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Sample records for caged mitochondrial uncouplers

  1. Uncoupling Mitochondrial Respiration for Diabesity.

    Science.gov (United States)

    Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

    2016-08-01

    Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity. PMID:27378359

  2. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  3. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik;

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...

  4. Mitochondrial uncoupling protein is required for efficient photosynthesis

    OpenAIRE

    Sweetlove, Lee J.; Lytovchenko, Anna; Morgan, Megan; Nunes-Nesi, Adriano; Taylor, Nicolas L.; Baxter, Charles J.; Eickmeier, Ira; Fernie, Alisdair R.

    2006-01-01

    Uncoupling proteins (UCPs) occur in the inner mitochondrial membrane and dissipate the proton gradient across this membrane that is normally used for ATP synthesis. Although the catalytic function and regulation of plant UCPs have been described, the physiological purpose of UCP in plants has not been established. Here, biochemical and physiological analyses of an insertional knockout of one of the Arabidopsis UCP genes (AtUCP1) are presented that resolve this issue. Absence of UCP1 results i...

  5. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

    DEFF Research Database (Denmark)

    Fernström, Maria; Tonkonogi, Michail; Sahlin, Kent

    2004-01-01

    increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled...... of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly......Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in...

  6. Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

    OpenAIRE

    Sander L J Wijers; Schrauwen, Patrick; Saris, Wim H. M.; van Marken Lichtenbelt, Wouter D.

    2008-01-01

    Background Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupli...

  7. Possible physiological roles of mitochondrial uncoupling proteins-UCPn

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr

    2002-01-01

    Roč. 34, č. 10 (2002), s. 1190-1206. ISSN 1357-2725 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling proteins * diabetes * obesity Subject RIV: ED - Physiology Impact factor: 3.044, year: 2002

  8. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

    OpenAIRE

    Hesselink, M.K.C.; Greenhaff, P L; Constantin-Teodosu, D.; Hultman, E; Saris, W. H. M.; Nieuwlaat, R.; Schaart, G.; Kornips, C.F.P.; P. Schrauwen

    2003-01-01

    Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (L...

  9. N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler.

    Directory of Open Access Journals (Sweden)

    Alexandra I Sorochkina

    Full Text Available Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA. The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents.

  10. N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler.

    Science.gov (United States)

    Sorochkina, Alexandra I; Plotnikov, Egor Y; Rokitskaya, Tatyana I; Kovalchuk, Sergei I; Kotova, Elena A; Sychev, Sergei V; Zorov, Dmitry B; Antonenko, Yuri N

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents. PMID:22911866

  11. Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an experimental study in the zebra finch.

    Science.gov (United States)

    Stier, Antoine; Bize, Pierre; Roussel, Damien; Schull, Quentin; Massemin, Sylvie; Criscuolo, François

    2014-10-01

    Mitochondria have a fundamental role in the transduction of energy from food into ATP. The coupling between food oxidation and ATP production is never perfect, but may nevertheless be of evolutionary significance. The 'uncoupling to survive' hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective mechanism against the excessive production of damaging reactive oxygen species (ROS). Because resource allocation and ROS production are thought to shape animal life histories, alternative life-history trajectories might be driven by individual variation in the degree of mitochondrial uncoupling. We tested this hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol (DNP) over a 32-month period. In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory immune response in treated birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis may not be applicable for zebra finches, presumably because of lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than in mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life-history regulator of traits such as fecundity and immunity at adulthood, even with food supplied ad libitum. PMID:25063856

  12. Regulation of Thermogenesis In Plants: The Interaction of Alternative Oxidase and Plant Uncoupling Mitochondrial Protein

    Institute of Scientific and Technical Information of China (English)

    Yan Zhu; Jianfei Lu; Jing Wang; Fu Chen; Feifan Leng; Hongyu Li

    2011-01-01

    Thermogenesis is a process of heat production in living organisms.It is rare in plants,but it does occur in some species of angiosperm.The heat iS generated via plant mitochondrial respiration.As possible Involvement in thermogenesis of mitochondrial factors,alternative oxidases(AOXs)and plant uncoupling mitochondrial proteins(PUMPs)have been well studied.AOXs and PUMPs are ubiquitously present in the inner membrane of plant mitochondria.They serve as two major energy dissipation systems that balance mitochondrial respiration and uncoupled phosphorylation by dissipating the H+ redox energy and proton electrochemical gradient(△μH+)as heat,respectively.AOXs and PUMPs exert similar physiological functions during homeothermic heat production in thermogenic plants.AOXs have five isoforms,while PUMPs have six.Both AOXS and PUMPS are encoded by small nuclear multigene families.Multiple isoforms are expressed in different tissues or organs.Extensive studies have been done in the area of thermogenesis in higher plants.In this review,we focus on the involvement and regulation of AOXs and PUMPs in thermogenesis.

  13. Mitochondrial Hormesis in Pancreatic β Cells: Does Uncoupling Protein 2 Play a Role?

    Directory of Open Access Journals (Sweden)

    Ning Li

    2012-01-01

    Full Text Available In pancreatic β cells, mitochondrial metabolism translates glucose sensing into signals regulating insulin secretion. Chronic exposure of β cells to excessive nutrients, namely, glucolipotoxicity, impairs β-cell function. This is associated with elevated ROS production from overstimulated mitochondria. Mitochondria are not only the major source of cellular ROS, they are also the primary target of ROS attacks. The mitochondrial uncoupling protein UCP2, even though its uncoupling properties are debated, has been associated with protective functions against ROS toxicity. Hormesis, an adaptive response to cellular stresses, might contribute to the protection against β-cell death, possibly limiting the development of type 2 diabetes. Mitochondrial hormesis, or mitohormesis, is a defense mechanism observed in ROS-induced stress-responses by mitochondria. In β cells, mitochondrial damages induced by sublethal exogenous H2O2 can induce secondary repair and defense mechanisms. In this context, UCP2 is a marker of mitohormesis, being upregulated following stress conditions. When overexpressed in nonstressed naïve cells, UCP2 confers resistance to oxidative stress. Whether treatment with mitohormetic inducers is sufficient to restore or ameliorate secretory function of β cells remains to be determined.

  14. Mitochondrial uncoupler 2, 4-dinitrophenol (DNP) counters radiation induced cell death by stimulating anti-oxidant defence system

    International Nuclear Information System (INIS)

    Mitochondrial uncoupling has been shown to be cyto-protective under various stress conditions and studies with uncouplers suggest that mitochondrial uncoupling could be an attractive approach to promote lifespan extension by preventing the formation of reactive oxygen species (ROS). Our earlier studies have established that uncoupling of mitochondrial respiration to attain high glycolytic rate in cancer cells increased cellular radio-resistance. Therefore, we tested the hypothesis that mild mitochondrial uncoupling using DNP protects normal cells from radiation induced cell death by reducing oxidative stress. Human Embryonic Kidney (HEK293) and Mouse Monocytic (RAW264.7) cells were treated with DNP (10 μM),1 hour prior to radiation exposure (gamma rays, Cobalt-60). Cells treated with DNP before irradiation showed enhanced cell number (1.4 fold) as compared to radiation alone. We also observed 40 % decrease (significant level) in radiation induced ROS, 4 hours after exposure in DNP pre-treated cells with concomitant increase in anti-oxidant defence potential. The decreased ROS production and increased antioxidant defence potential correlated well with enhanced MnSOD and catalase expression. Although, DNP increased mitochondrial biogenesis, radiation induced mitochondrial biogenesis, (a consequence of mitochondrial damage), was not increased further in these cells, thereby suggesting that DNP protects the mitochondria from radiation induced damage, possibly by increasing MnSOD expression. These findings provide evidence that mild mitochondrial uncoupling using DNP attributes to the highly coordinated activation of the anti oxidant defence system in cells and provides survival advantage. Further mechanistic studies to understand the DNP induced radioprotection of cells is under progress. (author)

  15. Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.

    Science.gov (United States)

    Suzuki, Toshiyuki; Kikuchi, Haruhisa; Ogura, Masato; Homma, Miwako K; Oshima, Yoshiteru; Homma, Yoshimi

    2015-01-01

    Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity. PMID:25668511

  16. Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Suzuki

    Full Text Available Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity.

  17. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

    Science.gov (United States)

    Dejonghe, Wim; Kuenen, Sabine; Mylle, Evelien; Vasileva, Mina; Keech, Olivier; Viotti, Corrado; Swerts, Jef; Fendrych, Matyáš; Ortiz-Morea, Fausto Andres; Mishev, Kiril; Delang, Simon; Scholl, Stefan; Zarza, Xavier; Heilmann, Mareike; Kourelis, Jiorgos; Kasprowicz, Jaroslaw; Nguyen, Le Son Long; Drozdzecki, Andrzej; Van Houtte, Isabelle; Szatmári, Anna-Mária; Majda, Mateusz; Baisa, Gary; Bednarek, Sebastian York; Robert, Stéphanie; Audenaert, Dominique; Testerink, Christa; Munnik, Teun; Van Damme, Daniël; Heilmann, Ingo; Schumacher, Karin; Winne, Johan; Friml, Jiří; Verstreken, Patrik; Russinova, Eugenia

    2016-01-01

    ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane. PMID:27271794

  18. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    International Nuclear Information System (INIS)

    Highlights: ► The impact of UCP-2 over expression on mitochondrial function is controversial. ► We tested mitochondrial functions at defined levels of overexpression. ► We find minor increases of fatty acid oxidation and uncoupling. ► Effects were seen only at high level (fourfold) of over expression. ► Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 μg/ml of doxycycline (dox) induced UCP-2 fourfold (424 ± 113%, mean ± SEM) and 0.1 μg/ml twofold (178 ± 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 ± 11%) as well as D-[U-14C]-glucose oxidation (+5 ± 9% at 11 mM glucose). Oxidation of [1-14C]-oleate was increased from 4088 to 5797 fmol/μg prot/2 h at 3.3 mM glucose, p 14C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as

  19. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The impact of UCP-2 over expression on mitochondrial function is controversial. Black-Right-Pointing-Pointer We tested mitochondrial functions at defined levels of overexpression. Black-Right-Pointing-Pointer We find minor increases of fatty acid oxidation and uncoupling. Black-Right-Pointing-Pointer Effects were seen only at high level (fourfold) of over expression. Black-Right-Pointing-Pointer Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 {mu}g/ml of doxycycline (dox) induced UCP-2 fourfold (424 {+-} 113%, mean {+-} SEM) and 0.1 {mu}g/ml twofold (178 {+-} 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 {+-} 11%) as well as D-[U-{sup 14}C]-glucose oxidation (+5 {+-} 9% at 11 mM glucose). Oxidation of [1-{sup 14}C]-oleate was increased from 4088 to 5797 fmol/{mu}g prot/2 h at 3.3 mM glucose, p < 0.03. Oxidation of L-[{sup 14}C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the

  20. Complete nucleotide and derived amino acid sequence of cDNA encoding the mitochondrial uncoupling protein of rat brown adipose tissue: lack of a mitochondrial targeting presequence.

    OpenAIRE

    Ridley, R. G.; Patel, H. V.; Gerber, G E; Morton, R C; Freeman, K. B.

    1986-01-01

    A cDNA clone spanning the entire amino acid sequence of the nuclear-encoded uncoupling protein of rat brown adipose tissue mitochondria has been isolated and sequenced. With the exception of the N-terminal methionine the deduced N-terminus of the newly synthesized uncoupling protein is identical to the N-terminal 30 amino acids of the native uncoupling protein as determined by protein sequencing. This proves that the protein contains no N-terminal mitochondrial targeting prepiece and that a t...

  1. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    International Nuclear Information System (INIS)

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3

  2. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  3. Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

    International Nuclear Information System (INIS)

    In order to characterize the biogenesis of unique thermogenic mitochondria of brown adipose tissue, differentiation of precursor cells isolated from mouse brown adipose tissue was studied in cell culture. Synthesis of mitochondrial uncoupling protein (UCP), F1-ATPase, and cytochrome oxidase was examined by L-[35S]methionine labeling and immunoblotting. For the first time, synthesis of physiological amounts of the UCP, a key and tissue-specific component of thermogenic mitochondria, was observed in cultures at about confluence (day 6), indicating that a complete differentiation of brown adipocytes was achieved in vitro. In postconfluent cells (day 8) the content of UCP decreased rapidly, in contrast to some other mitochondrial proteins (beta subunit of F1-ATPase, cytochrome oxidase). In these cells, it was possible, by using norepinephrine, to induce specifically the synthesis of the UCP but not of F1-ATPase or cytochrome oxidase. The maximal response was observed at 0.1 microM norepinephrine and the synthesis of UCP remained activated for at least 24 h. Detailed analysis revealed a major role of the beta-adrenergic receptors and elevated intracellular concentration of cAMP in stimulation of UCP synthesis. A quantitative recovery of the newly synthesized UCP in the mitochondrial fraction indicated completed biogenesis of functionally competent thermogenic mitochondria

  4. Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival.

    Science.gov (United States)

    Barnstable, Colin J; Reddy, Rajini; Li, Hong; Horvath, Tamas L

    2016-04-01

    In the brain, mitochondrial uncoupling protein 2 (UCP2) has emerged as a stress signal associated with neuronal survival. In the retina, UCP2 is expressed primarily by retinal ganglion cells. Here, we investigated the functional relevance of UCP2 in the mouse retina. Increased expression of UCP2 significantly reduced apoptosis during the critical developmental period resulting in elevated numbers of retinal ganglion cells in the adult. Elevated UCP2 levels also protected against excitotoxic cell death induced by intraocular injection of either NMDA or kainic acid. In monolayer cultures of retinal cells, elevated UCP2 levels increased cell survival and rendered the cells independent of the survival-promoting effects of the neurotrophic factors BDNF and CNTF. Taken together, these data implicate UCP2 as an important regulator of retinal neuron survival both during development and in adult animals. PMID:26846222

  5. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  6. Mitochondria as pharmacological targets: the discovery of novel anti-obesity mitochondrial uncouplers from Africa's medicinal plants.

    Science.gov (United States)

    Ocloo, Augustine; Dongdem, Julius Tieroyaare

    2012-01-01

    Obesity results from prolonged positive imbalance between energy in take and expenditure. When food intake chronically exceeds the body's energy need, an efficient metabolism results in the storage of the excess energy as fat. Mitochondria are the main centre for energy production in eukaryotic cells. Mitochondrial proton cycling is responsible for a significant proportion of basal or standard metabolic rate, therefore, further uncoupling of mitochondria may be a good way to increase energy expenditure and hence represent a good pharmacological target for the treatment of obesity. This implies that, any chemical agent or photochemical compound that further uncouples the mitochondria in vivo without having any effect on mitochondria activity could be a potential target in finding treatment for obesity. In the past, uncoupling by 2, 4-dinitrophenol has been used this way with notable success. This paper discusses the mitochondria as targets in the discovery of potential plant natural anti-obesity products from Africa's rich rainforests. PMID:23983343

  7. Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

    Directory of Open Access Journals (Sweden)

    Mario Ost

    Full Text Available Transgenic (UCP1-TG mice with ectopic expression of UCP1 in skeletal muscle (SM show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21 from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress

  8. N-Terminally Glutamate-Substituted Analogue of Gramicidin A as Protonophore and Selective Mitochondrial Uncoupler

    OpenAIRE

    Alexandra I Sorochkina; Egor Y Plotnikov; Rokitskaya, Tatyana I.; Kovalchuk, Sergei I.; Elena A Kotova; Sergei V Sychev; Zorov, Dmitry B.; Antonenko, Yuri N.

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling acti...

  9. Evaluation of the electron transport chain inhibition and uncoupling of mitochondrial bioelectrocatalysis with antibiotics and nitro-based compounds

    International Nuclear Information System (INIS)

    Mitochondrial bioelectrocatalysis can be useful for sensing applications due to the unique metabolic pathways than can be selectively inhibited and uncoupled in mitochondria. This paper details the comparison of different inhibitors and nitro-containing explosive uncouplers in a mitochondria-catalyzed biofuel cell for self-powered explosive sensing. Previous research has reported inhibition of pyruvate oxidation at a mitochondria-modified electrode followed by nitroaromatic uncoupling of current and power. We have previously used oligomycin as the antibiotic and nitrobenzene as the uncoupler of the membrane in the mitochondria-catalyzed biofuel cell, but no comprehensive comparison of various mitochondria inhibitors or explosives has been performed. Results are discussed here for inhibitors targeting complex I, complex III, ATP synthases, adenine nucleotide transport and monocarboxylic acid transport. Reactivation with nitrobenzene was possible in the presence of these inhibitors: oligomycin, 3,3'-diindolylmethane, atractyloside, rotenone, α-cyano-4-hydroxy cinnamic acid and antimycin A. All eleven explosives studied, including: 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), caused uncoupling of the mitochondria function and could be detected by the biosensor.

  10. Mitochondria as Pharmacological Targets: The Discovery of Novel Anti-Obesity Mitochondrial Uncouplers from Africa's Medicinal Plants

    OpenAIRE

    Ocloo, Augustine; Dongdem, Julius Tieroyaare

    2011-01-01

    Obesity results from prolonged positive imbalance between energy in take and expenditure. When food intake chronically exceeds the body's energy need, an efficient metabolism results in the storage of the excess energy as fat. Mitochondria are the main centre for energy production in eukaryotic cells. Mitochondrial proton cycling is responsible for a significant proportion of basal or standard metabolic rate, therefore, further uncoupling of mitochondria may be a good way to increase energy e...

  11. Age-related changes of serum mitochondrial uncoupling 1, rumen and rectal temperature in goats.

    Science.gov (United States)

    Arfuso, Francesca; Rizzo, Maria; Giannetto, Claudia; Giudice, Elisabetta; Fazio, Francesco; Piccione, Giuseppe

    2016-07-01

    Thermoregulatory processes are induced not only by exposure to cold or heat but also by a variety of physiological situations including age, fasting and food intake that result in changes in body temperature. The aim of the present study was to evaluate the differences in serum mitochondrial uncoupling protein 1 (UCP1), rumen temperature (TRUMEN) and rectal temperature (TRECTAL) values between adult and kids goats. Ten adult male Maltese goats aged 3-5 years old (Group A) and 30 male kids, raised for meat, were enrolled in this study. The kids were equally divided into 3 groups according to their age: Group B included kids aged 3 months, Group C included kids aged 4 months and Group D included kids aged 5 months. Blood samples and measurements of TRUMEN and TRECTAL were obtained from each animal. One-way repeated measures analysis of variance (ANOVA) was applied to evaluate the effect of age on the studied parameters. Statistically significant higher serum UCP1 levels (P<0.001) were found in Group A as compared to Groups B, C and D. Higher TRUMEN values (P<0.001) were found in Group A than in Groups B, C and D, and in Group B than in Groups C and D. Group A showed lower TRECTAL values (P<0.001) than Groups B, C and D. The Pearson's Correlation test was applied to assess significant relationship among studied parameters showing a statistically significant negative correlation between the values of TRECTAL and serum UCP1 in all studied Groups (P<0.001). These results indicate that goats have good control of body temperature suggesting that further details about the thermogenic capacity and the function of UCP1 in kids and adult goats are worth exploring. PMID:27264887

  12. Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

    Science.gov (United States)

    Kim, Sangkyu; Myers, Leann; Ravussin, Eric; Cherry, Katie E; Jazwinski, S Michal

    2016-08-01

    Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging. PMID:26965008

  13. Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice

    OpenAIRE

    Keipert, Susanne; Voigt, Anja; Klaus, Susanne

    2011-01-01

    Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisynthetic diets differing in macronutrient ratio: control (high-carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat (HCHF), and low-carbohydrate/high-fat (...

  14. The Role of Mitochondrial Uncoupling in the Development of Diabetic Nephropathy

    OpenAIRE

    Friederich Persson, Malou

    2012-01-01

    Diabetes is closely associated with increased oxidative stress, especially originating from the mitochondria. A mechanism to reduce increased mitochondria superoxide production is to reduce the mitochondria membrane potential by releasing protons across the mitochondria membrane. This phenomenon is referred to as mitochondria uncoupling since oxygen is consumed independently of ATP being produced and can be mediated by Uncoupling Proteins (UCPs). However, increased oxygen consumption is poten...

  15. Opening of the mitochondrial permeability transition pore by uncoupling or inorganic phosphate in the presence of Ca2+ is dependent on mitochondrial-generated reactive oxygen species.

    Science.gov (United States)

    Kowaltowski, A J; Castilho, R F; Vercesi, A E

    1996-01-01

    In this study, we show that mitochondrial membrane permeability transition in Ca(2+)-loaded mitochondria treated with carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) or inorganic phosphate (P(i)) is preceded by enhanced production of H2O2. This production is inhibited either by ethylene glycobis(b-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) or Mg2+, but not by cyclosporin A. Permeability transition is prevented either by EGTA, catalase or dithiothreitol, suggesting the involvement of Ca2+, H2O2 and oxidation of membrane protein thiols in this mechanism. When mitochondria are incubated under anaerobiosis, no permeabilization or H2O2 production occurs. Based on these results we conclude that mitochondrial permeability transition induced by P(i) or FCCP-uncoupling is dependent on mitochondrial-generated reactive oxygen species. PMID:8549822

  16. Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships.

    Science.gov (United States)

    Kovacic, Peter; Pozos, Robert S; Somanathan, Ratnasamy; Shangari, Nandita; O'Brien, Peter J

    2005-01-01

    The biology of the mitochondrial electron transport chain is summarized. Our approach to the mechanism of uncouplers, inhibitors, and toxins is based on electron transfer (ET) and reactive oxygen species (ROS). Extensive supporting evidence, which is broadly applicable, is cited. ROS can be generated either endogenously or exogenously. Generally, the reactive entities arise via redox cycling by ET functionalities, such as, quinones (or precursors), metal compounds, imines (or iminiums), and aromatic nitro compounds (or reduced metabolites). In most cases, the ET functions are formed metabolically. The toxic substances belong to many categories, e.g., medicinals, industrial chemicals, abused drugs, and pesticides. Structure-activity relationships are presented from the ET-ROS perspective, and also quantitatively. Evidence for the theoretical framework is provided by the protective effect of antioxidants. Among other topics addressed are proton flux, membrane pores, and apoptosis. There is support for the thesis that mitochondrial insult may contribute to illnesses and aging. PMID:16248817

  17. Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

    Czech Academy of Sciences Publication Activity Database

    Klaus, S.; Keipert, S.; Rossmeisl, Martin; Kopecký, Jan

    2012-01-01

    Roč. 7, č. 3 (2012), s. 369-386. ISSN 1555-8932 R&D Projects: GA MZd(CZ) NS10528; GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008 Institutional research plan: CEZ:AV0Z50110509 Keywords : adipose tissue * skeletal muscle * uncoupling protein * transgenic mice * insulin sensitivity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.329, year: 2012

  18. Antioxidant activity by a synergy of redox-sensitive mitochondrial phospholipase A2 and uncoupling protein-2 in lung and spleen

    Czech Academy of Sciences Publication Activity Database

    Jabůrek, Martin; Ježek, Jan; Zelenka, Jaroslav; Ježek, Petr

    2013-01-01

    Roč. 45, č. 4 (2013), s. 816-825. ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP303/11/P320; GA MŠk(CZ) ME09018 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling protein UCP2 * mitochondrial phospholipase A(2) isoform gamma * mitochondrial oxidative stress attenuation * fatty acid * antioxidant mechanism Subject RIV: ED - Physiology Impact factor: 4.240, year: 2013

  19. Mitochondrial uncoupling protein 2 gene transcript levels are elevated in maturating erythroid cells

    Czech Academy of Sciences Publication Activity Database

    Flachs, Pavel; Šponarová, Jana; Kopecký, P.; Horváth, Ondřej; Šedivá, A.; Nibbelink, M.; Casteilla, L.; Medříková, Daša; Neckář, Jan; Kolář, František; Kopecký, Jan

    2007-01-01

    Roč. 581, č. 6 (2007), s. 1093-1097. ISSN 0014-5793 Grant ostatní: the Wellcome Trust(XE) 070821/Z/03/Z; EARNEST(XE) FOOD-CT-2005-007036 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514 Source of funding: N - neverejné zdroje ; R - rámcový projekt EK Keywords : uncoupling protein 2 * erythropoiesis * hypoxia Subject RIV: ED - Physiology Impact factor: 3.263, year: 2007

  20. Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Olejár, Tomáš; Smolková, Katarína; Ježek, Jan; Dlasková, Andrea; Plecitá-Hlavatá, Lydie; Zelenka, Jaroslav; Špaček, Tomáš; Engstová, Hana; Reguera Pajuelo, David; Jabůrek, Martin

    2014-01-01

    Roč. 63, Suppl.1 (2014), S73-S91. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GAP305/12/1247; GA ČR(CZ) GPP304/10/P204; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : mitochondria * uncoupling protein UCP2 * pancreatic beta-cells * reactive oxygen species * glucose-stimulated insulin secretion Subject RIV: EA - Cell Biology Impact factor: 1.293, year: 2014

  1. Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.

    Science.gov (United States)

    Zhou, Yuling; Ning, Zhixin; Lee, Yvonne; Hambly, Brett D; McLachlan, Craig S

    2016-12-01

    Current debate in type 2 diabetes (T2DM) has focused on shortened leukocyte telomere length (LTL) as the result of a number of possible causes, including polymorphisms in mitochondrial uncoupling proteins (UCPs) leading to oxidative stress, telomere regulatory pathway gene polymorphisms, or as a direct result of associated cardiovascular complications inducing tissue organ inflammation and oxidative stress. There is evidence that a heritable shorter telomere trait is a risk factor for development of T2DM. This review discusses the contribution and balance of genetic regulation of UCPs and telomere pathways in the context of T2DM. We discuss genotypes that are well known to influence the shortening of LTL, in particular OBFC1 and telomerase genotypes such as TERC. Interestingly, the interaction between short telomeres and T2DM risk appears to involve mitochondrial dysfunction as an intermediate process. A hypothesis is presented that genetic heterogeneity within UCPs may directly affect oxidative stress that feeds back to influence the fine balance of telomere regulation, cell cycle regulation and diabetes risk and/or metabolic disease progression. PMID:26951191

  2. Effects of rosiglitazone on global ischemia-induced hippocampal injury and expression of mitochondrial uncoupling protein 2

    International Nuclear Information System (INIS)

    We investigate the effect of rosiglitazone, a ligand for peroxisome proliferator-activated receptor-γ (PPARγ) with anti-inflammatory and anti-oxidative actions, on hippocampal injury and its roles in mitochondrial uncoupling protein 2 (UCP2) expression caused by transient global ischemia (TGI) in rats. Increased UCP2 expression was observed in mitochondria of hippocampal CA1 2-24 h after TGI/reperfusion, with maximal expression levels at 6-18 h. Administration of rosiglitazone to hippocampus 30 min prior to the onset of TGI further enhanced mitochondrial UCP2 expression 2-6 h following TGI/reperfusion. Rats subjected to TGI/reperfusion displayed a significant increase in lipid peroxidation, based on increased malondialdehyde (MDA) levels, in hippocampal CA1 mitochondria 2-6 h after reperfusion. Rosiglitazone significantly attenuated TGI/reperfusion-induced lipid peroxidation and suppressed hippocampal CA1 neuronal death based on the surviving neuronal counts. In conclusion, our results provide correlative evidence for the 'PPARγ → UCP2 → neuroprotection' cascade in ischemic brain injury

  3. Glucocorticoids Suppress Mitochondrial Oxidant Production via Upregulation of Uncoupling Protein 2 in Hyperglycemic Endothelial Cells.

    Science.gov (United States)

    Gerö, Domokos; Szabo, Csaba

    2016-01-01

    Diabetic complications are the leading cause of morbidity and mortality in diabetic patients. Elevated blood glucose contributes to the development of endothelial and vascular dysfunction, and, consequently, to diabetic micro- and macrovascular complications, because it increases the mitochondrial proton gradient and mitochondrial oxidant production. Therapeutic approaches designed to counteract glucose-induced mitochondrial reactive oxygen species (ROS) production in the vasculature are expected to show efficacy against all diabetic complications, but direct pharmacological targeting (scavenging) of mitochondrial oxidants remains challenging due to the high reactivity of some of these oxidant species. In a recent study, we have conducted a medium-throughput cell-based screening of a focused library of well-annotated pharmacologically active compounds and identified glucocorticoids as inhibitors of mitochondrial superoxide production in microvascular endothelial cells exposed to elevated extracellular glucose. The goal of the current study was to investigate the mechanism of glucocorticoids' action. Our findings show that glucocorticoids induce the expression of the mitochondrial UCP2 protein and decrease the mitochondrial potential. UCP2 silencing prevents the protective effect of the glucocorticoids on ROS production. UCP2 induction also increases the oxygen consumption and the "proton leak" in microvascular endothelial cells. Furthermore, glutamine supplementation augments the effect of glucocorticoids via further enhancing the expression of UCP2 at the translational level. We conclude that UCP2 induction represents a novel experimental therapeutic intervention in diabetic vascular complications. While direct repurposing of glucocorticoids may not be possible for the therapy of diabetic complications due to their significant side effects that develop during chronic administration, the UCP2 pathway may be therapeutically targetable by other, glucocorticoid

  4. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    Directory of Open Access Journals (Sweden)

    Viggiano E

    2016-07-01

    Full Text Available Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD, which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

  5. Effects of endurance exercise on mitochondrial efficiency, uncoupling and lipid oxidation in human skeletal muscle

    OpenAIRE

    Fernström, Maria

    2007-01-01

    During the lest years the importance of muscle mitochondria, and mitochondrial function, not only for performance but else for health has been highlighted. The main function of the mitochondria is to produce ATP by oxidative phosphorylation (coupled respiration). In skeletal muscle a substantial part of the energy is lost in non-coupled reactions, it has been estimated that non-coupled respiration accounts for as much as 20-25% of the total energy expenditure. It is now almo...

  6. Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling

    Czech Academy of Sciences Publication Activity Database

    Ježek, Jan; Jabůrek, Martin; Zelenka, Jaroslav; Ježek, Petr

    2010-01-01

    Roč. 59, č. 5 (2010), s. 737-747. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA303/07/0105; GA MŠk ME09018; GA AV ČR(CZ) KJB500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : Heart mitochondrial phospholipase A2 * Fatty Acids * Adenine nucleotide translocase Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  7. Serum levels of mitochondrial uncoupling protein 1, leptin, and lipids during late pregnancy and the early postpartum period in mares.

    Science.gov (United States)

    Arfuso, F; Giannetto, C; Rizzo, M; Fazio, F; Giudice, E; Piccione, G

    2016-09-15

    The aim of this study was to investigate the changes of serum mitochondrial uncoupling protein 1 (UCP1) and leptin levels as well as of lipid and lipoprotein profiles in mares during the peripartum period. Ten pregnant mares (group A) were monitored from 15 ± 3 days of pregnancy until 15 days after foaling, and 10 nonpregnant nonlactating mares constituted the control (group B). In group A, blood sampling was performed on Days 15 ± 3 and 7 ± 3 before foaling, on the day of foaling, and on Days 7 and 15 after foaling. In group B, blood sampling was performed on the same days as in group A. Serum levels were determined for UCP1, leptin, total lipids, phospholipids, triglycerides, total cholesterol (Total-Chol), high-density lipoproteins, low-density lipoproteins (LDLs), and very low-density lipoproteins (VLDLs). Two-way repeated-measures ANOVA was applied to evaluate the effects of peripartum period and group membership. All studied parameters except phospholipid levels (P > 0.05) showed significant changes in group A over the peripartum period (P leptin and total lipids, triglycerides, VLDLs, Total-Chol, and LDLs. These changes observed in mares during the peripartum period could represent a response to hormonal and metabolic adaptations occurring during specific physiological conditions such as late pregnancy and early postpartum. These changes should compensate for the energy loss occurring during these particular life phases and ensure a good body condition to protect mares against negative energy balance. PMID:27165993

  8. Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels.

    Science.gov (United States)

    Kaczara, Patrycja; Motterlini, Roberto; Rosen, Gerald M; Augustynek, Bartlomiej; Bednarczyk, Piotr; Szewczyk, Adam; Foresti, Roberta; Chlopicki, Stefan

    2015-10-01

    Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100μM) induced a persistent increase in the oxygen consumption rate (OCR) that was accompanied by inhibition of glycolysis (extracellular acidification rate, ECAR) and a decrease in ATP-turnover. Furthermore, CORM-401 increased proton leak, diminished mitochondrial reserve capacity and enhanced non-mitochondrial respiration. Inactive CORM-401 (iCORM-401) neither induced mitochondrial uncoupling nor inhibited glycolysis, supporting a direct role of CO in the endothelial metabolic response induced by CORM-401. Interestingly, blockade of mitochondrial large-conductance calcium-regulated potassium ion channels (mitoBKCa) with paxilline abolished the increase in OCR promoted by CORM-401 without affecting ECAR; patch-clamp experiments confirmed that CO derived from CORM-401 activated mitoBKCa channels present in mitochondria. Conversely, stabilization of glycolysis by MG132 prevented CORM-401-mediated decrease in ECAR but did not modify the OCR response. In summary, we demonstrated in intact endothelial cells that CO induces a two-component metabolic response: uncoupling of mitochondrial respiration dependent on the activation of mitoBKCa channels and inhibition of glycolysis independent of mitoBKCa channels. PMID:26185029

  9. Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells

    Directory of Open Access Journals (Sweden)

    Jonathan Barlow

    2015-04-01

    Full Text Available High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2 and that UCP2 knockdown does not affect palmitate-induced MitoSOX oxidation. Palmitoleate does not influence MitoSOX oxidation in INS-1E cells ±UCP2 and largely prevents the palmitate-induced effects. Importantly, UCP2 knockdown amplifies the preventive effect of palmitoleate on palmitate-induced ROS. Consistently, viability effects of palmitate and palmitoleate are similar between cells ±UCP2, but UCP2 knockdown significantly augments the palmitoleate protection against palmitate-induced cell loss at high glucose. We conclude that UCP2 neither mediates palmitate-induced mitochondrial ROS generation and the associated cell loss, nor protects against these deleterious effects. Instead, UCP2 dampens palmitoleate protection against palmitate toxicity.

  10. Mitochondrial uncoupler carbonyl cyanide M-chlorophenylhydrazone induces the multimer assembly and activity of repair enzyme protein L-isoaspartyl methyltransferase.

    Science.gov (United States)

    Fanélus, Irvens; Desrosiers, Richard R

    2013-07-01

    The protein L-isoaspartyl methyltransferase (PIMT) repairs damaged aspartyl residues in proteins. It is commonly described as a cytosolic protein highly expressed in brain tissues. Here, we report that PIMT is an active monomeric as well as a multimeric protein in mitochondria isolated from neuroblastoma cells. Upon treatments with mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), PIMT monomers level decreased by half while that of PIMT multimers was higher. Gel electrophoresis under reducing conditions of CCCP-induced PIMT multimers led to PIMT monomers accumulation, indicating that multimers resulted from disulfide-linked PIMT monomers. The antioxidant ascorbic acid significantly lowered CCCP-induced formation of PIMT multimers, suggesting that reactive oxygen species contributed to PIMT multimerization. In addition, the elevation of PIMT multimers catalytic activity upon treatments with CCCP was severely inhibited by the reducing agent dithiothreitol. This indicated that PIMT monomers have lower enzymatic activity following CCCP treatments and that activation of PIMT multimers is essentially dependent on the formation of disulfide-linked monomers of PIMT. Furthermore, the perturbation of mitochondrial function by CCCP promoted the accumulation of damaged aspartyl residues in proteins with high molecular weights. Thus, this study demonstrates the formation of active PIMT multimers associated with mitochondria that could play a key role in repairing damaged proteins accumulating during mitochondrial dysfunction. PMID:23319267

  11. Role of mitochondrial uncoupling protein-2 (UCP2 in higher brain functions, neuronal plasticity and network oscillation

    Directory of Open Access Journals (Sweden)

    Gretchen Hermes

    2016-06-01

    Conclusions: We conclude that disruptions in mitochondrial function may play a critical role in pathophysiology of mental illness. Specifically, we have shown that NMDA driven behavioral, synaptic, and brain oscillatory functions are impaired in UCP2 knockout mice.

  12. c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway[S

    OpenAIRE

    Mollica, Maria Pina; Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Cocca, Ennio; Gaita, Marcello; Della-Gatta, Antonio; Marano, Angela; Mazzarella, Giuseppe; Bergamo, Paolo

    2014-01-01

    Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA iso...

  13. PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling.

    Science.gov (United States)

    Morais, Vanessa A; Haddad, Dominik; Craessaerts, Katleen; De Bock, Pieter-Jan; Swerts, Jef; Vilain, Sven; Aerts, Liesbeth; Overbergh, Lut; Grünewald, Anne; Seibler, Philip; Klein, Christine; Gevaert, Kris; Verstreken, Patrik; De Strooper, Bart

    2014-04-11

    Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations. PMID:24652937

  14. Adipocyte-Specific Deletion of Manganese Superoxide Dismutase Protects From Diet-Induced Obesity Through Increased Mitochondrial Uncoupling and Biogenesis.

    Science.gov (United States)

    Han, Yong Hwan; Buffolo, Márcio; Pires, Karla Maria; Pei, Shaobo; Scherer, Philipp E; Boudina, Sihem

    2016-09-01

    Obesity and insulin resistance are associated with oxidative stress (OS). The causal role of adipose OS in the pathogenesis of these conditions is unknown. To address this issue, we generated mice with an adipocyte-selective deletion of manganese superoxide dismutase (MnSOD). When fed a high-fat diet (HFD), the AdSod2 knockout (KO) mice exhibited less adiposity, reduced adipocyte hypertrophy, and decreased circulating leptin. The resistance to diet-induced adiposity was the result of an increased metabolic rate and energy expenditure. Furthermore, palmitate oxidation was elevated in the white adipose tissue (WAT) and brown adipose tissue of AdSod2 KO mice fed an HFD, and the expression of key fatty acid oxidation genes was increased. To gain mechanistic insight into the increased fat oxidation in HFD-fed AdSod2 KO mice, we quantified the mitochondrial function and mitochondrial content in WAT and found that MnSOD deletion increased mitochondrial oxygen consumption and induced mitochondrial biogenesis. This effect was preserved in cultured adipocytes from AdSod2 KO mice in vitro. As expected from the enhanced fat oxidation, circulating levels of free fatty acids were reduced in the HFD-fed AdSod2 KO mice. Finally, HFD-fed AdSod2 KO mice were protected from hepatic steatosis, adipose tissue inflammation, and glucose and insulin intolerance. Taken together, these results demonstrate that MnSOD deletion in adipocytes triggered an adaptive stress response that activated mitochondrial biogenesis and enhanced mitochondrial fatty acid oxidation, thereby preventing diet-induced obesity and insulin resistance. PMID:27284109

  15. Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation

    OpenAIRE

    Gretchen Hermes; David Nagy; Michael Waterson; Attila Zsarnovszky; Luis Varela; Mihaly Hajos; Horvath, Tamas L.

    2016-01-01

    Background/Purpose: Major psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the neurobiology of mental illness. These experiments interrogated the importance of mitochondrial flex...

  16. Whole body metabolism, muscle and mitochondrial function, and the role of uncoupling protein-3 in a mouse model of sepsis

    OpenAIRE

    Zolfaghari, P. S.

    2012-01-01

    Sepsis, the exaggerated systemic inflammatory response to infection, often leads to multi-organ failure (MOF) and death. Skeletal muscle function is often profoundly affected, with patients requiring prolonged ventilatory support and rehabilitation. The pathophysiology underlying MOF and muscle failure in sepsis remains poorly understood. Recent evidence points to mitochondrial dysfunction and cellular energetic down-regulation, related in part to excess generation of reacti...

  17. Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes

    Science.gov (United States)

    Fan, Zhuo; Wen, Ting; Chen, Yaoxu; Huang, Lijie; Lin, Wei; Yin, Chunxia; Tan, Wen

    2016-01-01

    KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria. PMID:26949448

  18. ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein whose affinity to fatty acid is increased with the introduction of a His pair at the second matrix loop

    International Nuclear Information System (INIS)

    Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic acid (LA)-mediated H+ efflux with K m of 56.36 ± 0.27 μM and V max of 66.9 μmol H+ min-1 (mg prot)-1. LA-mediated H+ fluxes were sensitive to ATP inhibition with K i of 2.61 ± 0.36 mM (at pH 7.2), a value similar to those for dicot UCPs. ZmPUMP was also used to investigate the importance of a histidine pair present in the second matrix loop of mammalian UCP1 and absent in plant UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55-fold increase in LA-affinity while its activity remained unchanged. Our data indicate conserved properties of plant UCPs and suggest an enhancing but not essential role of the histidine pair in proton transport mechanism

  19. Role of Uncoupling Proteins in Cancer

    International Nuclear Information System (INIS)

    Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance

  20. Role of Uncoupling Proteins in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Adamo; Oliver, Jordi; Roca, Pilar, E-mail: pilar.roca@uib.es [Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d' Investigació en Ciències de la Salut, Universitat de les Illes Balears/Cra. Valldemossa km 7.5, E-07122, Palma de Mallorca, Illes Balears (Spain)

    2010-04-16

    Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

  1. Role of Uncoupling Proteins in Cancer

    Directory of Open Access Journals (Sweden)

    Adamo Valle

    2010-04-01

    Full Text Available Uncoupling proteins (UCPs are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS. Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

  2. Stimulation of potato tuber respiration by cold stress is associated with an increased capacity of both plant uncoupling mitochondrial protein (PUMP) and alternative oxidase

    Czech Academy of Sciences Publication Activity Database

    Calegario, F. F.; Cosso, R. G.; Fagian, M. M.; Almeida, F. V.; Jardim, W. F.; Ježek, Petr; Arruda, P.; Vercesi, A. E.

    2003-01-01

    Roč. 35, č. 3 (2003), s. 211-220. ISSN 0145-479X R&D Projects: GA ČR GA521/02/0183 Institutional research plan: CEZ:AV0Z5011922 Keywords : potato respiration * plant uncoupling protein * cold adaptation Subject RIV: EF - Botanics Impact factor: 3.424, year: 2003

  3. Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3

    Czech Academy of Sciences Publication Activity Database

    Žáčková, Markéta; Škobisová, Eva; Urbánková, Eva; Ježek, Petr

    2003-01-01

    Roč. 278, č. 23 (2003), s. 20761-20769. ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling protein-2 * polyunsaturated fatty acids * recombinant yeast expression Subject RIV: CE - Biochemistry Impact factor: 6.482, year: 2003

  4. *601693 UNCOUPLING PROTEIN 2; UCP2 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 601693 FIELD TI 601693 UNCOUPLING PROTEIN 2; UCP2 FIELD TX CLONING The mitochondrial pr ... els of UCP2 and UCP3 (602044) mRNA in skeletal muscle an d adipose tissue from both lean ... and obese individu ... tion of gene expression observed during fasting in lean ... and obese subjects show that there is no major alt ...

  5. Bacterial resistance to uncouplers.

    Science.gov (United States)

    Lewis, K; Naroditskaya, V; Ferrante, A; Fokina, I

    1994-12-01

    Uncoupler resistance presents a potential challenge to the conventional chemiosmotic coupling mechanism. In E. coli, an adaptive response to uncouplers was found in cell growing under conditions requiring oxidative phosphorylation. It is suggested that uncoupler-resistant mutants described in the earlier literature might represent a constitutive state of expression of this "low energy shock" adaptive response. In the environment, bacteria are confronted by nonclassical uncoupling factors such as organic solvents, heat, and extremes of pH. It is suggested that the low energy shock response will aid the cell in coping with the effects of natural uncoupling factors. The genetic analysis of uncoupler resistance has only recently began, and is yielding interesting and largely unexpected results. In Bacillus subtilis, a mutation in fatty acid desaturase causes an increased content of saturated fatty acids in the membrane and increased uncoupler resistance. The protonophoric efficiency of uncouplers remains unchanged in the mutants, inviting nonorthodox interpretations of the mechanism of resistance. In E. coli, two loci conferring resistance to CCCP and TSA were cloned and were found to encode multidrug resistance pumps. Resistance to one of the uncouplers, TTFB, remained unchanged in strains mutated for the MDRs, suggesting a resistance mechanism different from uncoupler extrusion. PMID:7721726

  6. Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp

    2011-01-01

    Uncoupling proteins (UCPs) are mitochondrial proteins able to dissipate the proton gradient of the inner mitochondrial membrane when activated. This decreases ATP-generation through oxidation of fuels and may theoretically decrease energy expenditure leading to obesity. Evidence from Ucp...

  7. Uncoupling protein 1 (UCP1 of brown adipocyte, the only uncoupler: historical perspective

    Directory of Open Access Journals (Sweden)

    Daniel eRicquier

    2011-12-01

    Full Text Available Uncoupling protein 1 - UCP1, is a unique mitochondrial membranous protein devoted to adaptive thermogenesis, a specialized function operated by the highly specialized oxidative brown adipocytes. Whereas the family of mitochondrial metabolite carriers comprises ~40 members including UCP1, the UCP1 is specifically identified by its ability to translocate protons through the inner membrane of brown adipocyte mitochondria. Doing that, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation of oxidative energy as heat while, in parallel it markedly stimulates respiration and activates fatty acid oxidation. UCP1 homologues were identified but they are biochemically and physiologically different from UCP1. Thirty five years after its identification, UCP1 still appears as a fascinating component, and the recent renewal of the interest in human brown adipose tissue makes UCP1 as a potential target for strategies of treatment of metabolic disorders.

  8. Uncoupling proteins of invertebrates: A review.

    Science.gov (United States)

    Slocinska, Malgorzata; Barylski, Jakub; Jarmuszkiewicz, Wieslawa

    2016-09-01

    Uncoupling proteins (UCPs) mediate inducible proton conductance in the mitochondrial inner membrane. Herein, we summarize our knowledge regarding UCPs in invertebrates. Since 2001, the presence of UCPs has been demonstrated in nematodes, mollusks, amphioxi, and insects. We discuss the following important issues concerning invertebrate UCPs: their evolutionary relationships, molecular and functional properties, and physiological impact. Evolutionary analysis indicates that the branch of vertebrate and invertebrate UCP4-5 diverged early in the evolutionary process prior to the divergence of the animal groups. Several proposed physiological roles of invertebrate UCPs are energy control, metabolic balance, and preventive action against oxidative stress. © 2016 IUBMB Life, 68(9):691-699, 2016. PMID:27385510

  9. Possible basic and specific functions of plant uncoupling proteins (pUCP)

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Borecký, Jiří; Žáčková, Markéta; Costa, A. D. T.; Arruda, P.

