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Sample records for reduction underlies mitochondrial

  1. Use of Raman spectroscopy to study reduction state of mitochondrial cytochromes in an isolated heart under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Brazhe, N. A.; Treiman, M.; Faricelli, B.

    2013-01-01

    to 1606 cm-1). As expected from a decreased reduction of electron transport chain upon uncoupling, the presence of FCCP in the perfusion caused a decrease in the intensity of cytochromal peaks with no change of Mb peaks. Global stop-flow ischemia of 35 min elicited a progressive increase in the intensity...

  2. Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

    Directory of Open Access Journals (Sweden)

    James Haorah

    Full Text Available Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1 and cPT2 levels. The mitochondrial outer (cPT1 and inner (cPT2 membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function can cause a negative impact on ATP production (complex V function. Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2 prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10 was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

  3. Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

    Science.gov (United States)

    Haorah, James; Rump, Travis J; Xiong, Huangui

    2013-01-01

    Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC) that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v) and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1) and cPT2 levels. The mitochondrial outer (cPT1) and inner (cPT2) membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function) can cause a negative impact on ATP production (complex V function). Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence) and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2) prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10) was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

  4. Mitochondrial dysfunction underlying outer retinal diseases

    DEFF Research Database (Denmark)

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali

    2017-01-01

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer...

  5. Chemical model reduction under uncertainty

    KAUST Repository

    Najm, Habib; Galassi, R. Malpica; Valorani, M.

    2016-01-01

    We outline a strategy for chemical kinetic model reduction under uncertainty. We present highlights of our existing deterministic model reduction strategy, and describe the extension of the formulation to include parametric uncertainty in the detailed mechanism. We discuss the utility of this construction, as applied to hydrocarbon fuel-air kinetics, and the associated use of uncertainty-aware measures of error between predictions from detailed and simplified models.

  6. Chemical model reduction under uncertainty

    KAUST Repository

    Najm, Habib

    2016-01-05

    We outline a strategy for chemical kinetic model reduction under uncertainty. We present highlights of our existing deterministic model reduction strategy, and describe the extension of the formulation to include parametric uncertainty in the detailed mechanism. We discuss the utility of this construction, as applied to hydrocarbon fuel-air kinetics, and the associated use of uncertainty-aware measures of error between predictions from detailed and simplified models.

  7. Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.

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    Kanae Iijima-Ando

    2009-12-01

    Full Text Available The amyloid-beta 42 (Abeta42 is thought to play a central role in the pathogenesis of Alzheimer's disease (AD. However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Abeta42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Abeta42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Abeta42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo.

  8. Chemical model reduction under uncertainty

    KAUST Repository

    Malpica Galassi, Riccardo; Valorani, Mauro; Najm, Habib N.; Safta, Cosmin; Khalil, Mohammad; Ciottoli, Pietro P.

    2017-01-01

    A general strategy for analysis and reduction of uncertain chemical kinetic models is presented, and its utility is illustrated in the context of ignition of hydrocarbon fuel–air mixtures. The strategy is based on a deterministic analysis

  9. Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint.

    Science.gov (United States)

    Yamamori, Tohru; Yasui, Hironobu; Yamazumi, Masayuki; Wada, Yusuke; Nakamura, Yoshinari; Nakamura, Hideo; Inanami, Osamu

    2012-07-15

    Whereas ionizing radiation (Ir) instantaneously causes the formation of water radiolysis products that contain some reactive oxygen species (ROS), ROS are also suggested to be released from biological sources in irradiated cells. It is now becoming clear that these ROS generated secondarily after Ir have a variety of biological roles. Although mitochondria are assumed to be responsible for this Ir-induced ROS production, it remains to be elucidated how Ir triggers it. Therefore, we conducted this study to decipher the mechanism of Ir-induced mitochondrial ROS production. In human lung carcinoma A549 cells, Ir (10 Gy of X-rays) induced a time-dependent increase in the mitochondrial ROS level. Ir also increased mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production, suggesting upregulation of the mitochondrial electron transport chain (ETC) function after Ir. Although we found that Ir slightly enhanced mitochondrial ETC complex II activity, the complex II inhibitor 3-nitropropionic acid failed to reduce Ir-induced mitochondrial ROS production. Meanwhile, we observed that the mitochondrial mass and mitochondrial DNA level were upregulated after Ir, indicating that Ir increased the mitochondrial content of the cell. Because irradiated cells are known to undergo cell cycle arrest under control of the checkpoint mechanisms, we examined the relationships between cell cycle and mitochondrial content and cellular oxidative stress level. We found that the cells in the G2/M phase had a higher mitochondrial content and cellular oxidative stress level than cells in the G1 or S phase, regardless of whether the cells were irradiated. We also found that Ir-induced accumulation of the cells in the G2/M phase led to an increase in cells with a high mitochondrial content and cellular oxidative stress level. This suggested that Ir upregulated mitochondrial ETC function and mitochondrial content, resulting in mitochondrial ROS production, and that

  10. Chemical model reduction under uncertainty

    KAUST Repository

    Malpica Galassi, Riccardo

    2017-03-06

    A general strategy for analysis and reduction of uncertain chemical kinetic models is presented, and its utility is illustrated in the context of ignition of hydrocarbon fuel–air mixtures. The strategy is based on a deterministic analysis and reduction method which employs computational singular perturbation analysis to generate simplified kinetic mechanisms, starting from a detailed reference mechanism. We model uncertain quantities in the reference mechanism, namely the Arrhenius rate parameters, as random variables with prescribed uncertainty factors. We propagate this uncertainty to obtain the probability of inclusion of each reaction in the simplified mechanism. We propose probabilistic error measures to compare predictions from the uncertain reference and simplified models, based on the comparison of the uncertain dynamics of the state variables, where the mixture entropy is chosen as progress variable. We employ the construction for the simplification of an uncertain mechanism in an n-butane–air mixture homogeneous ignition case, where a 176-species, 1111-reactions detailed kinetic model for the oxidation of n-butane is used with uncertainty factors assigned to each Arrhenius rate pre-exponential coefficient. This illustration is employed to highlight the utility of the construction, and the performance of a family of simplified models produced depending on chosen thresholds on importance and marginal probabilities of the reactions.

  11. Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia

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    Hiroaki Nagai

    2017-10-01

    Full Text Available Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain. Furthermore, ivermectin inhibited the hypertrophic response of human induced pluripotent stem cell-derived cardiomyocytes. Pharmacological inhibition of importin β, one of the targets of ivermectin, exhibited protection against mitochondrial ATP decline and cardiomyocyte hypertrophy. These findings indicate that maintaining mitochondrial ATP under hypoxia may prevent hypertrophy and improve cardiac function, providing therapeutic options for mitochondrial dysfunction.

  12. Transient burnout under rapid flow reduction condition

    International Nuclear Information System (INIS)

    Iwamura, Takamichi

    1987-01-01

    Burnout characteristics were experimentally studied using uniformly heated tube and annular test sections under rapid flow reduction conditions. Observations indicated that the onset of burnout under a flow reduction transient is caused by the dryout of a liquid film on the heated surface. The decrease in burnout mass velocity at the channel inlet with increasing flow reduction rate is attributed to the fact that the vapor flow rate continues to increase and sustain the liquid film flow after the inlet flow rate reaches the steady-state burnout flow rate. This is because the movement of the boiling boundary cannot keep up with the rapid reduction of inlet flow rate. A burnout model for the local condition could be applied to the burnout phenomena with the flow reduction under pressures of 0.5 ∼ 3.9 MPa and flow reduction rates of 0.6 ∼ 35 %/s. Based on this model, a method to predict the burnout time under a flow reduction condition was presented. The calculated burnout times agreed well with experimental results obtained by some investigators. (author)

  13. Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture

    International Nuclear Information System (INIS)

    Pillich, Rudolf Tito; Scarsella, Gianfranco; Risuleo, Gianfranco

    2005-01-01

    It is shown in literature that stress, such as deprivation of trophic factors and hypoxia, induces apoptosis in cultured cells and in tissues. In light of these results, we explored the possibility of protecting cells from programmed death by improving the metabolism of the mitochondrion. To this end, acetyl-L-carnitine was administered at various concentrations under conditions of serum deprivation. The choice of this drug was based on the accepted notion that acetyl-L-carnitine is able to stabilize mitochondrial membranes and to increase the supply of energy to the organelle. The results presented here indicate that the drug protects cells from apoptotic death: this is demonstrated by a lower positivity to the TUNEL reaction and by a strong reduction of the apoptotic DNA ladder in serum-deprived cells. The involvement of the mitochondrial apoptotic pathway was assessed by cytochrome C release and immunoreactivity to caspase 3. Moreover, acetyl-L-carnitine stimulates cell proliferation

  14. Burnout characteristics under flow reduction condition

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Kuroyanagai, Toshiyuki

    1982-01-01

    Burnout characteristics in a uniformly heated, vertically oriented tube, under flow reduction condition, were experimentally studied. Test pressures ranged 0.5 -- 3.9 MPa and flow reduction rates 0.6 -- 35%/s. An analytical method was developed to obtain the local mass velocity during a transient condition. The local mass velocity at the burnout location with an increasing flow reduction rate was slightly different from that measured in steady state tests. The system pressure had a significant effect on the difference. An empirical correlation was presented to give the ratio between the transient and steady state burnout mass velocities at the burnout location as a function of the steam-water density ratio and the flow reduction rate. Experimental results of previous work were compared with this correlation. (author)

  15. Oxidation-reduction enzymes of myocardium under ionizing radiation effect

    International Nuclear Information System (INIS)

    Uteshev, A.B.

    1988-01-01

    Tissue respiration proceses under radiation effect were investigated which allowed one to reveal slight biochemical disturbances in a cell which make up the base of functional changes of different organs and tissues and to get to know the essence of tissue respiration processes. An attempt to explain significant value of oxidation enzyme system radiosensitivity in the course of cell respiration process altogether is made when studying the state of separate links of oxidation-reduction chain. It is shown that at early periods of radiation injury activity of catalase, dehydrogenases (isocitric, α-ketoglutaric, malic, succinic acids) is suppressed, concentration of a number of cytochromes is reduced and general ferrum content is increased which is connected with conformation changes of ultrastructure of mitochondrial membranes

  16. Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

    Science.gov (United States)

    Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.

    2018-01-01

    Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

  17. Mitochondrial isocitrate dehydrogenase is inactivated upon oxidation and reactivated by thioredoxin-dependent reduction in Arabidopsis

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    Keisuke eYoshida

    2014-09-01

    Full Text Available Regulation of mitochondrial metabolism is essential for ensuring cellular growth and maintenance in plants. Based on redox-proteomics analysis, several proteins involved in diverse mitochondrial reactions have been identified as potential redox-regulated proteins. NAD+-dependent isocitrate dehydrogenase (IDH, a key enzyme in the tricarboxylic acid cycle, is one such candidate. In this study, we investigated the redox regulation mechanisms of IDH by biochemical procedures. In contrast to mammalian and yeast counterparts reported to date, recombinant IDH in Arabidopsis mitochondria did not show adenylate-dependent changes in enzymatic activity. Instead, IDH was inactivated by oxidation treatment and partially reactivated by subsequent reduction. Functional IDH forms a heterodimer comprising regulatory (IDH-r and catalytic (IDH-c subunits. IDH-r was determined to be the target of oxidative modifications forming an oligomer via intermolecular disulfide bonds. Mass spectrometric analysis combined with tryptic digestion of IDH-r indicated that Cys128 and Cys216 are involved in intermolecular disulfide bond formation. Furthermore, we showed that mitochondria-localized o-type thioredoxin (Trx-o promotes the reduction of oxidized IDH-r. These results suggest that IDH-r is susceptible to oxidative stress, and Trx-o serves to convert oxidized IDH-r to the reduced form that is necessary for active IDH complex.

  18. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

    Science.gov (United States)

    Sanz-Blasco, Sara; Valero, Ruth A; Rodríguez-Crespo, Ignacio; Villalobos, Carlos; Núñez, Lucía

    2008-07-23

    Dysregulation of intracellular Ca(2+) homeostasis may underlie amyloid beta peptide (Abeta) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42) oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+) in neurons and promote mitochondrial Ca(2+) overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+) overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+) overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i) mitochondrial Ca(2+) overload underlies the neurotoxicity induced by Abeta oligomers and ii) inhibition of mitochondrial Ca(2+) overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  19. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

    Directory of Open Access Journals (Sweden)

    Sara Sanz-Blasco

    Full Text Available Dysregulation of intracellular Ca(2+ homeostasis may underlie amyloid beta peptide (Abeta toxicity in Alzheimer's Disease (AD but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+ in neurons and promote mitochondrial Ca(2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+ overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i mitochondrial Ca(2+ overload underlies the neurotoxicity induced by Abeta oligomers and ii inhibition of mitochondrial Ca(2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  20. Mitochondrial genome evolution in Alismatales: Size reduction and extensive loss of ribosomal protein genes

    DEFF Research Database (Denmark)

    Petersen, Gitte; Cuenca, Argelia; Zervas, Athanasios

    2017-01-01

    The order Alismatales is a hotspot for evolution of plant mitochondrial genomes characterized by remarkable differences in genome size, substitution rates, RNA editing, retrotranscription, gene loss and intron loss. Here we have sequenced the complete mitogenomes of Zostera marina and Stratiotes...... aloides, which together with previously sequenced mitogenomes from Butomus and Spirodela, provide new evolutionary evidence of genome size reduction, gene loss and transfer to the nucleus. The Zostera mitogenome includes a large portion of DNA transferred from the plastome, yet it is the smallest known...... mitogenome from a non-parasitic plant. Using a broad sample of the Alismatales, the evolutionary history of ribosomal protein gene loss is analyzed. In Zostera almost all ribosomal protein genes are lost from the mitogenome, but only some can be found in the nucleus....

  1. Ca2+ and Mg2+-enhanced reduction of arsenazo III to its anion free radical metabolite and generation of superoxide anion by an outer mitochondrial membrane azoreductase.

    Science.gov (United States)

    Moreno, S N; Mason, R P; Docampo, R

    1984-12-10

    At the concentrations usually employed as a Ca2+ indicator, arsenazo III underwent a one-electron reduction by rat liver mitochondria to produce an azo anion radical as demonstrated by electron-spin resonance spectroscopy. Either NADH or NADPH could serve as a source of reducing equivalents for the production of this free radical by intact rat liver mitochondria. Under aerobic conditions, addition of arsenazo III to rat liver mitochondria produced an increase in electron flow from NAD(P)H to molecular oxygen, generating superoxide anion. NAD(P)H generated from endogenous mitochondrial NAD(P)+ by intramitochondrial reactions could not be used for the NAD(P)H azoreductase reaction unless the mitochondria were solubilized by detergent or anaerobiosis. In addition, NAD(P)H azoreductase activity was higher in the crude outer mitochondrial membrane fraction than in mitoplasts and intact mitochondria. The steady-state concentration of the azo anion radical and the arsenazo III-stimulated cyanide-insensitive oxygen consumption were enhanced by calcium and magnesium, suggesting that, in addition to an enhanced azo anion radical-stabilization by complexation with the metal ions, enhanced reduction of arsenazo III also occurred. Accordingly, addition of cations to crude outer mitochondrial membrane preparations increased arsenazo III-stimulated cyanide-insensitive O2 consumption, H2O2 formation, and NAD(P)H oxidation. Antipyrylazo III was much less effective than arsenazo III in increasing superoxide anion formation by rat liver mitochondria and gave a much weaker electron spin resonance spectrum of an azo anion radical. These results provide direct evidence of an azoreductase activity associated with the outer mitochondrial membrane and of a stimulation of arsenazo III reduction by cations.

