalbumin was negatively corrclated with podocytes and positively correlated with αvβ3 integrin expression. Conclusion The upregulation of αvβ3 integrin and decreased expression of podocyte in kidney of type 1 diabetic rats play a key role in DN.

  1. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  2. The heme oxygenase system suppresses perirenal visceral adiposity, abates renal inflammation and ameliorates diabetic nephropathy in Zucker diabetic fatty rats.

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    Full Text Available The growing incidence of chronic kidney disease remains a global health problem. Obesity is a major risk factor for type-2 diabetes and renal impairment. Perirenal adiposity, by virtue of its anatomical proximity to the kidneys may cause kidney disease through paracrine mechanisms that include increased production of inflammatory cytokines. Although heme-oxygenase (HO is cytoprotective, its effects on perirenal adiposity and diabetic nephropathy in Zucker-diabetic fatty rats (ZDFs remains largely unclear. Upregulating the HO-system with hemin normalised glycemia, reduced perirenal adiposity and suppressed several pro-inflammatory/oxidative mediators in perirenal fat including macrophage-inflammatory-protein-1α (MIP-1α, endothelin (ET-1, 8-isoprostane, TNF-α, IL-6 and IL-1β. Furthermore, hemin reduced ED1, a marker of pro-inflammatory macrophage-M1-phenotype, but interestingly, enhanced markers associated with anti-inflammatory M2-phenotype such as ED2, CD206 and IL-10, suggesting that hemin selectively modulates macrophage polarization towards the anti-inflammatory M2-phenotype. These effects were accompanied by increased adiponectin, HO-1, HO-activity, atrial-natriuretic peptide (ANP, and its surrogate marker, urinary-cGMP. Furthermore, hemin reduced renal histological lesions and abated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, an important transmembrane protein which forms the scaffolding of the podocyte slit-diaphragm allowing ions to filter but not massive excretion of proteins, hence proteinuria. Correspondingly, hemin increased nephrin expression in ZDFs, reduced markers of renal damage including, albuminuria/proteinuria, but increased creatinine-clearance, suggesting improved renal function. Conversely, the HO-blocker, stannous-mesoporphyrin nullified the hemin effects, aggravating glucose metabolism, and exacerbating renal injury and function. The hemin effects were less

  3. Orientation-tuned surround suppression in mouse visual cortex

    NARCIS (Netherlands)

    Self, Matthew W; Lorteije, Jeannette A M; Vangeneugden, Joris; van Beest, Enny H; Grigore, Mihaela E; Levelt, Christiaan N; Heimel, J.A.; Roelfsema, Pieter R

    2014-01-01

    The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those contai

  4. Tactical Checkpoint: Hail/Warn Suppress/Stop (Poster)

    Science.gov (United States)

    2010-11-15

    distractor , optical suppression , human behavior, checkpoint, ambient light, driver suppression , human experimentation, light, paintball, obscuration...HAIL/WARN AND - SUPPRESS /STOP Poster Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER...warning to a driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression

  5. Microbial populations responsible for specific soil suppressiveness to plant pathogens

    NARCIS (Netherlands)

    Weller, D.M.; Raaijmakers, J.M.; McSpadden Gardener, B.B.; Thomashow, L.S.

    2002-01-01

    Agricultural soils suppressive to soilborne plant pathogens occur worldwide, and for several of these soils the biological basis of suppressiveness has been described. Two classical types of suppressiveness are known. General suppression owes its activity to the total microbial biomass in soil and i

  6. Suppression of behavior by timeout punishment when suppression results in loss of positive reinforcement.

    Science.gov (United States)

    Kaufman, A; Baron, A

    1968-09-01

    This investigation, using rats as subjects and punishment by timeout for responses maintained on a ratio schedule, sought to determine whether behavior would be suppressed by timeout punishment when such suppression also reduced reinforcement density or frequency. A series of experiments indicated that timeout punishment suppressed responding, with the degree of suppression increasing as a function of the duration of the timeout period. Suppressive effects were found to decrease as a function of increases in deprivation (body weight) and were eliminated when the punished response also was reinforced. It was concluded that timeout can produce aversive effects even when loss of reinforcement results. An alternative interpretation of the findings, based on the effects of extinction periods and delay of reinforcement on chained behavior, was discussed.

  7. Star formation suppression in compact group galaxies

    DEFF Research Database (Denmark)

    Alatalo, K.; Appleton, P. N.; Lisenfeld, U.;

    2015-01-01

    We present CO(1-0) maps of 12 warm H-2-selected Hickson Compact Groups (HCGs), covering 14 individually imaged warm H2 bright galaxies, with the Combined Array for Research in Millimeter Astronomy. We found a variety of molecular gas distributions within the HCGs, including regularly rotating disks...... of = 10 +/- 5, distributed bimodally, with five objects exhibiting suppressions of S greater than or similar to 10 and depletion timescales greater than or similar to 10 Gyr. This SF inefficiency is also seen in the efficiency per freefall time of Krumholz et al. We investigate the gas......-to-dust ratios of these galaxies to determine if an incorrect LCO-M(H2) conversion caused the apparent suppression and find that HCGs have normal gas-to-dust ratios. It is likely that the cause of the apparent suppression in these objects is associated with shocks injecting turbulence into the molecular gas...

  8. Weed suppression ability of spring barley varieties

    DEFF Research Database (Denmark)

    Christensen, Svend

    1995-01-01

    Three years of experiments with spring barley showed significant differences in weed suppression ability among varieties. Weed dry matter in the most suppressive variety, Ida, was 48% lower than the mean weed dry matter of all varieties, whereas it was 31% higher in the least suppressive variety......, Grit. Ranking varietal responses to weed competition in terms of grain yield loss corresponded well to ranking weed dry matter produced in crop weed mixtures. There was no correspondence between the varietal grain yields in pure stands and their competitiveness, suggesting that breeding to optimize...... interception model was developed to describe the light interception profiles of the varieties. A study of the estimated parameters showed significant correlation between weed dry matter, rate of canopy height development and the light interception profile. However, when estimates were standardized to eliminate...

  9. Suppression of fertility in adult cats

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Wehrend, A.; Georgiev, P.

    2014-01-01

    Contents: Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible......, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific...... and clinical options are available for the suppression of fertility in adult cats and the decision as to which should be chosen - independent of the legal registration of any state - depends on different facts: (i) feral or privately owned animal? (ii) temporary or permanent suppression of fertility wanted...

  10. Implicitly learned suppression of irrelevant spatial locations.

    Science.gov (United States)

    Leber, Andrew B; Gwinn, Rachael E; Hong, Yoolim; O'Toole, Ryan J

    2016-12-01

    How do we ignore a salient, irrelevant stimulus whose location is predictable? A variety of studies using instructional manipulations have shown that participants possess the capacity to exert location-based suppression. However, for the visual search challenges we face in daily life, we are not often provided explicit instructions and are unlikely to consciously deliberate on what our best strategy might be. Instead, we might rely on our past experience-in the form of implicit learning-to exert strategic control. In this paper, we tested whether implicit learning could drive spatial suppression. In Experiment 1, participants searched displays in which one location contained a target, while another contained a salient distractor. An arrow cue pointed to the target location with 70 % validity. Also, unbeknownst to the participants, the same arrow cue predicted the distractor location with 70 % validity. Results showed facilitated RTs to the predicted target location, confirming target enhancement. Critically, distractor interference was reduced at the predicted distractor location, revealing that participants used spatial suppression. Further, we found that participants had no explicit knowledge of the cue-distractor contingencies, confirming that the learning was implicit. In Experiment 2, to seek further evidence for suppression, we modified the task to include occasional masked probes following the arrow cue; we found worse probe identification accuracy at the predicted distractor location than control locations, providing converging evidence that observers spatially suppressed the predicted distractor locations. These results reveal an ecologically desirable mechanism of suppression, which functions without the need for conscious knowledge or externally guided instructions.

  11. Jet suppression measurement with the ATLAS detector

    CERN Document Server

    Slovak, Radim; The ATLAS collaboration

    2016-01-01

    A hot medium with a high density of unscreened color charges is produced in relativistic heavy ion collisions. Jets are produced at the early stages of this collision and are known to become attenuated as they propagate through the hot matter. One manifestation of this energy loss is a lower yield of jets emerging from the medium than expected in the absence of medium effects. Another manifestation of the energy loss is the modification of the dijet balance and the modification of fragmentation functions. In these proceedings, the latest ATLAS results on single jet suppression, dijet suppression, and modification of the jet internal structure in \\PbPb~collisions are presented.

  12. Star formation suppression in compact group galaxies

    DEFF Research Database (Denmark)

    Alatalo, K.; Appleton, P. N.; Lisenfeld, U.;

    2015-01-01

    , bars, rings, tidal tails, and possibly nuclear outflows, though the molecular gas morphologies are more consistent with spirals and earlytype galaxies than mergers and interacting systems. Our CO-imaged HCG galaxies, when plotted on the Kennicutt-Schmidt relation, shows star formation (SF) suppression...... color space. This supports the idea that at least some galaxies in HCGs are transitioning objects, where a disruption of the existing molecular gas in the system suppresses SF by inhibiting the molecular gas from collapsing and forming stars efficiently. These observations, combined with recent work...

  13. Suppression of crosstalk in coupled plasmonic waveguides

    CERN Document Server

    Kuznetsov, E V; Zyablovsky, A A; Vinogradov, A P; Lisyansky, A A

    2016-01-01

    We demonstrate the suppression of crosstalk between two dielectric nanowaveguides by placing an auxiliary linear waveguide between loaded waveguides spaced by one wavelength. The total cross-sectional dimension of the system containing two transmission lines is less than two microns that is hundred times smaller than a cross-section of a system made of dielectric fiber. The propagating modes in these waveguides are the sum and the difference of symmetric and antisymmetric modes of the coupled system. Crosstalk is suppressed by matching the wavenumbers of these modes. The analytically obtained results are confirmed by numerical simulation.

  14. Suppression of photoionization by a static field.

    Science.gov (United States)

    Gilary, Ido; Sajeev, Yesodharan; Ciappina, Marcelo F; Croy, Alexander; Goletz, Christoph M; Klaiman, Shachar; Sindelka, Milan; Winter, Martin; Wustmann, Waltraut; Moiseyev, Nimrod

    2008-10-17

    The dc field Stark effect is studied theoretically for atoms in high intensity laser fields. We prove that the first-order perturbation corrections for the energy and photoionization rate vanish when the dc field strength serves as a perturbational strength parameter. Our calculations show that by applying a dc field in the same direction as the polarization direction of the ac field, the photoinduced ionization rate is almost entirely suppressed. This suppression is attributed to changes in the phase shift of the continuum atomic wave functions which can be controlled by the dc field.

  15. Dynamic Optimization for Vortex Shedding Suppression

    Directory of Open Access Journals (Sweden)

    Bonis Ioannis

    2016-01-01

    Full Text Available Flows around structures exhibiting vortex shedding induce vibrations that can potentially damage the structure. A way to avoid it is to suppress vortex shedding by controlling the wake. Wake control of laminar flow behind a rotating cylinder is formulated herein as a dynamic optimization problem. Angular cylinder speed is the manipulated variable that is adjusted to suppress vortex shedding by minimizing lift coefficient variation. The optimal angular speed is assumed to be periodic like wake formation. The control problem is solved for different time horizons tH. The impact of tH to control is evaluated and the need for feedback is assessed.

  16. Immune suppressive mechanisms in the tumor microenvironment.

    Science.gov (United States)

    Munn, David H; Bronte, Vincenzo

    2016-04-01

    Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of immunotherapy of cancer.

  17. FLUTTER SUPPRESSION USING DISTRIBUTED PIEZOELECTRIC ACTUATORS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Flutter suppression using distributed piezoelectric actuators has been analyzed and tested. In constructing the finite element equation, effects of piezoelectric matrices are investigated. LQG method is used in designing the control law. In reducing the order of the control law, both balance realization and LK methods are used. For the rational approximation of the unsteady aerodynamic forces LS method is improved. In determining the piezoelectric constants d31 a new dynamic response method is developed. Laser vibrameter is used to pick up the model response and in ground resonance test the model is excited by piezoelectric actuators. Reasonable agreement of the wind tunnel flutter suppression test with calculated results is obtained.

  18. Research on the development of weed-suppressing rice varieties

    Institute of Scientific and Technical Information of China (English)

    Shaochuan ZHOU; Decheng LU; Hong LI; Daoqiang HUANG; Ruowei MIAO

    2009-01-01

    This study was conducted to develop weed-suppressing rice varieties in a weed-suppressing nursery by specific secondary metabolite markers of allelopathic potential. Weed-suppressing rice variety Feng-Hua-Zhan was screened out by a specific secondary metabolite marker of allelopathic potential. Weed-suppressing rice No. 1, a new rice line with good quality, was also developed using this method. The genetic backgrounds and research directions of weed-suppressing rice varieties are discussed in this paper.

  19. Contour detection by surround suppression of texture

    NARCIS (Netherlands)

    Petkov, Nicolai; Tavares, JMRS; Jorge, RMN

    2007-01-01

    Based on a keynote lecture at Complmage 2006, Coimbra, Oct. 20-21, 2006, an overview is given of our activities in modelling and using surround inhibition for contour detection. The effect of suppression of a line or edge stimulus by similar surrounding stimuli is known from visual perception studie

  20. Magnetoelastic metastructures for passive broadband vibration suppression

    Science.gov (United States)

    Hobeck, Jared D.; Inman, Daniel J.

    2015-04-01

    This paper presents an experimental and theoretical analysis of a novel metamaterial-inspired distributed vibration suppression system. The proposed research takes advantage of uniquely designed cantilevered zigzag structures that can have natural frequencies orders of magnitude lower than a simple cantilever of the same scale. A key advantage of the proposed vibration suppression system is that the dynamic response of each zigzag structure can be made highly nonlinear with the use of magnets. Arrays of these compact linear and nonlinear zigzag structures are integrated into a host structure to form what is referred to here as a metastructure. The proposed and experimentally validated analytical model employs a Rayleigh-Ritz formulation for a linear metastructure represented as a cantilever beam with a distributed array of attached single degree of freedom oscillators. These attached oscillators are lumped parameter representations of the zigzag structures. Experimental modal analysis results are shown comparing the response of the nonlinear metastructure to that of both the linear metastructure and also to the host structure with no vibration suppression. Results show that the linear system can reduce the maximum response of the host structure by 41.0% while the nonlinear system can achieve over twice that with a reduction of 84.5%. These promising preliminary results provide motivation for future work to be focused on developing nonlinear metastructures for vibration suppression.

  1. Active suppression after involuntary capture of attention.

    Science.gov (United States)

    Sawaki, Risa; Luck, Steven J

    2013-04-01

    After attention has been involuntarily captured by a distractor, how is it reoriented toward a target? One possibility is that attention to the distractor passively fades over time, allowing the target to become attended. Another possibility is that the captured location is actively suppressed so that attention can be directed toward the target location. The present study investigated this issue with event-related potentials (ERPs), focusing on the N2pc component (a neural measure of attentional deployment) and the Pd component (a neural measure of attentional suppression). Observers identified a color-defined target in a search array, which was preceded by a task-irrelevant cue array. When the cue array contained an item that matched the target color, this item captured attention (as measured both behaviorally and with the N2pc component). This capture of attention was followed by active suppression (indexed by the Pd component), and this was then followed by a reorienting of attention toward the target in the search array (indexed by the N2pc component). These findings indicate that the involuntary capture of attention by a distractor is followed by an active suppression process that presumably facilitates the subsequent voluntary orienting of attention to the target.

  2. Strong suppression of weak localization in graphene

    NARCIS (Netherlands)

    Morozov, S.V.; Novoselov, K.S.; Katsnelson, M.I.; Schedin, F.; Ponomarenko, L.A.; Jiang, D.; Geim, A.K.

    2006-01-01

    Low-field magnetoresistance is ubiquitous in low-dimensional metallic systems with high resistivity and well understood as arising due to quantum interference on self-intersecting diffusive trajectories. We have found that in graphene this weak-localization magnetoresistance is strongly suppressed a

  3. Characterization of Immune Suppression Induced by Polyribonucleotides.

    Science.gov (United States)

    1985-12-01

    RD-0162 482 CHARACTERIZATION OF IMMUNE SUPPRESSION INDUCED Y v i POLYRIDONUCLEOTIDES(U) MINNESOTA UNIV DULUTH DEPT OF MEDICAL MICROBIOLOGY AND...Polyribonucleotides by Marilyn J. Odean and Arthur G. Johnson Dept. of Medical Microbiology /Immunology University of Minnesota-Duluth 55812 DTICS ELECTE DEC 18

  4. UAV visual signature suppression via adaptive materials

    NARCIS (Netherlands)

    Barrett, R.; Melkert, J.

    2005-01-01

    Visual signature suppression (VSS) methods for several classes of aircraft from WWII on are examined and historically summarized. This study shows that for some classes of uninhabited aerial vehicles (UAVs), primary mission threats do not stem from infrared or radar signatures, but from the amount t

  5. Ion Suppression Study for Tetracyclines in Feed

    Directory of Open Access Journals (Sweden)

    Joaquim Chico

    2012-01-01

    Full Text Available Ion suppression in analysis of tetracyclines in feed was studied. The conventional analysis consists of a liquid extraction followed by a clean-up step using solid phase extraction (SPE technique and analysis of the tetracyclines by liquid chromatography and mass spectrometric detection. Various strategies for extraction and cleanup were tested in the present work, and the effectiveness to decrease the ion suppression on the MS/MS signals was evaluated. Four sample treatment methods were tested with five different feed samples. Extraction solvents tested were McIlvaine buffer and a mixture of McIlvaine buffer dichloromethane (3 : 1. SPE cartridges for cleanup were Oasis HLB, Oasis MCX, and Oasis MAX. The effectiveness of the methods was evaluated in terms of decreasing the ion suppression effect but also of decreasing the variability of ion suppression between samples. The method that provided the most satisfactory results involved a clean-up step based on SPE using mixed-mode cation exchange cartridges (Oasis MCX.

  6. Radio Science Measurements with Suppressed Carrier

    Science.gov (United States)

    Asmar, Sami; Divsalar, Dariush; Oudrhiri, Kamal

    2013-01-01

    Radio Science started when it became apparent with early Solar missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. Type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use Cramer-Rao bound (CRB). The CRB for the suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of CRB for non-ideal data wiping is an innovative method that presented here. Some numerical results are provided for coded system.

  7. Emotions shape memory suppression in trait anxiety

    Directory of Open Access Journals (Sweden)

    Tessa eMarzi

    2014-01-01

    Full Text Available The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive and neutral, participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase, participants were again shown each word and asked to recall the paired scene. The results show that memory control is influenced by high trait anxiety and emotions. Low trait anxiety individuals showed a memory suppression effect, whereas there was a lack of memory suppression in high trait anxious individuals, especially for emotionally negative scenes. Thus, we suggest that individuals with anxiety may have difficulty exerting cognitive control over memories with a negative valence. These findings provide evidence that memory suppression can be impaired by anxiety thus highlighting the crucial relation between cognitive control, emotions and individual differences in regulating emotions.

  8. Emotions shape memory suppression in trait anxiety.

    Science.gov (United States)

    Marzi, Tessa; Regina, Antonio; Righi, Stefania

    2014-01-01

    The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive, and neutral), participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase, participants were again shown each word and asked to recall the paired scene. The results show that memory control is influenced by high trait anxiety and emotions. Low trait anxiety individuals showed a memory suppression effect, whereas there was a lack of memory suppression in high trait anxious individuals, especially for emotionally negative scenes. Thus, we suggest that individuals with anxiety may have difficulty exerting cognitive control over memories with a negative valence. These findings provide evidence that memory suppression can be impaired by anxiety thus highlighting the crucial relation between cognitive control, emotions, and individual differences in regulating emotions.

  9. Benchmark enclosure fire suppression experiments - phase 1 test report.

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  10. Glare suppression by coherence gated negation

    CERN Document Server

    Zhou, Edward Haojiang; Brake, Joshua; Ruan, Haowen; Yang, Changhuei

    2016-01-01

    Imaging of a weak target hidden behind a scattering medium can be significantly confounded by glare. We report a method, termed coherence gated negation (CGN), that uses destructive optical interference to suppress glare and allow improved imaging of a weak target. As a demonstration, we show that by permuting through a set range of amplitude and phase values for a reference beam interfering with the optical field from the glare and target reflection, we can suppress glare by an order of magnitude, even when the optical wavefront is highly disordered. This strategy significantly departs from conventional coherence gating methods in that CGN actively 'gates out' the unwanted optical contributions while conventional methods 'gate in' the target optical signal. We further show that the CGN method can outperform conventional coherence gating image quality in certain scenarios by more effectively rejecting unwanted optical contributions.

  11. Speckle Suppression Method for SAR Image

    Directory of Open Access Journals (Sweden)

    Jiming Guo

    2013-04-01

    Full Text Available In this study, a new speckle reduction method was proposed in terms of by Bidimensional Empirical Mode Decomposition (BEMD. In this method, the SAR image containing speckle noise was decomposed into a number of elementary components by using BEMD and then the extremal points are done the boundary equivalent extension after screening and the residual continue to be done the boundary equivalent extension until screening is completed, finally, the image was reconstructed, which reduced the speckle noise. Experimental results show that this method has good effect on suppressing speckle noise, compared to the average filter, median filter and gaussian filter and has advantages of sufficiently retaining edge and detail information while suppressing speckle noise.

  12. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    Science.gov (United States)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  13. Immersion diuresis without expected suppression of vasopressin

    Science.gov (United States)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  14. Quarkonium suppression: Gluonic dissociation vs. colour screening

    Indian Academy of Sciences (India)

    Binoy Krishna Patra; Dinesh Kumar Srivastava

    2003-05-01

    We evaluate the suppression of / production in an equilibrating quark gluon plasma for two competing mechanisms: Debye screening of colour interaction and dissociation due to energetic gluons. Results are obtained for S + S and Au + Au collisions at RHIC and LHC energies. At RHIC energies the gluonic dissociation of the charmonium is found to be equally important for both the systems while the screening of the interaction plays a significant role only for the larger systems. At LHC energies the Debye mechanism is found to dominate both the systems. While considering the suppression of directly produced $\\Upsilon$ at LHC energies, we find that only the gluonic dissociation mechanism comes into play for the initial conditions taken from the self screened parton cascade model in these studies.

  15. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    Science.gov (United States)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-01-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin. PMID:23679639

  16. Managing for soil health can suppress pests

    Directory of Open Access Journals (Sweden)

    Amanda Hodson

    2016-08-01

    Full Text Available A “healthy” soil can be thought of as one that functions well, both agronomically and ecologically, and one in which soil biodiversity and crop management work in synergy to suppress pests and diseases. UC researchers have pioneered many ways of managing soil biology for pest management, including strategies such as soil solarization, steam treatment and anaerobic soil disinfestation, as well as improvements on traditional methods, such as reducing tillage, amending soil with organic materials, and cover cropping. As managing for soil health becomes more of an explicit focus due to restrictions on the use of soil fumigants, integrated soil health tests will be needed that are validated for use in California. Other research needs include breeding crops for disease resistance and pest suppressive microbial communities as well as knowledge of how beneficial organisms influence plant health.

  17. Reversing Breast Cancer-Induced Immune Suppression

    Science.gov (United States)

    2014-09-01

    GCL (Glutamate-Cysteine Ligase), and cystine transport genes xCT and 4F2 [19, 23] Cystine transport and Nrf2 may contribute to MDSC survival. We... cystine (via the xC - cystine /glutamate antiporter) and its reduction to cysteine are rate-limiting for the synthesis of the antioxidant glutathione (GSH...Nr2 regulates tumor-bearer survival and MDSC suppressive activity. Aim 3: Determine if blocking cystine transport into MDSC while providing T cells

  18. Currently available cough suppressants for chronic cough.

    Science.gov (United States)

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

  19. FGF Suppresses Poldip2 Expression in Osteoblasts.

    Science.gov (United States)

    Katsumura, Sakie; Izu, Yayoi; Yamada, Takayuki; Griendling, Kathy; Harada, Kiyoshi; Noda, Masaki; Ezura, Yoichi

    2016-12-05

    Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modern world. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cell migration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cells were not known. Therefore, we examined the Poldip2 mRNA expression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulation was investigated in these cells. FGF suppressed the expression of Poldip2 in MC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed the migration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. J. Cell. Biochem. 9999: 1-8, 2017. © 2016 Wiley Periodicals, Inc.

  20. A Mathematical Model for Suppression Subtractive Hybridization

    OpenAIRE

    2002-01-01

    Suppression subtractive hybridization (SSH) is frequently used to unearth differentially expressed genes on a whole-genome scale. Its versatility is based on combining cDNA library subtraction and normalization, which allows the isolation of sequences of varying degrees of abundance and differential expression. SSH is a complex process with many adjustable parameters that affect the outcome of gene isolation.We present a mathematical model of SSH based on DNA hybridization kinetics for assess...