    2001-01-01

    Roč. 21, č. 2 (2001), s. 237-245. ISSN 0144-8463 R&D Projects: GA ČR GA301/98/0568; GA AV ČR IAA5011106 Institutional research plan: CEZ:AV0Z5011922 Keywords : fatty acid-induced uncoupling * plant uncoupling mitochondrial protein * plant mitochondria Subject RIV: CE - Biochemistry Impact factor: 0.921, year: 2001

  10. Chronic Alcohol Consumption Leads to a Tissue Specific Expression of Uncoupling Protein-2

    OpenAIRE

    Graw, Jan A.; von Haefen, Clarissa; Poyraz, Deniz; Möbius, Nadine; Sifringer, Marco; Spies, Claudia D.

    2015-01-01

    Uncoupling proteins (UCPs) are anion channels that can decouple the mitochondrial respiratory chain. "Mild uncoupling" of internal respiration reduces free radical production and oxidative cell stress. Chronic alcohol consumption is a potent inducer of oxidative stress in multiple tissues and regulates UCP-2 and -4 expression in the brain. To analyse the impact of chronic alcohol intake on UCP-2 expression in tissues with high endogenous UCP-2 contents, male Wistar rats (n=34) were treated wi...

  11. Achromatic and Uncoupled Medical Gantry

    Science.gov (United States)

    Tsoupas, N.; Kayran, D.; Litvinenko, V.

    One of the functions of a medical gantry is to irradiate a tumor from different angles to reduce the dose received by the healthy tissue which surrounds the tumor. The rotation of the gantry rotates also its quadrupoles that focus the beam, as a result the beam is "coupled" in the sense that the horizontal motion of the beam particles is affected by the vertical motion and vice-versa therefore the beam spot size at the tumor may vary with the angular orientation of the gantry. Although such a beam-coupling is inevitable in a rotated gantry in which the horizontal plane is not the symmetry plane of the quadrupoles, it is possible to find a solution that the optics of the gantry"appears uncoupled" at any angular orientation of the gantry. As we show in the paper, the condition of an uncoupled gantry is equivalent to an uncoupled linear-beam-transport-matrix which is independent of the angular orientation of the gantry, therefore the beam spot size at the location of the tumor is independent of the orientation of the gantry. In this paper we present the theoretical basis to generate the beam optics for a gantry which is constrained to provide uncoupled and also achromatic beamtransport to the location of the tumor. In addition we present the layout of the magnetic elements and the optics of a medical gantrywhich satisfies the achromaticity and uncoupled conditions.

  12. Cyanide-induced Death of Dopaminergic Cells is Mediated by Uncoupling Protein-2 Up-regulation and Reduced Bcl-2 Expression

    OpenAIRE

    Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

    2009-01-01

    Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell l...

  13. Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

    International Nuclear Information System (INIS)

    Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 270C although 3H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

  14. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

    2009-01-15

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

  15. Asiatic acid uncouples respiration in isolated mouse liver mitochondria and induces HepG2 cells death.

    Science.gov (United States)

    Lu, Yapeng; Liu, Siyuan; Wang, Ying; Wang, Dang; Gao, Jing; Zhu, Li

    2016-09-01

    Asiatic acid, one of the triterpenoid components isolated from Centella asiatica, has received increasing attention due to a wide variety of biological activities. To date, little is known about its mechanisms of action. Here we examined the cytotoxic effect of asiatic acid on HepG2 cells and elucidated some of the underlying mechanisms. Asiatic acid induced rapid cell death, as well as mitochondrial membrane potential (MMP) dissipation, ATP depletion and cytochrome c release from mitochondria to the cytosol in HepG2 cells. In mitochondria isolated from mouse liver, asiatic acid treatment significantly stimulated the succinate-supported state 4 respiration rate, dissipated the MMP, increased Ca(2+) release from Ca(2+)-loaded mitochondria, decreased ATP content and promoted cytochrome c release, indicating the uncoupling effect of asiatic acid. Hydrogen peroxide (H2O2) produced by succinate-supported mitochondrial respiration was also significantly inhibited by asiatic acid. In addition, asiatic acid inhibited Ca(2+)-induced mitochondrial swelling but did not induce mitochondrial swelling in hyposmotic potassium acetate medium which suggested that asiatic acid may not act as a protonophoric uncoupler. Inhibition of uncoupling proteins (UCPs) or blockade of adenine nucleotide transporter (ANT) attenuated the effect of asiatic acid on MMP dissipation, Ca(2+) release, mitochondrial respiration and HepG2 cell death. When combined inhibition of UCPs and ANT, asiatic acid-mediated uncoupling effect was noticeably alleviated. These results suggested that both UCPs and ANT partially contribute to the uncoupling properties of asiatic acid. In conclusion, asiatic acid is a novel mitochondrial uncoupler and this property is potentially involved in its toxicity on HepG2 cells. PMID:27288117

  16. Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation.

    Science.gov (United States)

    Skulachev, V P

    1991-12-01

    Free fatty acids, natural uncouplers of oxidative phosphorylation, are shown to differ from artificial ones in that they fail to increase conductance of phospholipid bilayers which are permeable for the protonated form of fatty acids but impermeable for their anionic form. Recent studies have revealed that uncoupling by fatty acids in mitochondria is mediated by the ATP/ADP antiporter and, in brown fat, by thermogenin which is structurally very similar to the antiporter. It is suggested that both the ATP/ADP antiporter and thermogenin facilitate translocation of the fatty anions through the mitochondrial membrane. PMID:1756853

  17. Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2

    Czech Academy of Sciences Publication Activity Database

    Malingriaux, E. A.; Rupprecht, A.; Gille, L.; Jovanovic, O.; Ježek, Petr; Jabůrek, Martin; Pohl, E. E.

    2013-01-01

    Roč. 8, č. 10 (2013), e77786. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling proteins * 4-hydroxy-2-nonenal * fatty acids Subject RIV: EA - Cell Biology Impact factor: 3.534, year: 2013

  18. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  19. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  20. Doped golden fullerene cages

    OpenAIRE

    Baletto, Francesca; Ferrando, Riccardo

    2015-01-01

    A first-principles investigation of the effect of the doping of golden cages of 32 atoms is proposed. It is shown that Ag and Cu doping affects the geometrical stability of the icosahedral fullerene Au-32 cage, where Ag-doping leads to a new, low symmetric, and prolate motif while Cu-doping leads to a lump, incomplete decahedral shape. Most significantly, the HOMO-LUMO gap depends strongly on the cluster geometry while its dependence on the cluster chemical composition seems to be weaker.

  1. Novel reptilian uncoupling proteins: molecular evolution and gene expression during cold acclimation

    OpenAIRE

    Schwartz, Tonia S.; Murray, Shauna; Seebacher, Frank

    2008-01-01

    Many animals upregulate metabolism in response to cold. Uncoupling proteins (UCPs) increase proton conductance across the mitochondrial membrane and can thereby alleviate damage from reactive oxygen species that may form as a result of metabolic upregulation. Our aim in this study was to determine whether reptiles (Crocodylus porosus) possess UCP genes. If so, we aimed to place reptilian UCP genes within a phylogenetic context and to determine whether the expression of UCP genes is increased ...

  2. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    OpenAIRE

    Maioli Emanuela; Torricelli Claudia; Fortino Vittoria; Carlucci Filippo; Tommassini Valentina; Pacini Adriana

    2009-01-01

    Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried o...

  3. Evidence of hollow golden cages

    OpenAIRE

    Bulusu, Satya; Li, Xi; Wang, Lai-Sheng; Zeng, Xiao Cheng

    2006-01-01

    The fullerenes are the first “free-standing” elemental hollow cages identified by spectroscopy experiments and synthesized in the bulk. Here, we report experimental and theoretical evidence of hollow cages consisting of pure metal atoms, Aun− (n = 16–18); to our knowledge, free-standing metal hollow cages have not been previously detected in the laboratory. These hollow golden cages (“bucky gold”) have an average diameter >5.5 Å, which can easily accommodate one guest atom inside.

  4. John Cage Discusses Fluxus.

    Science.gov (United States)

    Snyder, Ellsworth

    1992-01-01

    Presents an informal discussion with composer John Cage which includes his response to George Maciunas' work, his recollections of Marcel Duchamp, the complex relationship between inelegant material and revealing works of art, neo-Dada and neo-Fluxus, Wittgenstein and the artist's ultimate responsibility to initiate a change in the viewer or…

  5. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Han Wern; Lim, Hwee Ying [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore); Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)

    2009-11-06

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  6. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    International Nuclear Information System (INIS)

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  7. Critical appraisal of the MTT assay in the presence of rottlerin and uncouplers.

    Science.gov (United States)

    Maioli, Emanuela; Torricelli, Claudia; Fortino, Vittoria; Carlucci, Filippo; Tommassini, Valentina; Pacini, Adriana

    2009-01-01

    Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general. PMID:19957063

  8. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    Directory of Open Access Journals (Sweden)

    Carlucci Filippo

    2009-01-01

    Full Text Available Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general.

  9. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    Directory of Open Access Journals (Sweden)

    Maioli Emanuela

    2009-12-01

    Full Text Available Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general.

  10. Building a better Faraday cage

    Science.gov (United States)

    MartinAlfven; Wright, David; skocpol; Rounce, Graham; Richfield, Jon; W, Nick; wheelsonfire

    2015-11-01

    In reply to the physicsworld.com news article “Are Faraday cages less effective than previously thought?” (15 September, http://ow.ly/SfklO), about a study that indicated, based on mathematical modelling, that conducting wire-mesh cages may not be as good at excluding electromagnetic radiation as is commonly assumed.

  11. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  12. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  13. Cage-based performance capture

    CERN Document Server

    Savoye, Yann

    2014-01-01

    Nowadays, highly-detailed animations of live-actor performances are increasingly easier to acquire and 3D Video has reached considerable attentions in visual media production. In this book, we address the problem of extracting or acquiring and then reusing non-rigid parametrization for video-based animations. At first sight, a crucial challenge is to reproduce plausible boneless deformations while preserving global and local captured properties of dynamic surfaces with a limited number of controllable, flexible and reusable parameters. To solve this challenge, we directly rely on a skin-detached dimension reduction thanks to the well-known cage-based paradigm. First, we achieve Scalable Inverse Cage-based Modeling by transposing the inverse kinematics paradigm on surfaces. Thus, we introduce a cage inversion process with user-specified screen-space constraints. Secondly, we convert non-rigid animated surfaces into a sequence of optimal cage parameters via Cage-based Animation Conversion. Building upon this re...

  14. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  15. Blueprints for dodecahedral DNA cages

    International Nuclear Information System (INIS)

    Cage structures engineered from nucleic acids are of interest in nanotechnology, for example as a means of drug delivery (Destito et al 2007). Until now, most experimentally realized DNA cages have crystallographic symmetry, such as the shape of a cube (Chen and Seeman 1991 Nature 350 631-3), a tetrahedron (Goodman et al 2005 Science 310 1661-5), an octahedron (Shih et al 2004 Nature 427 618-21) or a truncated octahedron (Zhang and Seeman 1994 J. Am. Chem. Soc. 116 1661-9). Two examples of cages with non-crystallographic symmetry, a dodecahedron and a buckyball, have been realized recently (He et al 2008 Nature 452 198-201). A characteristic feature of these realizations is the fact that the cages are built from a number of identical building blocks called tiles: 20 for the case of the dodecahedron, and 60 for the case of the buckyball. We derive here a blueprint for the organization of nucleic acid in a dodecahedral cage such that the final product has a minimal number of strands. In particular, we show that a dodecahedral cage can be realized in terms of only two circular DNA molecules. We focus on the dodecahedral cage, because the volume to surface ratio of such a cage is larger than that of its crystallographic counterparts given the same fixed radial distance of the polyhedral vertices from the centre of the structure, whilst still requiring a smaller complexity than the truncated icosahedron (buckyball). We therefore expect that the dodecahedral DNA cages discussed here may be of interest in further applications in nanotechnology

  16. Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein.

    Science.gov (United States)

    Simonyan, R A; Skulachev, V P

    1998-09-25

    Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6 degrees C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances delta psi in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the 'mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used). PMID:9771898

  17. Unraveling biochemical pathways affected by mitochondrial dysfunctions using metabolomic approaches.

    Science.gov (United States)

    Demine, Stéphane; Reddy, Nagabushana; Renard, Patricia; Raes, Martine; Arnould, Thierry

    2014-01-01

    Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. PMID:25257998

  18. Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

    Directory of Open Access Journals (Sweden)

    Stéphane Demine

    2014-09-01

    Full Text Available Mitochondrial dysfunction(s (MDs can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy in the obesity and insulin resistance thematic.

  19. *602044 UNCOUPLING PROTEIN 3; UCP3 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 602044 FIELD TI 602044 UNCOUPLING PROTEIN 3; UCP3 FIELD TX CLONING Boss et al. (1997) a ... 3 is expressed as a 2.3-kb message in skeletal muscle an d heart. In rat tissue, UCP3 transcripts were foun ... n the levels of UCP2 and UCP3 mRNA in skeletal muscle an d adipose tissue from both lean ... and obese individu ...

  20. A procedure for noise uncoupling in laser interferometry

    International Nuclear Information System (INIS)

    A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output

  1. A procedure for noise uncoupling in laser interferometry

    CERN Document Server

    Barone, F; Rosa, R D; Eleuteri, A; Milano, L; Qipiani, K

    2002-01-01

    A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output.

  2. Noise studies of uncoupled dc-SQUIDs

    International Nuclear Information System (INIS)

    We have performed noise measurements of uncoupled dc SQUIDs with similar square washer geometries. Mappings consisting of hundreds of flux noise measurements at different points of operation have been carried out using a dc SQUID preamplifier and a computer controlled measurement system. The white and low frequency noise, dynamic resistance, and the flux-to-voltage transfer function have been measured. The dc SQUID noise performance is described using equivalent current noise sources, and the voltage noise is observed to be linearly proportional to dynamic resistance Rdyn. (orig.)

  3. Physical Fitness and Mitochondrial Respiratory Capacity in Horse Skeletal Muscle

    OpenAIRE

    Votion, Dominique-Marie; Gnaiger, Erich; Lemieux, Hélène; Mouithys-Mickalad, Ange; Serteyn, Didier

    2012-01-01

    Background Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general. Methodology/Principal Findings We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0–2.5 mg) permeabilized muscle fibres sampled from triceps ...

  4. An evaluation of intra-cage ventilation in three animal caging systems.

    Science.gov (United States)

    Keller, L S; White, W J; Snider, M T; Lang, C M

    1989-05-01

    Although temperature and relative humidity have been quantitated and their effects on research data studied, few studies have measured the air turnover rates at cage level. We evaluated the air distribution and air turnover rates in unoccupied shoe-box mouse cages, filter-top covered cages and shoe-box mouse cages housed in a flexible film isolator by using discontinuous gas chromatography/mass spectrometry and smoke. Results showed that air turnover was most rapid in the unoccupied shoe-box mouse cage and slowest in the filter-top covered cage. Placing mice in the filter-top covered cage did not significantly improve the air turnover rate. Although filter-top covered cages reduce cage-to-cage transmission of disease, the poor airflow observed within these cages could lead to a buildup of gaseous pollutants that may adversely affect the animal's health. PMID:2724925

  5. Cage culture of sea bass in Malaysia

    OpenAIRE

    1994-01-01

    The article discusses the cage culture practice of sea bass (Lates calcarifer) in Malaysia. Problems on feed and seed supply and overcrowding are also discussed. Despite these problems, seabass cage culture still continuously booms.

  6. DNA Cages with Icosahedral Symmetry in Bionanotechnology

    Science.gov (United States)

    Jonoska, Nataša; Taormina, Anne; Twarock, Reidun

    Blueprints for polyhedral cages with icosahedral symmetry made of circular DNA molecules are provided. The basic rule is that every edge of the cage is met twice in opposite directions by the DNA strand(s), and vertex junctions are realized by a set of admissible junction types. As nanocontainers for cargo storage and delivery, the icosidodecahedral cages are of special interest because they have the largest volume per surface ratio of all cages discussed here.

  7. A Mobile Phone Faraday Cage

    Science.gov (United States)

    French, M. M. J.

    2011-01-01

    A Faraday cage is an interesting physical phenomenon where an electromagnetic wave can be excluded from a volume of space by enclosure with an electrically conducting material. The practical application of this in the classroom is to block the signal to a mobile phone by enclosing it in a metal can. The background of the physics behind this is…

  8. Gating of the Mitochondrial Permeability Transition Pore by Long Chain Fatty Acyl Analogs in Vivo*

    OpenAIRE

    Samovski, Dmitri; Kalderon, Bella; Yehuda-Shnaidman, Einav; Bar-Tana, Jacob

    2009-01-01

    The role played by long chain fatty acids (LCFA) in promoting energy expenditure is confounded by their dual function as substrates for oxidation and as putative classic uncouplers of mitochondrial oxidative phosphorylation. LCFA analogs of the MEDICA (MEthyl-substituted DICarboxylic Acids) series are neither esterified into lipids nor β-oxidized and may thus simulate the uncoupling activity of natural LCFA in vivo, independently of their substrate role. Treatment of rats or cell lines with M...

  9. Seismic coupling and uncoupling at subduction zones

    Science.gov (United States)

    Ruff, L.; Kanamori, H.

    1983-01-01

    Some of the correlations concerning the properties of subduction zones are reviewed. A quantitative global comparison of many subduction zones reveals that the largest earthquakes occur in zones with young lithosphere and fast convergence rates. Maximum earthquake size is directly related to the asperity distribution on the fault plane. This observation can be translated into a simple model of seismic coupling where the horizontal compressive stress between two plates is proportional to the ratio of the summed asperity area to the total area of the contact surface. Plate age and rate can control asperity distribution directly through the horizontal compressive stress associated with the vertical and horizontal velocities of subducting slabs. The basalt to eclogite phase change in the down-going oceanic crust may be largely responsible for the uncoupling of subduction zones below a depth of about 40 km.

  10. Electronic cages for living cells.

    Science.gov (United States)

    Al Saeed, Sarah; Bakewell, David J

    2015-08-01

    Design and construction of an electronic cage is described which enables real-time manipulation of live and dead eukaryotic cells. Non-uniform, radio frequency (RF) AC electric fields are used to enable translational and rotational movement of cells, known as dielectrophoresis (DEP) and electro-rotation (EROT), and distinguish their state as viable and non-viable. A concentric multilayered mathematical model, applicable for eukaryotic cells, is also developed, coded and implemented. The simulations predict three dielectric dispersions in the DEP and EROT spectra, though in practice the third is very small so that two are observed. The cage is part of a multi-staged project incorporating controller and DEP/EROT digital signal generator and image processing. PMID:26736401

  11. Expression of human uncoupling protein-3 in insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan

    OpenAIRE

    Humphrey, Dickon M.; Toivonen, Janne M.; Giannakou, Maria; Partridge, Linda; Brand, Martin D.

    2009-01-01

    Abstract Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by increasing the proton conductance of the inner membrane and through this effect could decrease ROS production, ameliorate oxidative stress and extend lifespan. We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific expression of human UCP3 (hUCP3) in adult Drosophila melanogaster affected lifespan. Low, ubiquitous expression of hUCP3 at levels found in rodent skeletal mus...

  12. Mitochondrial Morphology and Fundamental Parameters of the Mitochondrial Respiratory Chain Are Altered in Caenorhabditis elegans Strains Deficient in Mitochondrial Dynamics and Homeostasis Processes

    Science.gov (United States)

    Luz, Anthony L.; Rooney, John P.; Kubik, Laura L.; Gonzalez, Claudia P.; Song, Dong Hoon; Meyer, Joel N.

    2015-01-01

    Mitochondrial dysfunction has been linked to myriad human diseases and toxicant exposures, highlighting the need for assays capable of rapidly assessing mitochondrial health in vivo. Here, using the Seahorse XFe24 Analyzer and the pharmacological inhibitors dicyclohexylcarbodiimide and oligomycin (ATP-synthase inhibitors), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (mitochondrial uncoupler) and sodium azide (cytochrome c oxidase inhibitor), we measured the fundamental parameters of mitochondrial respiratory chain function: basal oxygen consumption, ATP-linked respiration, maximal respiratory capacity, spare respiratory capacity and proton leak in the model organism Caenhorhabditis elegans. Since mutations in mitochondrial homeostasis genes cause mitochondrial dysfunction and have been linked to human disease, we measured mitochondrial respiratory function in mitochondrial fission (drp-1)-, fusion (fzo-1)-, mitophagy (pdr-1, pink-1)-, and electron transport chain complex III (isp-1)-deficient C. elegans. All showed altered function, but the nature of the alterations varied between the tested strains. We report increased basal oxygen consumption in drp-1; reduced maximal respiration in drp-1, fzo-1, and isp-1; reduced spare respiratory capacity in drp-1 and fzo-1; reduced proton leak in fzo-1 and isp-1; and increased proton leak in pink-1 nematodes. As mitochondrial morphology can play a role in mitochondrial energetics, we also quantified the mitochondrial aspect ratio for each mutant strain using a novel method, and for the first time report increased aspect ratios in pdr-1- and pink-1-deficient nematodes. PMID:26106885

  13. Uncoupling and reactive oxygen species (ROS)--a double-edged sword for β-cell function? "Moderation in all things".

    Science.gov (United States)

    Collins, Sheila; Pi, Jingbo; Yehuda-Shnaidman, Einav

    2012-12-01

    The ability of the mitochondrion to (a) manage fuel import to oxidize for adenosine tri-phosphate (ATP) generation while (b) protecting itself and the cellular environment from electron leak, which can generate highly reactive oxygen species (ROS) is a delicate balancing act. ATP is the currency of the cell and as such serves a signaling function as a substrate partner to many kinases and ion channels. While various ROS species have been viewed as a dangerous and toxic group of molecules, it also has a role as a signal derived from mitochondria, as well as other enzymatic sources: a double-edged sword. Current efforts to understand the biochemical mechanisms affected by ROS as a signal--usually noted to be hydrogen peroxide (H(2)O(2))--are exciting, but this duality of ROS effects also pose challenges in managing its levels to protect cells. The mitochondrial uncoupling protein-2 (UCP2), UCP3, and the permeability transition pore have been integral to efforts to try to understand what role mitochondrial-derived ROS have in cells. In this piece we reflect on mitochondrial ROS and uncoupling proteins as signaling regulators. It seems that when it comes to ROS and uncoupling the proverb "Moderation in all things" is apt. PMID:23168277

  14. Polymers containing borane or carborane cage compounds and related applications

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, III, Daniel E; Eastwood, Eric A

    2013-04-23

    Polymers comprising residues of cage compound monomers having at least one polyalkoxy silyl substituent are provided. The cage compound monomers are selected from borane cage compound monomers comprising at least 7 cage atoms and/or carborane cage compound monomers comprising 7 to 11 cage compound monomers. Such polymers can further comprise one or more reactive matrices and/or co-monomers covalently bound with the cage compound monomer residues. Articles of manufacture comprising such polymers are also disclosed.

  15. Mitochondrial haplogroups

    DEFF Research Database (Denmark)

    Benn, Marianne; Schwartz, Marianne; Nordestgaard, Børge G;

    2008-01-01

    Rare mutations in the mitochondrial genome may cause disease. Mitochondrial haplogroups defined by common polymorphisms have been associated with risk of disease and longevity. We tested the hypothesis that common haplogroups predict risk of ischemic cardiovascular disease, morbidity from other...

  16. Uncoupling protein 3 expression and intramyocellular lipid accumulation by NMR following local burn trauma.

    Science.gov (United States)

    Zhang, Qunhao; Cao, Haihui; Astrakas, Loukas G; Mintzopoulos, Dionyssios; Mindrinos, Michael N; Schulz, John; Tompkins, Ronald G; Rahme, Laurence G; Tzika, A Aria

    2006-12-01

    Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e.g., starvation, fasting, cancer, sepsis). The aim of this study was to explore the effects of burn trauma on UCP3 expression, intramyocellular lipids, and plasma-free fatty acids. Mice were studied at 6 h, 1 d and 3 d after nonlethal hindlimb burn trauma. Intramyocellular lipids in hindlimb skeletal muscle samples collected from burned and normal mice were measured using 1H NMR spectroscopy on a Bruker 14.1 Tesla spectrometer at 4 degrees C. UCP3 mRNA and protein levels were also measured in these samples. Plasma-free fatty acids were measured in burned and normal mice. Local burn trauma was found to result in: 1) upregulation of UCP3 mRNA and protein expression in hindlimb myoskeletal mitochondria by 6 h postburn; 2) increased intramyocellular lipids; and 3) increased plasma-free fatty acids. Our findings show that the increase in UCP3 after burn trauma may be linked to burn-induced alterations in lipid metabolism. Such a link could reveal novel insights into how processes related to energy metabolism are controlled in burn and suggest that induction of UCP3 by burn in skeletal muscle is protective by either activating cellular redox signaling and/or mitochondrial uncoupling. PMID:17089030

  17. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

    Directory of Open Access Journals (Sweden)

    Jakob D Wikstrom

    Full Text Available BACKGROUND: The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets. METHODOLOGY/PRINCIPAL FINDINGS: The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets. CONCLUSIONS/SIGNIFICANCE: The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

  18. Cleaning Animals' Cages With Little Water

    Science.gov (United States)

    Harman, Benjamin J.

    1989-01-01

    Proposed freeze/thaw method for cleaning animals' cages requires little extra weight and consumes little power and water. Cleaning concept developed for maintaining experimental rat cages on extended space missions. Adaptable as well to similar use on Earth. Reduces cleaning time. Makes use of already available facilities such as refrigerator, glove box, and autoclave. Rat waste adheres to steel-wire-mesh floor of cage. Feces removed by loosening action of freezing-and-thawing process, followed by blast of air.

  19. Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

    International Nuclear Information System (INIS)

    Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes

  20. Listening to Cage: Nonintentional philosophy and music

    Directory of Open Access Journals (Sweden)

    Richard Fleming

    2016-12-01

    Full Text Available Listening to Cage: Nonintentional Philosophy and Music threads together the writings of ordinary language philosophy and the music of John Cage, responding specifically to requests made by Cage and Stanley Cavell. While many texts downplay or ignore the philosophical demands in Cage’s music and other texts find grandiose spiritual and philosophical material tied to his work, this text rejects both efforts. It challenges the basic directions of the growing secondary source material on Cage, finding it largely contrary to what Cage himself and his music teaches. That secondary material constantly offers an intentional approach to the music which is to make Cage understandable or easier to understand. The present text makes him appropriately difficult and basically unapproachable, asking the reader for serious acknowledgment of what Cage says he does, namely, “I have nothing to say and I am saying it.” While there is little hope of stopping the Cage industry that academia and publishers have grown, this text wishes at least to try to slow it down. The footnotes of this text include direct conversation material with Cage from the 1980s and 1990s regarding many subjects—his own compositions, our life struggles, remarks on Wittgenstein, Thoreau, philosophy, and music—all with a new context for their hearing.

  1. Humidity and Cage and Bedding Temperatures in Unoccupied Static Mouse Caging after Steam Sterilization

    OpenAIRE

    Ward, Gina M; Cole, Kelly; Faerber, Jennifer; Hankenson, F Claire

    2009-01-01

    Contemporary rodent caging and equipment often are sterilized by steam autoclaves prior to use in facilities. This work assessed the microenvironment of unoccupied static mouse cages after steam sterilization to determine when internal temperatures had cooled to levels appropriate for rodent housing. Polycarbonate static cages containing food and corncob bedding were stacked (10 rows × 7 columns) in duplicate (front and back; n = 140 cages) on a storage truck and autoclaved to 249 °F (121 °C)...

  2. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence.

    Directory of Open Access Journals (Sweden)

    João F Passos

    2007-05-01

    Full Text Available Aging is an inherently stochastic process, and its hallmark is heterogeneity between organisms, cell types, and clonal populations, even in identical environments. The replicative lifespan of primary human cells is telomere dependent; however, its heterogeneity is not understood. We show that mitochondrial superoxide production increases with replicative age in human fibroblasts despite an adaptive UCP-2-dependent mitochondrial uncoupling. This mitochondrial dysfunction is accompanied by compromised [Ca(2+]i homeostasis and other indicators of a retrograde response in senescent cells. Replicative senescence of human fibroblasts is delayed by mild mitochondrial uncoupling. Uncoupling reduces mitochondrial superoxide generation, slows down telomere shortening, and delays formation of telomeric gamma-H2A.X foci. This indicates mitochondrial production of reactive oxygen species (ROS as one of the causes of replicative senescence. By sorting early senescent (SES cells from young proliferating fibroblast cultures, we show that SES cells have higher ROS levels, dysfunctional mitochondria, shorter telomeres, and telomeric gamma-H2A.X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan.

  3. Uncoupled thermoelasticity solutions applied on beam dumps

    Science.gov (United States)

    Ouzia, A.; Antonakakis, T.

    2016-06-01

    In particle accelerators the process of beam absorption is vital. At CERN particle beams are accelerated at energies of the order of TeV. In the event of a system failure or following collisions, the beam needs to be safely absorbed by dedicated protecting blocks. The thermal shock caused by the rapid energy deposition within the absorbing block causes thermal stresses that may rise above critical levels. The present paper provides a convenient expression of such stresses under hypotheses described hereafter. The temperature field caused by the beam energy deposition is assumed to be Gaussian. Such a field models a non-diffusive heat deposition. These effects are described as thermoelastic as long as the stresses remain below the proportional limit and can be analytically modeled by the coupled equations of thermoelasticity. The analytical solution to the uncoupled thermoelastic problem in an infinite domain is presented herein and matched with a finite unit radius sphere. The assumption of zero diffusion as well as the validity of the match with a finite geometry is quantified such that the obtained solutions can be rigorously applied to real problems. Furthermore, truncated series solutions, which are not novel, are used for comparison purposes. All quantities are nondimensional and the problem reduces to a dependence of five dimensionless parameters. The equations of elasticity are presented in the potential formulation where the shear potential is assumed to be nil due to the source being a gradient and the absence of boundaries. Nevertheless equivalent three-dimensional stresses are computed using the compressive potential and optimized using standard analytical optimization methods. An alternative algorithm for finding the critical points of the three-dimensional stress function is presented. Finally, a case study concerning the proton synchrotron booster dump is presented where the aforementioned analytical solutions are used and the preceding assumptions

  4. Mitochondrial vasculopathy

    Science.gov (United States)

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-01-01

    Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications. PMID:27231520

  5. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  6. Natural and Semisynthetic Mammea-Type Isoprenlated Dihydroxycoumarins Uncouple Cellular Respiration

    Science.gov (United States)

    Du, Lin; Mahdi, Fakhri; Jekabsons, Mika B.; Nagle, Dale G.; Zhou, Yu-Dong

    2011-01-01

    In an effort to identify natural product-based molecular-targeted antitumor agents, mammea-type coumarins from the tropical/subtropical plant Mammea americana were found to inhibit the activation of HIF-1 (hypoxia-inducible factor-1) in human breast and prostate tumor cells. In addition to the recently reported mammea E/BB (15), bioassay-guided fractionation of the active extract yielded fourteen mammea-type coumarins including three new compounds mammea F/BB 1 (1), mammea F/BA (2), and C/AA (3). The absolute configuration of C-1′ in 1 was determined by the modified Mosher’s method on a methylated derivative. These coumarins were evaluated for their effects on mitochondrial respiration, HIF-1 signaling, and tumor cell proliferation/viability. Acetylation of 1 afforded a triacetoxylated product (A-2) that inhibited HIF-1 activation with increased potency in both T47D (IC50 0.83 μM for hypoxia-induced) and PC3 cells (IC50 0.94 μM for hypoxia-induced). Coumarins possessing a 6-prenyl-8-(3-methyl-oxobutyl)-substituent pattern exhibited enhanced HIF-1 inhibitory effects. The O-methylated derivatives were less active at inhibiting HIF-1 and suppressing cell proliferation/viability. Mechanistic studies indicate that these compounds act as anionic protonophores that potently uncouple mitochondrial electron transport and disrupt hypoxic signaling. PMID:21214226

  7. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    International Nuclear Information System (INIS)

    Research highlights: → Invertebrates, for example amphioxus, do express uncoupling proteins. → Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. → UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  8. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kun [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Sun, Guoxun [Department of Hematology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001 (China); Lv, Zhiyuan; Wang, Chen [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Jiang, Xueyuan, E-mail: xueyuanjiang@yahoo.com.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Li, Donghai, E-mail: lidonghai@gmail.com [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Zhang, Chenyu, E-mail: cyzhang@nju.edu.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China)

    2010-10-01

    Research highlights: {yields} Invertebrates, for example amphioxus, do express uncoupling proteins. {yields} Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. {yields} UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  9. High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

    International Nuclear Information System (INIS)

    Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants

  10. Development of a no-wash assay for mitochondrial membrane potential using the styryl dye DASPEI

    DEFF Research Database (Denmark)

    Reveles Jensen, Kristian; Rekling, Jens C

    2010-01-01

    Mitochondrial dysfunction is a hallmark of several diseases and may also result from drugs with unwanted side effects on mitochondrial biochemistry. The mitochondrial membrane potential is a good indicator of mitochondrial function. Here, the authors have developed a no-wash mitochondrial membrane......-handling stability, and thus is suitable for large-scale screening efforts. In summary, the DASPEI assay is simple and rapid and may be of use in toxicological testing, drug target discovery, and mechanistic models of diseases involving mitochondrial dysfunction....... potential assay using 2-(4-(dimethylamino)styryl)-N-ethylpyridinium iodide (DASPEI), a rarely used mitochondrial potentiometric probe, in a 96-well format using a fluorescent plate reader. The assay was validated using 2 protonophores (CCCP, DNP), which are known uncouplers, and the neuroleptic thioridazine...

  11. Diabetes or peroxisome proliferator-activated receptor alpha agonist increases mitochondrial thioesterase I activity in heart

    Science.gov (United States)

    Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of pr...

  12. Imaging the Breakdown of Molecular Frame Dynamics through Rotational Uncoupling

    CERN Document Server

    Zipp, Lucas J; Bucksbaum, Philip H

    2016-01-01

    We have observed directly in the time domain the uncoupling of electron motion from the molecular frame due to rotational-electronic coupling in a molecular Rydberg system. In contrast to Born- Oppenheimer dynamics, in which the electron is firmly fixed to the molecular frame, there exists a regime of molecular dynamics known as $l$-uncoupling where the motion of a non-penetrating Rydberg electron decouples from the instantaneous alignment of the molecular frame. We have imaged this unusual regime in time-dependent photoelectron angular distributions of a coherently prepared electron wave packet in the 4$f$ manifold of $N_2$.

  13. Mitochondrial Myopathy

    Science.gov (United States)

    ... NINDS supports research focused on effective treatments and cures for mitochondrial myopathies and other mitochondrial diseases. Scientists are investigating the possible benefits of exercise programs and nutritional supplements, primarily natural and synthetic versions of CoQ10. While CoQ10 has ...

  14. Active cage model of glassy dynamics.

    Science.gov (United States)

    Fodor, Étienne; Hayakawa, Hisao; Visco, Paolo; van Wijland, Frédéric

    2016-07-01

    We build up a phenomenological picture in terms of the effective dynamics of a tracer confined in a cage experiencing random hops to capture some characteristics of glassy systems. This minimal description exhibits scale invariance properties for the small-displacement distribution that echo experimental observations. We predict the existence of exponential tails as a crossover between two Gaussian regimes. Moreover, we demonstrate that the onset of glassy behavior is controlled only by two dimensionless numbers: the number of hops occurring during the relaxation of the particle within a local cage and the ratio of the hopping length to the cage size. PMID:27575182

  15. Mitochondrial cytopathies.

    Science.gov (United States)

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-09-01

    Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Most of mitochondrial proteins are encoded by the nuclear DNA (nDNA) whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction which leads to a wide range of cellular perturbations including aberrant calcium homeostasis, excessive reactive oxygen species production, dysregulated apoptosis, and insufficient energy generation to meet the needs of various organs, particularly those with high energy demand. Impaired mitochondrial function in various tissues and organs results in the multi-organ manifestations of mitochondrial diseases including epilepsy, intellectual disability, skeletal and cardiac myopathies, hepatopathies, endocrinopathies, and nephropathies. Defects in nDNA genes can be inherited in an autosomal or X-linked manners, whereas, mtDNA is maternally inherited. Mitochondrial diseases can result from mutations of nDNA genes encoding subunits of the electron transport chain complexes or their assembly factors, proteins associated with the mitochondrial import or networking, mitochondrial translation factors, or proteins involved in mtDNA maintenance. MtDNA defects can be either point mutations or rearrangements. The diagnosis of mitochondrial disorders can be challenging in many cases and is based on clinical recognition, biochemical screening, histopathological studies, functional studies, and molecular genetic testing. Currently, there are no satisfactory therapies available for mitochondrial disorders that significantly alter the course of the disease. Therapeutic options include symptomatic treatment, cofactor supplementation, and exercise. PMID:26996063

  16. Potent non-protonophore uncouplers acting on natural and artificial membranes

    OpenAIRE

    Routaboul, Jean-Marc; Taillandier, Georges; Tissut, Michel

    1994-01-01

    The uncoupling properties of 10 new symmetrical phenylureas, including N,N′-bis-(4-trifluoromethylphenyl)-urea, were investigated. Four compounds were shown to be powerful uncouplers. The result is a proton transfer across the organelle's membrane. These symmetrical phenylureas cannot be classified among the main class of uncouplers (acting through a protonophoric mechanism), due to their inability to exchange protons in a range of pHs between 2 and 9. The most potent uncouplers of the ...

  17. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  18. Compositions containing borane or carborane cage compounds and related applications

    Science.gov (United States)

    Bowen, III, Daniel E; Eastwood, Eric A

    2013-05-28

    Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

  19. Compositions containing borane or carborane cage compounds and related applications

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, III, Daniel E; Eastwood, Eric A

    2014-11-11

    Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

  20. Compositions containing borane or carborane cage compounds and related applications

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, III, Daniel E.; Eastwood, Eric A.

    2015-09-15

    Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

  1. Oxidative stress, thermogenesis and evolution of uncoupling proteins

    OpenAIRE

    Rial, Eduardo; Zardoya, Rafael

    2009-01-01

    The uncoupling protein UCP1 provides eutherian mammals with an efficient thermogenic mechanism. Recent work published in BMC Evolutionary Biology, following the identification of UCP1 orthologs in non-eutherians, concludes that this unique function appeared after sequence divergence and purifying selection that allowed functional co-option.

  2. Synthesis of caged Garcinia xanthone analogues

    OpenAIRE

    Cho, Woo Cheal

    2009-01-01

    A new synthetic strategy is developed toward the synthesis of the caged Garcinia xanthone analogues. The key to the strategy is a Pd-catalyzed reverse prenylation reaction. This new synthetic approach provides a rapid and efficient access to various caged analogues, including cluvenone which is known to induce apoptosis and exhibit significant cytotoxicity in various cancer cell lines. Evaluation of their growth inhibitory activities also leads to identification of the pharmacophoric motif of...

  3. Mitochondrial reactive oxygen species modulate mosquito susceptibility to Plasmodium infection.

    Directory of Open Access Journals (Sweden)

    Renata L S Gonçalves

    Full Text Available BACKGROUND: Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS that modulate redox metabolism. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1, is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. CONCLUSION: We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection.

  4. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    Science.gov (United States)

    Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Oliveira, Pedro L.; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925

  5. Welfare assessment of laying hens in furnished cages and non-cage systems: an on-farm comparison

    NARCIS (Netherlands)

    Rodenburg, T.B.; Tuyttens, F.; Reu, de K.; Herman, L.; Zoons, J.; Sonck, B.

    2008-01-01

    From 2012 onwards, all laying hens in Europe will need to be housed either in furnished cages or non-cage systems (aviaries or floor-housing systems). In terms of animal welfare, furnished cages and non-cage systems both have advantages and disadvantages. Data on direct comparisons between the two,

  6. Control mechanisms in mitochondrial oxidative phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Jana Hroudová; Zdeněk Fi(s)ar

    2013-01-01

    Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism–firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.

  7. Uncoupler resistance in E. coli Tuv and Cuv is due to the exclusion of uncoupler by the outer membrane

    DEFF Research Database (Denmark)

    Haworth, Robert S.; Jensen, Peter Ruhdal; Michelsen, Ole;

    1990-01-01

    freely permeable to both TPP+ and hydroxymethylinulin. Tuv and Cuv are able to exclude these compounds. EDTA treatment was necessary prior to measuring membrane potentials in Tuv and Cuv. Under conditions where Δψ could be measured, uncouplers acted to dissipate Δψ with equal potency in all strains...

  8. Mitochondrial Diseases

    Science.gov (United States)

    ... in your body tissues. If you have a metabolic disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are small structures that produce energy in ...

  9. Novel water-soluble methanofullerenes C60[C13H18O4(OH)4]6 and C60[C9H10O4(OH)4]6: Promising uncouplers of respiration and phosphorylation.

    Science.gov (United States)

    Kalacheva, Natalia V; Gubskaya, Valentina P; Fazleeva, Guzel M; Igtisamova, Gulzada R; Nuretdinov, Ildus A; Rizvanov, Albert A; Cherepnev, Georgi V

    2015-11-15

    Here, we report for the first time on two novel water-soluble polyol-methanofullerenes which uncouple respiration and oxidative phosphorylation. A cytofluorimetric JC-1-based ratiometric assay was used to quantify mitochondrial potential Ψm in Yarrowia lipolytica cells exposed to the fullerenes tested. Both methanofullerenes significantly downregulated Ψm, thereby decreasing the subset of cells with high mitochondrial potential compared with intact control cells. The Ψm-low subset of Yarrowia lipolytica cells resulted from methanofullerenes exposure preserved physiological cell size and granularity patterns. PMID:26483197

  10. Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Wickes, W.A.; Wiskich, J.T.

    1976-01-01

    The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

  11. Materials for Chemical-Looping with Oxygen Uncoupling

    OpenAIRE

    Tobias Mattisson

    2013-01-01

    Chemical-looping with oxygen uncoupling (CLOU) is a novel combustion technology with inherent separation of carbon dioxide. The process is a three-step process which utilizes a circulating oxygen carrier to transfer oxygen from the combustion air to the fuel. The process utilizes two interconnected fluidized bed reactors, an air reactor and a fuel reactor. In the fuel reactor, the metal oxide decomposes with the release of gas phase oxygen (step 1), which reacts directly with the fuel through...

  12. Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance

    DEFF Research Database (Denmark)

    Vernochet, Cecile; Mourier, Arnaud; Bezy, Olivier;

    2012-01-01

    oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has...

  13. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  14. Phosphonate Based High Nuclearity Magnetic Cages.

    Science.gov (United States)

    Sheikh, Javeed Ahmad; Jena, Himanshu Sekhar; Clearfield, Abraham; Konar, Sanjit

    2016-06-21

    Transition metal based high nuclearity molecular magnetic cages are a very important class of compounds owing to their potential applications in fabricating new generation molecular magnets such as single molecular magnets, magnetic refrigerants, etc. Most of the reported polynuclear cages contain carboxylates or alkoxides as ligands. However, the binding ability of phosphonates with transition metal ions is stronger than the carboxylates or alkoxides. The presence of three oxygen donor sites enables phosphonates to bridge up to nine metal centers simultaneously. But very few phosphonate based transition metal cages were reported in the literature until recently, mainly because of synthetic difficulties, propensity to result in layered compounds, and also their poor crystalline properties. Accordingly, various synthetic strategies have been followed by several groups in order to overcome such synthetic difficulties. These strategies mainly include use of small preformed metal precursors, proper choice of coligands along with the phosphonate ligands, and use of sterically hindered bulky phosphonate ligands. Currently, the phosphonate system offers a library of high nuclearity transition metal and mixed metal (3d-4f) cages with aesthetically pleasing structures and interesting magnetic properties. This Account is in the form of a research landscape on our efforts to synthesize and characterize new types of phosphonate based high nuclearity paramagnetic transition metal cages. We quite often experienced synthetic difficulties with such versatile systems in assembling high nuclearity metal cages. Few methods have been emphasized for the self-assembly of phosphonate systems with suitable transition metal ions in achieving high nuclearity. We highlighted our journey from 2005 until today for phosphonate based high nuclearity transition metal cages with V(IV/V), Mn(II/III), Fe(III), Co(II), Ni(II), and Cu(II) metal ions and their magnetic properties. We observed that

  15. Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.

    Science.gov (United States)

    Guarini, Giacinta; Kiyooka, Takahiko; Ohanyan, Vahagn; Pung, Yuh Fen; Marzilli, Mario; Chen, Yeong Renn; Chen, Chwen Lih; Kang, Patrick T; Hardwick, James P; Kolz, Christopher L; Yin, Liya; Wilson, Glenn L; Shokolenko, Inna; Dobson, James G; Fenton, Richard; Chilian, William M

    2016-05-01

    Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process. PMID:27040114

  16. Assessment of ToxCast Phase II for Mitochondrial Liabilities Using a High-Throughput Respirometric Assay.

    Science.gov (United States)

    Wills, Lauren P; Beeson, Gyda C; Hoover, Douglas B; Schnellmann, Rick G; Beeson, Craig C

    2015-08-01

    Previous high-throughput screens to identify mitochondrial toxicants used immortalized cell lines and focused on changes in mitochondrial membrane potential, which may not be sufficient and do not identify different types of mitochondrial dysfunction. Primary cultures of renal proximal tubule cells (RPTC) were examined with the Seahorse Extracellular Flux Analyzer to screen 676 compounds (5 μM; 1 h) from the ToxCast Phase II library for mitochondrial toxicants. Of the 676 compounds, 19 were classified as cytotoxicants, 376 were electron transport chain (ETC) inhibitors, and 5 were uncouplers. The remaining 276 compounds were examined after a 5-h exposure to identify slower acting mitochondrial toxicants. This experiment identified 3 cytotoxicants, 110 ETC inhibitors, and 163 compounds with no effect. A subset of the ToxCast Phase II library was also examined in immortalized human renal cells (HK2) to determine differences in susceptibility to mitochondrial toxicity. Of the 131 RPTC ETC inhibitors tested, only 14 were ETC inhibitors in HK2 cells. Of the 5 RPTC uncouplers, 1 compound was an uncoupler in HK2 cells. These results demonstrate that 73% (491/676) of the compounds in the ToxCast Phase II library compounds exhibit RPTC mitochondrial toxicity, overwhelmingly ETC inhibition. In contrast, renal HK2 cells are markedly less sensitive and only identified 6% of the compounds as mitochondrial toxicants. We suggest caution is needed when studying mitochondrial toxicity in immortalized cell lines. This information will provide mechanisms and chemical-based criteria for assessing and predicting mitochondrial liabilities of new drugs, consumer products, and environmental agents. PMID:25926417

  17. Multiple Targets for Drug-Induced Mitochondrial Toxicity.

    Science.gov (United States)

    Wallace, Kendall B

    2015-01-01

    Mitochondrial toxicity is rapidly gaining the interest of researchers and practitioners as a prominent liability in drug discovery and development, accounting for a growing proportion of preclinical drug attrition and post-market withdrawals or black box warnings by the U.S. FDA. To date, the focus of registries of drugs that elicit mitochondrial toxicity has been largely restricted to those that either inhibit the mitochondrial electron transport chain (ETC) or uncouple mitochondrial oxidative phosphorylation. Less appreciated are the toxicities that are secondary to the drug affecting either the molecular regulation, assembly or incorporation of the ETC into the inner mitochondrial membrane or those that limit substrate availability. The current article describes the complexities of molecular events and biochemical pathways required to sustain mitochondrial fidelity and substrate homeostasis with examples of drugs that interfere which the various pathways. The principal objective of this review is to shed light on the broader scope of drug-induced mitochondrial toxicities and how these secondary targets may account for a large portion of drug failures. PMID:25973981

  18. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    OpenAIRE

    Messina, Giovanni

    2016-01-01

    Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Scie...