  2. Multigas reduction strategy under climate stabilization target

    Energy Technology Data Exchange (ETDEWEB)

    Kurosawa, A. [Inst. of Applied Energy, Tokyo (Japan)

    2005-07-01

    Global warming can be mitigated through the abatement of carbon dioxide (CO{sub 2}), methane (CH{sub 4}), nitrous oxide (N{sub 2}O), hydrofluorocarbons (HFCs), perfluorocarbons (PFCs) and sulfur hexafluoride (SF{sub 6}). This study argued that multiple gas reduction flexibility should be assessed when considering effective greenhouse gas (GHG) mitigation strategies. Emissions of non-CO{sub 2} GHGs were calculated endogenously using an integrated assessment model. Multigas reduction potential was measured in relation to long-term atmospheric temperature targets, and the effects on gas life as well as abatement timing uncertainty were considered in terms of cost and technological availability. The model consisted of 5 nodules which considered issues related to energy, climate, land use, macroeconomics, and environmental impacts. The time horizon of the model was 2000 to 2100. An economic utility maximization technology was used to consider global trade balances. Emissions of non-CO{sub 2} gases from specific sources was calculated by multiplying the emission factor and the endogenous parameters within the model. Results were presented for GHG emissions and concentrations in 2 simulation cases: (1) a no climate policy case (NCP); and (2) a transient temperature stabilization (TTS) case. Actions to reduce non-CO{sub 2} GHGs included activity level changes in production and consumption, and additional reductions in abatement costs without sector activity changes. Results of the study showed that reducing global dependency on fossil fuels was an effective way to reduce GHG effects from CO{sub 2}, CH{sub 4} and N{sub 2}O. Additional abatements to reduce N{sub 2}O emissions are required in the agricultural sector. Economic incentives and public outreach programs are needed to offset the high transaction costs of GHG mitigation strategies. It was concluded that both short-term and long-term policies are required to reduce GHG in all sectors. Multigas mitigation is needed to

  3. Morphological and molecular variations induce mitochondrial dysfunction as a possible underlying mechanism of athletic amenorrhea.

    Science.gov (United States)

    Xiong, Ruo-Hong; Wen, Shi-Lei; Wang, Qiang; Zhou, Hong-Ying; Feng, Shi

    2018-01-01

    Female athletes may experience difficulties in achieving pregnancy due to athletic amenorrhea (AA); however, the underlying mechanisms of AA remain unknown. The present study focuses on the mitochondrial alteration and its function in detecting the possible mechanism of AA. An AA rat model was established by excessive swimming. Hematoxylin and eosin staining, and transmission electron microscopic methods were performed to evaluate the morphological changes of the ovary, immunohistochemical examinations and radioimmunoassays were used to detect the reproductive hormones and corresponding receptors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to test the mtDNA copy number. PCR and western blot analysis were used to test the expression of ND2. The change of morphological features of the rat ovaries revealed evident abnormalities. Particularly, the features of the mitochondria were markedly altered. In addition, reproductive hormones in the serum and tissues of AA rats were also detected to evaluate the function of the ovaries, and the levels of these hormones were significantly decreased. Furthermore, the mitochondrial DNA copy number (mtDNA) and expression of NADH dehydrogenase subunit 2 (ND2) were quantitated by qPCR or western blot analysis. Accordingly, the mtDNA copy number and expression of ND2 expression were markedly reduced in the AA rats. In conclusion, mitochondrial dysfunction in AA may affect the cellular energy supply and, therefore, result in dysfunction of the ovary. Thus, mitochondrial dysfunction may be considered as a possible underlying mechanism for the occurrence of AA.

  4. Thermodynamics and kinetics of reduction and species conversion at a hydrophobic surface for mitochondrial cytochromes c and their cardiolipin adducts

    International Nuclear Information System (INIS)

    Ranieri, Antonio; Di Rocco, Giulia; Millo, Diego; Battistuzzi, Gianantonio; Bortolotti, Carlo A.; Lancellotti, Lidia; Borsari, Marco; Sola, Marco

    2015-01-01

    Highlights: • Cytochrome c and its adduct with cardiolipin can be immobilized on a hydrophobic SAM. • Adsorbed cytochrome c and its adduct undergo extensive unfolding and axial ligand substitution. • An equilibrium between a six-coordinated and a five-coordinated form is observed in both cases. • The reduced five-coordinated form is stabilized by cardiolipin binding. • Immobilized cytochrome c exchanges electrons more slowly upon cardiolipin binding. - Abstract: Cytochrome c (cytc) and its adduct with cardiolipin (CL) were immobilized on a hydrophobic SAM-coated electrode surface yielding a construct which mimics the environment experienced by the complex at the inner mitochondrial membrane where it plays a role in cell apoptosis. Under these conditions, both species undergo an equilibrium between a six-coordinated His/His-ligated and a five-coordinated His/- ligated forms stable in the oxidized and in the reduced state, respectively. The thermodynamics of the oxidation-state dependent species conversion were determined by temperature-dependent diffusionless voltammetry experiments. CL binding stabilizes the immobilized reduced His/- ligated form of cytc which was found previously to catalytically reduce dioxygen. Here, this adduct is also found to show pseudoperoxidase activity, catalysing reduction of hydrogen peroxide. These effects would impart CL with an additional role in the cytc-mediated peroxidation leading to programmed cell death. Moreover, immobilized cytc exchanges electrons more slowly upon CL binding possibly due to changes in solvent reorganization effects at the protein-SAM interface

  5. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition

    Directory of Open Access Journals (Sweden)

    Lesley Hart

    2014-05-01

    Full Text Available Wolf-Hirschhorn syndrome (WHS represents an archetypical example of a contiguous gene deletion disorder – a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca2+] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  6. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition.

    Science.gov (United States)

    Hart, Lesley; Rauch, Anita; Carr, Antony M; Vermeesch, Joris R; O'Driscoll, Mark

    2014-05-01

    Wolf-Hirschhorn syndrome (WHS) represents an archetypical example of a contiguous gene deletion disorder - a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca(2+)] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  7. Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington's disease

    DEFF Research Database (Denmark)

    Petersen, Maria Hvidberg; Budtz-Jørgensen, Esben; Sørensen, Sven Asger

    2014-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led to the inve......Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led...

  8. Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics.

    Science.gov (United States)

    Scandurra, Francesca M; Gnaiger, Erich

    2010-01-01

    When oxygen supply to tissues is limiting, mitochondrial respiration and ATP production are compromised. To assess the bioenergetic consequences under normoxia and hypoxia, quantitative evaluation of mitochondrial oxygen kinetics is required. Using high-resolution respirometry, the "apparent K (m)" for oxygen or p (50) of respiration in 32D cells was determined at 0.05 +/- 0.01 kPa (0.4 mmHg, 0.5 microM, 0.25% air saturation). Close agreement with p (50) of isolated mitochondria indicates that intracellular gradients are small in small cells at routine activity. At intracellular p (O2) respiration is limited by >2% with a p (50) of 0.05 kPa. Over-estimation of p (50) at 0.4 kPa (3 mmHg) would imply significant (>17%) oxygen limitation of respiration under intracellular normoxia. Based on a critical review, we conclude that p (50) ranges from 0.01 to 0.10 kPa in mitochondria and small cells in the absence of inhibitors of cytochrome c oxidase, whereas experimental artefacts explain the controversial >200-fold range of p (50) in the literature on mitochondrial oxygen kinetics.

  9. HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

    Energy Technology Data Exchange (ETDEWEB)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Hrubik, Jelena; Glisic, Branka; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

    2015-01-01

    Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATP level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig

  10. HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

    International Nuclear Information System (INIS)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Hrubik, Jelena; Glisic, Branka; Kovacevic, Radmila; Andric, Nebojsa

    2015-01-01

    Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATP level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig

  11. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

    2014-01-01

    Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

  12. Intussusception in children: Hydrostatic reduction under US guidance - own experience

    International Nuclear Information System (INIS)

    Roik, D.; Brzewski, M.; Biejat, A.; Marcinski, M.

    2008-01-01

    Intussusception in children is a common abdominal emergency. Recent years have brought a New promising method of nonsurgical invagination treatment, hydrostatic reduction under sonographic (US) guidance. The major advantage of this method is lack of the ionized radiation. The aim of our study is to asses the safety and effectiveness of hydrostatic reduction under US guidance used as a first choice method of invagination treatment in our department. >From July 2006 to December 2007, 33 procedures of hydrostatic reduction under US guidance were performed in 27 children, aged from 7 months to 6 years and 10 months. The procedure was performed in US room by radiologist and surgeon with the use of self-constructed set for saline enema. The sedation of patient was routinely performed. The initial procedure was effective in 23 patients (pts) (85%). In 5 pts the recurrence of intussusception occurred and in 3 of them next attempt of the reduction was successful. In 4 cases the initial procedures failed, and those children were operated. Total amount of 6 pts underwent an operation. We do not observe any complications connected with the procedure. Hydrostatic reduction of children intusussception under US-guidance is safe and effective method. Our initial results meet the recommended limits of successful reduction rates. It encouraged us to evaluation and further implementation of this method. Water enema is a first choice method of invagination treatment in our hospital. (authors)

  13. Study of transient burnout under flow reduction condition

    International Nuclear Information System (INIS)

    Iwamura, Takamichi

    1986-09-01

    Transient burnout characteristics of a fuel rod under a rapid flow reduction condition of a light water reactor were experimentally and analytically studied. The test sections were uniformly heated vertical tube and annulus with the heated length of 800 mm. Test pressures ranged 0.5 ∼ 3.9 MPa, heat fluxes 2,160 ∼ 3,860 KW/m 2 , and flow reduction rates 0.44 ∼ 770 %/s. The local flow condition during flow reduction transients were calculated with a separate flow model. The two-fluid/three-field thermal-hydraulic code, COBRA/TRAC, was also used to investigate the liquid film behavior on the heated surface. The major results obtained in the present study are as follows: The onset of burnout under a rapid flow reduction condition was caused by a liquid film dryout on the heated surface. With increasing flow reduction rate beyond a threshold, the burnout mass velocity at the inlet became lower than the steady-state burnout mass velocity. This is explained by the fact that the vapor flow rate continues to increase due to the delay of boiling boundary movement and the resultant high vapor velocity sustains the liquid film flow after the inlet flow rate reaches the steady-state burnout flow rate. The ratio of inlet burnout mass velocities between flow reduction transient and steady-state became smaller with increasing system pressure because of the lower vapor velocity due to the lower vapor specific volume. Flow reduction burnout occurred when the outlet quality agreed with the steady-state burnout quality within 10 %, suggesting that the local condition burnout model can be used for flow reduction transients. Based on this model, a method to predict the time to burnout under a flow reduction condition in a uniformly heated tube was developed. The calculated times to burnout agreed well with some experimental results obtained by the Author, Cumo et al., and Moxon et al. (author)

  14. Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Shruti; Amar, Saroj Kumar [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow (India); Dubey, Divya; Pal, Manish Kumar [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Singh, Jyoti [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow (India); Verma, Ankit; Kushwaha, Hari Narayan [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Ray, Ratan Singh, E-mail: ratanray.2011@rediffmail.com [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India)

    2015-12-30

    Highlights: • Photodegradation and formation of photoproduct. • Involvement of ROS in PPD phototoxicity. • Role of ROS in DNA damage, CPD and micronuclei formation. • PPD induced lysosomal destabilization and release of cathepsin B. • Cleavage of Bid and activation of mitochondrial apoptosis. - Abstract: Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings.

  15. Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

    International Nuclear Information System (INIS)

    Goyal, Shruti; Amar, Saroj Kumar; Dubey, Divya; Pal, Manish Kumar; Singh, Jyoti; Verma, Ankit; Kushwaha, Hari Narayan; Ray, Ratan Singh

    2015-01-01

    Highlights: • Photodegradation and formation of photoproduct. • Involvement of ROS in PPD phototoxicity. • Role of ROS in DNA damage, CPD and micronuclei formation. • PPD induced lysosomal destabilization and release of cathepsin B. • Cleavage of Bid and activation of mitochondrial apoptosis. - Abstract: Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings.

  16. Study of transient burnout characteristics under flow reduction condition

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Kuroyanagi, Toshiyuki

    1984-03-01

    As part of a study of the thermal behavior of fuel rods during Power-Cooling-Mismatch (PCM) accidents in light water reactors, burnout characteristics in a uniformly heated, vertically oriented tube or annulus, under flow reduction condition, were experimentally studied. Test pressures ranged 0.1--3.9 MPa and flow reduction rates 0.44--1100%/s. An analytical method is developed to obtain the local mass velocity during a transient condition. The major results are as follows: With increasing flow reduction rate beyond a threshold, transient burnout mass velocity at the inlet was lower than that in steady state tests under the experimental pressures. The higher system pressure resulted in the less transient effects. At pressures higher than 2.0 MPa and flow reduction rates lower than 20%/s, the local burnout mass velocity agreed with the steady state burnout mass velocity, whereas the local burnout mass velocity became higher than the steady state burnout mass velocity at flow reduction rates higher than 20%/s. At pressures lower than 1 MPa, with increasing flow reduction rate beyond the threshold value of 2%/s, the local burnout mass velocity was lower than the steady state burnout mass velocity. An empirical correlation is presented to give the ratio of the transient to the steady state burnout mass velocities at the burnout location as a function of the steam-water density ratio and the flow reduction rate. The experimental results by Cumo et al. agree with the correlation. The correlation, however, cannot predict the experimental results at higher flow reduction rates beyond 40%/s. (author)

  17. Genetic reduction of mitochondrial complex I function does not lead to loss of dopamine neurons in vivo.

    Science.gov (United States)

    Kim, Hyung-Wook; Choi, Won-Seok; Sorscher, Noah; Park, Hyung Joon; Tronche, François; Palmiter, Richard D; Xia, Zhengui

    2015-09-01

    Inhibition of mitochondrial complex I activity is hypothesized to be one of the major mechanisms responsible for dopaminergic neuron death in Parkinson's disease. However, loss of complex I activity by systemic deletion of the Ndufs4 gene, one of the subunits comprising complex I, does not cause dopaminergic neuron death in culture. Here, we generated mice with conditional Ndufs4 knockout in dopaminergic neurons (Ndufs4 conditional knockout mice [cKO]) to examine the effect of complex I inhibition on dopaminergic neuron function and survival during aging and on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in vivo. Ndufs4 cKO mice did not show enhanced dopaminergic neuron loss in the substantia nigra pars compacta or dopamine-dependent motor deficits over the 24-month life span. These mice were just as susceptible to MPTP as control mice. However, compared with control mice, Ndufs4 cKO mice exhibited an age-dependent reduction of dopamine in the striatum and increased α-synuclein phosphorylation in dopaminergic neurons of the substantia nigra pars compacta. We also used an inducible Ndufs4 knockout mouse strain (Ndufs4 inducible knockout) in which Ndufs4 is conditionally deleted in all cells in adult to examine the effect of adult onset, complex I inhibition on MPTP sensitivity of dopaminergic neurons. The Ndufs4 inducible knockout mice exhibited similar sensitivity to MPTP as control littermates. These data suggest that mitochondrial complex I inhibition in dopaminergic neurons does contribute to dopamine loss and the development of α-synuclein pathology. However, it is not sufficient to cause cell-autonomous dopaminergic neuron death during the normal life span of mice. Furthermore, mitochondrial complex I inhibition does not underlie MPTP toxicity in vivo in either cell autonomous or nonautonomous manner. These results provide strong evidence that inhibition of mitochondrial complex I activity is not sufficient to cause dopaminergic neuron

  18. 3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

    Directory of Open Access Journals (Sweden)

    He N. Xu

    2014-03-01

    Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

  19. 3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

    Science.gov (United States)

    Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

    2014-03-01

    The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo . Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD + couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH ( p = 0.038). No significant change in Fp was found ( p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D

  20. Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research.