  1. Suppression of Ostwald Ripening by Chemical Reactions

    Science.gov (United States)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-03-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable and coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Ostwald ripening must thus be suppressed to stabilize emulsions, e.g. to control the properties of pharmaceuticals, food, or cosmetics. Suppression of Ostwald ripening is also important in biological cells, which contain stable liquid-like compartments, e.g. germ granules, Cajal-bodies, and centrosomes. Such systems are often driven away from equilibrium by chemical reactions and can thus be called active emulsions. Here, we show that non-equilibrium chemical reactions can suppress Ostwald Ripening, leading to stable, monodisperse emulsions. We derive analytical approximations of the typical droplet size, droplet count, and time scale of the dynamics from a coarse-grained description of the droplet dynamics. We also compare these results to numerical simulations of the continuous concentration fields. Generally, we thus show how chemical reactions can be used to stabilize emulsions and to control their properties in technology and nature.

  2. Suppressing bullfrog larvae with carbon dioxide

    Science.gov (United States)

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  3. Suppressing Super-Horizon Curvature Perturbations

    CERN Document Server

    Sloth, M S

    2006-01-01

    We consider the possibility of suppressing superhorizon curvature perturbations after the end of the ordinary slow-roll inflationary stage. This is the opposite of the curvaton limit. We assume that large curvature perturbations are created by the inflaton and investigate to which extent they can be diluted or suppressed by a second very homogeneous field which starts to dominate the energy density of the universe shortly after the end of inflation. The suppression is non-trivial to achieve, but we demonstrate two examples where it works. The mechanism is shown to work if the decay rate of the second field has a certain time-dependence leading to an intrinsic non-adiabatic energy transfer or if the second field is an axion field with a very non-linear periodic potential leading to a non-vanishing intrinsic non-adiabatic pressure perturbation. This opens the possibility of having much larger inflaton perturbations created during inflation than normally allowed by the COBE bound. It relaxes the upper bound on t...

  4. Conditionals, Context, and the Suppression Effect.

    Science.gov (United States)

    Cariani, Fabrizio; Rips, Lance J

    2016-02-01

    Modus ponens is the argument from premises of the form If A, then B and A to the conclusion B (e.g., from If it rained, Alicia got wet and It rained to Alicia got wet). Nearly all participants agree that the modus ponens conclusion logically follows when the argument appears in this Basic form. However, adding a further premise (e.g., If she forgot her umbrella, Alicia got wet) can lower participants' rate of agreement-an effect called suppression. We propose a theory of suppression that draws on contemporary ideas about conditional sentences in linguistics and philosophy. Semantically, the theory assumes that people interpret an indicative conditional as a context-sensitive strict conditional: true if and only if its consequent is true in each of a contextually determined set of situations in which its antecedent is true. Pragmatically, the theory claims that context changes in response to new assertions, including new conditional premises. Thus, the conclusion of a modus ponens argument may no longer be accepted in the changed context. Psychologically, the theory describes people as capable of reasoning about broad classes of possible situations, ordered by typicality, without having to reason about individual possible worlds. The theory accounts for the main suppression phenomena, and it generates some novel predictions that new experiments confirm.

  5. Neural Networks for Mindfulness and Emotion Suppression.

    Science.gov (United States)

    Murakami, Hiroki; Katsunuma, Ruri; Oba, Kentaro; Terasawa, Yuri; Motomura, Yuki; Mishima, Kazuo; Moriguchi, Yoshiya

    2015-01-01

    Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  6. Neural Networks for Mindfulness and Emotion Suppression.

    Directory of Open Access Journals (Sweden)

    Hiroki Murakami

    Full Text Available Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  7. Cough suppression therapy: does it work?

    Science.gov (United States)

    Chamberlain, Sarah; Garrod, Rachel; Birring, Surinder S

    2013-10-01

    Cough suppression therapy (CST), also known as cough suppression physiotherapy and speech pathology management is a promising non-pharmacological therapeutic option for patients with refractory chronic cough. CST may consist of education, improving laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and counselling. It is an out-patient therapy delivered in 2-4 sessions. There is evidence to support the efficacy of CST: a randomised controlled trial reported a significant reduction in cough symptoms and other studies have reported improved cough related quality of life, reduced cough reflex hypersensitivity and cough frequency. The mechanism of action of CST is not clear, but it has been shown to reduce cough reflex sensitivity, paradoxical vocal fold movement (PVFM) and extrathoracic hyperresponsiveness. Further research is needed to determine the optimal components of CST, the characteristics of patients in whom it is most effective and to increase the understanding of its mechanisms of action. The effectiveness of CST in other respiratory conditions such as asthma, pulmonary fibrosis, chronic obstructive pulmonary disease and sarcoidosis should also be investigated.

  8. System and method for suppressing sublimation using opacified aerogel

    Science.gov (United States)

    Sakamoto, Jeff S. (Inventor); Snyder, G. Jeffrey (Inventor); Calliat, Thierry (Inventor); Fleurial, Jean-Pierre (Inventor); Jones, Steven M. (Inventor); Palk, Jong-Ah (Inventor)

    2008-01-01

    The present invention relates to a castable, aerogel-based, ultra-low thermal conductivity opacified insulation to suppress sublimation. More specifically, the present invention relates to an aerogel opacified with various opacifying or reflecting constituents to suppress sublimation and provide thermal insulation in thermoelectric modules. The opacifying constituent can be graded within the aerogel for increased sublimation suppression, and the density of the aerogel can similarly be graded to achieve optimal thermal insulation and sublimation suppression.

  9. Coating Thermoelectric Devices To Suppress Sublimation

    Science.gov (United States)

    Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

    2007-01-01

    A technique for suppressing sublimation of key elements from skutterudite compounds in advanced thermoelectric devices has been demonstrated. The essence of the technique is to cover what would otherwise be the exposed skutterudite surface of such a device with a thin, continuous film of a chemically and physically compatible metal. Although similar to other sublimation-suppression techniques, this technique has been specifically tailored for application to skutterudite antimonides. The primary cause of deterioration of most thermoelectric materials is thermal decomposition or sublimation - one or more elements sublime from the hot side of a thermoelectric couple, changing the stoichiometry of the device. Examples of elements that sublime from their respective thermoelectric materials are Ge from SiGe, Te from Pb/Te, and now Sb from skutterudite antimonides. The skutterudite antimonides of primary interest are CoSb3 [electron-donor (n) type] and CeFe(3-x)Co(x)Sb12 [electron-acceptor (p) type]. When these compounds are subjected to typical operating conditions [temperature of 700 C and pressure sublimes from their surfaces, with the result that Sb depletion layers form and advance toward their interiors. As the depletion layer advances in a given device, the change in stoichiometry diminishes the thermal-to-electric conversion efficiency of the device. The problem, then, is to prevent sublimation, or at least reduce it to an acceptably low level. In preparation for an experiment on suppression of sublimation, a specimen of CoSb3 was tightly wrapped in a foil of niobium, which was selected for its chemical stability. In the experiment, the wrapped specimen was heated to a temperature of 700 C in a vacuum of residual pressure sublimation of antimony at 700 C. This was a considerable improvement, considering that uncoated CoSb3 had been found to decompose to form the lowest antimonide at the surface at only 600 C. Evidently, because the mean free path of Sb at the

  10. Noise Suppression of a single Frequency Fiber Laser

    Institute of Scientific and Technical Information of China (English)

    LIU Kui; CUI Shu-Zhen; ZHANG Hai-Long; ZHANG Jun-Xiang; GAO Jiang-Rui

    2011-01-01

    We present an experimental demonstration of fiber laser noise suppression by the mode cleaner.The intensity noise of a single frequency fiber laser is suppressed near the shot noise limit after a sideband frequency of 3 MHz.Two series mode cleaners are used to improve the noise suppression.The noise reduction is over 27 dB at 3 MHz.

  11. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields.

    Science.gov (United States)

    Todorovic, Ana; de Lange, Floris P

    2012-09-26

    Repetition of a stimulus, as well as valid expectation that a stimulus will occur, both attenuate the neural response to it. These effects, repetition suppression and expectation suppression, are typically confounded in paradigms in which the nonrepeated stimulus is also relatively rare (e.g., in oddball blocks of mismatch negativity paradigms, or in repetition suppression paradigms with multiple repetitions before an alternation). However, recent hierarchical models of sensory processing inspire the hypothesis that the two might be separable in time, with repetition suppression occurring earlier, as a consequence of local transition probabilities, and suppression by expectation occurring later, as a consequence of learnt statistical regularities. Here we test this hypothesis in an auditory experiment by orthogonally manipulating stimulus repetition and stimulus expectation and, using magnetoencephalography, measuring the neural response over time in human subjects. We found that stimulus repetition (but not stimulus expectation) attenuates the early auditory response (40-60 ms), while stimulus expectation (but not stimulus repetition) attenuates the subsequent, intermediate stage of auditory processing (100-200 ms). These findings are well in line with hierarchical predictive coding models, which posit sequential stages of prediction error resolution, contingent on the level at which the hypothesis is generated.

  12. Unsuppressible Repetition Suppression and exemplar-specific Expectation Suppression in the Fusiform Face Area.

    Science.gov (United States)

    Pajani, Auréliane; Kouider, Sid; Roux, Paul; de Gardelle, Vincent

    2017-12-01

    Recent work casts Repetition Suppression (RS), i.e. the reduced neural response to repeated stimuli, as the consequence of reduced surprise for repeated inputs. This research, along with other studies documenting Expectation Suppression, i.e. reduced responses to expected stimuli, emphasizes the role of expectations and predictive codes in perception. Here, we use fMRI to further characterize the nature of predictive signals in the human brain. Prior to scanning, participants were implicitly exposed to associations within face pairs. Critically, we found that this resulted in exemplar-specific Expectation Suppression in the fusiform face-sensitive area (FFA): individual faces that could be predicted from the associations elicited reduced FFA responses, as compared to unpredictable faces. Thus, predictive signals in the FFA are specific to face exemplars, and not only generic to the category of face stimuli. In addition, we show that under such circumstances, the occurrence of surprising repetitions did not trigger enhanced brain responses, as had been recently hypothesized, but still suppressed responses, suggesting that repetition suppression might be partly 'unsuppressible'. Repetition effects cannot be fully modulated by expectations, which supports the recent view that expectation and repetition effects rest on partially independent mechanisms. Altogether, our study sheds light on the nature of expectation signals along the perceptual system.

  13. Individual Differences in Spontaneous Expressive Suppression Predict Amygdala Responses to Fearful Stimuli: The Role of Suppression Priming

    Science.gov (United States)

    Chen, Shengdong; Deng, Zhongyan; Xu, Yin; Long, Quanshan; Yang, Jiemin; Yuan, Jiajin

    2017-01-01

    Though the spontaneous emotion regulation has received long discussions, few studies have explored the regulatory effects of spontaneous expressive suppression in neural activations, especially in collectivistic cultural context. The functional magnetic resonance imaging (fMRI) study aimed to examine whether individual differences in the tendency to use suppression are correlated with amygdala responses to negative situations when individuals are unconsciously primed with expressive suppression. Twenty-three healthy Chinese undergraduates completed an fMRI paradigm involving fear processing, and a synonym matching task was added to prime participants with the unconscious (automatic) expressive suppression goal. Participants completed measures of typical emotion regulation use (reappraisal and suppression), trait anxiety, and neuroticism. Results indicated that only in emotion suppression prime condition, greater use of suppression in everyday life was related to decreased amygdala activity. These associations were not attributable to variation in trait anxiety, neuroticism, or the habitual use of reappraisal. These findings suggest that in collectivistic cultural settings, individual differences in expressive suppression do not alter fear-related neural activation during suppression-irrelevant context. However, unconscious suppression priming facilitates the manifestation of individual differences in the neural consequence of expressive suppression, as reflected by the priming-specific decrease of emotional subcortical activations with more use of expressive suppression. PMID:28197108

  14. Leuprolide acetate suppresses pedophilic urges and arousability.

    Science.gov (United States)

    Schober, Justine M; Kuhn, Phyllis J; Kovacs, Paul G; Earle, James H; Byrne, Peter M; Fries, Ruth A

    2005-12-01

    Cognitive-behavioral psychotherapy was compared with cognitive-behavioral psychotherapy augmented by leuprolide acetate (LA) for suppression of pedophilic behavior. Five male pedophiles (M age, 50 years; range, 36-58) were administered LA by Depo injection for 12 months, followed by saline placebo for 12 months. Testosterone levels, sexual interest preference by visual reaction time (Abel Assessment), penile tumescence (Monarch Penile Plethysmography, PPG), as well as strong sexual urges toward children and masturbatory frequency involving thoughts of children (polygraph), were measured every 3 months. On LA, testosterone decreased to castrate levels. Penile tumescence was significantly suppressed compared with baseline, but sufficient response remained to detect pedophilic interest. Pedophilic interest was also detected by visual reaction times. When asked about having pedophilic urges and masturbating to thoughts of children, all subjects self-reported a decrease. Polygraph responses indicated subjects were not deceptive. On placebo, testosterone and physiologic arousal eventually rose to baseline. As noted by polygraph, at baseline and on placebo, subjects were deceptive regarding increased pedophilic urges and masturbatory frequency. Interest preference, as measured by Abel Assessment and Monarch PPG, was generally unchanged throughout the study. Cognitive-behavioral psychotherapy augmented with LA significantly reduced pedophilic fantasies, urges, and masturbation; however, pedophilic interest did not change during 1 year of therapy. Deceptive responses by polygraph suggested that self-report was unreliable. Follow-up utilizing objective measures is essential for monitoring efficacy of treatment in pedophilia. Our study supports the premise that suppression of pedophilic behavior is possible. LA may augment cognitive-behavioral psychotherapy and help break the sequence leading to a re-offense.

  15. Chaos suppression in gas-solid fluidization.

    Science.gov (United States)

    Pence, Deborah V.; Beasley, Donald E.

    1998-06-01

    Fluidization in granular materials occurs primarily as a result of a dynamic balance between gravitational forces and forces resulting from the flow of a fluid through a bed of discrete particles. For systems where the fluidizing medium and the particles have significantly different densities, density wave instabilities create local pockets of very high void fraction termed bubbles. The fluidization regime is termed the bubbling regime. Such a system is appropriately termed a self-excited nonlinear system. The present study examines chaos suppression resulting from an opposing oscillatory flow in gas-solid fluidization. Time series data representing local, instantaneous pressure were acquired at the surface of a horizontal cylinder submerged in a bubbling fluidized bed. The particles had a weight mean diameter of 345 &mgr;m and a narrow size distribution. The state of fluidization corresponded to the bubbling regime and total air flow rates employed in the present study ranged from 10% to 40% greater than that required for minimum fluidization. The behavior of time-varying local pressure in fluidized beds in the absence of a secondary flow is consistent with deterministic chaos. Kolmogorov entropy estimates from local, instantaneous pressure suggest that the degree of chaotic behavior can be substantially suppressed by the presence of an opposing, oscillatory secondary flow. Pressure signals clearly show a "phase-locking" phenomenon coincident with the imposed frequency. In the present study, the greatest degree of suppression occurred for operating conditions with low primary and secondary flow rates, and a secondary flow oscillation frequency of 15 Hz. (c) 1998 American Institute of Physics.

  16. Overvoltage Suppression for UHV Transmission Lines

    Institute of Scientific and Technical Information of China (English)

    LI Yongli; LIU Taihua; LI Zhongqing; JING Lei; LONG Ying; FAN Jianzhong

    2008-01-01

    The overvoltage phenomena of ultra high voltage (UHV) transmission lines are analyzed and verified by EMTDC/PSCAD simulation. Referring to the theoretical analyses and operating experiences of extra high voltage (EHV) transmission lines in China and UHV transmission lines in Russia and Japan, the methods to suppress the internal overvoltage in UHV transmission lines by protection and control strategies are discussed. Through the cooperation among the recloser, shunt reactor, tripping and closing resistance, and metal oxide varistor (MOV), the overvoltage can be restrained within an acceptable level.

  17. Suppression of Aspergillus by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Jensen, Britt Guillaume; Jelsbak, Lars; Søndergaard, Ib

    culture plates. After 24 hours incubation at 37 °C, a P. aeruginosa overnight culture diluted to 108 CFU/ml was streaked out perpendicular to the fungal streak. The plates were incubated at 37 °C for 5 days, examined and plugs were extracted for HPLC and LC-DAD-MS analysis. Results: P. aeruginosa PAO1...... suppressed growth of A. fumigatus, A. niger, A. flavus, A. oryzae, A. terreus and E. nidulans. HPLC and LC-DAD-MS results showed an increase in phenazine-1-carboxylic acid and phenazine-1-carboxamide production by P. aeruginosa in the contact area of Aspergillus. Different quinolones were also identified...

  18. New Respirable Dust Suppression Systems for Coal Mines

    Institute of Scientific and Technical Information of China (English)

    XIE Yao-she; FAN Gao-xian; DAI Jun-wei; SONG Xiao-bo

    2007-01-01

    Dust suppression in coal mines is a worldwide problem which has not been solved effectively. The application of negative pressure secondary dust removal (NPSDR) is a breakthrough in the coal mine safety field. In this paper, NPSDR technology and ultrasonic dust suppression systems are introduced. High pressure water is supplied to the NPSDR device which is mounted on the shearer. A negative pressure field is formed in the device. At the same time, the dusty air around the shearer drum will be sucked into, and purged from, the NPSDR device by the negative pressure field. An ultrasonic dust suppression system uses water and compressed air to produce micron sized droplets which suppress respirable coal dust effectively. The NPSDR technology can be used for shearer dust suppression while ultrasonic dust suppression can be applied in areas such as the transportation positions. These dust suppression methods have the following advantages: high efficiency, wide applicability, simple structure, high reliability and low cost.

  19. Suppression of Ostwald ripening in active emulsions

    Science.gov (United States)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-07-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable since they coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Stability of emulsions is relevant not only in complex fluids but also in biological cells, which contain liquidlike compartments, e.g., germ granules, Cajal bodies, and centrosomes. Such cellular systems are driven away from equilibrium, e.g., by chemical reactions, and thus can be called active emulsions. In this paper, we study such active emulsions by developing a coarse-grained description of the droplet dynamics, which we analyze for two different chemical reaction schemes. We first consider the simple case of first-order reactions, which leads to stable, monodisperse emulsions in which Ostwald ripening is suppressed within a range of chemical reaction rates. We then consider autocatalytic droplets, which catalyze the production of their own droplet material. Spontaneous nucleation of autocatalytic droplets is strongly suppressed and their emulsions are typically unstable. We show that autocatalytic droplets can be nucleated reliably and their emulsions stabilized by the help of chemically active cores, which catalyze the production of droplet material. In summary, different reaction schemes and catalytic cores can be used to stabilize emulsions and to control their properties.

  20. Inhibition of saccades elicits attentional suppression.

    Science.gov (United States)

    Dhawan, Saurabh; Deubel, Heiner; Jonikaitis, Donatas

    2013-05-17

    Visuospatial attention has been shown to have a central role in planning and generation of saccades but what role, if any, it plays in inhibition of saccades remains unclear. In this study, we used an oculomotor delayed match- or nonmatch-to-sample task in which a cued location has to be encoded and memorized for one of two very different goals-to plan a saccade to it or to avoid making a saccade to it. We measured the spatial allocation of attention during the delay and found that while marking a location as a future saccade target resulted in an attentional benefit at that location, marking it as forbidden to saccades led to an attentional cost. Additionally, saccade trajectories were found to deviate away more from the "don't look" location than from a saccade-irrelevant distractor confirming greater inhibition of an actively forbidden location in oculomotor programming. Our finding that attention is suppressed at locations forbidden to saccades confirms and complements the claim of a selective and obligatory coupling between saccades and attention-saccades at the memorized location could neither be planned nor suppressed independent of a corresponding effect on attentional performance.

  1. Selective suppression of judged sweetness by ziziphins.

    Science.gov (United States)

    Smith, V V; Halpern, B P

    1983-06-01

    The effects of ziziphins and of control treatments upon judgments by human adults of the sweetness, sourness, bitterness, and saltiness of American apple cider or apple juice were measured with a category estimation method during repeated trials before, during (90 sec treatment duration only), and after, treatment. Sweetness was reduced after either a 10 sec or a 90 sec whole mouth treatment with ziziphins, but not after quinine sulfate or apple juice control treatment. No differences in after-treatment sourness, bitterness, or saltiness occurred between treatments. The reduction in sweetness was weak with 10 sec 3.5% W/V ziziphins treatment, but strong after 90 sec 0.88% W/V ziziphins treatment; duration of suppression was ca. 70 sec. The mechanism was identified as taste modification since adaptation, cross-adaptation, and mixture suppression were eliminated by control treatments and by post-treatment rests and rinse. Comparisons with known gymnemic acids effects suggest that net dissociation of ziziphins from taste receptor membranes and/or inactivation in the membrane may be much faster than with gymnemic acids.

  2. Using biologically soft surfactants for dust suppression

    Energy Technology Data Exchange (ETDEWEB)

    Tkachenko, N.G.; Kolodiichak, V.K.; Motrii, A.E.; Severin, V.D.

    1982-07-01

    This article discusses environmental aspects of using surfactants in coal mines for dust suppression. Surfactants for underground black coal mines in the USSR are divided into three classes: so-called soft surfactants with a decomposition period from 1 to 3 days, hard surfactants with decomposition exceeding a month and an intermediary group. The decomposition process is analyzed; the role played by fermentation is stressed. Environmental effects of surfactant decomposition are evaluated. Selected surfactants tested in Soviet laboratories are described. The results of experimental use of diethanolamide as a surfactant for water injection in coal seams are evaluated. Wetting time amounts to 1 s when a 0.2% concentration is used. When surfactant concentration in water is reduced to 0.05% wetting time does not change; when concentration decreases to 0.025% wetting time increases to 3 s. Surfactant efficiency is investigated under operational conditions in a Donbass mine. Specifications of the working face, mining system and air pollution caused by a shearer loader are discussed. When diethanolamide is used dust suppression efficiency ranges from 86.4 to 90.4%. During the tests diethanolamide concentration in water was 0.05%.

  3. Electroproduction of Baryon Resonances and Strangeness Suppression

    CERN Document Server

    Santopinto, E; Tecocoatzi, H Garcia

    2016-01-01

    We describe the electroproduction ratios of baryon-meson states from nucleon using an extension of the quark model that takes into account the sea. As a result we provide, with no adjustable parameters, the predictions of ratios of exclusive meson-baryon final states: Lambda K , Sigma K, p pion, and n pion. These predictions are in agreement with the new Jlab experimental data showing that sea quarks play an important role in the electroproduction. We also predicted further ratios of exclusive reactions that can be measured and tested in future experiments. In particular, we suggested new experiments on deuterium and tritium. Such measurements can provide crucial test of different predictions concerning the structure of nucleon and its sea quarks helping to solve an outstanding problem. Finally, we computed the so called strangeness suppression factor, lambda s, that is the suppression of strange quark-antiquarks compared to nonstrange pairs, and we found that our finding with this simple extension of the qua...

  4. Jet noise suppression by porous plug nozzles

    Science.gov (United States)

    Bauer, A. B.; Kibens, V.; Wlezien, R. W.

    1982-01-01

    Jet noise suppression data presented earlier by Maestrello for porous plug nozzles were supplemented by the testing of a family of nozzles having an equivalent throat diameter of 11.77 cm. Two circular reference nozzles and eight plug nozzles having radius ratios of either 0.53 or 0.80 were tested at total pressure ratios of 1.60 to 4.00. Data were taken both with and without a forward motion or coannular flow jet, and some tests were made with a heated jet. Jet thrust was measured. The data were analyzed to show the effects of suppressor geometry on nozzle propulsive efficiency and jet noise. Aerodynamic testing of the nozzles was carried out in order to study the physical features that lead to the noise suppression. The aerodynamic flow phenomena were examined by the use of high speed shadowgraph cinematography, still shadowgraphs, extensive static pressure probe measurements, and two component laser Doppler velocimeter studies. The different measurement techniques correlated well with each other and demonstrated that the porous plug changes the shock cell structure of a standard nozzle into a series of smaller, periodic cell structures without strong shock waves. These structures become smaller in dimension and have reduced pressure variations as either the plug diameter or the porosity is increased, changes that also reduce the jet noise and decrease thrust efficiency.

  5. Tagging and suppression of pileup jets

    CERN Document Server

    The ATLAS collaboration

    2014-01-01

    The suppression of pileup jets has been a crucial component of many physics analyses using 2012 LHC proton-proton collisions. In ATLAS, tracking information has been used to calculate a variable called the jet-vertex-fraction, which is the fraction of the total mo- mentum of tracks in the jet which is associated to the primary vertex. Imposing a minimum on this variable rejects the majority of pileup jets, but leads to hard-scatter jet efficiencies that depend on the number of reconstructed primary vertices in the event ($N_{Vtx}$). In this note, new track-based variables to suppress pileup jets are developed in such a way that the resulting hard-scatter jet efficiency is stable as a function of $N_{Vtx}$. A multivariate combina- tion of two such variables called the jet-vertex-tagger is constructed. In addition, it is shown that jet-vertex association can be applied to large-R jets, providing a track-based grooming technique that is as powerful as calorimeter-based trimming but based on complementary trackin...