  19. Cage RACK ventilation options for laboratory animal facilities.

    Science.gov (United States)

    Stakutis, Richard E

    2003-09-01

    Individually ventilated cage systems have become the method of choice for housing rodents. The author describes the various options for cage ventilation, from using supply and exhaust fans to directly connecting the racks to the building ventilation system. PMID:12966448

  20. High-throughput Transcriptome analysis, CAGE and beyond

    KAUST Repository

    Kodzius, Rimantas

    2008-11-25

    1. Current research - PhD work on discovery of new allergens - Postdoctoral work on Transcriptional Start Sites a) Tag based technologies allow higher throughput b) CAGE technology to define promoters c) CAGE data analysis to understand Transcription - Wo

  1. Chemical contamination of animal feeding systems: evaluation of two caging systems and standard cage-washing equipment.

    Science.gov (United States)

    Fox, J G; Helfrich-Smith, M E

    1980-12-01

    Sodium fluorescein was added as a tracer to an ager gel diet which was fed for 5 day to 90 of 180 rats housed in two different polycarbonate caging systems, shoe-box cages and suspension solid-bottom cages. Cage racks, supplementary equipment, and case washer surfaces were analysed for fluorescein both before and after a complete wash and rinse cycle. Efficacy of washing was greater than 99% for both the inside and outside of the suspended cages and greater than 99% for the inside, but only 93% for the outside, of the shoe-box cages. The shoe-box cages, which were larger than the suspended cages, were spaced closer together on the washer rack, which may account for this variation in cleaning effectiveness. The cage washer surfaces and the water, which was recirculated during each cycle, also became contaminated with fluorescein. Strict adherence to proper cage-washing procedures and careful selection of cage design are important factors in controlling the potential for residual contamination of caging and cage-washing equipment. PMID:7464031

  2. Convective Cage Release in Model Colloidal Glasses.

    Science.gov (United States)

    Jacob, Alan R; Poulos, Andreas S; Kim, Sunhyung; Vermant, Jan; Petekidis, George

    2015-11-20

    The mechanism of flow in glassy materials is interrogated using mechanical spectroscopy applied to model nearly hard sphere colloidal glasses during flow. Superimposing a small amplitude oscillatory motion orthogonal onto steady shear flow makes it possible to directly evaluate the effect of a steady state flow on the out-of-cage (α) relaxation as well as the in-cage motions. To this end, the crossover frequency deduced from the viscoelastic spectra is used as a direct measure of the inverse microstructural relaxation time, during flow. The latter is found to scale linearly with the rate of deformation. The microscopic mechanism of flow can then be identified as a convective cage release. Further insights are provided when the viscoelastic spectra at different shear rates are shifted to scale the alpha relaxation and produce a strain rate-orthogonal frequency superposition, the colloidal analogue of time temperature superposition in polymers with the flow strength playing the role of temperature. Whereas the scaling works well for the α relaxation, deviations are observed both at low and high frequencies. Brownian dynamics simulations point to the origins of these deviations; at high frequencies these are due to the deformation of the cages which slows down the short-time diffusion, while at low frequency, deviations are most probably caused by some mild hydroclustering. PMID:26636876

  3. Stabilizing a 22 karat nanogolden cage

    Science.gov (United States)

    Wang, Q.; Sun, Q.; Jena, P.

    2009-11-01

    Since the discovery of C60 fullerene, considerable efforts have been devoted to find other elements with similar hollow cage structures. However, search for hollow metallic cages with a diameter similar to that of C60 fullerene has been elusive. We describe a procedure for the rational design of metallic cages by suitably choosing their size, composition, and charge state. A 22 karat nanogolden cage with a diameter of about 8.5 Å and consisting of 12 Al and 20 Au atoms is found to be metastable, which can be stabilized by embedding a Mn4 cluster. In contrast to bulk Mn, which is antiferromagnetic, and isolated Mn4 cluster, which is ferromagnetic with a giant magnetic moment of 20μB, the Mn4@Al12Au20 endohedral complex exhibits magnetic bistability with 0μB and 14μB configurations being energetically nearly degenerate. These results, based on density functional theory, open the door to design a novel class of endohedral complexes with possible applications.

  4. 50 CFR 648.75 - Cage identification.

    Science.gov (United States)

    2010-10-01

    ... are issued, or if rendered null and void in accordance with 15 CFR part 904. (d) Return. Tags that... Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Clam and Ocean Quahog Fisheries § 648.75 Cage identification. Except as provided in § 648.76,...

  5. An Easy Synthesis of Two Cage Hydrocarbons.

    Science.gov (United States)

    Dong, Dao Cong

    1982-01-01

    Describes a simple, three-step synthesis of two cage molecules, birdcage hydrocarbon (VIII) and its homologue, the homobirdcage hydrocarbon IX. Indicates that all products are easily purified and formed in high yields in this activity suitable for advanced undergraduate laboratory courses. (Author/JN)

  6. Activation of brown adipose tissue mitochondrial GDP binding sites

    International Nuclear Information System (INIS)

    The primary function of brown adipose tissue (BAT) is heat production. This ability is attributed to the existence of a unique inner mitochondrial membrane protein termed the uncoupling protein or thermogenin. This protein is permeable to H+ and thus allows respiration (and therefore thermogenesis) to proceed at a rapid rate, independent of ADP phosphorylation. Proton conductance can be inhibited by the binding of purine nucleotides to the uncoupling protein. The binding of [3H]-GDP to BAT mitochondria is frequently used as a measure of BAT thermogenic activity. Rats fed a diet that was low but adequate in protein exhibited a decrease in feed efficiency. In addition, BAT thermogenesis was activated as indicated by an elevation in the level of GDP binding to BAT mitochondria. This phenomena occurred in older rats and persisted over time

  7. Activation of brown adipose tissue mitochondrial GDP binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Swick, A.G.

    1987-01-01

    The primary function of brown adipose tissue (BAT) is heat production. This ability is attributed to the existence of a unique inner mitochondrial membrane protein termed the uncoupling protein or thermogenin. This protein is permeable to H+ and thus allows respiration (and therefore thermogenesis) to proceed at a rapid rate, independent of ADP phosphorylation. Proton conductance can be inhibited by the binding of purine nucleotides to the uncoupling protein. The binding of (/sup 3/H)-GDP to BAT mitochondria is frequently used as a measure of BAT thermogenic activity. Rats fed a diet that was low but adequate in protein exhibited a decrease in feed efficiency. In addition, BAT thermogenesis was activated as indicated by an elevation in the level of GDP binding to BAT mitochondria. This phenomena occurred in older rats and persisted over time.

  8. Study on the Beam Quality of Uncoupled Laser Diode Arrays

    Institute of Scientific and Technical Information of China (English)

    GAO Chunqing; WEI Guanghui

    2001-01-01

    The beam quality of uncoupled laser diode array is studied theoretically and experimentally. By calculating the second order moments of the beam emitted from the laser diode array, the dependence of the M2-factor of the laser diode array on the M2-factor of the single emitter, the ratio of the emitting region to the non-emitting space, and the number of emitters, has been deduced. From the measurement of the beam propagation the M2-factor of a laser diode bar is experimentally determined. The measured M2-factor of the laser diode bar agrees with the theoretical prediction.

  9. Mitochondrial Evolution

    OpenAIRE

    Gray, Michael W

    2012-01-01

    Viewed through the lens of the genome it contains, the mitochondrion is of unquestioned bacterial ancestry, originating from within the bacterial phylum α-Proteobacteria (Alphaproteobacteria). Accordingly, the endosymbiont hypothesis—the idea that the mitochondrion evolved from a bacterial progenitor via symbiosis within an essentially eukaryotic host cell—has assumed the status of a theory. Yet mitochondrial genome evolution has taken radically different pathways in diverse eukaryotic lineag...

  10. Effects of the Czech Propolis on Sperm Mitochondrial Function

    Science.gov (United States)

    Cedikova, Miroslava; Miklikova, Michaela; Stachova, Lenka; Grundmanova, Martina; Tuma, Zdenek; Vetvicka, Vaclav; Zech, Nicolas; Kralickova, Milena; Kuncova, Jitka

    2014-01-01

    Propolis is a natural product that honeybees collect from various plants. It is known for its beneficial pharmacological effects. The aim of our study was to evaluate the impact of propolis on human sperm motility, mitochondrial respiratory activity, and membrane potential. Semen samples from 10 normozoospermic donors were processed according to the World Health Organization criteria. Propolis effects on the sperm motility and mitochondrial activity parameters were tested in the fresh ejaculate and purified spermatozoa. Propolis preserved progressive motility of spermatozoa in the native semen samples. Oxygen consumption determined in purified permeabilized spermatozoa by high-resolution respirometry in the presence of adenosine diphosphate and substrates of complex I and complex II (state OXPHOSI+II) was significantly increased in the propolis-treated samples. Propolis also increased uncoupled respiration in the presence of rotenone (state ETSII) and complex IV activity, but it did not influence state LEAK induced by oligomycin. Mitochondrial membrane potential was not affected by propolis. This study demonstrates that propolis maintains sperm motility in the native ejaculates and increases activities of mitochondrial respiratory complexes II and IV without affecting mitochondrial membrane potential. The data suggest that propolis improves the total mitochondrial respiratory efficiency in the human spermatozoa in vitro thereby having potential to improve sperm motility. PMID:25104965

  11. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  12. Chromatin Assembly at Kinetochores Is Uncoupled from DNA Replication

    Science.gov (United States)

    Shelby, Richard D.; Monier, Karine; Sullivan, Kevin F.

    2000-01-01

    The specification of metazoan centromeres does not depend strictly on centromeric DNA sequences, but also requires epigenetic factors. The mechanistic basis for establishing a centromeric “state” on the DNA remains unclear. In this work, we have directly examined replication timing of the prekinetochore domain of human chromosomes. Kinetochores were labeled by expression of epitope-tagged CENP-A, which stably marks prekinetochore domains in human cells. By immunoprecipitating CENP-A mononucleosomes from synchronized cells pulsed with [3H]thymidine we demonstrate that CENP-A–associated DNA is replicated in mid-to-late S phase. Cytological analysis of DNA replication further demonstrated that centromeres replicate asynchronously in parallel with numerous other genomic regions. In contrast, quantitative Western blot analysis demonstrates that CENP-A protein synthesis occurs later, in G2. Quantitative fluorescence microscopy and transient transfection in the presence of aphidicolin, an inhibitor of DNA replication, show that CENP-A can assemble into centromeres in the absence of DNA replication. Thus, unlike most genomic chromatin, histone synthesis and assembly are uncoupled from DNA replication at the kinetochore. Uncoupling DNA replication from CENP-A synthesis suggests that regulated chromatin assembly or remodeling could play a role in epigenetic centromere propagation. PMID:11086012

  13. Cline coupling and uncoupling in a stickleback hybrid zone.

    Science.gov (United States)

    Vines, Timothy H; Dalziel, Anne C; Albert, Arianne Y K; Veen, Thor; Schulte, Patricia M; Schluter, Dolph

    2016-05-01

    Strong ecological selection on a genetic locus can maintain allele frequency differences between populations in different environments, even in the face of hybridization. When alleles at divergent loci come into tight linkage disequilibrium, selection acts on them as a unit and can significantly reduce gene flow. For populations interbreeding across a hybrid zone, linkage disequilibria between loci can force clines to share the same slopes and centers. However, strong ecological selection on a locus can also pull its cline away from the others, reducing linkage disequilibrium and weakening the barrier to gene flow. We looked for this "cline uncoupling" effect in a hybrid zone between stream resident and anadromous sticklebacks at two genes known to be under divergent natural selection (Eda and ATP1a1) and five morphological traits that repeatedly evolve in freshwater stickleback. These clines were all steep and located together at the top of the estuary, such that we found no evidence for cline uncoupling. However, we did not observe the stepped shape normally associated with steep concordant clines. It thus remains possible that these clines cluster together because their individual selection regimes are identical, but this would be very surprising given their diverse roles in osmoregulation, body armor, and swimming performance. PMID:27061719

  14. Increased ER–mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress

    Science.gov (United States)

    Bravo, Roberto; Vicencio, Jose Miguel; Parra, Valentina; Troncoso, Rodrigo; Munoz, Juan Pablo; Bui, Michael; Quiroga, Clara; Rodriguez, Andrea E.; Verdejo, Hugo E.; Ferreira, Jorge; Iglewski, Myriam; Chiong, Mario; Simmen, Thomas; Zorzano, Antonio; Hill, Joseph A.; Rothermel, Beverly A.; Szabadkai, Gyorgy; Lavandero, Sergio

    2011-01-01

    Increasing evidence indicates that endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR), but that beyond a certain degree of ER damage, this response triggers apoptotic pathways. The general mechanisms of the UPR and its apoptotic pathways are well characterized. However, the metabolic events that occur during the adaptive phase of ER stress, before the cell death response, remain unknown. Here, we show that, during the onset of ER stress, the reticular and mitochondrial networks are redistributed towards the perinuclear area and their points of connection are increased in a microtubule-dependent fashion. A localized increase in mitochondrial transmembrane potential is observed only in redistributed mitochondria, whereas mitochondria that remain in other subcellular zones display no significant changes. Spatial re-organization of these organelles correlates with an increase in ATP levels, oxygen consumption, reductive power and increased mitochondrial Ca2+ uptake. Accordingly, uncoupling of the organelles or blocking Ca2+ transfer impaired the metabolic response, rendering cells more vulnerable to ER stress. Overall, these data indicate that ER stress induces an early increase in mitochondrial metabolism that depends crucially upon organelle coupling and Ca2+ transfer, which, by enhancing cellular bioenergetics, establishes the metabolic basis for the adaptation to this response. PMID:21628424

  15. Porous Organic Cages for Sulfur Hexafluoride Separation.

    Science.gov (United States)

    Hasell, Tom; Miklitz, Marcin; Stephenson, Andrew; Little, Marc A; Chong, Samantha Y; Clowes, Rob; Chen, Linjiang; Holden, Daniel; Tribello, Gareth A; Jelfs, Kim E; Cooper, Andrew I

    2016-02-10

    A series of porous organic cages is examined for the selective adsorption of sulfur hexafluoride (SF6) over nitrogen. Despite lacking any metal sites, a porous cage, CC3, shows the highest SF6/N2 selectivity reported for any material at ambient temperature and pressure, which translates to real separations in a gas breakthrough column. The SF6 uptake of these materials is considerably higher than would be expected from the static pore structures. The location of SF6 within these materials is elucidated by X-ray crystallography, and it is shown that cooperative diffusion and structural rearrangements in these molecular crystals can rationalize their superior SF6/N2 selectivity. PMID:26757885

  16. Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria

    Directory of Open Access Journals (Sweden)

    Servais Stéphane

    2010-04-01

    Full Text Available Abstract Background Although identified in several bird species, the biological role of the avian homolog of mammalian uncoupling proteins (avUCP remains extensively debated. In the present study, the functional properties of isolated mitochondria were examined in physiological or pharmacological situations that induce large changes in avUCP expression in duckling skeletal muscle. Results The abundance of avUCP mRNA, as detected by RT-PCR in gastrocnemius muscle but not in the liver, was markedly increased by cold acclimation (CA or pharmacological hyperthyroidism but was down-regulated by hypothyroidism. Activators of UCPs, such as superoxide with low doses of fatty acids, stimulated a GDP-sensitive proton conductance across the inner membrane of muscle mitochondria from CA or hyperthyroid ducklings. The stimulation was much weaker in controls and not observed in hypothyroid ducklings or in any liver mitochondrial preparations. The production of endogenous mitochondrial reactive oxygen species (ROS was much lower in muscle mitochondria from CA and hyperthyroid ducklings than in the control or hypothyroid groups. The addition of GDP markedly increased the mitochondrial ROS production of CA or hyperthyroid birds up to, or above, the level of control or hypothyroid ducklings. Differences in ROS production among groups could not be attributed to changes in antioxidant enzyme activities (superoxide dismutase or glutathione peroxidase. Conclusion This work provides the first functional in vitro evidence that avian UCP regulates mitochondrial ROS production in situations of enhanced metabolic activity.

  17. Cathodic Cage Plasma Nitriding: An Innovative Technique

    OpenAIRE

    de Sousa, R. R. M.; de Araújo, F. O.; da Costa, J. A. P.; A. de S. Brandim; de Brito, R. A.; Alves, C

    2012-01-01

    Cylindrical samples of AISI 1020, AISI 316, and AISI 420 steels, with different heights, were simultaneously treated by a new technique of ionic nitriding, entitled cathodic cage plasma nitriding (CCPN), in order to evaluate the efficiency of this technique to produce nitrided layers with better properties compared with those obtained using conventional ionic nitriding technique. This method is able to eliminate the edge effect in the samples, promoting a better uniformity of temperature, and...

  18. Titanium mesh cages (TMC) in spine surgery

    OpenAIRE

    Grob, Dieter; Daehn, Sylvia; Mannion, Anne F.

    2004-01-01

    The introduction of the titanium mesh cage (TMC) in spinal surgery has opened up a variety of applications that are realizable as a result of the versatility of the implant. Differing applications of TMCs in the whole spine are described in a series of 150 patients. Replacement and reinforcement of the anterior column represent the classic use of cylindrical TMCs. The TMC as a multisegmental concave support in kyphotic deformities and as a posterior interlaminar spacer or lamina replacement a...

  19. Trace element kinetics in caged Mytilus galloprovincialis

    OpenAIRE

    Richir, Jonathan; Lepoint, Gilles; Donnay, Annick; Gobert, Sylvie

    2014-01-01

    Trace elements (TEs) remain contaminants of concern because of their persistence, ability to concentrate in organisms and toxicity. The Mediterranean mussel Mytilus galloprovincialis Lamarck, 1819 is a relevant bioindicator of TE coastal contamination. However, little research has studied the combined influence of environmental condition changes and physiological processes on their kinetics in that species. Caged M. galloprovincialis were thus immerged in 2 contrasted pristine Corsican (Franc...

  20. Biomechanische Untersuchungen von LWS-Cages

    OpenAIRE

    Gottwald, Maria

    2004-01-01

    Fragestellung: Cages sind Implantate, die der Fusionierung von Wirbelkörpern dienen. Zu ihren wichtigsten biomechanischen Eigenschaften gehört die Gewährleistung einer hohen Stabilität unmittelbar nach Implantation - der Primärstabilität -, die Aufrechterhaltung dieser Stabilität auch nach wiederholten Belastungen - Langzeitstabilität - und eine geringe Sinterungsneigung, worunter man das eindringen der Implantate in die angrenzenden Wirbelkörper versteht. Ziel dieser Arbeit war es nun zwe...

  1. Calcium-induced alteration of mitochondrial morphology and mitochondrial-endoplasmic reticulum contacts in rat brown adipocytes.

    Science.gov (United States)

    Golic, I; Velickovic, K; Markelic, M; Stancic, A; Jankovic, A; Vucetic, M; Otasevic, V; Buzadzic, B; Korac, B; Korac, A

    2014-01-01

    Mitochondria are key organelles maintaining cellular bioenergetics and integrity, and their regulation of [Ca2+]i homeostasis has been investigated in many cell types. We investigated the short-term Ca-SANDOZ® treatment on brown adipocyte mitochondria, using imaging and molecular biology techniques. Two-month-old male Wistar rats were divided into two groups: Ca-SANDOZ® drinking or tap water (control) drinking for three days. Alizarin Red S staining showed increased Ca2+ level in the brown adipocytes of treated rats, and potassium pyroantimonate staining localized electron-dense regions in the cytoplasm, mitochondria and around lipid droplets. Ca-SANDOZ® decreased mitochondrial number, but increased their size and mitochondrial cristae volume. Transmission electron microscopy revealed numerous enlarged and fusioned-like mitochondria in the Ca-SANDOZ® treated group compared to the control, and megamitochondria in some brown adipocytes. The Ca2+ diet affected mitochondrial fusion as mitofusin 1 (MFN1) and mitofusin 2 (MFN2) were increased, and mitochondrial fission as dynamin related protein 1 (DRP1) was decreased. Confocal microscopy showed a higher colocalization rate between functional mitochondria and endoplasmic reticulum (ER). The level of uncoupling protein-1 (UCP1) was elevated, which was confirmed by immunohistochemistry and Western blot analysis. These results suggest that Ca-SANDOZ® stimulates mitochondrial fusion, increases mitochondrial-ER contacts and the thermogenic capacity of brown adipocytes. PMID:25308841

  2. Calcium-induced alteration of mitochondrial morphology and mitochondrial-endoplasmic reticulum contacts in rat brown adipocytes

    Directory of Open Access Journals (Sweden)

    I. Golic

    2014-09-01

    Full Text Available Mitochondria are key organelles maintaining cellular bioenergetics and integrity, and their regulation of [Ca2+]i homeostasis has been investigated in many cell types. We investigated the short-term Ca-SANDOZ® treatment on brown adipocyte mitochondria, using imaging and molecular biology techniques. Two-month-old male Wistar rats were divided into two groups: Ca-SANDOZ® drinking or tap water (control drinking for three days. Alizarin Red S staining showed increased Ca2+ level in the brown adipocytes of treated rats, and potassium pyroantimonate staining localized electron-dense regions in the cytoplasm, mitochondria and around lipid droplets. Ca-SANDOZ® decreased mitochondrial number, but increased their size and mitochondrial cristae volume. Transmission electron microscopy revealed numerous enlarged and fusioned-like mitochondria in the Ca-SANDOZ® treated group compared to the control, and megamitochondria in some brown adipocytes. The Ca2+ diet affected mitochondrial fusion as mitofusin 1 (MFN1 and mitofusin 2 (MFN2 were increased, and mitochondrial fission as dynamin related protein 1 (DRP1 was decreased. Confocal microscopy showed a higher colocalization rate between functional mitochondria and endoplasmic reticulum (ER. The level of uncoupling protein-1 (UCP1 was elevated, which was confirmed by immunohistochemistry and Western blot analysis. These results suggest that Ca-SANDOZ® stimulates mitochondrial fusion, increases mitochondrial-ER contacts and the thermogenic capacity of brown adipocytes

  3. Defects in mitochondrial fission protein dynamin-related protein 1 are linked to apoptotic resistance and autophagy in a lung cancer model.

    Directory of Open Access Journals (Sweden)

    Kelly Jean Thomas

    Full Text Available Evasion of apoptosis is implicated in almost all aspects of cancer progression, as well as treatment resistance. In this study, resistance to apoptosis was identified in tumorigenic lung epithelial (A549 cells as a consequence of defects in mitochondrial and autophagic function. Mitochondrial function is determined in part by mitochondrial morphology, a process regulated by mitochondrial dynamics whereby the joining of two mitochondria, fusion, inhibits apoptosis while fission, the division of a mitochondrion, initiates apoptosis. Mitochondrial morphology of A549 cells displayed an elongated phenotype-mimicking cells deficient in mitochondrial fission protein, Dynamin-related protein 1 (Drp1. A549 cells had impaired Drp1 mitochondrial recruitment and decreased Drp1-dependent fission. Cytochrome c release and caspase-3 and PARP cleavage were impaired both basally and with apoptotic stimuli in A549 cells. Increased mitochondrial mass was observed in A549 cells, suggesting defects in mitophagy (mitochondrial selective autophagy. A549 cells had decreased LC3-II lipidation and lysosomal inhibition suggesting defects in autophagy occur upstream of lysosomal degradation. Immunostaining indicated mitochondrial localized LC3 punctae in A549 cells increased after mitochondrial uncoupling or with a combination of mitochondrial depolarization and ectopic Drp1 expression. Increased inhibition of apoptosis in A549 cells is correlated with impeded mitochondrial fission and mitophagy. We suggest mitochondrial fission defects contribute to apoptotic resistance in A549 cells.

  4. Changes in GDP binding to brown adipose tissue mitochondria and the uncoupling protein

    International Nuclear Information System (INIS)

    Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of [3H]GDP. The effect of Mg2+ appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from rat BAT mitochondria. Application of this method indicates that uncoupling protein from cold-acclimated rats binds twice as much GDP as uncoupling protein from cold-acclimated rats that were briefly returned to thermoneutrality, paralleling changes in GDP binding to the mitochondria. Incubation of BAT mitochondria with Mg2+ led to a smaller increase in GDP binding to the subsequently purified uncoupling protein, suggesting that divalent cations may somehow participate in the regulation of the activity of the uncoupling protein

  5. Uncoupling effect of fatty acids in halo- and alkalotolerant bacterium Bacillus pseudofirmus FTU.

    Science.gov (United States)

    Popova, I V; Bodrova, M E; Mokhova, E N; Muntyan, M S

    2004-10-01

    Natural uncouplers of oxidative phosphorylation, long-chain non-esterified fatty acids, cause uncoupling in the alkalo- and halotolerant bacterium Bacillus pseudofirmus FTU. The uncoupling effect in the bacterial cells was manifested as decrease of membrane potential and increase of respiratory activity. The membrane potential decrease was detected only in bacterial cells exhausted by their endogenous substrates. In proteoliposomes containing reconstituted bacterial cytochrome c oxidase, fatty acids caused a "mild" uncoupling effect by reducing membrane potential only at low rate of membrane potential generation. "Free respiration" induced by the "mild" uncouplers, the fatty acids, can be considered as possible mechanism responsible for adaptation of the bacteria to a constantly changed environment. PMID:15527418

  6. Evaluation of a mitochondrial test for the determination of chemical toxicity

    OpenAIRE

    Shannon, Robert David

    1988-01-01

    The feasibility of using rat liver mitochondria respiratory parameters as a short-term toxicity test was investigated. Mitochondrial fractions were exposed to six concentrations of five chlorophenols. Respiratory parameters were measured and compared to control experiments. The toxicity of the chlorophenos, measured by the 50% uncoupling concentration (UC50), increased with increasing chloro substitution. The UC50 values for the five chlorophenols were compared to six phy...

  7. Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

    International Nuclear Information System (INIS)

    Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H2O2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H2O2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H2O2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

  8. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system.

    Science.gov (United States)

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D; Jelokhani-Niaraki, Masoud

    2015-01-01

    Mitochondrial inner membrane uncoupling proteins (UCPs) facilitate transmembrane (TM) proton flux and consequently reduce the membrane potential and ATP production. It has been proposed that the three neuronal human UCPs (UCP2, UCP4 and UCP5) in the central nervous system (CNS) play significant roles in reducing cellular oxidative stress. However, the structure and ion transport mechanism of these proteins remain relatively unexplored. Recently, we reported a novel expression system for obtaining functionally folded UCP1 in bacterial membranes and applied this system to obtain highly pure neuronal UCPs in high yields. In the present study, we report on the structure and function of the three neuronal UCP homologues. Reconstituted neuronal UCPs were dominantly helical in lipid membranes and transported protons in the presence of physiologically-relevant fatty acid (FA) activators. Under similar conditions, all neuronal UCPs also exhibited chloride transport activities that were partially inhibited by FAs. CD, fluorescence and MS measurements and semi-native gel electrophoresis collectively suggest that the reconstituted proteins self-associate in the lipid membranes. Based on SDS titration experiments and other evidence, a general molecular model for the monomeric, dimeric and tetrameric functional forms of UCPs in lipid membranes is proposed. In addition to their shared structural and ion transport features, neuronal UCPs differ in their conformations and proton transport activities (and possibly mechanism) in the presence of different FA activators. The differences in FA-activated UCP-mediated proton transport could serve as an essential factor in understanding and differentiating the physiological roles of UCP homologues in the CNS. PMID:26182433

  9. Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Guangsheng; Wang, Jianlu; Xu, Kesen; Dong, Jiahong

    2016-07-01

    Gemcitabine (GEM), a commonly used chemotherapeutic agent in hepatocellular carcinoma (HCC) patients, uses oxidative stress induction as a common effector pathway. However, GEM alone or in combination with oxaliplatin hardly renders any survival benefits to HCC patients. We have recently shown that this is part due to the overexpression of the mitochondrial uncoupling protein 2 (UCP2) that in turn mediates resistance to GEM in HCC patients. However, not much is known about regulatory mechanisms underlying UCP2 overexpression in HCC. Differential protein expression in HCC cell lines did not show a concomitant change in UCP2 transcript level, indicating post-transcriptional or post-translational regulatory mechanism. In situ analysis revealed that UCP2 is a putative target of miR-214 miR-214 expression is significantly down-regulated in HCC patient samples as compared with normal adjacent tissues and in cell line, human hepatoblastoma cells (HuH6), with high UCP2 protein expression. We demonstrated using miR-214 mimic and antagomir that the miRNA targeted UCP2 expression by directly targeting the wild-type, but not a miR-214 seed mutant, 3' UTR of UCP2 Overexpression of miR-214 significantly attenuated cell proliferation. Finally, analysis in 20 HCC patients revealed an inverse correlation in expression of UCP2 and miR-214 (Pearson's correlation coefficient, r=-0.9792). Cumulatively, our data indicate that in the context of HCC, miR-214 acts as a putative tumour suppressor by targeting UCP2 and defines a novel mechanism of regulation of UCP2. PMID:27129291

  10. The effect of pesticide residue on caged mosquito bioassays.

    Science.gov (United States)

    Barber, J A S; Greer, Mike; Coughlin, Jamie

    2006-09-01

    Wind tunnel experiments showed that secondary pickup of insecticide residue by mosquitoes in cage bioassays had a significant effect on mortality. Cage bioassays using adult Ochlerotatus taeniorhynchus (Wiedemann) investigated the effect of exposure time to a contaminated surface. Cages were dosed in a wind tunnel using the LC50 for naled (0.124 mg a.i./ml) and an LC25 (0.0772 mg a.i./ml) for naled. Half of the bioassay mosquitoes were moved directly into clean cages with the other half remaining in the sprayed, hence contaminated, cage. Treatment mortality was assessed at 8, 15, 30, 60, 120, 240, and 1,440 min postapplication. Cage contamination had a significant effect on mosquito mortality for both the LC25 and LC50 between 15 and 30 min postapplication. PMID:17067048

  11. Uncoupling primer and releaser responses to pheromone in honey bees

    Science.gov (United States)

    Grozinger, Christina M.; Fischer, Patrick; Hampton, Jacob E.

    2007-05-01

    Pheromones produce dramatic behavioral and physiological responses in a wide variety of species. Releaser pheromones elicit rapid responses within seconds or minutes, while primer pheromones produce long-term changes which may take days to manifest. Honeybee queen mandibular pheromone (QMP) elicits multiple distinct behavioral and physiological responses in worker bees, as both a releaser and primer, and thus produces responses on vastly different time scales. In this study, we demonstrate that releaser and primer responses to QMP can be uncoupled. First, treatment with the juvenile hormone analog methoprene leaves a releaser response (attraction to QMP) intact, but modulates QMP’s primer effects on sucrose responsiveness. Secondly, two components of QMP (9-ODA and 9-HDA) do not elicit a releaser response (attraction) but are as effective as QMP at modulating a primer response, downregulation of foraging-related brain gene expression. These results suggest that different responses to a single pheromone may be produced via distinct pathways.

  12. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus;

    2014-01-01

    determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  13. A secure and economical system for caging venomous snakes

    OpenAIRE

    Powell, R. L.

    2003-01-01

    This paper describes an inexpensive and secure cage system for housing venomous snakes. The cages are easily constructed from commercially available plastic containers and are lightweight and can be stacked, minimizing the area needed to house numerous animals. They allow easy access to the animal and can be adequately disinfected. These cages can be individually locked and also allow for full viewing of the animal.

  14. PROBLEMS OF BIOFOULING ON FISH–CAGE NETS IN AQUACULTURE

    OpenAIRE

    Merica Slišković; Gorana Jelić

    2002-01-01

    Biofouling on fish–cage netting is a serious technical and economical problem to aquaculture worldwide. Compensation for the effects of biofouling must be included in cage system design and planning, as fouling can dramatically increase both weight and drag. Settlements of sessile plants and animals, with accumulation of the detritus diminish the size of mesh and can rapidly occlude mesh. Negative effect of smaller mesh size is changing in water flow trough the cages. Biofouling problems nece...

  15. THE PROCEDURE AND THE CRITERIA FOR FISH CAGES ALLOCATION

    OpenAIRE

    Valentina Andrić; Gordana Jelić Mrčelić; Merica Slišković; Ivana Miletić

    2010-01-01

    In the Republic of Croatia, fish cage farming is one of the most important economic activities. Fish cage farms inevitably influence the quality of marine environment. Environment protection measures are established in order to minimize negative effects on the stability of ecosystem. The aim of this paper is to give an overview on the procedure of fish cage farm allocation, environment protection measures, as also as program of monitoring before, during and after fish farming allocation.

  16. THE PROCEDURE AND THE CRITERIA FOR FISH CAGES ALLOCATION

    Directory of Open Access Journals (Sweden)

    Valentina Andrić

    2010-10-01

    Full Text Available In the Republic of Croatia, fish cage farming is one of the most important economic activities. Fish cage farms inevitably influence the quality of marine environment. Environment protection measures are established in order to minimize negative effects on the stability of ecosystem. The aim of this paper is to give an overview on the procedure of fish cage farm allocation, environment protection measures, as also as program of monitoring before, during and after fish farming allocation.

  17. Gating of the mitochondrial permeability transition pore by long chain fatty acyl analogs in vivo.

    Science.gov (United States)

    Samovski, Dmitri; Kalderon, Bella; Yehuda-Shnaidman, Einav; Bar-Tana, Jacob

    2010-03-01

    The role played by long chain fatty acids (LCFA) in promoting energy expenditure is confounded by their dual function as substrates for oxidation and as putative classic uncouplers of mitochondrial oxidative phosphorylation. LCFA analogs of the MEDICA (MEthyl-substituted DICarboxylic Acids) series are neither esterified into lipids nor beta-oxidized and may thus simulate the uncoupling activity of natural LCFA in vivo, independently of their substrate role. Treatment of rats or cell lines with MEDICA analogs results in low conductance gating of the mitochondrial permeability transition pore (PTP), with 10-40% decrease in the inner mitochondrial membrane potential. PTP gating by MEDICA analogs is accounted for by inhibition of Raf1 expression and kinase activity, resulting in suppression of the MAPK/RSK1 and the adenylate cyclase/PKA transduction pathways. Suppression of RSK1 and PKA results in a decrease in phosphorylation of their respective downstream targets, Bad(Ser-112) and Bad(Ser-155). Decrease in Bad(Ser-112, Ser-155) phosphorylation results in increased binding of Bad to mitochondrial Bcl2 with concomitant displacement of Bax, followed by PTP gating induced by free mitochondrial Bax. Low conductance PTP gating by LCFA/MEDICA may account for their thyromimetic calorigenic activity in vivo. PMID:20037159

  18. Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.

    Science.gov (United States)

    Wada, Jun; Nakatsuka, Atsuko

    2016-06-01

    The mitochondria are involved in active and dynamic processes, such as mitochondrial biogenesis, fission, fusion and mitophagy to maintain mitochondrial and cellular functions. In obesity and type 2 diabetes, impaired oxidation, reduced mitochondrial contents, lowered rates of oxidative phosphorylation and excessive reactive oxygen species (ROS) production have been reported. Mitochondrial biogenesis is regulated by various transcription factors such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs). Mitochondrial fusion is promoted by mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1), while fission is governed by the recruitment of dynamin-related protein 1 (DRP1) by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51), and fission 1 (FIS1). Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARKIN promote DRP1-dependent mitochondrial fission, and the outer mitochondrial adaptor MiD51 is required in DRP1 recruitment and PARKIN-dependent mitophagy. This review describes the molecular mechanism of mitochondrial dynamics, its abnormality in diabetes and obesity, and pharmaceuticals targeting mitochondrial biogenesis, fission, fusion and mitophagy. PMID:27339203

  19. Advanced behavioural screening: automated home cage ethology.

    Science.gov (United States)

    Spruijt, Berry M; DeVisser, Leonie

    2006-01-01

    Animal behaviour has been studied using two approaches, (1) well-controlled experiments focusing on specific responses and (2) those with natural - fuzzy - but biologically relevant conditions. Ideally, one behavioural test should be able to address both. The home cage provided with various stimuli is proposed as an all-in-one possibility. This, however, results in an exponential increase in complexity regarding observation and analysis tools. It seems difficult to accept that behavioural expressions need a mathematical approach to unravel its organisation and meaning. Developments in artificial intelligence and data mining are essential to accelerate this necessary evolution in behavioural sciences.: PMID:24980412

  20. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  1. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

    DEFF Research Database (Denmark)

    Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen;

    2013-01-01

    Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system......-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and...... compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in complex II and complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to...

  2. Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter

    DEFF Research Database (Denmark)

    Gnaiger, E; Boushel, R; Søndergaard, H;

    2015-01-01

    During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating...... and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high...... latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation....

  3. Influence of metabolic cage on Wistar rat physiological state

    Directory of Open Access Journals (Sweden)

    Judita Zymantiene

    2016-03-01

    Full Text Available The aim of this study was to investigate the influence of metabolic cage housing on the Wistar rat physiological state and to analyze the correlation between the minerals in blood and urine. Thirty male rats were used in the experiment. Fifteen rats (control group were housed individually in standard polycarbonate cages and fifteen rats (experimental group in metabolic cages (Techniplast, Italy for two weeks. Body weight, respiration rate, water and food consumptions were recorded for each animal at the beginning of the experiment. The same parameters, as well as blood and urine parameters of control and experimental animals were recorded during the experiment after 72 h, 168 h and 336 h of housing in standard cages and metabolic cages. Urine collection was measured only in the experimental group. Rats weight decreased from 3.84 % to 18.59 % (P<0.05, respiration rate from 18.65 % to 24.59 % (P<0.05 when rats were housed in metabolic cages. Consumption of food and water by the rat depended on how long the animal was kept in metabolic cage. Glucose concentration increased on average by 15.37 %, WBC count decreased by 5.83 % in the blood of rats housed in metabolic cages compared to the animals housed in standard cages. We did not observe significant changes of triglycerides concentration, red blood cells count and total protein between all rats. The positive moderate correlation of rat housing in a metabolic cage was between K blood and K urine, P blood and P urine, Na blood and K blood, between Na urine and P urine and significant negative moderate correlation was determined between K urine and P urine. These present study findings indicate that metabolism cage housing significantly affects rat’s physiological parameters and potentially may influence animal health and well being.

  4. Computed tomography measurement of rib cage morphometry in emphysema.

    Directory of Open Access Journals (Sweden)

    Nicola Sverzellati

    Full Text Available BACKGROUND: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. METHODS: Rib cage diameters and areas (calculated from the inner surface of the rib cage in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT. CTs were analyzed with software, which allows quantification of total emphysema (emphysema%. The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. RESULTS: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1%, and forced vital capacity (FVC% fit best with the rib cage measurements (R(2 = 64% for the rib cage area variation at the lower anatomical level. Gender had the biggest impact on rib cage diameter and area (105.3 cm(2; 95% CI: 111.7 to 98.8 for male lower area. Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm(2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%. Lower rib cage areas decreased as FVC% decreased (5.1 cm(2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation. CONCLUSIONS: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema.

  5. Preinjector for Linac 1, Faraday cage

    CERN Multimedia

    1974-01-01

    The 50 MeV Linac 1 started up in 1958 as injector to the 26 GeV PS, with a 520 kV Cockcroft-Walton generator as its preinjector, housed in a vast Faraday cage, visible here. When the Cockcroft-Walton broke down in 1973, it was replaced by a much smaller SAMES generator, of the kind used for electrostatic separators. From 1980 on, Linac 2 took over as injector for the 800 MeV Booster, and Linac 1 continued as injector for LEAR. In 1984, the electrostatic preinjector (i.e. the Faraday cage with its contents, SAMES generator and all) was replaced by a 520 keV RFQ. At the lower left corner we see the HV connectors to the SAMES generator, at the right edge part of the opened electronics-platform. Jean-Luc Vallet sees to it that all parts are properly grounded. See also 7403073X, 7403074X, 7403081X, 7403083X.

  6. Activation of PPARδ up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic β-cells

    International Nuclear Information System (INIS)

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor δ (PPARδ) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic β-cells. After HIT-T15 cells (a β-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPARδ), we found that administration of GW increased the expression of PPARδ mRNA. GW-induced activation of PPARδ up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPARδ plays an important role in protecting pancreatic β-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  7. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  8. Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter.

    Science.gov (United States)

    Gnaiger, E; Boushel, R; Søndergaard, H; Munch-Andersen, T; Damsgaard, R; Hagen, C; Díez-Sánchez, C; Ara, I; Wright-Paradis, C; Schrauwen, P; Hesselink, M; Calbet, J A L; Christiansen, M; Helge, J W; Saltin, B

    2015-12-01

    During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation. PMID:26589126

  9. Morphosynthesis of cubic silver cages on monolithic activated carbon.

    Science.gov (United States)

    Wang, Fei; Zhao, Hong; Lai, Yijian; Liu, Siyu; Zhao, Binyuan; Ning, Yuesheng; Hu, Xiaobin

    2013-11-14

    Cubic silver cages were prepared on monolithic activated carbon (MAC) pre-absorbed with Cl(-), SO4(2-), or PO4(3-) anions. Silver insoluble salts served as templates for the morphosynthesis of silver cages. The silver ions were reduced by reductive functional groups on MAC micropores through a galvanic cell reaction mechanism. PMID:24080952

  10. 48 CFR 204.7202-1 - CAGE codes.

    Science.gov (United States)

    2010-10-01

    ...)(1) If a prospective contractor located in the United States must register in the Central Contractor... registrants must obtain a North Atlantic Treaty Organization CAGE (NCAGE) code in order to register in the CCR... dial-up capability; or (D) The Internet to access the CAGE Lookup Server at...

  11. Design of the UHVDC Corona Cage in China

    Institute of Scientific and Technical Information of China (English)

    GUO Jian; LU Jiayu; ZHANG Wenliang

    2013-01-01

    For the purpose of testing and analysing the corona characteristics of UHVDC bundle conductors,UHVDC corona cage would be built in China.Corona cage is one of the indispensable equipments for conductor corona performance researches.Tests of conductor cotona characteristics in corona cages can overcome the shortages of those with test lines.The dimensions of several corona cages constructed overseas were introduced in this paper.Based on foreign experiences and the requirement of State Grid Corporation of China,the UHVDC corona cage was designed as double-cage,double-layer,three-seetions,and catenary shape with the size of 70 m×22 m× 13 m.The corona loss measurement system,radio interference measuring system,and the audible noise measuring system are also detailed,including the measurement theory,connection with the cage,the parameters and the designing basis.The UHVDC corona cage has been put into service.It now undergoes a large amount of audible noise and radio frequency interference tests.

  12. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    Science.gov (United States)

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  13. Polymers containing borane or carborane cage compounds and related applications

    Science.gov (United States)

    Bowen, III, Daniel E.; Eastwood, Eric A.

    2012-06-05

    Polymers comprising residues of borane and/or carborane cage compound monomers having at least one polyalkoxy silyl substituent. Such polymers can further comprise one or more reactive matrices and/or co-monomers covalently bound with the cage compound monomer residues. Methods of making and applications for using such polymers are also disclosed.

  14. Ammonia Levels and Urine-Spot Characteristics as Cage-Change Indicators for High-Density Individually Ventilated Mouse Cages.

    Science.gov (United States)

    Washington, Ida M; Payton, Mark E

    2016-01-01

    Mouse cage and bedding changes are potentially stressful to mice and are also labor- and resource-intensive. These changes are often performed on a calendar-based schedule to maintain a clean microenvironment and limit the concentrations of ammonia to which mice and workers are exposed. The current study sought to establish a performance-based approach to mouse cage-changing that uses urine spot characteristics as visual indicators of intracage ammonia levels. Colorimetric ammonia indicators were used to measure ammonia levels in individually-ventilated cages (IVC) housing male or female mice (n =5 per cage) of various strains at 1 to 16 d after cage change. Urine spot characteristics were correlated with ammonia levels to create a visual indicator of the cage-change criterion of 25 ppm ammonia. Results demonstrated a consistent increase in ammonia levels with days since cage change, with cages reaching the cage-change criterion at approximately 10 d for IVC containing male mice and 16 d for those with female mice. Ammonia levels were higher for male than female mice but were not correlated with mouse age. However, urine spot diameter, color, and edge characteristics were strongly correlated with ammonia levels. Husbandry practices based on using urine spot characteristics as indicators of ammonia levels led to fewer weekly cage changes and concomitant savings in labor and resources. Therefore, urine spot characteristics can be used as visual indicators of intracage ammonia levels for use of a performance (urine spot)-based approach to cage-changing frequency that maintains animal health and wellbeing. PMID:27177558

  15. Mitochondrial disease and epilepsy.

    Science.gov (United States)

    Rahman, Shamima

    2012-05-01

    Mitochondrial respiratory chain disorders are relatively common inborn errors of energy metabolism, with a combined prevalence of one in 5000. These disorders typically affect tissues with high energy requirements, and cerebral involvement occurs frequently in childhood, often manifesting in seizures. Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded genes and more than 80 nuclear genes. The major genetic causes of mitochondrial epilepsy are mitochondrial DNA mutations (including those typically associated with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS] and myoclonic epilepsy with ragged red fibres [MERRF] syndromes); mutations in POLG (classically associated with Alpers syndrome but also presenting as the mitochondrial recessive ataxia syndrome [MIRAS], spinocerebellar ataxia with epilepsy [SCAE], and myoclonus, epilepsy, myopathy, sensory ataxia [MEMSA] syndromes in older individuals) and other disorders of mitochondrial DNA maintenance; complex I deficiency; disorders of coenzyme Q(10) biosynthesis; and disorders of mitochondrial translation such as RARS2 mutations. It is not clear why some genetic defects, but not others, are particularly associated with seizures. Epilepsy may be the presenting feature of mitochondrial disease but is often part of a multisystem clinical presentation. Mitochondrial epilepsy may be very difficult to manage, and is often a poor prognostic feature. At present there are no curative treatments for mitochondrial disease. Individuals with mitochondrial epilepsy are frequently prescribed multiple anticonvulsants, and the role of vitamins and other nutritional supplements and the ketogenic diet remain unproven. PMID:22283595

  16. Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast.