    Science.gov (United States)

    Paraskevaidi, Maria; Martin-Hirsch, Pierre L; Kyrgiou, Maria; Martin, Francis L

    2017-05-01

    Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell's functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels

    Directory of Open Access Journals (Sweden)

    Ichinomiya Taiga

    2012-03-01

    Full Text Available Abstract Background The current study was carried out to determine whether fasudil hydrochloride (fasudil, a Rho-kinase inhibitor, has myocardial postconditioning (PostC activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP channels. Methods Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg or high-dose (0.5 mg/kg fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD, an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR. Results Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively compared with that in the control (42 ± 7%. Under hyperglycemia, low-dose fasudil (40 ± 11% and diazoxide (44 ± 14% could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%. 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%. Conclusion Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

  2. Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

    Science.gov (United States)

    Smeland, Olav B; Hadera, Mussie G; McDonald, Tanya S; Sonnewald, Ursula; Borges, Karin

    2013-01-01

    Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine–status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5–4 weeks after SE with [1,2-13C]glucose before microwave fixation of the head. Using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography—mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine–SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. PMID:23611869

  3. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

    Science.gov (United States)

    Metallo, Christian M.; Gameiro, Paulo A.; Bell, Eric L.; Mattaini, Katherine R.; Yang, Juanjuan; Hiller, Karsten; Jewell, Christopher M.; Johnson, Zachary R.; Irvine, Darrell J.; Guarente, Leonard; Kelleher, Joanne K.; Vander Heiden, Matthew G.; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-01-01

    Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and adenosine triphosphate citrate lyase (ACL) in the cytosol1-3. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle (TCA) and fatty acid synthesis4. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis5, the regulation and utilization of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells employ reductive metabolism of alpha-ketoglutarate (αKG) to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase 1 (IDH1) dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived αKG for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau (VHL) tumor suppressor protein preferentially utilize reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon utilization in order to produce AcCoA and support lipid synthesis in mammalian cells. PMID:22101433

  4. Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity

    DEFF Research Database (Denmark)

    Boushel, Robert; Gnaiger, E.; Larsen, F. J.

    2015-01-01

    We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy ...... at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max , and that mitochondrial volume can be downregulated by chronic energy demand....

  5. Reduction of nitrate and nitrite salts under hydrothermal conditions

    International Nuclear Information System (INIS)

    Foy, B.R.; Dell'Orco, P.C.; Wilmanns, E.; McInroy, R.; Ely, J.; Robinson, J.M.; Buelow, S.J.

    1994-01-01

    The feasibility of reducing nitrate/nitrite salts under hydrothermal conditions for the treatment of aqueous mixed wastes stored in the underground tanks at the Department of Energy site at Hanford, Washington was studied. The reduction of nitrate and nitrite salts by reaction with EDTA using a tank waste simulant was examined at temperatures between 623K and 800K and pressures between 0.6 and 1.2 kbar. Continuous flow reactors were used to determine kinetics and products of reactions. All reactions were studied under pressures high enough to produce single phase conditions. The reactions are rapid, go to completion in less than a minute, and produce simple products, such as carbonate, nitrogen, and nitrous oxide gases. The experimental results demonstrate the ability of chemical reactions under hydrothermal conditions to reduce the nitrate and nitrite salts and destroy organic compounds in the waste mixtures

  6. Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation.

    Science.gov (United States)

    Goyal, Shruti; Amar, Saroj Kumar; Dubey, Divya; Pal, Manish Kumar; Singh, Jyoti; Verma, Ankit; Kushwaha, Hari Narayan; Ray, Ratan Singh

    2015-12-30

    Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Analysis and Reduction of Complex Networks Under Uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Knio, Omar M

    2014-04-09

    This is a collaborative proposal that aims at developing new methods for the analysis and reduction of complex multiscale networks under uncertainty. The approach is based on combining methods of computational singular perturbation (CSP) and probabilistic uncertainty quantification. In deterministic settings, CSP yields asymptotic approximations of reduced-dimensionality “slow manifolds” on which a multiscale dynamical system evolves. Introducing uncertainty raises fundamentally new issues, particularly concerning its impact on the topology of slow manifolds, and means to represent and quantify associated variability. To address these challenges, this project uses polynomial chaos (PC) methods to reformulate uncertain network models, and to analyze them using CSP in probabilistic terms. Specific objectives include (1) developing effective algorithms that can be used to illuminate fundamental and unexplored connections among model reduction, multiscale behavior, and uncertainty, and (2) demonstrating the performance of these algorithms through applications to model problems.

  8. Reductions in labour capacity from heat stress under climate warming

    Science.gov (United States)

    Dunne, John P.; Stouffer, Ronald J.; John, Jasmin G.

    2013-06-01

    A fundamental aspect of greenhouse-gas-induced warming is a global-scale increase in absolute humidity. Under continued warming, this response has been shown to pose increasingly severe limitations on human activity in tropical and mid-latitudes during peak months of heat stress. One heat-stress metric with broad occupational health applications is wet-bulb globe temperature. We combine wet-bulb globe temperatures from global climate historical reanalysis and Earth System Model (ESM2M) projections with industrial and military guidelines for an acclimated individual's occupational capacity to safely perform sustained labour under environmental heat stress (labour capacity)--here defined as a global population-weighted metric temporally fixed at the 2010 distribution. We estimate that environmental heat stress has reduced labour capacity to 90% in peak months over the past few decades. ESM2M projects labour capacity reduction to 80% in peak months by 2050. Under the highest scenario considered (Representative Concentration Pathway 8.5), ESM2M projects labour capacity reduction to less than 40% by 2200 in peak months, with most tropical and mid-latitudes experiencing extreme climatological heat stress. Uncertainties and caveats associated with these projections include climate sensitivity, climate warming patterns, CO2 emissions, future population distributions, and technological and societal change.

  9. Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate.

    Science.gov (United States)

    Liu, Ning; Wu, Jichao; Zhang, Linxue; Gao, Zhaopeng; Sun, Yu; Yu, Miao; Zhao, Yajun; Dong, Shiyun; Lu, Fanghao; Zhang, Weihua

    2017-12-01

    Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H 2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H 2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H 2 S production and CSE expression in RAECs. Then, the antioxidative effect of H 2 S was proved in RAECs under high glucose and palmitate to reduce mitochondrial ROS level. We also showed that exogenous H 2 S inhibited mitochondrial apoptosis in RAECs under high glucose and palmitate. Using Mito Tracker and transmission electron microscopy assay, we revealed that exogenous H 2 S decreased mitochondrial fragments and significantly reduced the expression of p-Drp-1/Drp-1 and Fis1 compared to high-glucose and high-palmitate group, whereas it increased mitophagy by transmission electron microscopy assay. We demonstrated that exogenous H 2 S facilitated Parkin recruited by PINK1 by immunoprecipitation and immunostaining assays and then ubiquitylated mitofusin 2 (Mfn2), which illuminated the mechanism of exogenous H 2 S on mitophagy. Parkin siRNA suppressed the expression of Mfn2, Nix and LC3B, which revealed that it eliminated mitophagy. In summary, exogenous H 2 S could protect RAECs against apoptosis under high glucose and palmitate by suppressing oxidative stress, decreasing mitochondrial fragments and promoting mitophagy. Based on these results, we proposed a new mechanism of H 2 S on protecting endothelium, which might provide a new strategy for type II diabetes vascular complication. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

  10. Involvement of Reactive Oxygen Species and Mitochondrial Proteins in Biophoton Emission in Roots of Soybean Plants under Flooding Stress.

    Science.gov (United States)

    Kamal, Abu Hena Mostafa; Komatsu, Setsuko

    2015-05-01

    To understand the mechanism of biophoton emission, ROS and mitochondrial proteins were analyzed in soybean plants under flooding stress. Enzyme activity and biophoton emission were increased in the flooding stress samples when assayed in reaction mixes specific for antioxidant enzymes and reactive oxygen species; although the level of the hydroxyl radicals was increased at day 4 (2 days of flooding) compared to nonflooding at day 4, the emission of biophotons did not change. Mitochondria were isolated and purified from the roots of soybean plants grown under flooding stress by using a Percoll gradient, and proteins were analyzed by a gel-free proteomic technique. Out of the 98 mitochondrial proteins that significantly changed abundance under flooding stress, 47 increased and 51 decreased at day 4. The mitochondrial enzymes fumarase, glutathione-S-transferase, and aldehyde dehydrogenase increased at day 4 in protein abundance and enzyme activity. Enzyme activity and biophoton emission decreased at day 4 by the assay of lipoxygenase under stress. Aconitase, acyl CoA oxidase, succinate dehydrogenase, and NADH ubiquinone dehydrogenase were up-regulated at the transcription level. These results indicate that oxidation and peroxide scavenging might lead to biophoton emission and oxidative damage in the roots of soybean plants under flooding stress.

  11. Mitochondrial cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Ayman W. El-Hattab

    2016-07-01

    Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  12. Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity.

    Science.gov (United States)

    Schirris, Tom J J; Ritschel, Tina; Herma Renkema, G; Willems, Peter H G M; Smeitink, Jan A M; Russel, Frans G M

    2015-09-29

    Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre-clinical dog study with mitochondrial dysfunction. Here, we studied the molecular mechanism by which ibipinabant induces mitochondrial toxicity. We observed a strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional characterization of mitochondria revealed increased cellular reactive oxygen species generation and a decreased ATP production capacity, without effects on the catalytic activities of mitochondrial enzyme complexes I-V or the complex specific-driven oxygen consumption. Using in silico off-target prediction modelling, combined with in vitro validation in isolated mitochondria and mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying ibipinabant-induced toxicity. Minor structural modification of ibipinabant could abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with the ibipinabant derivative CB23. Our results will be instrumental in the development of new types of safer CB1R antagonists.

  13. HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation

    International Nuclear Information System (INIS)

    Kim, Hak-June; Nagano, Yoshito; Choi, Su Jin; Park, Song Yi; Kim, Hongtae; Yao, Tso-Pang; Lee, Joo-Yong

    2015-01-01

    Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress. - Highlights: • Hypoxic stress induces the interaction between HDAC6 and MFN2. • Hypoxic stress activates MARCH5 in HDAC6 deficient cells to degrade MFN2. • HDAC6 is required to maintain mitochondrial connectivity under hypoxia. • MARCH5 is increased and promotes the degradation of MFN2 in HDAC6 KO ALS mice

  14. HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hak-June [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Nagano, Yoshito [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, 734-8551 (Japan); Choi, Su Jin; Park, Song Yi [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Kim, Hongtae [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon, 440-746 (Korea, Republic of); Yao, Tso-Pang, E-mail: tsopang.yao@duke.edu [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Lee, Joo-Yong, E-mail: leejooyong@cnu.ac.kr [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of)

    2015-09-04

    Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress. - Highlights: • Hypoxic stress induces the interaction between HDAC6 and MFN2. • Hypoxic stress activates MARCH5 in HDAC6 deficient cells to degrade MFN2. • HDAC6 is required to maintain mitochondrial connectivity under hypoxia. • MARCH5 is increased and promotes the degradation of MFN2 in HDAC6 KO ALS mice.

  15. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  16. Hydrazine and hydroxylamine as probes for O2-reduction site of mitochondrial cytochrome c oxidase.

    Science.gov (United States)

    Kubota, T; Yoshikawa, S

    1993-01-01

    Reactions of hydrazine and hydroxylamine with bovine heart cytochrome c oxidase in the fully reduced state were investigated under anaerobic conditions following the visible-Soret spectral change. Hydrazine gave a sharp band at 575 nm with 20% decrease in the alpha band at 603 nm, and hydroxylamine induced a 2 nm blue-shift for the alpha band without any clear splitting. The Soret band at 443 nm was decreased significantly in intensity, with the concomitant appearance of a shoulder with hydrazine or a peak with hydroxylamine, both near 430 nm. The dependence on pH of the affinity of these reagents for the enzyme indicates that only the deprotonated forms of these reagents bind to the enzyme, suggesting a highly hydrophobic environment of the haem ligand-biding site. These spectral changes were largely removed by addition of cyanide or CO. However, detailed analysis of these spectral changes indicates that hydrazine perturbs the shape of the spectral change induced by cyanide and hydroxylamine perturbs that induced by CO. These results suggest that these aldehyde reagents bind to haem a3 iron as well as to a second site which is most likely to be the formyl group on the haem periphery, and that these two sites bind these reagents anti-cooperatively with each other. PMID:8389138

  17. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    Using histochemical methods offering high topographical resolution for evaluation of changes in the ischemic focus and the penumbra, the mitochondrial electron transport chain (ETC) complexes I, II, and IV were examined in rats subjected to 2 h of proximal occlusion of the middle cerebral artery...

  18. Reduction of irradiated tumor cells viability under effect of hyperglycemia

    International Nuclear Information System (INIS)

    Meshcherikova, V.V.; Voloshina, E.A.

    1983-01-01

    On Ehrlich carcinoma cells adapted to growth in vivo and in vitro, cellular mechanisms of short-term hyperglycemia effect have been studied. It has been found that SH by itself leads to the loss of viability of a part of cells of ELD solid tumors manifesting during the first 24 hours upon irradiation according to the interphase death type. Tumor cell radiation injuries arising under the effect of irradiation, usually non realized up to the first division, under SH conditions potentiate its injury effect. The phenomena observed explain partially selective injury of tumoral cells in the course of irradiation under SH conditions which testifies to the prospects of its use in clinics

  19. Reduction in cardiolipin decreases mitochondrial spare respiratory capacity and increases glucose transport into and across human brain cerebral microvascular endothelial cells.