  6. Suppression of glioma progression by Egln3.

    Directory of Open Access Journals (Sweden)

    Vicki A Sciorra

    Full Text Available Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3, a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

  7. Reinstatement of Conditioned Suppression in Mice

    Directory of Open Access Journals (Sweden)

    Trinette Dirikx

    2006-03-01

    Full Text Available Return of fear after successful exposure therapy calls for a better understanding of the mechanisms of relapse. Classical conditioning research provides a useful framework for conceptualising the acquisition, extinction and reappearance of fear. The present paper focuses on reinstatement, the return of extinguished conditioned responses due to the experience of one or more unconditioned stimuli (USs after extinction. This phenomenon illustrates that unpredictable USs can lead to a return of fear after successful exposure. The data we present is one of the first demonstrations that conditioned suppression of instrumental behaviour can be used as an index of classical conditioning in laboratory mice. The procedure proves to be a promising instrument for assessing fear in mice, both in the context of research aimed at unravelling the functional characteristics of learning and memory in healthy mice and in the context of research aimed at unravelling the neurobiological substrate of psychiatric disorders, e.g., in studies with transgenic and knockout mice. Using this procedure, we report the first observation of reinstatement of conditioned suppression in this species.

  8. Phase noise suppression through parametric filtering

    Science.gov (United States)

    Cassella, Cristian; Strachan, Scott; Shaw, Steven W.; Piazza, Gianluca

    2017-02-01

    In this work, we introduce and experimentally demonstrate a parametric phase noise suppression technique, which we call "parametric phase noise filtering." This technique is based on the use of a solid-state parametric amplifier operating in its instability region and included in a non-autonomous feedback loop connected at the output of a noisy oscillator. We demonstrate that such a system behaves as a parametrically driven Duffing resonator and can operate at special points where it becomes largely immune to the phase fluctuations that affect the oscillator output signal. A prototype of a parametric phase noise filter (PFIL) was designed and fabricated to operate in the very-high-frequency range. The PFIL prototype allowed us to significantly reduce the phase noise at the output of a commercial signal generator operating around 220 MHz. Noise reduction of 16 dB (40×) and 13 dB (20×) were obtained, respectively, at 1 and 10 kHz offsets from the carrier frequency. The demonstration of this phase noise suppression technique opens up scenarios in the development of passive and low-cost phase noise cancellation circuits for any application demanding high quality frequency generation.

  9. Inhibition of SIRT2 suppresses hepatic fibrosis.

    Science.gov (United States)

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

  10. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  11. Suppressed epidemics in multi-relational networks

    CERN Document Server

    Xu, Elvis H W; Xu, C; Tang, Ming; Do, Younghae; Hui, P M

    2014-01-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1-p, respectively. The fraction of infected nodes rho(p) shows a non-monotonic behavior, with rho drops with p for small p and increases for large p. For small to moderate w1/w0 ratios, rho(p) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range p_L =p_R. A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clu...

  12. Wireless Inductive Power Device Suppresses Blade Vibrations

    Science.gov (United States)

    Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

    2011-01-01

    Vibration in turbomachinery can cause blade failures and leads to the use of heavier, thicker blades that result in lower aerodynamic efficiency and increased noise. Metal and/or composite fatigue in the blades of jet engines has resulted in blade destruction and loss of lives. Techniques for suppressing low-frequency blade vibration, such as gtuned circuit resistive dissipation of vibratory energy, h or simply "passive damping," can require electronics incorporating coils of unwieldy dimensions and adding unwanted weight to the rotor. Other approaches, using vibration-dampening devices or damping material, could add undesirable weight to the blades or hub, making them less efficient. A wireless inductive power device (WIPD) was designed, fabricated, and developed for use in the NASA Glenn's "Dynamic Spin Rig" (DSR) facility. The DSR is used to simulate the functionality of turbomachinery. The relatively small and lightweight device [10 lb (approx.=4.5 kg)] replaces the existing venerable and bulky slip-ring. The goal is the eventual integration of this technology into actual turbomachinery such as jet engines or electric power generators, wherein the device will facilitate the suppression of potentially destructive vibrations in fan blades. This technology obviates slip rings, which require cooling and can prove unreliable or be problematic over time. The WIPD consists of two parts: a remote element, which is positioned on the rotor and provides up to 100 W of electrical power to thin, lightweight piezoelectric patches strategically placed on/in fan blades; and a stationary base unit that wirelessly communicates with the remote unit. The base unit supplies inductive power, and also acts as an input and output corridor for wireless measurement, and active control command to the remote unit. Efficient engine operation necessitates minimal disturbance to the gas flow across the turbine blades in any effort to moderate blade vibration. This innovation makes it

  13. Effects of triperygium wilfordii polyglucoside on kidney structure and nephrin expression in podocytes in rats with diabetic nephropathy%雷公藤多苷对糖尿病肾病大鼠肾组织结构及足细胞nephrin蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵芊; 郑妙艳; 李玉荣; 常宝成; 陈莉明

    2012-01-01

    Objective To explore the effects of triperygium wilfordii polyglucoside (TWP) on proteinuria,podocytes damages,nephrin expression in rats with diabetic nephropathy.Methods Diabetic nephropathy was established in rats using high lipids diet combined with streptozotocin (STZ).Diabetic rats were randomized into diabetic nephropathy model,low dosage of TWP( 6 mg · kg- 1 · d-1) and high dosage of TWP( 12 mg · kg-1 · d-1 )group.Normal rats were used as control and 12 rats for each group.After intervention for 12 weeks,24 h urinary protein excretion rate (UAER),serum creatinine and plasma urea nitrogen were accessed.The pathological changes of kidney were evaluated by Haematoxylin and eosin( HE),Periodic acid schiff(PAS),Masson staining.Ultrastructural alteration was examined by transmission electron microscope.The expressions of nephrin were evaluated by immunohistochemical staining.Results Compared with normal rats [ ( 3.28 ± 0.26 ) mg/24 h ],macroalbuminuia increased in diabetic rats [ ( 27.60 ± 0.24 ) mg/24 h],whereas the level of urine protein significantly decreased in 6 and 12 mg · kg-1 · d-1 TWP treatment for 12 weeks[ ( 12.63 ±0.21 ) and( 10.50 ± 0.15 ) mg/24 h ].There was no significant statistical difference between high and low dose of TWP group( P <0.05 ).In renal pathologic examination of diabetic nephropathy model group,the glomerular were sclerosis,with thicker basement membranes,deformed renal tubules,vacuolar degenerated epithelial cells and sclerosed interstitial were observed.The foot processes of podocyte were widen and fused,and the number of podocyte was also decreased.However,the kidney and podocyte lesions were improved significantly both in high and low dose of TWP groups.The expressions of nephrin by immunohistochemistry were also increased in both TWP treatment groups,with more statistical improvement in high dose group.Conclusions TWP may exert its protective effect on podocytes function in diabetic nephropathy through increasing

  14. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys.

    Science.gov (United States)

    Pollack, S; Rossan, R N; Davidson, D E; Escajadillo, A

    1987-02-01

    Clinical observation has suggested that iron deficiency may be protective in malaria, and we have found that desferrioxamine (DF), an iron-specific chelating agent, inhibited Plasmodium falciparum growth in vitro. It was difficult to be confident that DF would be effective in an intact animal, however, because continuous exposure to DF was required in vitro and, in vivo, DF is rapidly excreted. Also, the in vitro effect of DF was overcome by addition of iron to the culture and in vivo there are potentially high local iron concentrations when iron is absorbed from the diet or released from reticuloendothelial cells. We now show that DF given by constant subcutaneous infusion does suppress parasitemia in P. falciparum-infected Aotus monkeys.

  15. Suppressing photochemical reactions with quantized light fields

    CERN Document Server

    Galego, Javier; Feist, Johannes

    2016-01-01

    Photoisomerization, i.e., a change of molecular structure after absorption of a photon, is one of the most fundamental photochemical processes. It can perform desirable functionality, e.g., as the primary photochemical event in human vision, where it stores electronic energy in the molecular structure, or for possible applications in solar energy storage and as memories, switches, and actuators; but it can also have detrimental effects, for example as an important damage pathway under solar irradiation of DNA, or as a limiting factor for the efficiency of organic solar cells. While photoisomerization can be avoided by shielding the system from light, this is of course not a viable pathway for approaches that rely on the interaction with external light (such as solar cells or solar energy storage). Here, we show that strong coupling of organic molecules to a confined light mode can be used to strongly suppress photoisomerization, and thus convert molecules that normally show fast photodegradation into photosta...

  16. Suppressing Electron Cloud in Future Linear Colliders

    CERN Document Server

    Pivi, M T F; Le Pimpec, Frederic; Raubenheimer, Tor O

    2005-01-01

    Any accelerator circulating positively charged beams can suffer from a build-up of an electron cloud in the beam pipe. The cloud develops through ionization of residual gases, synchrotron radiation and secondary electron emission and, when severe, can cause instability, emittance blow-up or loss of the circulating beam. The electron cloud is potentially a limiting effect for both the Large Hadron Collider (LHC) and the International Linear Collider (ILC). For the ILC positron damping ring, the development of the electron cloud must be suppressed. This paper presents the various effects of the electron cloud and evaluates their significance. It also discusses the state-of-the-art of the ongoing international R&D program to study potential remedies to reduce the secondary electron yield to acceptably low levels.

  17. Infinite volume suppression versus quantum fluctuations

    CERN Document Server

    Kartavtsev, Alexander

    2014-01-01

    It is routinely argued that tunneling of the Higgs field along the minimum of the Mexican hat potential is suppressed by the infinite space volume. In the path integral formalism this conclusion is drawn from the analysis of paths on which the field is homogeneous in the whole infinite space. Here we demonstrate that this approach fails to reproduce vacuum properties of even the simplest systems like free real scalar field. On the other hand, adding also the contributions of inhomogeneous field configurations we obtain for the free field the established results. This casts some doubt on the conclusions drawn for the Higgs field using the `homogeneous paths' approach and might call for a careful reanalysis of the mechanism of spontaneous symmetry breaking in quantum field theory.

  18. Latest results on $J/$ anomalous suppression

    Indian Academy of Sciences (India)

    Sérgio Ramos; NA50 Collaboration; B Allessandro; C Alexa; R Arnaldi; M Atayan; C Baglin; A Baldit; M Bedjidian; S Beolè; V Boldea; P Bordalo; S R Borenstein; G Borges; A Bussière; L Capelli; C Castanier; J Castor; B Chaurand; B Cheynis; E Chiavassa; C Cicalo; T Claudino; M P Comets; S Constantinescu; P Cortese; J Cruz; A DeFalco; N DeMarco; G Dellacasa; A Devaux; S Dita; O Drapier; B Espagnon; J Fargeix; P Force; M Gallio; Y K Gavrilov; C Gerschel; P Giubellino; M B Golubeva; M Gonin; A A Grigorian; S Grigorian; J Y Grossiord; F F Guber; A Guichard; H Gulkanyan; R Hakobyan; R Haroutunian; M Idzik; D Jouan; T L Karavitcheva; L Kluberg; A B Kurepin; Y Le Bornée; C Lourenço; P Macciotta; M Mac Cormick; A Marzari-Chiesa; M Masera; A Masoni; M Monteno; A Musso; P Petiau; A Piccotti; J R Pizzi; W L Prado da Silva; F Prino; G Puddu; C Quintans; L Ramello; S Ramos; P Rato Mendes; L Riccati; A Romana; H Santos; P Saturnini; E Scalas; E Scomparin; S Serci; R Shahoyan; F Sigaudo; M Sitta; P Sonderegger; X Tarrago; N S Topilskaya; G L Usai; E Vercellin; L Villatte; N Willis; T Wu

    2004-03-01

    The NA50 experiment deals with Pb–Pb collisions at 158 GeV/nucleon at the CERN SPS accelerator. The $J/$ production is studied through the muon decay channel, using the Drell–Yan dimuons as a reference. New results based on recent analyses, from data taken with improved experimental conditions and using different centrality estimators, are presented and compared to an update of those already obtained from previous data samples. The stepwise pattern of the anomalous $J/$ suppression as a function of centrality, already present in these previous results, is confirmed. This observation could be a fingerprint of the theoretically predicted melting of charmonia resonances in a deconfined quark–gluon plasma.

  19. Suppression of Instability in Rotatory Hydromagnetic Convection

    Indian Academy of Sciences (India)

    Joginder S Dhiman

    2000-08-01

    Recently discovered hydrodynamic instability [1], in a simple Bénard configuration in the parameter regime 02 > 1 under the action of a nonadverse temperature gradient, is shown to be suppressed by the simultaneous action of a uniform rotation and a uniform magnetic field both acting parallel to gravity for oscillatory perturbations whenever $(\\mathscr{Q}_1/^2+\\mathscr{J}/^4) > 1$ and the effective Rayleigh number $\\mathcal{R}$(1-02) is dominated by either 274(1 + 1/1)/4 or 274/2 according as 1 ≥ 1 or 1 ≤ 1 respectively. Here 0 is the temperature of the lower boundary while 2 is the coefficient of specific heat at constant volume due to temperature variation and 1, $\\mathcal{R}, \\mathscr{Q}$ and $\\mathscr{T}$ respectively denote the magnetic Prandtl number, the Rayleigh number, the Chandrasekhar number and the Taylor number.

  20. Probe suppression in conformal phased array

    CERN Document Server

    Singh, Hema; Neethu, P S

    2017-01-01

    This book considers a cylindrical phased array with microstrip patch antenna elements and half-wavelength dipole antenna elements. The effect of platform and mutual coupling effect is included in the analysis. The non-planar geometry is tackled by using Euler's transformation towards the calculation of array manifold. Results are presented for both conducting and dielectric cylinder. The optimal weights obtained are used to generate adapted pattern according to a given signal scenario. It is shown that array along with adaptive algorithm is able to cater to an arbitrary signal environment even when the platform effect and mutual coupling is taken into account. This book provides a step-by-step approach for analyzing the probe suppression in non-planar geometry. Its detailed illustrations and analysis will be a useful text for graduate and research students, scientists and engineers working in the area of phased arrays, low-observables and stealth technology.

  1. Gel fire suppressants for controlling underground heating

    Institute of Scientific and Technical Information of China (English)

    HU Sheng-gen; XUE Sheng

    2011-01-01

    One of the major safety issues in coal mining is heatings and the resultant spontaneous combustion in underground coal mines.CSIRO researchers have developed a number of polymer gels suitable for controlling heatings in coal mines.These gels were developed to meet strict selection criteria including easy preparation,no or low toxicity,controllable gelation time,adaptable to mine water chemistry,adjustable viscosity,relatively long gel life,thermally and chemically stable and low cost.The HPAM-Aluminum Citrate gel system was identified to be the most favourable gel system for fire suppression in underground coal mines.These gels can be applied to the areas undergoing coal heating or gas leakage at a controllable gelation time and impermeable gel barriers can be formed in the areas to block ingress of air.

  2. Ion suppression from blood collection devices

    DEFF Research Database (Denmark)

    Hasselstrøm, Jørgen Bo; Sejr Gothelf, Aase

    The aim of the study was to examine the variation in ion suppression in ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS-MS) methods when using different blood collection devices. Three different methods measuring 18 antidepressants and antipsychotics in total were...... studied. The blood collection devices were all designed to activate clot formation. They were made of glass with or without silicone coating or plastic containing silicate particles, thrombin or polystyrene particles coated with kaolin. The blood collection devises Venoject and Venosafe were supplied from...... Terumo, S-monovette from Sarstedt, Vacuette from Greiner Bio-One and three BD Vacutainer serum tubes from BD. These seven different blood collection devices were used to withdraw blood from five healthy drug free donors (n=35) in random order. The samples were centrifuged and serum from each sample...

  3. Suppressing Redundancy in Wireless Sensor Network Traffic

    Science.gov (United States)

    Abe, Rey; Honiden, Shinichi

    Redundancy suppression is a network traffic compression technique that, by caching recurring transmission contents at receiving nodes, avoids repeatedly sending duplicate data. Existing implementations require abundant memory both to analyze recent traffic for redundancy and to maintain the cache. Wireless sensor nodes at the same time cannot provide such resources due to hardware constraints. The diversity of protocols and traffic patterns in sensor networks furthermore makes the frequencies and proportions of redundancy in traffic unpredictable. The common practice of narrowing down search parameters based on characteristics of representative packet traces when dissecting data for redundancy thus becomes inappropriate. Such difficulties made us devise a novel protocol that conducts a probabilistic traffic analysis to identify and cache only the subset of redundant transfers that yields most traffic savings. We verified this approach to perform close enough to a solution built on exhaustive analysis and unconstrained caching to be practicable.

  4. Are Patents used to Suppress Useful Technology?

    DEFF Research Database (Denmark)

    Howells, John

    2006-01-01

    This article examines the evidence behind claims that innovation is hindered or blocked (termed technology suppression) by corporations' use of patents. In other words, are there ways in which the exploitation of the exclusive development right of the patent can be shown to retard the process...... of innovation, other than in the trivial sense of excluding third parties from the right to develop the technology covered by the patent? There are many references to this possibility in the management, economic and legal literatures, but two highly-cited papers stand out for grounding their claims of corporate...... and the difference between economic monopoly and an exclusive right. It is argued here that what is at issue in this work is the proper function of the patent institution. It is shown early in this paper that the understanding of the patent institution as a system of development prospects makes better sense...

  5. In-Beam Background Suppression Shield

    CERN Document Server

    Santoro, V; DiJulio, D D; Ansell, S; Bentley, P M

    2015-01-01

    The long (3ms) proton pulse of the European Spallation Source (ESS) gives rise to unique and potentially high backgrounds for the instrument suite. In such a source an instrument capabilities will be limited by it's Signal to Noise (S/N) ratio. The instruments with a direct view of the moderator, which do not use a bender to help mitigate the fast neutron background, are the most challenging. For these beam lines we propose the innovative shielding of placing blocks of material directly into the guide system, which allow a minimum attenuation of the cold and thermal fluxes relative to the background suppression. This shielding configuration has been worked into a beam line model using Geant4. We study particularly the advantages of single crystal sapphire and silicon blocks .

  6. Interpretations of J/$\\psi$ suppression

    CERN Document Server

    Armesto-Pérez, Nestor

    1997-01-01

    We review the two main interpretations of $J/\\psi$ suppression proposed in the literature. The phase transition (or deconfining) scenario assumes that below some critical value of the local energy density (or of some other geometrical quantity which depends both on the colliding systems and on the centrality of the collision), there is only nuclear absorption. Above this critical value the absorptive cross-section is taken to be infinite, i.e. no $J/\\psi$ can survive in this hot region. In the hadronic scenario the $J/\\psi$ dissociates due both to nuclear absorption and to its interactions with co-moving hadrons produced in the collision. No discontinuity exists in physical observables. We show that an equally good description of the present data is possible in either scenario.

  7. Pulse compression and prepulse suppression apparatus

    Science.gov (United States)

    Dane, C.B.; Hackel, L.A.; George, E.V.; Miller, J.L.; Krupke, W.F.

    1993-11-09

    A pulse compression and prepulse suppression apparatus (10) for time compressing the output of a laser (14). A pump pulse (46) is separated from a seed pulse (48) by a first polarized beam splitter (20) according to the orientation of a half wave plate (18). The seed pulse (48) is directed into an SBS oscillator (44) by two plane mirrors (22, 26) and a corner mirror (24), the corner mirror (24) being movable to adjust timing. The pump pulse (46) is directed into an SBS amplifier 34 wherein SBS occurs. The seed pulse (48), having been propagated from the SBS oscillator (44), is then directed through the SBS amplifier (34) wherein it sweeps the energy of the pump pulse (46) out of the SBS amplifier (34) and is simultaneously compressed, and the time compressed pump pulse (46) is emitted as a pulse output (52). A second polarized beam splitter (38) directs any undepleted pump pulse 58 away from the SBS oscillator (44).

  8. Axionic suppression of plasma wakefield acceleration

    Science.gov (United States)

    Burton, D. A.; Noble, A.; Walton, T. J.

    2016-09-01

    Contemporary attempts to explain the existence of ultra-high energy cosmic rays using plasma-based wakefield acceleration deliberately avoid non-standard model particle physics. However, such proposals exploit some of the most extreme environments in the Universe and it is conceivable that hypothetical particles outside the standard model have significant implications for the effectiveness of the acceleration process. Axions solve the strong CP problem and provide one of the most important candidates for cold dark matter, and their potential significance in the present context should not be overlooked. Our analysis of the field equations describing a plasma augmented with axions uncovers a dramatic axion-induced suppression of the energy gained by a test particle in the wakefield driven by a particle bunch, or an intense pulse of electromagnetic radiation, propagating at ultra-relativistic speeds within the strongest magnetic fields in the Universe.

  9. Suppression of decoherence by bath ordering

    Institute of Scientific and Technical Information of China (English)

    Jing Jun; Ma Hong-Ru

    2007-01-01

    The dynamics of two coupled spins-1/2 coupled to a spin-bath is studied as an extended model of the TessieriWilkie Hamiltonian. The pair of spins served as an open subsystem is prepared in one of the Bell states and the bath consisting of some spins-1/2 is in a thermal equilibrium state from the very beginning. It is found that with increasing coupling strength of the bath spins, the bath forms a resonant antiferromagnetic order. The polarization correlation between the two spins of the subsystem and the concurrence of it are recovered to some extent in the isolated subsystem. This suppression of the subsystem decoherence may be used to control the quantum devices in practical applications.

  10. Fever: suppress or let it ride?

    Science.gov (United States)

    Ray, Juliet J; Schulman, Carl I

    2015-12-01

    While our ability to detect and manage fever has evolved since its conceptualization in the 5(th) century BC, controversy remains over the best evidence-based practices regarding if and when to treat this physiologic derangement in the critically ill. There are two basic fields of thought: (I) fever should be suppressed because its metabolic costs outweigh its potential physiologic benefit in an already stressed host; vs. (II) fever is a protective adaptive response that should be allowed to run its course under most circumstances. The latter approach, sometime referred to as the "let it ride" philosophy, has been supported by several recent randomized controlled trials like that of Young et al. [2015], which are challenging earlier observational studies and may be pushing the pendulum away from the Pavlovian treatment response.

  11. Obtuse triangle suppression in anisotropic meshes

    KAUST Repository

    Sun, Feng

    2011-12-01

    Anisotropic triangle meshes are used for efficient approximation of surfaces and flow data in finite element analysis, and in these applications it is desirable to have as few obtuse triangles as possible to reduce the discretization error. We present a variational approach to suppressing obtuse triangles in anisotropic meshes. Specifically, we introduce a hexagonal Minkowski metric, which is sensitive to triangle orientation, to give a new formulation of the centroidal Voronoi tessellation (CVT) method. Furthermore, we prove several relevant properties of the CVT method with the newly introduced metric. Experiments show that our algorithm produces anisotropic meshes with much fewer obtuse triangles than using existing methods while maintaining mesh anisotropy. © 2011 Elsevier B.V. All rights reserved.

  12. Upsilon suppression in the QGP at the LHC

    Science.gov (United States)

    Wolschin, Georg

    2016-12-01

    The suppression of ϒ-mesons in the hot quark-gluon medium in PbPb collisions is accounted for in a model that encompasses gluodissociation, collisional damping, screening, and reduced feed-down. Theoretical results for centrality-dependent suppression factors of the ϒ (1 S) and ϒ (2 S) states are compared with CMS data. The measured ground state suppression is well represented, but discrepancies between data and model persist for peripheral ϒ (2 S)-events that require additional suppression mechanisms. The pT-dependence of the suppression is discussed and a prediction for the centrality-dependent ϒ (1 S) suppression in 5.02 TeV PbPb is made.

  13. Probiotic Diversity Enhances Rhizosphere Microbiome Function and Plant Disease Suppression

    OpenAIRE

    Hu, Jie; Wei, Zhong; Friman, Ville Petri; Gu, Shao-Hua; Wang, Xiao-Fang; Eisenhauer, Nico; Yang, Tian-jie; Ma, Jing; Shen, Qi-Rong; Xu, Yang-chun; Jousset, Alexandre

    2016-01-01

    Bacterial communities associated with plant roots play an important role in the suppression of soil-borne pathogens, and multispecies probiotic consortia may enhance disease suppression efficacy. Here we introduced defined Pseudomonas species consortia into naturally complex microbial communities and measured the importance of Pseudomonas community diversity for their survival and the suppression of the bacterial plant pathogen Ralstonia solanacearum in the tomato rhizosphere microbiome. The ...

  14. Methods for suppressing isomerization of olefin metathesis products

    Energy Technology Data Exchange (ETDEWEB)

    Firth, Bruce E.; Kirk, Sharon E.; Gavaskar, Vasudeo S.