    Science.gov (United States)

    Reinhold, Robert; Bareth, Bettina; Balleininger, Martina; Wissel, Mirjam; Rehling, Peter; Mick, David U

    2011-06-15

    Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a severe encephalomyopathy in infancy, frequently caused by mutations in SURF1. SURF1, termed Shy1 in Saccharomyces cerevisiae, is a conserved assembly factor for the terminal enzyme of the respiratory chain, cytochrome c oxidase. Although the molecular function of SURF1/Shy1 is still enigmatic, loss of function leads to cytochrome c oxidase deficiency and reduced expression of the central subunit Cox1 in yeast. Here, we provide insights into the molecular mechanisms leading to disease through missense mutations in codons of the most conserved amino acids in SURF1. Mutations affecting G(124) do not compromise import of the SURF1 precursor protein but lead to fast turnover of the mature protein within the mitochondria. Interestingly, an Y(274)D exchange neither affects stability nor localization of the protein. Instead, SURF1(Y274D) accumulates in a 200 kDa cytochrome c oxidase assembly intermediate. Using yeast as a model, we demonstrate that the corresponding Shy1(Y344D) is able to overcome the stage where cytochrome c oxidase assembly links to the feedback regulation of mitochondrial Cox1 expression. However, Shy1(Y344D) impairs the assembly at later steps, most apparent at low temperature and exhibits a dominant-negative phenotype upon overexpression. Thus, exchanging the conserved tyrosine (Y(344)) with aspartate in yeast uncouples translational regulation of Cox1 from cytochrome c oxidase assembly and provides evidence for the dual functionality of Shy1. PMID:21470975

  17. Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

  18. American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured β Cells

    Directory of Open Access Journals (Sweden)

    John Zeqi Luo

    2006-01-01

    Full Text Available American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2 has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism. To test the hypothesis, the serum-deprived quiescent β cells were cultured with or without interleukin-1β (IL-1β, (200 pg ml−1, a cytokine to induce β cell apoptosis and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.

  19. Electrofriction method of manufacturing squirrel cage rotors

    Science.gov (United States)

    Hsu, John S.

    2005-04-12

    A method of making a squirrel cage rotor of copper material for use in AC or DC motors, includes forming a core with longitudinal slots, inserting bars of conductive material in the slots, with ends extending out of opposite ends of the core, and joining the end rings to the bars, wherein the conductive material of either the end rings or the bars is copper. Various methods of joining the end rings to the bars are disclosed including electrofriction welding, current pulse welding and brazing, transient liquid phase joining and casting. Pressure is also applied to the end rings to improve contact and reduce areas of small or uneven contact between the bar ends and the end rings. Rotors made with such methods are also disclosed.

  20. Protein Cages as Containers for Gold Nanoparticles.

    Science.gov (United States)

    Liu, Aijie; Verwegen, Martijn; de Ruiter, Mark V; Maassen, Stan J; Traulsen, Christoph H-H; Cornelissen, Jeroen J L M

    2016-07-01

    Abundant and highly diverse, viruses offer new scaffolds in nanotechnology for the encapsulation, organization, or even synthesis of novel materials. In this work the coat protein of the cowpea chlorotic mottle virus (CCMV) is used to encapsulate gold nanoparticles with different sizes and stabilizing ligands yielding stable particles in buffered solutions at neutral pH. The sizes of the virus-like particles correspond to T = 1, 2, and 3 Caspar-Klug icosahedral triangulation numbers. We developed a simple one-step process enabling the encapsulation of commercially available gold nanoparticles without prior modification with up to 97% efficiency. The encapsulation efficiency is further increased using bis-p-(sufonatophenyl)phenyl phosphine surfactants up to 99%. Our work provides a simplified procedure for the preparation of metallic particles stabilized in CCMV protein cages. The presented results are expected to enable the preparation of a variety of similar virus-based colloids for current focus areas. PMID:27135176

  1. Cathodic Cage Plasma Nitriding: An Innovative Technique

    Directory of Open Access Journals (Sweden)

    R. R. M. de Sousa

    2012-01-01

    Full Text Available Cylindrical samples of AISI 1020, AISI 316, and AISI 420 steels, with different heights, were simultaneously treated by a new technique of ionic nitriding, entitled cathodic cage plasma nitriding (CCPN, in order to evaluate the efficiency of this technique to produce nitrided layers with better properties compared with those obtained using conventional ionic nitriding technique. This method is able to eliminate the edge effect in the samples, promoting a better uniformity of temperature, and consequently, a smaller variation of the thickness/height relation can be obtained. The compound layers were characterized by X-ray diffraction, optical microscopy, and microhardness test profile. The results were compared with the properties of samples obtained with the conventional nitriding, for the three steel types. It was verified that samples treated by CCPN process presented, at the same temperature, a better uniformity in the thickness and absence of the edge effect.

  2. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  3. Effect of overexpression of uncoupling protein 1 on brown adipose tissue in aP2-Ucp mice

    International Nuclear Information System (INIS)

    The aim of the present study was assess the function of mitochondria in brown fat of the transgenic animals in order to explain the functional involution of brown adipose tissue (BAT). This study was based on measurements of transmembrane electrochemical potential (Δψ) and estimation of [3H]GDP binding to isolated brown fat mitochondria, as well as on immunochemical analysis of trans-gene expression. Fluorescent cationic dye Rhodamine 123 was used to follow the changes in Δψ of isolated brown fat mitochondria. The fluorescence is quenched as the dye is accumulated in mitochondria in response to membrane energization. Titration by the inhibitory ligand of mitochondrial uncoupling protein 1 (UCP1), GDP (in presence of substrate), indicated a 3-fold lower sensitivity to GDP in mitochondria from transgenic compared with non-transgenic animals. Binding of [3H]GDP to both types of brown fat mitochondria was measured. Maximum number of specific GDP-binding sites was estimated from Scatchard plots. In accordance with the activity measurements, number of GDP-binding sites was approximately 3- to 5-fold higher in mitochondria isolated from the transgenic animals. (authors)

  4. Fusion of the Endoplasmic Reticulum and Mitochondrial Outer Membrane in Rats Brown Adipose Tissue: Activation of Thermogenesis by Ca2+

    OpenAIRE

    de Meis, Leopoldo; Ketzer, Luisa A.; da Costa, Rodrigo Madeiro; de Andrade, Ivone Rosa; Benchimol, Marlene

    2010-01-01

    Brown adipose tissue (BAT) mitochondria thermogenesis is regulated by uncoupling protein 1 (UCP 1), GDP and fatty acids. In this report, we observed fusion of the endoplasmic reticulum (ER) membrane with the mitochondrial outer membrane of rats BAT. Ca2+-ATPase (SERCA 1) was identified by immunoelectron microscopy in both ER and mitochondria. This finding led us to test the Ca2+ effect in BAT mitochondria thermogenesis. We found that Ca2+ increased the rate of respiration and heat production ...

  5. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Science.gov (United States)

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude

    2016-03-14

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  6. Performance and welfare of rabbit does in various caging systems.

    Science.gov (United States)

    Mikó, A; Matics, Zs; Gerencsér, Zs; Odermatt, M; Radnai, I; Nagy, I; Szendrő, K; Szendrő, Zs

    2014-07-01

    The objective of the study was to compare production and welfare of rabbit does and their kits housed in various types of cages. Female rabbits were randomly allocated to four groups with the following cage types: CN: common wire-mesh flat-deck cage, without footrest; CF: cage similar to the CN but with plastic footrest; ECWP: enlarged cage with wire-mesh platform; and ECPP: extra enlarged cage with plastic-mesh platform. All does were inseminated on the same day, 11 days after kindlings. Reproductive performance was evaluated during the first five consecutive kindlings. Severity of sore hocks was scored at each insemination. Location preference of the does and the platform usage of their kits were evaluated. Kindling rate, litter size (total born, born alive, alive at 21 and 35 days) and kit mortality were not significantly influenced by the cage types. The litter weight at 21 days was higher in ECWP and ECPP cages than in the CF group (3516, 3576 and 3291 g, respectively; P2.5 cm) and 3 to 4 (3=callus opened, cracks present; 4=wounds) were 58%, 60%, 78% and 48%, and 0%, 5%, 0% and 48% in groups ECPP, ECWP, CF and CN, respectively. Higher number of daily nest visits was observed for CF does than for ECWP does (12.5 v. 5.9; P2/day) was higher in the CF group than in the ECWP group (12.1 v. 3.2%; Pplastic footrests and plastic-mesh platforms in conventional and/or large cages reduced sore hocks' problems, plastic-mesh platforms were more used by both does and kits compared with the wire-mesh platforms. PMID:26263030

  7. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori;

    2016-01-01

    -production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory...... control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired...... mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity....

  8. Endohedral dynamics of push-pull rotor-functionalized cages.

    Science.gov (United States)

    Krick, Marcel; Holstein, Julian; Würtele, Christian; Clever, Guido H

    2016-08-16

    A series of [Pd2L4] coordination cages featuring endohedral functionalities in central backbone positions was synthesized. Although attached via C[double bond, length as m-dash]C double bonds, the substituents behave as molecular rotors. This is explained by their pronounced donor-acceptor character which lowers rotational barriers and allows for electronic control over the spinning rates inside the cage. The dynamic behaviour of the free ligands, assembled cages and host-guest complexes is compared with the aid of NMR experiments, X-ray structure analysis and molecular modelling. PMID:27484435

  9. The planimetric unfold method of fullerene cage structure

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Two kinds of planimetric diagrams, which consist of the boat form F6 and F5, the storm petrel form F6 and F5, respectively, were proposed to express the geometric structure of fullerene cage in this study. There are two chief advantages using the diagrams: (ⅰ) the spatial symmetrical characteristic of fullerene cage is not destroyed; (ⅱ) the coordination forms of F5 and F6 in the structure can be clearly expressed. This work has laid the foundation for studying the structural geometry of fullerene cage and its quantum chemistry and property.

  10. Bemisia tabaci: A new clip-cage for biological studies

    OpenAIRE

    Muñiz, M.; Nombela, G.

    2001-01-01

    This new clip-cage has been designed in our laboratory. It is a transparent plastic truncated cone clip-cage (3.6 cm x 2.6 cm diameter; 4 cm high). A very thin polypropylene mesh (30 holes/inch) is attached to the bottom by paraffin wax. We have used this clip-cage attached to the under surface of the leaves in our studies on the biology of both B and Q biotypes of Bemisia tabaci with excellent results.

  11. Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration

    International Nuclear Information System (INIS)

    Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II + III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II + III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others

  12. Strokes in mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    N V Pizova

    2012-06-01

    Full Text Available It is suggested that mitochondrial diseases might be identified in 22—33% of cryptogenic stroke cases in young subjects. The incidence of mitochondrial disorders in patients with stroke is unknown; it is 0.8 to 7.2% according to the data of some authors. The paper gives data on the prevalence, pathogenesis, and clinical manifestations of mitochondrial diseases, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS and insulin-like episodes; myoclonic epilepsy and ragged-red fibers (MERRF syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology.

  13. UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

    Science.gov (United States)

    Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

    2016-02-25

    The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. PMID:26919426

  14. Mediator-assisted Simultaneous probing of Cytosolic and Mitochondrial Redox activity in living cells

    DEFF Research Database (Denmark)

    Heiskanen, Arto; Spegel, Christer; Kostesha, Natalie;

    2009-01-01

    ferricyanide-menadione double mediator system to study the effect of dicoumarol, an inhibitor of cytosolic and mitochondrial oxidoreductases and an uncoupler of the electron transport chain. Evaluation of the role of NAD(P)H-producing pathways in mediating biological effects is facilitated by introducing...... either fructose or glucose as the carbon source, yielding either NADH or NADPH through the glycolytic or pen-rose phosphate pathway, respectively. Respiratory noncompetent cells show greater inhibition of cytosolic menadione-reducing enzymes when NADH rather than NADPH is produced. Spectrophotometric in...... vitro assays show no difference between the cofactors. Respiratory competent cells show cytosolic inhibition only when NADPH is produced, whereas production of NADH reveals uncoupling at low dicoumarol concentrations and inhibition of complexes III and IV at higher concentrations. Spectrophotometric...

  15. Linear diffusion into a Faraday cage.

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry Kevin; Lin, Yau Tang; Merewether, Kimball O.; Chen, Kenneth C.

    2011-11-01

    Linear lightning diffusion into a Faraday cage is studied. An early-time integral valid for large ratios of enclosure size to enclosure thickness and small relative permeability ({mu}/{mu}{sub 0} {le} 10) is used for this study. Existing solutions for nearby lightning impulse responses of electrically thick-wall enclosures are refined and extended to calculate the nearby lightning magnetic field (H) and time-derivative magnetic field (HDOT) inside enclosures of varying thickness caused by a decaying exponential excitation. For a direct strike scenario, the early-time integral for a worst-case line source outside the enclosure caused by an impulse is simplified and numerically integrated to give the interior H and HDOT at the location closest to the source as well as a function of distance from the source. H and HDOT enclosure response functions for decaying exponentials are considered for an enclosure wall of any thickness. Simple formulas are derived to provide a description of enclosure interior H and HDOT as well. Direct strike voltage and current bounds for a single-turn optimally-coupled loop for all three waveforms are also given.

  16. La cage qui cache : La Cage Dorée de Ruben Alves

    Directory of Open Access Journals (Sweden)

    Cristina Marinho

    2015-12-01

    Full Text Available The French Comedy La Cage Dorée (produced by the luso descendant Ruben Alves, 2013 success seems to be mainly due to its clichés of Portuguese epics in Paris, and its miseries may not have been underlined enough. Thus, under this apparently naif portrait an intriguing painting of Portuguese immigrants’ French dis-integration may really be hiding, which is the aim of this essay, on one hand, to bring out and, on the other one, to clarify, by questioning comparative critical common denominators of the two countries.

  17. La cage qui cache : La Cage Dorée de Ruben Alves

    Directory of Open Access Journals (Sweden)

    Cristina Marinho

    2015-01-01

    Full Text Available The French Comedy La Cage Dorée (produced by the luso descendant Ruben Alves, 2013 success seems to be mainly due to its clichés of Portuguese epics in Paris, and its miseries may not have been underlined enough. Thus, under this apparently naif portrait an intriguing painting of Portuguese immigrants’ French dis-integration may really be hiding, which is the aim of this essay, on one hand, to bring out and, on the other one, to clarify, by questioning comparative critical common denominators of the two countries.

  18. Evaluation of the pharmacophoric motif of the caged Garcinia xanthones†

    OpenAIRE

    Chantarasriwong, Oraphin; Cho, Woo Cheal; Batova, Ayse; Chavasiri, Warinthorn; Moore, Curtis; Rheingold, Arnold L.; Theodorakis, Emmanuel A.

    2009-01-01

    The combination of unique structure and potent bioactivity exhibited by several family members of the caged Garcinia xanthones, led us to evaluate their pharmacophore. We have developed a Pd(0)-catalyzed method for the reverse prenylation of catechols that, together with a Claisen/Diels–Alder reaction cascade, provides rapid and efficient access to various caged analogues. Evaluation of the growth inhibitory activity of these compounds leads to the conclusion that the intact ABC ring system c...

  19. Cage experiments in an East African mangrove forest: a synthesis

    OpenAIRE

    Schrijvers, J.; Vincx, M.

    1997-01-01

    The impact of epibenthos on endobenthos has frequently been investigated for temperate saltmarsh regions by using cage exclusion experiments. Although the insight into the function of the endobenthos of mangrove forests is crucial for their management, very few cage experiments have so far been carried out in such areas. The present paper summarises the result of such experiments in a typical East African mangrove forest at Gazi Bay about 60 km south of Mombasa, Kenya. Epibenthic animals were...

  20. Catalogue Note on Taner Ceylan's Cage of Flesh (2012)

    OpenAIRE

    Cakirlar, C.; Delice, S.

    2012-01-01

    Cage of Flesh (Ten Kafesi), the most recent piece by the photorealist painter Taner Ceylan, engages with the politics of and the erotics within representation in Orientalist painting by confronting the viewer with a re-imagined figure of an odalisque. Following his highly acclaimed Lost Painting Series that featured Fake World (2011), 1640 (2011), 1879 (2011), 1923 (2010) and 1881 (2010), Cage of Flesh uses an ingenious amalgam of allusions to both Orientalist eroticisation of female flesh an...

  1. Experimental setup for the measurement of induction motor cage currents

    International Nuclear Information System (INIS)

    An experimental setup for measurement of the currents flowing in the rotor bars of induction motors during synchronous no-load tests is described in the paper. The experimental verification of the high-frequency phenomena in the rotor cage is fundamental for a deep insight of the additional loss estimation by numerical methods. The attention is mainly focused on the analysis and design of the transducers developed for the cage current measurement

  2. Thermodynamics of Anharmonic Systems: Uncoupled Mode Approximations for Molecules.

    Science.gov (United States)

    Li, Yi-Pei; Bell, Alexis T; Head-Gordon, Martin

    2016-06-14

    The partition functions, heat capacities, entropies, and enthalpies of selected molecules were calculated using uncoupled mode (UM) approximations, where the full-dimensional potential energy surface for internal motions was modeled as a sum of independent one-dimensional potentials for each mode. The computational cost of such approaches scales the same with molecular size as standard harmonic oscillator vibrational analysis using harmonic frequencies (HO(hf)). To compute thermodynamic properties, a computational protocol for obtaining the energy levels of each mode was established. The accuracy of the UM approximation depends strongly on how the one-dimensional potentials of each modes are defined. If the potentials are determined by the energy as a function of displacement along each normal mode (UM-N), the accuracies of the calculated thermodynamic properties are not significantly improved versus the HO(hf) model. Significant improvements can be achieved by constructing potentials for internal rotations and vibrations using the energy surfaces along the torsional coordinates and the remaining vibrational normal modes, respectively (UM-VT). For hydrogen peroxide and its isotopologs at 300 K, UM-VT captures more than 70% of the partition functions on average. By contrast, the HO(hf) model and UM-N can capture no more than 50%. For a selected test set of C2 to C8 linear and branched alkanes and species with different moieties, the enthalpies calculated using the HO(hf) model, UM-N, and UM-VT are all quite accurate comparing with reference values though the RMS errors of the HO model and UM-N are slightly higher than UM-VT. However, the accuracies in entropy calculations differ significantly between these three models. For the same test set, the RMS error of the standard entropies calculated by UM-VT is 2.18 cal mol(-1) K(-1) at 1000 K. By contrast, the RMS error obtained using the HO model and UM-N are 6.42 and 5.73 cal mol(-1) K(-1), respectively. For a test set

  3. Anterior cervical discectomy and fusion: Comparison of titanium and polyetheretherketone cages

    OpenAIRE

    Cabraja Mario; Oezdemir Soner; Koeppen Daniel; Kroppenstedt Stefan

    2012-01-01

    Abstract Background Titanium (TTN) cages have a higher modulus of elasticity when compared with polyetheretherketone (PEEK) cages. This suggests that TTN-cages could show more frequent cage subsidence after anterior cervical discectomy and fusion (ACDF) and therefore might lead to a higher loss of correction. We compared the long term results of stand-alone PEEK- and TTN-cages in a comparable patient collective that was operated under identical operative settings. Methods From 2002 to 2007 15...

  4. Quantification of uncoupling protein 2 reveals its main expression in immune cells and selective up-regulation during T-cell proliferation.

    Directory of Open Access Journals (Sweden)

    Anne Rupprecht

    Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing that UCP2 is mainly expressed in organs and cells associated with the immune system. Although the UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the protein was not detectable in neurons under physiological conditions. Instead, we could detect UCP2 in microglia, which act in the immune defense of the central nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2 protein expression simultaneously to the increase in levels of other mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the selective increase of UCP2. The highest detected level of UCP2 expression in stimulated T-cells (0.54 ng/(µg total cellular protein was approximately 200 times lower than the level of UCP1 in brown adipose tissue from room temperature acclimated mice. Both the UCP2 expression pattern and the time course of up-regulation in stimulated T-cells imply UCP2's involvement in the immune response, probably by controlling the metabolism during cell proliferation.

  5. Uncoupling proteins, dietary fat and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Warden Craig H

    2006-09-01

    Full Text Available Abstract There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome.

  6. Uncoupling effect of fatty acids on heart muscle mitochondria and submitochondrial particles.

    Science.gov (United States)

    Dedukhova, V I; Mokhova, E N; Skulachev, V P; Starkov, A A; Arrigoni-Martelli, E; Bobyleva, V A

    1991-12-16

    The effect of ATP/ADP-antiporter inhibitors on palmitate-induced uncoupling was studied in heart muscle mitochondria and inside-out submitochondrial particles. In both systems palmitate is found to decrease the respiration-generated membrane potential. In mitochondria, this effect is specifically abolished by carboxyatractylate (CAtr) a non-penetrating inhibitor of antiporter. In submitochondrial particles, CAtr does not abolish the palmitate-induced potential decrease. At the same time, bongkrekic acid, a penetrating inhibitor of the antiporter, suppresses the palmitate effect on the potential both in mitochondria and particles. Palmitoyl-CoA which is known to inhibit the antiporter in mitochondria as well as in particles decreases the palmitate uncoupling efficiency in both these systems. These data are in agreement with the hypothesis that the ATP/ADP-antiporter is involved in the action of free fatty acids as natural uncouplers of oxidative phosphorylation. PMID:1765167

  7. Evaluation of individually ventilated cage systems for laboratory rodents: cage environment and animal health aspects.

    Science.gov (United States)

    Höglund, A U; Renström, A

    2001-01-01

    The use of individually ventilated cage (IVC) systems has become an attractive housing regime of laboratory rodents. The benefits of IVC systems are, reportedly, a high degree of containment combined with relative ease of handling, and a high degree of protection from allergenes. In the present study we tested whether two IVC systems (BioZone VentiRack, IVC1 and Techniplast SealSafe, IVC2S), in which we held mature male NMRI mice, were constructed to maintain a constant differential pressure, positive or negative, during a prolonged period of time. We also measured ammonia (NH3) concentrations after about 2 weeks of use, and CO2 build-up during a 60 min simulated power failure situation. In addition, animal weight development and bite-wound frequency were recorded (Renström et al. 2000). From the present study it is concluded that the IVC1 air handling system provides a more uniform and balanced differential pressure than the IVC2S. Both systems effectively scavenge NH3 when bedding material is not soaked by urine. Although the IVCs are dependent on the continual function of the fans to work properly, it seems unlikely that CO2 concentrations increase to hazardous levels, as a result of a one hour power failure, with the type of cages used in this study. Differences in weight development and bite-wound occurrence were noted between the two IVC systems. Causes for these differences could not be established and need more investigation. PMID:11201288

  8. 14C-age tracers in global ocean circulation models

    Science.gov (United States)

    Koeve, W.; Wagner, H.; Kähler, P.; Oschlies, A.

    2015-07-01

    The natural abundance of 14C in total CO2 dissolved in seawater (DIC) is a property applied to evaluate the water age structure and circulation in the ocean and in ocean models. In this study we use three different representations of the global ocean circulation augmented with a suite of idealised tracers to study the potential and limitations of using natural 14C to determine water age, which is the time elapsed since a body of water has been in contact with the atmosphere. We find that, globally, bulk 14C-age is dominated by two equally important components, one associated with ageing, i.e. the time component of circulation, and one associated with a "preformed 14C-age". The latter quantity exists because of the slow and incomplete atmosphere-ocean equilibration of 14C particularly in high latitudes where many water masses form. In the ocean's interior, preformed 14C-age behaves like a passive tracer. The relative contribution of the preformed component to bulk 14C-age varies regionally within a given model, but also between models. Regional variability in the Atlantic Ocean is associated with the mixing of waters with very different end members of preformed 14C-age. Here, variations in the preformed component over space and time mask the circulation component to an extent that its patterns are not detectable from bulk 14C-age. Between models, the variability of preformed 14C-age can also be considerable (factor of 2), related to the combination of physical model parameters, which influence circulation dynamics or gas exchange. The preformed component was found to be very sensitive to gas exchange and moderately sensitive to ice cover. In our model evaluation, the choice of the gas-exchange constant from within the currently accepted range of uncertainty had such a strong influence on preformed and bulk 14C-age that if model evaluation would be based on bulk 14C-age, it could easily impair the evaluation and tuning of a model's circulation on global and regional

  9. Multicomponent Protein Cage Architectures for Photocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Arunava [Univ. of Alabama, Tuscaloosa, AL (United States); Prevelige, Peter E [Univ. of Alabama, Birmingham, AL (United States)

    2016-01-04

    The primary goal of the project was to develop protein-templated approaches for the synthesis and directed assembly of semiconductor nanomaterials that are efficient for visible light absorption and hydrogen production. In general, visible-light-driven photocatalysis reactions exhibit low quantum efficiency for solar energy conversion primarily because of materials-related issues and limitations, such as the control of the band gap, band structure, photochemical stability, and available reactive surface area of the photocatalyst. Synthesis of multicomponent hierarchical nano-architectures, consisting of semiconductor nanoparticles (NPs) with desired optical properties fabricated to maximize spatial proximity for optimum electron and energy transfer represents an attractive route for addressing the problem. Virus capsids are highly symmetrical, self-assembling protein cage nanoparticles that exist in a range of sizes and symmetries. Selective deposition of inorganic, by design, at specific locations on virus capsids affords precise control over the size, spacing, and assembly of nanomaterials, resulting in uniform and reproducible nano-architectures. We utilized the self-assembling capabilities of the 420 subunit, 60 nm icosahedral, P22 virus capsid to direct the nucleation, growth, and proximity of a range of component materials. Controlled fabrication on the exterior of the temperature stable shell was achieved by genetically encoding specific binding peptides into an externally exposed loop which is displayed on each of the 420 coat protein subunits. Localization of complimentary materials to the interior of the particle was achieved through the use “scaffolding-fusion proteins. The scaffolding domain drives coat protein polymerization resulting in a coat protein shell surrounding a core of approximately 300 scaffolding/fusion molecules. The fusion domain comprises a peptide which specifically binds the semiconductor material of interest.

  10. Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ding-I Yang

    2011-10-01

    Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

  11. Syringaresinol induces mitochondrial biogenesis through activation of PPARβ pathway in skeletal muscle cells.

    Science.gov (United States)

    Thach, Trung Thanh; Lee, Chan-Kyu; Park, Hyun Woo; Lee, Sang-Jun; Lee, Sung-Joon

    2016-08-15

    Activation of peroxisome proliferator-activated receptors (PPARs) plays a crucial role in cellular energy metabolism that directly impacts mitochondrial biogenesis. In this study, we demonstrate that syringaresinol, a pharmacological lignan extracted from Panax ginseng berry, moderately binds to and activates PPARβ with KD and EC50 values of 27.62±15.76μM and 18.11±4.77μM, respectively. Subsequently, the expression of peroxisome proliferator-activated receptor γ coactivator-1α together with PPARβ transcriptional targets, mitochondrial carnitine palmitoyltransferase 1 and uncoupling protein 2, was also enhanced in terms of both mRNA and protein levels. The activation of these proteins induced mitochondrial biogenesis by enrichment of mitochondrial replication and density within C2C12 myotubes. Importantly, knockdown of PPARβ reduced the syringaresinol-induced protein expression followed by the significant reduction of mitochondrial biogenesis. Taken together, our results indicate that syringaresinol induces mitochondrial biogenesis by activating PPARβ pathway. PMID:27450788

  12. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Amy C. Keller

    2016-01-01

    Full Text Available Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS, and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS- mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK and the Wistar control rat were exposed to high glucose (25 mM. At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p<0.05. Mitochondrial superoxide increased with high glucose in Wistar SMCs (p<0.05 with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets.

  13. CAGE BREEDING OF WARM WATER FRESHWATER FISH SPECIES

    Directory of Open Access Journals (Sweden)

    Roman Safner

    2008-10-01

    Full Text Available In the 1970s, Croatia became actively involved in the contemporary trend of breeding fish in floating cages. In addition to various species of marine fishes, breeding was attempted with trout, carp, catfish, cisco and salmon. Of the above freshwater fish species, specific standards were established only for the cage breeding of rainbow trout. Cage breeding of the remaining species remained at the level of occasional attempts, with more of an experimental than a commercial character. The regular attempts to master this technique for cage breeding of warm water freshwater fish species were aimed at achieving the known benefits of such breeding, such as simplicity of implementing technological measures, easier establishment of the breeding system, simpler manipulation, the possibility of denser colonies per unit volume with a high level of production, easier adaptations to market conditions and fewer initial structural investments. Despite the many advantages, the main reasons for the lack of greater implementation of the cage breeding technology for warm water species of freshwater fish include problems in obtaining the appropriate category and quantity of healthy fry, the specificity and applicability of physical and chemical properties of the recipients and human error. In evaluating the advantages and disadvantages, the final decision on the justification of cage breeding for individual warm water freshwater species must be based on both biological and economic factors. Based on the knowledge of cage breeding acquired to date, the rule for virtually all intensive breeding systems is that it is only recommended for those species with high market demand and a high market price. The technology that demands nutrition with highly concentrated feed and other production expenditures is costly, and is therefore not profitable with less expensive fish species. Furthermore, production must be market oriented, i.e. the appropriate market research measures

  14. Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1.

    Science.gov (United States)

    Chouchani, Edward T; Kazak, Lawrence; Jedrychowski, Mark P; Lu, Gina Z; Erickson, Brian K; Szpyt, John; Pierce, Kerry A; Laznik-Bogoslavski, Dina; Vetrivelan, Ramalingam; Clish, Clary B; Robinson, Alan J; Gygi, Steve P; Spiegelman, Bruce M

    2016-04-01

    Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders. PMID:27027295

  15. Mitochondrial morphology and cardiovascular disease

    OpenAIRE

    Ong, Sang-Bing; Hausenloy, Derek J

    2010-01-01

    Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a...

  16. Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

    International Nuclear Information System (INIS)

    Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications. Four major molecular mechanisms have been implicated in hyperglycemia-induced tissue damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway flux, increased advanced glycation end product (AGE) formation, and increased polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the causal link between high glucose and the pathways responsible for hyperglycemic damage. In fact, diabetes is typically accompanied by increased production of free radicals and/or impaired antioxidant defense capabilities, indicating a central contribution for reactive oxygen species (ROS) in the onset, progression, and pathological consequences of diabetes. Besides oxidative stress, a growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. Mutations in mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and nuclear-encoded uncoupling proteins (UCPs) in β-cell glucose toxicity. This review focuses on a range of mitochondrial factors important in the pathogenesis of diabetes. We review the published literature regarding the direct effects of hyperglycemia on mitochondrial function and suggest the possibility of regulation of mitochondrial function at a transcriptional level in response to hyperglycemia. The main goal of this review is to include a fresh consideration of pathways involved in hyperglycemia-induced diabetic complications

  17. Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes.

    Science.gov (United States)

    Coughlan, Melinda T; Nguyen, Tuong-Vi; Penfold, Sally A; Higgins, Gavin C; Thallas-Bonke, Vicki; Tan, Sih Min; Van Bergen, Nicole J; Sourris, Karly C; Harcourt, Brooke E; Thorburn, David R; Trounce, Ian A; Cooper, Mark E; Forbes, Josephine M

    2016-05-01

    Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD. PMID:26831938

  18. PROBLEMS OF BIOFOULING ON FISH–CAGE NETS IN AQUACULTURE

    Directory of Open Access Journals (Sweden)

    Merica Slišković

    2002-09-01

    Full Text Available Biofouling on fish–cage netting is a serious technical and economical problem to aquaculture worldwide. Compensation for the effects of biofouling must be included in cage system design and planning, as fouling can dramatically increase both weight and drag. Settlements of sessile plants and animals, with accumulation of the detritus diminish the size of mesh and can rapidly occlude mesh. Negative effect of smaller mesh size is changing in water flow trough the cages. Biofouling problems necessitating purchase of a second sets of nets or more, and frequent cleaning and changing of biofouling. Changing and cleaning frequency depend on many factors such as: location of cages (near the coast or off shore, productivity of that location, time of the year, time period in which the cages are placed on that location (cause of loading of phosphorus and nitrogen from the unconsumed food in the sediment. Net changing and cleaning procedures are labor and capital intensive. Process of the cleaning of the nets is inadequate, especially when there isnžt adequate equipment available as it is case in smaller aquaculture industry. Chemical control of biofouling e. g. use of antifoulants is questioningly cause of their possible negative effects on breeding species and environment.

  19. Genomic characterization of the European sea bass Dicentrarchus labrax reveals the presence of a novel uncoupling protein (UCP gene family member in the teleost fish lineage

    Directory of Open Access Journals (Sweden)

    Tine Mbaye

    2012-05-01

    Full Text Available Abstract Background Uncoupling proteins (UCP are evolutionary conserved mitochondrial carriers that control energy metabolism and therefore play important roles in several physiological processes such as thermogenesis, regulation of reactive oxygen species (ROS, growth control, lipid metabolism and regulation of insulin secretion. Despite their importance in various physiological processes, their molecular function remains controversial. The evolution and phylogenetic distribution may assist to identify their general biological function and structure-function relationships. The exact number of uncoupling protein genes in the fish genome and their evolution is unresolved. Results Here we report the first characterisation of UCP gene family members in sea bass, Dicentrarchus labrax, and then retrace the evolution of the protein family in vertebrates. Four UCP genes that are shared by five other fish species were identified in sea bass genome. Phylogenetic reconstitution among vertebrate species and synteny analysis revealed that UCP1, UCP2 and UCP3 evolved from duplication events that occurred in the common ancestor of vertebrates, whereas the novel fourth UCP originated specifically in the teleost lineage. Functional divergence analysis among teleost species revealed specific amino acid positions that have been subjected to altered functional constraints after duplications. Conclusions This work provides the first unambiguous evidence for the presence of a fourth UCP gene in teleost fish genome and brings new insights into the evolutionary history of the gene family. Our results suggest functional divergence among paralogues which might result from long-term and differential selective pressures, and therefore, provide the indication that UCP genes may have diverse physiological functions in teleost fishes. Further experimental analysis of the critical amino acids identified here may provide valuable information on the physiological functions of

  20. Myoclonus in mitochondrial disorders.

    Science.gov (United States)

    Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Catteruccia, Michela; Pegoraro, Elena; Carelli, Valerio; Valentino, Maria L; Comi, Giacomo P; Minetti, Carlo; Bruno, Claudio; Moggio, Maurizio; Ienco, Elena Caldarazzo; Mongini, Tiziana; Vercelli, Liliana; Primiano, Guido; Servidei, Serenella; Tonin, Paola; Scarpelli, Mauro; Toscano, Antonio; Musumeci, Olimpia; Moroni, Isabella; Uziel, Graziella; Santorelli, Filippo M; Nesti, Claudia; Filosto, Massimiliano; Lamperti, Costanza; Zeviani, Massimo; Siciliano, Gabriele

    2014-05-01

    Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). However, its prevalence in mitochondrial diseases is not known. The aims of this study are the evaluation of the prevalence of myoclonus in a big cohort of mitochondrial patients and the clinical characterization of these subjects. Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases," we reviewed the clinical and molecular data of mitochondrial patients with myoclonus among their clinical features. Myoclonus is a rather uncommon clinical feature of mitochondrial diseases (3.6% of 1,086 patients registered in our database). It is not strictly linked to a specific genotype or phenotype, and only 1 of 3 patients with MERRF harbors the 8344A>G mutation (frequently labeled as "the MERRF mutation"). Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. In a myoclonic patient, evidences of mitochondrial dysfunction must be investigated, even though myoclonus is not a common sign of mitochondriopathy. Clinical, histological, and biochemical data may predict the finding of a mitochondrial or nuclear DNA mutation. Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term "myoclonic epilepsy" seems inadequate and potentially misleading. PMID:24510442

  1. Mitochondrial Dynamics in Diabetes

    OpenAIRE

    Yoon, Yisang; Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

    2011-01-01

    Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emergin...

  2. Uncoupled achromatic condition of a dog-leg system with the presence of RF cavities

    CERN Document Server

    Geng, Huiping

    2013-01-01

    To merge the beam from either of the two injectors to the main linac, a dog-leg system will be employed in the second Medium Energy Beam Transport (MEBT2) line of the China ADS driving accelerator. The achromatic condition has to be guaranteed to avoid beam center excursion against energy jitter. RF cavities were found indispensable to control the bunch length growth in the dog-leg system of MEBT2. The full uncoupling between transverse and longitudinal plane is desired to minimize the growth of projected rms emittances. The uncoupled achromatic condition of this dogleg system with the presence of RF bunching cavities will be deduced using the method of transfer matrixes. It is found that to fulfil the uncoupling condition, the distance between the bunching cavities is uniquely determined by the maximum energy gain of the RF cavities. The theoretical analysis is verified by the simulation code TraceWin. The space charge effect on the uncoupled achromatic condition and the beam emittance growth will also be di...

  3. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    Science.gov (United States)

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  4. Roles of p53 in ionizing radiation-induced cell cycle uncoupling

    International Nuclear Information System (INIS)

    Objective: To explore the roles of p53 in ionizing radiation induced MCF-7 cell cycle uncoupling. Methods: The p53 knock-down models was established in MCF-7 with retrovirus packaged particles from 293T cells through calcium acid phosphate co-precipitation, then Western blot was used to detect the protein expression. Flow cytometry(FCM) was used to analyze the cell cycle uncoupling and polyploid after irradiation. Results: Compared with p53+/+ group, the percentages of G0/G1 cells in p53-/- group decreased, while those of S and G2 + M increased (P0/G1, S cells, and the increase of G2 + M cells. The increase of 2N cells and decrease of 4N and 8N cells were observed in both p53+/+ and p53-/- cells. Compared with p53+/+ + IR group, the decrease of G0/G1 and S cells and the increase of G2 + M cells were significant (P-/- + IR groups. 2N cells decreased, 4N cells increased, but no changes in 8 N cells occurred. Conclusion: Radiation might induce G2 arrest and cycle uncoupling, p53 plays a role in the regulation of G2 arrest, but no role in cycle uncoupling. (authors)

  5. Effects of Furnished Cage Type on Behavior and Welfare of Laying Hens

    OpenAIRE

    LI, XIANG; Chen, Donghua; Li, Jianhong; Bao, Jun

    2015-01-01

    This study was conducted to compare the effects of layout of furniture (a perch, nest, and sandbox) in cages on behavior and welfare of hens. Two hundred and sixteen Hyline Brown laying hens were divided into five groups (treatments) with four replicates per group: small furnished cages (SFC), medium furnished cages type I (MFC-I), medium furnished cages type II (MFC-II), and medium furnished cages type III (MFC-III) and conventional cages (CC). The experiment started at 18 week of age and fi...

  6. Hexaphosphapentaprismane: a new gateway to organophosphorus cage compound chemistry.

    Science.gov (United States)

    al-Ktaifani, Mahmoud M; Bauer, Walter; Bergsträsser, Uwe; Breit, Bernhard; Francis, Matthew D; Heinemann, Frank W; Hitchcock, Peter B; Mack, Andreas; Nixon, John F; Pritzkow, Hans; Regitz, Manfred; Zeller, Matthias; Zenneck, Ulrich

    2002-06-01

    Several independent synthetic routes are described leading to the formation of a novel unsaturated tetracyclic phosphorus carbon cage compound tBu4C4P6 (1), which undergoes a light-induced valence isomerization to produce the first hexaphosphapentaprismane cage tBu4C4P6 (2). A second unsaturated isomer tBu4C4P6 (9) of 1 and the bis-[W(CO)5] complex 13 of 1 are stable towards similar isomerization reactions. Another starting material for the synthesis of the hexaphosphapentaprismane cage tBu4C4P6 (2) is the trimeric mercury complex [(tBu4C4P6)Hg]3 (11), which undergoes elimination of mercury to afford the title compound 2. Single-crystal X-ray structural determinations have been carried out on compounds 1, 2, 9, 11, and 13. PMID:12180342

  7. Biologically tunable reactivity of energetic nanomaterials using protein cages.

    Science.gov (United States)

    Slocik, Joseph M; Crouse, Christopher A; Spowart, Jonathan E; Naik, Rajesh R

    2013-06-12

    The performance of aluminum nanomaterial based energetic formulations is dependent on the mass transport, diffusion distance, and stability of reactive components. Here we use a biologically inspired approach to direct the assembly of oxidizer loaded protein cages onto the surface of aluminum nanoparticles to improve reaction kinetics by reducing the diffusion distance between the reactants. Ferritin protein cages were loaded with ammonium perchlorate (AP) or iron oxide and assembled with nAl to create an oxidation-reduction based energetic reaction and the first demonstration of a nanoscale biobased thermite material. Both materials showed enhanced exothermic behavior in comparison to nanothermite mixtures of bulk free AP or synthesized iron oxide nanopowders prepared without the use of ferritin. In addition, by utilizing a layer-by-layer (LbL) process to build multiple layers of protein cages containing iron oxide and iron oxide/AP on nAl, stoichiometric conditions and energetic performance can be optimized. PMID:23713514

  8. Encapsulation of cobalt nanoparticles in cross-linked-polymer cages

    Energy Technology Data Exchange (ETDEWEB)

    Hatamie, Shadie [Department of Electronic-Science, Fergusson College, Pune 411 004 (India); Dhole, S.D. [Department of Physics, University of Pune, Pune 411 007 (India); Ding, J. [Department of Materials Science and Engineering, National University of Singapore, 7, Engineering Drive 1, Singapore 117574 (Singapore); Kale, S.N. [Department of Electronic-Science, Fergusson College, Pune 411 004 (India)], E-mail: sangeetakale2004@gmail.com

    2009-07-15

    Nanoparticles embedded in polymeric cages give rise to interesting applications ranging from nanocatalysis to drug-delivery systems. In this context, we report on synthesis of cobalt (Co) nanoparticles trapped in polyvinyl alcohol (PVA) matrix to yield self-supporting magnetic films in PVA slime. A 20 nm, Co formed in FCC geometry encapsulated with a weak citrate coat when caged in PVA matrix exhibited persistence of magnetism and good radio-frequency response. Cross-linking of PVA chains to form cage-like structures to arrest Co nanoparticles therein, is believed to be the reason for oxide-free nature of Co, promising applications in biomedicine as well as in radio-frequency shielding.

  9. Mice Do Not Habituate to Metabolism Cage Housing

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten Rosenmaj; Darusman, Huda Shalahudin;

    2013-01-01

    abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in...... in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased......The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of...

  10. A Post-Functionalizable Iso-Polyoxotitanate Cage Cluster.

    Science.gov (United States)

    Hou, Jie; Hu, Junyi; Sun, Qing; Zhang, Guanyun; Tung, Chen-Ho; Wang, Yifeng

    2016-07-18

    During solvothermal alcoholysis of a mixture of TiI4 and Ti(O(i)Pr)4, a {I@Ti22} cage cluster encapsulating an OH and iodide guests is crystallized. The {I@Ti22} host-guest cluster surface is postfunctionalizable with catecholate and carboxylate ligands. The synthetic details, structural characterization, spectroscopic properties of the obtained cages clusters are provided. The present study provides candidates for modeling ligand exchange and electron-hole transfer at the titanate nanoparticle surface, and meanwhile offers new opportunities for understanding the TiO2 nanocrystalline formation in solvothermal processes. PMID:27351728

  11. Laboratory animal welfare: cage enrichment and mouse behaviour.

    Science.gov (United States)

    Wolfer, David P; Litvin, Oxana; Morf, Samuel; Nitsch, Roger M; Lipp, Hans-Peter; Würbel, Hanno

    2004-12-16

    Mice housed in standard cages show impaired brain development, abnormal repetitive behaviours (stereotypies) and an anxious behavioural profile, all of which can be lessened by making the cage environment more stimulating. But concerns have been raised that enriched housing might disrupt standardization and so affect the precision and reproducibility of behavioural-test results (for example, see ref. 4). Here we show that environmental enrichment increases neither individual variability in behavioural tests nor the risk of obtaining conflicting data in replicate studies. Our findings indicate that the housing conditions of laboratory mice can be markedly improved without affecting the standardization of results. PMID:15602544

  12. Equivalence Between Squirrel Cage and Sheet Rotor Induction Motor

    Science.gov (United States)

    Dwivedi, Ankita; Singh, S. K.; Srivastava, R. K.

    2016-06-01

    Due to topological changes in dual stator induction motor and high cost of its fabrication, it is convenient to replace the squirrel cage rotor with a composite sheet rotor. For an experimental machine, the inner and outer stator stampings are normally available whereas the procurement of rotor stampings is quite cumbersome and is not always cost effective. In this paper, the equivalence between sheet/solid rotor induction motor and squirrel cage induction motor has been investigated using layer theory of electrical machines, so as to enable one to utilize sheet/solid rotor in dual port experimental machines.