    Science.gov (United States)

    Nguyen, Hieu M; Mejia, Edgard M; Chang, Wenguang; Wang, Ying; Watson, Emily; On, Ngoc; Miller, Donald W; Hatch, Grant M

    2016-10-01

    Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin is a mitochondrial phospholipid required for function of the electron transport chain and ATP generation. We examined the role of cardiolipin in maintaining mitochondrial function necessary to support barrier properties of brain microvessel endothelial cells. Knockdown of the terminal enzyme of cardiolipin synthesis, cardiolipin synthase, in hCMEC/D3 cells resulted in decreased cellular cardiolipin levels compared to controls. The reduction in cardiolipin resulted in decreased mitochondrial spare respiratory capacity, increased pyruvate kinase activity, and increased 2-deoxy-[(3) H]glucose uptake and glucose transporter-1 expression and localization to membranes in hCMEC/D3 cells compared to controls. The mechanism for the increase in glucose uptake was an increase in adenosine-5'-monophosphate kinase and protein kinase B activity and decreased glycogen synthase kinase 3 beta activity. Knockdown of cardiolipin synthase did not affect permeability of fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell(®) inserts. In contrast, knockdown of cardiolipin synthase resulted in an increase in 2-deoxy-[(3) H]glucose transport across these monolayers compared to controls. The data indicate that in hCMEC/D3 cells, spare respiratory capacity is dependent on cardiolipin. In addition, reduction in cardiolipin in these cells alters their cellular energy status and this results in increased glucose transport into and across hCMEC/D3 monolayers. Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. In human adult brain endothelial cell hCMEC/D3 monolayers cultured on Transwell(®) plates, knockdown of cardiolipin synthase results in decrease in mitochondrial

  20. Mitochondrial Biogenesis in Diverse Cauliflower Cultivars under Mild and Severe Drought. Impaired Coordination of Selected Transcript and Proteomic Responses, and Regulation of Various Multifunctional Proteins

    Directory of Open Access Journals (Sweden)

    Michał Rurek

    2018-04-01

    Full Text Available Mitochondrial responses under drought within Brassica genus are poorly understood. The main goal of this study was to investigate mitochondrial biogenesis of three cauliflower (Brassica oleracea var. botrytis cultivars with varying drought tolerance. Diverse quantitative changes (decreases in abundance mostly in the mitochondrial proteome were assessed by two-dimensional gel electrophoresis (2D PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS. Respiratory (e.g., complex II, IV (CII, CIV and ATP synthase subunits, transporter (including diverse porin isoforms and matrix multifunctional proteins (e.g., components of RNA editing machinery were diversely affected in their abundance under two drought levels. Western immunoassays showed additional cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related tryptic peptides (found in several 2D spots immunopositive with dehydrin-specific antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought response. The abundance of selected mRNAs participating in drought response was also determined. We conclude that mitochondrial biogenesis was strongly, but diversely affected in various cauliflower cultivars, and associated with drought tolerance at the proteomic and functional levels. However, discussed alternative oxidase (AOX regulation at the RNA and protein level were largely uncoordinated due to the altered availability of transcripts for translation, mRNA/ribosome interactions, and/or miRNA impact on transcript abundance and translation.

  1. Mitochondrial Biogenesis in Diverse Cauliflower Cultivars under Mild and Severe Drought. Impaired Coordination of Selected Transcript and Proteomic Responses, and Regulation of Various Multifunctional Proteins

    Science.gov (United States)

    Rurek, Michał; Czołpińska, Magdalena; Staszak, Aleksandra Maria; Nowak, Witold; Krzesiński, Włodzimierz; Spiżewski, Tomasz

    2018-01-01

    Mitochondrial responses under drought within Brassica genus are poorly understood. The main goal of this study was to investigate mitochondrial biogenesis of three cauliflower (Brassica oleracea var. botrytis) cultivars with varying drought tolerance. Diverse quantitative changes (decreases in abundance mostly) in the mitochondrial proteome were assessed by two-dimensional gel electrophoresis (2D PAGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Respiratory (e.g., complex II, IV (CII, CIV) and ATP synthase subunits), transporter (including diverse porin isoforms) and matrix multifunctional proteins (e.g., components of RNA editing machinery) were diversely affected in their abundance under two drought levels. Western immunoassays showed additional cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related tryptic peptides (found in several 2D spots) immunopositive with dehydrin-specific antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought response. The abundance of selected mRNAs participating in drought response was also determined. We conclude that mitochondrial biogenesis was strongly, but diversely affected in various cauliflower cultivars, and associated with drought tolerance at the proteomic and functional levels. However, discussed alternative oxidase (AOX) regulation at the RNA and protein level were largely uncoordinated due to the altered availability of transcripts for translation, mRNA/ribosome interactions, and/or miRNA impact on transcript abundance and translation. PMID:29642585

  2. Reductive precipitation of neptunium on iron surfaces under anaerobic conditions

    Science.gov (United States)

    Yang, H.; Cui, D.; Grolimund, D.; Rondinella, V. V.; Brütsch, R.; Amme, M.; Kutahyali, C.; Wiss, A. T.; Puranen, A.; Spahiu, K.

    2017-12-01

    Reductive precipitation of the radiotoxic nuclide 237Np from nuclear waste on the surface of iron canister material at simulated deep repository conditions was investigated. Pristine polished as well as pre-corroded iron specimens were interacted in a deoxygenated solution containing 10-100 μM Np(V), with 10 mM NaCl and 2 mM NaHCO3 as background electrolytes. The reactivity of each of the two different systems was investigated by analyzing the temporal evolution of the Np concentration in the reservoir. It was observed that pre-oxidized iron specimen with a 40 μm Fe3O4 corrosion layer are considerably more reactive regarding the reduction and immobilization of aqueous Np(V) as compared to pristine polished Fe(0) surfaces. 237Np immobilized by the reactive iron surfaces was characterized by scanning electron microscopy as well as synchrotron-based micro-X-ray fluorescence and X-ray absorption spectroscopy. At the end of experiments, a 5-8 μm thick Np-rich layer was observed to be formed ontop of the Fe3O4 corrosion layer on the iron specimen. The findings from this work are significant in the context of performance assessments of deep geologic repositories using iron as high level radioactive waste (HLW) canister material and are of relevance regarding removing pollutants from contaminated soil or groundwater aquifer systems.

  3. Protective effects of potassium transport in mitochondria from rat myometrium under activation of mitochondrial permeability transition pore

    Directory of Open Access Journals (Sweden)

    O. B. Vadzyuk

    2015-12-01

    Full Text Available We demonstrated using PBFI K+-sensitive fluorescent probe an enhancement of both components of K+-cycle – the ATP-sensitive K+-uptake and quinine-sensitive K+/H+-exchange – under the Ca2+ induced opening­ of mitochondrial permeability transition pore (MPTP in rat myometrium mitochondria. Addition of CaCl2 (100 μM to K+-free medium results in the enhancement of reactive oxygen species (ROS production, which was eliminated by cyclosporine A. Addition of CaCl2 to K+-rich medium did not increase the rate of ROS production, but blocking of mitoK+ATP-channels with glybenclamide (10 μM increased production of ROS. We conclude that K+-cycle exerts a protective influence in mitochondria from rat myometrium by regulation of matrix volume and rate of ROS production under the condition of Ca2+-induced MPTP.

  4. Analysis and Reduction of Complex Networks Under Uncertainty.

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Roger G [University of Southern California

    2014-07-31

    This effort was a collaboration with Youssef Marzouk of MIT, Omar Knio of Duke University (at the time at Johns Hopkins University) and Habib Najm of Sandia National Laboratories. The objective of this effort was to develop the mathematical and algorithmic capacity to analyze complex networks under uncertainty. Of interest were chemical reaction networks and smart grid networks. The statements of work for USC focused on the development of stochastic reduced models for uncertain networks. The USC team was led by Professor Roger Ghanem and consisted of one graduate student and a postdoc. The contributions completed by the USC team consisted of 1) methodology and algorithms to address the eigenvalue problem, a problem of significance in the stability of networks under stochastic perturbations, 2) methodology and algorithms to characterize probability measures on graph structures with random flows. This is an important problem in characterizing random demand (encountered in smart grid) and random degradation (encountered in infrastructure systems), as well as modeling errors in Markov Chains (with ubiquitous relevance !). 3) methodology and algorithms for treating inequalities in uncertain systems. This is an important problem in the context of models for material failure and network flows under uncertainty where conditions of failure or flow are described in the form of inequalities between the state variables.

  5. Acrylamide reduction under different pre-treatments in French fries

    DEFF Research Database (Denmark)

    Pedreschi, Franco; Kaack, Karl; Granby, Kit

    2007-01-01

    of similar to 40 g water/100 g (total basis). Prior to frying, potato strips were treated in one of the following ways: (i) immersed in distilled water for 0 min (control), 60 min and 120 min; (ii) immersed in a citric acid solution of 10 g/L for an hour; (iii) immersed in a sodium pyrophosphate solution...... strips before frying. Immersed strips in water for 120 min showed a reduction of acrylamide formation of 33%, 21% and 27% at 150, 170 and 190 degrees C, respectively, when they were compared against the control. Potato strips blanched at 50 degrees C for 80 min had the lowest acrylamide content when...... compared against strips blanched at different conditions and fried at the same temperature (135, 327 and 564 mu m acrylamide/kg for 150, 170 and 190 degrees C, respectively). Potato strip immersion in citric acid solution of 10 g/L reduced much more the acrylamide formation after frying than the strip...

  6. Research on CO2 Emission Reduction Mechanism of China’s Iron and Steel Industry under Various Emission Reduction Policies

    Directory of Open Access Journals (Sweden)

    Ye Duan

    2017-12-01

    Full Text Available In this paper, a two-stage dynamic game model of China’s iron and steel industry is constructed. Carbon tax levy, product subsidy, carbon capture and sequestration (CCS and other factors are included in the emission reduction mechanism. The effects of emissions reduction and the economic impact of China’s overall steel industry (and that of its six main regions are investigated for the first time under different scenarios. As new findings, we report the following: (1 Not all factors declined. The overall social welfare, consumer surplus, output and emissions decrease with a gradual increase in the reduction target, whereas the carbon tax value, unit value of product subsidies and total subsidies show a rising trend; (2 A combination of multiple emissions reduction policies is more effective than a single policy. With the implementation of a combined policy, regional output polarization has eased; (3 Steel output does not exceed 950 million tons, far below the current peak. These results will help the industry to formulate reasonable emissions reduction and output targets. In short, in effort to eliminate industry poverty and to alleviate overcapacity, the industry should not only adopt the various coordinated reduction policies, but also fully consider regional differences and reduction needs.

  7. Preclinical evidence of mitochondrial nicotinamide adenine dinucleotide as an effective alarm parameter under hypoxia

    Science.gov (United States)

    Shi, Hua; Sun, Nannan; Mayevsky, Avraham; Zhang, Zhihong; Luo, Qingming

    2014-01-01

    Early detection of tissue hypoxia in the intensive care unit is essential for effective treatment. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of tissue oxygenation at the mitochondrial level. However, no experimental evidence comparing the kinetics of changes in NADH and other physiological parameters has been provided. The aim of this study is to obtain the missing data in a systematic and reliable manner. We constructed four acute hypoxia models, including hypoxic hypoxia, hypemic hypoxia, circulatory hypoxia, and histogenous hypoxia, and measured NADH fluorescence, tissue reflectance, cerebral blood flow, respiration, and electrocardiography simultaneously from the induction of hypoxia until death. We found that NADH was not always the first onset parameter responding to hypoxia. The order of responses was mainly affected by the cause of hypoxia. However, NADH reached its alarm level earlier than the other monitored parameters, ranging from several seconds to >10 min. As such, we suggest that the NADH can be used as a hypoxia indicator, although the exact level that should be used must be further investigated. When the NADH alarm is detected, the body still has a chance to recover if appropriate and timely treatment is provided.

  8. Selection of risk reduction portfolios under interval-valued probabilities

    International Nuclear Information System (INIS)

    Toppila, Antti; Salo, Ahti

    2017-01-01

    A central problem in risk management is that of identifying the optimal combination (or portfolio) of improvements that enhance the reliability of the system most through reducing failure event probabilities, subject to the availability of resources. This optimal portfolio can be sensitive with regard to epistemic uncertainties about the failure events' probabilities. In this paper, we develop an optimization model to support the allocation of resources to improvements that mitigate risks in coherent systems in which interval-valued probabilities defined by lower and upper bounds are employed to capture epistemic uncertainties. Decision recommendations are based on portfolio dominance: a resource allocation portfolio is dominated if there exists another portfolio that improves system reliability (i) at least as much for all feasible failure probabilities and (ii) strictly more for some feasible probabilities. Based on non-dominated portfolios, recommendations about improvements to implement are derived by inspecting in how many non-dominated portfolios a given improvement is contained. We present an exact method for computing the non-dominated portfolios. We also present an approximate method that simplifies the reliability function using total order interactions so that larger problem instances can be solved with reasonable computational effort. - Highlights: • Reliability allocation under epistemic uncertainty about probabilities. • Comparison of alternatives using dominance. • Computational methods for generating the non-dominated alternatives. • Deriving decision recommendations that are robust with respect to epistemic uncertainty.

  9. Reduction of photosynthetically active radiation under extreme stratospheric aerosol loads

    International Nuclear Information System (INIS)

    Gerstl, S.A.W.; Zardecki, A.

    1981-08-01

    The recently published hypothesis that the Cretaceous-Tertiary extinctions might be caused by an obstruction of sunlight is tested by model calculations. First we compute the total mass of stratospheric aerosols under normal atmospheric conditions for four different (measured) aerosol size distributions and vertical profiles. For comparison, the stratospheric dust masses after four volcanic eruptions are also evaluated. Detailed solar radiative transfer calculations are then performed for artificially increased aerosol amounts until the postulated darkness scenario is obtained. Thus we find that a total stratospheric aerosol mass between 1 and 4 times 10 1 g is sufficient to reduce photosynthesis to 10 -3 of normal. We also infer from this result tha the impact of a 0.4- to 3-km-diameter asteroid or a close encounter with a Halley-size comet may deposit that amount of particulates into the stratosphere. The darkness scenario of Alvarez et al. is thus shown to be a possible extinction mechanism, even with smaller size asteroids of comets than previously estimated

  10. DJ-1 KNOCK-DOWN IMPAIRS ASTROCYTE MITOCHONDRIAL FUNCTION

    Science.gov (United States)

    LARSEN, N. J.; AMBROSI, G.; MULLETT, S. J.; BERMAN, S. B.; HINKLE, D. A.