    2015-09-22

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. The isomerization suppression agent is phosphorous acid, a phosphorous acid ester, phosphinic acid, a phosphinic acid ester or combinations thereof. Methods of refining natural oils are described.

  15. The ups and downs of J/psi suppression

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, R.

    2000-10-17

    An overview of the present status of J/psi suppression in pA and nucleus-nucleus interactions is presented. In both cases, model predictions are summarized and compared to the data. The ''anomalous'' J/psi suppression in Pb+Pb collisions is discussed in some detail. Predictions are also shown for quarkonium suppression at collider energies.

  16. Efecto de la administración de espironolactona sobre la pérdida de podocitos y la progresión de la nefropatía diabética experimental Effects of spironolactone administration on the podocytes loss and progression of experimental diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2012-12-01

    Full Text Available Objetivos. Evaluar el efecto de espironolactona (SPL sobre la pérdida de los podocitos durante la progresión de la nefropatía diabética (ND experimental. Materiales y métodos. Aleatoriamente un grupo de ratas macho Holtzman recibieron estreptozotocina (grupo diabético o citrato buffer (grupo control. Las ratas diabéticas fueron tratadas con SPL (50 mg/kg/día. El área glomerular y la celularidad fueron evaluadas por métodos histomorfométricos. La lesión y pérdida de podocitos fue evaluada por la expresión de desmina y Wt-1, respectivamente. La expresión génica del TGF-β1 se evaluó mediante RT-PCR. Resultados. Los niveles de glucosa, el área glomerular, la expansión mesangial y el contenido de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de SPL previno estos cambios sin modificar los niveles de glucosa. La inmunotinción para Wt-1 se redujo significativamente, mientras que la inmunotinción para desmina se incrementó drásticamente en las ratas diabéticas. El tratamiento con SPL previno el incremento de expresión de desmina y la pérdida de expresión de Wt-1. Asimismo, la administración de SPL previno el incremento de la expresión del mRNA del TGF-β1 en las ratas diabéticas. Conclusiones. El tratamiento con SPL, a través de efectos glucosa independientes, atenúa la perdida de podocitos y la progresión de los cambios morfológicos de la ND. Los presentes resultados sugieren que estos efectos son mediados, al menos en parte, por la inhibición de la la expresión del mRNA del TGF-β1.Objectives. Evaluate the effect of spironolactone (SPL on the loss of podocytes during the progression of experimental diabetic nephropathy (DN. Materials and methods. A group of male Holtzman rats randomly received streptozotocin (diabetic group or a buffer citrate (control group. Diabetic rats were treated with SPL (50 mg/kg/day. The glomerular area and the cellularity were evaluated by

  17. Effect of gypenoside on the podocyte injury and its mechanism in rats with diabetic nephropathy%绞股蓝总皂苷对糖尿病肾病大鼠足细胞损伤的影响及机制

    Institute of Scientific and Technical Information of China (English)

    黄平; 王雁秋

    2012-01-01

    目的:研究绞股蓝总皂苷对糖尿病肾病(DN)大鼠肾脏足细胞相关分子( nephrin)、血管通透因子(VEGF)mRNA表达的影响,探讨其降低尿蛋白、保护肾脏的机制.方法:采用单侧肾切除加链脲佐菌素( STZ)注射法改良复制DN模型,实验分为正常组、模型组、治疗组(绞股蓝总皂苷高、中、低剂量组)和缬沙坦组.干预4周后电镜观察肾小球超微结构改变,RT-PCR检测nephrin、VEGF mRNA表达.结果:各治疗组病理变化较模型组均有不同程度改善:足突增宽或部分融合,基底膜增厚减轻,同时nephrin mRNA表达水平较模型组明显上调(P<0.01),VEGF表达明显抑制(P<0.01),其中高剂量组和缬沙坦组效果类似,明显优于低剂量组(P<0.01).结论:绞股蓝总皂苷可能通过上调足细胞相关分子nephrin表达,抑制分泌VEGF过表达,减轻足细胞超微结构改变,从而保护足细胞,降低尿蛋白,延缓肾小球硬化.%Objective: To investigate the effect of gypenoside on the expressions of nephrin, vascular endothelial growth factor (VEGF) in rats with diabetic nephropathy (DN) and explore its mechanism of the reduction of proteinuria and renal protection. Methods: DN model was established by uninephrectomized and induced with streptozotocin (STZ), then randomly divided into model group and treatment groups (groups of high, medium, low dose of gypenoside, and valsartan group), with normal rats as the control group. All the rats received daily gavage for 4 weeks, and then the ultramicrostructure changes of the glomerulus were observed with transmission electron microscope. The expressions of Nephrin, VEGF mRNA in the podocytes were detected by real-time quantitative PCR. Results: Comparing to the model group, the pathological changes of every treatment groups were improved in different degree: the extension and fusion of foot processes and the thickness of glomerular basement membrane were all ameliorated. Simultaneously, the

  18. Chatter Suppression with Ultrasonic Elliptical Vibration Based on Energy Principle

    Institute of Scientific and Technical Information of China (English)

    MA Chun-xiang; E Shamoto; T Moriwaki

    2005-01-01

    A new method is proposed to suppress chatter, in which the ultrasonic elliptical vibration is added on the cutting tool edge. It results in the fact that the rake face of tool is separated from the chip and the direction of the frictional force between the rake face and the chip is reversed in each cycle of elliptical vibration cutting. The experimental investigations show that the chatter can be suppressed effectively by adding ultrasonic elliptical vibration on the cutting tool edge. In order to make clear the reason of chatter suppression, the mechanism of chatter suppression is analyzed theoretically from the viewpoint of energy.

  19. DC-SIGN expression on podocytes and its role in immune and inflammatory responses of lupus nephritis%足细胞DC-SIGN表达及其在狼疮肾炎免疫炎性反应中的作用

    Institute of Scientific and Technical Information of China (English)

    蔡敏超; 周同; 黄娟; 王轩; 袁伟杰

    2014-01-01

    目的:观察足细胞树突状细胞(DC)表型分子DC⁃SIGN的表达,以及探讨其对狼疮肾炎(LN)局部免疫炎性反应的作用。方法利用免疫组化及免疫荧光观察LN患者肾组织DC⁃SIGN及IgG1表达。选取4周龄LN小鼠随机分为实验组、干预组,另取C57BL/6J小鼠作为正常对照组。干预组于小鼠第6周龄注入抗DC⁃SIGN抗体,分别于第16、20、24、28周龄处死各组小鼠,观察小鼠肾功能及肾组织病理变化,并采用免疫组化及免疫荧光观察肾组织DC⁃SIGN及IgG1表达。此外取小鼠足细胞给予LN鼠血清处理,流式细胞术观察足细胞主要组织相容性复合体II(MHC II)、CD80、DC⁃SIGN表达;混合淋巴细胞反应(MLR)检测共培养后其刺激T细胞增殖的能力;ELISA法测定MLR上清中γ干扰素(IFN⁃γ)、IL⁃4含量。结果(1)LN患者肾小球可见DC⁃SIGN及IgG1表达。(2)LN小鼠自20周龄起伴随尿蛋白增加(P<0.01),肾小球亦见DC⁃SIGN及IgG1表达,至24周龄Scr显著增加(P<0.01);经针对DC⁃SIGN抗体干预后,尿蛋白减少(P<0.01),肾功能明显改善(P<0.01)。(3)经LN鼠血清刺激后,小鼠足细胞DC⁃SIGN、MHC II、CD80表达上调,体外刺激T细胞增殖能力增强(P<0.01),且T细胞分泌的IFN⁃γ/IL⁃4比值增高(P<0.01);经抗DC⁃SIGN抗体干预,足细胞DC⁃SIGN、MHC II、CD80表达均下调,且刺激T细胞增殖能力减弱(P<0.01),IFN⁃γ/IL⁃4比值下降(P<0.01)。结论 LN足细胞可通过表达DC⁃SIGN发挥DC样细胞功能,可能参与LN局部组织免疫炎性反应;而抑制DC⁃SIGN可调抑足细胞免疫功能,并产生防治效应。%Objective To explore the expression of DC⁃SIGN, the phenotype of dendritic cells (DCs), on podocytes, and its role in immune and inflammatory responses of lupus nephritis (LN). Methods DC⁃SIGN and IgG1 expression in renal

  20. Influence of angiotensinⅡand losartan on GLUT4 expression in cultured mouse podocyte cells%血管紧张素Ⅱ及氯沙坦对小鼠足细胞葡萄糖转运蛋白4表达的影响

    Institute of Scientific and Technical Information of China (English)

    王泽彬; 傅君舟; 周姗姗

    2014-01-01

    Objective To investigate the influence of angiotensinⅡ(AngⅡ) on the expression of GLUT4 and whether losartan (Lo) could depress the function of AngⅡon podocytes. Methods The mouse podocyte clone 5 (MPC5) were divided into five groups: the control group, AngⅡ at the concentration of 10-6, 10-8, 10-10 mmol/L groups, and Lo 10-6 mmol/L+AngⅡ10-6 mmol/L group. The GLUT4 mRNA level was detected by semi-quantitative RT-PCR and the expression of GLUT4 by indirect immunofluorescence. Results Compared to the control group, in group AngⅡ10-6 mmol/L, the GLUT4 expression and protein synthesis were significantly decreased, GLUT4 mRNA transcription was decreased by 56.1%(P=0.041), and indirect immunofluorescence expression was decreased by 54.9%. The GLUT4 expression of AngⅡ10-10 mmol/L and AngⅡ10-8 mmol/L group was decreased compared with the control group, but there were no statistically significant difference. AngⅡ10-8 mmol/L depressed more GLUT4 expression than the AngⅡ10-10 mmol/L did, and there were also no statistically significant difference (P>0.05). As for the Lo 10-6 mmol/L+AngⅡ10-6 mmol/L group, the GLUT4 expression was significantly increased, when compared with the AngⅡ10-6 group its GLUT4 mRNA transcription was increased by 176.3%(P=0.006), and indirect immunofluorescence expres-sion increased by 87.8%(P0.05),AngⅡ10-8 mmol/L组对GLUT4抑制强于AngⅡ10-10 mmol/L组,两组间差异无统计学意义(P>0.05)。Lo 10-6 mmol/L+AngⅡ10-6 mmol/L组GLUT4的表达显著升高,与AngⅡ10-6组相比,mRNA升高176.3%(P=0.006),蛋白表达升高87.8%(P<0.05)。结论 AngⅡ能够显著抑制足细胞GLUT4的表达及合成,具有浓度依赖性,这种作用能被氯沙坦所阻断。

  1. One-tone suppression in the frog auditory nerve

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    frequencies ranged from 700 to 1200 Hz. Spontaneous activities for the fibers showing one-tone suppression ranged from 3 to 75 spikes/s. Spontaneous activities above 40 spikes/s and the phenomenon of one-tone suppression itself has not been reported previously for frogs. The population of fibers showing one...

  2. Microbial populations responsible for specific soil suppressiveness to plant pathogens.

    Science.gov (United States)

    Weller, David M; Raaijmakers, Jos M; Gardener, Brian B McSpadden; Thomashow, Linda S

    2002-01-01

    Agricultural soils suppressive to soilborne plant pathogens occur worldwide, and for several of these soils the biological basis of suppressiveness has been described. Two classical types of suppressiveness are known. General suppression owes its activity to the total microbial biomass in soil and is not transferable between soils. Specific suppression owes its activity to the effects of individual or select groups of microorganisms and is transferable. The microbial basis of specific suppression to four diseases, Fusarium wilts, potato scab, apple replant disease, and take-all, is discussed. One of the best-described examples occurs in take-all decline soils. In Washington State, take-all decline results from the buildup of fluorescent Pseudomonas spp. that produce the antifungal metabolite 2,4-diacetylphloroglucinol. Producers of this metabolite may have a broader role in disease-suppressive soils worldwide. By coupling molecular technologies with traditional approaches used in plant pathology and microbiology, it is possible to dissect the microbial composition and complex interactions in suppressive soils.

  3. Chronic Juvenile Delinquency and the "Suppression Effect": An Exploratory Study.

    Science.gov (United States)

    Fraser, Mark; Norman, Michael

    1988-01-01

    Notes that fear of apprehension and punishment have been reported to suppress juvenile crime. Discusses suppression effect in regard to the correlates of chronic juvenile delinquency and exploratory evidence that youth who commit large volume of crime do not fear sanctions imposed by juvenile court any more than youth who commit only one offense…

  4. Eye Contact Facilitates Awareness of Faces during Interocular Suppression

    Science.gov (United States)

    Stein, Timo; Senju, Atsushi; Peelen, Marius V.; Sterzer, Philipp

    2011-01-01

    Eye contact captures attention and receives prioritized visual processing. Here we asked whether eye contact might be processed outside conscious awareness. Faces with direct and averted gaze were rendered invisible using interocular suppression. In two experiments we found that faces with direct gaze overcame such suppression more rapidly than…

  5. Socioeconomic Inequality and Giftedness: Suppression and Distortion of High Ability

    Science.gov (United States)

    Ambrose, Don

    2013-01-01

    Severe socioeconomic inequality strongly suppresses and distorts the discovery of aspirations and the concomitant development of talents among the gifted. More comprehensive understanding of this suppression and distortion is available through a wide-ranging interdisciplinary search for research findings and theories that illuminate economic,…

  6. Social Hierarchy and Depression: The Role of Emotion Suppression

    Science.gov (United States)

    Langner, Carrie A.; Epel, Elissa; Matthews, Karen; Moskowitz, Judith T.; Adler, Nancy

    2017-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The Coronary Artery Risk Development in Young Adults (CARDIA) study). Similar to Study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression. PMID:22808688

  7. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    DEFF Research Database (Denmark)

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc;

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  8. Ejector Noise Suppression with Auxiliary Jet Injection

    Science.gov (United States)

    Berman, Charles H.; Andersen, Otto P., Jr.

    1997-01-01

    An experimental program to reduce aircraft jet turbulence noise investigated the interaction of small auxiliary jets with a larger main jet. Significant reductions in the far field jet noise were obtained over a range of auxiliary jet pressures and flow rates when used in conjunction with an acoustically lined ejector. While the concept is similar to that of conventional ejector suppressors that use mechanical mixing devices, the present approach should improve thrust and lead to lower weight and less complex noise suppression systems since no hardware needs to be located in the main jet flow. A variety of auxiliary jet and ejector configurations and operating conditions were studied. The best conditions tested produced peak to peak noise reductions ranging from 11 to 16 dB, depending on measurement angle, for auxiliary jet mass flows that were 6.6% of the main jet flow with ejectors that were 8 times the main jet diameter in length. Much larger reductions in noise were found at the original peak frequencies of the unsuppressed jet over a range of far field measurement angles.

  9. A dual purpose Compton suppression spectrometer

    CERN Document Server

    Parus, J; Raab, W; Donohue, D

    2003-01-01

    A gamma-ray spectrometer with a passive and an active shield is described. It consists of a HPGe coaxial detector of 42% efficiency and 4 NaI(Tl) detectors. The energy output pulses of the Ge detector are delivered into the 3 spectrometry chains giving the normal, anti- and coincidence spectra. From the spectra of a number of sup 1 sup 3 sup 7 Cs and sup 6 sup 0 Co sources a Compton suppression factor, SF and a Compton reduction factor, RF, as the parameters characterizing the system performance, were calculated as a function of energy and source activity and compared with those given in literature. The natural background is reduced about 8 times in the anticoincidence mode of operation, compared to the normal spectrum which results in decreasing the detection limits for non-coincident gamma-rays up to a factor of 3. In the presence of other gamma-ray activities, in the range from 5 to 11 kBq, non- and coincident, the detection limits can be decreased for some nuclides by a factor of 3 to 5.7.

  10. Heavy quarkonium suppression in a fireball

    Energy Technology Data Exchange (ETDEWEB)

    Escobedo, Miguel Ángel [Physik-Department, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany Institut de Physique Théorique, CEA Saclay, F-91191 Gif-sur-Yvette (France)

    2016-01-22

    The dissociation of heavy quarkonium seen in heavy-ion collisions is a phenomena that allows to extract information of the produced thermal medium. This was believed to be due to the screening of the static potential but recently perturbative computations and some lattice studies have pointed out the possibility of having an imaginary part of the potential that would also contribute to dissociation. In recent years a program to study heavy quarkonium with the use of non-relativistic effective field theories (EFTs) has been started, this allows to make the computations in a more systematic way by defining a more suitable power counting and making it more difficult to miss necessary resummations. However until now these studies have been done assuming thermal equilibrium. In this work we will discuss what happens in the EFT formalism when heavy quarkonium is in a medium that is not in thermal equilibrium and what is the expected suppression when a medium with a time dependent effective temperature that follows Bjorken evolution is considered. This will be done adapting previous results from different temperature regimes.

  11. Rotator cuff injury: fat suppression MR image

    Energy Technology Data Exchange (ETDEWEB)

    Won, Jong Yoon; Suh, Jin Suck; Park, Chang Yun; Lee, Yeon Hee [Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Soo [Inje University College of Medicine, Busan (Korea, Republic of)

    1994-04-15

    We performed the study prospectively to evaluate the advantage of fat suppression MR in the diagnosis of rotator cuff injury. Ten symptomatic patients were studied with both conventional T2WI and FST2WI using chemical shift technique. Each image was analyzed for the assessment of injuries, conspicuity of the lesion, the presence of effusion in subacromical bursae and joint space, and presence of humeral head injury. Arthroscopy was done in 4 patients following MRI. We could made presumptive diagnoses on FSMR as identical as on conventional MR in six cases(1 normal, 2 tendinitis, 2 partial thickness tear, 1 full thickness tear), two of them were confirmed by arthroscopic procedures. Two cases of partial thickness tear proved by arthroscopy were detected on FST2WI, whereas they were considered tendinitis on conventional T2WI. There were another 2 cases who showed tendinitis on FSMR, but normal on conventional T2WI. They, however, were not confirmed by either arthroscopy or surgical procedure. We found the FSMR were superior to conventional T2WI in the conspicuity of lesions and detection of joint effusion and abnormalities on the humeral head. We think FSMR of the shoulder could have significant diagnostic advantages over the conventional spin-echo MR imaging.

  12. Mucins Suppress Virulence Traits of Candida albicans

    Science.gov (United States)

    Kavanaugh, Nicole L.; Zhang, Angela Q.; Nobile, Clarissa J.; Johnson, Alexander D.

    2014-01-01

    ABSTRACT Candida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodates C. albicans as part of the normal microbiota, where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, rendering C. albicans impaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulate C. albicans physiology, and we hypothesize that they are key environmental signals for retaining C. albicans in the host-compatible, commensal state. PMID:25389175

  13. The SSM with Suppressed SUSY Charge

    Directory of Open Access Journals (Sweden)

    John A. Dixon

    2016-10-01

    Full Text Available The concept of Suppressed SUSY Charge, introduced in a recent Letter, is used here to assemble a new version of the SSM. This new SSM has no need for Squarks or Sleptons. It does not need spontaneous breaking of SUSY, so that the cosmological constant problem does not arise (at least at tree level. It mimics the usual non-supersymmetric Standard Model very well, and the absence of large flavour changing neutral currents is natural. There is no need for a hidden sector, or a messenger sector, or explicit ‘soft’ breaking of SUSY. Spontaneous Gauge Symmetry Breaking from SU(3×SU(2×U(1 to SU(3×U(1 in the model assembled here implies the existence of two new very heavy Higgs Bosons with mass 13.4 TeV, slightly smaller than the energy of the LHC at 14 TeV. There is also a curious set of Gauginos and Higgsinos which have exactly the same masses as the Higgs and Gauge Bosons. These do not couple to the Quarks and Leptons, except through the Higgs and Gauge Bosons. As it stands, this model probably gives rise to too many W+ decays to be consistent with experiment. The Feynman loop expansion of this theory also needs further examination.

  14. The SSM with Suppressed SUSY Charge

    Science.gov (United States)

    Dixon, John A.

    2016-10-01

    The concept of Suppressed SUSY Charge, introduced in a recent Letter, is used here to assemble a new version of the SSM. This new SSM has no need for Squarks or Sleptons. It does not need spontaneous breaking of SUSY, so that the cosmological constant problem does not arise (at least at tree level). It mimics the usual non-supersymmetric Standard Model very well, and the absence of large flavour changing neutral currents is natural. There is no need for a hidden sector, or a messenger sector, or explicit 'soft' breaking of SUSY. Spontaneous Gauge Symmetry Breaking from SU (3) × SU (2) × U (1) to SU (3) × U (1) in the model assembled here implies the existence of two new very heavy Higgs Bosons with mass 13.4 TeV, slightly smaller than the energy of the LHC at 14 TeV. There is also a curious set of Gauginos and Higgsinos which have exactly the same masses as the Higgs and Gauge Bosons. These do not couple to the Quarks and Leptons, except through the Higgs and Gauge Bosons. As it stands, this model probably gives rise to too many W+ decays to be consistent with experiment. The Feynman loop expansion of this theory also needs further examination.

  15. 't Hooft suppression and holographic entropy

    CERN Document Server

    Kelly, William R; Marolf, Donald

    2015-01-01

    Recent works have related the bulk first law of black hole mechanics to the first law of entanglement in a dual CFT. These are first order relations, and receive corrections for finite changes. In particular, the latter is naively expected to be accurate only for small changes in the quantum state. But when Newton's constant is small relative to the AdS scale, the former holds to good approximation even for classical perturbations that contain many quanta. This suggests that -- for appropriate states -- corrections to the first law of entanglement are suppressed by powers of $N$ in CFTs whose correlators satisfy 't Hooft large-$N$ power counting. We take first steps toward verifying that this is so by studying the large-$N$ structure of the entropy of spatial regions for a class of CFT states motivated by those created from the vacuum by acting with real-time single-trace sources. We show that $1/N$ counting matches bulk predictions, though we require the effect of the source on the modular hamiltonian to be ...

  16. 't Hooft suppression and holographic entropy

    Science.gov (United States)

    Kelly, William R.; Kuns, Kevin; Marolf, Donald

    2015-10-01

    Recent works have related the bulk first law of black hole mechanics to the first law of entanglement in a dual CFT. These are first order relations, and receive corrections for finite changes. In particular, the latter is naively expected to be accurate only for small changes in the quantum state. But when Newton's constant is small relative to the AdS scale, the former holds to good approximation even for classical perturbations that contain many quanta. This suggests that — for appropriate states — corrections to the first law of entanglement are suppressed by powers of N in CFTs whose correlators satisfy 't Hooft large- N power counting. We take first steps toward verifying that this is so by studying the large- N structure of the entropy of spatial regions for a class of CFT states motivate dby those created from the vacuum by acting with real-time single-trace sources. We show that 1 /N counting matches bulk predictions, though we require the effect of the source on the modular hamiltonian to be non-singular. The magnitude of our sources is ɛ N with ɛ fixed-but-small as N → ∞. Our results also provide a perturbative derivation — without relying on the replica trick — of the subleading Faulkner-Lewkowycz-Maldacena correction to the Ryu-Takayagi and Hubeny-Rangamani-Takayanagi conjectures at all orders in 1 /N.

  17. Interference suppression in noise radar systems

    Science.gov (United States)

    Djukanović, Slobodan; Daković, Miloš; Thayaparan, Thayananthan; Stanković, Ljubiša

    2011-06-01

    This paper addresses the issue of interference suppression in noise radars. The proposed methods can be divided into non-parametric and parametric ones. The considered non-parametric methods are based on linear time-frequency (TF) tools, namely the short-time Fourier transform (STFT) and local polynomial Fourier transform (LPFT). The STFT is the simplest TF method, but, due to the resolution problem, it performs poorly with highly nonstationary interferences. The LPFT resolves the resolution problem, however at the cost of increased complexity. In parametric methods, the phase of interference is locally approximated by a polynomial, which is motivated by the Weierstrass's theorem. Using the phase approximation, the corrupted received signal is demodulated and successively filtered. Two methods for polynomial phase approximation are considered, the high-order ambiguity function (HAF) and product high-order ambiguity function (PHAF). The method based on the HAF is computationally efficient; however, it suffers from the identifiability problem when multicomponent signals are considered. The identifiability problem can be resolved using the PHAF.

  18. An electrophysiological assessment of distractor suppression in visual search tasks.

    Science.gov (United States)

    Mazza, Veronica; Turatto, Massimo; Caramazza, Alfonso

    2009-07-01

    We investigated whether the N2pc is unequivocally linked to distractor-suppression mechanisms, as is commonly assumed. According to the distractor-suppression account of the N2pc, no suppression, and thus no N2pc, should occur when homogeneous distractors help in selecting the target, such as when the target feature is unpredictable. Participants performed a simple detection or a finer discrimination on a singleton target, which had either a variable or a constant color. Contrary to the distractor-suppression account, an N2pc was present for both the variable and the constant conditions, and for both tasks. Additionally, target feature consistency correlated with earlier N2pc onsets relative to variable blocks. Both results indicate that the N2pc is not unequivocally linked to distractor-suppression mechanisms, but may index mechanisms involved in identifying and localizing relevant stimuli through enhancement of their features.