  13. 14C-age tracers in global ocean circulation models

    Directory of Open Access Journals (Sweden)

    W. Koeve

    2014-10-01

    Full Text Available The natural abundance of 14C in total CO2 dissolved in seawater is a property applied to evaluate the water age structure and circulation in the ocean and in ocean models. In this study we use three different representations of the global ocean circulation augmented with a suite of idealised tracers to study the potential and limitations of using natural 14C to determine water age, the time elapsed since a body of water had contact with the atmosphere. We find that, globally, bulk 14C-age is dominated by two equally important components, one associated with aging, i.e. the time component of circulation and one associated with a "preformed 14C-age". This latter quantity exists because of the slow and incomplete atmosphere/ocean equilibration of 14C in particular in high latitudes where many water masses form. The relative contribution of the preformed component to bulk 14C-age varies regionally within a given model, but also between models. Regional variability, e.g. in the Atlantic Ocean is associated with the mixing of waters with very different end members of preformed 14C-age. In the Atlantic, variations in the preformed component over space and time mask the circulation component to an extent that its patterns are not detectable from bulk 14C-age alone. Between models the variability of age can also be considerable (factor of 2, related to the combinations of physical model parameters, which influence circulation dynamics, and gas exchange in the models. The preformed component was found to be very sensitive to gas exchange and moderately sensitive to ice cover. In our model evaluation exercise, the choice of the gas exchange constant from within the current range of uncertainty had such a strong influence on preformed and bulk 14C-age that if model evaluation would be based on bulk 14C-age it could easily impair the evaluation and tuning of a models circulation on global and regional scales. Based on the results of this study, we propose

  14. Sex effect in mutual olfactory relationships of individually caged rabbits

    OpenAIRE

    Alessandro Finzi; Paolo Negretti; Giovanna Bianconi; Pedro González-Redondo

    2015-01-01

    To assess the sex influence on sniffing behavior of rabbits, sets of three rabbits each were located for seven days in contiguous cages divided by a metal wall with holes that prevented the neighboring rabbits to see each other. A buck was located in the central cage, with a doe at each side. Rabbit behavior was video recorded to observe animals sniffing with the muzzle near the wall. The bucks displayed an olfactory preference towards one of the two does, which decreased in few days. The sig...

  15. Reproductive performance of mice in disposable and standard individually ventilated cages.

    Science.gov (United States)

    Ferguson, Danielle R; Bailey, Michele M

    2013-01-01

    This study assessed the reproductive performance of mice housed in 2 types of individually ventilated caging systems. Breeding pairs from 48 female and 24 male mice of 3 established transgenic mouse breeding colonies were placed in either a standard or disposable ventilated caging system. For 3 breeding cycles, the number of pups born, pup survival rate to weaning, time interval between litters, and pup weights were monitored for each breeding pair. Disposable and standard cages were maintained in the same location during breeding. Environmental parameters included intracage temperature, humidity, and ammonia and carbon dioxide levels and room light intensity and sound. Overall, 776 offspring were produced. Breeding performance did not differ significantly between the 2 cage types. By 11 wk of age, the weights of pups from both cage types were equivalent. The intracage temperature was 1.1 °F warmer and light intensity at the site of the nest was 34 lx dimmer in disposable cages than in standard caging. The difference in lighting likely was due to nest location; the nests in the disposable cages were at the back of the cages and away from the anterior air supply, whereas in standard caging, nests were at the front of the cages, with the air supply at the rear. Under these husbandry conditions, mice housed in disposable caging systems have comparable breeding performance to those housed in standard individually ventilated cages. PMID:23849403

  16. Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes.

    Science.gov (United States)

    Weatherly, Lisa M; Shim, Juyoung; Hashmi, Hina N; Kennedy, Rachel H; Hess, Samuel T; Gosse, Julie A

    2016-06-01

    Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care products, at ~10 mm. Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this finding in human mast cells (HMC-1.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free, galactose-containing media (95% confidence interval EC50 = 7.5-9.7 µm), without causing cytotoxicity. Using these same glucose-free conditions, 15 µm TCS dampens RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC-1.2 cells (EC50 4.2-13.7 µm), NIH-3 T3 mouse fibroblasts (EC50 4.8-7.4 µm) and primary human keratinocytes (EC50 3.0-4.1 µm) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS-methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non-cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5 µm TCS inhibits thapsigargin-stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26204821

  17. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

    Science.gov (United States)

    Hoeks, Joris; van Herpen, Noud A.; Mensink, Marco; Moonen-Kornips, Esther; van Beurden, Denis; Hesselink, Matthijs K.C.; Schrauwen, Patrick

    2010-01-01

    OBJECTIVE Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS These findings confirm that the insulin-resistant state has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible

  18. Mitochondrial diseases and epilepsy.

    Science.gov (United States)

    Bindoff, Laurence A; Engelsen, Bernt A

    2012-09-01

    The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age and affects any tissue. However, irrespective of genetic defect, epilepsy is common and there is a significant risk of status epilepticus. This review summarizes our current understanding of the epilepsy that occurs in mitochondrial disease, focusing on three of the most common disorders: mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy and ragged-red fibers (MERRF), and polymerase gamma (POLG) related disease. In addition, we review the pathogenesis and possible treatment of these disorders. PMID:22946726

  19. Play Caging Benefits the Behavior of Singly Housed Laboratory Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Griffis, Caroline M; Martin, Allison L; Perlman, Jaine E; Bloomsmith, Mollie A

    2013-01-01

    This study addresses a recommendation in The Guide for the Care and Use of Laboratory Animals to provide singly housed nonhuman primates with intermittent access to large, enriched (play) caging. Research on the potential benefits of this type of caging is limited. The present study examines the effects of play caging on behavior, activity, and enrichment use. Singly housed, adult male, rhesus macaques (n = 10) underwent a baseline phase in their home cages, a 2-wk treatment phase with housin...

  20. Rearing Laying Hens in Aviaries Reduces Fearfulness following Transfer to Furnished Cages

    OpenAIRE

    Brantsæter, Margrethe; Tahamtani, Fernanda M.; Moe, Randi O; Hansen, Tone B.; Orritt, Rachel; Nicol, Christine; Janczak, Andrew M.

    2016-01-01

    Appropriate rearing is essential for ensuring the welfare and productivity of laying hens. Early experience has the potential to affect the development of fearfulness. This study tested whether rearing in aviaries, as opposed to cages, reduces the fearfulness of laying hens after transfer to furnished cages. Fear responses were recorded as avoidance of a novel object in the home cage. Lohmann Selected Leghorns were reared in an aviary system or conventional rearing cages and then transported ...

  1. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model.

    Science.gov (United States)

    Keller, Amy C; Knaub, Leslie A; McClatchey, P Mason; Connon, Chelsea A; Bouchard, Ron; Miller, Matthew W; Geary, Kate E; Walker, Lori A; Klemm, Dwight J; Reusch, Jane E B

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets. PMID:27034743

  2. Caged polyprenylated xanthones from the resin of Garcinia hanburyi.

    Science.gov (United States)

    Chen, Yu; He, Shiwen; Tang, Chu; Li, Jun; Yang, Guangzhong

    2016-03-01

    Five new caged polyprenylated xanthones (1a, 2a, 3, 10a and 10b), and 12 known related compounds were isolated from the resin of Garcinia hanburyi. Their structures were elucidated by detailed spectroscopic analyses and their α-glucosidase inhibitory activities were investigated in vitro. Most of xanthones showed modest inhibitory activity against α-glucosidase. PMID:26688377

  3. Pathogen Prevalence From Traditional Cage and Free Range Production

    Science.gov (United States)

    Overview: A study was conducted to determine if differences in pathogen prevalence occurred between a sister flock of conventional cage and free range laying hens. Both environmental and egg microbiology was monitored throughout 20 – 79 weeks of age. Salmonella, Campylobacter, and Listeria preval...

  4. Environmental Impact of Cage Culture on Poondi Reservoir, Tamil Nadu

    Directory of Open Access Journals (Sweden)

    P. Anusuya Devi

    2015-12-01

    Full Text Available The present investigation was carried out in Poondi reservoir, Tamil Nadu, for a period of 8 months from September, 2014 to April, 2015 where the cage culture has been already initiated by the state fisheries department. The water and sediment samples were collected from the reservoir at point and non- point sources of the cage culture units and were analyzed for their physico-chemical parameters. The total microbial load, E. coli and feacal streptococci population were also assessed from the reservoir. During the study period, pH, sulphate, nitrate and BOD values were found within the permissible range for drinking water quality. The alkalinity values were found optimum in the reservoir water. The sediment characteristics such as pH, electrical conductivity, total organic carbon and available phosphorus values were also found to be within the standard limit. The optimum water and sediment quality characteristics and the absence of E. coli and feacal streptococci observed in the cage culture unit clearly showed that the small cage farming in the reservoir does not have major environmental impacts on the water and sediment quality.

  5. Sex effect in mutual olfactory relationships of individually caged rabbits

    Directory of Open Access Journals (Sweden)

    Alessandro Finzi

    2015-12-01

    Full Text Available To assess the sex influence on sniffing behavior of rabbits, sets of three rabbits each were located for seven days in contiguous cages divided by a metal wall with holes that prevented the neighboring rabbits to see each other. A buck was located in the central cage, with a doe at each side. Rabbit behavior was video recorded to observe animals sniffing with the muzzle near the wall. The bucks displayed an olfactory preference towards one of the two does, which decreased in few days. The significance was p  0.05. The interest of bucks towards the does was also characterized by a frenetic scratching of the separation wall, contemporary with intense sniffing, displayed only for the first 35 min of the first day. The sniffing behavior of does at the central cage housing the male was not so marked as in bucks, and it progressively changed across the trial (p < 0.01. In conclusion, rabbits establish a transitory sex-oriented olfactory relationship with the conspecifics housed in contiguous cages, which looks no longer necessary once the rabbits have recognized each other.

  6. EFFECTS OF CAGING DENSITY ON PITUITARY AND TESTICLE RELATED RESPONSES

    Science.gov (United States)

    Effects of caging density on pituitary and testicle related responses A significant negative correlation between the incidence of testicular interstitial cell tumors (ICT) and of pituitary tumors (PT) in control male F344 rats is reported associated with the number of ani...

  7. Assessment of the Usability of the Workbench Faraday Cage Method

    DEFF Research Database (Denmark)

    Sørensen, Morten; Franek, Ondrej; Christensen, Søren K.; Pedersen, Gert Frølund; Ebert, Hans

    The workbench Faraday Cage method (WBFC) is a time efficient module pre-compliance test regarding radiated emission. This work investigates the method’s usability and credibility and concludes that for this particular case the WBFC perform a tolerable compliance test for frequencies below 360 MHz...

  8. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  9. Photoregulation of protein plasmid expression in vitro and in vivo using BHQ caging group

    Institute of Scientific and Technical Information of China (English)

    Zhi Ping Zhang; Yi Ming Li; Xiao Yun Chen; Qing Xiang Guo

    2011-01-01

    Green fluorescent protein (GFP) plasmid was caged by 8-bromo-7-hydroxyquinolinyl chromophore (BHQ) for controlling its expression with exact spatiotemporal resolution. In vitro and in vivo experiments clearly verified that, comparing with Bhc caging, the expression level of caged GFP plasmid was dramatically decreased and then efficiently restored after subsequent photolysis.

  10. High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms.

    Science.gov (United States)

    White, C Roger; Giordano, Samantha; Anantharamaiah, G M

    2016-09-01

    Ischemic injury is associated with acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and open heart surgery. The timely re-establishment of blood flow is critical in order to minimize cardiac complications. Reperfusion after a prolonged ischemic period, however, can induce severe cardiomyocyte dysfunction with mitochondria serving as a major target of ischemia/reperfusion (I/R) injury. An increase in the formation of reactive oxygen species (ROS) induces damage to mitochondrial respiratory complexes leading to uncoupling of oxidative phosphorylation. Mitochondrial membrane perturbations also contribute to calcium overload, opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic mediators into the cytoplasm. Clinical and experimental studies show that ischemic preconditioning (ICPRE) and postconditioning (ICPOST) attenuate mitochondrial injury and improve cardiac function in the context of I/R injury. This is achieved by the activation of two principal cell survival cascades: 1) the Reperfusion Injury Salvage Kinase (RISK) pathway; and 2) the Survivor Activating Factor Enhancement (SAFE) pathway. Recent data suggest that high density lipoprotein (HDL) mimics the effects of conditioning protocols and attenuates myocardial I/R injury via activation of the RISK and SAFE signaling cascades. In this review, we discuss the roles of apolipoproteinA-I (apoA-I), the major protein constituent of HDL, and sphingosine 1-phosphate (S1P), a lysosphingolipid associated with small, dense HDL particles as mediators of cardiomyocyte survival. Both apoA-I and S1P exert an infarct-sparing effect by preventing ROS-dependent injury and inhibiting the opening of the mPTP. PMID:27150975

  11. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  12. Oxidation of intramyocellular lipids is dependent on mitochondrial function and the availability of extracellular fatty acids

    DEFF Research Database (Denmark)

    Corpeleijn, Eva; Hessvik, Nina P; Bakke, Siril S;

    2010-01-01

    were extended by comparing these processes in primary cultured myotubes established from healthy lean and obese type 2 diabetic (T2D) individuals, two extremes in a range of metabolic phenotypes. ICLs were prelabeled for 2 days with 100 microM [(14)C]oleic acid (OA). ICL(OX) was studied using a (14)CO......Obesity and insulin resistance are related to both enlarged intramyocellular triacylglycerol stores and accumulation of lipid intermediates. We investigated how lipid overflow can change the oxidation of intramyocellular lipids (ICL(OX)) and intramyocellular lipid storage (ICL). These experiments...... all, a lower mitochondrial mass and lower ICL(OX) were related to a higher cell-associated OA accumulation. Second, myotubes established from obese T2D individuals showed reduced ICL(OX). ICL(OX) remained lower during uncoupling (P <0.001), even with comparable mitochondrial mass, suggesting decreased...

  13. Social communication in mice--are there optimal cage conditions?

    Directory of Open Access Journals (Sweden)

    Allain-Thibeault Ferhat

    Full Text Available Social communication is heavily affected in patients with neuropsychiatric disorders. Accordingly, mouse models designed to study the mechanisms leading to these disorders are tested for this phenotypic trait. Test conditions vary between different models, and the effect of these test conditions on the quantity and quality of social interactions and ultrasonic communication is unknown. The present study examines to which extent the habituation time to the test cage as well as the shape/size of the cage influence social communication in freely interacting mice. We tested 8 pairs of male mice in free dyadic social interactions, with two habituation times (20 min and 30 min and three cage formats (rectangle, round, square. We tested the effect of these conditions on the different types of social contacts, approach-escape sequences, follow behavior, and the time each animal spent in the vision field of the other one, as well as on the emission of ultrasonic vocalizations and their contexts of emission. We provide for the first time an integrated analysis of the social interaction behavior and ultrasonic vocalizations. Surprisingly, we did not highlight any significant effect of habituation time and cage shape/size on the behavioral events examined. There was only a slight increase of social interactions with the longer habituation time in the round cage. Remarkably, we also showed that vocalizations were emitted during specific behavioral sequences especially during close contact or approach behaviors. The present study provides a protocol reliably eliciting social contacts and ultrasonic vocalizations in adult male mice. This protocol is therefore well adapted for standardized investigation of social interactions in mouse models of neuropsychiatric disorders.

  14. Cage Versus Noncage Laying-Hen Housings: Worker Respiratory Health.

    Science.gov (United States)

    Mitchell, Diane; Arteaga, Veronica; Armitage, Tracey; Mitloehner, Frank; Tancredi, Daniel; Kenyon, Nicholas; Schenker, Marc

    2015-01-01

    The objective of this study was to compare respiratory health of poultry workers in conventional cage, enriched cage and aviary layer housing on a single commercial facility, motivated by changing requirements for humane housing of hens. Three workers were randomly assigned daily, one to each of conventional cage, enriched cage, and aviary housing in a crossover repeated-measures design for three observation periods (for a total of 123 worker-days, eight different workers). Workers' exposure to particles were assessed (Arteaga et al. J Agromedicine. 2015;20:this issue) and spirometry, exhaled nitric oxide, respiratory symptoms, and questionnaires were conducted pre- and post-shift. Personal exposures to particles and endotoxin were significantly higher in the aviary than the other housings (Arteaga et al., 2015). The use of respiratory protection was high; the median usage was 70% of the shift. Mixed-effects multivariate regression models of respiratory cross-shift changes were marginally significant, but the aviary system consistently posted the highest decrements for forced expiratory volume in 1 and 6 seconds (FEV1 and FEV6) compared with the enriched or conventional housing. The adjusted mean difference in FEV1 aviary - enriched cage housing was -47 mL/s, 95% confidence interval (CI): (-99 to 4.9), P = .07. Similarly, for FEV6, aviary - conventional housing adjusted mean difference was -52.9 mL/6 s, 95% CI: (-108 to 2.4), P = .06. Workers adopting greater than median use of respiratory protection were less likely to exhibit negative cross-shift pulmonary function changes. Although aviary housing exposed workers to significantly higher respiratory exposures, cross-shift pulmonary function changes did not differ significantly between houses. Higher levels of mask use were protective; poultry workers should wear respiratory protection as appropriate to avoid health decrements. PMID:26237715

  15. Complexation and aggregation of a surfactant cage molecule

    International Nuclear Information System (INIS)

    For applications in selective extraction chemistry, new surfactant cage molecules have been developed and their micellar aqueous solutions studied. With the objective of separating the surfactant properties from the complexing ones, the molecules have been designed with a di-block structure. They have been synthesized by grafting one (or more) surfactant unit to an aza crown macrocycle which is able to selectively complex cations. We have changed the number of linked surfactant (1 or 2) on the aza type cage. The complexing properties of those surfactant cage molecules with Na+ and K+ ions have been shown by mass-spectroscopy. The shape and aggregation number of the micelles are determined by fitting a molecular constrained model of the small angle X-ray and neutron scattering data simultaneously. The surfactant unit displays ellipsoidal to cylindrical micelles and bilayers while increasing the alkyl chain length. On the other hand, the surfactant cage molecules form ellipsoidal micelles whose structure is quite independent of the charge of the molecule. The structure is mostly controlled by the nature and the number of linked surfactants via their steric hindrance added to the volume of the macrocycle. In the last part of this work, we have rescaled a ionic flotation apparatus to dimensions suitable with a small quantity of available product. The surfactant is foaming in the flotation column. With this technic, we can study die adsorption equilibrium at the air/water interface. It is either the adsorption of the counter-ions of a ionic surfactant or the complexation of a cation with a macrocycle ligand at the interface. We have applied this method to a surfactant cage molecule in order to evaluate its extraction properties. (author)

  16. Cage Clusters of Gold and Tin: Golden Buckyballs and Stannaspherene

    Science.gov (United States)

    Wang, Lai-Sheng

    2008-03-01

    Photoelectron spectroscopy (PES) yields direct electronic structure information for size-selected clusters. Combining PES with theoretical calculations has become an effective approach to obtain structural information for small and medium-sized clusters. We present recent discoveries of two classes of cage clusters in gold and tin. Negatively charged gold clusters (Aun^-) have been shown to exhibit a remarkable structural diversity from 2D structures for n = 4-12 and the pyramidal structure for n = 20. Using PES and DFT calculations, we have found that gold clusters with n = 16-18 possess unprecedented hollow cage structures. We have been able to successfully dope a variety of transition-metal atoms into the empty spaces in the golden cages, confirming their structural robustness, as well as demonstrating chemical tuning of their electronic, magnetic, and catalytic properties. Unlike carbon, the heavier congeners of the group 14 elements are not known to form hollow cage structures similar to the fullerenes. In PES studies of tin clusters, we noted that the spectrum of Sn12^- is distinctly different from that of its neighbors or its Si/Ge counterpart. This observation led to our discovery of a highly symmetric and stable icosahedral Sn12^2- cage, for which we coined a name ``stannaspherene'' to describe its high symmetry and spherical pi bonding. We have also shown that all transition metals including the f-block elements can be doped inside Sn12^2- to form a whole class of endohedral stannaspherenes, which may be used as potential building blocks for new cluster-assembled materials. In a preliminary experiment to synthesize stannaspherene in the bulk, a new cluster, Pd2@Sn18^4-, was crystallized and characterized, suggesting all stannaspherene and endohedral stannasphernes may be fabricated in the bulk under suitable conditions.

  17. Mitochondrial dynamics and apoptosis

    OpenAIRE

    Suen, Der-Fen; Norris, Kristi L.; Youle, Richard J.

    2008-01-01

    In healthy cells, mitochondria continually divide and fuse to form a dynamic interconnecting network. The molecular machinery that mediates this organelle fission and fusion is necessary to maintain mitochondrial integrity, perhaps by facilitating DNA or protein quality control. This network disintegrates during apoptosis at the time of cytochrome c release and prior to caspase activation, yielding more numerous and smaller mitochondria. Recent work shows that proteins involved in mitochondri...

  18. The plant mitochondrial proteome

    DEFF Research Database (Denmark)

    Millar, A.H.; Heazlewood, J.L.; Kristensen, B.K.;

    2005-01-01

    The plant mitochondrial proteome might contain as many as 2000-3000 different gene products, each of which might undergo post-translational modification. Recent studies using analytical methods, such as one-, two- and three-dimensional gel electrophoresis and one- and two-dimensional liquid...... context to be defined for them. There are indications that some of these proteins add novel activities to mitochondrial protein complexes in plants....

  19. Mitochondrial metabolism and diabetes

    OpenAIRE

    Kwak, Soo Heon; Park, Kyong Soo; Lee, Ki‐Up; Lee, Hong Kyu

    2010-01-01

    Abstract The oversupply of calories and sedentary lifestyle has resulted in a rapid increase of diabetes prevalence worldwide. During the past two decades, lines of evidence suggest that mitochondrial dysfunction plays a key role in the pathophysiology of diabetes. Mitochondria are vital to most of the eukaryotic cells as they provide energy in the form of adenosine triphosphate by oxidative phosphorylation. In addition, mitochondrial function is an integral part of glucose‐stimulated insulin...

  20. Inherited mitochondrial neuropathies.

    Science.gov (United States)

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  1. Intra-cage dynamics of molecular hydrogen confined in cages of two different dimensions of clathrate hydrates

    Science.gov (United States)

    Russina, Margarita; Kemner, Ewout; Mezei, Ferenc

    2016-01-01

    In porous materials the molecular confinement is often realized by means of weak Van der Waals interactions between the molecule and the pore surface. The understanding of the mechanism of such interactions is important for a number of applications. In order to establish the role of the confinement size we have studied the microscopic dynamics of molecular hydrogen stored in the nanocages of clathrate hydrates of two different dimensions. We have found that by varying the size of the pore the diffusive mobility of confined hydrogen can be modified in both directions, i.e. reduced or enhanced compared to that in the bulk solid at the same temperatures. In the small cages with a mean crystallographic radius of 3.95 Å the confinement reduces diffusive mobility by orders of magnitude. In contrast, in large cages with a mean radius of 4.75 Å hydrogen molecules displays diffusive jump motion between different equilibrium sites inside the cages, visible at temperatures where bulk H2 is solid. The localization of H2 molecules observed in small cages can promote improved functional properties valuable for hydrogen storage applications. PMID:27270444

  2. Multiplexed Analysis of Cage and Cage Free Chicken Egg Fatty Acids Using Stable Isotope Labeling and Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Richard G. Torde

    2013-12-01

    Full Text Available Binary stable isotope labeling couple with LC-ESI-MS has been used as a powerful non-targeted approach for the relative quantification of lipids, amino acids, and many other important metabolite classes. A multiplexed approach using three or more isotopic labeling reagents greatly reduces analytical run-time while maintaining excellent sensitivity and reproducibility. Three isotopic cholamine labeling reagents have been developed to take advantage of the pre-ionized character of cholamine, for ESI, and the ease by which stable isotopes can be incorporated into the cholamine structure. These three cholamine labeling reagents have been used to relatively quantify three fatty acid samples simultaneously. The quantification resulted in the observation of 12 fatty acids that had an average absolute error of 0.9% and an average coefficient of variation of 6.1%. Caged versus cage-free isotope labeling experiments showed that cage-free eggs have an increased level of omega-3 fatty acids as compared to caged eggs. This multiplexed fatty acid analysis provides an inexpensive and expedited tool for broad-based lipid profiling that will further aid discoveries in the mechanisms of fatty acid action in cells.

  3. Impaired fear extinction as displayed by serotonin transporter knockout rats housed in open cages is disrupted by IVC cage housing.

    Directory of Open Access Journals (Sweden)

    Ling Shan

    Full Text Available Anxiety disorders are influenced by both environmental and genetic factors. A well-known example for gene x environment interactions in psychiatry is the low activity (s allelic variant of the serotonin transporter (5-HTT promoter polymorphism (5-HTTLPR that in the context of stress increases risk for depression and post-traumatic stress disorder (PTSD. Previously, we observed robust anxiety-related phenotypes, such as an impairment in fear extinction, in 5-HTT knockout (5-HTT-/- versus wild-type (5-HTT+/+ rats housed in open cages. Recently, housing conditions were changed from open cages to individually ventilated cages (IVC, which are associated with a high ventilation fold and noise. This switch in housing conditions prompted an unplanned 5-HTT gene x environment interaction study in our rats. The current study shows that lifetime stress by means of IVC cage housing abolished genotype differences in fear extinction between 5-HTT-/- and 5-HTT+/+ rats. Although this effect was not attributed specifically to either the 5-HTT+/+ or the 5-HTT-/- genotype, the findings are in agreement with the modulatory role of serotonin in the processing of environmental stimuli. Our findings also underline the possibility that housing conditions confound the interpretation of anxiety-related behaviours in rodents.

  4. Intra-cage dynamics of molecular hydrogen confined in cages of two different dimensions of clathrate hydrates

    Science.gov (United States)

    Russina, Margarita; Kemner, Ewout; Mezei, Ferenc

    2016-06-01

    In porous materials the molecular confinement is often realized by means of weak Van der Waals interactions between the molecule and the pore surface. The understanding of the mechanism of such interactions is important for a number of applications. In order to establish the role of the confinement size we have studied the microscopic dynamics of molecular hydrogen stored in the nanocages of clathrate hydrates of two different dimensions. We have found that by varying the size of the pore the diffusive mobility of confined hydrogen can be modified in both directions, i.e. reduced or enhanced compared to that in the bulk solid at the same temperatures. In the small cages with a mean crystallographic radius of 3.95 Å the confinement reduces diffusive mobility by orders of magnitude. In contrast, in large cages with a mean radius of 4.75 Å hydrogen molecules displays diffusive jump motion between different equilibrium sites inside the cages, visible at temperatures where bulk H2 is solid. The localization of H2 molecules observed in small cages can promote improved functional properties valuable for hydrogen storage applications.

  5. Interactions of copper and thermal stress on mitochondrial bioenergetics in rainbow trout, Oncorhynchus mykiss

    Energy Technology Data Exchange (ETDEWEB)

    Sappal, Ravinder [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); MacDonald, Nicole [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Fast, Mark [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Siah, Ahmed [British Columbia Centre for Aquatic Health Sciences, 871A Island Highway, Campbell River, BC V9W 2C2 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada)

    2014-12-15

    Highlights: • Interacting effects of Cu and temperature were investigated in rainbow trout liver mitochondria. • Mitochondrial functional indices are highly sensitive to temperature change. • High and low temperatures sensitize mitochondria to adverse effects of Cu. • Cu induces a highly temperature-sensitive mitochondrial permeability transition pore. • Cu-imposed mitochondrial membrane potential dissipation is mediated by reactive oxygen species. - Abstract: Thermal stress may influence how organisms respond to concurrent or subsequent chemical, physical and biotic stressors. To unveil the potential mechanisms via which thermal stress modulates metals-induced bioenergetic disturbances, the interacting effects of temperature and copper (Cu) were investigated in vitro. Mitochondria isolated from rainbow trout livers were exposed to a range of Cu concentrations at three temperatures (5, 15 and 25 °C) with measurement of mitochondrial complex I (mtCI)-driven respiratory flux indices and uncoupler-stimulated respiration. Additional studies assessed effects of temperature and Cu on mtCI enzyme activity, induction of mitochondrial permeability transition pore (MPTP), swelling kinetics and mitochondrial membrane potential (MMP). Maximal and basal respiration rates, as well as the proton leak, increased with temperature with the Q{sub 10} effects being higher at lower temperatures. The effect of Cu depended on the mitochondrial functional state in that the maximal respiration was monotonically inhibited by Cu exposure while low and high Cu concentrations stimulated and inhibited the basal respiration/proton leak, respectively. Importantly, temperature exacerbated the effects of Cu by lowering the concentration of the metal required for toxicity and causing loss of thermal dependence of mitochondrial respiration. Mitochondrial complex I activity was inhibited by Cu but was not affected by incubation temperature. Compared with the calcium (Ca) positive control

  6. Interactions of copper and thermal stress on mitochondrial bioenergetics in rainbow trout, Oncorhynchus mykiss

    International Nuclear Information System (INIS)

    Highlights: • Interacting effects of Cu and temperature were investigated in rainbow trout liver mitochondria. • Mitochondrial functional indices are highly sensitive to temperature change. • High and low temperatures sensitize mitochondria to adverse effects of Cu. • Cu induces a highly temperature-sensitive mitochondrial permeability transition pore. • Cu-imposed mitochondrial membrane potential dissipation is mediated by reactive oxygen species. - Abstract: Thermal stress may influence how organisms respond to concurrent or subsequent chemical, physical and biotic stressors. To unveil the potential mechanisms via which thermal stress modulates metals-induced bioenergetic disturbances, the interacting effects of temperature and copper (Cu) were investigated in vitro. Mitochondria isolated from rainbow trout livers were exposed to a range of Cu concentrations at three temperatures (5, 15 and 25 °C) with measurement of mitochondrial complex I (mtCI)-driven respiratory flux indices and uncoupler-stimulated respiration. Additional studies assessed effects of temperature and Cu on mtCI enzyme activity, induction of mitochondrial permeability transition pore (MPTP), swelling kinetics and mitochondrial membrane potential (MMP). Maximal and basal respiration rates, as well as the proton leak, increased with temperature with the Q10 effects being higher at lower temperatures. The effect of Cu depended on the mitochondrial functional state in that the maximal respiration was monotonically inhibited by Cu exposure while low and high Cu concentrations stimulated and inhibited the basal respiration/proton leak, respectively. Importantly, temperature exacerbated the effects of Cu by lowering the concentration of the metal required for toxicity and causing loss of thermal dependence of mitochondrial respiration. Mitochondrial complex I activity was inhibited by Cu but was not affected by incubation temperature. Compared with the calcium (Ca) positive control, Cu

  7. Effects of cage density, sanitation frequency, and bedding type on animal wellbeing and health and cage environment in mice and rats.

    Science.gov (United States)

    Horn, Mandy J; Hudson, Shanice V; Bostrom, Linda A; Cooper, Dale M

    2012-11-01

    The objective of the current study was to evaluate the effects of cage density, sanitation frequency, and bedding type on animal growth and welfare. At weaning, Sprague-Dawley rats and C57BL/6 mice were allocated to treatment groups according to sex, bedding type (shredded aspen, cellulose, or a 50:50 mixture), and cage density and sanitation frequency (inhouse cage density standards and sanitation procedures measured against Guide recommendations) for an 8-wk period. Body weight, feed disappearance, cage ammonia, ATP concentrations, behavior, morbidity, and mortality were assessed weekly; fecal corticosterone, microbiology, and lung histopathology (rats only) were evaluated at the culmination of the trial. In both rats and mice, parameters indicative of animal health and welfare were not significantly affected by cage density and sanitation frequency or bedding type. Occasional effects of feed disappearance and cage ammonia concentrations due to density and sanitation guidelines were noted in rat cages, and bedding type affected cage ammonia and ATP concentrations. Periodic spikes of cage ammonia and ATP concentrations were recorded in mouse cages maintained according to inhouse compared with Guide standards and in cages containing aspen compared with cellulose or aspen-cellulose mixed bedding. Ongoing studies and historical data support the finding that deviations or exceptions from the cage density and sanitation frequency standards set forth in the Guide do not negatively affect animal health, welfare, or production parameters at our institution. These parameters appear to be credible measures of animal health and wellbeing and may be useful for evaluating performance standards for animal husbandry. PMID:23294884

  8. Effects of Cage Density, Sanitation Frequency, and Bedding Type on Animal Wellbeing and Health and Cage Environment in Mice and Rats

    OpenAIRE

    Horn, Mandy J; Hudson, Shanice V.; Bostrom, Linda A; Cooper, Dale M

    2012-01-01

    The objective of the current study was to evaluate the effects of cage density, sanitation frequency, and bedding type on animal growth and welfare. At weaning, Sprague–Dawley rats and C57BL/6 mice were allocated to treatment groups according to sex, bedding type (shredded aspen, cellulose, or a 50:50 mixture), and cage density and sanitation frequency (inhouse cage density standards and sanitation procedures measured against Guide recommendations) for an 8-wk period. Body weight, feed disapp...

  9. Uncoupling of reading and IQ over time: empirical evidence for a definition of dyslexia.

    Science.gov (United States)

    Ferrer, Emilio; Shaywitz, Bennett A; Holahan, John M; Marchione, Karen; Shaywitz, Sally E

    2010-01-01

    Developmental dyslexia is defined as an unexpected difficulty in reading in individuals who otherwise possess the intelligence and motivation considered necessary for fluent reading, and who also have had reasonable reading instruction. Identifying factors associated with normative and impaired reading development has implications for diagnosis, intervention, and prevention. We show that in typical readers, reading and IQ development are dynamically linked over time. Such mutual interrelationships are not perceptible in dyslexic readers, which suggests that reading and cognition develop more independently in these individuals. To our knowledge, these findings provide the first empirical demonstration of a coupling between cognition and reading in typical readers and a developmental uncoupling between cognition and reading in dyslexic readers. This uncoupling was the core concept of the initial description of dyslexia and remains the focus of the current definitional model of this learning disability. PMID:20424029

  10. Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Kovář, J.; Syrový, Ivo; Flachs, Pavel; Bobková, D.; Kolář, František; Poledne, R.; Kopecký, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 835-844. ISSN 1071-7323 R&D Projects: GA ČR(CZ) GP303/03/P127; GA ČR(CZ) GA303/02/1220 Institutional research plan: CEZ:AV0Z5011922 Keywords : adipose tissue * uncoupling protein * lipoprotein lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.972, year: 2005

  11. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system

    OpenAIRE

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D.; Jelokhani-Niaraki, Masoud

    2015-01-01

    Uncoupling proteins (UCP)2, UCP4 and UCP5 transport protons across the inner membrane of mitochondria in the central nervous system (CNS). Novel recombinant protein expression allowed expression of UCPs in Escherichia coli membranes. Functional neuronal UCPs formed multimers in membranes and interacted with various fatty acids (FAs) to transport protons. Self-association and unique ion transport properties of UCPs distinguish their physiological roles in the CNS.

  12. Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced hepatic steatosis

    OpenAIRE

    Ma Shuangtao; Yang Dachun; Li; Tan Yan; Tang Bing; Yang Yongjian

    2012-01-01

    Abstract Background Uncoupling protein 2 (UCP2) was reported to be involved in lipid metabolism through regulating the production of superoxide anion. However, the role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized that UCP2 might regulate hepatic steatosis via suppressing oxidative stress. Results We tested this hypothesis in an in vitro model of hepatocytic steatosis in HepG2 cell lines induced by palmitic acid (PA). We found that treatment with PA induced an obv...

  13. Uncoupling of longevity and paraquat resistance in mutants of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Fujii, Michihiko; Tanaka, Nanae; Miki, Kensuke; Hossain, Mohammad Nazir; Endoh, Morio; Ayusawa, Dai

    2005-10-01

    To analyze the relationship between resistance to oxidative stress and longevity, we isolated three novel paraquat-resistant mutants, mev-5, mev-6, and mev-7, from the nematode Caenorhabditis elegans. They all showed the Dyf (defective in dye filling) phenotype, but not always resistance to heat or UV. Life-span extension was observed only in the mev-5 mutant at 26 degrees C. These results indicate that longevity is uncoupled with the phenotype of paraquat resistance. PMID:16244463

  14. THE CALCULATION OF INITIAL SHOCK WAVE IN ROCK WITH UNCOUPLING CHARGE BLASTING

    Institute of Scientific and Technical Information of China (English)

    李玉民; 倪芝芳; 黄忆龙

    1997-01-01

    According to the structure of explosive charge in rock blasting, a physical model has been set up in this paper. Based on the model, a methodology for calculating initial shock wave of uncoupling charge has been given. The pressure P3 has been calculated when high explosives act on granite, limestone, marble and shale respectively. Some important conclusions are also gained by the analysis of results.

  15. Kidney Function After In Vivo Gene Silencing of Uncoupling Protein-2 in Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Persson, Malou Friederich; Welch, William. J; Wilcox, Christopher S; Palm, Fredrik

    2013-01-01

    Kidney uncoupling protein 2 (UCP-2) increases in streptozotocin-induced diabetes, resulting in mitochondria uncoupling, i.e., increased oxygen consumption unrelated to active transport. The present study aimed to investigate the role of UCP-2 for normal and diabetic kidney function utilizing small interference RNA (siRNA) to reduce protein expression. Diabetic animals had increased glomerular filtration rate and kidney oxygen consumption, resulting in decreased oxygen tension and transported ...

  16. Effects of single caging and cage size on behavior and stress level of domestic neutered cats housed in an animal shelter.

    Science.gov (United States)

    Uetake, Katsuji; Goto, Akihiro; Koyama, Rumi; Kikuchi, Rieko; Tanaka, Toshio

    2013-03-01

    Cats need a minimum amount of space even in animal shelters. In this study the effects of single caging and cage size on the behavior and stress level of domestic cats were investigated. Six neutered cats (2-15 years old) that had been housed in a group for at least 7 months were moved to three kinds of single cages (small, medium and large) by rotation on a Latin square design. They experienced each cage size for 6 days. Cats could use vertical dimensions when housed in a group room and the large cage. Behavioral observation was conducted for 3 h in the evening, and stress levels were assessed by urine cortisol-to-creatinine ratios. The amounts (estimated proportions) of time spent in locomotion and social/solitary play were lower even in large cages than in group housing (both P < 0.05). Conversely, the amount of time spent resting tended to increase when housed singly (P = 0.104). The urine cortisol-to-creatinine ratios of singly housed cats tended to be higher than that of group-housed cats (P = 0.086). The results indicate that cats become less active when they are housed singly in cages regardless of the cage size. Cats seem to feel no undue stress even in small cages if the stay is short. PMID:23480709

  17. Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism.

    Science.gov (United States)

    Gabrielová, Eva; Jabůrek, Martin; Gažák, Radek; Vostálová, Jitka; Ježek, Jan; Křen, Vladimír; Modrianský, Martin

    2010-12-01

    Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence. Experiments evaluating oxygen consumption and membrane potential revealed that dehydrosilybin uncouples the respiration of isolated rat heart mitochondria albeit with a much lower potency than synthetic uncouplers. Furthermore, dehydrosilybin revealed a very high potency in suppressing ROS formation in isolated rat heart mitochondria with IC(50) = 0.15 μM. It is far more effective than its effect in a purely chemical system generating superoxide or in cells capable of oxidative burst, where the IC(50) for dehydrosilybin exceeds 50 μM. Dehydrosilybin also attenuated ROS formation caused by rotenone in the primary cultures of neonatal rat cardiomyocytes. We infer that the apparent uncoupler-like activity of dehydrosilybin is the basis of its ROS modulation effect in neonatal rat cardiomyocytes and leads us to propose a hypothesis on natural ischemia preconditioning by dietary polyphenols. PMID:21153691

  18. The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.

    Science.gov (United States)

    Vincent, Amy E; Ng, Yi Shiau; White, Kathryn; Davey, Tracey; Mannella, Carmen; Falkous, Gavin; Feeney, Catherine; Schaefer, Andrew M; McFarland, Robert; Gorman, Grainne S; Taylor, Robert W; Turnbull, Doug M; Picard, Martin

    2016-01-01

    Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease. PMID:27506553

  19. Neurological mitochondrial cytopathies.

    Directory of Open Access Journals (Sweden)

    Mehndiratta M

    2002-04-01

    Full Text Available The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years. Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes, three had MERRF (myoclonic epilepsy and ragged red fibre myopathy, three cases had KSS (Kearns-Sayre Syndrome and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%. Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.

  20. Lanthanides caged by the organic chelates; structural properties

    Science.gov (United States)

    Smentek, Lidia

    2011-04-01

    The structure, in particular symmetry, geometry and morphology of organic chelates coordinated with the lanthanide ions are analyzed in the present review. This is the first part of a complete presentation of a theoretical description of the properties of systems, which are widely used in technology, but most of all, in molecular biology and medicine. The discussion is focused on the symmetry and geometry of the cages, since these features play a dominant role in the spectroscopic activity of the lanthanides caged by organic chelates. At the same time, the spectroscopic properties require more formal presentation in the language of Racah algebra, and deserve a separate analysis. In addition to the parent systems of DOTA, DOTP, EDTMP and CDTMP presented here, their modifications by various antennas are analyzed. The conclusions that have a strong impact upon the theory of the energy transfer and the sensitized luminescence of these systems are based on the results of numerical density functional theory calculations.

  1. Jamming vs Caging in Three Dimensional Jamming Percolation

    Science.gov (United States)

    Shokef, Yair; Segall, Nimrod; Teomy, Eial

    We study a three-dimensional kinetically-constrained lattice-gas model, in which the ability of a particle to move depends on the occupation of neighboring sites in an orientational manner. The kinetic rules are constructed such that chains of permanently-frozen particles reach an infinite length at the critical density of directed percolation. Thus at this critical density the system undergoes a jamming transition, above which there is a finite fraction of jammed particles. We demonstrate that the three-dimensional mesh-like structure of the one-dimensional jammed chains enables the free particles to propagate through the holes in this mesh. This diffusive motion is terminated at a second critical density above which all particles are caged. The largest and second largest clusters of dynamically-connected sites exhibit singularities at both densities. Thus our model assists in separating between the two distinct phenomena of jamming and caging.

  2. Cages and Anomalous Diffusion in Vibrated Dense Granular Media

    Science.gov (United States)

    Scalliet, Camille; Gnoli, Andrea; Puglisi, Andrea; Vulpiani, Angelo

    2015-05-01

    A vertically shaken granular medium hosts a blade rotating around a fixed vertical axis, which acts as a mesorheological probe. At high densities, independently of the shaking intensity, the blade's dynamics shows strong caging effects, marked by transient subdiffusion and a maximum in the velocity power density spectrum, at a resonant frequency ˜10 Hz . Interpreting the data through a diffusing harmonic cage model allows us to retrieve the elastic constant of the granular medium and its collective diffusion coefficient. For high frequencies f , a tail ˜1 /f in the velocity power density spectrum reveals nontrivial correlations in the intracage microdynamics. At very long times (larger than 10 s), a superdiffusive behavior emerges, ballistic in the most extreme cases. Consistently, the distribution of slow velocity inversion times τ displays a power-law decay, likely due to persistent collective fluctuations of the host medium.

  3. Cages and anomalous diffusion in vibrated dense granular media.

    Science.gov (United States)

    Scalliet, Camille; Gnoli, Andrea; Puglisi, Andrea; Vulpiani, Angelo

    2015-05-15

    A vertically shaken granular medium hosts a blade rotating around a fixed vertical axis, which acts as a mesorheological probe. At high densities, independently of the shaking intensity, the blade's dynamics shows strong caging effects, marked by transient subdiffusion and a maximum in the velocity power density spectrum, at a resonant frequency ~10 Hz. Interpreting the data through a diffusing harmonic cage model allows us to retrieve the elastic constant of the granular medium and its collective diffusion coefficient. For high frequencies f, a tail ~1/f in the velocity power density spectrum reveals nontrivial correlations in the intracage microdynamics. At very long times (larger than 10 s), a superdiffusive behavior emerges, ballistic in the most extreme cases. Consistently, the distribution of slow velocity inversion times τ displays a power-law decay, likely due to persistent collective fluctuations of the host medium. PMID:26024199

  4. Rotational Brownian Dynamics simulations of clathrin cage formation

    International Nuclear Information System (INIS)

    The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage

  5. Mitochondrial fusion and inheritance of the mitochondrial genome.

    Science.gov (United States)

    Takano, Hiroyoshi; Onoue, Kenta; Kawano, Shigeyuki

    2010-03-01

    Although maternal or uniparental inheritance of mitochondrial genomes is a general rule, biparental inheritance is sometimes observed in protists and fungi,including yeasts. In yeast, recombination occurs between the mitochondrial genomes inherited from both parents.Mitochondrial fusion observed in yeast zygotes is thought to set up a space for DNA recombination. In the last decade,a universal mitochondrial fusion mechanism has been uncovered, using yeast as a model. On the other hand, an alternative mitochondrial fusion mechanism has been identified in the true slime mold Physarum polycephalum.A specific mitochondrial plasmid, mF, has been detected as the genetic material that causes mitochondrial fusion in P. polycephalum. Without mF, fusion of the mitochondria is not observed throughout the life cycle, suggesting that Physarum has no constitutive mitochondrial fusion mechanism.Conversely, mitochondria fuse in zygotes and during sporulation with mF. The complete mF sequence suggests that one gene, ORF640, encodes a fusogen for Physarum mitochondria. Although in general, mitochondria are inherited uniparentally, biparental inheritance occurs with specific sexual crossing in P. polycephalum.An analysis of the transmission of mitochondrial genomes has shown that recombinations between two parental mitochondrial genomes require mitochondrial fusion,mediated by mF. Physarum is a unique organism for studying mitochondrial fusion. PMID:20196232

  6. Faraday cage angled-etching of nanostructures in bulk dielectrics

    OpenAIRE

    Latawiec, Pawel; Burek, Michael J.; Sohn, Young-Ik; Lončar, Marko

    2016-01-01

    For many emerging optoelectronic materials, heteroepitaxial growth techniques do not offer the same high material quality afforded by bulk, single-crystal growth. However, the need for optical, electrical, or mechanical isolation at the nanoscale level often necessitates the use of a dissimilar substrate, upon which the active device layer stands. Faraday cage angled-etching (FCAE) obviates the need for these planar, thin-film technologies by enabling in-situ device release and isolation thro...

  7. Environmental Enrichment Reduces Signs of Boredom in Caged Mink

    OpenAIRE

    Meagher, Rebecca K.; Mason, Georgia J

    2012-01-01

    Animals housed in impoverished cages are often labelled ‘bored’. They have also been called ‘apathetic’ or ‘depressed’, particularly when profoundly inactive. However, these terms are rarely operationally defined and validated. As a negative state caused by under-stimulation, boredom should increase interest in stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as decreased interest in all stimuli, while anhedonia (loss of pleasure, a depressive symptom) should spec...

  8. Effect of Cage-Wash Temperature on the Removal of Infectious Agents from Caging and the Detection of Infectious Agents on the Filters of Animal Bedding-Disposal Cabinets by PCR Analysis

    OpenAIRE

    Compton, Susan R; Macy, James D

    2015-01-01

    Efficient, effective cage decontamination and the detection of infection are important to sustainable biosecurity within animal facilities. This study compared the efficacy of cage washing at 110 and 180 °F on preventing pathogen transmission. Soiled cages from mice infected with mouse parvovirus (MPV) and mouse hepatitis virus (MHV) were washed at 110 or 180 °F or were not washed. Sentinels from washed cages did not seroconvert to either virus, whereas sentinels in unwashed cages seroconvert...