    2012-01-01

    Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson’s disease (PD). PD brain tissues show evidence for mitochondrial respiratory chain Complex I deficiency. Pharmacological inhibitors of Complex I, such as rotenone, cause experimental parkinsonism. The cytoprotective protein DJ-1, whose deletion is sufficient to cause genetic PD, is also known to have mitochondria-stabilizing properties. We have previously shown that DJ-1 is over-expressed in PD astrocytes, and that DJ-1 deficiency impairs the capacity of astrocytes to protect co-cultured neurons against rotenone. Since DJ-1 modulated, astrocyte-mediated neuroprotection against rotenone may depend upon proper astrocytic mitochondrial functioning, we hypothesized that DJ-1 deficiency would impair astrocyte mitochondrial motility, fission/fusion dynamics, membrane potential maintenance, and respiration, both at baseline and as an enhancement of rotenone-induced mitochondrial dysfunction. In astrocyte-enriched cultures, we observed that DJ-1 knock-down reduced mitochondrial motility primarily in the cellular processes of both untreated and rotenone treated cells. In these same cultures, DJ-1 knock-down did not appreciably affect mitochondrial fission, fusion, or respiration, but did enhance rotenone-induced reductions in the mitochondrial membrane potential. In neuron–astrocyte co-cultures, astrocytic DJ-1 knock-down reduced astrocyte process mitochondrial motility in untreated cells, but this effect was not maintained in the presence of rotenone. In the same co-cultures, astrocytic DJ-1 knock-down significantly reduced mitochondrial fusion in the astrocyte cell bodies, but not the processes, under the same conditions of rotenone treatment in which DJ-1 deficiency is known to impair astrocyte-mediated neuroprotection. Our studies therefore demonstrated the following new findings: (i) DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, (ii) astrocyte

  11. Lack of mitochondrial thioredoxin o1 is compensated by antioxidant components under salinity in Arabidopsis thaliana plants.

    Science.gov (United States)

    Calderón, Aingeru; Sánchez-Guerrero, Antonio; Ortiz-Espín, Ana; Martínez-Alcalá, Isabel; Camejo, Daymi; Jiménez, Ana; Sevilla, Francisca

    2018-02-15

    In a changing environment, plants are able to acclimate to the new conditions by regulating their metabolism through the antioxidant and redox systems involved in the stress response. Here we studied a mitochondrial thioredoxin in wild type (WT) Arabidopis thaliana and two Attrxo1 mutant lines grown in the absence or presence of 100 mM NaCl. Compared to WT plants, no evident phenotype was observed in the mutant plants in control condition, although they had higher number of stomata, loss of water, nitric oxide and carbonyl protein contents as well as higher activity of superoxide dismutase (SOD) and catalase enzymes than WT plants. Under salinity, the mutants presented lower water loss and higher stomatal closure, H 2 O 2 and lipid peroxidation levels accompanied by higher enzymatic activity of catalase and the different SOD isoenzymes compared to WT plants. These inductions may collaborate in the maintenance of plant integrity and growth observed under saline conditions, possibly as a way to compensate the lack of TRXo1. We discuss the potential of TRXo1 to influence the development of the whole plant under saline conditions, which have great value for the agronomy of plants growing under unfavourable environment. This article is protected by copyright. All rights reserved.

  12. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  13. Mitochondrial Disease

    OpenAIRE

    Bulent Kurt; Turgut Topal

    2013-01-01

    Mitochondria are the major energy source of cells. Mitochondrial disease occurs due to a defect in mitochondrial energy production. A valuable energy production in mitochondria depend a healthy interconnection between nuclear and mitochondrial DNA. A mutation in nuclear or mitochondrial DNA may cause abnormalities in ATP production and single or multiple organ dysfunctions, secondarily. In this review, we summarize mitochondrial physiology, mitochondrial genetics, and clinical expression and ...

  14. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

    Science.gov (United States)

    Yu, Chuanfei; Li, Yang; Holmes, Andrew; Szafranski, Karol; Faulkes, Chris G; Coen, Clive W; Buffenstein, Rochelle; Platzer, Matthias; de Magalhães, João Pedro; Church, George M

    2011-01-01

    The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  15. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

    Directory of Open Access Journals (Sweden)

    Chuanfei Yu

    Full Text Available The naked mole-rat (Heterocephalus glaber is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam, a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m, and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  16. 75 FR 71079 - Determination on Use of Cooperative Threat Reduction Funds in Pakistan and Afghanistan Under...

    Science.gov (United States)

    2010-11-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary Determination on Use of Cooperative Threat Reduction Funds in Pakistan and Afghanistan Under Section 1308 of the National Defense Authorization Act for... Threat Reduction (CTR) funds for the implementation of CTR programs in Pakistan and Afghanistan will...

  17. Reductive dechlorination of hexachlorocyclohexane (HCH) isomers in soil under anaerobic conditions

    NARCIS (Netherlands)

    Middeldorp, P.J.M.; Doesburg, van W.C.J.; Schraa, G.; Stams, A.J.M.

    2005-01-01

    The biological anaerobic reductive dechlorination of -hexachlorocyclohexane under methanogenic conditions was tested in a number of contaminated soil samples from two locations in the Netherlands. Soils from a heavily polluted location showed rapid dechlorination of -hexachlorocyclohexane to benzene

  18. m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

    Science.gov (United States)

    Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

    2018-05-01

    For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

  19. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

    Full Text Available Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines.

  20. 76 FR 27609 - Reduction of Foreign Tax Credit Limitation Categories Under Section 904(d); Correction

    Science.gov (United States)

    2011-05-12

    ... Reduction of Foreign Tax Credit Limitation Categories Under Section 904(d); Correction AGENCY: Internal... foreign tax credit limitation categories under section 904(d) of the Internal Revenue Code. DATES: This... in and Losses With Respect to the Pre-2007 Separate Category for High Withholding Tax Interest...

  1. Albania; Request for a Three-Year Arrangement Under the Poverty Reduction and Growth Facility

    OpenAIRE

    International Monetary Fund

    2002-01-01

    This paper evaluates Albania’s Request for a Three-Year Arrangement Under the Poverty Reduction and Growth Facility (PRGF). Sound financial policies under the previous PRGF-supported program helped stabilize the economy and restore high growth, but poverty remains widespread. The authorities’ medium-term strategy aims to promote inclusive growth, as the country continues to be plagued by poverty. The proposed PRGF arrangement is justified by the authorities’ commendable performance under the ...

  2. Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

    Science.gov (United States)

    Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

    2018-05-02

    Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

  3. β-Hydroxybutyrate Boosts Mitochondrial and Neuronal Metabolism but is not Preferred Over Glucose Under Activated Conditions.

    Science.gov (United States)

    Achanta, Lavanya B; Rowlands, Benjamin D; Thomas, Donald S; Housley, Gary D; Rae, Caroline D

    2017-06-01

    The ketone body, β-hydroxybutyrate (βOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which βOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U- 13 C]D-βOHB in conjunction with [1- 13 C]D-glucose under conditions of normo- and hypoglycaemia, as well as under high potassium (40 mmol/L K + ) depolarization in normo- and hypoglycaemic conditions. The contribution of βOHB to synthesis of GABA was also probed by inhibiting the synthesis of glutamine, a GABA precursor, with methionine sulfoximine (MSO). [U- 13 C]D-βOHB at lower concentrations (0.25 and 1.25 mmol/L) stimulated mitochondrial metabolism, producing greater total incorporation of label into glutamate and GABA but did not have a similar effect in the cytosolic compartment where labelling of glutamine was reduced at 1.25 mmol/L [U- 13 C]D-βOHB. At higher concentrations (2.5 mmol/L) [U- 13 C]D-βOHB inhibited metabolism of [1- 13 C]D-glucose, and reduced total label incorporation and total metabolite pools. When glucose levels were reduced, βOHB was able to partially restore the loss of glutamate and GABA caused by hypoglycaemia, but was not able to supplement levels of lactate, glutamine or alanine or to prevent the increase in aspartate. Under depolarizing conditions glucose was the preferred substrate over βOHB, even in hypoglycaemic conditions where comparatively less βOHB was incorporated except into aspartate isotopomers. Inhibition of glutamine synthesis with MSO had no significant effect on incorporation of label from [U- 13 C]D-βOHB into GABA C2,1 indicating that the majority of this GABA was synthesized in GABAergic neurons from [U- 13 C]D-βOHB rather than from Gln C4,5 imported from astrocytes.

  4. Comparisons of receive array interference reduction techniques under erroneous generalized transmit beamforming

    KAUST Repository

    Radaydeh, Redha Mahmoud

    2014-02-01

    This paper studies generalized single-stream transmit beamforming employing receive array co-channel interference reduction algorithms under slow and flat fading multiuser wireless systems. The impact of imperfect prediction of channel state information for the desired user spatially uncorrelated transmit channels on the effectiveness of transmit beamforming for different interference reduction techniques is investigated. The case of over-loaded receive array with closely-spaced elements is considered, wherein it can be configured to specified interfering sources. Both dominant interference reduction and adaptive interference reduction techniques for statistically ordered and unordered interferers powers, respectively, are thoroughly studied. The effect of outdated statistical ordering of the interferers powers on the efficiency of dominant interference reduction is studied and then compared against the adaptive interference reduction. For the system models described above, new analytical formulations for the statistics of combined signal-to-interference-plus-noise ratio are presented, from which results for conventional maximum ratio transmission and single-antenna best transmit selection can be directly deduced as limiting cases. These results are then utilized to obtain quantitative measures for various performance metrics. They are also used to compare the achieved performance of various configuration models under consideration. © 1972-2012 IEEE.

  5. Mitochondrial shaping cuts.

    Science.gov (United States)

    Escobar-Henriques, Mafalda; Langer, Thomas

    2006-01-01

    A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.

  6. Haiti; Request for Extension of the Arrangement Under the Poverty Reduction and Growth Facility: Staff Report

    OpenAIRE

    International Monetary Fund

    2011-01-01

    According to the fifth review of the Poverty Reduction and Growth Facility (PRGF) arrangement, the Haitian authorities remain committed to macroeconomic stability under the program. On completion of the fifth review of the PRGF, they requested a new three-year Extended Credit Facility (ECF) arrangement to help sustain economic growth and to preserve macroeconomic stability. The IMF Board approved a three-year arrangement for Haiti under the PRGF. This will help ensure that endorsement of poli...

  7. Reduction of Under-Determined Linear Systems by Sparce Block Matrix Technique

    DEFF Research Database (Denmark)

    Tarp-Johansen, Niels Jacob; Poulsen, Peter Noe; Damkilde, Lars

    1996-01-01

    numerical stability of the aforementioned reduction. Moreover the coefficient matrix for the equilibrium equations is typically very sparse. The objective is to deal efficiently with the full pivoting reduction of sparse rectangular matrices using a dynamic storage scheme based on the block matrix concept.......Under-determined linear equation systems occur in different engineering applications. In structural engineering they typically appear when applying the force method. As an example one could mention limit load analysis based on The Lower Bound Theorem. In this application there is a set of under......-determined equilibrium equation restrictions in an LP-problem. A significant reduction of computer time spent on solving the LP-problem is achieved if the equilib rium equations are reduced before going into the optimization procedure. Experience has shown that for some structures one must apply full pivoting to ensure...

  8. 48 CFR 301.106 - Office of Management and Budget approval under the Paperwork Reduction Act.

    Science.gov (United States)

    2010-10-01

    ... Issuance 301.106 Office of Management and Budget approval under the Paperwork Reduction Act. (a) The... approval from the Office of Management and Budget (OMB) before collecting the same information from 10 or... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Office of Management and...

  9. Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

    NARCIS (Netherlands)

    Frintrop, Linda; Liesbrock, Johanna; Paulukat, Lisa; Johann, Sonja; Kas, Martien J; Tolba, Rene; Heussen, Nicole; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2017-01-01

    OBJECTIVES: Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal

  10. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  11. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-01-01

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  12. Reduction Behaviors of Carbon Composite Iron Oxide Briquette Under Oxidation Atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki-Woo; Kim, Kang-Min; Kwon, Jae-Hong; Han, Jeong-Whan [Inha University, Incheon (Korea, Republic of); Son, Sang-Han [POSCO, Pohang (Korea, Republic of)

    2017-01-15

    The carbon composite iron oxide briquette (CCB) is considered a potential solution to the upcoming use of low grade iron resources in the ironmaking process. CCB is able to reduce raw material cost by enabling the use of low grade powdered iron ores and coal. Additionally, the fast reduction of iron oxides by direct contact with coal can be utilized. In this study, the reduction behaviors of CCB were investigated in the temperature range of 200-1200 ℃ under oxidizing atmosphere. Briquettes were prepared by mixing iron ore and coal in a weight ratio of 8:2. Then reduction experiments were carried out in a mixed gas atmosphere of N{sub 2}, O{sub 2}, and CO{sub 2}. Compressive strength tests and quantitative analysis were performed by taking samples at each target temperature. In addition, the reduction degree depending on the reaction time was evaluated by off-gas analysis during the reduction test. It was found that the compressive strength and the metallization degree of the reduced briquettes increased with increases in the reaction temperature and holding time. However, it tended to decrease when the re-oxidation phenomenon was caused by injected oxygen. The degree of reduction reached a maximum value in 26 minutes. Therefore, the re-oxidation phenomenon becomes dominant after 26 minutes.

  13. Applicability and Effectiveness of Closed Reduction of Nasal Fractures under Local Anesthesia

    Directory of Open Access Journals (Sweden)

    Vilela, Fernando

    2014-03-01

    Full Text Available Introduction A significant portion of patients treated in emergency departments have nasal fracture. It is important that the otolaryngologist know how to treat such damage. Objectives To evaluate the effectiveness of nasal fracture reduction under local anesthesia and tolerance to the procedure. Methods Twenty-four patients treated in the emergency department with closed reduction under local anesthesia were prospectively followed. Epidemiologic information and data regarding pain and complications during the management were noted. The degree of satisfaction was researched by visual analog scale. Results The majority of patients were male (75%, and the most common cause of injury was motor vehicle accident. We found a significant association between time to reduction and referred pain during the procedure. In patients in whom the procedure was delayed (over 3 days, there was less pain, and those who bled during the procedure had a shorter average time to reduction than the group of patients who did not bleed. Most patients were very satisfied, with more than 95% of these willing to undergo the same process again, if necessary. Conclusions The closed approach in the clinic under local anesthesia was effective and safe in restoration of the nose.

  14. Carbon Emission Reduction with Capital Constraint under Greening Financing and Cost Sharing Contract.

    Science.gov (United States)

    Qin, Juanjuan; Zhao, Yuhui; Xia, Liangjie

    2018-04-13

    Motivated by the industrial practices, this work explores the carbon emission reductions for the manufacturer, while taking into account the capital constraint and the cap-and-trade regulation. To alleviate the capital constraint, two contracts are analyzed: greening financing and cost sharing. We use the Stackelberg game to model four cases as follows: (1) in Case A1, the manufacturer has no greening financing and no cost sharing; (2) in Case A2, the manufacturer has greening financing, but no cost sharing; (3) in Case B1, the manufacturer has no greening financing but has cost sharing; and, (4) in Case B2, the manufacturer has greening financing and cost sharing. Then, using the backward induction method, we derive and compare the equilibrium decisions and profits of the participants in the four cases. We find that the interest rate of green finance does not always negatively affect the carbon emission reduction of the manufacturer. Meanwhile, the cost sharing from the retailer does not always positively affect the carbon emission reduction of the manufacturer. When the cost sharing is low, both of the participants' profits in Case B1 (under no greening finance) are not less than that in Case B2 (under greening finance). When the cost sharing is high, both of the participants' profits in Case B1 (under no greening finance) are less than that in Case B2 (under greening finance).