  19. Cytokine treatment of macrophage suppression of T cell activation.

    Science.gov (United States)

    Silberman, Daniel; Bucknum, Amanda; Kozlowski, Megan; Matlack, Robin; Riggs, James

    2010-01-01

    High Mphi:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNgamma-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mphi expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mphi:T cell ratios found in many tumors.

  20. Evolution of cancer suppression as revealed by mammalian comparative genomics.

    Science.gov (United States)

    Tollis, Marc; Schiffman, Joshua D; Boddy, Amy M

    2017-02-02

    Cancer suppression is an important feature in the evolution of large and long-lived animals. While some tumor suppression pathways are conserved among all multicellular organisms, others mechanisms of cancer resistance are uniquely lineage specific. Comparative genomics has become a powerful tool to discover these unique and shared molecular adaptations in respect to cancer suppression. These findings may one day be translated to human patients through evolutionary medicine. Here, we will review theory and methods of comparative cancer genomics and highlight major findings of cancer suppression across mammals. Our current knowledge of cancer genomics suggests that more efficient DNA repair and higher sensitivity to DNA damage may be the key to tumor suppression in large or long-lived mammals.

  1. Surround suppression and sparse coding in visual and barrel cortices

    Directory of Open Access Journals (Sweden)

    Robert N S Sachdev

    2012-07-01

    Full Text Available During natural vision the entire retina is stimulated. Likewise, during natural tactile behaviors, spatially extensive regions of the somatosensory surface are co-activated. The large spatial extent of naturalistic stimulation means that surround suppression, a phenomenon whose neural mechanisms remain a matter of debate, must arise during natural behavior. To identify common neural motifs that might instantiate surround suppression across modalities, we review models of surround suppression and compare the evidence supporting the competing ideas that surround suppression has either cortical or sub-cortical origins in visual and barrel cortex. In the visual system there is general agreement lateral inhibitory mechanisms contribute to surround suppression, but little direct experimental evidence that intracortical inhibition plays a major role. Two intracellular recording studies of V1, one using naturalistic stimuli (Haider et al., 2010, the other sinusoidal gratings (Ozeki et al., 2009, sought to identify the causes of reduced activity in V1 with increasing stimulus size, a hallmark of surround suppression. The former attributed this effect to increased inhibition, the latter to largely balanced withdrawal of excitation and inhibition. In rodent primary somatosensory barrel cortex, multi-whisker responses are generally weaker than single whisker responses, suggesting multi-whisker stimulation engages similar surround suppressive mechanisms. The origins of suppression in S1 remain elusive: studies have implicated brainstem lateral/internuclear interactions and both thalamic and cortical inhibition. Although the anatomical organization and instantiation of surround suppression in the visual and somatosensory systems differ, we consider the idea that one common function of surround suppression, in both modalities, is to remove the statistical redundancies associated with natural stimuli by increasing the sparseness or selectivity of sensory

  2. 野生型和突变型小鼠动力蛋白激活蛋白1真核表达载体的构建及其在小鼠足细胞中的表达%Construction of mouse wide-type and mutant dynactin-1 vectors and their expression in mouse podocytes

    Institute of Scientific and Technical Information of China (English)

    王春花; 李林; 傅鹏; 李金花; 原爱红; 孙向华; 蒋晓峰; 余晨

    2012-01-01

    Objective To construct mouse wide-type and mutant dynactin-1 expression vectors and investigate their expression in mouse podocytes. Methods Mouse cDNA was synthesized from mouse total RNA and was used as a template for PCR amplification to obtain full length dynactin-1 cDNA. The DNA fragment was then cloned into pcDNA3. 1( + )-FLAG and pEGFP-N1 vector to produce wide-type dynactin-1 vector. The mutant dynactin-1 was obtained by site-direct mutagenesis kit. All the constructs were verified by restriction enzyme digestion, sequenced, and then transfected into mouse podocyte clone 5 (MPC5). Western blotting analysis and immunofluorescence microscopy were employed to determine dynactin-1 protein expression. Results The amplified mouse dynactin-1 cDNA fragment was analyzed by agarose gel electrophoresis and a single discrete band of the correct size (3. 8 kb) was observed. The vectors containing mouse dynactin-1 were subjected to restriction enzyme digestion and two vector fragments (pcDNA3.1[+]-FLAG(5. 4 kb) and pEGFP-N1[4. 7 kb] individually) and the 3. 8 kb insert fragment were observed by electrophoresis. The result of sequencing showed that the sequence of cloned dynactin-1 was identical to that reported in Genbank. Dynactin-1 protein band with the correct relative molecular weight was detected by Western blotting analysis, and immunofluorescence microscopy showed dynactin-1 protein expression in the cytoplasm of the mouse podocytes. Conclusion We have successfully constructed wide-type and mutant dynactin-1 vectors and expressed them in mouse podocytes, which provides a foundation for future research on dynactin-1.%目的 构建野生型和突变型小鼠动力蛋白激活蛋白1(dynactin-1)真核表达载体,并观察其在小鼠足细胞中表达.方法 以总RNA反转录合成的cDNA为模板,通过PCR扩增得到小鼠dynactin-1的全长cDNA,将该片段克隆到真核表达载体pcDNA3.1(+)-FLAG和pEGFP-N1;利用部位特异性突变插入方法构建突

  3. Suitable level of suppression in Pinus sylvestris

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, Mats

    1999-10-01

    It is `well known` among Swedish foresters that pine trees need light and cannot grow suppressed. It is also `well known` that old trees that have grown slowly are unable to react with good growth. However, these facts can be questioned in the light of new research as it has been found that thinning reaction is not correlated with age. It is also well known that the commercial value of a pine is closely related to the growth at young age. If the first 20 annual rings close to pith are wide (>3 mm) the log cannot be accepted as first class. This is related to number and size of branches on the young tree and to the features of the juvenile wood. This is to say that a pine must not grow fast when it is small and if this has happened it cannot be cured by artificial debranching or by growing the tree slowly at higher age. Accordingly, young pines should be grown under bigger trees that in their young age were grown under big trees, and so on. Today, when clear cutting is the dominating forest management system, the only way to obtain high quality pine trees is to start the rotation age with stands of very high density. This is of course a very expensive way as dense planting, followed by intensive thinning requires a lot of input. However, if pine is a pioneer species and cannot be grown in multistoried stands, then the economic solution is not present. This was the reason why the annual increment of three pines was measured. They were selected because their different growth pattern showed that old `well known facts` should be revised Working papers 139. 3 refs, 7 figs, 1 tab

  4. Enhancing Soil Quality and Plant Health Through Suppressive Organic Amendments

    Directory of Open Access Journals (Sweden)

    Francisco M. Cazorla

    2012-12-01

    Full Text Available The practice of adding organic amendments to crop soils is undergoing resurgence as an efficient way to restore soil organic matter content and to improve soil quality. The quantity and quality of the organic matter inputs affect soil physicochemical properties and soil microbiota, influencing different parameters such as microbial biomass and diversity, community structure and microbial activities or functions. The influence of organic amendments on soil quality has also effects on crop production and plant health. The enhancement of soil suppressiveness using organic amendments has been widely described, especially for soil-borne diseases. However, there is great variability in the effectiveness of suppression depending on the nature of the amendment, the crop, the pathogen, and the environmental conditions. Although the effects of organic amendments on soil properties have been widely studied, relationships between these properties and soil suppressiveness are not still well understood. Changes in soil physicochemical parameters may modulate the efficacy of suppression. However, the parameters more frequently associated to disease suppression appear to be related to soil microbiota, such as microbial biomass and activity, the abundance of specific microbial groups and some hydrolytic activities. This review focuses on the effect of organic amendments on soil microbial populations, diversity and activities; their ability to enhance plant health through disease suppression; and which of the parameters affected by the organic amendments are potentially involved in soil suppressiveness.

  5. fMRI repetition suppression: neuronal adaptation or stimulus expectation?

    Science.gov (United States)

    Larsson, Jonas; Smith, Andrew T

    2012-03-01

    Measurements of repetition suppression with functional magnetic resonance imaging (fMRI adaptation) have been used widely to probe neuronal population response properties in human cerebral cortex. fMRI adaptation techniques assume that fMRI repetition suppression reflects neuronal adaptation, an assumption that has been challenged on the basis of evidence that repetition-related response changes may reflect unrelated factors, such as attention and stimulus expectation. Specifically, Summerfield et al. (Summerfield C, Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006) reported that the relative frequency of stimulus repetitions and non-repetitions influenced the magnitude of repetition suppression in the fusiform face area, suggesting that stimulus expectation accounted for most of the effect of repetition. We confirm that stimulus expectation can significantly influence fMRI repetition suppression throughout visual cortex and show that it occurs with long as well as short adaptation durations. However, the effect was attention dependent: When attention was diverted away from the stimuli, the effects of stimulus expectation completely disappeared. Nonetheless, robust and significant repetition suppression was still evident. These results suggest that fMRI repetition suppression reflects a combination of neuronal adaptation and attention-dependent expectation effects that can be experimentally dissociated. This implies that with an appropriate experimental design, fMRI adaptation can provide valid measures of neuronal adaptation and hence response specificity.

  6. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  7. Dynamical Suppression of Decoherence in Two-Qubit Quantum Memory

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In this paper, we have detailedly studied the dynamical suppression of the phase damping for the two-qubit quantum memory of Ising model by the quantum "bang-bang" technique. We find the sequence of periodic radiofrequency pulses repetitively to flip the state of the two-qubit system and quantitatively find that these pulses can be used to effectively suppress the phase damping decoherence of the quantum memory and freeze the system state into its initial state. The general sequence of periodic radio-frequency pulses to suppress the phase damping of multi-qubit of Ising model is also given.

  8. The Etiology and Outcome Analysis of Neonatal Burst Suppression EEG

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lian; ZHOU Yanxia; XU Sanqing

    2007-01-01

    The neonatal burst suppression is a severe EEG pattern and always demonstrates serious damage of nerve system. But the outcome of these patients depends on the different etiology. A total of 256 cases of video EEG recordings were analyzed in order to summarize the etiology and outcome of burst suppression. The results showed that some patients in all 17 cases of burst suppression showed EEG improvement. The etiology was the dominant factor in long term outcome. It was sug-gested that effective video EEG monitoring is helpful for etiologic study and prognosis evaluation.

  9. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    OpenAIRE

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five...

  10. A simple configuration setup for compton suppression spectroscopy

    CERN Document Server

    Hai, N X; Dien, N N; Tan, V H; Hoa, N D

    2013-01-01

    The fast timing, standard timing and easy timing are popular timing configurations of compton suppression spectroscopy. Such spectroscopes always use a module of coincidence or time-to-amplitude converter (TAC). A compton suppression spectroscopy with semi-timing configuration is presented in this paper. The semi-timing configuration is relatively simple and easy system setup, especially this spectroscopy does not need to use module of coincidence or TAC. The performance of spectroscopy was tested and summarized. The count rate background, full peak efficiency and the ratios of area/background of peaks in suppressed and unsuppressed modes were comparative.

  11. Suppression of strike-slip fault systems

    Science.gov (United States)

    Curren, I. S.

    2012-12-01

    depth. Selected areas on Earth with anomalously undeveloped strike-slip faulting where plate models would predict otherwise were compared with results from the analog model experiments in this study. Physical similarities between this model and Brothers Fault Zone (BFZ), Walker Lane (WL) and the South Iceland Seismic Zone (SISZ) imply that strike-slip faulting may be suppressed at the surface in these regions due to the presence of pre-existing structures. Filled circles show offset required for breakthrough faulting, empty circles denote lower limit of breakthrough. Triangles show clay offset as a fraction of box offset. Note that clays with pre-existing structures showed larger offsets although breakthrough did not occur.

  12. Probiotic Diversity Enhances Rhizosphere Microbiome Function and Plant Disease Suppression

    Directory of Open Access Journals (Sweden)

    Jie Hu

    2016-12-01

    Full Text Available Bacterial communities associated with plant roots play an important role in the suppression of soil-borne pathogens, and multispecies probiotic consortia may enhance disease suppression efficacy. Here we introduced defined Pseudomonas species consortia into naturally complex microbial communities and measured the importance of Pseudomonas community diversity for their survival and the suppression of the bacterial plant pathogen Ralstonia solanacearum in the tomato rhizosphere microbiome. The survival of introduced Pseudomonas consortia increased with increasing diversity. Further, high Pseudomonas diversity reduced pathogen density in the rhizosphere and decreased the disease incidence due to both intensified resource competition and interference with the pathogen. These results provide novel mechanistic insights into elevated pathogen suppression by diverse probiotic consortia in naturally diverse plant rhizospheres. Ecologically based community assembly rules could thus play a key role in engineering functionally reliable microbiome applications.

  13. Attention-dependent early cortical suppression contributes to crowding.

    Science.gov (United States)

    Chen, Juan; He, Yingchen; Zhu, Ziyun; Zhou, Tiangang; Peng, Yujia; Zhang, Xilin; Fang, Fang

    2014-08-01

    Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.

  14. Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry

    Science.gov (United States)

    Colizza, Kevin; Mahoney, Keira E.; Yevdokimov, Alexander V.; Smith, James L.; Oxley, Jimmie C.

    2016-11-01

    Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression.

  15. Unnoticed intrusions: dissociations of meta-consciousness in thought suppression.

    Science.gov (United States)

    Baird, Benjamin; Smallwood, Jonathan; Fishman, Daniel J F; Mrazek, Michael D; Schooler, Jonathan W

    2013-09-01

    The current research investigates the interaction between thought suppression and individuals' explicit awareness of their thoughts. Participants in three experiments attempted to suppress thoughts of a prior romantic relationship and their success at doing so was measured using a combination of self-catching and experience-sampling. In addition to thoughts that individuals spontaneously noticed, individuals were frequently caught engaging in thoughts of their previous partner at experience-sampling probes. Furthermore, probe-caught thoughts were: (i) associated with stronger decoupling of attention from the environment, (ii) more likely to occur under cognitive load, (iii) more frequent for individuals with a desire to reconcile, and (iv) associated with individual differences in the tendency to suppress thoughts. Together, these data suggest that individuals can lack meta-awareness that they have begun to think about a topic they are attempting to suppress, providing novel insight into the cognitive processes that are involved in attempting to control undesired mental states.

  16. Optical frequency tripling with improved suppression and sideband selection.

    Science.gov (United States)

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre.

  17. Critical suppression of spin Seebeck effect by magnetic fields

    Science.gov (United States)

    Kikkawa, Takashi; Uchida, Ken-ichi; Daimon, Shunsuke; Qiu, Zhiyong; Shiomi, Yuki; Saitoh, Eiji

    2015-08-01

    The longitudinal spin Seebeck effect (LSSE) in Pt /Y3Fe5O12(YIG ) junction systems has been investigated at various magnetic fields and temperatures. We found that the LSSE voltage in a Pt/YIG-slab system is suppressed by applying high magnetic fields and this suppression is critically enhanced at low temperatures. The field-induced suppression of the LSSE in the Pt/YIG-slab system is too large at around room temperature to be explained simply by considering the effect of the Zeeman gap in magnon excitation. This result requires us to introduce a magnon-frequency-dependent mechanism into the scenario of LSSE; low-frequency magnons dominantly contribute to the LSSE. The magnetic field dependence of the LSSE voltage was observed to change by changing the thickness of YIG, suggesting that the thermospin conversion by the low-frequency magnons is suppressed in thin YIG films due to the long characteristic lengths of such magnons.

  18. Sidelobe Suppression with Null Steering by Independent Weight Control

    Directory of Open Access Journals (Sweden)

    Zafar-Ullah Khan

    2015-01-01

    Full Text Available A uniform linear array of n antenna elements can steer up to n-1 nulls. In situations where less than n-1 nulls are required to be steered, the existing algorithms have no criterion to utilize the remaining weights for sidelobe suppression. This work combines sidelobe suppression capability with null steering by independent weight control. For this purpose, the array factor is transformed as the product of two polynomials. One of the polynomials is used for null steering by independent weight control, while the second one is for sidelobe suppression whose coefficients or weights are determined by using convex optimization. Finally, a new structure is proposed to incorporate the product of two polynomials such that sidelobe suppression weights are decoupled from those of null steering weights. Simulation results validate the effectiveness of the proposed scheme.

  19. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  20. Ambiguity functions and noise floor suppression in random noise radar

    Science.gov (United States)

    Axelsson, Sune R. J.

    2006-09-01

    Noise radar can be used in a great number of applications including SAR. The non-periodic waveform suppresses the range ambiguity and reduces the probability of intercept and interference. Due to the randomness of the waveform, a noise floor limiting the possible side lobe suppression accompanies the correlation integral involved. In strong clutter scenes with dominant reflectors, the induced noise floor can be too high and further suppression is needed. In this paper, the ambiguity function of random noise waveforms is first analyzed, and an improved formulation is introduced to include the noise floor effect. The use of mismatched filtering for improved sidelobe suppression is then discussed. Finally, an iterative subtraction algorithm is analyzed for noise floor cancellation in the presence of dominating reflectors. This method is successfully tested on random step frequency radar data and noise sodar data.

  1. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  2. Immune Suppression by Dermal Application of JP-8 Jet Fuel

    Science.gov (United States)

    2008-10-13

    transmitting the immunosuppressive signal from the skin to the immune system ( Limon -Flores, et al., Mast Cells mediate the Immune suppression Induced by...human and murine data. Nat Rev Immunol 7, 93-104. Byrne, S. N., Limon -Flores, A. Y. and Ullrich, S. E. (2008). Mast cell migration from the skin to...Ramos, G., Limon -Flores, A. Y. and Ullrich, S. E. (2007). Dermal exposure to jet fuel suppresses delayed-type hypersensitivity: a critical role

  3. Signal Enhancement and Suppression During Visual-Spatial Selective Attention

    OpenAIRE

    Couperus, J. W.; Mangun, G.R.

    2010-01-01

    Selective attention involves the relative enhancement of relevant versus irrelevant stimuli. However, whether this relative enhancement involves primarily enhancement of attended stimuli, or suppression of irrelevant stimuli, remains controversial. Moreover, if both enhancement and suppression are involved, whether they result from a single mechanism or separate mechanisms during attentional control or selection is not known. In two experiments using a spatial cuing paradigm with task-relevan...

  4. Predictors for partial suppression of spermatogenesis of hormonal male contraception

    Institute of Scientific and Technical Information of China (English)

    Jing-Wen Li; Yi-Qun Gu

    2008-01-01

    Aim: To analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception. Methods: A nested case-control study was conducted, involving 43 subjects, who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate (TU), defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis (complete suppressors). Sperm density, serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations at the baseline and the suppression phase were compared between partial and complete suppressors. Polymorphisms of androgen receptor (AR) and three single nucleotide variants and their haplotypes of FSH receptor (FSHR) genes determined by polymerase chain reaction (PCR) and DNA sequencing technique were compared between 29 partial and 34 complete suppressors. Results: Baseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors. Additionally, in a logistic regression analysis larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, testosterone and sperm concentrations were associated with degree of suppression. The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors. In cases with incomplete FSH suppression (FSH > 0.2 IU/L), the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats. Conclusion: Partial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes.

  5. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs. The ...... phenomenologically using compression or expansion of the system output. This was obtained by shifting the operating-point on the input-output-characteristic in relation to the ICI....

  6. Voluntary driven elbow orthosis with speed controlled tremor suppression

    Directory of Open Access Journals (Sweden)

    Gil eHerrnstadt

    2016-03-01

    Full Text Available Robotic technology is gradually becoming commonplace in the medical sector and in the service of patients. Medical conditions that have benefited from significant technological development include stroke, for which rehabilitation with robotic devices is administered, and surgery assisted by robots. Robotic devices have also been proposed for assistance of movement disorders. Pathological tremor, among the most common movement disorders, is such one example. In practice, the dissemination and availability of tremor suppression robotic systems has been limited. Devices in the marketplace tend to either be non-ambulatory or to target specific functions such as eating and drinking.We have developed a one degree-of-freedom (DOF elbow orthosis that could be worn by an individual with tremor. A speed controlled voluntary driven suppression approach is implemented with the orthosis. Typically tremor suppression methods estimate the tremor component of the signal and produce a canceling counterpart signal. The suggested approach, instead estimates the voluntary component of the motion. A controller then actuates the orthosis based on the voluntary signal while simultaneously rejecting the tremorous motion.In this work, we tested the suppressive orthosis using a 1 DOF robotic system that simulates the human arm. The suggested suppression approach does not require a model of the human arm. Moreover, the human input along with the orthosis forearm gravitational forces, of nonlinear nature, are considered as part of the disturbance to the suppression system. Therefore, the suppression system can be modeled linearly. Nevertheless, the orthosis forearm gravitational forces can be compensated by the suppression system.The electromechanical design of the orthosis is presented, and data from an Essential Tremor patient is used as the human input. Velocity tracking results demonstrate an RMS error of 0.31 rad/s, and a power spectral density shows a reduction of

  7. A sidelobe suppression method with experiment for underwater acoustic imaging

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this paper,a sidelobe suppression method using nonuniformly spaced array with aperture apodization processing is proposed for underwater acoustic imaging in near field,which is studied both in theory and experiment.The focused beamforming based on spherical wave propagation theory is used in the method.Firstly,the nonuniform array with low sidelobe is designed for suppressing the sidelobe of one-way beam pattern by spacing perturbation.Then, applying the aperture apodization technique to underwater ac...

  8. Methods for suppressing isomerization of olefin metathesis products

    Energy Technology Data Exchange (ETDEWEB)

    Firth, Bruce E.; Kirk, Sharon E.

    2015-10-27

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent that includes nitric acid to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. Methods of refining a natural oil are described.

  9. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories

    Directory of Open Access Journals (Sweden)

    Saima eNoreen

    2016-03-01

    Full Text Available Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one's attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC and the mid-ventrolateral prefrontal cortex (VLPFC regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think or to suppress (no-think the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution. Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

  10. Application of phase coherent transform to cloud clutter suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ng, L.C. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    This paper describes a tracking algorithm using frame-to-frame correlation with frequency domain clutter suppression. Clutter suppression was mechanized via a `Phase Coherent Transform` (PCT) approach. This approach was applied to explore the feasibility of tracking a post-boost rocket from a low earth orbit satellite with real cloud background data. Simulation results show that the PCT/correlation tracking algorithm can perform satisfactorily at signal-to-clutter ratio (SCR) as low as 5 or 7 dB.

  11. An Artefact suppressing fast-recovery myoelectric amplifier

    OpenAIRE

    1999-01-01

    An amplifier for recording myoelectric signals using surface electrodes has been developed. The special features are suppression of stimulation artefacts and motion artefacts from electrodes. It is designed for recording of myoelectric signals from a muscle that is being stimulated with short impulses. The artifact suppression is achieved by using fast-recovery instrumentation amplifiers and having a nonlinear feedback loop for automatic compensation of changes in DC-offset

  12. Epigenetic Suppression of T-DNA Insertion Mutants in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Yangbin Gao; Yunde Zhao

    2013-01-01

    T-DNA insertion mutants have been widely used to define gene functions in Arabidopsis and in other plants.Here,we report an unexpected phenomenon of epigenetic suppression of T-DNA insertion mutants in Arabidopsis.When the two T-DNA insertion mutants,yucl-1 and ag-TD,were crossed together,the defects in all of the ag-TD plants in the F2 population were partially suppressed regardless of the presence of yucl-1.Conversion of ag-TD to the suppressed ag-TD (named as ag-TD*) did not follow the laws of Mendelian genetics.The ag-TD* could be stably transmitted for many generations without reverting to ag-TD,and ag-TD* had the capacity to convert ag-TD to ag-TD*.We show that epigenetic suppression of T-DNA mutants is not a rare event,but certain structural features in the T-DNA mutants are needed in order for the suppression to take place.The suppressed T-DNA mutants we observed were all intronic T-DNA mutants and the T-DNA fragments in both the trigger T-DNA as well as in the suppressed T-DNA shared stretches of identical sequences.We demonstrate that the suppression of intronic T-DNA mutants is mediated by trans-interactions between two ToDNA insertions.This work shows that caution is needed when intronic T-DNA mutants are used.

  13. A Designated Harmonic Suppression Technology for Sampled SPWM

    Institute of Scientific and Technical Information of China (English)

    YANG Ping

    2005-01-01

    Sampled SPWM is an excellent VVVF method of motor speed control, meanwhile the harmonic components of the output wave impairs its applications in practice. A designated harmonic suppression technology is presented for sampled SPWM, which is an improved algorithm for the harmonic suppression in high voltage and high frequency spectrum. As the technology is applied in whole speed adjusting range, the voltage can be conveniently controlled and high frequency harmonic of SP WM is also improved.