  9. Energy saving work of frequency controlled induction cage machine

    International Nuclear Information System (INIS)

    Energy saving work, understood as lowering the supply voltage when load torque is much less than rated, is one way of reducing power losses in an induction cage machine working with a variable load. Reduction in power losses also affects the thermal properties of an induction machine because the energy saving work allows the temperature rise of the windings to decrease. Thanks to a lower temperature of the windings, the same load torque can be carried by a machine of less rated power. The ability of energy saving work to reduce the temperature of windings depends on the thermal properties of an induction machine, which are different in the case of a machine with foreign ventilation and its own ventilation. This paper deals with the thermal effect of energy saving work on a frequency controlled induction cage machine. A comparison of the properties of a machine with its own and outside ventilation is presented. The results of the investigations are shown for a 3 kW induction cage machine with the two previously mentioned ways of ventilation: one provided with a fan placed on a shaft and the other provided with a fan driven by an auxiliary motor

  10. Genotoxicity monitoring of freshwater environments using caged carp (Cyprinus carpio).

    Science.gov (United States)

    Klobucar, Göran I V; Stambuk, Anamaria; Pavlica, Mirjana; Sertić Perić, Mirela; Kutuzović Hackenberger, Branimir; Hylland, Ketil

    2010-01-01

    The present study deals with genotoxicity assessment of freshwaters using caged carp (Cyprinus carpio). Carps were transplanted from a fish-farm to three differently polluted sites in eastern Croatia. Two polluted sites were situated in the river Drava, downstream from the cities of Belisće and Osijek, while the reference site was in the Nature Park Kopacki rit, a preserved wetland area with limited anthropogenic influence. Exposure lasted for 3 weeks and was repeated for 3 years (2002-2004). DNA damage was assessed in erythrocytes of the exposed animals by the Comet assay and micronucleus test (MNT). In order to evaluate possible differences in stress responses to polluted water in situ and in aquaria a laboratory exposure was performed with water from the studied location in the second year of the study. Carp from the sites with high anthropogenic influence (Belisće and Osijek) had higher average DNA damage as expressed in both the MNT and Comet assay. Of the two, the Comet assay appeared to be more sensitive following both caging and aquaria exposures. The results from this study suggest that 3 weeks caging exposure of C. carpio may be a useful strategy to monitor for genotoxic agents in freshwater ecosystems. PMID:19626438

  11. Prevalence of Salmonella in flocks housed in enriched cages.

    Science.gov (United States)

    Zongo, P; Ducrot, A; Burie, J-B; Beaumont, C

    2015-04-01

    Salmonellosis is a foodborne disease of humans and animals caused by infection with Salmonella. The aim of this paper is to improve a deterministic model (DM) and an individual-based model (IBM) with reference to Salmonella propagation in flocks of laying hens taking into account variations in hens housed in the same cage and to compare both models. The spatio-temporal evolution, the basic reproduction number, R 0, and the speed of wave propagation were computed for both models. While in most cases the DM allows summary of all the features of the model in the formula for computation of R 0, slight differences between individuals or groups may be observed with the IBM that could not be expected from the DM, especially when initial environmental contamination is very low and some cages may get rid of bacteria. Both models suggest that the cage size plays a role on the risk and speed of propagation of the bacteria, which should be considered when designing new breeding systems. PMID:25084397

  12. Mitochondrial Dysfunction and Psychiatric Disorders

    OpenAIRE

    Shaw-Hwa Jou; Nan-Yin Chiu; Chin-San Liu

    2009-01-01

    Mitochondria are intracellular organelles crucial in the production of cellular energy.Mitochondrial diseases may result from malfunctions in this biochemical cascade. Severalinvestigators have proposed that mitochondrial dysfunction is related to the pathophysiologyof bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Theauthors reviewed recent study findings and tried to delineate the current understanding of thecorrelation between mitochondrial dysfunction and p...

  13. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

  14. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet.

    Science.gov (United States)

    Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo

    2015-01-01

    In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism. PMID:26301251

  15. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Alessandra Ferramosca

    2015-01-01

    Full Text Available In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group, a diet with 35% fat (HF group, or a high-fat diet supplemented with 2.5% krill oil (HF+KO group. The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

  16. The Level of ALR is Regulated by the Quantity of Mitochondrial DNA.

    Science.gov (United States)

    Balogh, Tibor; Lőrincz, Tamás; Stiller, Ibolya; Mandl, József; Bánhegyi, Gábor; Szarka, András

    2016-04-01

    Augmenter of liver regeneration (ALR) contributes to mitochondrial biogenesis, maintenance and to the physiological operation of mitochondria. The depletion of ALR has been widely studied and had serious consequences on the mitochondrial functions. However the inverse direction, the effect of the depletion of mitochondrial electron transfer chain and mtDNA on ALR expression has not been investigated yet. Thus mtDNA depleted, ρ(0) cell line was prepared to investigate the role of mitochondrial electron transfer chain and mtDNA on ALR expression. The depletion of mtDNA has not caused any difference at mRNA level, but at protein level the expression of ALR has been markedly increased. The regulatory role of ATP and ROS levels could be ruled out because the treatment of the parental cell line with different respiratory inhibitors and uncoupling agent could not provoke any changes in the protein level of ALR. The effect of mtDNA depletion on the protein level of ALR has been proved not to be liver specific, since the phenomenon could be observed in the case of two other, non-hepatic cell lines. It seems the level of mtDNA and/or its products may have regulatory role on the protein level of ALR. The up-regulation of ALR can be a part of the adaptive response in ρ(0) cells that preserves the structural integrity and the transmembrane potential despite the absence of protein components encoded by the mtDNA. PMID:26584568

  17. Flow Field Characteristics of the Rotor Cage in Turbo Air Classifiers

    Institute of Scientific and Technical Information of China (English)

    GUO Lijie; LIU Jiaxiang; LIU Shengzhao

    2009-01-01

    The turbo air classifier is widely used powder classification equipment in a variety of fields. The flow field characteristics of the turbo air classifier are important basis for the improvement of the turbo air classifier's structural design. The flow field characteristics of the rotor cage in turbo air classifiers were investigated under different operating conditions by laser Doppler velocimeter(LDV), and a measure diminishing the axial velocity is proposed. The investigation results show that the tangential velocity of the air flow inside the rotor cage is different from the rotary speed of the rotor cage on the same measurement point due to the influences of both the negative pressure at the exit and the rotation of the rotor cage. The tangential velocity of the air flow likewise decreases as the radius decreases in the case of the rotor cage's low rotary speed. In contrast, the tangential velocity of the air flow increases as the radius decreases in the case of the rotor cage's high rotary speed. Meanwhile, the vortex inside the rotor cage is found to occur near the pressure side of the blade when the rotor cage's rotary speed is less than the tangential velocity of air flow. On the contrary, the vortex is found to occur near the blade suction side once the rotor cage's rotary speed is higher than the tangential velocity of air flow. Inside the rotor cage, the axial velocity could not be disregarded and is largely determined by the distances between the measurement point and the exit.

  18. Influence of 5 Different Caging Types and the Use of Cage-Changing Stations on Mouse Allergen Exposure

    OpenAIRE

    Feistenauer, Susan; Sander, Ingrid; Schmidt, Jörg; Zahradnik, Eva; Raulf, Monika; Brielmeier, Markus

    2014-01-01

    Animal allergens constitute a serious health risk in laboratory animal facilities. To assess possibilities for allergen reduction by technical and organizational measures, we studied personnel exposure to mouse urinary aeroallergens in an animal facility with a holding capacity of 30,000 cages. Short-term (2 h) and intermediate-term (12 h) stationary samples (n = 107) and short-term (2 h) personnel samples (n = 119) were collected on polytetrafluorethylene filters by using air pumps. Long-ter...

  19. New caged neurotransmitter analogs selective for glutamate receptor sub-types based on methoxynitroindoline and nitrophenylethoxycarbonyl caging groups

    Czech Academy of Sciences Publication Activity Database

    Palma-Cerda, F.; Auger, C.; Crawford, D.J.; Hodgson, A.C.C.; Reynolds, S.J.; Cowell, J.K.; Swift, K.A.D.; Cais, Ondřej; Vyklický ml., Ladislav; Corrie, J.E.T.; Ogden, D.

    2012-01-01

    Roč. 63, č. 4 (2012), s. 624-634. ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA309/07/0271 Grant ostatní: EC(XE) LSHM-CT-2007-037765 Institutional research plan: CEZ:AV0Z50110509 Keywords : photolysis * glutamate receptors * caged neurotransmitters Subject RIV: ED - Physiology Impact factor: 4.114, year: 2012

  20. Effects of Furnished Cage Type on Behavior and Welfare of Laying Hens.

    Science.gov (United States)

    Li, Xiang; Chen, Donghua; Li, Jianhong; Bao, Jun

    2016-06-01

    This study was conducted to compare the effects of layout of furniture (a perch, nest, and sandbox) in cages on behavior and welfare of hens. Two hundred and sixteen Hyline Brown laying hens were divided into five groups (treatments) with four replicates per group: small furnished cages (SFC), medium furnished cages type I (MFC-I), medium furnished cages type II (MFC-II), and medium furnished cages type III (MFC-III) and conventional cages (CC). The experiment started at 18 week of age and finished at 52 week of age. Hens' behaviors were filmed during the following periods: 8:00 to 10:00; 13:00 to 14:00; 16:00 to 17:00 on three separate days and two hens from each cage were measured for welfare parameters at 50 wk of age. The results showed that feeding and laying of all hens showed no effect by cage type (p>0.05), and the hens in the furnished cages had significantly lower standing and higher walking than CC hens (phens between the furnished cages (p>0.05). The hens in MFC-I, -II, and -III showed a significant higher socializing behavior than SFC and CC (phens in SFC and the highest perching found for the hens in MFC-III. Overall, the hens in CC showed poorer welfare conditions than the furnished cages, in which the feather condition score, gait score and tonic immobility duration of the hens in CC was significantly higher than SFC, MFC-I, MFC-II, and MFC-III (phens. Overall, MFC-III cage design was better than SFC, MFC-I, and MFC-II cage designs. PMID:26954171

  1. Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

    Science.gov (United States)

    Deng, Qian-Xing; Ou, Yun-Sheng; Zhu, Yong; Zhao, Zeng-Hui; Liu, Bo; Huang, Qiu; Du, Xing; Jiang, Dian-Ming

    2016-06-01

    This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF. PMID:27091044

  2. Mitochondrial Processing Peptidase

    Czech Academy of Sciences Publication Activity Database

    Kutejová, Eva; Kučera, Tomáš; Matušková, Anna; Janata, Jiří

    Vol. 1. Oxford : Oxford: Academic Press, 2013 - (Rawlings, N.; Salvesen, G.), s. 1435-1442 ISBN 978-0-12-382219-2 R&D Projects: GA MŠk 2B08064 Institutional support: RVO:61388971 Keywords : mitochondria * mitochondrial peptidase Subject RIV: CE - Biochemistry

  3. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    KayFMacleod

    2013-12-01

    Full Text Available A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability and other more conventional aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the sigificance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis and spatial dynamics and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knockon effects for cell proliferation and growth. Scientifically, there is also scope for defining what mitochondria dysfunction is and here we address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

  4. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  5. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227. ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  6. Mitochondrial dysfunction in epilepsy

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Kunz, W.S.

    2012-01-01

    Roč. 12, č. 1 (2012), s. 35-40. ISSN 1567-7249 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : epilepsy * mitochondrial dysfunction * neurodegeneration Subject RIV: FH - Neurology Impact factor: 4.025, year: 2012

  7. Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

    International Nuclear Information System (INIS)

    Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 μg/m3 for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS

  8. The Tropical Intraseasonal Oscillation in SAMIL Coupled and Uncoupled General Circulation Models

    Institute of Scientific and Technical Information of China (English)

    YANG Jing; BAO Qing; WANG Xiaocong; ZHOU Tianjun

    2012-01-01

    Simulations of tropical intraseasonal oscillation (TISO) in SAMIL,the Spectral Atmospheric Model from the Institute of Atmospheric Physics (IAP) State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (LASG) coupled and uncoupled general circulation models were comprehensively evaluated in this study.Compared to the uncoupled model,the atmosphere-ocean coupled model improved the TISO simulation in the following aspects:(1) the spectral intensity for the 30-80-day peak eastward periods was more realistic; (2) the eastward propagation signals over western Pacific were stronger; and (3) the variance distribution and stronger signals of Kelvin waves and mixed Rossby gravity waves were more realistic. Better performance in the coupled run was assumed to be associated with a better mean state and a more realistic relationship between precipitation and SST.In both the coupled and uncoupled runs,the unrealistic simulation of the eastward propagation over the equatorial Indian Ocean might have been associated with the biases of the precipitation mean state over the Indian Ocean,and the unrealistic split of maximum TISO precipitation variance over the Pacific might have corresponded to the exaggeration of the double Intertropical Convergence Zone (ITCZ) structure in precipitation mean state.However,whether a better mean state leads to better TISO activity remains questionable.Notably,the northward propagation over the Indian Ocean during summer was not improved in the mean lead-lag correlation analysis,but case studies have shown some strong cases to yield remarkably realistic northward propagation in coupled runs.

  9. Synchronization of uncoupled excitable systems induced by white and coloured noise

    International Nuclear Information System (INIS)

    We study, both numerically and experimentally, the synchronization of uncoupled excitable systems due to a common noise. We consider two identical FitzHugh-Nagumo systems, which display both spiking and non-spiking behaviours in chaotic or periodic regimes. An electronic circuit provides a laboratory implementation of these dynamics. Synchronization is tested with both white and coloured noise, showing that coloured noise is more effective in inducing synchronization of the systems. We also study the effects on the synchronization of parameter mismatch and of the presence of intrinsic (not common) noise, and we conclude that the best performance of coloured noise is robust under these distortions.

  10. Genetic analysis on 3'-terminal flanking region of uncoupling protein 3 in different pig breeds

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 3′-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicatedthat Erhualian had extraordinary gene frequency, presented most significant difference by χ2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results canbe concluded that Taihu pigs have special genetic characteristics among pig breeds.

  11. Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity.

    Directory of Open Access Journals (Sweden)

    Nicole G Barra

    Full Text Available Interleukin-15 (IL-15 is an immunomodulatory cytokine that affects body mass regulation independent of lymphocytes; however, the underlying mechanism(s involved remains unknown. In an effort to investigate these mechanisms, we performed metabolic cage studies, assessed intestinal bacterial diversity and macronutrient absorption, and examined adipose mitochondrial activity in cultured adipocytes and in lean IL-15 transgenic (IL-15tg, overweight IL-15 deficient (IL-15-/-, and control C57Bl/6 (B6 mice. Here we show that differences in body weight are not the result of differential activity level, food intake, or respiratory exchange ratio. Although intestinal microbiota differences between obese and lean individuals are known to impact macronutrient absorption, differing gut bacteria profiles in these murine strains does not translate to differences in body weight in colonized germ free animals and macronutrient absorption. Due to its contribution to body weight variation, we examined mitochondrial factors and found that IL-15 treatment in cultured adipocytes resulted in increased mitochondrial membrane potential and decreased lipid deposition. Lastly, IL-15tg mice have significantly elevated mitochondrial activity and mass in adipose tissue compared to B6 and IL-15-/- mice. Altogether, these results suggest that IL-15 is involved in adipose tissue regulation and linked to altered mitochondrial function.

  12. Cutaneous mitochondrial respirometry: non-invasive monitoring of mitochondrial function.

    Science.gov (United States)

    Harms, Floor A; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

    2015-08-01

    The recently developed technique for measuring cutaneous mitochondrial oxygen tension (mitoPO2) by means of the Protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT) provides new opportunities for assessing mitochondrial function in vivo. The aims of this work were to study whether cutaneous mitochondrial measurements reflect mitochondrial status in other parts of the body and to demonstrate the feasibility of the technique for potential clinical use. The first part of this paper demonstrates a correlation between alterations in mitochondrial parameters in skin and other tissues during endotoxemia. Experiments were performed in rats in which mitochondrial dysfunction was induced by a lipopolysaccharide-induced sepsis (n = 5) and a time control group (n = 5). MitoPO2 and mitochondrial oxygen consumption (mitoVO2) were measured using PpIX-TSLT in skin, liver and buccal mucosa of the mouth. Both skin and buccal mucosa show a significant mitoPO2-independent decrease (P paper describes the clinical concept of monitoring cutaneous mitochondrial respiration in man. A first prototype of a clinical PpIX-TSLT monitor is described and its usability is demonstrated on human skin. We expect that clinical implementation of this device will greatly contribute to our understanding of mitochondrial oxygenation and oxygen metabolism in perioperative medicine and in critical illness. Our ultimate goal is to develop a clinical monitor for mitochondrial function and the current results are an important step forward. PMID:25388510

  13. Reproductive Performance of Mice in Disposable and Standard Individually Ventilated Cages

    OpenAIRE

    Ferguson, Danielle R; Bailey, Michele M

    2013-01-01

    This study assessed the reproductive performance of mice housed in 2 types of individually ventilated caging systems. Breeding pairs from 48 female and 24 male mice of 3 established transgenic mouse breeding colonies were placed in either a standard or disposable ventilated caging system. For 3 breeding cycles, the number of pups born, pup survival rate to weaning, time interval between litters, and pup weights were monitored for each breeding pair. Disposable and standard cages were maintain...

  14. Are assemblages of the fireworm Hermodice carunculata enhanced in sediments beneath offshore fish cages?

    Institute of Scientific and Technical Information of China (English)

    Rodrigo Riera; Oscar Prez; Myriam Rodrguez; Eva Ramos; scar Monterroso

    2014-01-01

    Abundances of the fireworm Hermodice carunculata were counted through a monitoring assessment study of fish cages in Barranco Hondo (NE Tenerife). Seven campaigns were conducted from November 2007 to June 2010 and temporal variations were found, as well as differences among sampling stations. The poly-chaete H. carunculata obtained its highest abundance in sediments beneath fish cages throughout the study period. Thus, the assemblages of this omnivorous species were favoured by the presence of fish cages.

  15. Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion

    OpenAIRE

    Xue, Qingyun; Li, Haisheng; Zou, Xuenong; Bünger, Mathias; Egund, Niels; Lind, Martin; Christensen, Finn Bjarke; Bünger, Cody

    2004-01-01

    This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily ...

  16. Animal Welfare and Food Safety Aspects of Confining Broiler Chickens to Cages

    OpenAIRE

    Sara Shields; Michael Greger

    2013-01-01

    Simple Summary In commercial chicken meat production, broiler chickens are usually kept on the floor in ware-house like buildings, but the use of cages is becoming more common. Confining chickens to cages is a welfare problem, as has been thoroughly demonstrated for laying hens used for egg production. Caged broiler chickens may suffer from poor bone strength due to lack of exercise, feather loss, and restriction of natural behavior. There are also potential food safety concerns associated wi...

  17. Individually Ventilated Cages Impose Cold Stress on Laboratory Mice: A Source of Systemic Experimental Variability

    OpenAIRE

    David, John M.; Knowles, Scott; Lamkin, Donald M.; Stout, David B.

    2013-01-01

    Individual ventilated cages (IVC) are increasing in popularity. Although mice avoid IVC in preference testing, they show no aversion when provided additional nesting material or the cage is not ventilated. Given the high ventilation rate in IVC, we developed 3 hypotheses: that mice housed in IVC experience more cold stress than do mice housed in static cages; that IVC-induced cold stress affects the results of experiments using mice; and that, when provided shelters, mice behaviorally thermor...

  18. Haematological and Biochemical Parameters during the Laying Period in Common Pheasant Hens Housed in Enhanced Cages

    OpenAIRE

    Petra Hrabčáková; Eva Voslářová; Iveta Bedáňová; Vladimíra Pištěková; Jan Chloupek; Vladimír Večerek

    2014-01-01

    The development of selected haematological and biochemical parameters during the laying period was monitored in common pheasant hens housed in an enhanced cage system. The cages were enhanced by the addition of two perches and a shelter formed by strips of cloth hanging in the corner of the cage. The results showed significant changes in the haematological and biochemical parameters monitored during egg laying. At the time when laying capacity approached a maximum, a decrease was observed (P ...

  19. Cage Change Influences Serum Corticosterone and Anxiety-Like Behaviors in the Mouse

    OpenAIRE

    Rasmussen, Skye; Miller, Melinda M.; Filipski, Sarah B.; Tolwani, Ravi J.

    2011-01-01

    Environmental variables and husbandry practices can influence physiology and alter behavior in mice. Our study evaluated the effects of cage change on serum corticosterone levels and anxiety-like behaviors in C57BL/6 male mice. We examined the effects of 3 different methods of performing cage transfer and of transferring mice to a clean or a dirty familiar cage microenvironment. The 3 different handling methods were forceps transfer, gentle transfer with gloved hands, and a passive transfer t...

  20. Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    OpenAIRE

    Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.

    2016-01-01

    In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized fem...

  1. Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA.

    Directory of Open Access Journals (Sweden)

    Philippe A Parone

    Full Text Available Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS. At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.

  2. Stand-alone LLIF Lateral Cage Migration: A Case Report.

    Science.gov (United States)

    Towers, Wendy S; Kurtom, Khalid H

    2015-01-01

    Lateral approaches to the lumbar disc space have become popular in recent years with very few reported complications. We report on a rare case of a stand-alone cage migration. A 77-year-old female presented with a right L2-3 radiculopathy that was refractory to maximum medical management. This was secondary to foraminal compression at L2-3 and L3-4 due to degenerative disc disease and levoscoliosis, as well as Grade 1 spondylolisthesis at both levels. A left-sided approach lateral lumbar interbody fusion was performed at L2-3 and L3-4 using a lordotic polyetheretherketone (PEEK) graft (50 mm length x 18 mm width x 9 mm height) packed with demineralized bone matrix (DBM). A contralateral release of the annulus fibrosis was performed during the decompression prior to graft insertion. Postoperative anteroposterior and lateral x-ray imaging confirmed good position of interbody grafts, correction of scoliosis as well as spondylolisthesis, and restoration of disc height achieving foraminal indirect decompression. A routine postoperative x-ray at three months demonstrated asymptomatic ipsilateral cage migration at the L2-3 level with evidence of arthrodesis in the disc space. This was managed conservatively without further surgical intervention. Placement of a lateral plate or interbody intradiscal plating system in patients with scoliosis and significant coronal deformity is an option that can be considered to prevent this rare LLIF complication. Moreover, asymptomatic cage migration may be conservatively managed without reoperation. PMID:26623202

  3. Hollow Gold Cages and Their Topological Relationship to Dual Fullerenes.

    Science.gov (United States)

    Trombach, Lukas; Rampino, Sergio; Wang, Lai-Sheng; Schwerdtfeger, Peter

    2016-06-20

    Golden fullerenes have recently been identified by photoelectron spectra by Bulusu et al. [S. Bulusu, X. Li, L.-S. Wang, X. C. Zeng, PNAS 2006, 103, 8326-8330]. These unique triangulations of a sphere are related to fullerene duals having exactly 12 vertices of degree five, and the icosahedral hollow gold cages previously postulated are related to the Goldberg-Coxeter transforms of C20 starting from a triangulated surface (hexagonal lattice, dual of a graphene sheet). This also relates topologically the (chiral) gold nanowires observed to the (chiral) carbon nanotubes. In fact, the Mackay icosahedra well known in gold cluster chemistry are related topologically to the dual halma transforms of the smallest possible fullerene C20 . The basic building block here is the (111) fcc sheet of bulk gold which is dual to graphene. Because of this interesting one-to-one relationship through Euler's polyhedral formula, there are as many golden fullerene isomers as there are fullerene isomers, with the number of isomers Niso increasing polynomially as O(Niso9 ). For the recently observed Au16- , Au17- , and Au18- we present simulated photoelectron spectra including all isomers. We also predict the photoelectron spectrum of Au32- . The stability of the golden fullerenes is discussed in relation with the more compact structures for the neutral and negatively charged Au12 to Au20 and Au32 clusters. As for the compact gold clusters we observe a clear trend in stability of the hollow gold cages towards the (111) fcc sheet. The high stability of the (111) fcc sheet of gold compared to the bulk 3D structure explains the unusual stability of these hollow gold cages. PMID:27244703

  4. A high-precision instrument for analyzing nonlinear dynamic behavior of bearing cage

    Science.gov (United States)

    Yang, Z.; Chen, H.; Yu, T.; Li, B.

    2016-08-01

    The high-precision ball bearing is fundamental to the performance of complex mechanical systems. As the speed increases, the cage behavior becomes a key factor in influencing the bearing performance, especially life and reliability. This paper develops a high-precision instrument for analyzing nonlinear dynamic behavior of the bearing cage. The trajectory of the rotational center and non-repetitive run-out (NRRO) of the cage are used to evaluate the instability of cage motion. This instrument applied an aerostatic spindle to support and spin test the bearing to decrease the influence of system error. Then, a high-speed camera is used to capture images when the bearing works at high speeds. A 3D trajectory tracking software tema Motion is used to track the spot which marked the cage surface. Finally, by developing the matlab program, a Lissajous' figure was used to evaluate the nonlinear dynamic behavior of the cage with different speeds. The trajectory of rotational center and NRRO of the cage with various speeds are analyzed. The results can be used to predict the initial failure and optimize cage structural parameters. In addition, the repeatability precision of instrument is also validated. In the future, the motorized spindle will be applied to increase testing speed and image processing algorithms will be developed to analyze the trajectory of the cage.

  5. Temporal variation of the static electric field inside an animal cage.

    Science.gov (United States)

    Shigemitsu, T; Tsuchida, Y; Nishiyama, F; Matsumoto, G; Nakamura, H; Shimizu, K

    1981-01-01

    The temporal variation of a static electric field inside an animal cage was investigated with a newly developed small, simple field meter. The field inside the cage was found to be highly dependent on the surface conductivity of the dielectric material. As the surface of the cage became dirty because of animal occupancy, the static electric field inside it became considerably smaller from the moment the field was turned on. Clean cages also modified the static electric field inside them, the field decaying from an initial to a much lower value over several hours. The mechanism of field attenuation for both cases is surface leakage. Surface leakage for a clean cage takes place much more slowly than for a dirty cage. This was confirmed by measuring DC insulation resistance. To examine this phenomenon further, the field in a metal cage width high electrical conductivity was measured. The static electric field inside the metal cage was also found to be reduced. An improved cage design that avoids these problems, is suggested for the study of the biologic effects of static electric fields. PMID:7326060

  6. A stochastic frontier analysis of technical efficiency of fish cage culture in Peninsular Malaysia.

    Science.gov (United States)

    Islam, Gazi Md Nurul; Tai, Shzee Yew; Kusairi, Mohd Noh

    2016-01-01

    Cage culture plays an important role in achieving higher output and generating more export earnings in Malaysia. However, the cost of fingerlings, feed and labour have increased substantially for cage culture in the coastal areas in Peninsular Malaysia. This paper uses farm level data gathered from Manjung, Perak and Kota Tinggi, Johor to investigate the technical efficiency of brackish water fish cage culture using the stochastic frontier approach. The technical efficiency was estimated and specifically the factors affecting technical inefficiencies of fish cage culture system in Malaysia was investigated. On average, 37 percent of the sampled fish cage farms are technically efficient. The results suggest very high degrees of technical inefficiency exist among the cage culturists. This implies that great potential exists to increase fish production through improved efficiency in cage culture management in Peninsular Malaysia. The results indicate that farmers obtained grouper fingerlings from other neighboring countries due to scarcity of fingerlings from wild sources. The cost of feeding for grouper (Epinephelus fuscoguttatus) requires relatively higher costs compared to seabass (Lates calcarifer) production in cage farms in the study areas. Initiatives to undertake extension programmes at the farm level are needed to help cage culturists in utilizing their resources more efficiently in order to substantially enhance their fish production. PMID:27478744

  7. Rearing Laying Hens in Aviaries Reduces Fearfulness following Transfer to Furnished Cages.

    Science.gov (United States)

    Brantsæter, Margrethe; Tahamtani, Fernanda M; Moe, Randi O; Hansen, Tone B; Orritt, Rachel; Nicol, Christine; Janczak, Andrew M

    2016-01-01

    Appropriate rearing is essential for ensuring the welfare and productivity of laying hens. Early experience has the potential to affect the development of fearfulness. This study tested whether rearing in aviaries, as opposed to cages, reduces the fearfulness of laying hens after transfer to furnished cages. Fear responses were recorded as avoidance of a novel object in the home cage. Lohmann Selected Leghorns were reared in an aviary system or conventional rearing cages and then transported to furnished cages at 16 weeks, before the onset of lay. Observations of a selection of birds were conducted at 19 (N = 50 independent cages) and 21 (N = 48 independent cages) weeks of age. At 19 and 21 weeks, cage-reared birds showed higher levels of fearfulness indicated by spending more time away from the novel object compared to aviary-reared birds. These results suggest that rearing in an enriched aviary environment reduces fearfulness up to the fifth week after transfer to a new housing system, compared to rearing in cages. PMID:26955634

  8. Size effect of fullerene cages and encaged clusters in M3N@C2n

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on the calculated findings that the sizes of encaged clusters determine the structures and the stability of C80-based trimetallic nitride fullerenes (TNFs), more extensive density functional theory calculations were performed on M3N@C68, M3N@C78 and M3N@C80 (M=Sc, Y and La). The calculated results demonstrated that the structures and stability undergo a transition with the increasing of the sizes of the cages and clusters. Sc3N is planar inside the three considered cages, Y3N is slightly pyramidal inside C68-6140 and C78-5 and planar inside I h C80-7, however, La3N is pyramidal inside all the three cages. Those cages with pyramidal clusters inside deformed considerably, compared with their parent cages. In these cases, the bonding of metallic atoms toward the cages does not play an impor-tant role, and the encaged cluster tends to be located inside the cages with the largest M-M and M-C distances so that the strain energy can be released mostly. These calculations revealed the size effect of fullerene cages and encaged clusters, and can explain the position priority of M3N inside fullerene cages and the differences in yield of M3N@C2n.

  9. Rearing Laying Hens in Aviaries Reduces Fearfulness following Transfer to Furnished Cages

    Science.gov (United States)

    Brantsæter, Margrethe; Tahamtani, Fernanda M.; Moe, Randi O.; Hansen, Tone B.; Orritt, Rachel; Nicol, Christine; Janczak, Andrew M.

    2016-01-01

    Appropriate rearing is essential for ensuring the welfare and productivity of laying hens. Early experience has the potential to affect the development of fearfulness. This study tested whether rearing in aviaries, as opposed to cages, reduces the fearfulness of laying hens after transfer to furnished cages. Fear responses were recorded as avoidance of a novel object in the home cage. Lohmann Selected Leghorns were reared in an aviary system or conventional rearing cages and then transported to furnished cages at 16 weeks, before the onset of lay. Observations of a selection of birds were conducted at 19 (N = 50 independent cages) and 21 (N = 48 independent cages) weeks of age. At 19 and 21 weeks, cage-reared birds showed higher levels of fearfulness indicated by spending more time away from the novel object compared to aviary-reared birds. These results suggest that rearing in an enriched aviary environment reduces fearfulness up to the fifth week after transfer to a new housing system, compared to rearing in cages. PMID:26955634

  10. Effects of Cage Density on the Performance of Laying Hens During High Summer Temperatures

    OpenAIRE

    Altan, Ali; ALTAN, Özge; ÖZKAN, Sezen; ÖZKAN, Kahraman; AKBAŞ, Yavuz; Ayhan, Veysel

    2002-01-01

    This study was conducted to determine the effects of different cage densities on laying performance of white and brown hybrid layers during high summer temperatures. White layers, 68 weeks of age, were housed at a density of 3, 4 or 5 hens/cage (respectively 640, 480 and 384 cm2/hen); brown layers were housed at 3 or 4 hens/cage (respectively 640 and 480 cm2/hen). The results indicated that housing at 3 or 4 hens/cage did not affect egg production or egg quality significantly. Increasing t...

  11. Effects of Nominal Differences in Cage Height and Floor Space on the Wellbeing of Rabbits.

    Science.gov (United States)

    Stewart, Kay L; Suckow, Mark A

    2016-03-01

    The 8th edition of the Guide for the Care and Use of Laboratory Animals recommends a cage height of 16 in. for rabbits, compared with 14 in. in the previous edition. In contrast, the Animal Welfare Act Regulations prescribes a cage height of 14 in. for rabbits. A review of the literature failed to identify published data that support an advantage to rabbits having 16 in. of cage height compared with 14 or 15 in. The study described here evaluated the effect of a 3-in. difference in cage height on the health, growth, behavior, and overall wellbeing of rabbits. Groups of 10 New Zealand white rabbits were housed in cages that provided either 15 in. of interior cage height (720 in(2) of floor space) or 18 in. of interior height (784 in(2) of floor space). The rabbits were observed during 25 periods (1 h each) over 7 wk, and various behavioral parameters were scored. In addition, rabbits were weighed weekly, and general clinical health was assessed. After 4 wk, the groups were switched to the alternate housing. No significant differences in body weight gain or behavioral parameters were detected between groups housed in cages with different heights and amounts of floor space, nor were significant behavioral differences noted in individual rabbits when moved from one cage type to the other. In addition, all rabbits remained clinically healthy throughout the study. These results demonstrate that these differences in interior cage height neither benefit nor harm rabbits. PMID:27025808

  12. The effects of climbing cages on behaviour of female mink during the lactation period

    DEFF Research Database (Denmark)

    Lidfors, L.; Axelsson, H.; Loberg, J.;

    2012-01-01

    The aim was to investigate if there were differences in behaviour of female mink when kept in a climbing cage compared with a standard cage during the lactation period. The study was carried out on 90 mink of the colour type "black cross". Females were housed in either climbing cages (4.350 cm², n......=46) or standard cages (2.550 cm², n=44). Behavioural observations were made four weeks before birth until kits were nine weeks old with one-zero sampling during two hours before feeding. During week 1-4 after females had given birth they were mostly recorded in the nest box and there were no...... differences between cage types. Week 5-8 after giving birth females in climbing cages were less in the nest box, less active out in the cage and had fewer abnormal behaviours, but were on the platforms and more inactive out in the cage. In the bottom cage females were more often walking, grooming and inactive...

  13. Characterization of manures from fish cage farming in Chile.

    Science.gov (United States)

    Salazar, F J; Saldana, R C

    2007-12-01

    This study aims to characterize salmonid manures and to determine their potential use in agricultural soils. Sampling was carried out below salmon and trout cages in farms located in lakes and in the sea in the South of Chile during 2002-2003. Manure was analyzed for macronutrients, micronutrients and heavy metals. Results showed a high variability between samples and differences between sea and lake manure. Dry matter contents were low averaging c. 12-15%. Manures showed low OM contents with values heavy metal contents and a potential use in agricultural soils, which could reduce the risks of water pollution on water from fish farming. PMID:16962324

  14. DESIGN OF AUTOMATED ROTORY CAGE TYPE FIXTURE FOR CYLINDER BLOCK

    Directory of Open Access Journals (Sweden)

    Y.S.Kapnichor

    2014-07-01

    Full Text Available Project gives feasible solution to move and rotate the component with full proofing fixturing for special purpose operations like drilling, Tapping, deburring, washing, drying involve in manufacturing and assembly unit of industry. Rotary cage type fixture is made for handling the cylinder head inside the cleaning machine use for making fully ready component before assembly operation .System is useful to save time manpower and deliver perfect cleaned and dry component .system involved all the mechanical components along with the sensors used to restrict the rotating operations, stop and go operations etc.

  15. Design of Automated Rotory Cage Type Fixture for Cylinder Block

    Directory of Open Access Journals (Sweden)

    Y.S.Kapnichor

    2014-08-01

    Full Text Available Project gives feasible solution to move and rotate the component with full proofing fixturing for special purpose operations like drilling, Tapping, deburring, washing, drying involve in manufacturing and assembly unit of industry. Rotary cage type fixture is made for handling the cylinder head inside the cleaning machine use for making fully ready component before assembly operation .System is useful to save time manpower and deliver perfect cleaned and dry component .system involved all the mechanical components along with the sensors used to restrict the rotating operations, stop and go operations etc.

  16. Experimental Determination of Stray Load Losses in Cage Induction Machines

    OpenAIRE

    Aoulkadi, M´hamed

    2011-01-01

    With different purposeful measurements like for the stray load losses and the flux densities, on two low-voltage squirrel-cage rotor asynchronous generators for 1.5 MW wind turbines with different types of the stator winding (litz and round wire), the sources of the losses and the causes for the winding overheating are localized and defined. Different measures to reduce the stray load losses due the skin effect in the stator of the round wire winding generator are successfully tested and impl...

  17. Regioselective nitration of aromatic substrates in zeolite cages

    Indian Academy of Sciences (India)

    T Esakkidurai; M Kumarraja; K Pitchumani

    2003-04-01

    Phenol is nitrated regioselectively by fuming nitric acid inside the cages of faujasite zeolites (dependent on the loading level) and a remarkable orthoselectivity is observed in solid state nitration. Toluene and chlorobenzene also containing ortho-/para-orienting substituents, undergo faster nitration, though the regioselectivity is less significant in zeolite media. The results are explained on the basis of diffusion and binding of phenol inside zeolite, which facilitate regioselectivity (and which is absent in toluene and chlorobenzene). Other advantages of employing zeolites as media for mild and selective nitration are also highlighted.

  18. Preinjector for Linac 1, inside the Faraday cage

    CERN Multimedia

    1974-01-01

    For a description of the Linac 1 preinjector, please see first 7403070X. Here, the view is towards the upper level of the Faraday cage. Far to the right, a technician is peering through the service door. The huge box-shaped cubicle is the electronics platform, at 520 kV potential during operation. The "bull eye" at the left back sits at the top end of the accelerating column (see 7403081X) and houses the ion source with its electronics (see 7403083X). The SAMES generator, providing the 520 kV HV (7403074) sits on the floor and is not visible here.

  19. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

    Science.gov (United States)

    Long, Jonathan Z; Svensson, Katrin J; Bateman, Leslie A; Lin, Hua; Kamenecka, Theodore; Lokurkar, Isha A; Lou, Jesse; Rao, Rajesh R; Chang, Mi Ra; Jedrychowski, Mark P; Paulo, Joao A; Gygi, Steven P; Griffin, Patrick R; Nomura, Daniel K; Spiegelman, Bruce M

    2016-07-14

    Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders. PMID:27374330

  20. Radiochemical synthesis and photochemical properites of the uncoupler 2-azido-4-nitrophenol, a versatile photoaffinity labeling

    International Nuclear Information System (INIS)

    2-Amino-4-nitrophenol was tritiated in an acid catalyzed hydrogen exchange reaction. Radioactive 2-azido-4-nitrophenol with a specific radioactivity up to 21 mCi/mmol was synthesized from 2-amino-4-nitrophenol by diazotization and azide coupling. The photochemical properties of the uncoupler, 2-azido-4-nitrophenol, were studied as free solute and as ligand bound to uncoupler binding sites in bovine serum albumin and mitochondria. Based on product analyses, irradiation of free or bound 2-azido-4-nitrophenolate with visible light results in the formation of nitrene intermediates with a singlet to triplet ratio of 6:1 to 9:1. 2-Azido-4-nitrophenolate and bovine serum albumin form a strong 1:1 complex (K/sub D/ = 0.7 μM) which can be converted into a photoproduct with a covalent bond between the label and the protein. The acid dissociation constant of the protein-bound 2-amino-4-nitrophenol moiely is strongly pH dependent. Photoaffinity labeling of mitochondria by 2-azido-4-nitrophenolate follows a pattern expected from equilibrium binding studies using normal and lipid-depleted particles: polypeptides were found to bear 90 to 95% of the radioactive label, and 5 to 10% of the latter was bound to phospholipids. Two polypeptides (approximately 56,000 and 31,000 daltons) were associated with 60% of the label, indicating a high degree of specific photochemical labeling

  1. Explicit thin-lens solution for an arbitrary four by four uncoupled beam transfer matrix

    Energy Technology Data Exchange (ETDEWEB)

    Balandin, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Orlov, S. [Moscow State Univ. (Russian Federation). Faculty of Computational Mathematics and Cybernetics

    2011-10-15

    In the design of beam transport lines one often meets the problem of constructing a quadrupole lens system that will produce desired transfer matrices in both the horizontal and vertical planes. Nowadays this problem is typically approached with the help of computer routines, but searching for the numerical solution one has to remember that it is not proven yet that an arbitrary four by four uncoupled beam transfer matrix can be represented by using a finite number of drifts and quadrupoles (representation problem) and the answer to this questions is not known not only for more or less realistic quadrupole field models but also for the both most commonly used approximations of quadrupole focusing, namely thick and thin quadrupole lenses. In this paper we make a step forward in resolving the representation problem and, by giving an explicit solution, we prove that an arbitrary four by four uncoupled beam transfer matrix actually can be obtained as a product of a finite number of thin-lenses and drifts. (orig.)

  2. Uncoupling fertility from fertility-associated pheromones in worker honeybees (Apis mellifera).

    Science.gov (United States)

    Malka, Osnat; Katzav-Gozansky, Tamar; Hefetz, Abraham

    2009-03-01

    Fertility-associated pheromones, chemical signals delineating ovarian development, were favourably selected in the course of evolution because it is in the best interest of both the signallers (in recruiting help from other colony members) and the receivers (in assisting them to reach an informed decision of how to maximize fitness). Such signals therefore should constitute honest, deception-proof indicators of ovarian development, suggesting, theoretically, that the processes of ovarian development and signal production are irreversibly coupled. Here we demonstrate that these processes can be uncoupled by treating queenless (QL) honeybee callow workers with methoprene, a juvenile hormone (JH) analog. While methoprene effectively inhibited ovarian development, it neither inhibited Dufour's fertility signal nor the mandibular glands' dominance signal. In fact, there was even a slight augmentation of both in the methoprene-treated bees. Thus, although fertility and fertility signals are tightly associated, they can be uncoupled by experimental manipulation. These results are consistent with the hypothesis that ovarian development and fertility-associated signal production are triggered by a common event/signal (e.g. queen pheromone disappearance) but comprise different regulatory systems. The evolutionary implication is that these two traits have evolved independently and may have been co-opted to emphasize the reproductive status of workers in the competition for reproduction. PMID:19041321

  3. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology. PMID:25425472

  4. Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Onukwufor, John O. [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada)

    2015-01-15

    Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q{sub 10} values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and

  5. Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q10 values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and intensifying the

  6. Cancer: Mitochondrial Origins

    OpenAIRE

    Stefano, George B.; Kream, Richard M.

    2015-01-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial ma...

  7. Mitochondrial Subversion in Cancer

    OpenAIRE

    Chatterjee, Aditi; Dasgupta, Santanu; Sidransky, David

    2011-01-01

    Mitochondria control essential cellular activities including generation of ATP via oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations in the regulatory D-loop region and somatic mtDNA mutations are common in primary human cancers. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell trans...

  8. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  9. Anterior cervical discectomy and fusion: Comparison of titanium and polyetheretherketone cages

    Directory of Open Access Journals (Sweden)

    Cabraja Mario

    2012-09-01

    Full Text Available Abstract Background Titanium (TTN cages have a higher modulus of elasticity when compared with polyetheretherketone (PEEK cages. This suggests that TTN-cages could show more frequent cage subsidence after anterior cervical discectomy and fusion (ACDF and therefore might lead to a higher loss of correction. We compared the long term results of stand-alone PEEK- and TTN-cages in a comparable patient collective that was operated under identical operative settings. Methods From 2002 to 2007 154 patients underwent single-level ACDF for degenerative disc disease (DDD. Clinical and radiological outcome were assessed in 86 eligible patients after a mean of 28.4 months. 44 patients received a TTN- and 42 patients a PEEK-cage. Results Solid arthrodesis was found in 93.2% of the TTN-group and 88.1% of the PEEK-group. Cage subsidence was observed in 20.5% of the TTN- and 14.3% of the PEEK-group. A significant segmental lordotic correction was achieved by both cage-types. Even though a loss of correction was found at the last follow-up in both groups, it did not reach the level of statistical significance. Statistical analysis of these results revealed no differences between the TTN- and PEEK-group. When assessed with the neck disability index (NDI, the visual analogue scale (VAS of neck and arm pain and Odom’s criteria the clinical data showed no significant differences between the groups. Conclusions Clinical and radiological outcomes of ACDF with TTN- or PEEK-cages do not appear to be influenced by the chosen synthetic graft. The modulus of elasticity represents only one of many physical properties of a cage. Design, shape, size, surface architecture of a cage as well as bone density, endplate preparation and applied distraction during surgery need to be considered as further important factors.

  10. Outcome of single level anterior cervical discectomy and fusion using nano-hydroxyapatite/polyamide-66 cage

    Directory of Open Access Journals (Sweden)

    Xi Yang

    2014-01-01

    Full Text Available Background: Cages have been widely used for the anterior reconstruction and fusion of cervical spine. Nonmetal cages have become popular due to prominent stress shielding and high rate of subsidence of metallic cages. This study aims to assess fusion with n-HA/PA66 cage following one level anterior cervical discectomy. Materials and Methods: Forty seven consecutive patients with radiculopathy or myelopathy underwent single level ACDF using n-HA/PA66 cage. We measured the segmental lordosis and intervertebral disc height on preoperative radiographs and then calculated the loss of segmental lordosis correction and cage subsidence over followup. Fusion status was evaluated on CT scans. Odom criteria, Japanese Orthopedic Association (JOA and Visual Analog Pain Scales (VAS scores were used to assess the clinical results. Statistically quantitative data were analyzed while Categorical data by χ2 test. Results: Mean correction of segmental lordosis from surgery was 6.9 ± 3.0° with a mean loss of correction of 1.7 ± 1.9°. Mean cage subsidence was 1.2 ± 0.6 mm and the rate of cage subsidence (>2 mm was 2%. The rate of fusion success was 100%. No significant difference was found on clinical or radiographic outcomes between the patients (n=27 who were fused by n-HA/PA66 cage with pure local bone and the ones (n=20 with hybrid bone (local bone associating with bone from iliac crest. Conclusions: The n-HA/PA66 cage is a satisfactory reconstructing implant after anterior cervical discectomy, which can effectively promote bone graft fusion and prevent cage subsidence.