  15. Carbon Emission Reduction with Capital Constraint under Greening Financing and Cost Sharing Contract

    Science.gov (United States)

    Qin, Juanjuan; Zhao, Yuhui; Xia, Liangjie

    2018-01-01

    Motivated by the industrial practices, this work explores the carbon emission reductions for the manufacturer, while taking into account the capital constraint and the cap-and-trade regulation. To alleviate the capital constraint, two contracts are analyzed: greening financing and cost sharing. We use the Stackelberg game to model four cases as follows: (1) in Case A1, the manufacturer has no greening financing and no cost sharing; (2) in Case A2, the manufacturer has greening financing, but no cost sharing; (3) in Case B1, the manufacturer has no greening financing but has cost sharing; and, (4) in Case B2, the manufacturer has greening financing and cost sharing. Then, using the backward induction method, we derive and compare the equilibrium decisions and profits of the participants in the four cases. We find that the interest rate of green finance does not always negatively affect the carbon emission reduction of the manufacturer. Meanwhile, the cost sharing from the retailer does not always positively affect the carbon emission reduction of the manufacturer. When the cost sharing is low, both of the participants’ profits in Case B1 (under no greening finance) are not less than that in Case B2 (under greening finance). When the cost sharing is high, both of the participants’ profits in Case B1 (under no greening finance) are less than that in Case B2 (under greening finance). PMID:29652859

  16. [Changes in polarization of myometrial cells plasma and internal mitochondrial membranes under calixarenes action as inhibitors of plasma membrane Na+, K+-ATPase].

    Science.gov (United States)

    Danylovych, H V; Danylovych, Iu V; Kolomiiets', O V; Kosterin, S O; Rodik, R V; Cherenok, S O; Kal'chenko, V I; Chunikhin, O Iu; Horchev, V F; Karakhim, S O

    2012-01-01

    The influence of supramolecular macrocyclic compounds--calix[4]arenes C-97, C-99, C-107, which are ouabainomymetic high affinity inhibitors of Na+, K(+)-ATPase, on the polarization level of plasmic and mitochondrial membranes of rat uterine smooth muscle cells was investigated. The influence of these compounds on the myocytes characteristic size was studied. By using a confocal microscopy and specific for mitochondrial MitoTracker Orange CM-H2TMRos dye it was proved that the potential-sensitive fluorescent probe DiOC6(3) interacts with mitochondria. Artificial potential collapse of plasmic membrane in this case was modeled by myocytes preincubation with ouabain (1 mM). Further experiments performed using the method of flow cytometry with DiOC6(3) have shown that the compounds C-97, C-99 and C-107 at concentration 50-100 nM caused depolarization of the plasma membrane (at the level of 30% relative to control values) in conditions of artificial collapse of mitochondrial potential by myocytes preincubation in the presence of 5 mM of sodium azide. Under artificial sarcolemma depolarization by ouabain, calixarenes C-97, C-99 and C-107 at 100 nM concentrations caused a transient increase of mitochondrial membrane potential, that is 40% of the control level and lasted about 5 minutes. Calixarenes C-99 and C-107 caused a significant increase in fluorescence of myocytes in these conditions, which was confirmed by confocal microscopy too. It was proved by photon correlation spectroscopy method that the C-99 and C-107 caused an increase of characteristic size of myocytes.

  17. Laser-Induced Reductive Sintering of Nickel Oxide Nanoparticles under Ambient Conditions

    KAUST Repository

    Paeng, Dongwoo; Lee, Daeho; Yeo, Junyeob; Yoo, Jae-Hyuck; Allen, Frances I.; Kim, Eunpa; So, Hongyun; Park, Hee K.; Minor, Andrew M.; Grigoropoulos, Costas P.

    2015-01-01

    © 2015 American Chemical Society. This work is concerned with the kinetics of laser-induced reductive sintering of nonstoichiometric crystalline nickel oxide (NiO) nanoparticles (NPs) under ambient conditions. The mechanism of photophysical reductive sintering upon irradiation using a 514.5 nm continuous-wave (CW) laser on NiO NP thin films has been studied through modulating the laser power density and illumination time. Protons produced due to high-temperature decomposition of the solvent present in the NiO NP ink, oxygen vacancies in the NiO NPs, and electronic excitation in the NiO NPs by laser irradiation all affect the early stage of the reductive sintering process. Once NiO NPs are reduced by laser irradiation to Ni, they begin to coalesce, forming a conducting material. In situ optical and electrical measurements during the reductive sintering process take advantage of the distinct differences between the oxide and the metallic phases to monitor the transient evolution of the process. We observe four regimes: oxidation, reduction, sintering, and reoxidation. A characteristic time scale is assigned to each regime.

  18. Growing Pereskia aculeata under intermittent irrigation according to levels of matric potential reduction

    Directory of Open Access Journals (Sweden)

    Carla Regina Amorim dos Anjos Queiroz

    2015-03-01

    Full Text Available Pereskia aculeata Mill., popularly known in Brazil as “Ora-pro-nobis”, is an unconventional edible vegetable. Taking into account its potential for agronomic cultivation, this study aimed to evaluate the growth response of this plant under intermittent drought through controlled reductions in the substrate matric potential, in a greenhouse. Treatments consisted of adding to the pots a volume of water to raise the matric potential to -5 kPa, according to the water retention curve in the substrate, whenever the mean substrate matric potential reached values between -10 kPa and -70 kPa, depending on the treatment. At 140 days after transplanting, leaf area and dry mass of leaves, stems and roots were determined. The intermittent reduction of the matric potential in the root zone of “Ora-pro-nobis” affected less the dry mass accumulation in leaves (reduction of 21.4% than in stems (reduction of 48.1% and roots (reduction of 63.7%, and that is interesting because leaves are the main commercial product of this plant. The treatment also modified the proportionality of dry mass allocation among plant parts and reduced the photosynthetic efficiency of leaves, fact evidenced by the linear increase of the specific leaf area (0.63 cm2 g-1kPa-1 and leaf area ratio (0.39 cm-2 g-1kPa-1, although not affecting directly the leaf area.

  19. Laser-Induced Reductive Sintering of Nickel Oxide Nanoparticles under Ambient Conditions

    KAUST Repository

    Paeng, Dongwoo

    2015-03-19

    © 2015 American Chemical Society. This work is concerned with the kinetics of laser-induced reductive sintering of nonstoichiometric crystalline nickel oxide (NiO) nanoparticles (NPs) under ambient conditions. The mechanism of photophysical reductive sintering upon irradiation using a 514.5 nm continuous-wave (CW) laser on NiO NP thin films has been studied through modulating the laser power density and illumination time. Protons produced due to high-temperature decomposition of the solvent present in the NiO NP ink, oxygen vacancies in the NiO NPs, and electronic excitation in the NiO NPs by laser irradiation all affect the early stage of the reductive sintering process. Once NiO NPs are reduced by laser irradiation to Ni, they begin to coalesce, forming a conducting material. In situ optical and electrical measurements during the reductive sintering process take advantage of the distinct differences between the oxide and the metallic phases to monitor the transient evolution of the process. We observe four regimes: oxidation, reduction, sintering, and reoxidation. A characteristic time scale is assigned to each regime.

  20. Inhibition of CLIC4 enhances autophagy and triggers mitochondrial and ER stress-induced apoptosis in human glioma U251 cells under starvation.

    Directory of Open Access Journals (Sweden)

    Jiateng Zhong

    Full Text Available CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER, nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation.

  1. Mitochondrial myopathies.

    Science.gov (United States)

    DiMauro, Salvatore

    2006-11-01

    Our understanding of mitochondrial diseases (defined restrictively as defects of the mitochondrial respiratory chain) is expanding rapidly. In this review, I will give the latest information on disorders affecting predominantly or exclusively skeletal muscle. The most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency and mutations in genes controlling mitochondrial DNA abundance and structure, such as POLG, TK2, and MPV17. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with decreased amount and altered structure of cardiolipin, the main phospholipid of the inner mitochondrial membrane, but a secondary impairment of respiratory chain function is plausible. The role of mutations in protein-coding genes of mitochondrial DNA in causing isolated myopathies has been confirmed. Mutations in tRNA genes of mitochondrial DNA can also cause predominantly myopathic syndromes and--contrary to conventional wisdom--these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, cramps, recurrent myoglobinuria, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.

  2. Unique mitochondrial localization of arginase 1 and 2 in hepatocytes of air-breathing walking catfish, Clarias batrachus and their differential expression patterns under hyper-ammonia stress.

    Science.gov (United States)

    Banerjee, Bodhisattwa; Koner, Debaprasad; Lal, Priyanka; Saha, Nirmalendu

    2017-07-30

    Arginase (ARG) catalyzes the final step of ornithine-urea cycle (OUC) leading to a conversion of L-arginine to L-ornithine and urea. Several isoforms of ARG have been reported in vertebrates, out of which the two predominant isoforms are the cytosolic ARG1 and the mitochondrial ARG2. The air-breathing walking catfish (Clarias batrachus) is frequently being challenged by different environmental insults such as hyper-ammonia, dehydration and osmotic stresses in their natural habitats throughout the year. The present study investigated the active presence of ARG1 and ARG2 isoforms in hepatocytes along with unique localization of both the isoforms inside the mitochondria, and also their specific expression patterns under hyper-ammonia stress (5mM NH 4 Cl) in isolated hepatocytes of walking catfish. Initially, full length sequences of both arg1 and arg2 genes were obtained by RACE-PCR. Studies on molecular characterization demonstrated the presence of all the conserved amino acids required for stability and activity of binuclear metal center in both the isoforms. Phylogenetic analysis of the amino acid sequences of ARG isoforms showed a differentiation of the ARG1 and ARG2 into two distinct clusters with their respective isoforms from other species. Most interestingly, both the isoforms of ARG in hepatocytes were found to be localized inside the mitochondria as evidenced by the presence of mitochondrial target peptide (mTP) in N-terminal of the derived amino acid sequences, and exclusive localization of ARG activity in the mitochondrial fraction. This was additionally confirmed by Western blot analysis of ARGs in mitochondrial and cytosolic fractions, and by immunocytochemical analysis in isolated hepatocytes. Although the possible reasons associated with the presence of both the isoforms of ARGs inside the mitochondria is not clearly understood, perhaps this mitochondrial localization of ARG is functionally advantageous in this catfish for the synthesis of N

  3. Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

    Science.gov (United States)

    Frintrop, Linda; Liesbrock, Johanna; Paulukat, Lisa; Johann, Sonja; Kas, Martien J; Tolba, Rene; Heussen, Nicole; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-04-01

    Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA). Female rats had 24 h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks. In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression. Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.

  4. Fullerene-catalyzed reduction of azo derivatives in water under UV irradiation

    KAUST Repository

    Guo, Yong; Li, Wengang; Yan, Jingjing; Moosa, Basem; Amad, Maan H.; Werth, Charles; Khashab, Niveen M.

    2012-01-01

    Metal-free fullerene (C60) was found to be an effective catalyst for the reduction of azo groups in basic aqueous solution under UV irradiation in the presence of NaBH4. Use of NaBH4 by itself is not sufficient to reduce the azo dyes without the assistance of a metal catalyst such as Pd and Ag. Experimental and theoretical results suggest that C 60 catalyzes this reaction by using its vacant orbital to accept the electron in the bonding orbital of azo dyes, which leads to the activation of the N=N bond. UV irradiation increases the ability of C60 to interact with electron-donor moieties in azo dyes. Filling a vacancy: Experimental and theoretical methods have been combined to show that C60-catalyzed reductions of azo compounds form aromatic amines under UV irradiation (see scheme). The obtained results show that C60 acts as an electron acceptor to catalyze the reduction of azo compounds, and the role of UV irradiation is to increase the ability of C60 to interact with electron-donor moieties in azo compounds. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Fullerene-catalyzed reduction of azo derivatives in water under UV irradiation

    KAUST Repository

    Guo, Yong

    2012-09-27

    Metal-free fullerene (C60) was found to be an effective catalyst for the reduction of azo groups in basic aqueous solution under UV irradiation in the presence of NaBH4. Use of NaBH4 by itself is not sufficient to reduce the azo dyes without the assistance of a metal catalyst such as Pd and Ag. Experimental and theoretical results suggest that C 60 catalyzes this reaction by using its vacant orbital to accept the electron in the bonding orbital of azo dyes, which leads to the activation of the N=N bond. UV irradiation increases the ability of C60 to interact with electron-donor moieties in azo dyes. Filling a vacancy: Experimental and theoretical methods have been combined to show that C60-catalyzed reductions of azo compounds form aromatic amines under UV irradiation (see scheme). The obtained results show that C60 acts as an electron acceptor to catalyze the reduction of azo compounds, and the role of UV irradiation is to increase the ability of C60 to interact with electron-donor moieties in azo compounds. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier

    Directory of Open Access Journals (Sweden)

    Yue-Hong Zhang

    2017-07-01

    Full Text Available AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123 alone and in the presence of P-gp inhibitor (Tariquidar using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

  7. Mitochondrial C4375T mutation might be a molecular risk factor in a maternal Chinese hypertensive family under haplotype C.

    Science.gov (United States)

    Chen, Hong; Sun, Min; Fan, Zhen; Tong, Maoqing; Chen, Guodong; Li, Danhui; Ye, Jihui; Yang, Yumin; Zhu, Yongding; Zhu, Jianhua

    2017-12-04

    Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.

  8. EdiPy: a resource to simulate the evolution of plant mitochondrial genes under the RNA editing.

    Science.gov (United States)

    Picardi, Ernesto; Quagliariello, Carla

    2006-02-01

    EdiPy is an online resource appropriately designed to simulate the evolution of plant mitochondrial genes in a biologically realistic fashion. EdiPy takes into account the presence of sites subjected to RNA editing and provides multiple artificial alignments corresponding to both genomic and cDNA sequences. Each artificial data set can successively be submitted to main and widespread evolutionary and phylogenetic software packages such as PAUP, Phyml, PAML and Phylip. As an online bioinformatic resource, EdiPy is available at the following web page: http://biologia.unical.it/py_script/index.html.

  9. Effects of sulfur dioxide and nitric oxide on mercury oxidation and reduction under homogeneous conditions

    Energy Technology Data Exchange (ETDEWEB)

    Yongxin Zhao; Michael D. Mann; Edwin S. Olson; John H. Pavlish; Grant E. Dunham [University of North Dakota, Grand Forks, ND (United States). Department of Chemical Engineering

    2006-05-15

    This paper is particularly related to elemental mercury (Hg{sup 0}) oxidation and divalent mercury (Hg{sup 2+} reduction under simulated flue gas conditions in the presence of nitric oxide (NO) and sulfur dioxide (SO{sub 2}). As a powerful oxidant and chlorinating reagent, Cl{sub 2} has the potential for Hg oxidation. However, the detailed mechanism for the interactions, especially among chlorine (Cl)-containing species, SO{sub 2}, NO, as well as H{sub 2}O, remains ambiguous. Research described in this paper therefore focused on the impacts of SO{sub 2} and NO on Hg{sup 0} oxidation and Hg{sup 2+} reduction with the intent of unraveling unrecognized interactions among Cl species, SO{sub 2}, and NO most importantly in the presence of H{sub 2}O. The experimental results demonstrated that SO{sub 2} and NO had pronounced inhibitory effects on Hg{sup 0} oxidation at high temperatures when H{sub 2}O was also present in the gas blend. Such a demonstration was further confirmed by the reduction of Hg{sup 2+} back into its elemental form. Data revealed that SO{sub 2} and NO were capable of promoting homogeneous reduction of Hg{sup 2+} to Hg{sup 0} with H{sub 2}O being present. However, the above inhibition or promotion disappeared under homogeneous conditions when H{sub 2}O was removed from the gas blend. 23 refs., 8 figs.