  14. Azimuth Phase Coding for Range Ambiguity Suppression in SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Kusk, Anders

    2004-01-01

    A novel ambiguity suppression technique is proposed. Range ambiguities in synthetic aperture radar (SAR) images are eliminated with an azimuth filter after having applied an azimuth phase modulation to the transmitted pulses and a corresponding demodulation to the received pulses. The technique...... by the antenna elevation dimension. The fundamental antenna area constraint still applies, but the PRF can be chosen with more freedom. In addition to ambiguity suppression, potential applications include nadir return elimination and signal-to-noise ratio improvement....

  15. Social responses to expressive suppression: The role of personality judgments.

    Science.gov (United States)

    Tackman, Allison M; Srivastava, Sanjay

    2016-04-01

    Why do people who suppress their emotion-expressive behavior have difficulty forming close, supportive relationships? Previous studies have found that suppression disrupts the dynamics of social interactions and existing relationships. We evaluated a complementary hypothesis: that suppression functions as a behavioral cue leading others to form negative personality impressions of suppressors, even at zero-acquaintance. In 2 studies, participants reported personality judgments and other impressions of targets who either suppressed or expressed their emotion-expressive behavior in response to amusing or sad film clips. In findings replicated across studies, targets who suppressed either amusement or sadness were judged as less extraverted, less agreeable, and more interpersonally avoidant and anxious than targets who expressed emotions, and participants were less interested in affiliating with suppressors compared with expressers. Effects were amplified when targets suppressed amusement (compared with sadness) and when participants knew the emotional context (compared with when they did not) and, thus, could form expectations about what emotions targets should be showing. Extraversion and agreeableness judgments mediated the effect of suppression on participants' disinterest in affiliating. In Study 2, which extended Study 1 in several ways, effects were pronounced for the enthusiasm aspect of extraversion and the compassion aspect of agreeableness. We also found evidence that judgments of suppressors do not simply fall between neutral and fully expressing targets; rather, judgments of suppressors are qualitatively different. We discuss implications for understanding the social consequences of emotion regulation-in particular, how beyond disrupting relationships, suppression may prevent some relationships from even forming in the first place.

  16. Proactive selective response suppression is implemented via the basal ganglia.

    Science.gov (United States)

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R

    2013-08-14

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  17. Suppression of aggressive rorschach responses among violent offenders and nonoffenders.

    Science.gov (United States)

    Benjestorf, Sue TaVoularis; Viglione, Donald J; Lamb, Judy D; Giromini, Luciano

    2013-10-01

    This Rorschach study explored the suppression of aggression content when violent offenders and nonoffenders are asked to present themselves as not posing a threat of dangerousness in a court role-playing context. Aggressive content and complexity in this suppressive role-play context was compared to a neutral control condition. A total of 41 participants, approximately half violent offenders and half nonoffenders took the Rorschach under both conditions. Results indicate that both groups suppressed aggression content on the Rorschach without altering response complexity. This large effect size for testing condition may partly explain the inconsistencies across previous studies. It is possible that violent offenders have typically been tested in highly suppressive conditions whereas nonoffender or normative groups may have been tested in relatively low suppression conditions. If so, aggression score differences may be a reflection of the testing condition, not group differences. Both instructional sets produced similar levels of complexity, so that individuals do not simplify responses when they screen out aggressive attributions. Violent offenders did not differ from nonviolent offenders in terms of aggression content, but did produce more simplistic records. In addition, this study also undertook a semantic, textual analysis and found that individuals in the suppressive condition tended to eliminate many response elaborations, particularly those with negative of threatening connotations.

  18. Chaos Suppression in a Sine Square Map through Nonlinear Coupling

    Institute of Scientific and Technical Information of China (English)

    Eduardo L. Brugnago; Paulo C. Rech

    2011-01-01

    We study a pair of nonlinearly coupled identical chaotic sine square maps.More specifically,we investigate the chaos suppression associated with the variation of two parameters.Two-dimensional parameter-space regions where the chaotic dynamics of the individual chaotic sine square map is driven towards regular dynamics are delimited.Additionally,the dynamics of the coupled system is numerically characterized as the parameters are changed.In recent years,many efforts have been devoted to chaos suppression in a nonlinear dynamics field.Iglesias et al.[1] reported a chaos suppression method through numerical truncation and rounding errors,with applications in discrete-time systems.Hénon map[2] and the Burgers map[3] were used to illustrate the method.A method of feedback impulsive chaos suppression was introduced by Osipov et al.[4]It is an algorithm of suppressing chaos in continuoustime dissipative systems with an external impulsive force,whose necessary condition is a reduction of the continuous flow to a discrete-time one-dimensional map.%We study a pair of nonlinearly coupled identical chaotic sine square maps. More specifically, we investigate the chaos suppression associated with the variation of two parameters. Two-dimensional parameter-space regions where the chaotic dynamics of the individual chaotic sine square map is driven towards regular dynamics are delimited. Additionally, the dynamics of the coupled system is numerically characterized as the parameters are changed.

  19. Suppression of pool fires with HRC-125 in a simulated engine nacelle.

    Energy Technology Data Exchange (ETDEWEB)

    Keyser, David R. (INS, Inc., Lexington Park, MD); Hewson, John C.

    2007-06-01

    CFD simulations are conducted to predict the distribution of fire suppressant in an engine nacelle and to predict the suppression of pool fires by the application of this suppressant. In the baseline configuration, which is based on an installed system, suppressant is injected through four nozzles at a rate fast enough to suppress all simulated pool fires. Variations that reduce the mass of the suppression system (reducing the impact of the suppression system on meeting mission needs) are considered, including a reduction in the rate of suppressant injection, a reduction in the mass of suppressant and a reduction in the number of nozzles. In general, these variations should work to reduce the effectiveness of the suppression system, but the CFD results point out certain changes that have negligible impact, at least for the range of phenomena considered here. The results are compared with measurements where available. Comparisons with suppressant measurements are reasonable. A series of twenty-three fire suppression tests were conducted to check the predictions. The pre-test predictions were generally successful in identifying the range of successful suppression tests. In two separate cases, each where one nozzle of the suppression system was capped, the simulation results did indicate a failure to suppress for a condition where the tests indicated successful suppression. When the test-suppressant discharge rate was reduced by roughly 25%, the tests were in agreement with the predictions. That is, the simulations predict a failure to suppress slightly before observed in these cases.

  20. Arsenite suppression of BMP signaling in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Marjorie A.; Qin, Qin [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States); Hu, Qin; Zhao, Bin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Rice, Robert H., E-mail: rhrice@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States)

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte

  1. Tinnitus suppression by electric stimulation of the auditory nerve

    Directory of Open Access Journals (Sweden)

    Janice Erica Chang

    2012-03-01

    Full Text Available Electric stimulation of the auditory nerve via a cochlear implant (CI has been observed to suppress tinnitus, but parameters of an effective electric stimulus remain unexplored. Here we used CI research processors to systematically vary pulse rate, electrode place, and current amplitude of electric stimuli, and measure their effects on tinnitus loudness and stimulus loudness as a function of stimulus duration. Thirteen tinnitus subjects who used CIs were tested, with 9 (70% being Responders who achieved greater than 30% tinnitus loudness reduction in response to at least one stimulation condition and the remaining 4 (30% being Non-Responders who had less than 30% tinnitus loudness reduction in response to any stimulus condition tested. Despite large individual variability, several interesting observations were made between stimulation parameters, tinnitus characteristics, and tinnitus suppression. If a subject’s tinnitus was suppressed by one stimulus, then it was more likely to be suppressed by another stimulus. If the tinnitus contained a pulsating component, then it would be more likely suppressed by a given combination of stimulus parameters than tinnitus without these components. There was also a disassociation between the subjects’ clinical speech processor and our research processor in terms of their effectiveness in tinnitus suppression. Finally, an interesting dichotomy was observed between loudness adaptation to electric stimuli and their effects on tinnitus loudness, with the Responders exhibiting higher degrees of loudness adaptation than the Non-Responders. Although the mechanisms underlying these observations remain to be resolved, their clinical implications are clear. When using a CI to manage tinnitus, the clinical processor that is optimized for speech perception needs to be customized for optimal tinnitus suppression.

  2. A simplified model of decontamination by BWR steam suppression pools

    Energy Technology Data Exchange (ETDEWEB)

    Powers, D.A.

    1997-05-01

    Phenomena that can decontaminate aerosol-laden gases sparging through steam suppression pools of boiling water reactors during reactor accidents are described. Uncertainties in aerosol properties, aerosol behavior within gas bubbles, and bubble behavior in plumes affect predictions of decontamination by steam suppression pools. Uncertainties in the boundary and initial conditions that are dictated by the progression of severe reactor accidents and that will affect predictions of decontamination by steam suppression pools are discussed. Ten parameters that characterize boundary and initial condition uncertainties, nine parameters that characterize aerosol property and behavior uncertainties, and eleven parameters that characterize uncertainties in the behavior of bubbles in steam suppression pools are identified. Ranges for the values of these parameters and subjective probability distributions for parametric values within the ranges are defined. These uncertain parameters are used in Monte Carlo uncertainty analyses to develop uncertainty distributions for the decontamination that can be achieved by steam suppression pools and the size distribution of aerosols that do emerge from such pools. A simplified model of decontamination by steam suppression pools is developed by correlating features of the uncertainty distributions for total decontamination factor, DF(total), mean size of emerging aerosol particles, d{sub p}, and the standard deviation of the emerging aerosol size distribution, {sigma}, with pool depth, H. Correlations of the median values of the uncertainty distributions are suggested as the best estimate of decontamination by suppression pools. Correlations of the 10 percentile and 90 percentile values of the uncertainty distributions characterize the uncertainty in the best estimates. 295 refs., 121 figs., 113 tabs.

  3. 肾小球微小病变与局灶节段性肾小球硬化症足细胞中线粒体形态的定量研究%Stereological analysis on mitochondria in podocytes of minimal change disease and focal segmental glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    任雅丽

    2011-01-01

    目的 探索肾小球微小病变( MCD)与局灶节段性肾小球硬化症(rSGS)两种肾小球病中足细胞内线粒体的形态学差异.方法 选择5例MCD和5例FSGS病例,在透射电镜放大30 000倍的情况下,根据等距离曲线移动原则对每个病例拍照40张.根据Merz曲线和Gunderson测试系统选择线粒体和足细胞,测算并获得包括线粒体截面面积(A)、周长(C)、体积密度(VV)及面数密度(NA)等指标进行分析.结果 MCD和FSGS足细胞中线粒体相关参数的变异度及P值如下:A:0.47 vs 1.73,P=0.970;C:4.89 vs 24.71,P=0.590;VV:0.49 vs 1.74,P=0.946;NA:0.26 vs0.58,P=0.602.结论 FSGS和MCD足细胞中线粒体的A、C、VV和NA等参数无统计学差异(所有P >0.05),但FSGS中所有参数的变异度均比MCD中的更明显,仍需进一步进行体视学研究.%Objective To explore the difference of mitochondria in podocytes between minimal change disease(MCD) and focal segmental glomerulosclerosis(FSGS) by stereologic analysis.Methods We selected 5 cases of primary MCD and 5 cases of primary FSGS whose diagnosis were definite and had no any other complicated nephropathy.For each case,we took 40 photos under the magnification of 30 000 according to the rule of equidistant zigzag movement.Merz curve and Gunderson testing system were set to select mitochondria and podocytes and the associated parameters were obtained including profile area( A),circumference( C),volu me fraction( VV ),and numerical density per area( NA ) of mitochondria.Results The standard deviation value and P value of the parameters were as following in MCD vs FSGS:A(0.47vs 1.73,P =0.970),C(4.89 vs 24.71,P =0.590),VV(0.49 vs 1.74,P =0.946),and NA(0.26vs 0.58,P =0.602) Conclusion The parameters of A,C,VV,and NA did not demonstrate statistically significance( all P > 0.05),but all of them showed larger value of standard deviation in FSGS cases by comparison with that of MCD.

  4. 硫辛酸对糖尿病肾病大鼠足细胞氧化应激的保护作用%Protce tive effect of the alpha-lipoic acid on oix datvi e stress in podocytes of rats with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    刘洁; 王红杰; 侯明辉; 张晶; 张海松

    2015-01-01

    [Abts ract] Objective To investigate the protective effect of alpha-lipoic acid ( ALA ) on oxidative stress in the podocytes of rats with diabetic nephropathy.Methods After the rat models with diabetic nephropathy were successfully established,the 10 rats were randomly selected as diabetic nephropathy group (group B), the other 10 rats were regarded as ALA intervention group (group C),at the sime time, 10 normal rats were served as control group (group A).The animals were sacrificed at th end of 13weeks ,and the renal tissues specimens were harvested .The expression levels of nephrin and podocin were detected by Western Blot and immunohistochemistry.The contents of malondialdehyde ( MDA) in renal tissues were measured by thiobarbituric acid (TAB) method and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase ( GSH-PX) in renal tissues were detected by xanthine oxidase and dithio-2 nitrobenzoic acid method,respectively. Resu lts As compared with those in group A,the concentrations of MDA in group B were significantly increased, however, the acticities of T-SOD ,GSH-PX and the expression levels of nephrin, podocin were significantly decreased ( P <0.05).As compared with those in group B, the concentrations of MDA were obviously decereased, but the acticities of TS-OD ,GSH-PX and the expression levels of nephrin, podocin were significantly increased in group C ( P <0.05).Conclusion ALA can inhibit the apoptosis of podocyte, reduce the urine protein and delay the pathogenesis and development of diabetic nephropathy through antioxidative stress effects.%目的:探讨硫辛酸对糖尿病肾病(DN)大鼠足细胞氧化应激的保护作用。方法制备糖尿病肾病( DN)大鼠模型,成模后随机选取10只作为 DN组( B组),10只作为硫辛酸干预组( C组),并设立正常对照组(A组)。实验共13周,于第13周末收集各组大鼠肾组织标本,分别应用硫代巴比妥酸( TAB)法、黄嘌

  5. The experimental study of the effects of forkhead transcription factor O1 on the podocyte injury in diabetic rats%叉头状转录因子O1对糖尿病大鼠足细胞影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    张媛媛; 王庆祝; 秦贵军; 周英旎; 马晓君

    2014-01-01

    目的 探讨叉头状转录因子O1(Fox01)对糖尿病大鼠足细胞的影响.方法 链脲佐菌素(STZ)诱导构建糖尿病大鼠模型90只,并采用简单随机抽样法分为糖尿病(DM)+空慢病毒载体(LV-pSC-GFP)感染组(LV-NC组,n=30),DM+大鼠结构性活性FoxO1慢病毒载体(LV-CA-FoxO1)感染组(LV-CA组,n=30),DM组(n=30),另设对照组(NG组,n=30)注射相应体积的柠檬酸钠-柠檬酸缓冲液.于慢病毒感染后的2、4、8周末,测大鼠尿白蛋白、体重、血糖、血肌酐、尿素氮,光镜和透射电镜观察肾小球及其足细胞结构变化,实时定量聚合酶链反应(RT-PCR)和Western blotting法检测大鼠肾皮质中FoxO1、足盂蛋白(PCX)、nephrin mRNA和蛋白的表达.多组间比较采用单因素方差分析.结果 与LV-NC、DM组相比,LV-CA组大鼠肾脏中FoxO1 mRNA、蛋白表达水平明显升高(F8W值分别为10 919.75、3 867.34,均P<0.05),尿白蛋白、血肌酐、尿素氮明显降低(2周除外)(F8W值分别为132.72、187.68、503.69,均P<0.05),肾脏中PCX、nephrin mRNA和蛋白水平明显升高(mRNA F8w值分别为778.94、478.10;蛋白F8W值分别为393.64、255.79,均P<0.05),肾脏病理学变化也明显改善,可见肾小球体积减小,系膜细胞及基底膜增生程度降低,足突融合也有一定程度改善.结论 通过靶向注射慢病毒载体来上调FoxO1的表达可改善DM大鼠足细胞的损伤.%Objective To study the effects of forkhead transcription factor O1 (FoxO1) on the podocyte injury in diabetic rats.Methods 90 Streptozotocin-induced diabetic rats were divided into three groups:diabetic rats (DM,n=30),rats transfected with blank lentiviral vectors (DM plus LV-pSC-GFP group,designated LV-NC,n=30) and rats which were transfected with lentiviral vectors carrying constitutively active FoxO1 (DM plus LV-CA-FoxO1 group,designated LV-CA,n=30).The rats which received an injection of diluent buffer served as normal control (NG,n=30).At 2,4,and 8 weeks after

  6. Central administration of neuromedin U suppresses food intake in chicks.

    Science.gov (United States)

    Kamisoyama, Hiroshi; Honda, Kazuhisa; Saneyasu, Takaoki; Sugahara, Kunio; Hasegawa, Shin

    2007-06-08

    The appetite-suppressive action of brain-gut peptides is similar in both chickens and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF), oxytocin, and arginine-vasopressin. In chickens, central administration of CRF, oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine-vasopressin) suppresses food intake. However, the anorexigenic action of NMU in chickens has not yet been identified. In the present study, we analyzed the effects of the central administration of NMU on food intake and hypothalamic mRNA levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in chicks. Intracerebroventricular administration of NMU in chicks significantly suppressed food intake and induced wing-flapping behavior. NMU also significantly upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression of mesotocin in the hypothalamus. These results suggest that NMU functions as an appetite-suppressive peptide via CRF and AVT in the central nervous system in chicks.

  7. Attention selection, distractor suppression and N2pc.

    Science.gov (United States)

    Mazza, Veronica; Turatto, Massimo; Caramazza, Alfonso

    2009-01-01

    N2pc is generally interpreted as the electrocortical correlate of the distractor-suppression mechanisms through which attention selection takes place in humans. Here, we present data that challenge this common N2pc interpretation. In Experiment 1, multiple distractors induced greater N2pc amplitudes even when they facilitated target identification, despite the suppression account of the N2pc predicted the contrary; in Experiment 2, spatial proximity between target and distractors did not affect the N2pc amplitude, despite resulting in more interference in response times; in Experiment 3, heterogeneous distractors delayed response times but did not elicit a greater N2pc relative to homogeneous distractors again in contrast with what would have predicted the suppression hypothesis. These results do not support the notion that the N2pc unequivocally mirrors distractor-suppression processes. We propose that the N2pc indexes mechanisms involved in identifying and localizing relevant stimuli in the scene through enhancement of their features and not suppression of distractors.

  8. Detection of burst suppression patterns in EEG using recurrence rate.

    Science.gov (United States)

    Liang, Zhenhu; Wang, Yinghua; Ren, Yongshao; Li, Duan; Voss, Logan; Sleigh, Jamie; Li, Xiaoli

    2014-01-01

    Burst suppression is a unique electroencephalogram (EEG) pattern commonly seen in cases of severely reduced brain activity such as overdose of general anesthesia. It is important to detect burst suppression reliably during the administration of anesthetic or sedative agents, especially for cerebral-protective treatments in various neurosurgical diseases. This study investigates recurrent plot (RP) analysis for the detection of the burst suppression pattern (BSP) in EEG. The RP analysis is applied to EEG data containing BSPs collected from 14 patients. Firstly we obtain the best selection of parameters for RP analysis. Then, the recurrence rate (RR), determinism (DET), and entropy (ENTR) are calculated. Then RR was selected as the best BSP index one-way analysis of variance (ANOVA) and multiple comparison tests. Finally, the performance of RR analysis is compared with spectral analysis, bispectral analysis, approximate entropy, and the nonlinear energy operator (NLEO). ANOVA and multiple comparison tests showed that the RR could detect BSP and that it was superior to other measures with the highest sensitivity of suppression detection (96.49%, P = 0.03). Tracking BSP patterns is essential for clinical monitoring in critically ill and anesthetized patients. The purposed RR may provide an effective burst suppression detector for developing new patient monitoring systems.

  9. Detection of Burst Suppression Patterns in EEG Using Recurrence Rate

    Directory of Open Access Journals (Sweden)

    Zhenhu Liang

    2014-01-01

    Full Text Available Burst suppression is a unique electroencephalogram (EEG pattern commonly seen in cases of severely reduced brain activity such as overdose of general anesthesia. It is important to detect burst suppression reliably during the administration of anesthetic or sedative agents, especially for cerebral-protective treatments in various neurosurgical diseases. This study investigates recurrent plot (RP analysis for the detection of the burst suppression pattern (BSP in EEG. The RP analysis is applied to EEG data containing BSPs collected from 14 patients. Firstly we obtain the best selection of parameters for RP analysis. Then, the recurrence rate (RR, determinism (DET, and entropy (ENTR are calculated. Then RR was selected as the best BSP index one-way analysis of variance (ANOVA and multiple comparison tests. Finally, the performance of RR analysis is compared with spectral analysis, bispectral analysis, approximate entropy, and the nonlinear energy operator (NLEO. ANOVA and multiple comparison tests showed that the RR could detect BSP and that it was superior to other measures with the highest sensitivity of suppression detection (96.49%,  P=0.03. Tracking BSP patterns is essential for clinical monitoring in critically ill and anesthetized patients. The purposed RR may provide an effective burst suppression detector for developing new patient monitoring systems.

  10. EBF noise suppression and aerodynamic penalties. [Externally Blown Flaps

    Science.gov (United States)

    Mckinzie, L. J., Jr.

    1978-01-01

    Acoustic tests were conducted at model scale to determine the noise produced in the flyover and sideline planes at reduced separation distances between the nozzle exhaust plane and the flaps of an under-the-wing (UTW) externally blown flap (EBF) configuration in its approach attitude. Tests were also made to determine the noise suppression effectiveness of two types of passive devices which were located on the jet impingement surfaces of the configuration. In addition, static aerodynamic performance data were obtained to evaluate the penalties produced by these suppression devices. Broadband low frequency noise reductions were achieved by reducing the separation distance between the nozzle and flaps. However, mid and high frequency noise was produced which exceeded that of the reference configuration. Two passive noise suppression devices located on the flaps produced moderate to large noise reductions at reduced separation distances. Consideration of the static aerodynamic performance data obtained for the configurations tested suggests that specific broadband noise suppression characteristics may be obtained through a trade-off with aerodynamic performance penalties by the careful selection of suppression devices.

  11. Suppressive effects of anthrax lethal toxin on megakaryopoiesis.

    Directory of Open Access Journals (Sweden)

    Po-Kong Chen

    Full Text Available Anthrax lethal toxin (LT is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogen-activated protein kinases (MAPKs, which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34(+ cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

  12. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    Science.gov (United States)

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

  13. Investigation of a hybrid structure gaseous detector for ion backflow suppression suppression

    CERN Document Server

    Zhang, YuLian; Hu, BiTao

    2016-01-01

    A new concept for ion backflow suppression in future time projection chamber with Micropattern Gas Detectors readout is presented. It is a hybrid structure cascaded Gas Electron Multiplier with Micromegas with the goal to reduce ion backflow from the amplification region towards the drift volume. Gas Electron Multiplier also acting as a preamplifer and shares gas gain with Micromegas. In this way a lower voltage difference has to be applied to the Micromegas and risk of sparking is reduced. Feasibility tests for the hybrid detector is performed using an $^{55}$Fe X-ray source to evaluate the energy resolution, its gain properties and the ion backflow. %The properties of this novel structure in terms of gain and ion backflow are investigated. The energy resolution is better than 27$\\%$ FWHM for 5.9 keV X-rays. It is demonstrated that at a gain up to 6000, a backflow ratio less than 0.3$\\%$ is reachable in the hybrid readout structure.

  14. Stroop interference and negative priming (NP) suppression in normal aging.

    Science.gov (United States)

    Mayas, J; Fuentes, L J; Ballesteros, S

    2012-01-01

    Age-related differences in the reduction of Stroop interference were explored by comparing the performance of 18 younger (of mean age: 30.0±3.9 years) and 18 older healthy adults (of mean age: 75±7.2 years) in a color-word Stroop task. The aim of this study was to determine whether a decrease in the efficiency of inhibitory mechanisms associated with aging could account for age-related differences in the ability to suppress a pre-potent response. Participants performed a Stroop task to assess Stroop interference and NP suppression concurrently. Results showed a greater Stroop interference in older than in young adults. On the other hand, the NP effect was only reliable in the younger group, the older group not showing NP suppression. These findings suggest that the slowing hypothesis alone cannot explain this pattern of results and that the age-related differences must also involve an inhibitory breakdown during aging.

  15. A new solvent suppression method via radiation damping effect

    Institute of Scientific and Technical Information of China (English)

    Cui Xiao-Hong; Peng Ling; Zhang Zhen-Min; Cai Shu-Hui; Chen Zhong

    2011-01-01

    Radiation damping effects induced by the dominated solvent in a solution sample can be applied to suppress the solvent signal.The precession pathway and rate back to equilibrium state between solute and solvent spins are different under radiation damping.In this paper,a series of pulse sequences using radiation damping were designed for the solvent suppression in nuclear magnetic resonance (NMR) spectroscopy.Compared to the WATERGATE method,the solute signals adjacent to the solvent would not be influenced by using the radiation damping method.The one-dimensional (1D) 1H NMR,two-dimensional (2D) gCOSY,and J-resolved experimental results show the practicability of solvent suppression via radiation damping effects in 1D and 2D NMR spectroscopy.