  11. Animal welfare beyond the cage...and beyond the evidence?

    Science.gov (United States)

    Blanchard, Robert J

    2010-01-01

    In "Laboratory Rodent Welfare: Thinking Outside the Cage," Balcombe (2010/this issue) suggests that laboratory cage housing is damaging to rats and mice because it does not meet their evolved needs and may damage their psychological and physical health. The article also indicates that larger and more enriched spaces reduce aggression and mortality and improve the health and friendliness of rodents in the laboratory. Remarkably, many of the studies cited as supporting these assertions fail to provide data bearing on the issues involved or may even report findings opposite to those described by Balcombe, whereas many studies that are highly relevant to these issues are not cited or described. Moreover, although the "evolved needs" of rats and mice are presented as the basis for an analysis of rodent welfare, the important and well-documented changes in needs- or motivation-related behaviors of a rodent in the laboratory (due to human selection over hundreds of generations) is ignored. This pattern of disconnections between data and conclusions is so pervasive as to demolish the scientific value of the exposition. PMID:20017049

  12. [Supplementation of swine feed rations with zeolite during cage rearing].

    Science.gov (United States)

    Bartko, P; Chabada, J; Vrzgula, L; Solár, I; Blazovský, J

    1983-07-01

    The effect of the addition of zeolite to pig feed ration was studied in the cage rearing system under production conditions. Zeolite was mixed in the COS I and COS II feed mixtures directly in the feed plant, the mixing ratio being 100 kg feed mixture + 5 kg zeolite. The feed mixture was administered in granular form ad libitum. The test group had 648 weanlings and the control group 674 weanlings; the piglets, kept in two-story cages in four sections, were arranged so that the test group could be a mirror-like reflection of the control group. The trial lasted 45 days. The piglets given the fortified feed ration had daily weight gains higher by 0.017 kg and feed consumption lower by 0.234 kg per 1 kg of gain, as compared with the control animals. The costs of the feed ration required for producing a kilogram of gain were 8.55 Cz. crowns in the zeolite group and 9.422 crowns in the control group. PMID:6312666

  13. Optical triggered seizures using a caged 4-Aminopyridine

    Directory of Open Access Journals (Sweden)

    Mingrui eZhao

    2015-02-01

    Full Text Available Animal models of epilepsy are critical not only for understanding the fundamental mechanism of epilepsy but also for testing the efficacy of new antiepileptic drugs and novel therapeutic interventions. Photorelease of caged molecules is widely used in biological research to control pharmacologic events with high spatio-temporal resolution. We developed a technique for in vivo optical triggering of neocortical seizures using a novel caged compound based on ruthenium photochemistry (RuBi-4AP. Epileptiform events were induced with blue light illumination. Multi-electrode array recording and optical techniques were used to characterize the propagation of these epileptic events. Epileptiform events including interictal spikes, polyspikes, and ictal discharges were induced with blue light illumination. This model can be induced in vivo with both whole brain and focal illumination to provide high spatio-temporal control of the site of ictal onset. These results demonstrate a novel optically-triggered seizure model that may have widespread application in the investigation of ictal onset, propagation and in novel light-based therapeutic interventions.

  14. Abnormal behavior in caged birds kept as pets.

    Science.gov (United States)

    van Hoek, C S; ten Cate, C

    1998-01-01

    There are a limited number of studies dealing with abnormal behavior in caged birds kept as pets. However, these studies demonstrate the presence of abnormal behavior in both songbirds and parrots. Ethological studies on these birds, as well as studies on domestic and zoo birds, indicate that inappropriate rearing and housing conditions may lead to behavioral abnormalities. Together these data indicate that behavioral abnormalities occur among both wild-caught and domesticated pet birds. The severity and magnitude of these abnormalities is probably underestimated, and there is a need for systematic studies on the nature, origin, variability, species-specificity, and reversibility of behavioral problems in pet birds. Abnormal behavior in caged birds may to some extent be prevented and reduced by environmental enrichment. However, most enrichment studies are anecdotal and not based on a thorough analysis of the behavioral abnormalities, which may lead to measures resulting in a reduction of symptoms rather than the underlying causes. Although it is likely that several of these problems could be reduced by modifying rearing and housing conditions, the current insights into the causal mechanisms underlying abnormal behavior of domesticated and wild-caught pet birds are limited, as are the insights into the possibilities of preventing or curing abnormal behavior. PMID:16363987

  15. Protection characteristics of a Faraday cage compromised by lightning burnthrough.

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry Kevin; Bystrom, Edward; Jorgenson, Roy Eberhardt; Montoya, Sandra L.; Merewether, Kimball O.; Coats, Rebecca Sue; Martinez, Leonard E.; Jojola, John M.

    2012-01-01

    A lightning flash consists of multiple, high-amplitude but short duration return strokes. Between the return strokes is a lower amplitude, continuing current which flows for longer duration. If the walls of a Faraday cage are made of thin enough metal, the continuing current can melt a hole through the metal in a process called burnthrough. A subsequent return stroke can couple energy through this newly-formed hole. This LDRD is a study of the protection provided by a Faraday cage when it has been compromised by burnthrough. We initially repeated some previous experiments and expanded on them in terms of scope and diagnostics to form a knowledge baseline of the coupling phenomena. We then used a combination of experiment, analysis and numerical modeling to study four coupling mechanisms: indirect electric field coupling, indirect magnetic field coupling, conduction through plasma and breakdown through the hole. We discovered voltages higher than those encountered in the previous set of experiments (on the order of several hundreds of volts).

  16. Cage Versus Noncage Laying-Hen Housings: Respiratory Exposures.

    Science.gov (United States)

    Arteaga, Veronica; Mitchell, Diane; Armitage, Tracey; Tancredi, Daniel; Schenker, Marc; Mitloehner, Frank

    2015-01-01

    The objective of this study was to compare the personal respiratory exposures of poultry workers in three different types of layer housing under commercial production conditions. Workers were randomly assigned to each of conventional cage, enriched cage, and aviary barns in a crossover repeated-measures design for three observation periods over the hens' lifetime. Inhalable and fine particulate matter (PM) and endotoxin in both size fractions were assessed by personal and area samplers over the work shift. Concentrations of inhalable PM, PM2.5 (PM with an aerodynamic diameter Geometric means (95% confidence intervals [CIs]) of inhalable PM and endotoxin for the aviary, conventional, and enriched barns were 8.9 (6.8-11.5) mg/m(3) and 7517.9 (5403.2-10,460.2) EU/m(3), 3.7 (2.8-4.8) mg/m(3) and 1655.7 (1144.6-2395.2) EU/m(3), 2.4 (1.8-3.3) mg/m(3) and 1404.8 (983.3-2007.0) EU/m(3), respectively. Area samplers recorded a lower mean inhalable PM concentration and higher PM2.5 concentration than personal samplers. Ammonia concentrations were low throughout three monitoring seasons. These findings show that the aviary barns pose higher respiratory exposures to poultry workers than either conventional or enriched barns. PMID:26237714

  17. Large-scale clustering of CAGE tag expression data

    Directory of Open Access Journals (Sweden)

    Kawai Jun

    2007-05-01

    Full Text Available Abstract Background Recent analyses have suggested that many genes possess multiple transcription start sites (TSSs that are differentially utilized in different tissues and cell lines. We have identified a huge number of TSSs mapped onto the mouse genome using the cap analysis of gene expression (CAGE method. The standard hierarchical clustering algorithm, which gives us easily understandable graphical tree images, has difficulties in processing such huge amounts of TSS data and a better method to calculate and display the results is needed. Results We use a combination of hierarchical and non-hierarchical clustering to cluster expression profiles of TSSs based on a large amount of CAGE data to profit from the best of both methods. We processed the genome-wide expression data, including 159,075 TSSs derived from 127 RNA samples of various organs of mouse, and succeeded in categorizing them into 70–100 clusters. The clusters exhibited intriguing biological features: a cluster supergroup with a ubiquitous expression profile, tissue-specific patterns, a distinct distribution of non-coding RNA and functional TSS groups. Conclusion Our approach succeeded in greatly reducing the calculation cost, and is an appropriate solution for analyzing large-scale TSS usage data.

  18. Cage Opening of a Carborane Ligand by Metal Cluster Complexes.

    Science.gov (United States)

    Adams, Richard D; Kiprotich, Joseph; Peryshkov, Dmitry V; Wong, Yuen Onn

    2016-05-01

    The reaction of Os3 (CO)10 (NCMe)2 with closo-o-C2 B10 H10 has yielded two interconvertible isomers Os3 (CO)9 (μ3 -4,5,9-C2 B10 H8 )(μ-H)2 (1 a) and Os3 (CO)9 (μ3 -3,4,8-C2 B10 H8 )(μ-H)2 (1 b) formed by the loss of the two NCMe ligands and one CO ligand from the Os3 cluster. Two BH bonds of the o-C2 B10 H10 were activated in its addition to the osmium cluster. A second triosmium cluster was added to the 1 a/1 b mixture to yield the complex Os3 (CO)9 (μ-H)2 (μ3 -4,5,9-μ3 -7,11,12-C2 B10 H7 )Os3 (CO)9 (μ-H)3 (2) that contains two triosmium triangles attached to the same carborane cage. When heated, 2 was transformed to the complex Os3 (CO)9 (μ-H)(μ3 -3,4,8-μ3 -7,11,12-C2 B10 H8 )Os3 (CO)9 (μ-H) (3) by a novel opening of the carborane cage with loss of H2 . PMID:26971388

  19. Polymorphisms of mitochondrially encoded proteins.

    OpenAIRE

    Spinner, N B; King, M. C.

    1986-01-01

    Polymorphisms of mitochondrially encoded proteins can be detected in human lymphocytes by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Using an SDS-polyacrylamide 8 M urea system, 17 mitochondrially encoded proteins are distinguishable. Three of these (ME-6, ME-8, and ME-17) were polymorphic among 92 individuals screened, and these polymorphisms are reported here for the first time. With SDS-polyacrylamide electrophoresis without urea, 18 mitochondrial proteins are de...

  20. Mitochondrial Dysfunction and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Shaw-Hwa Jou

    2009-10-01

    Full Text Available Mitochondria are intracellular organelles crucial in the production of cellular energy.Mitochondrial diseases may result from malfunctions in this biochemical cascade. Severalinvestigators have proposed that mitochondrial dysfunction is related to the pathophysiologyof bipolar disorder (BD, major depressive disorder (MDD and schizophrenia (SZ. Theauthors reviewed recent study findings and tried to delineate the current understanding of thecorrelation between mitochondrial dysfunction and psychiatric disorders. A growing body ofevidence suggests that mitochondrial dysfunction is important in patients with psychiatricdisorders. The evidence include impaired energy metabolism in the brain detected usingresults of magnetic resonance spectroscopy, electron microscopy, co-morbidity with mitochondrialdiseases, the effects of psychotropics on mitochondria, increased mitochondrialDNA (mtDNA deletion in the brain, and association with mtDNA mutations/polymorphismsor nuclear-encoded mitochondrial genes. It is possible that the new information willlead to a focus on psychiatric disorder as a metabolic disease. Treatment with psychotropicsmight ultimately enhance energy metabolism and reduce the damage of oxidative stress. Thenext step in the study of mitochondrial dysfunction in patients with psychiatric disordersshould be clarification of how mitochondrial dysfunction, a nonspecific risk factor, causesspecific symptoms. Further study of mitochondrial dysfunction in patients with psychiatricdisorder is expected to be useful for the development of cellular disease markers and newpsychotropics.

  1. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D;

    2013-01-01

    Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...... myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...

  2. Evaluation of the mitochondrial system in the gonad-digestive gland complex of Biomphalaria glabrata (Mollusca, Gastropoda) after infection by Echinostoma paraensei (Trematoda, Echinostomatidae).

    Science.gov (United States)

    Tunholi, Victor Menezes; Tunholi-Alves, Vinícius Menezes; Santos, Anderson Teixeira; Garcia, Juberlan da Silva; Maldonado, Arnaldo; da-Silva, Wagner Seixas; Rodrigues, Maria de Lurdes de Azevedo; Pinheiro, Jairo

    2016-05-01

    The effect of infection by Echinostoma paraensei on the mitochondrial physiology of Biomphalaria glabrata was investigated after exposure to 50 miracidia. The snails were dissected one, two, three and four weeks after infection for collection and mechanical permeabilization of the gonad-digestive gland (DGG) complex. The results obtained indicate that prepatent infection by this echinostomatid fluke significantly suppresses the phosphorylation state (respiratory state 3) and basal oxygen consumption of B. glabrata, demonstrating that the infection reduces the ability of the intermediate host to carry out aerobic oxidative reactions. Additionally, relevant variations related to the uncoupled mitochondrial (state 3u) of B. glabrata infected by E. paraensei were observed. Four weeks after exposure, a significant reduction in mitochondrial oxygen consumption after addition of ADP (3.68±0.26pmol O2/mg proteins) was observed in the infected snails in comparison with the respective control group (5.14±0.25). In the uncoupled state, the infected snails consumed about 62% less oxygen than the infected snails (7.87±0.84pmol O2/mg proteins) in the same period. These results demonstrate a reduction in oxidative decarboxylation rate of the tricarboxylic acid cycle and faster anaerobic degradation of carbohydrates in the infected snails. The possible mechanisms that explain this new metabolic condition in the infected organisms are discussed. PMID:27079167

  3. Self-Assembly, Guest Capture, and NMR Spectroscopy of a Metal-Organic Cage in Water

    Science.gov (United States)

    Go, Eun Bin; Srisuknimit, Veerasak; Cheng, Stephanie L.; Vosburg, David A.

    2016-01-01

    A green organic-inorganic laboratory experiment has been developed in which students prepare a self-assembling iron cage in D[subscript 2]O at room temperature. The tetrahedral cage captures a small, neutral molecule such as cyclohexane or tetrahydrofuran. [Superscript 1]H NMR analysis distinguishes captured and free guests through diagnostic…

  4. Biomechanische Untersuchung eines biodegradierbaren Cages zur interkorporellen Spondylodese der Halswirbelsäule.

    OpenAIRE

    Gumnior, Sarah Nicole Stephanie

    2010-01-01

    Biomechanical evaluation of a biodegradable cage for interbody fusion at the cervical spine Biomechanical evaluation of a biodegradable cage for interbody fusion in the cervical spine. A in vivo animal study in a sheep model.   Abstract Background Anterior interbody fusion using an intervertebral spacer is a widely accepted surgical treatment for patients with degenerative and traumatic cervical spinal-c...

  5. Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion.

    Science.gov (United States)

    Xue, Qingyun; Li, Haisheng; Zou, Xuenong; Bünger, Mathias; Egund, Niels; Lind, Martin; Christensen, Finn Bjarke; Bünger, Cody

    2005-04-01

    This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS), respectively. No statistical difference was found between the same grafted cage comparing two groups. The histological fusion rate was 7/10 in all autograft cage levels and 5/10 in combined allograft cage levels. No fusion was found at all in empty cage levels. With the numbers available, no statistically significant difference was found in histological fusion between autograft and allograft applications. There was a significant difference of mean bone volume between autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did not demonstrate different healing properties of alendronate-treated and non-treated allograft for anterior lumbar interbody fusion in pigs. PMID:15248057

  6. Animal Welfare and Food Safety Aspects of Confining Broiler Chickens to Cages.

    Science.gov (United States)

    Shields, Sara; Greger, Michael

    2013-01-01

    In most areas of the world, broiler chickens are raised in floor systems, but cage confinement is becoming more common. The welfare of broiler chickens in cages is affected by movement restriction, poor bone strength due to lack of exercise, and prevention of key behavioral patterns such as dustbathing and ground scratching. Cages for broiler chickens also have a long history of causing skin and leg conditions that could further compromise welfare, but a lack of controlled studies makes it difficult to draw conclusions about newer cage designs. Cage environments are usually stocked at a higher density than open floor systems, and the limited studies available suggest that caging may lead to increased levels of fear and stress in the birds. Further, birds reared on the floor appear less likely to harbor and shed Salmonella, as litter may serve as a seeding agent for competitive exclusion by other microorganisms. Cages for laying hens used in egg production have met with substantial opposition due to welfare concerns and caging broiler chickens will likely be subject to the same kinds of social disapproval. PMID:26487409

  7. Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2014-11-01

    Full Text Available Intricate caged molecular frameworks are assembled by an atom economical process via a Diels–Alder (DA reaction, a Claisen rearrangement, a ring-closing metathesis (RCM and an alkenyl Grignard addition. The introduction of olefinic moieties in the pentacycloundecane (PCUD framework at appropriate positions followed by RCM led to the formation of novel heptacyclic cage systems.

  8. Alterations of diaphragm and rib cage morphometry in severe COPD patients by CT analysis.

    Science.gov (United States)

    Salito, C; Luoni, E; Aliverti, A

    2015-08-01

    Although it is known that in patients with COPD acute hyperinflation determines shortening of the inspiratory muscles, its effects on both diaphragm and rib cage morphology are still to be investigated. In this preliminary study the relationships between hyperinflation, emphysema, diaphragm and rib cage geometry were studied in 5 severe COPD patients and 5 healthy subjects. An automatic software was developed to obtain the 3-D reconstruction of diaphragm and rib cage from CT scans taken at total lung capacity (TLC) and residual volume (RV). Dome surface area (Ado), radius of curvature, length (Ld) and position (referred to xiphoid level) of the diaphragm and antero-posterior (A-P) and transverse (T) diameters of rib cage were calculated at both volumes. Ado and Ld were similar in COPD and controls when compared at similar absolute lung volumes. Radius of curvature was significantly higher in COPD than in controls only at TLC. In COPD, the range of diaphragm position was invariantly below the xiphoid level, while in controls the top of diaphragm dome was always above it. Rib cage diameters were not different at TLC. A-P diameter was greater in COPD than in controls at RV, while T diameters were similar. In conclusion, in severe COPD diaphragm and rib cage geometry is altered at RV. The lower position of diaphragm is associated to smaller A-P but not transversal rib cage diameters, such that rib cage adopts a more circular shape. PMID:26737755

  9. Tuneable dynamics of a scandium nitride cluster inside an Ih-C80 cage.

    Science.gov (United States)

    Feng, Yongqiang; Wang, Taishan; Xiang, Junfeng; Gan, Lihua; Wu, Bo; Jiang, Li; Wang, Chunru

    2015-02-01

    The internal clusters in metallofullerenes usually exhibit certain motion that is potentially usable in molecular gyroscopes and nano-machines. Based on (45)Sc NMR, the motion of the scandium nitride cluster within the C80 cage was investigated via varying the temperature and modifying the cage, and by changing the cluster size. PMID:25558825

  10. Standard methods for maintaining adult Apis mellifera in cages under in vitro laboratory conditions

    NARCIS (Netherlands)

    Williams, G.R.; Alaux, C.; Costa, C.; Csaki, C.; Steen, van der J.J.M.

    2013-01-01

    Adult honey bees are maintained in vitro in laboratory cages for a variety of purposes. For example, researchers may wish to perform experiments on honey bees caged individually or in groups to study aspects of parasitology, toxicology, or physiology under highly controlled conditions, or they may c

  11. Immobilization of two organometallic complexes into a single cage to construct protein-based microcompartments.

    Science.gov (United States)

    Maity, Basudev; Fukumori, Kazuki; Abe, Satoshi; Ueno, Takafumi

    2016-04-01

    Natural protein-based microcompartments containing multiple enzymes promote cascade reactions within cells. We use the apo-ferritin protein cage to mimic such biocompartments by immobilizing two organometallic Ir and Pd complexes into the single protein cage. Precise locations of the metals and their accumulation mechanism were studied by X-ray crystallography. PMID:27021005

  12. Recombinant expression and purification of 'virus-like' bacterial encapsulin protein cages

    NARCIS (Netherlands)

    Rurup, W.F.; Cornelissen, J.J.L.M.; Koay, M.S.T.; Orner, Brendan P.

    2014-01-01

    Ultracentrifugation, particularly the use of sucrose or cesium chloride density gradients, is a highly reliable and efficient technique for the purification of virus-like particles and protein cages. Since virus-like particles and protein cages have a unique size compared to cellular macromolecules

  13. Modulation of aggression in male mice : influence of group size and cage size

    NARCIS (Netherlands)

    Van Loo, PLP; Mol, JA; Koolhaas, JM; Van Zutphen, BFM; Baumans, [No Value; Koolhaas, Jaap M.; Zutphen, Bert F.M. van; Baumans, Vera

    2001-01-01

    Aggression in group-housed male mice is known to be influenced by both cage size and group size. However, the interdependency of these two parameters has not been studied yet. In this study, the level of aggression in groups of three, five, or eight male BALB/c mice housed in cages with a floor size

  14. A pyrrolo-tetrathiafulvalene cage: Synthesis and X-ray crystal structure

    DEFF Research Database (Denmark)

    Nielsen, Kent A.; Jeppesen, Jan O.; Levillain, Eric;

    2002-01-01

    A novel type of tetrathiafulvalene-cage 4 containing three monopyrrolo-tetrathiafulvalene units has been prepared employing a general and efficient synthetic approach. X-ray crystal structure analysis revealed that the cage is able to accommodate solvent molecules within a cavity in the solid state....

  15. Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

    Energy Technology Data Exchange (ETDEWEB)

    Grinkova, Yelena V.; Denisov, Ilia G.; McLean, Mark A. [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States); Sligar, Stephen G., E-mail: s-sligar@illinois.edu [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States)

    2013-01-25

    Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

  16. Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

    International Nuclear Information System (INIS)

    Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

  17. Effects of TCDD on the expression of nuclear encoded mitochondrial genes

    International Nuclear Information System (INIS)

    Generation of mitochondrial reactive oxygen species (ROS) can be perturbed following exposure to environmental chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Reports indicate that the aryl hydrocarbon receptor (AhR) mediates TCDD-induced sustained hepatic oxidative stress by decreasing hepatic ATP levels and through hyperpolarization of the inner mitochondrial membrane. To further elucidate the effects of TCDD on the mitochondria, high-throughput quantitative real-time PCR (HTP-QRTPCR) was used to evaluate the expression of 90 nuclear genes encoding mitochondrial proteins involved in electron transport, oxidative phosphorylation, uncoupling, and associated chaperones. HTP-QRTPCR analysis of time course (30 μg/kg TCDD at 2, 4, 8, 12, 18, 24, 72, and 168 h) liver samples obtained from orally gavaged immature, ovariectomized C57BL/6 mice identified 54 differentially expressed genes (|fold change| > 1.5 and P-value < 0.1). Of these, 8 exhibited a sigmoidal or exponential dose-response profile (0.03 to 300 μg/kg TCDD) at 4, 24 or 72 h. Dose-responsive genes encoded proteins associated with electron transport chain (ETC) complexes I (NADH dehydrogenase), III (cytochrome c reductase), IV (cytochrome c oxidase), and V (ATP synthase) and could be generally categorized as having proton gradient, ATP synthesis, and chaperone activities. In contrast, transcript levels of ETC complex II, succinate dehydrogenase, remained unchanged. Putative dioxin response elements were computationally found in the promoter regions of all 8 dose-responsive genes. This high-throughput approach suggests that TCDD alters the expression of genes associated with mitochondrial function which may contribute to TCDD-elicited mitochondrial toxicity.

  18. Physical fitness and mitochondrial respiratory capacity in horse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Dominique-Marie Votion

    Full Text Available BACKGROUND: Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general. METHODOLOGY/PRINCIPAL FINDINGS: We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0-2.5 mg permeabilized muscle fibres sampled from triceps brachii of healthy horses. Oxidative phosphorylation (OXPHOS capacity (pmol O(2 • s(-1 • mg(-1 wet weight with combined Complex I and II (CI+II substrate supply (malate+glutamate+succinate increased from 77 ± 18 in overweight horses to 103 ± 18, 122 ± 15, and 129 ± 12 in untrained, trained and competitive horses (N = 3, 8, 16, and 5, respectively. Similar to human muscle mitochondria, equine OXPHOS capacity was limited by the phosphorylation system to 0.85 ± 0.10 (N = 32 of electron transfer capacity, independent of fitness level. In 15 trained horses, OXPHOS capacity increased from 119 ± 12 to 134 ± 37 when pyruvate was included in the CI+II substrate cocktail. Relative to this maximum OXPHOS capacity, Complex I (CI-linked OXPHOS capacities were only 50% with glutamate+malate, 64% with pyruvate+malate, and 68% with pyruvate+malate+glutamate, and ~78% with CII-linked succinate+rotenone. OXPHOS capacity with glutamate+malate increased with fitness relative to CI+II-supported ETS capacity from a flux control ratio of 0.38 to 0.40, 0.41 and 0.46 in overweight to competitive horses, whereas the CII/CI+II substrate control ratio remained constant at 0.70. Therefore, the apparent deficit of the CI- over CII-linked pathway capacity was reduced with physical fitness. CONCLUSIONS/SIGNIFICANCE: The scope of mitochondrial density-dependent OXPHOS capacity and the density-independent (qualitative increase of CI-linked respiratory capacity with increased

  19. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    International Nuclear Information System (INIS)

    for the decreased ATP production. • Mild uncoupling prevents mitochondrial oxidative damage

  20. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  1. Solid state and aqueous behavior of uranyl peroxide cage clusters

    Science.gov (United States)

    Pellegrini, Kristi Lynn

    Uranyl peroxide cage clusters include a large family of more than 50 published clusters of a variety of sizes, which can incorporate various ligands including pyrophosphate and oxalate. Previous studies have reported that uranyl clusters can be used as a method to separate uranium from a solid matrix, with potential applications in reprocessing of irradiated nuclear fuel. Because of the potential applications of these novel structures in an advanced nuclear fuel cycle and their likely presence in areas of contamination, it is important to understand their behavior in both solid state and aqueous systems, including complex environments where other ions are present. In this thesis, I examine the aqueous behavior of U24Pp 12, as well as aqueous cluster systems with added mono-, di-, and trivalent cations. The resulting solutions were analyzed using dynamic light scattering and ultra-small angle X-ray scattering to evaluate the species in solution. Precipitates of these systems were analyzed using powder X-ray diffraction, X-ray fluorescence spectrometry, and Raman spectroscopy. The results of these analyses demonstrate the importance of cation size, charge, and concentration of added cations on the aqueous behavior of uranium macroions. Specifically, aggregates of various sizes and shapes form rapidly upon addition of cations, and in some cases these aggregates appear to precipitate into an X-ray amorphous material that still contains U24Pp12 clusters. In addition, I probe aggregation of U24Pp12 and U60, another uranyl peroxide cage cluster, in mixed solvent water-alcohol systems. The aggregation of uranyl clusters in water-alcohol systems is a result of hydrogen bonding with polar organic molecules and the reduction of the dielectric constant of the system. Studies of aggregation of uranyl clusters also allow for comparison between the newer uranyl polyoxometalate family and century-old transition metal polyoxometalates. To complement the solution studies of uranyl

  2. Environmental enrichment reduces signs of boredom in caged mink.

    Directory of Open Access Journals (Sweden)

    Rebecca K Meagher

    Full Text Available Animals housed in impoverished cages are often labelled 'bored'. They have also been called 'apathetic' or 'depressed', particularly when profoundly inactive. However, these terms are rarely operationally defined and validated. As a negative state caused by under-stimulation, boredom should increase interest in stimuli of all kinds. Apathy (lack of interest, by contrast, should manifest as decreased interest in all stimuli, while anhedonia (loss of pleasure, a depressive symptom should specifically decrease interest in normally rewarding stimuli. We tested the hypotheses that mink, a model carnivore, experience more boredom, depression-like apathy, or anhedonia in non-enriched (NE cages than in complex, enriched (E cages. We exposed 29 subjects (13 E, 16 NE to ten stimuli categorized a priori as aversive (e.g. air puffs, rewarding (e.g. evoking chasing or ambiguous/neutral (e.g. candles. Interest in stimuli was assessed via latencies to contact, contact durations, and durations oriented to stimuli. NE mink contacted all stimuli faster (P = 0.003 than E mink, and spent longer oriented to/in contact with them, albeit only significantly so for ambiguous ones (treatment*type P<0.013. With stimulus category removed from statistical models, interest in all stimuli was consistently higher among NE mink (P<0.0001 for all measures. NE mink also consumed more food rewards (P = 0.037. Finally, we investigated whether lying down while awake and stereotypic behaviour (both increased by NE housing predicted these responses. Lying awake positively co-varied with certain measures of increased exploration. In contrast, stereotypic 'scrabbling' or locomotion (e.g. pacing did not. Overall, NE mink showed no evidence of apathy or depression, but instead a heightened investigation of diverse stimuli consistent with boredom. This state was potentially indicated by spending much time lying still but awake (although this result requires replication. Boredom can

  3. Uncoupled correlated variational function in (e, 2e) and (e, 3e) calculations for ionization of the helium atom

    CERN Document Server

    Chuluunbaatar, O; Vinitsky, S I

    2002-01-01

    The uncoupled correlated variational function of the helium atom ground state declared earlier is examined in calculations of differential cross sections of fast electron impact single and double binary ionization processes. An optimal one-parametric set of orthogonal basic functions is generated to provide the considerable coincidence with the experiment and calculations with the alternative multiparametric trial wave functions.

  4. Outcome of instrumented lumbar fusion for low grade spondylolisthesis; Evaluation of interbody fusion with & without cages

    Science.gov (United States)

    Fathy, Mostafa; Fahmy, Mohamed; Fakhri, Mazen; Aref, Khaled; Abdin, Khaled; Zidan, Ihab

    2010-01-01

    Object: The aim is to evalute the outcome of posterior lumbar interbody fusion with autologous bone graft versus titanium Cages, BAK system (Bagby – Kuslich, Spine Tech, Inc. Minneapolis, MN) for low grade spondyloisthesis (Grade1,11). Interbody cages have been developed to replace tricortical Interbody grafts in posterior lumbar interbody fusion (PLIF) procedures. The cages provide immediate post operative stability and facilitate bony union with cancellous bone packed in the cage itself. METHOD: We Evaluated 50 consecutive patients in whom surgery was performed between June 2000 to June 2003 in the Main Alexandria University Hospital at EGYPT. Twenty five patients were operated using autologous bone graft and 25 patients using the BAK cages. The neuro–radiologic al work up consisted of; plain X – ray lumbosacral spine including dynamic films preoperative and postoperative follow up; C.T lumbosacral spine and MRI lumbosacral spine. The surgery was performed at L4-5 level in 34 cases and at L5-S1 level in 16 cases. The median follow up was 15 months. RESULTS: Satisfactory fusion was obtained at all levels at a minimum one year follow – up. The fusion rate was 96% (24 patients) for the cage group and 80% (20 patients) for bone graft group however clinical improvement was 64% (16 patients) for those with bone graft group. CONCLUSION: A higher fusion rates and a better clinical outcome have been obtained by Instrumented PLIF with titanium cages that with bone graft. Inderbody fusion cages help to stabilize spainal segment primarily by distracting them as well as by allowing bone ingrowth and fusion. The procedure is safe and effective with 96% fusion rate and 76% overall Satisfactory rate. The use of cages help to distract the space between the vertebral bodies making the correction of the degree of spondylolisthesis easier. Long term follow up revealed better fusion rate and better realignment and less resorption with cages than with bone grafts. PMID

  5. Hydrodynamical simulations of coupled and uncoupled quintessence models II: Galaxy clusters

    CERN Document Server

    Carlesi, Edoardo; Lewis, Geraint F; Yepes, Gustavo

    2014-01-01

    We study the $z=0$ properties of clusters (and large groups) of galaxies within the context of interacting and non-interacting quintessence cosmological models, using a series of adiabatic SPH simulations. Initially, we examine the average properties of groups and clusters, quantifying their differences in LCDM, uncoupled Dark Energy (\\ude) and coupled Dark Energy (\\cde) cosmologies. In particular, we focus upon radial profiles of the gas density, temperature and pressure, and we also investigate how the standard hydrodynamic equilibrium hypothesis holds in quintessence cosmologies. While we are able to confirm previous results about the distribution of baryons, we also find that the main discrepancy (with differences up to $20\\%$) can be seen in cluster pressure profiles. We then switch attention to individual structures, mapping each halo in quintessence cosmology to its \\LCDM\\ counterpart. We are able to identify a series of small correlations between the coupling in the dark sector and halo spin, triaxial...

  6. Thermohaline circulation stability: a box model study - Part I: uncoupled model

    CERN Document Server

    Lucarini, V; Lucarini, Valerio; Stone, Peter H.

    2004-01-01

    A thorough analysis of the stability of the uncoupled Rooth interhemispheric 3-box model of thermohaline circulation (THC) is presented. The model consists of a northern high latitudes box, a tropical box, and a southern high latitudes box, which respectively correspond to the northern, tropical and southern Atlantic ocean. We adopt restoring boundary conditions for the temperature variables and flux boundary conditions for the salinity variables. We study how the strength of THC changes when the system undergoes forcings that are analogous to those of global warming conditions by applying to the equilibrium state perturbations to the moisture and heat fluxes into the three boxes. In each class of experiments, we determine, using suitably de- fined metrics, the boundary dividing the set of forcing scenarios that lead the system to equilibria characterized by a THC pattern similar to the present one, from those that drive the system to equilibria with a reversed THC. Fast increases in the moisture flux into th...

  7. Transverse dynamics of a beam in a chain of uncoupled resonators

    International Nuclear Information System (INIS)

    A method is proposed and realized for full-scale numerical simulation of the transverse dynamics of a train of point charged bunches accelerated in a chain of identical uncoupled resonators. Selfconsistent system of equations of transverse motion of such bunches in a total field of spontaneous transition radiation of the predecessors of each bunch at f11 frequency of defocusing TM110-oscillations of the resonators is reduced to the system of the finite number of algebraic equations for amplitudes of generalized shift moments of such bunches in each resonator. Numerical solutions of this system are presented for a number of specific values of the parameters of the accelerating structure and accelerating beam as well as various starting conditions at the structure's inlet. The obtained results are used for controlling reliability level of the known methods of analytical description of the dynamics under consideration. 6 refs.; 3 figs

  8. Comparison of coupled and uncoupled load simulations on a jacket support structure

    DEFF Research Database (Denmark)

    Haselbach, Philipp Ulrich; Natarajan, Anand; Jiwinangun, Randi Gusto; Branner, Kim

    2013-01-01

    In this article, a comparison of the moments and forces at the joints of a jacket structure is made between fully coupled aerohydroelastic simulations in HAWC2 and uncoupled load predictions in the finite element software Abaqus. The jacket sub structure is modelled in moderate deep waters of 50m......-legged jacket structure similar to the Upwind reference jacket is developed in the Abaqus environment, to which is added the transition piece and tower. The aeroelastic loads determined in normal operating conditions of the turbine is integrated and centralized as nodal forces and moments acting at the tower...... and linking the loads to the components as nodal forces. In both simulation cases, the integrated loads acting on the jacket legs are computed as time series and as damage equivalent loading. The analysis and comparison of the fully coupled and decoupled simulation method show that the results vary...

  9. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.

    Science.gov (United States)

    Lappe-Siefke, Corinna; Goebbels, Sandra; Gravel, Michel; Nicksch, Eva; Lee, John; Braun, Peter E; Griffiths, Ian R; Nave, Klaus-Armin

    2003-03-01

    Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss. PMID:12590258

  10. Coherent population transfer between uncoupled or weakly coupled states in ladder-type superconducting qutrits.

    Science.gov (United States)

    Xu, H K; Song, C; Liu, W Y; Xue, G M; Su, F F; Deng, H; Tian, Ye; Zheng, D N; Han, Siyuan; Zhong, Y P; Wang, H; Liu, Yu-Xi; Zhao, S P

    2016-01-01

    Stimulated Raman adiabatic passage offers significant advantages for coherent population transfer between uncoupled or weakly coupled states and has the potential of realizing efficient quantum gate, qubit entanglement and quantum information transfer. Here we report on the realization of the process in the superconducting Xmon and phase qutrits-two ladder-type three-level systems in which the ground state population is coherently transferred to the second excited state via the dark state subspace. We demonstrate that the population transfer efficiency is no less than 96% and 67% for the two devices, which agree well with the numerical simulation of the master equation. Population transfer via stimulated Raman adiabatic passage is significantly more robust against variations of the experimental parameters compared with that via the conventional resonant π pulse method. Our work opens up a new venue for exploring the process for quantum information processing using the superconducting artificial atoms. PMID:27009972

  11. Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition.

    Science.gov (United States)

    Di Paola, Marco; Lorusso, Michele

    2006-01-01

    Long chain free fatty acids (FFA) exert, according to their actual concentration, different effects on the energy conserving system of mitochondria. Sub-micromolar concentrations of arachidonic acid (AA) rescue DeltapH-dependent depression of the proton pumping activity of the bc1 complex. This effect appears to be due to a direct interaction of AA with the proton-input mouth of the pump. At micromolar concentrations FFA increase the proton conductance of the inner membrane acting as protonophores. FFA can act as natural uncouplers, causing a mild uncoupling, which prevents reactive oxygen species production in the respiratory resting state. When Ca(2+)-loaded mitochondria are exposed to micromolar concentrations of FFA, the permeability of the inner membrane increases, resulting in matrix swelling, rupture of the outer membrane and release of intermembrane pro-apoptotic proteins. The characteristics of AA-induced swelling appear markedly different in mitochondria isolated from heart or liver. While in the latter it presents the canonical features of the classical permeability transition (PT), in heart mitochondria substantial differences are observed concerning CsA sensitivity, DeltaPsi dependence, reversibility by BSA and specificity for the activating divalent cation. In heart mitochondria, the AA-dependent increase of the inner membrane permeability is affected by ANT ligands such as adenine nucleotides and atractyloside. AA apparently causes a Ca2+-mediated conversion of ANT from a translocator to a channel system. Upon diamide treatment of heart mitochondria, the Ca2+/AA-induced CsA insensitive channel is converted into the classical PT pore. The relevance of these observations in terms of tissue-specific components of the putative PTP and heart ischemic and post-ischemic process is discussed. PMID:16697347

  12. Resonance Spectra of Caged Stringy Black Hole and Its Spectroscopy

    CERN Document Server

    Sakalli, I

    2015-01-01

    The Maggiore's method (MM), which evaluates the transition frequency that appears in the adiabatic invariant from the highly damped quasinormal mode (QNM) frequencies, is used to investigate the entropy/area spectra of the Garfinkle--Horowitz--Strominger black hole (GHSBH). Instead of the ordinary QNMs, we compute the boxed QNMs (BQNMs) that are the characteristic resonance spectra of the confined scalar fields in the GHSBH geometry. For this purpose, we assume that the GHSBH has a confining cavity (mirror) placed in the vicinity of the event horizon. We then show how the complex resonant frequencies of the caged GHSBH are computed using the Bessel differential equation that arises when the scalar perturbations around the event horizon are considered. Although the entropy/area is characterized by the GHSBH parameters, their quantization is shown to be independent of those parameters. However, both spectra are equally spaced.

  13. Magnetotactic Bacterial Cages as Safe and Smart Gene Delivery Vehicles

    KAUST Repository

    Alsaiari, Shahad K.

    2016-07-27

    In spite of the huge advances in the area of synthetic carriers, their efficiency still poorly compares to natural vectors. Herein, we report the use of unmodified magnetotactic bacteria as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). High cargo loading is established under anaerobic conditions (bacteria is alive) through endocytosis where AuNPs are employed as transmembrane proteins mimics (facilitate endocytosis) as well as imaging agents to verify and quantify loading and release. The naturally bio-mineralized magnetosomes, within the bacteria, induce heat generation inside bacteria through magnetic hyperthermia. Most importantly after exposing the system to air (bacteria is dead) the cell wall stays intact providing an efficient bacterial vessel. Upon incubation with THP-1 cells, the magnetotactic bacterial cages (MBCs) adhere to the cell wall and are directly engulfed through the phagocytic activity of these cells. Applying magnetic hyperthermia leads to the dissociation of the bacterial microcarrier and eventual release of cargo.

  14. CAGE Analysis of China’s Trade Globalization

    Directory of Open Access Journals (Sweden)

    Emmanuel Olusegun STOBER

    2014-06-01

    Full Text Available Gravity model of international trade states that trade interaction between two countries is in direct proportion to their size measured by Gross Domestic Product and in inverse proportion to the geographic distance. Conley and Ligon (2001 argued that the relevant economic distance between countries is often not the geographic distance. Thus, this study uses original datasets on economic distance to structure observed variations, to decompose the multidimensional CAGE distance framework of globalization derived from the Newton’s Law of gravitation as it applies to China’s international interaction, to evaluate bilateral trade patterns in identifying and prioritizing the importance of cross-border flows and differences that accounted for the development of China’s global strategies. This study confirms that distance must be accounted for in the decision making of any country’s globalization process or any firm’s global expansion as the effects on cross-border economic activities are enormous.

  15. Electrostatic capacitance and Faraday cage behavior of carbon nanotube forests

    International Nuclear Information System (INIS)

    Understanding of the electrostatic properties of carbon nanotube (CNT) forests is essential to enable their integration in microelectronic and micromechanical devices. In this study, we sought to understand how the hierarchical geometry and morphology of CNT forests determines their capacitance. First, we find that at small gaps, solid micropillars have greater capacitance, yet at larger gaps the capacitance of the CNT forests is greater. The surface area of the CNT forest accessible to the electrostatic field was extracted by analysis of the measured capacitance, and, by relating the capacitance to the average density of CNTs in the forest, we find that the penetration depth of the electrostatic field is on the order of several microns. Therefore, CNT forests can behave as a miniature Faraday cage. The unique electrostatic properties of CNT forests could therefore enable their use as long-range proximity sensors and as shielding elements for miniature electronic devices

  16. Nonlinear vs. linear biasing in Trp-cage folding simulations

    Energy Technology Data Exchange (ETDEWEB)

    Spiwok, Vojtěch, E-mail: spiwokv@vscht.cz; Oborský, Pavel; Králová, Blanka [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28 (Czech Republic); Pazúriková, Jana [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Křenek, Aleš [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Center CERIT-SC, Masaryk Univerzity, Šumavská 416/15, 602 00 Brno (Czech Republic)

    2015-03-21

    Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable.

  17. Nonlinear vs. linear biasing in Trp-cage folding simulations

    International Nuclear Information System (INIS)

    Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable

  18. Gaiola de metabolismo para equinos Metabolism cage for horses

    Directory of Open Access Journals (Sweden)

    Dorinha Miriam Silber Schmidt Vitti

    2000-05-01

    Full Text Available A gaiola de metabolismo, modelo proposto neste trabalho, foi construida na Seção de Oficina da FCAV-Unesp, Jaboticabal-SP e utilizada no Laboratório de Ciências Animais do Cena-USP, Piracicaba-SP. Este equipamento permite alojar eqüinos machos com idade a partir do desmame. Os animais foram treinados (condicionados diariamente a permanecer na gaiola de metabolismo por um período de aproximadamente 30 dias antes do início do experimento. O material necessário e a construção de uma gaiola metabólica para eqüinos machos é descrita e ilustrada. A estrutura principal da gaiola (2,68 m de comprimento x 0,80 m de largura x 2,02 m de altura é constituida por canos de metal de duas polegadas e todas as unidades de apoio - tábuas do piso, grade de urina, bebedouro, comedouro, bandeja coletora de urina e barras de contenção - estão fixas à estrutura principal de modo a serem removidas desta, faciltando o manejo e a limpeza do equipamento. O equipamento foi projetado para alojar animais de vários tamanhos e também para ser efetiva na coleta total de fezes e urina e no fornecimento de alimento e água. Os animais permaneceram em pé durante todo o período de confinamento, sem contudo ter havido a ocorrência de edemas graves nos membros. O modelo proposto foi testado em experimentos de metabolismo de fósforo utilizando-se radioisótopos.The metabolism cage here proposed was built at FCAV-Unesp, Jaboticabal, state of São Paulo, Brazil, and used in the Animal Science Laboratory at Cena-USP, Piracicaba, state of São Paulo, Brazil. The equipment allows to host male horses from weaning to adult age. Before starting the experiment, the animals were daily conditioned for a 30-day period to remain in the cage. The necessary material and the building process of the horse metabolic cage are described and illustrated. The main structure of the cage (2.68m long x 0.80 m wide x 2.02 m high was made of 2-inch-diameter metal tube, and all the

  19. Molecular Genetics of Mitochondrial Disorders

    Science.gov (United States)

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  20. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper;

    ) and in silico-predicted mitochondrial proteins (2000-3000). Thus, before starting to look for oxidized peptides, we wanted to expand the current compendium of plant mitochondrial proteins while obtaining what could be termed the "baseline proteome" from our model organelle, the potato tuber...

  1. Biochemical diagnosis of mitochondrial disorders

    NARCIS (Netherlands)

    Rodenburg, R.J.T.

    2011-01-01

    Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patie

  2. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hey-Mogensen, Martin; Sahlin, Kent; Fernström, Maria;

    2007-01-01

    We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy......-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria....... Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were...

  3. Role of cage material, working style and hearing sensitivity in perception of animal care noise.

    Science.gov (United States)

    Voipio, H-M; Nevalainen, T; Halonen, P; Hakumäki, M; Björk, E

    2006-10-01

    During daily care, laboratory animals are exposed to a variety of sounds which may have effects on welfare and also cause physiological and behavioural changes. So far, almost no attention has been paid to individual sounds or the sound level caused by animal care or the sound level inside the animal cage. In this study, sounds from selected rat care procedures were recorded: pulling cage out of the rack, placing it onto a table and replacing the cage back into the rack; with measurements made inside the rat cage and in the adjacent cage. Diet was poured into the food hopper and sounds were recorded inside the cage and also the adjacent cage. The work was repeated in a calm and also in a hurried style, using stainless steel and polycarbonate cages. Finally, the sounds produced by running tap water were recorded. Differences between rat and human hearing were compared using novel species-specific sound level weightings: R-weighting for rats dB(R) and H-weighting for human dB(H). Hurried work with steel caused sound exposure levels exceeding 90 dB(R) when the cages were placed into the rack and about 80 dB(R) when pulling them out of the rack or placing onto a table. With polycarbonate, the levels were 10-15 dB(R) lower. Unhurried calm working produced lower sound exposure levels than hurried working in many procedures. When the procedures were repeated with measurements in the adjacent cage, the sound exposure levels were lower, but the results were similar. Pouring food pellets into a hopper above the rat's head caused 15 dB(R) higher sound exposure levels than pouring food to an adjacent cage. In general, humans hear these sounds about 10-15 dB louder than rats. In conclusion, cage material, working style and hearing sensitivity all have an impact on the sound exposure level in the rodent cage. With correct working methods, high sound levels can be efficiently avoided in most cases. PMID:17018211

  4. Mitochondrial and glycolytic activity of UV-irradiated human keratinocytes and its stimulation by a Saccharomyces cerevisiae autolysate.