  10. 77 FR 75195 - Notice of Approval for South Carolina for Avoidance of 2012 Credit Reduction Under the Federal...

    Science.gov (United States)

    2012-12-19

    ... for Avoidance of 2012 Credit Reduction Under the Federal Unemployment Tax Act AGENCY: Employment and... Unemployment Tax Act (FUTA) provide that employers in a state that has an outstanding balance of advances under... subject to a reduction in credits otherwise available against the FUTA tax for a calendar year, if a...

  11. Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

    Directory of Open Access Journals (Sweden)

    Stephen A Brose

    2016-11-01

    Full Text Available Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA biosynthesis (FAS followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FAS maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FAS inhibition on NADH2+/NAD+ and NADPH2+/NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FAS inhibitors, TOFA (inhibits Acetyl-CoA carboxylase and cerulenin (inhibits FA synthase, increased NADH2+/NAD+ and NADPH2+/NADP+ ratios under hypoxia. Further, FAS inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

  12. Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.

    Science.gov (United States)

    Brose, Stephen A; Golovko, Svetlana A; Golovko, Mikhail Y

    2016-01-01

    Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

  13. Microbial sulfate reduction under sequentially acidic conditions in an upflow anaerobic packed bed bioreactor

    Energy Technology Data Exchange (ETDEWEB)

    Jong, T.; Parry, D.L. [Charles Darwin University, Darwin, NT (Australia). Faculty for Educational Health & Science

    2006-07-15

    The aim of this study was to operate an upflow anaerobic packed bed reactor (UAPB) containing sulfate reducing bacteria (SRB) under acidic conditions similar to those found in acid mine drainage (AMD). The UAPB was filled with sand and operated under continuous flow at progressively lower pH and was shown to be capable of supporting sulfate reduction at pH values of 6.0, 5.0, 4.5, 4.0 and 3.5 in a synthetic medium containing 53.5 mmol l{sup -1} lactate. Sulfate reduction rates of 553-1052 mmol m{sup -3} d{sup -1} were obtained when the influent solution pH was progressively lowered from pH 6.0 to 4.0, under an optimal flow rate of 2.61 ml min{sup -1}. When the influent pH was further lowered to pH 3.5, sulfate reduction was substantially reduced with only about 1% sulfate removed at a rate of 3.35 mmol m{sup -3} d{sup -1} after 20 days of operation. However, viable SRB were recovered from the column, indicating that the SRB population was capable of surviving and metabolizing at low levels even at pH 3.5 conditions for at least 20 days. The changes in conductivity in the SRB column did not always occur with changes in pH and redox potential, suggesting that conductivity measurements may be more sensitive to SRB activity and could be used as an additional tool for monitoring SRB activity. The bioreactor containing SRB was able to reduce sulfate and generate alkalinity even when challenged with influent as low as pH 3.5, indicating that such treatment systems have potential for bioremediating highly acidic, sulfate contaminated waste waters.

  14. NO reduction by CO over noble-metal catalysts under cycled feedstreams

    International Nuclear Information System (INIS)

    Muraki, H.; Fujitani, Y.

    1986-01-01

    The reduction of NO with CO was studied over α-Al/sub 2/O/sub 3/-supported Pt, Pd, Rh, Ru, and Ir catalysts. The activities were measured by using cycled feeds and steady noncycled feed. The activity sequence of the catalysts tested was Rh > Ru > Ir > Pd > Pt. The activities of Pt and Pd catalysts were increased under the cycled feed. The periodic operation effect on the Pt catalyst was more predominant than that on the Pd catalyst. The order of periodic operation effect corresponded to the order of their susceptibility to CO self-poisoning

  15. Topotactic reduction of YBa2Cu4O8 under the electron beam

    International Nuclear Information System (INIS)

    Domenges, B.; Hervieu, M.; Raveau, B.; Karpinski, J.; Kaldis, E.; Rusiecki, S.

    1991-01-01

    The stability of the high oxygen-pressure 80K-superconductor YBa 2 Cu 4 O 8 under the electron beam was studied by high resolution electron microscopy. Several topotactic reductions were observed for which models are proposed. The most important feature deals with the topotactic transformation of YBa 2 Cu 4 O 8 into the 125-type phase Y 1+x Ba 2+2x Cu 5-3x O 9 (x = 0.14) involving order-disorder phenomena

  16. Oxidation and Reduction of Liquid SnPb (60/40) under Ambient and Vacuum Conditions

    DEFF Research Database (Denmark)

    Kuhmann, Jochen Friedrich; Maly, K.; Preuss, A.

    1998-01-01

    One of the most straightforward approaches to fluxless solder bonding is using vacuum conditions to prevent further oxidation and, where needed, to reduce solder oxides by the use of molecular hydrogen (H-2).(1-3) This study On oxidation and reduction of solder oxides on SnPb (60/40) is aimed...... to provide a better understanding for fluxless solder bonding applications under controlled atmospheric conditions; By means of scanning Auger spectroscopy it is shown, that growth of oxide films on metallic SnPb above the eutectic temperature can be significantly reduced by decreasing the O-2 partial...

  17. Expression of the nuclear gene TaF(A)d is under mitochondrial retrograde regulation in anthers of male sterile wheat plants with timopheevii cytoplasm.

    Science.gov (United States)

    Xu, Pei; Yang, Yuwen; Zhang, Zhengzhi; Chen, Weihua; Zhang, Caiqin; Zhang, Lixia; Zou, Sixiang; Ma, Zhengqiang

    2008-01-01

    Alterations of mitochondrial-encoded subunits of the F(o)F(1)-ATP synthase are frequently associated with cytoplasmic male sterility (CMS) in plants; however, little is known about the relationship of the nuclear encoded subunits of this enzyme with CMS. In the present study, the full cDNA of the gene TaF(A)d that encodes the putative F(A)d subunit of the F(o)F(1)-ATP synthase was isolated from the wheat (Triticum aestivum) fertility restorer '2114' for timopheevii cytoplasm-based CMS. The deduced 238 amino acid polypeptide is highly similar to its counterparts in dicots and other monocots but has low homology to its mammalian equivalents. TaF(A)d is a single copy gene in wheat and maps to the short arm of the group 6 chromosomes. Transient expression of the TaF(A)d-GFP fusion in onion epidermal cells demonstrated TaF(A)d's mitochondrial location. TaF(A)d was expressed abundantly in stem, leaf, anther, and ovary tissues of 2114. Nevertheless, its expression was repressed in anthers of CMS plants with timopheevii cytoplasm. Genic male sterility did not affect its expression in anthers. The expression of the nuclear gene encoding the 20 kDa subunit of F(o) was down-regulated in a manner similar to TaF(A)d in the T-CMS anthers while that of genes encoding the 6 kDa subunit of F(o) and the gamma subunit of F(1) was unaffected. These observations implied that TaF(A)d is under mitochondrial retrograde regulation in the anthers of CMS plants with timopheevii cytoplasm.

  18. Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease.

    Science.gov (United States)

    Ay, Muhammet; Luo, Jie; Langley, Monica; Jin, Huajun; Anantharam, Vellareddy; Kanthasamy, Arthi; Kanthasamy, Anumantha G

    2017-06-01

    Quercetin, one of the major flavonoids in plants, has been recently reported to have neuroprotective effects against neurodegenerative processes. However, since the molecular signaling mechanisms governing these effects are not well clarified, we evaluated quercetin's effect on the neuroprotective signaling events in dopaminergic neuronal models and further tested its efficacy in the MitoPark transgenic mouse model of Parkinson's disease (PD). Western blot analysis revealed that quercetin significantly induced the activation of two major cell survival kinases, protein kinase D1 (PKD1) and Akt in MN9D dopaminergic neuronal cells. Furthermore, pharmacological inhibition or siRNA knockdown of PKD1 blocked the activation of Akt, suggesting that PKD1 acts as an upstream regulator of Akt in quercetin-mediated neuroprotective signaling. Quercetin also enhanced cAMP response-element binding protein phosphorylation and expression of the cAMP response-element binding protein target gene brain-derived neurotrophic factor. Results from qRT-PCR, Western blot analysis, mtDNA content analysis, and MitoTracker assay experiments revealed that quercetin augmented mitochondrial biogenesis. Quercetin also increased mitochondrial bioenergetics capacity and protected MN9D cells against 6-hydroxydopamine-induced neurotoxicity. To further evaluate the neuroprotective efficacy of quercetin against the mitochondrial dysfunction underlying PD, we used the progressive dopaminergic neurodegenerative MitoPark transgenic mouse model of PD. Oral administration of quercetin significantly reversed behavioral deficits, striatal dopamine depletion, and TH neuronal cell loss in MitoPark mice. Together, our findings demonstrate that quercetin activates the PKD1-Akt cell survival signaling axis and suggest that further exploration of quercetin as a promising neuroprotective agent for treating PD may offer clinical benefits. © 2017 International Society for Neurochemistry.

  19. Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

    Science.gov (United States)

    Chaves, Gabriela Costa; Hasenclever, Lia; Osorio-de-Castro, Claudia Garcia Serpa; Oliveira, Maria Auxiliadora

    2016-01-01

    ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation. PMID:26759969

  20. Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Costa Chaves

    2015-01-01

    Full Text Available ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement, 2012 and 2013 (after the establishment of the Partnership. CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

  1. Decomposition and reduction of N2O over Limestone under FBC Conditions

    DEFF Research Database (Denmark)

    Johnsson, Jan Erik; Jensen, Anker; Vaaben, Rikke

    1997-01-01

    The addition of limestone for sulfur retention in FBC has in many cases been observed to influence the emission of N2O. The catalytic activity of N2O over calcined Stevns Chalk for decomposition of N2O in a laboratory fixed bed quartz reactor was measured. It was found that calcined Stevns Chalk...... is a very active catalyst for N2O decomposition in an inert atmosphere, and the presence of 3 vol% CO increased the rate of N2O destruction by a factor of 5 due to the catalytic reduction of N2O by CO. The activity decreased with increasing CO2 concentration, and uncalcined or recarbonated limestone had...... negligible activity. Sulfation of the calcined limestone under oxidizing conditions lowered the activity, however sulfidation under reducing conditions showed that CaS is an active catalyst for the reduction of N2O by CO. Without CO present a gas solid reaction between N2O and CaS takes place and SO2...

  2. Probing adsorption phenomena on a single crystal Pt-alloy surface under oxygen reduction reaction conditions

    DEFF Research Database (Denmark)

    Bondarenko, Alexander S.; Stephens, Ifan E.L.; Bech, Lone

    2012-01-01

    The adsorption dynamics of *OH and *O species at Pt(111) and Cu/Pt(111) near-surface alloy (NSA) surfaces in oxygen-free and O2-saturated 0.1M HClO4 was investigated. Subsurface Cu modifies the electronic structure at the Pt(111) surface resulting in weaker bonding to adsorbates like *OH, *H or *O....... This provides a basis for the high oxygen reduction activity of the NSA, as predicted by density functional theory calculations. The shift in *OH adsorption of around 0.16V towards more positive potentials can be clearly monitored in absence of O2 and under the oxygen reduction reaction (ORR) conditions...... for the Cu/Pt(111) NSA. In both cases, for Pt(111) and NSA, the *OH(*O) adsorption dynamics is very similar in the absence of oxygen and under ORR conditions. Therefore, theoretical assumptions about the coverage of adsorbates in the absence of oxygen can be reasonably extrapolated to the situation when...

  3. Probing adsorption phenomena on a single crystal Pt-alloy surface under oxygen reduction reaction conditions

    International Nuclear Information System (INIS)

    Bondarenko, Alexander S.; Stephens, Ifan E.L.; Bech, Lone; Chorkendorff, Ib

    2012-01-01

    Highlights: ► Impedance spectroscopy of Cu/Pt(1 1 1) near-surface alloy and Pt(1 1 1). ► Presence of oxygen changes little the adsorption dynamics. ► Adsorption dynamics similar on alloy and Pt(1 1 1). ► Electrosorption phenomena on alloy shifted in potential, relative to Pt(1 1 1). - Abstract: The adsorption dynamics of *OH and *O species at Pt(1 1 1) and Cu/Pt(1 1 1) near-surface alloy (NSA) surfaces in oxygen-free and O 2 -saturated 0.1 M HClO 4 was investigated. Subsurface Cu modifies the electronic structure at the Pt(1 1 1) surface resulting in weaker bonding to adsorbates like *OH, *H or *O. This provides a basis for the high oxygen reduction activity of the NSA, as predicted by density functional theory calculations. The shift in *OH adsorption of around 0.16 V towards more positive potentials can be clearly monitored in absence of O 2 and under the oxygen reduction reaction (ORR) conditions for the Cu/Pt(1 1 1) NSA. In both cases, for Pt(1 1 1) and NSA, the *OH(*O) adsorption dynamics is very similar in the absence of oxygen and under ORR conditions. Therefore, theoretical assumptions about the coverage of adsorbates in the absence of oxygen can be reasonably extrapolated to the situation when oxygen reduction takes place at the surface. A ∼5-fold improvement in the ORR activity over the Pt(1 1 1) at 0.9 V (RHE) was measured for the Cu/Pt(1 1 1) near-surface alloy.

  4. Mitochondrial Myopathies

    Science.gov (United States)

    ... noting “soft signs” in unaffected relatives. These include deaf- ness, short stature, migraine headaches and PEO. Muscle ... mitochondrial defects and provide valuable information for family planning. Perhaps most important, knowing the genetic defects that ...

  5. Inhibiting c-Jun N-terminal kinase partially attenuates caffeine-dependent cell death without alleviating the caffeine-induced reduction in mitochondrial respiration in C2C12 skeletal myotubes

    International Nuclear Information System (INIS)

    Downs, R.M.; Hughes, M.A.; Kinsey, S.T.; Johnson, M.C.; Baumgarner, B.L.