  16. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    Science.gov (United States)

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  17. Alpinetin targets glioma stem cells by suppressing Notch pathway.

    Science.gov (United States)

    Wang, Jianpeng; Yan, Zhiyong; Liu, Xia; Che, Shusheng; Wang, Chao; Yao, Weicheng

    2016-07-01

    Glioma is among the most common human malignancies with poor prognosis. Glioma stem cells (GSCs) are the culprit of glioma, suggesting that GSCs are potential therapeutic targets. Notch signaling pathway plays a pivotal role for the function of GSCs, implying that suppression of Notch pathway may be an effective strategy for GSC-targeting therapy. In this study, we found that alpinetin, a natural compound, can suppress the proliferation and invasiveness of GSCs and induce apoptosis in GSCs. Immunoblot analysis and luciferase assay revealed that Notch signaling was suppressed by alpinetin. Furthermore, restoration of Notch signaling activity rescued the effect of alpinetin on GSC's function. The anti-tumor activity of alpinetin was further confirmed in an animal model. Collectively, targeting of GSC by alpinetin is an effective strategy for glioma therapy.

  18. Functional imaging correlates of impaired distractor suppression following sleep deprivation.

    Science.gov (United States)

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2012-05-15

    Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived.

  19. Investigation of chemical suppressants for inactivation of sulfide ores

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to investigate the effective control method of spontaneous combustion in the mining of sulfide ore deposits, This paper presents the testing results of several selected chemicals (water glass, calcium chloride, calcium oxide, magnesium oxide and their composites) as oxidation suppressants for sulfide ores. A weight increment scaling method was used to measure suppressant performance, and this method proved to be accurate, simple and convenient. Based on a large number of experiments, the test results show that four types of chemical mixtures demonstrate a good performance in reducing the oxidation rate of seven active sulfide ore samples by up to 27% to 100% during an initial 76 d period. The mixtures of water glass mixed with calcium chloride and magnesium oxide mixed with calcium chloride can also act as fire suppressants when used with fire sprinkling systems.

  20. Suppression of autophagy exacerbates Mefloquine-mediated cell death.

    Science.gov (United States)

    Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Kim, Eun Sung; Kang, Hee; Park, Ji-Ho; Lee, Eunjoo H; Cho, Dong-Hyung

    2012-05-02

    Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.

  1. Suppression of Dielectronic Recombination Due to Finite Density Effects

    CERN Document Server

    Nikolić, D; Korista, K T; Ferland, G J; Badnell, N R

    2013-01-01

    We have developed a general model for determining density-dependent effective dielectronic recombination (DR) rate coefficients in order to explore finite-density effects on the ionization balance of plasmas. Our model consists of multiplying by a suppression factor those highly-accurate total zero-density DR rate coefficients which have been produced from state-of-the-art theoretical calculations and which have been benchmarked by experiment. The suppression factor is based-upon earlier detailed collision-radiative calculations which were made for a wide range of ions at various densities and temperatures, but used a simplified treatment of DR. A general suppression formula is then developed as a function of isoelectronic sequence, charge, density, and temperature. These density-dependent effective DR rate coefficients are then used in the plasma simulation code Cloudy to compute ionization balance curves for both collisionally ionized and photoionized plasmas at very low (ne = 1 cm^-3) and finite (ne=10^10 ...

  2. Reactor Neutrino Flux Uncertainty Suppression on Multiple Detector Experiments

    CERN Document Server

    Cucoanes, Andi; Cabrera, Anatael; Fallot, Muriel; Onillon, Anthony; Obolensky, Michel; Yermia, Frederic

    2015-01-01

    This publication provides a coherent treatment for the reactor neutrino flux uncertainties suppression, specially focussed on the latest $\\theta_{13}$ measurement. The treatment starts with single detector in single reactor site, most relevant for all reactor experiments beyond $\\theta_{13}$. We demonstrate there is no trivial error cancellation, thus the flux systematic error can remain dominant even after the adoption of multi-detector configurations. However, three mechanisms for flux error suppression have been identified and calculated in the context of Double Chooz, Daya Bay and RENO sites. Our analysis computes the error {\\it suppression fraction} using simplified scenarios to maximise relative comparison among experiments. We have validated the only mechanism exploited so far by experiments to improve the precision of the published $\\theta_{13}$. The other two newly identified mechanisms could lead to total error flux cancellation under specific conditions and are expected to have major implications o...

  3. Suppression induction in vivo by a T helper clone?

    DEFF Research Database (Denmark)

    Crispe, I N; Owens, T

    1985-01-01

    We have previously described a helper T cell clone which augments in vivo cytotoxic T cell responses when injected at 10(4) cells per mouse, but not at 10(5) per mouse (Crispe, I. N. et al., Immunology 1984. 52:55). To test whether this dose-response relationship was due to the induction...... of suppression, naive syngeneic mice were injected with 10(5) cloned T helper cells, and their spleen cells were subsequently assayed for suppressive activity in adoptive transfer experiments. Lymphocytes from such mice indeed suppressed an antigen-specific cytotoxic response, but only in the presence...... of the same T helper cell clone freshly added at the time of adoptive transfer. On this basis we argue that the distinction between T helper cell activity and T suppressor-inducer activity corresponds to differences in cell numbers, rather than to two separate cell lineages....

  4. Mu suppression and human movement responses to the Rorschach test.

    Science.gov (United States)

    Pineda, Jaime A; Giromini, Luciano; Porcelli, Piero; Parolin, Laura; Viglione, Donald J

    2011-03-30

    Electroencephalographic μ wave suppression was investigated using all 10 static, ambiguous Rorschach stimuli. In an earlier study using four Rorschach stimuli, the two stimuli that elicited feelings of movement were associated with μ suppression. In this study, we replicated this relationship using all 10 Rorschach stimuli while overcoming a number of other earlier limitations. The results strongly support the hypothesis that internal representation of the feeling of movement is sufficient to suppress the μ rhythm even when minimal external cues are present. This outcome increases the generalizability and ecological validity of this approach and gives support to the traditional interpretation of the Rorschach human movement responses as being associated with cognitive functioning, empathy, and social cognition.

  5. Deconstructing p53 transcriptional networks in tumor suppression.

    Science.gov (United States)

    Bieging, Kathryn T; Attardi, Laura D

    2012-02-01

    p53 is a pivotal tumor suppressor that induces apoptosis, cell-cycle arrest and senescence in response to stress signals. Although p53 transcriptional activation is important for these responses, the mechanisms underlying tumor suppression have been elusive. To date, no single or compound mouse knockout of specific p53 target genes has recapitulated the dramatic tumor predisposition that characterizes p53-null mice. Recently, however, analysis of knock-in mice expressing p53 transactivation domain mutants has revealed a group of primarily novel direct p53 target genes that may mediate tumor suppression in vivo. We present here an overview of well-known p53 target genes and the tumor phenotypes of the cognate knockout mice, and address the recent identification of new p53 transcriptional targets and how they enhance our understanding of p53 transcriptional networks central for tumor suppression.

  6. Suppression of Rayleigh-scattering-induced noise in OEOs.

    Science.gov (United States)

    Okusaga, Olukayode; Cahill, James P; Docherty, Andrew; Menyuk, Curtis R; Zhou, Weimin; Carter, Gary M

    2013-09-23

    Optoelectronic oscillators (OEOs) are hybrid RF-photonic devices that promise to be environmentally robust high-frequency RF sources with very low phase noise. Previously, we showed that Rayleigh-scattering-induced noise in optical fibers coupled with amplitude-to-phase noise conversion in photodetectors and amplifiers leads to fiber-length-dependent noise in OEOs. In this work, we report on two methods for the suppression of this fiber-length-dependent noise: altering the amplitude-dependent phase delay of the OEO loops and suppressing the Rayleigh-scattering-induced noise in optical fibers. We report a 20 dB reduction in the flicker phase noise of a 6 km OEO via these suppression techniques.

  7. Holographic Lifshitz fermions and exponentially suppressed spectral weight

    CERN Document Server

    Kim, Youngshin

    2016-01-01

    One of the unusual features of Lifshitz holography is the presence of a tunneling barrier that arises from the bulk geometry for probes carrying large transverse momentum. This leads to a decoupling of the horizon from the boundary, and in particular gives rise to an exponential suppression of spectral weight in the large transverse momentum limit. We compute the spin-1/2 holographic Green's function and show that this suppression has the same origin as in the scalar case. We furthermore demonstrate that the suppression factor is universal in the $\\hat\\omega\\to0$ limit where $\\hat\\omega=\\omega/|\\vec k|^z$. In particular, it depends only on $\\hat\\omega$ and the critical exponent $z$, and is independent of scaling dimension and spin.

  8. Strong Phases and Factorization for Color Suppressed Decays

    CERN Document Server

    Mantry, S; Stewart, I W; Mantry, Sonny; Pirjol, Dan; Stewart, Iain W.

    2003-01-01

    We prove a factorization theorem in QCD for the color suppressed decays B0-> D0 M0 and B0-> D*0 M0 where M is a light meson. Both the color-suppressed and W-exchange/annihilation amplitudes contribute at lowest order in LambdaQCD/Q where Q={mb, mc, Epi}, so no power suppression of annihilation contributions is found. A new mechanism is given for generating non-perturbative strong phases in the factorization framework. Model independent predictions that follow from our results include the equality of the B0 -> D0 M0 and B^0 -> D*0 M0 rates, and equality of non-perturbative strong phases between isospin amplitudes, delta(DM) = delta(D*M). Relations between amplitudes and phases for M=pi,rho are also derived. These results do not follow from large Nc factorization with heavy quark symmetry.

  9. Suppression of extraneous thermal noise in cavity optomechanics

    CERN Document Server

    Zhao, Yi; Ni, Kang-Kuen; Kimble, H Jeff

    2011-01-01

    Extraneous thermal motion can limit displacement sensitivity and radiation pressure effects, such as optical cooling, in a cavity-optomechanical system. Here we present an active noise suppression scheme and its experimental implementation. The main challenge is to selectively sense and suppress extraneous thermal noise without affecting motion of the oscillator. Our solution is to monitor two modes of the optical cavity, each with different sensitivity to the oscillator's motion but similar sensitivity to the extraneous thermal motion. This information is used to imprint "anti-noise" onto the frequency of the incident laser field. In our system, based on a nano-mechanical membrane coupled to a Fabry-P\\'{e}rot cavity, simulation and experiment demonstrate that extraneous thermal noise can be selectively suppressed and that the associated limit on optical cooling can be reduced.

  10. Neomycin is more efficient than streptomycin in suppressing frameshift mutations.

    Science.gov (United States)

    Phoenix, P; Gravel, M; Herrington, M B; Brakier-Gingras, L

    1985-12-01

    The effects of streptomycin and neomycin on the phenotypic suppression of frameshift mutations in the lacZ gene of Escherichia coli and on the efficiency of suppression of amber mutations in T4 phage by the informational supE tRNA nonsense suppressor were compared. Neomycin stimulated much more efficiently than streptomycin the phenotypic suppression of frameshift mutations. Because neomycin favors mismatches of the central codon base whereas streptomycin favors mismatches of the first codon base, this result suggests that mismatching of the central codon base pair and shifting of the reading frame are two correlated phenomena. In contrast, both streptomycin and neomycin stimulated about equally the efficiency of the tRNA nonsense suppressor, an effect probably related to their interference with the proofreading control in tRNA selection.

  11. Ion energy recovery experiment based on magnetic electro suppression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.; Stirling, W.L.; Dagenhart, W.K.; Barber, G.C.; Ponte, N.S.

    1980-05-01

    A proof-of-principle experiment on direct recovery of residual hydrogen ions based on a magnetic electron suppression scheme is described. Ions extracted from a source plasma a few kilovolts above the ground potential (approx. 20 A) are accelerated to 40 keV by a negative potential maintained on a neutralizer gas cell. As the residual ions exit the gas cell, they are deflected from the neutral beam by a magnetic field that also suppresses gas cell electrons and then recovered on a ground-potential surface. Under optimum conditions, a recovery efficiency (the ratio of the net recovered current to the available full-energy ion current) of 80% +- 20% has been obtained. Magnetic suppression of the beam plasma electrons was rather easily achieved; however, handling the fractional-energy ions originating from molecular species (H/sub 2//sup +/ and H/sub 3//sup +/) proved to be extremely important to recovery efficiency.

  12. An analysis of dynamical suppression of spontaneous emission

    CERN Document Server

    Berman, P R

    1998-01-01

    It has been shown recently [see, for example, S.-Y. Zhu and M. O. Scully, Phys. Rev. Lett. {\\bf 76}, 388 (1996)] that a dynamical suppression of spontaneous emission can occur in a three-level system when an external field drives transitions between a metastable state and {\\em two} decaying states. What is unusual in the decay scheme is that the decaying states are coupled directly by the vacuum radiation field. It is shown that decay dynamics required for total suppression of spontaneous emission necessarily implies that the level scheme is isomorphic to a three-level lambda system, in which the lower two levels are {\\em both} metastable, and each is coupled to the decaying state. As such, the total suppression of spontaneous emission can be explained in terms of conventional dark states and coherent population trapping.

  13. AN APPROACH TO SUPPRESS SPECKLE NOISE AND ENHANCE EDGE

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Anisotropic diffusion has good effect on reducing noise and preserving edge, but it may lose some details due to the blocky effect and can not suppress speckle effectively. The Laplacian factor is used to process the observed image which is considered as a piecewise planar image, so the Fourth Order Anisotropic Diffusion (FOAD) can avoid the blocky effect. The edge is preserved and enhanced by the Line Edge Detector (LED) based on stick technique and hypothesis test optimizing method. An approach called the Fourth Order Anisotropic Diffusion and Edge Enhancing (FOADEE), where the LED is combined with the FOAD, is presented. For quantitative evaluation and comparison with the LED, the FOAD and the FOADEE, two parameters as measure of the noise suppression and edge preservation are introduced. It is proved that the novel method can not only suppress speckle prominently but also preserve even enhance edge and useful details effectively by applying it to the phantoms and tissue images.

  14. Speckle Suppression with the Project 1640 Integral Field Spectrograph

    CERN Document Server

    Crepp, Justin R; Brenner, Douglas; Oppenheimer, Ben R; Zimmerman, Neil; Hinkley, Sasha; Parry, Ian; King, David; Vasisht, Gautam; Beichman, Charles; Hillenbrand, Lynne; Dekany, Richard; Shao, Mike; Burruss, Rick; Roberts, Lewis C; Bouchez, Antonin; Roberts, Jenny; Soummer, Remi

    2010-01-01

    Project 1640 is a high-contrast imaging instrument recently commissioned at Palomar observatory. A combination of a coronagraph with an integral field spectrograph (IFS), Project 1640 is designed to detect and characterize extrasolar planets, brown dwarfs, and circumstellar material orbiting nearby stars. In this paper, we present our data processing techniques for improving upon instrument raw sensitivity via the removal of quasi-static speckles. Our approach utilizes the chromatic image diversity provided by the IFS in combination with the locally-optimized combination of images (LOCI) algorithm to suppress the intensity of residual contaminating light in close angular proximity to target stars. We describe the Project 1640 speckle suppression pipeline (PSSP) and demonstrate the ability to detect companions with brightness comparable to and below that of initial speckle intensities using on-sky commissioning data. Our preliminary results indicate that suppression factors of at least one order of magnitude a...

  15. Parton Rescatterings in Large-x Nuclear Suppression at RHIC

    CERN Document Server

    Nemchik, J

    2008-01-01

    We demonstrate that strong suppression of the relative production rate (d+Au)/(p+p) of inclusive high-pT hadrons at forward rapidities observed at RHIC is due to parton multiple rescatterings in nuclear matter. The light-cone dipole approach-based calculations are in a good agreement with BRAHMS and STAR data. They also indicate a significant nuclear suppression at midrapidities with a weak onset of the coherence effects. This prediction is supported by the preliminary d+Au data from the PHENIX Collaboration. Moreover, since similar suppression pattern is also expected to show up at lower energies where effects of parton saturation are not expected, we are able to exclude from the interpretation of observed phenomena models based on the Color Glass Condensate.

  16. Technology Assessment of Dust Suppression Techniques Applied During Structural Demolition

    Energy Technology Data Exchange (ETDEWEB)

    Boudreaux, J.F.; Ebadian, M.A.; Williams, P.T.; Dua, S.K.

    1998-10-20

    Hanford, Fernald, Savannah River, and other sites are currently reviewing technologies that can be implemented to demolish buildings in a cost-effective manner. In order to demolish a structure properly and, at the same time, minimize the amount of dust generated from a given technology, an evaluation must be conducted to choose the most appropriate dust suppression technology given site-specific conditions. Thus, the purpose of this research, which was carried out at the Hemispheric Center for Environmental Technology (HCET) at Florida International University, was to conduct an experimental study of dust aerosol abatement (dust suppression) methods as applied to nuclear D and D. This experimental study targeted the problem of dust suppression during the demolition of nuclear facilities. The resulting data were employed to assist in the development of mathematical correlations that can be applied to predict dust generation during structural demolition.

  17. A model for explaining fusion suppression using classical trajectory method

    Science.gov (United States)

    Phookan, C. K.; Kalita, K.

    2015-01-01

    We adopt a semi-classical approach for explanation of projectile breakup and above barrier fusion suppression for the reactions 6Li+152Sm and 6Li+144Sm. The cut-off impact parameter for fusion is determined by employing quantum mechanical ideas. Within this cut-off impact parameter for fusion, the fraction of projectiles undergoing breakup is determined using the method of classical trajectory in two-dimensions. For obtaining the initial conditions of the equations of motion, a simplified model of the 6Li nucleus has been proposed. We introduce a simple formula for explanation of fusion suppression. We find excellent agreement between the experimental and calculated fusion cross section. A slight modification of the above formula for fusion suppression is also proposed for a three-dimensional model.

  18. A model for explaining fusion suppression using classical trajectory method

    Directory of Open Access Journals (Sweden)

    Phookan C. K.

    2015-01-01

    Full Text Available We adopt a semi-classical approach for explanation of projectile breakup and above barrier fusion suppression for the reactions 6Li+152Sm and 6Li+144Sm. The cut-off impact parameter for fusion is determined by employing quantum mechanical ideas. Within this cut-off impact parameter for fusion, the fraction of projectiles undergoing breakup is determined using the method of classical trajectory in two-dimensions. For obtaining the initial conditions of the equations of motion, a simplified model of the 6Li nucleus has been proposed. We introduce a simple formula for explanation of fusion suppression. We find excellent agreement between the experimental and calculated fusion cross section. A slight modification of the above formula for fusion suppression is also proposed for a three-dimensional model.

  19. Suppression of Collisionless Magnetic Reconnection in Asymmetric Current Sheets

    Science.gov (United States)

    Liu, Yi-Hsin; Hesse, Michael

    2016-01-01

    Using fully kinetic simulations, we study the suppression of asymmetric reconnection in the limit where the diamagnetic drift speed >> Alfven speed and the magnetic shear angle is moderate. We demonstrate that the slippage between electrons and the magnetic flux mitigates the suppression and can even result in fast reconnection that lacks one of the outflow jets. Through comparing a case where the diamagnetic drift is supported by the temperature gradient with a companion case that has a density gradient instead, we identify a robust suppression mechanism. The drift of the x-line is slowed down locally by the asymmetric nature of the x-line, and then the x-line is run over and swallowed by the faster-moving following flux.

  20. Binocular vision in amblyopia: structure, suppression and plasticity.

    Science.gov (United States)

    Hess, Robert F; Thompson, Benjamin; Baker, Daniel H

    2014-03-01

    The amblyopic visual system was once considered to be structurally monocular. However, it now evident that the capacity for binocular vision is present in many observers with amblyopia. This has led to new techniques for quantifying suppression that have provided insights into the relationship between suppression and the monocular and binocular visual deficits experienced by amblyopes. Furthermore, new treatments are emerging that directly target suppressive interactions within the visual cortex and, on the basis of initial data, appear to improve both binocular and monocular visual function, even in adults with amblyopia. The aim of this review is to provide an overview of recent studies that have investigated the structure, measurement and treatment of binocular vision in observers with strabismic, anisometropic and mixed amblyopia.

  1. Viscoelastic Suppression of Gravity-Driven Counterflow Instability

    CERN Document Server

    Beiersdorfer, P; Layne, D; Magee, E W

    2010-01-01

    Attempts to achieve ``top kill'' of actively flowing oil wells by insertion of dense drilling ``muds'', i.e., slurries of dense minerals, from above will fail if the Kelvin-Helmholtz instability in the gravity-driven counterflow produces turbulence that breaks up the denser fluid into small droplets. Here we estimate the droplet size to be sub-mm for fast flows and suggest the addition of a shear-thickening polymer to suppress turbulence. Laboratory experiments show a progression from droplet formation to complete turbulence suppression at the relevant high velocities, illustrating rich new physics accessible by using a shear-thickening liquid in gravity driven counter-streaming flows.

  2. Alumina Paste Sublimation Suppression Barrier for Thermoelectric Device

    Science.gov (United States)

    Paik, Jong-Ah (Inventor); Caillat, Thierry (Inventor)

    2014-01-01

    Alumina as a sublimation suppression barrier for a Zintl thermoelectric material in a thermoelectric power generation device operating at high temperature, e.g. at or above 1000K, is disclosed. The Zintl thermoelectric material may comprise Yb.sub.14MnSb.sub.11. The alumina may be applied as an adhesive paste dried and cured on a substantially oxide free surface of the Zintl thermoelectric material and polished to a final thickness. The sublimation suppression barrier may be finalized by baking out the alumina layer on the Zintl thermoelectric material until it becomes substantially clogged with ytterbia.

  3. Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

    Directory of Open Access Journals (Sweden)

    Fatemeh Esfahanian

    2010-08-01

    Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

  4. Suppressing chaos via Lyapunov-Krasovskii's method

    Energy Technology Data Exchange (ETDEWEB)

    Kuang, J.L. [Faculty of Science and Engineering, City University of Hong Kong, Hong Kong (China)] e-mail: kuangjinlu@hotmail.com; Meehan, P.A. [Department of Mechanical Engineering, University of Queensland, Brisbane, Qld 4072 (Australia)] e-mail: meehan@uq.edu.au; Leung, A.Y.T. [Faculty of Science and Engineering, City University of Hong Kong, Hong Kong (China)] e-mail: bcaleung@cityu.edu.hk

    2006-03-01

    An algorithm for suppressing the chaotic oscillations in non-linear dynamical systems with singular Jacobian matrices is developed using a linear feedback control law based upon the Lyapunov-Krasovskii (LK) method. It appears that the LK method can serve effectively as a generalised method for the suppression of chaotic oscillations for a wide range of systems. Based on this method, the resulting conditions for undisturbed motions to be locally or globally stable are sufficient and conservative. The generalized Lorenz system and disturbed gyrostat equations are exemplified for the validation of the proposed feedback control rule.

  5. Beyond the Immune Suppression: The Immunotherapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ida Silvestri

    2015-01-01

    Full Text Available Prostate cancer (PCa is the second most common cancer in men. As well in many other human cancers, inflammation and immune suppression have an important role in their development. We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression. Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX and provide possible future perspectives combining the immunotherapy to the traditional therapies.

  6. Studies onPaecilomyces marquandii from nematode suppressive chinampa soils.

    Science.gov (United States)

    Marban-Mendoza, N; Garcia-E, R; Dicklow, M B; Zuckerman, B M

    1992-05-01

    Two applications of isolates ofPaecilomyces marquandii from suppressive chinampa soils or P. lilacinus from Peru, fungi that parasitize nematode eggs, generally gave better control of tomato root-knot due toMeloidogyne incognita than did a single application. The effects on root galling by each of thePaecilomyces isolates varied between experiments; however, the ovicidal potential of the three isolates did not differ significantly. Proteins specific for each of the isolates were demonstrated by SDS gel electrophoresis. The results indicate thatP. marquandii is one of the natural soil organisms that contribute to nematode suppression in the chinampa agricultural soils.

  7. Suppression of plant parasitic nematodes in the chinampa agricultural soils.

    Science.gov (United States)

    Zuckerman, B M; Dicklow, M B; Coles, G C; Garcia-E, R; Marban-Mendoza, N

    1989-06-01

    Soil from the chinampa agricultural system in the Valley of Mexico suppressed damage by plant-parasitic nematodes to tomatoes and beans in greenhouse and growth chamber trials. Sterilization of the chinampa soil resulted in a loss of the suppressive effect, thereby indicating that one or more biotic factors were responsible for the low incidence of nematode damage. Nine organisms were isolated from chinampa soil, which showed antinematodal properties in culture. Naturally occurring populations of plant-parasitic nematodes were of lower incidence in chinampa soil than in Chapingo soil.