    Science.gov (United States)

    Schütz, Rolf; Kuratli, Karin; Richard, Nathalie; Stoll, Clarissa; Schwager, Joseph

    2016-06-01

    Cutaneous aging is correlated with mitochondrial dysfunction and a concomitant decline in energy metabolism that can be accelerated by extrinsic factors such as UV radiation (UVR). In this study we compared cellular bioenergetics of normal and UV-irradiated primary human epidermal keratinocytes. Moreover, we investigated the influence of a Saccharomyces cerevisiae autolysate (SCA) on stressed keratinocytes to regain cellular homeostasis. Cellular metabolism was assessed by extracellular flux analysis which measures oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as well as by ATP quantification. The expression level of ten mitochondria related genes in normal and UVR-stimulated (60mJ/cm(2) UVB) keratinocytes was quantified by real-time PCR and the impact of SCA addition was determined. Sublethal UV stress increased mitochondrial dysfunction in keratinocytes which resulted in reduced viability, uncoupled oxidative phosphorylation, and down-regulated mitochondrial gene expression. Particularly, gene expression of SHDA, UPC2, BID, and ATP5A1 was reduced about twofold within 4h. Treatment of keratinocytes with SCA shifted cellular metabolism towards a more energetic status by increasing the respiratory rate and glycolysis. SCA also stimulated cellular ATP production after short (4h) and prolonged (22h) incubations and induced the expression of genes related to mitochondrial function towards normal expression levels upon UV irradiation. The decreased respiratory capacity of UV-irradiated keratinocytes was partially compensated by the addition of SCA which enhanced glycolytic activity and thereby increased cellular resistance to environmental stress. PMID:27060217

  5. Digestibility and behavior of dogs housed in kennels or metabolic cages

    Directory of Open Access Journals (Sweden)

    Tabyta Tamara Sabchuk

    2012-01-01

    Full Text Available The objective of the present study was to compare the apparent digestibility coefficients of a commercial dog food, fecal consistency and behavior of dogs housed in kennels and metabolic cages. Six adult Beagle dogs were distributed in cross-over experimental design, with six replicates per treatment. Dogs were housed in two environments: metabolic cages and in masonry kennels with solarium. Dogs were fed for a five-day adaptation period, and the five following days were used for total feces collection. Dogs behavior was recorded during a 48-h period, with 10-min intervals. Apparent digestibility coefficients were not different between treatments. However, dogs housed in metabolic cages produced lower weight and more consistent feces as compared with dogs housed in kennels. Dogs spent most of the time sleeping in both housing systems; however, dogs housed in the metabolic cages slept more than those in kennels. Stress-related behaviors (barking, whimpering, stereotypies, etc were observed for no longer than 15 minutes per day, and were not different between dogs in kennels or in cages. There is no difference in food digestibility evaluated in dogs housed in metabolic cages or kennels; however, dogs kept in metabolic cages eliminate drier feces and spend more time inactive than those kept in kennels.

  6. Cage-induced stereotypies, perseveration and the effects of environmental enrichment in laboratory mice.

    Science.gov (United States)

    Gross, Alexandra N; Richter, S Helene; Engel, A Katarina J; Würbel, Hanno

    2012-09-01

    When kept in barren and restrictive cages, animals frequently develop stereotypic behaviour patterns that are characterized by high repetition rates, conspicuous invariance and an apparent lack of function. Although millions of animals are affected, the underlying causes and mechanisms are still unclear. Growing evidence suggests that cage-induced stereotypies may reflect pathological dysfunction within basal ganglia circuitry expressed by perseverative behaviour. In order to assess whether variation in stereotypy performance and variation in perseverative behaviour may have a common cause in ICR CD-1 mice, we assessed the effects of environmental enrichment on both phenomena. We raised 48 female ICR CD-1 mice in standard or enriched cages from three weeks to either 6 or 11 months of age and measured stereotypy level in the home cage and perseveration on an extinction task. We further examined whether enriched rearing conditions (early enrichment) protect mice from the developing stereotypies later in life and whether stereotypies developed in barren cages would persist in an enriched environment (late enrichment) by transferring standard mice to enriched cages and vice versa for 14 weeks after completion of the extinction task. We found no evidence for a causal relation between stereotypy and perseveration in mice. However, transfer to enriched cages reduced stereotypy levels significantly both at 6 and 11 months of age indicating that stereotypies had not become established yet. Finally, we found that removing enrichments at both ages did not induce higher stereotypy levels, thereby confirming earlier reports of a neuroprotective effect of early enrichment. PMID:22721674

  7. Evaluation of the 96/4 PLDLLA polymer resorbable lumbar interbody cage in a long term animal model.

    Science.gov (United States)

    Lazennec, Jean Y; Madi, Abdallah; Rousseau, Marc A; Roger, Bernard; Saillant, Gérard

    2006-10-01

    Arthrodesis using interbody cages has demonstrated high fusion rates. However, permanent cages are exposed to stress-shielding, corrosion, and may require explanation when necessary. Polylactic acid (PLA) bioresorbable cages are developed for avoiding these problems, but significant tissue reaction has been reported with 70/30 PLDLLA in some preclinical animal studies. The objective was to evaluate 96/4 PLDLLA cages in a sheep model over 3 years. Sixteen sheeps underwent one level anterior lumbar interbody fusion using 96/4 PLDLLA cages, filled and surrounded with cancellous bone graft from the iliac crest. Six groups of three animals were killed after 3, 6, 9, 12, 24, and 36 months. Harvested lumbar spine had radiographic, MRI, and CT evaluation and histological analysis. Histological results: cage swelling and slight signs of fragmentation associated to fibrocartilaginous tissue apposition at 3 months; bone remodeling around the cage with direct apposition of the mineralization front at 6 months; active cage degradation and complete fusion around the cage at 9 months; cage fragmentation and partial replacement by bone tissue at 12 months; bone bridges in and around the cage at 24 months; full resorption and intervertebral fusion at 36 months. Radiological results: partial arthrodesis at 3 months; definite peripheral arthrodesis at 6 months; similar aspect at 9 months; significant cage resorption at 12 months; definite inner and outer fusion at 24 months; complete cage resorption and calcification at the location of the cage at 36 months confirmed histological observations. Radiographic, CT scan, MRI, and histological data were consistent for showing progressive resorption of 96/4 PLDLLA, interbody fusion, and bone remodeling, with no significant signs of local intolerance reaction. These results are promising and suggest further development of 96/4 PLDLLA cages. PMID:16736199

  8. Lipid metabolism in mitochondrial membranes.

    Science.gov (United States)

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  9. The centrifugal Jahn-Teller effect in rare-earth cage systems

    OpenAIRE

    Amara, Mehdi

    2015-01-01

    The analysis of the properties of rare-earth based materials relies on the Crystalline Electric Field theory. This theory has to be reconsidered in case of cage-type compounds, where the rare-earth ion can substantially depart from its, high symmetry, average position. It is shown that, in case of an orbital degeneracy at the cage center, a specific Jahn-Teller effect develops in the paramagnetic range: at low temperature, the distribution of the magnetic ion spreads inside the cage, the magn...

  10. Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Chariya; Hahnvajanawong; Wongwarut; Boonyanugomol; Tapanawan; Nasomyon; Watcharin; Loilome; Nisana; Namwat; Natthinee; Anantachoke; Wichittra; Tassaneeyakul; Banchob; Sripa; Wises; Namwat; Vichai; Reutrakul

    2010-01-01

    AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 cells.METHODS:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(i.e.isomorellin,isomorellinol,forbesione and gambogic acid) were used in this study.Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay.Induction of apoptosis was assessed by observing cell morphology,ethidi...

  11. Laying Performance of Wareng Chicken under Free Choice Feeding and Different Cage Density

    OpenAIRE

    S Iskandar

    2011-01-01

    The aim of the experiment was to explore the possibility of using free choice feeding technique under different cage density for unselected native chicken. Eighty hens of laying Wareng chicken were divided into two feeding systems. Half of them were fed complete commercial diet of 17% crude protein, with 2800 kcal ME/kg and the other half were subjected to free choice diet. The diets were in mash form and placed in sufficient feed troughs in front of each cage. Each cage was occupied by four ...

  12. Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2015-08-01

    Full Text Available A simple synthetic strategy to C2-symmetric bis-spiro-pyrano cage compound 7 involving ring-closing metathesis is reported. The hexacyclic dione 10 was prepared from simple and readily available starting materials such as 1,4-naphthoquinone and cyclopentadiene. The synthesis of an unprecedented octacyclic cage compound through intramolecular Diels–Alder (DA reaction as a key step is described. The structures of three new cage compounds 7, 12 and 18 were confirmed by single crystal X-ray diffraction studies.

  13. Percutaneous Vertebroplasty in a Broken Vertebral Titanium Implant (Titanium Mesh Cage)

    International Nuclear Information System (INIS)

    We report the case of a percutaneous consolidation of a broken vertebral implant (Surgical Titanium Mesh Implants; DePuy Spine, Raynham, MA, USA) by vertebroplasty. Four years after anterior spondylectomy with cage implantation and stabilization with posterior instrumentation, the patient was admitted for excruciating back pain. Radiographs showed fracture of the cage, screw, and rod. An anterior surgical approach was deemed difficult and a percutaneous injection of polymethyl methacrylate into the cage was performed following posterior instrumentation replacement. This seems to be an interesting alternative to the classical anterior surgical approach, which is often difficult in postoperative conditions

  14. Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE

    DEFF Research Database (Denmark)

    Valen, Eivind; Pascarella, Giovanni; Chalk, Alistair;

    2009-01-01

    given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth...... of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect...

  15. Pet Birds. Cages and Practices of Domestication in Eighteenth-Century Paris

    OpenAIRE

    Breittruck, Julia

    2012-01-01

    This paper focuses on the genesis of the »pet making« of birds in eighteenth-century Paris. It examines the ways in which particular cages, and the corresponding imagination and practice of caretaking and domestication, construed birds as »pets.« The status of these animals in either their difference or similarity to »the human« is analyzed by looking at different kinds of bird-caging instructions. First, I found that bird caging developed as a cultural technique of domestication since it org...

  16. Integrating mitochondrial translation into the cellular context.

    Science.gov (United States)

    Richter-Dennerlein, Ricarda; Dennerlein, Sven; Rehling, Peter

    2015-10-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial-encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisingly, found to act as regulators of mitochondrial translation. In turn, translation in mitochondria controls cellular proliferation, and mitochondrial ribosomal subunits contribute to the cytoplasmic stress response. Thus, translation in mitochondria is apparently integrated into cellular processes. PMID:26535422

  17. Role of Pterocarpus santalinus against mitochondrial dysfunction and membrane lipid changes induced by ulcerogens in rat gastric mucosa.

    Science.gov (United States)

    Narayan, Shoba; Devi, R S; Devi, C S Shyamala

    2007-11-20

    Free radicals produced by ulcerogenic agents affect the TCA cycle enzymes located in the outer membrane of the mitochondria. Upon induction with ulcerogens, peroxidation of membrane lipids bring about alterations in the mitochondrial enzyme activity. This indicates an increase in the permeability levels of the mitochondrial membrane. The ability of PSE to scavenge the reactive oxygen species results in restoration of activities of TCA cycle enzymes. NSAIDs interfere with the mitochondrial beta-oxidation of fatty acids in vitro and in vivo, resulting in uncoupling of mitochondrial oxidative phosphorylation process. This usually results in diminished cellular ATP production. The recovery of gastric mucosal barrier function through maintenance of energy metabolism results in maintenance of ATP levels, as observed in this study upon treatment with PSE. Membrane integrity altered by peroxidation is known to have a modified fatty acid composition, a disruption of permeability, a decrease in electrical resistance, and increase in flip-flopping between monolayers and inactivated cross-linked proteins. The severe depletion of arachidonic acid in ulcer induced groups was prevented upon treatment with PSE. The acid inhibitory property of the herbal extract enables the maintenance of GL activity upon treatment with PSE. The ability to prevent membrane peroxidation has been traced to the presence of active constituents in the PSE. In essence, PSE has been found to prevent mitochondrial dysfunction, provide mitochondrial cell integrity, through the maintenance of lipid bilayer by its ability to provide a hydrophobic character to the gastric mucosa, further indicating its ability to reverse the action of NSAIDs and mast cell degranulators in gastric mucosa. PMID:17719569

  18. The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications

    International Nuclear Information System (INIS)

    Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 μM) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mitochondria, isolated from rat liver. In HepG2 cells GA decreased viability, dissipated mitochondrial membrane potential, depleted ATP and increased reactive oxygen species (ROS) levels. In isolated rat-liver mitochondria GA promoted membrane fluidity increase, cyclosporine A/EGTA-insensitive membrane permeabilization, uncoupling (membrane potential dissipation/state 4 respiration rate increase), Ca2+ efflux, ATP depletion, NAD(P)H depletion/oxidation and ROS levels increase. All effects in cells, except mitochondrial membrane potential dissipation, as well as NADPH depletion/oxidation and permeabilization in isolated mitochondria, were partly prevented by the a NAD(P)H regenerating substrate isocitrate. The results suggest the following sequence of events: 1) GA interaction with mitochondrial membrane promoting its permeabilization; 2) mitochondrial membrane potential dissipation; 3) NAD(P)H oxidation/depletion due to inability of membrane potential-sensitive NADP+ transhydrogenase of sustaining its reduced state; 4) ROS accumulation inside mitochondria and cells; 5) additional mitochondrial membrane permeabilization due to ROS; and 6) ATP depletion. These GA actions are potentially implicated in the well-documented anti-cancer property of GA/structure related compounds. - Graphical abstract: Guttiferone-A permeabilizes mitochondrial membrane and induces cancer cell death Display Omitted Highlights: → We addressed the involvement of mitochondria in guttiferone (GA) toxicity toward cancer cells. → GA promoted membrane permeabilization, membrane potential dissipation, NAD(P)H depletion, ROS accumulation and ATP depletion. → These actions could be

  19. A comparison of the direct and indirect effects of low LET radiation on mitochondrial oxygen consumption rate and induction of mtDNA mutations

    International Nuclear Information System (INIS)

    Full text: Growing evidence has recently accumulated showing that 'bystander effects' can be observed in cells that were not themselves irradiated, but where in the vicinity of irradiated cells, or exposed to medium from irradiated cells. The aim of this study was to examine if medium from irradiated cells could initiate irregular mitochondrial function in non-irradiated cells and compare this to mitochondrial function in directly irradiated cells. Human keratinocytes (HPV-G cell line) and Chinese hamster fibroblasts (CHO) were irradiated with 5.0 Gy γ rays. Cells were then either harvested and examined or the medium from these irradiated cells was transferred to non-irradiated cells and these cells then harvested and examined. The oxygen consumption rate of whole cells, permeabilised with digitonin, was determined in a Clarke-type oxygen electrode measuring state 4, state 3 and uncoupled rates of respiration. Mitochondrial DNA was extracted and selected regions of the mitochondrial genome amplified and mutations and small deletions identified by Single Strand Conformation Polymorphism analysis and Restriction Fragment Length Polymorphism analysis respectively. Reduced oxygen consumption was observed in both HPV-G cells and CHO cells as a result of both direct irradiation and exposure to medium from irradiated cells. Point mutations were observed in mitochondrial DNA from HPV-G and CHO cells that were directly irradiated, though no small deletions were identified. The data in this study suggests that mitochondrial dysfunction resulting from direct irradiation may be similarly induced in non-irradiated cells by a factor or number of factors released into growth medium from irradiated cells. The compact mitochondrial genome also incurs the generation of point mutations in irradiated cells, which may well result in the reduced or irregular synthesis of 1 or more of the 13 mitochondrially encoded polypeptides that make up subunits of complexes I, III, IV and V of

  20. Mitochondrial Defects in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Josefa Salgado

    2008-01-01

    Full Text Available Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe a variety of mitochondrial DNA alterations present in breast cancer. In this review article, we to provide a summary of the mitochondrial genomic alterations reported in breast cancer and their functional consequences.

  1. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  2. Integrating mitochondrial translation into the cellular context.

    OpenAIRE

    Richter-Dennerlein, R.; Dennerlein Sven, S.; Rehling, P

    2015-01-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial- encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisin...

  3. Mitochondrial transcript maturation and its disorders

    OpenAIRE

    Van Haute, Lindsey; Pearce, Sarah F.; Powell, Christopher A.; D’Souza, Aaron R.; Nicholls, Thomas J.; Minczuk, Michal

    2015-01-01

    Mitochondrial respiratory chain deficiencies exhibit a wide spectrum of clinical presentations owing to defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mitochondrial DNA (mtDNA) or mutations in nuclear genes coding for mitochondrially-targeted proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial biology including expression of mtDNA-encoded genes. Expression of the mi...

  4. Mitochondrial Stress: A Bridge between Mitochondrial Dysfunction and Metabolic Diseases?

    OpenAIRE

    Hu, Fang; Liu, Feng

    2011-01-01

    Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPRmt) and initiation of a retrograde stress signaling pathway. Defects in the UPRmt and the retrograde signaling pathways may disrupt the integrity and homeostasis of the mitochondria, resulting endoplasmic reticulum stress and insulin resistance. Improving the capacity of mitochondria to reduce stress may be an effective a...

  5. Storage of molecular hydrogen into leaky clathrate hydrate cages

    International Nuclear Information System (INIS)

    Full text: Efficient storage of hydrogen into compact media is an essential challenge to establish a hydrogen economy. A nanostructured compound made of water and gas molecules, which is called as clathrate hydrate, is one reasonable choice for this important task. Its structure consists of three-dimensional network of hydrogen-bonded water molecules (host cages) and small nonpolar molecules (guests) encaged within this network. The clathrate hydrate medium is chemically durable, environmentally benign, and also free from the necessity of expensive rare metals. Large amount of molecular hydrogen up to 3.8 wt.% was successfully stored into the structure II hydrogen clathrate hydrate (Fd3m space group, lattice constant ∼ 1.7 nm), while it is only synthesized at low temperature and/or high pressure conditions which are not suitable for industrial applications. Required pressure to put significant amount of hydrogen into the hydrate structure is much reducible by blending in additional guest species acting as a hydrate promoter. The promoter molecules added to the system occupy some of the cages to stabilize the hydrate structure at lower pressures, so that the hydrogen storage capacity is partly reduced instead. In addition to the problem of storage capacity, kinetic aspect of hydrogen clathrate hydrate synthesis is also essential for the expected application. Its conventional production scheme was by freezing promoter's solution contacting with pressurized hydrogen gas; it then takes long time for crystal growth. We have established an alternative scheme enabling much faster synthesis (Okuchi et al., Appl. Phys. Lett., 91, 171903, 2007). We found that when hydrogen-free clathrate hydrate powders including a promoter (tetrahydrofuran) was contacted with pressurized hydrogen gas, hydrogen was quickly absorbed into the hydrate medium. We observed the absorption kinetics by nuclear magnetic resonance spectroscopy as a function of hydrogen pressure and temperature. In

  6. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies.

    Science.gov (United States)

    Holt, I J; Harding, A E; Morgan-Hughes, J A

    1988-02-25

    In vitro studies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol-cytochrome c reductase) in adult cases. These two enzymes consist of approximately 36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA). The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome. PMID:2830540

  7. M8L12 cubic cages with all facial Δ or facial Λ configuration: effects of surface anions on the occupancy of the cage and anion exchange.

    Science.gov (United States)

    Yang, Jing; Chang, Xiao-Yong; Sham, Kiu-Chor; Yiu, Shek-Man; Kwong, Hoi-Lun; Che, Chi-Ming

    2016-05-21

    M8L12 cubic cages (M = Mn(II), Zn(II) or Cd(II)), with all eight metal ions having all facial Δ or facial Λ configurations and having an encapsulated anion, were prepared by the self-assembly of m-xylene-bridged imidazolyl-imine ligands and MX2 (X = PF6(-), SbF6(-), TfO(-)) salts; the encapsulated anion exchange with different anions (SbF6(-), Tf2N(-), NO3(-), TsO(-)) was studied and the results with NO3(-) and TsO(-) indicate that anions on the cage surfaces affect the encapsulated anion exchange and the occupancy of the cage. PMID:27064122

  8. Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase.

    Science.gov (United States)

    Bonaventura, Daniella; Lunardi, Claure N; Rodrigues, Gerson J; Neto, Mário A; Vercesi, Juliana A; de Lima, Renata G; da Silva, Roberto S; Bendhack, Lusiane M

    2009-10-01

    Nitrosyl ruthenium complexes have been characterized as nitric oxide (NO) donors that induce relaxation in the denuded rat aorta. There are some differences in their vascular relaxation mechanisms compared with sodium nitroprusside. This study investigates whether the endothelium could interfere with the [Ru(terpy)(bdq)NO](3+)-TERPY-induced vascular relaxation, by analyzing the maximal relaxation (Emax) and potency (pD(2)) of TERPY. Vascular reactivity experiments showed that the endothelium negatively modulates (pD(2): 6.17+/-0.07) the TERPY relaxation in intact rat aortic rings compared with the denuded rat aorta (pD(2): 6.65+/-0.07). This effect is abolished by a non-selective NO-synthase (NOS) inhibitor L-NAME (pD(2): 6.46+/-0.10), by the superoxide anion (O(2)(-)) scavenger TIRON (pD(2): 6.49+/-0.08), and by an NOS cofactor BH(4) (pD(2): 6.80+/-0.10). The selective dye for O(2)(-) (DHE) shows that TERPY enhances O(2)(-) concentration in isolated endothelial cells (intensity of fluorescence (IF):11258.00+/-317.75) compared with the basal concentration (IF: 7760.67+/-381.50), and this enhancement is blocked by L-NAME (IF: 8892.33+/-1074.41). Similar results were observed in vascular smooth muscle cells (concentration of superoxide after TERPY: 2.63+/-0.17% and after TERPY+L-NAME: -4.63+/-0.14%). Considering that TERPY could induce uncoupling NOS, thus producing O(2)(-), we have also investigated the involvement of prostanoids in the negative modulation of the endothelium. The non-selective cyclooxygenase (COX) inhibitor indomethacin and the selective tromboxane (TXA(2)) receptor antagonist SQ29548 reduce the effect of the endothelium on TERPY relaxation (pD(2) INDO: 6.80+/-0.17 and SQ29548: 6.85+/-0.15, respectively). However, a selective prostaglandin F(2alpha) receptor antagonist (AH6809) does not change the endothelium effect. Moreover, TERPY enhances the concentration of TXA(2) stable metabolite (TXB(2)), but this effect is blocked by L-NAME and TIRON. The

  9. The assembly of mitochondrial complex I : a product of nuclear-mitochondrial synergy

    NARCIS (Netherlands)

    Vogel, Rutger Oscar

    2007-01-01

    Mitochondria are essential to cellular energy production. Embedded in the mitochondrial inner membrane, the engine of the mitochondrial powerhouse is formed by the five enzymatic complexes of the oxidative phosphorylation (OXPHOS) system. Dysfunction of this system results in mitochondrial disease,

  10. Dephosphorylation of the Rieske iron-sulfur protein after induction of the mitochondrial permeability transition

    International Nuclear Information System (INIS)

    In the mitochondrial permeability transition (MPT), MPT pores open to cause the mitochondrial inner membrane to become non-selectively permeable to molecules of mass up to 1500 Da. In this study, we used proteomics to investigate protein changes after MPT induction. Isolated rat liver mitochondria were incubated with various MPT inducers, including CaCl2, tert-butylhydroperoxide, and phenylarsine oxide, in the presence and absence of the MPT inhibitor, cyclosporin A. MPT induction was confirmed by an absorbance swelling assay. Mitochondrial membrane proteins prepared from control and treated mitochondria were separated by two-dimensional (2D) gel electrophoresis and stained with SyproRuby or Coomassie blue. Proteins of interest were further identified by mass spectrometry. 2D gel electrophoresis by isoelectric focusing and SDS-PAGE consistently showed a protein spot that shifted to a more basic isoelectric point after the MPT. This shift was prevented by CsA but did not occur after protonophoric uncoupling. Mass spectrometry identified this protein as the Rieske iron-sulfur protein (RISP) of ubiquinol-cytochrome c reductase (Complex III). Phosphatase treatment of sonicated mitochondria caused the same shift in RISP as occurred in MPT inducer-treated mitochondria. 2D gel electrophoresis by blue-native-PAGE and SDS-PAGE showed that RISP existed as an apparent monomer in mitochondrial membranes in addition to forming a complex with ubiquinol-cytochrome c reductase. These findings suggest that RISP may be part of MPT pores and that dephosphorylation of RISP may play a role in regulation of the MPT

  11. Inhibition of mitochondrial functions by margosa oil: possible implications in the pathogenesis of Reye's syndrome.

    Science.gov (United States)

    Koga, Y; Yoshida, I; Kimura, A; Yoshino, M; Yamashita, F; Sinniah, D

    1987-08-01

    Margosa oil (MO), a fatty acid-rich extract of the seeds of the neem tree and a reported cause of Reye's syndrome, has been used in the induction of an experimental model of Reye's syndrome in rats. It has been reported that MO causes a decrease in in vivo mitochondrial enzyme activity similar to that seen in Reye's syndrome. We have attempted to uncover some of the biochemical mechanisms of MO's toxicity by examining its effect in vitro on isolated rat liver mitochondria. Male rat liver mitochondria were isolated by centrifugation; oxygen uptake, reduced forms of cytochrome b, c + c1, a + a3, and flavoprotein, intramitochondrial concentrations of acetyl coA, acid-soluble coA, acid-insoluble coA, and ATP content were measured after incubation with and without MO. Our results reveal that MO is a mitochondrial uncoupler. State 4 respiration was increased while the respiratory control ratio was decreased. The intramitochondrial content of ATP was also decreased. There were substantial changes in the reduction of the respiratory chain components after incubation of mitochondria with MO. This decelerative effect on mitochondrial electron transport was alleviated by the addition of coenzyme Q and/or carnitine. These effects of MO on mitochondrial respiration may be due to changes in fatty acid metabolism caused by MO as MO caused a shift in the proportion of acid-soluble or acid-insoluble coA esters. Supplementary therapy with L-carnitine and coenzyme Q may be useful in the management of MO-induced Reye's syndrome. PMID:3658544

  12. Bioenergetic roles of mitochondrial fusion.

    Science.gov (United States)

    Silva Ramos, Eduardo; Larsson, Nils-Göran; Mourier, Arnaud

    2016-08-01

    Mitochondria are bioenergetic hotspots, producing the bulk of ATP by the oxidative phosphorylation process. Mitochondria are also structurally dynamic and undergo coordinated fusion and fission to maintain their function. Recent studies of the mitochondrial fusion machinery have provided new evidence in detailing their role in mitochondrial metabolism. Remarkably, mitofusin 2, in addition to its role in fusion, is important for maintaining coenzyme Q levels and may be an integral player in the mevalonate synthesis pathway. Here, we review the bioenergetic roles of mitochondrial dynamics and emphasize the importance of the in vitro growth conditions when evaluating mitochondrial respiration. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016,' edited by Prof. Paolo Bernardi. PMID:27060252

  13. Bedding disposal cabinet for containment of aerosols generated by animal cage cleaning procedures.

    Science.gov (United States)

    Baldwin, C L; Sabel, F L; Henke, C B

    1976-02-01

    Laboratory tests with aerosolized spores and animal room tests with uranine dye indicate the effectiveness of a prototype bedding disposal cabinet in reducing airborne contamination generated by cage cleaning procedures. PMID:826219

  14. Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

    Science.gov (United States)

    Cullen, William; Misuraca, M. Cristina; Hunter, Christopher A.; Williams, Nicholas H.; Ward, Michael D.

    2016-03-01

    The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of kcat/kuncat is 2 × 105, due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments.

  15. Cooperative Veratryle and Nitroindoline Cages for Two-Photon Uncaging in the NIR.

    Science.gov (United States)

    Cueto Diaz, Eduardo; Picard, Sébastien; Klausen, Maxime; Hugues, Vincent; Pagano, Paolo; Genin, Emilie; Blanchard-Desce, Mireille

    2016-07-25

    Tandem uncaging systems in which a two-photon absorbing module and a cage moiety, linked via a phosphorous clip, that act together by Förster resonance energy transfer (FRET) have been developed. A library of these compounds, using different linkers and cages (7-nitroindolinyl or nitroveratryl) has been synthesized. The investigation of their uncaging and two-photon absorption properties demonstrates the scope and versatility of the engineering strategy towards efficient two-photon cages and reveals surprising cooperative and topological effects. The interactions between the 2PA module and the caging moiety are found to promote cooperative effects on the 2PA response while additional processes that enhance the uncaging efficiency are operative in well-oriented nitroindoline-derived dyads. These synergic effects combine to lead to record two-photon uncaging cross-section values (i.e., up to 20 GM) for uncaging of carboxylic acids. PMID:27346866

  16. The design of a cervical vertebra titanium plate-interbody fusion cage

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the biomechanical feature of a newly designed cervical vertebra internal fixation device and its clinical applications Methods: Some functional spinal units were fixed respectively with titanium plate, fusion cage and new device designed by ourselves, then a controlled biomechanical study including flexion, extension, torsion and lateral bending was performed and the results were analyzed. Results: As to the mechanical performance, fusion cage showed poor performance in extension test and so did the titanium plate in the distortion test. However, the new device showed good performance in every test. Conclusion: Both simple titanium plate fixation and simple fusion cage fixation have biomechanical defaults, but they are complementary. The titanium plate-interbody fusion cage avoids the defaults and has specific advantages.

  17. Feasibility of the sustainable freshwater cage culture in Hungary and Romania

    Directory of Open Access Journals (Sweden)

    Dénes Gál

    2011-12-01

    Full Text Available The intensive cage culture has an adverse effect on the quality of waters due to the highnutrient discharge of intensive fish culture. The combination of the intensive cage and the extensiveaquaculture exploits the advantages of traditional pond farming and intensive fish culture systems.Valuable predatory fish species can be produced in the intensive part of the system, whilst theintegration of an extensive pond as a treatment unit results in decreased nutrient loading to theenvironment and increased nutrient recovery in fish production. The combination of cage and pond fishfarming is a new method for predatory fish production in fishponds. By the exploiting of the traditionalfish ponds with intensive fish production in cages makes possible for the traditional carp farmers toincrease their production capacity, diversify the cultured species and recycle the nutrients within theproduction systems.

  18. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  19. [The effect of the homogenates from different developmental stages of the nematode Protostrongylus rufescens (Leuckart, 1895) on mitochondrial and lipid bilayer membranes].

    Science.gov (United States)

    Kuchboev, A E; Kazakov, I; Asrarov, M I; Isakova, D T; Azimov, D A; Golovanov, V I

    2007-01-01

    The effect of the homogenates from different developmental stages of the nematode Protostrongylus rufescens on mitochondrial and lipid bilayer membranes has been studied. The homogenate of P. rufescens affects efficiently the cell energy by the inhibition of the mitochondrial respiration in the metabolic state V3, uncouples oxidative phosphorylation and affects the functions of mitochondria at the level of cyclosporine A-sensitive pore by making it highly permeable. Moreover, the nematode homogenate at the concentration of 1 mkg/ml increases efficiently the integral permeability of lipid bilayer membranes. An increase in this permeability is connected apparently with the formation of single ion channels. The channels of lipid bilayer membranes induced by the nematode homogenate show cation selectivity. PMID:17460939

  20. p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Fjære, Even; Liaset, Bjørn;

    2016-01-01

    1-dependent uncoupled respiration and increased oxidation of glucose and fatty acids in brown or brown-like adipocytes, termed brite or beige, in relation to energy balance and homeostasis has been highlighted recently. UCP1-dependent uncoupled respiration in classic interscapular brown adipose...... tissue is central to cold-induced thermogenesis, whereas brite/beige adipocytes are of special importance in relation to diet-induced thermogenesis, where the importance of UCP1 is only clearly manifested in mice kept at thermoneutrality. We challenged wild-type and TRP53-deficient mice by high......-fat feeding under thermoneutral conditions. Interestingly, mice lacking TRP53 gained less weight compared with their wild-type counterparts. This was related to an increased expression of Ucp1 and other PPARGC1a and PPARGC1b target genes but not Ppargc1a or Ppargc1b in inguinal white adipose tissue of mice...

  1. Four-dimensional multi-site photolysis of caged neurotransmitters

    Directory of Open Access Journals (Sweden)

    Mary Ann eGo

    2013-12-01

    Full Text Available Neurons receive thousands of synaptic inputs that are distributed in space and time. The systematic study of how neurons process these inputs requires a technique to stimulate multiple yet highly targeted points of interest along the neuron's dendritic tree. Three-dimensional multi-focal patterns produced via holographic projection combined with two-photon photolysis of caged compounds can provide for highly localized release of neurotransmitters within each diffraction-limited focus, and in this way emulate simultaneous synaptic inputs to the neuron. However, this technique so far cannot achieve time-dependent stimulation patterns due to fundamental limitations of the hologram-encoding device and other factors that affect the consistency of controlled synaptic stimulation. Here, we report an advanced technique that enables the design and application of arbitrary spatio-temporal photostimulation patterns that resemble physiological synaptic inputs. By combining holographic projection with a programmable high-speed light-switching array, we have overcome temporal limitations with holographic projection, allowing us to mimic distributed activation of synaptic inputs leading to action potential generation. Our experiments uniquely demonstrate multi-site two-photon glutamate uncaging in three dimensions with submillisecond temporal resolution. Implementing this approach opens up new prospects for studying neuronal synaptic integration in four dimensions.

  2. Protein cages, rings and tubes: useful components of future nanodevices?

    Directory of Open Access Journals (Sweden)

    Jonathan G Heddle

    2008-11-01

    Full Text Available Jonathan G HeddleGlobal Edge Institute, Tokyo Institute of Technology, Nagatsuda, Midori-ku, Yokohama Kanagawa, JapanAbstract: There is a great deal of interest in the possibility that complex nanoscale devices can be designed and engineered. Such devices will lead to the development of new materials, electronics and smart drugs. Producing complex nanoscale devices, however will present many challenges and the components of such devices will require a number of special features. Devices will be engineered to incorporate desired functionalities but, because of the difficulties of controlling matter precisely at the nanoscale with current technology, the nanodevice components must self-assemble. In addition, nanocomponents that are to have wide applicability in various devices must have enough flexibility to integrate into a large number of potentially very different environments. These challenges are daunting and complex, and artificial nanodevices have not yet been constructed. However, the existence of nanomachines in nature in the form of proteins (eg, enzymes suggests that they will be possible to produce. As the material from which nature’s nanomachines are made, proteins seem ideal to form the basis of engineered components of such nanodevices. Initially, engineering projects may focus on building blocks such as rings, cages and tubes, examples of which exist in nature and may act as a useful start point for modification and further development. This review focuses on the recent research and possible future development of such protein building blocks.Keywords: bionanotechnology, protein engineering, nanomachine, building-blocks, synthetic biology

  3. Model of a generator end-winding cage

    International Nuclear Information System (INIS)

    This document presents some studies concerning the vibratory characterization of particular structures called: generator end-winding cages. These structures are mainly made up of the endings of armature windings. The question of their good mechanical behaviour is of prime importance, since they are submitted to high electromagnetic efforts during the different electrical ratings encountered during operation. The designer (GEC-Alsthom) and the user (EDF) have both undertaken numerical calculations in order to characterize a given machine, in this case a 600 MW bipolar generator; it appeared interesting to compare such calculations. The models realized respectively by GEC-Alsthom and EDF make use of different techniques and hypotheses. GEC-Alsthom represents the sets of rods and spacers by plates, which properties are determined by a pre-processor. The model is simplified to take into account the existing symmetries. It takes profit of previous experience and aims at a fast utilisation. The EDF model tends to allow a further comprehensive calculation, form the electromagnetic efforts to the determination of local stresses. The whole set of the constituting elements of the structure is modelled by beams, which leads to an important size for the model (21 000 degrees of freedom). The validation performed on the two models has been focused on the comparison between respective results and also with experimental results. Each model provides values for the first eigenfrequencies and the associated modes shapes. (authors). 3 refs., 3 figs., 2 tabs

  4. Four-dimensional multi-site photolysis of caged neurotransmitters

    Science.gov (United States)

    Go, Mary Ann; To, Minh-Son; Stricker, Christian; Redman, Stephen; Bachor, Hans-A.; Stuart, Greg J.; Daria, Vincent R.

    2013-01-01

    Neurons receive thousands of synaptic inputs that are distributed in space and time. The systematic study of how neurons process these inputs requires a technique to stimulate multiple yet highly targeted points of interest along the neuron's dendritic tree. Three-dimensional multi-focal patterns produced via holographic projection combined with two-photon photolysis of caged compounds can provide for highly localized release of neurotransmitters within each diffraction-limited focus, and in this way emulate simultaneous synaptic inputs to the neuron. However, this technique so far cannot achieve time-dependent stimulation patterns due to fundamental limitations of the hologram-encoding device and other factors that affect the consistency of controlled synaptic stimulation. Here, we report an advanced technique that enables the design and application of arbitrary spatio-temporal photostimulation patterns that resemble physiological synaptic inputs. By combining holographic projection with a programmable high-speed light-switching array, we have overcome temporal limitations with holographic projection, allowing us to mimic distributed activation of synaptic inputs leading to action potential generation. Our experiments uniquely demonstrate multi-site two-photon glutamate uncaging in three dimensions with submillisecond temporal resolution. Implementing this approach opens up new prospects for studying neuronal synaptic integration in four dimensions. PMID:24348330

  5. Bioresorbable polymers: heading for a new generation of spinal cages.

    Science.gov (United States)

    Wuisman, P I J M; Smit, T H

    2006-02-01

    The use of polymer-based bioresorbable materials is now expanding to the realm of spinal interbody fusion. Bioresorbable polymers have important advantages over metals, because they are temporary, much less stiff, and radiolucent. Most promising is a group of alpha-polyesters, in particular polylactide acids (PLAs). Their biocompatibility is excellent, and they have sufficient stiffness and strength to provide initial and intermediate-term stability required for bone healing. However, polylactides have characteristics that make them vulnerable to complications if not properly controlled. Degradation rate strongly depends on polymer type, impurities, manufacturing process, sterilization, device size, and the local environment. The fact that larger implants degrade faster is contra-intuitive, and should be considered in the design process. Also optimal surgical techniques, such as careful bone bed preparation, are required for a successful application of these materials. The purpose of this paper is to highlight the specific properties of these bioresorbable polymers and to discuss their potential and limitations. This is illustrated with early preclinical and clinical data.Bioresorbable cage technology is just emerging: their time-engineered degradation characteristics allow controlled dynamization in interbody applications, facilitating spinal fusion. Their radiolucency improves image assessment of fusion healing. Acceptance and use of bioresorbable implants may increase as further research and clinical studies report on their safety, efficacy, and proper usage. PMID:16292588

  6. Mitochondrial dysfunction and organophosphorus compounds

    International Nuclear Information System (INIS)

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP

  7. Mitochondrial transplantation for therapeutic use

    OpenAIRE

    McCully, James Donald; Levitsky, Sidney; del Nido, Pedro J.; Cowan, Douglas Burr

    2016-01-01

    Mitochondria play a key role in the homeostasis of the vast majority of the body’s cells. In the myocardium where mitochondria constitute 30 % of the total myocardial cell volume, temporary attenuation or obstruction of blood flow and as a result oxygen delivery to myocardial cells (ischemia) severely alters mitochondrial structure and function. These alterations in mitochondrial structure and function occur during ischemia and continue after blood flow and oxygen delivery to the myocardium i...

  8. Mitochondrial Dysfunction in Parkinson's Disease

    OpenAIRE

    Keane, P. C.; Kurzawa, M.; Blain, P G; Morris, C M

    2011-01-01

    Parkinson's disease (PD) is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial ...

  9. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  10. Mitochondrial Dysfunction in Neurodegenerative Diseases

    OpenAIRE

    Johri, Ashu; Beal, M. Flint

    2012-01-01

    Neurodegenerative diseases are a large group of disabling disorders of the nervous system, characterized by the relative selective death of neuronal subtypes. In most cases, there is overwhelming evidence of impaired mitochondrial function as a causative factor in these diseases. More recently, evidence has emerged for impaired mitochondrial dynamics (shape, size, fission-fusion, distribution, movement etc.) in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, amyo...

  11. Diaphragm muscle shortening modulates kinematics of lower rib cage in dogs

    OpenAIRE

    Chu, Iris; Fernandez, Cristina; Rodowicz, Kathleen Allen; Lopez, Michael A.; Lu, Raymond; Hubmayr, Rolf D.; Boriek, Aladin M.

    2010-01-01

    We tested the hypothesis that diaphragm muscle shortening modulates volume displacement and kinematics of the lower rib cage in dogs and that posture and mode of ventilation affect such modulation. Radiopaque markers were surgically attached to the lower three ribs of the rib cage and to the midcostal region of the diaphragm in six dogs of ∼8 kg body masses, and the locations of these markers were determined by a biplane fluoroscopy system. Three-dimensional software modeling techniques were ...

  12. Photorelease of GABA with Visible Light Using an Inorganic Caging Group

    OpenAIRE

    Rial Verde, Emiliano M.; Zayat, Leonardo; Etchenique, Roberto; Yuste, Rafael

    2008-01-01

    We describe the selective photorelease of γ-amino butyric acid (GABA) with a novel caged-GABA compound that uses a ruthenium complex as photosensor. This compound (“RuBi-GABA”) can be excited with visible wavelengths, providing greater tissue penetration, less photo-toxicity, and faster photorelease kinetics than currently used UV light-sensitive caged compounds. Using pyramidal neurons from neocortical brain slices, we show that RuBi-GABA uncaging induces GABA-A receptor-mediated responses, ...

  13. Control System for Producing Electricity with Dual Stator Winding Cage-Rotor Induction Generator

    OpenAIRE

    Lucian Nicolae Tutelea; Sorin Ioan Deaconu; Gabriel Nicolae Popa

    2014-01-01

    This paper will present the key design equations and control design model of the Dual Stator Winding Cage-Rotor Induction Generator (DSWIG) to achieve wide-speed-range operation with reduced capacity of the static power controller for low power wind or hydro applications. The proposed induction generator consists of a standard squirrel-cage rotor and a stator with two separate windings wound for a similar number of poles. Moreover, the system control strategy using the stato...

  14. Focusing of high intensity ultrasound through the rib cage using a therapeutic random phased array

    OpenAIRE

    Bobkova, Svetlana; Gavrilov, Leonid; Khokhlova, Vera; Shaw, Adam; Hand, Jeffrey; ,

    2010-01-01

    A method for focusing high intensity ultrasound through a rib cage that aims to minimize heating of the ribs whilst maintaining high intensities at the focus (or foci) is proposed and tested theoretically and experimentally. Two approaches, one based on geometric acoustics and the other accounting for diffraction effects associated with propagation through the rib cage, are investigated theoretically for idealized source conditions. It is shown that for an idealized radiator the diffraction a...

  15. A practical guide to the synthesis of dinitroindolinyl-caged neurotransmitters

    OpenAIRE

    Ellis-Davies, Graham C. R.

    2011-01-01

    This protocol describes a method for efficient chemical synthesis of dinitroindolinyl derivatives of glutamate and gamma-aminobutyric acid. these caged neurotransmitters are currently the most chemically and photochemically efficient probes for two-photon photolysis in living brain slices. the protocol only requires basic organic synthesis equipment, and no silica gel column chromatography or NMR spectroscopy is needed at any stage. Hplc is used to purify the caged transmitters at the end of ...

  16. Late Results of Anterior Cervical Discectomy and Fusion with Interbody Cages

    OpenAIRE

    Dağlı, Murat; Er, Uygur; Şimşek, Serkan; Bavbek, Murad

    2013-01-01

    Study Design Retrospective analysis. Purpose To evaluate the effectiveness of anterior cervical discectomy with fusion for degenerative cervical disc disease. Overview of Literature Anterior spinal surgery originated in the mid-1950s and graft for fusion was also employed. Currently anterior cervical microdiscectomy and fusion with an intervertebral cage is a widely accepted procedure for treatment of cervical disc hernia. Artificial grafts and cages for fusion are preferred because of their ...

  17. Synthesis of Silsesquioxane Cages from Phenyl-cis-tetrol,1,3-Divinyltetraethoxydisiloxane and Cyclopentyl Resins

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-hua; Alan R. Bassindale; Peter G. Taylor

    2004-01-01

    The synthesis of Ts, T10 and T12 silsesquioxane cages from a range of starting materials: phenyl-cistetrol, 1,3-divinyltetraethoxydisiloxane and cyclopentyl T resins by using tetra n-butylammonium fluoride (TBAF) as the catalyst is described in this paper. The reaction yields obtained via the current route are better compared to those via the literature routes. Some of the cage compounds have been characterized by X-ray crystallography.

  18. Multifunctional photoreactive inorganic cages for three-dimensional holographic data storage.

    Science.gov (United States)

    Lee, Seungwoo; Jeong, Yong-Cheol; Lee, Jihye; Park, Jung-Ki

    2009-10-15

    We demonstrate a holographic photopolymer based on multifunctional photoreactive inorganic cages, polyhedral oligomeric silsesquioxane (POSS). It is shown that a second photopolymerizable monomer, POSS, for the photopolymer, contributes to significantly enhance photosensitivity as well as refractive index modulation (Deltan). We also found that during the formation of holographic gratings, polymerization of POSS could effectively suppress volume shrinkage of photopolymer resin, owing to its filler-strengthening effect of inorganic cages accompanied with interpenetrating effect. PMID:19838237

  19. Economic analysis of the environmental impact on marine cage lobster aquaculture in Vietnam

    OpenAIRE

    Ly, Nguyen Thi Y

    2009-01-01

    In Vietnam, marine cage lobster aquaculture has been expanding significantly over the last years. Besides the economic contribution for locals living in the coastal areas in Central of Vietnam, this industry has created some problems that are relating to the marine environmental protection where trash fish feed is predominant. This paper investigates the environmental impact on cage marine lobster aquaculture in Vietnam by using the Change of Productivity method in which nitrogen releasing fr...

  20. Caged vanilloid ligands for activation of TRPV1 receptors by 1- and 2-photon excitation†

    OpenAIRE

    Zhao, Jun; Gover, Tony D; Muralidharan, Sukumaran; Auston, Darryl A.; Weinreich, Daniel; Kao, Joseph P.Y.

    2006-01-01

    Nociceptive neurons in the peripheral nervous system detect noxious stimuli and report the information to the central nervous system. Most nociceptive neurons express the vanilloid receptor, TRPV1, a non-selective cation channel gated by vanilloid ligands such as capsaicin, the pungent essence of chili peppers. Here, we report the synthesis and biological application of two caged vanilloids—biologically inert precursors that, when photolyzed, release bioactive vanilloid ligands. The two caged...