  8. Suppressing the QCD axion abundance by hidden monopoles

    Energy Technology Data Exchange (ETDEWEB)

    Kawasaki, Masahiro [Tokyo Univ., Chiba (Japan). Inst. for Cosmic Ray Research; Tokyo Univ., Chiba (Japan). Kavli IPMU (WPI), UTIAS; Takahashi, Fuminobu [Tokyo Univ., Miyagi (Japan). Dept. of Physics; Tokyo Univ., Chiba (Japan). Kavli IPMU (WPI), UTIAS; Yamada, Masaki [Tokyo Univ., Chiba (Japan). Inst. for Cosmic Ray Research; Tokyo Univ., Chiba (Japan). Kavli IPMU (WPI), UTIAS; DESY Hamburg (Germany)

    2015-11-15

    We study the Witten effect of hidden monopoles on the QCD axion dynamics, and show that its abundance as well as isocurvature perturbations can be significantly suppressed if there is a sufficient amount of hidden monopoles. When the hidden monopoles make up a significant fraction of dark matter, the Witten effect suppresses the abundance of axion with the decay constant smaller than 10{sup 12} GeV. The cosmological domain wall problem of the QCD axion can also be avoided, relaxing the upper bound on the decay constant when the Peccei-Quinn symmetry is spontaneously broken after inflation.

  9. Suppressing the QCD axion abundance by hidden monopoles

    Directory of Open Access Journals (Sweden)

    Masahiro Kawasaki

    2016-02-01

    Full Text Available We study the Witten effect of hidden monopoles on the QCD axion dynamics, and show that its abundance as well as isocurvature perturbations can be significantly suppressed if there is a sufficient amount of hidden monopoles. When the hidden monopoles make up a significant fraction of dark matter, the Witten effect suppresses the abundance of axion with the decay constant smaller than 1012GeV. The cosmological domain wall problem of the QCD axion can also be avoided, relaxing the upper bound on the decay constant when the Peccei–Quinn symmetry is spontaneously broken after inflation.

  10. Suppression of Beneficial Mutations in Dynamic Microbial Populations

    Science.gov (United States)

    Bittihn, Philip; Hasty, Jeff; Tsimring, Lev S.

    2017-01-01

    Quantitative predictions for the spread of mutations in bacterial populations are essential to interpret evolution experiments and to improve the stability of synthetic gene circuits. We derive analytical expressions for the suppression factor for beneficial mutations in populations that undergo periodic dilutions, covering arbitrary population sizes, dilution factors, and growth advantages in a single stochastic model. We find that the suppression factor grows with the dilution factor and depends nontrivially on the growth advantage, resulting in the preferential elimination of mutations with certain growth advantages. We confirm our results by extensive numerical simulations.

  11. Suppression of oscillations in mean-field diffusion

    Indian Academy of Sciences (India)

    Neeraj Kumar Kamal; Pooja Rani Sharma; Manish Dev Shrimali

    2015-02-01

    We study the role of mean-field diffusive coupling on suppression of oscillations for systems of limit cycle oscillators. We show that this coupling scheme not only induces amplitude death (AD) but also oscillation death (OD) in coupled identical systems. The suppression of oscillations in the parameter space crucially depends on the value of mean-field diffusion parameter. It is also found that the transition from oscillatory solutions to OD in conjugate coupling case is different from the case when the coupling is through similar variable. We rationalize our study using linear stability analysis.

  12. Bifurcation suppression of nonlinear systems via dynamic output feedback and its applications to rotating stall control

    Institute of Scientific and Technical Information of China (English)

    Pengnian CHEN; Huashu QIN; Shengwei MEI

    2005-01-01

    This paper deals with the problems of bifurcation suppression and bifurcation suppression with stability of nonlinear systems. Necessary conditions and sufficient conditions for bifurcation suppression via dynamic output feedback are presented;Sufficient conditions for bifurcation suppression with stability via dynamic output feedback are obtained. As an application, a dynamic compensator, which guarantees that the bifurcation point of rotating stall in axial flow compressors is stably suppressed, is constructed.

  13. Suppression of galactic outflows by cosmological infall and circumgalactic medium

    CERN Document Server

    Singh, Priyanka; Bagla, Jasjeet S; Nath, Biman B

    2016-01-01

    We investigate the relative importance of two galactic outflow suppression mechanisms : a) Cosmological infall of the intergalactic gas onto the galaxy, and b) the existence of a hot circumgalactic medium (CGM). Considering only radial motion, the infall reduces the speed of outflowing gas and even halts the outflow, depending on the mass and redshift of the galaxy. For star forming galaxies there exists an upper mass limit beyond which outflows are suppressed by the gravitational field of the galaxy. We find that infall can reduce this upper mass limit approximately by a factor of two (independent of the redshift). Massive galaxies ($\\gtrsim 10^{12} M_{\\odot}$) host large reservoir of hot, diffuse CGM around the central part of the galaxy. The CGM acts as a barrier between the infalling and outflowing gas and provides an additional source of outflow suppression. We find that at low redshifts ($z\\lesssim3.5$), the CGM is more effective than the infall in suppressing the outflows. Together, these two processes...

  14. Upsilon suppression in the Schrödinger-Langevin approach

    Science.gov (United States)

    Gossiaux, P. B.; Katz, R.

    2016-12-01

    We treat the question of bottomonia suppression in ultrarelativistic heavy ion collisions (URHIC) as a dynamical open quantum problem, tackled for the first time using the Schrödinger-Langevin equation. Coupling this equation to the EPOS2 event generator, predictions are made for the nuclear modification factor of ϒ (1 S) and ϒ (2 S).

  15. Upsilon suppression in the Schr\\"odinger-Langevin approach

    CERN Document Server

    Gossiaux, Pol Bernard

    2016-01-01

    We treat the question of bottomonia suppression in ultrarelativistic heavy ion collisions (URHIC) as a dynamical open quantum problem, tackled for the first time using the Schr\\"odinger-Langevin equation. Coupling this equation to the EPOS2 event generator, predictions are made for the nuclear modification factor of $\\Upsilon (1S)$ and $\\Upsilon (2S)$.

  16. Fission-suppressed hybrid reactor: the fusion breeder

    Energy Technology Data Exchange (ETDEWEB)

    Moir, R.W.; Lee, J.D.; Coops, M.S.

    1982-12-01

    Results of a conceptual design study of a /sup 233/U-producing fusion breeder are presented. The majority of the study was devoted to conceptual design and evaluation of a fission-suppressed blanket and to fuel cycle issues such as fuel reprocessing, fuel handling, and fuel management. Studies in the areas of fusion engineering, reactor safety, and economics were also performed.

  17. Weed-Suppressing Effect and Mechanism of Allelopathic Rice Accessions

    Institute of Scientific and Technical Information of China (English)

    HU Fei; KONG Chui-hua; XU Xiao-hua; ZHANG Chao-xian; CHEN Xiong-hui

    2004-01-01

    Two allelopathic rice accessions, PI312777 and Allelopathyl, significantly suppressedthe growth of associated weeds in the field. Moreover, their weed-suppressing effectswere correlated with the cultivation patterns. The weed-suppressing effects of throwingand transplanting were more effective than that of direct seeding. Furthermore, theamounts of allelochemicals (resorcinols, flavones and hydroxamic acids) produced andreleased from two allelopathic rice accessions were much higher than that from a non-allelopathic rice variety Hua-Jing-Xian 1, and reached the maximum concentration at the6th leaf stage. Differences in the weed-suppressing effects of rice accessions appear toresult from the accessions producing and releasing different amounts of allelochemicalsin the field. Further research confirmed that in PI312777 plants, allelochemicals weresynthesized by the above-ground parts, and then secreted through the root tissues. Roottissues of PI312777 plants never produced the allelochemicals. Root exudates fromPI312777 could significantly inhibit the growth of E. crus-galli surrounding rice plantsin water culture. However, when activated carbon was added to the culture solution, whichcould absorb allelochemicals from root exudates, the growth of E. crus-galli was nolonger significantly inhibited. Weed-suppressing effects of rice accessions depended onallelopathy, cultivation patterns and other factors in rice fields, while allelopathywas one of important factors. Interestingly, the amounts of allelochemicals produced andreleased from allelopathic rice plants may be induced by the presence of E. crus-galli.This suggests that there is a possible chemical recognition between rice and E. crus-galli.

  18. A weed suppressive index for spring barley (Hordeum vulgare) varieties

    DEFF Research Database (Denmark)

    Hansen, P K; Kristensen, K; Willas, J

    2008-01-01

    A screening programme for crop variety competitiveness would ideally be based on only a few, non-destructive measurements of key growth traits. In this study we measured the weed suppressive ability of 79 varieties of spring barley in two ways: (i) directly, by weed coverage assessments under wee...

  19. International measures to prevent and suppress the financing of terrorism

    OpenAIRE

    Eden, Paul

    2005-01-01

    This chapter considers the range of international measures adopted both before and after September 11, 2001 to deny terrorists and their supporters access to the international financial system including the International Convention for the Suppression of Financing of Terrorism, the terrorist financing aspects of Security Council Resolution 1373 and the role played by the Financial Action Task Force (FATF).

  20. Suppression of thermal conduction in a mirror-unstable plasma

    CERN Document Server

    Komarov, S V; Kunz, M W; Schekochihin, A A

    2016-01-01

    The ICM plasma is subject to firehose and mirror instabilities at scales of order the ion Larmor radius. The mirror instability generates fluctuations of magnetic-field strength $\\delta B / B \\sim 1$. These fluctuations act as magnetic traps for the heat-conducting electrons, suppressing their transport. We calculate the effective parallel thermal conductivity in the ICM in the presence of the mirror fluctuations for different stages of the evolution of the instability. The mirror fluctuations are limited in amplitude by the maximum and minimum values of the field strength, with no large deviations from the mean value. This key property leads to a finite suppression of thermal conduction at large scales. We find suppression down to $\\approx 0.2$ of the Spitzer value for the secular phase of the perturbations' growth, and $\\approx 0.3$ for their saturated phase. The effect operates in addition to other suppression mechanisms and independently of them. Globally, fluctuations $\\delta B / B \\sim 1$ can be present...

  1. Charge Recombination Suppressed by Destructive Quantum Interference in Heterojunction Materials

    NARCIS (Netherlands)

    Tempelaar, Roel; Koster, L. Jan Anton; Havenith, Remco W. A.; Knoester, Jasper; Jansen, Thomas L. C.

    2016-01-01

    We show that charge recombination in ordered heterojunctions depends sensitively on the degree of coherent delocalization of charges at the donor acceptor interface. Depending on the relative sign of the electron and hole transfer integrals, such delocalization can dramatically suppress recombinatio

  2. Signal enhancement and suppression during visual-spatial selective attention.

    Science.gov (United States)

    Couperus, J W; Mangun, G R

    2010-11-04

    Selective attention involves the relative enhancement of relevant versus irrelevant stimuli. However, whether this relative enhancement involves primarily enhancement of attended stimuli, or suppression of irrelevant stimuli, remains controversial. Moreover, if both enhancement and suppression are involved, whether they result from a single mechanism or separate mechanisms during attentional control or selection is not known. In two experiments using a spatial cuing paradigm with task-relevant targets and irrelevant distractors, target, and distractor processing was examined as a function of distractor expectancy. Additionally, in the second study the interaction of perceptual load and distractor expectancy was explored. In both experiments, distractors were either validly cued (70%) or invalidly cued (30%) in order to examine the effects of distractor expectancy on attentional control as well as target and distractor processing. The effects of distractor expectancy were assessed using event-related potentials recorded during the cue-to-target period (preparatory attention) and in response to the task-relevant target stimuli (selective stimulus processing). Analyses of distractor-present displays (anticipated versus unanticipated), showed modulations in brain activity during both the preparatory period and during target processing. The pattern of brain responses suggest both facilitation of attended targets and suppression of unattended distractors. These findings provide evidence for a two-process model of visual-spatial selective attention, where one mechanism (facilitation) influences relevant stimuli and another (suppression) acts to filter distracting stimuli.

  3. Heat transfer enhancement accompanying Leidenfrost state suppression at ultrahigh temperatures.

    Science.gov (United States)

    Shahriari, Arjang; Wurz, Jillian; Bahadur, Vaibhav

    2014-10-14

    The well-known Leidenfrost effect is the formation of a vapor layer between a liquid and an underlying hot surface. This insulating vapor layer severely degrades heat transfer and results in surface dryout. We measure the heat transfer enhancement and dryout prevention benefits accompanying electrostatic suppression of the Leidenfrost state. Interfacial electric fields in the vapor layer can attract liquid toward the surface and promote wetting. This principle can suppress dryout even at ultrahigh temperatures exceeding 500 °C, which is more than 8 times the Leidenfrost superheat for organic solvents. Robust Leidenfrost state suppression is observed for a variety of liquids, ranging from low electrical conductivity organic solvents to electrically conducting salt solutions. Elimination of the vapor layer increases heat dissipation capacity by more than 1 order of magnitude. Heat removal capacities exceeding 500 W/cm(2) are measured, which is 5 times the critical heat flux (CHF) of water on common engineering surfaces. Furthermore, the heat transfer rate can be electrically controlled by the applied voltage. The underlying science is explained via a multiphysics analytical model which captures the coupled electrostatic-fluid-thermal transport phenomena underlying electrostatic Leidenfrost state suppression. Overall, this work uncovers the physics underlying dryout prevention and demonstrates electrically tunable boiling heat transfer with ultralow power consumption.

  4. Managing Abiotic Factors of Compost to Increase Soilborne Disease Suppression

    Science.gov (United States)

    Griffin, Deirdre E.

    2012-01-01

    Soilborne pathogens can devastate crops, causing economic losses for farmers due to reduced yields and expensive management practices. Fumigants and fungicides have harmful impacts on the surrounding environment and can be toxic to humans. Therefore, alternative methods of disease management are important. The disease suppressive abilities of…

  5. Rosmarinus officinalis extract suppresses Propionibacterium acnes-induced inflammatory responses.

    Science.gov (United States)

    Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu; Tsai, Po-Jung

    2013-04-01

    Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes-induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes-stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes-induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes-induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes-induced inflammation.

  6. Global Enhancement but Local Suppression in Feature-based Attention.

    Science.gov (United States)

    Forschack, Norman; Andersen, Søren K; Müller, Matthias M

    2017-04-01

    A key property of feature-based attention is global facilitation of the attended feature throughout the visual field. Previously, we presented superimposed red and blue randomly moving dot kinematograms (RDKs) flickering at a different frequency each to elicit frequency-specific steady-state visual evoked potentials (SSVEPs) that allowed us to analyze neural dynamics in early visual cortex when participants shifted attention to one of the two colors. Results showed amplification of the attended and suppression of the unattended color as measured by SSVEP amplitudes. Here, we tested whether the suppression of the unattended color also operates globally. To this end, we presented superimposed flickering red and blue RDKs in the center of a screen and a red and blue RDK in the left and right periphery, respectively, also flickering at different frequencies. Participants shifted attention to one color of the superimposed RDKs in the center to discriminate coherent motion events in the attended from the unattended color RDK, whereas the peripheral RDKs were task irrelevant. SSVEP amplitudes elicited by the centrally presented RDKs confirmed the previous findings of amplification and suppression. For peripherally located RDKs, we found the expected SSVEP amplitude increase, relative to precue baseline when color matched the one of the centrally attended RDK. We found no reduction in SSVEP amplitude relative to precue baseline, when the peripheral color matched the unattended one of the central RDK, indicating that, while facilitation in feature-based attention operates globally, suppression seems to be linked to the location of focused attention.

  7. Stopping Speech Suppresses the Task-Irrelevant Hand

    Science.gov (United States)

    Cai, Weidong; Oldenkamp, Caitlin L.; Aron, Adam R.

    2012-01-01

    Some situations require one to quickly stop an initiated response. Recent evidence suggests that rapid stopping engages a mechanism that has diffuse effects on the motor system. For example, stopping the hand dampens the excitability of the task-irrelevant leg. However, it is unclear whether this "global suppression" could apply across wider motor…

  8. Discovery and early development of non-suppressed ion chromatography.

    Science.gov (United States)

    Fritz, James S; Gjerde, Douglas T

    2010-08-01

    This year marks the 30th anniversary of the publication of Non-Suppressed Ion Chromatography, which is a method for the rapid separation of anions with on-line conductimetric detection. In this method, the separation column is connected directly to the conductimetric detector. This single-column method is a simpler technique than the original suppressed ion chromatography method, which requires a large suppressor column to reduce the background conductance. In the new method, the background signal is reduced to a manageable level simply by using an ion-exchange separation column of low exchange capacity that lowers the eluent concentration needed for separation. The eluent ion used for separation is chosen based on having large, bulky structure, which lowers the equivalent conductance and facilitates detection of the sample anions. This is a personal account of the initial discovery and early development of non-suppressed ion chromatography. The circumstances for the discovery are recounted by the two authors. Methods are described for determination of anions, cations with indirect detection, and techniques for increasing detection sensitivity. A fundamental equation for the prediction of ion chromatography detector response is given, and the development of several types of detection schemes for ion chromatography is discussed. Finally, the impact of non-suppressed ion chromatography is discussed together with comments on the discovery process.

  9. Rudder gap cavitation: Fundamental understanding and its suppression devices

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Shin Hyung, E-mail: shr@snu.ac.k [Department of Naval Architecture and Ocean Engineering, Research Institute of Marine Systems Engineering, Seoul National University, 599 Gwanangno, Gwanak-ku, Seoul 151-744 (Korea, Republic of); Lee, Changmin; Lee, Hee Bum [Department of Naval Architecture and Ocean Engineering, Seoul National University, Seoul 151-744 (Korea, Republic of); Oh, Jungkeun [Jungseok Research Institute of International Logistics and Trade, Inha University, Incheon 402-751 (Korea, Republic of)

    2010-08-15

    With the increasing size and speed of cargo ships, which results in high speed flow in propeller slipstream, cavitation is frequently observed on and around the rudder system. Among the various types of cavitation on the rudder system, the rudder gap cavitation is the most difficult one to control and suppress. For the development of rudder gap cavitation suppression devices, both experimental and numerical analyses of the physical phenomenon are warranted. In the present study, experiments of the incipient cavitation and pressure measurement were carried out for typical cargo ship rudder sections with and without the suppression devices, which were suggested by the author. The experiments were simulated using computational fluid dynamics tools and the results were compared in terms of the cavitation inception and surface pressure distribution. Fundamental understanding of the rudder gap cavitation inception was obtained along with its relevance to the surface pressure distribution. It is confirmed that the gap flow blocking devices effectively suppress the rudder gap cavitation and, at the same time, augment lift.

  10. An Artefact suppressing fast-recovery myoelectric amplifier

    NARCIS (Netherlands)

    Thorsen, R.

    1999-01-01

    An amplifier for recording myoelectric signals using surface electrodes has been developed. The special features are suppression of stimulation artefacts and motion artefacts from electrodes. It is designed for recording of myoelectric signals from a muscle that is being stimulated with short impuls

  11. Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Boram; Kim, Ki Hyun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer Matairesinol suppresses mitochondrial ROS generation during hypoxia. Black-Right-Pointing-Pointer Matairesinol exhibits potent anti-angiogenic activity both in vitro and in vivo. Black-Right-Pointing-Pointer Matairesinol could be a basis for the development of novel anti-angiogenic agents. -- Abstract: Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation and progression and function as signaling molecules in many aspects of hypoxia and growth factor-mediated signaling. Here we report that matairesinol, a natural small molecule identified from the cell-based screening of 200 natural plants, suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic concentration of matairesinol inhibited the proliferation of human umbilical vein endothelial cells. The compound also suppressed in vitro angiogenesis of tube formation and chemoinvasion, as well as in vivo angiogenesis of the chorioallantoic membrane at non-toxic doses. Furthermore, matairesinol decreased hypoxia-inducible factor-1{alpha} in hypoxic HeLa cells. These results demonstrate that matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

  12. Secondary Voltage Control for Harmonics Suppression in Islanded Microgrids

    DEFF Research Database (Denmark)

    Wang, Xiongfei; Guerrero, Josep M.; Blaabjerg, Frede

    2011-01-01

    This paper proposes a secondary voltage waveform control approach to suppress harmonics in islanded microgrids. Compared with the secondary control for traditional large power systems, the proposed control scheme can regulate the voltage waveform instead of voltage magnitude of sensitive buses in...

  13. Oligotrophic bacteria and root disease suppression in organically managed soils

    NARCIS (Netherlands)

    Senechkin, I.V.

    2013-01-01

      The objective of this thesis was to obtain a better understanding of soil health in terms of microbial and chemical characteristics as well as suppression of soil borne plant pathogens. Organic soils were chosen as an appropriate model for studying soil health. Four different organic amendme

  14. Suppression of antibiotic resistance acquisition by combined use of antibiotics.

    Science.gov (United States)

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance.

  15. Weight Suppression Predicts Time to Remission from Bulimia Nervosa

    Science.gov (United States)

    Lowe, Michael R.; Berner, Laura A.; Swanson, Sonja A.; Clark, Vicki L.; Eddy, Kamryn T.; Franko, Debra L.; Shaw, Jena A.; Ross, Stephanie; Herzog, David B.

    2011-01-01

    Objective: To investigate whether, at study entry, (a) weight suppression (WS), the difference between highest past adult weight and current weight, prospectively predicts time to first full remission from bulimia nervosa (BN) over a follow-up period of 8 years, and (b) weight change over time mediates the relationship between WS and time to first…

  16. Suppression of Pest Lepidoptera by Releasing Partially Sterile Males

    Science.gov (United States)

    Knipling. E. F.

    1970-01-01

    Uses population growth models to calculate the theoretical suppression of reproduction achieved by releasing irradiated male moths carrying genetic sterility factors. Shows that releasing partially sterile males should be more effective than releasing fully sterile males. Discusses the costs and advantages of applying this approach to the control…

  17. Cross-cultural differences in emotion suppression in everyday interactions

    NARCIS (Netherlands)

    Huwae, Sylvia; Schaafsma, Juliëtte

    2016-01-01

    Previous research suggests that in collectivistic cultures, people tend to suppress their emotions more than in individualistic cultures. Little research, however, has explored cross-cultural differences in emotion regulation in everyday interactions. Using a daily social interaction method, we exam

  18. Calebin A downregulates osteoclastogenesis through suppression of RANKL signalling.

    Science.gov (United States)

    Tyagi, Amit K; Prasad, Sahdeo; Majeed, Muhammed; Aggarwal, Bharat B

    2016-03-01

    Osteoporosis is a bone disease that is exacerbated by aging and age-associated chronic diseases such as cancer. Cancer-induced bone loss is usually treated with bisphosphonates or denosumab, an antibody against receptor activator of nuclear factor (NF)-κB ligand (RANKL). Because these drugs are expensive and have numerous side effects and high rates of toxicity, safer, more effective, and more affordable therapies for osteoporosis are still needed. We identified a compound, calebin A (CA), derived from turmeric (Curcuma longa) that affects osteoclastogenesis through modulation of the RANKL signalling pathway. The CA's effect on NF-κB activation was examined by electrophoretic mobility shift assay. Using mouse macrophages in vitro model, we found that CA suppressed RANKL-induced osteoclast differentiation of macrophages into osteoclasts, and downregulate RANKL-induced osteoclastogenesis-related marker gene expression, including NFATc-1, TRAP, CTR, and cathepsin K. CA also suppressed the osteoclastogenesis induced by multiple myeloma and breast cancer cells. This effect of CA was correlated with suppression of the phosphorylation and degradation of inhibitor of κB and, thus, inhibition of NF-κB activation. Furthermore, we found that an NF-κB-specific inhibitory peptide blocked RANKL-induced osteoclastogenesis, demonstrating that the NF-κB signalling pathway is mandatory for RANKL-induced osteoclastogenesis. Our results conclusively indicate that CA downmodulates the osteoclastogenesis induced by RANKL and by tumour cells through suppression of NF-κB pathway.

  19. Suppressing the Morning Rise in Cortisol Impairs Free Recall

    Science.gov (United States)

    Rimmele, Ulrike; Meier, Flurina; Lange, Tanja; Born, Jan

    2010-01-01

    Elevated glucocorticoid levels impair memory retrieval. We investigated whether retrieval under naturally elevated glucocorticoid levels, i.e., during the morning rise in cortisol can be improved by suppressing cortisol. In a crossover study 16 men retrieved emotional and neutral texts and pictures (learned 3 d earlier) 30 min after morning…

  20. Relativistic Symmetry Suppresses Quark Spin-Orbit Splitting

    CERN Document Server

    Page, P R; Ginocchio, J N; Page, Philip R.; Goldman, Terry; Ginocchio, Joseph. N.

    2001-01-01

    Experimental data indicate small spin-orbit splittings in hadrons. Forheavy-light mesons we identify a relativistic symmetry that suppresses thesesplittings. We suggest an experimental test in electron-positron annihilation.Furthermore, we argue that the dynamics necessary for this symmetry arepossible in QCD.