    2016-01-01

    Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration. We specifically examined the role of c-Jun N-terminal kinase (JNK), which has previously been shown to simultaneously increase caspase-dependent cell death and reduce mitochondrial respiration in other mammalian cell lines. We found that caffeine promoted a dose-dependent increase in cell death in multinucleated myotubes but did not in mononucleated myoblasts. The addition of 10 μM Z-DEVD-FMK, a specific inhibitor of executioner caspases, completely inhibited caffeine-dependent cell death. Further, the addition of 400 μM dantrolene, a specific ryanodine receptor (RYR) inhibitor, prevented the caffeine-dependent increase in cell death and the reduction in basal and maximal OCR. We also discovered that caffeine treatment significantly increased the phosphorylation of JNK and that the addition of 30 μM SP600125 (JNKi), a specific JNK inhibitor, partially attenuated caffeine-induced cell death without preventing the caffeine-dependent reduction in basal and maximal OCR. Our results suggest that JNK partially mediates the increase in caspase-dependent cell death but does not contribute to reduced mitochondrial respiration in caffeine-treated skeletal muscle cells. We conclude that caffeine increased cell death and reduced mitochondrial respiration in a calcium-dependent manner by activating the RYR and promoting reticular calcium release. - Highlights: • Caffeine

  6. The development of a laterally confined laboratory fan delta under sediment supply reduction

    Science.gov (United States)

    Zhang, Xiaofeng; Wang, Siqiang; Wu, Xi; Xu, Shun; Li, Zhangyong

    2016-03-01

    In previous fan delta experiments, the effect of lateral confinement was generally ignored as these fans were usually unconfined with semiconical geometries. However, in gorge areas, fan development is usually laterally confined by valley walls. This study investigates autogenic processes of fan deltas in a laterally confined experimental tank. The experiment is divided into three phases. The sediment supply is held constant within each phase, so the autogenic processes of the fan are separated from the allogenic forcings. Results indicate that laterally confined fan deltas have higher progradation and aggradation potential, more regular channel braiding, and more even transverse sedimentation than unconfined fans. Besides, responses of fan deltas to sediment supply reduction are investigated in this research. At the initiation of the second and third phases, sediment feed rates are instantaneously reduced so that the allogenic forcings are predominant. Observations show that under sediment supply reduction, channelization on fan deltas are more pronounced and durations of the fluvial cycles are longer. The adjustment of fan morphology becomes slower as the self-regulation capacity of the fan decreases with reduced sediment supply.

  7. Reductive transformation and inhibitory effect of ethylene under methanogenic conditions in peat-soil

    DEFF Research Database (Denmark)

    Elsgaard, Lars

    2013-01-01

    Ethylene (C2H4), which is a potent gaseous plant hormone, has often been found to accumulate in anoxic soils where pathways of anaerobic C2H4 oxidation are so far unknown and other C2H4 transformation processes are uncommon. The present study shows that ethylene was reduced almost...... stoichiometrically (89–92%) to ethane (C2H6) in peat-soil microcosms incubated under methanogenic conditions. Methanogenesis started after a prolonged anoxic lag-phase (>29 weeks) where added ethylene prevailed despite the availability of nitrate (NO3−) as an alternative electron acceptor. Methanogenesis, as well...... as ethylene reduction to ethane, was inhibited by 90% at 1% oxygen. Likewise, methanogenesis and ethane formation was gradually inhibited (to a similar extent) by increasing ethylene concentrations above 0.2%; this inhibition eventually reached 90–95% at 2.2–4.5% C2H4. The present results extend the known...

  8. Communication: Enhanced oxygen reduction reaction and its underlying mechanism in Pd-Ir-Co trimetallic alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Hyung Chul; Hwang, Gyeong S., E-mail: gshwang@che.utexas.edu [Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712 (United States); Manogaran, Dhivya [Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712 (United States); Lee, Kang Hee; Jin, Seon-ah; You, Dae Jong; Pak, Chanho [Energy Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Suwon (Korea, Republic of); Kwon, Kyungjung [Department of Energy and Mineral Resources Engineering, Sejong University, Seoul 143-747 (Korea, Republic of)

    2013-11-28

    Based on a combined density functional theory and experimental study, we present that the electrochemical activity of Pd{sub 3}Co alloy catalysts toward oxygen reduction reaction (ORR) can be enhanced by adding a small amount of Ir. While Ir tends to favorably exist in the subsurface layers, the underlying Ir atoms are found to cause a substantial modification in the surface electronic structure. As a consequence, we find that the activation barriers of O/OH hydrogenation reactions are noticeably lowered, which would be mainly responsible for the enhanced ORR activity. Furthermore, our study suggests that the presence of Ir in the near-surface region can suppress Co out-diffusion from the Pd{sub 3}Co substrate, thereby improving the durability of Pd-Ir-Co catalysts. We also discuss the relative roles played by Ir and Co in enhancing the ORR activity relative to monometallic Pd catalysts.

  9. Biological reductive dechlorination of tetrachloroethylene and trichloroethylene to ethylene under methanogenic conditions

    International Nuclear Information System (INIS)

    Freedman, D.L.; Gossett, J.M.

    1989-01-01

    A biological process for remediation of groundwater contaminated with tetrachloroethylene (PCE) and trichloroethylene (TCE) can only be applied if the transformation products are environmentally acceptable. Studies with enrichment cultures of PCE- and TCE-degrading microorganisms provide evidence that, under methanogenic conditions, mixed cultures are able to completely dechlorinate PCE and TCE to ethylene, a product which is environmentally acceptable. Radiotracer studies with [ 14 C]PCE indicated that [ 14 C]ethylene was the terminal product; significant conversion to 14 CO 2 or 14 CH 4 was not observed. The rate-limiting step in the pathway appeared to be conversion of vinyl chloride to ethylene. To sustain reductive dechlorination of PCE and TCE, it was necessary to supply an electron donor; methanol was the most effective, although hydrogen, formate, acetate, and glucose also served. Studies with the inhibitor 2-bromoethanesulfonate suggested that methanogens played a key role in the observed biotransformations of PCE and TCE

  10. Evidence of enzymatic catalysis of oxygen reduction on stainless steels under marine biofilm.

    Science.gov (United States)

    Faimali, Marco; Benedetti, Alessandro; Pavanello, Giovanni; Chelossi, Elisabetta; Wrubl, Federico; Mollica, Alfonso

    2011-04-01

    Cathodic current trends on stainless steel samples with different surface percentages covered by biofilm and potentiostatically polarized in natural seawater were studied under oxygen concentration changes, temperature increases, and additions of enzymic inhibitors to the solution. The results showed that on each surface fraction covered by biofilm the oxygen reduction kinetics resembled a reaction catalyzed by an immobilised enzyme with high oxygen affinity (apparent Michaelis-Menten dissociation constant close to K(O(2))(M)  ≈ 10 μM) and low activation energy (W ≈ 20 KJ mole(-1)). The proposed enzyme rapidly degraded when the temperature was increased above the ambient (half-life time of ∼1 day at 25°C, and of a few minutes at 50°C). Furthermore, when reversible enzymic inhibitors (eg sodium azide and cyanide) were added, the cathodic current induced by biofilm growth was inhibited.

  11. Communication: Enhanced oxygen reduction reaction and its underlying mechanism in Pd-Ir-Co trimetallic alloys

    International Nuclear Information System (INIS)

    Ham, Hyung Chul; Hwang, Gyeong S.; Manogaran, Dhivya; Lee, Kang Hee; Jin, Seon-ah; You, Dae Jong; Pak, Chanho; Kwon, Kyungjung

    2013-01-01

    Based on a combined density functional theory and experimental study, we present that the electrochemical activity of Pd 3 Co alloy catalysts toward oxygen reduction reaction (ORR) can be enhanced by adding a small amount of Ir. While Ir tends to favorably exist in the subsurface layers, the underlying Ir atoms are found to cause a substantial modification in the surface electronic structure. As a consequence, we find that the activation barriers of O/OH hydrogenation reactions are noticeably lowered, which would be mainly responsible for the enhanced ORR activity. Furthermore, our study suggests that the presence of Ir in the near-surface region can suppress Co out-diffusion from the Pd 3 Co substrate, thereby improving the durability of Pd-Ir-Co catalysts. We also discuss the relative roles played by Ir and Co in enhancing the ORR activity relative to monometallic Pd catalysts

  12. Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

    International Nuclear Information System (INIS)

    Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

    2010-01-01

    Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

  13. 14 CFR 11.201 - Office of Management and Budget (OMB) control numbers assigned under the Paperwork Reduction Act.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Office of Management and Budget (OMB) control numbers assigned under the Paperwork Reduction Act. 11.201 Section 11.201 Aeronautics and Space... PROCEDURES Paperwork Reduction Act Control Numbers § 11.201 Office of Management and Budget (OMB) control...

  14. 78 FR 76327 - Notice of Approval of South Carolina's Application for Avoidance of 2013 Credit Reduction Under...

    Science.gov (United States)

    2013-12-17

    ... Application for Avoidance of 2013 Credit Reduction Under the Federal Unemployment Tax Act AGENCY: Employment... Federal Unemployment Tax Act (FUTA) provide that employers in a state that has an outstanding balance of... consecutive years are subject to a reduction in credits otherwise available against the FUTA tax for the...

  15. Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking.

    Science.gov (United States)

    Stangenberg, Stefanie; Nguyen, Long T; Chen, Hui; Al-Odat, Ibrahim; Killingsworth, Murray C; Gosnell, Martin E; Anwer, Ayad G; Goldys, Ewa M; Pollock, Carol A; Saad, Sonia

    2015-07-01

    An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The mitochondrial uncoupling proteins

    OpenAIRE

    Ledesma, Amalia; de Lacoba, Mario García; Rial, Eduardo

    2002-01-01

    The uncoupling proteins (UCPs) are transporters, present in the mitochondrial inner membrane, that mediate a regulated discharge of the proton gradient that is generated by the respiratory chain. This energy-dissipatory mechanism can serve functions such as thermogenesis, maintenance of the redox balance, or reduction in the production of reactive oxygen species. Some UCP homologs may not act as true uncouplers, however, and their activity has yet to be defined. The UCPs are integral membrane...

  17. Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells.

    Science.gov (United States)

    Zahedifard, Maryam; Faraj, Fadhil Lafta; Paydar, Mohammadjavad; Looi, Chung Yeng; Hasandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

    2015-01-01

    The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.

  18. Soot reduction under DC electric fields in counterflow non-premixed laminar ethylene flames

    KAUST Repository

    Park, Daegeun

    2014-04-23

    The effects of DC electric fields on non-premixed ethylene flames in a counterflow burner were studied experimentally with a focus on the reduction of soot particles. The experiment was conducted by connecting a high voltage terminal and a ground terminal to a lower (fuel) and upper (oxidizer) nozzle, respectively. We applied direct current (DC) potentials in a range of -5 kV < Vdc < 5 kV. Uniform electric fields were then generated in the gap between the two nozzles. The experimental conditions were selected to cover both soot formation (SF) and soot formation oxidation (SFO) flames. The flames subjected to the negative electric fields moved toward the fuel nozzle because of an ionic wind due to the Lorentz force acting on the positive ions in the flames. In addition, the yellow luminosity significantly decreased, indicating changes in the sooting characteristics. To analyze the sooting characteristics under the electric fields, planar laser induced incandescence (PLII) and fluorescence (PLIF) techniques were used to visualize the soot, polycyclic aromatic hydrocarbons (PAHs), and OH radicals. The sooting limits in terms of the fuel and oxygen mole fractions were measured. No substantial soot formation due to the effects of the DC electric fields for the tested range of voltages and reactant mole fractions could be identified. The detailed flame behaviors and sooting characteristics under the DC electric fields are discussed. Copyright © Taylor & Francis Group, LLC.

  19. Thermogravimetric studies on the silicothermic reduction of uranium tetrafluoride under nitrogen

    International Nuclear Information System (INIS)

    Venkataramani, R.; Bhatt, Y.J.; Krishnamurthy, N.; Garg, S.P.

    1986-01-01

    This paper presents details of the experimental procedure and results obtained by thermogravimetric studies on the preparation of uranium nitrides by silicothermic reduction of uranium tetrafluoride under a nitrogen atmosphere. The folowing sequential steps are involved during the reaction: 4UF 4 +Si->4UF 3 +SiF 4 (g), 2UF 3 +Si+N 2 ->2UNF+SiF 4 (g), 4UNF+Si+N 2 ->2U 2 N 3 +SiF 4 (g), the uranium sesquintride U 2 N 3 obtained in the above process then decomposed at 1370 K under a dynamic vacuum of less than 10 -2 Tor to yield uranium mononitride of purity better than 99.9%, according to reaction 2U 2 N 3 ->4UN+N 2 (g). The chemical composition of the intermediate products formed during the sequential steps of the process, assessed by thermogravimetric and differential thermogravimetric studies, were further confirmed by chemical and X-ray analysis

  20. Reduction of hexavalent chromium by Pannonibacter phragmitetus LSSE-09 stimulated with external electron donors under alkaline conditions

    International Nuclear Information System (INIS)

    Xu Lin; Luo Mingfang; Li Wangliang; Wei Xuetuan; Xie Keng; Liu Lijun; Jiang Chengying; Liu Huizhou

    2011-01-01

    Research highlights: → Growing cells have high Cr (VI) resistant and reducing ability aerobically. → Resting cells show strong anaerobic-reduction potential. → Acetate can highly stimulate both aerobic and anaerobic reduction process. - Abstract: A novel Cr (VI) resistant bacterial strain LSSE-09, identified as Pannonibacter phragmitetus, was isolated from industrial sludge. It has strong aerobic and anaerobic Cr (VI)-reduction potential under alkaline conditions. At 37 o C and pH 9.0, growing cells of strain LSSE-09 could completely reduce 100 and 1000 mg L -1 Cr (VI)-Cr (III) within 9 and 24 h, respectively under aerobic condition. Resting cells showed higher anaerobic reduction potential with the rate of 1.46 mg g -1 (dryweight) min -1 , comparing with their aerobic reduction rate, 0.21 mg g -1 min -1 . External electron donors, such as lactate, acetate, formate, pyruvate, citrate and glucose could highly increase the reduction rate, especially for aerobic reduction. The presence of 3000 mg L -1 acetate enhanced anaerobic and aerobic Cr (VI)-reduction rates up to 9.47 mg g -1 min -1 and 4.42 mg g -1 min -1 , respectively, which were 5 and 20 times faster than those without it. Strain LSSE-09 retained high activities over six batch cycles and NO 3 - and SO 4 2- had slightly negative effects on Cr (VI)-reduction rates. The results suggest that strain LSSE-09 has potential application for Cr (VI) detoxification in alkaline wastewater.

  1. Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

    OpenAIRE

    Galley, Helen F.; McCormick, Barry; Wilson, Kirsten L.; Lowes, Damon A.; Colvin, Lesley; Torsney, Carole

    2017-01-01

    Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction of mitoc...

  2. Endocrine disorders in mitochondrial disease.

    Science.gov (United States)

    Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

    2013-10-15

    Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Mitochondrial dysfunction in an animal model of diabetic neuropathy is associated with a reduction of neurosteroid synthesis. [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stephen R. Humble

    2018-03-01

    Full Text Available Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABAAR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO. This study explored the differential effect of diazepam on GABAAR modulation via neurosteroidogenesis in diabetic and wild type (WT mice. Methods: Whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from layer 2/3 cortical pyramidal neurons of the pain pathway from mice with type-II diabetic neuropathy (ob/ob and WT controls aged 60-80 days. Results: There was a key difference in the response of the WT and ob/ob cortical neurons to simultaneous incubation with diazepam and flumazenil. In contrast, diazepam and the 5a-reductase inhibitor finasteride, individually or in combination, produced the same response in both strains. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABAAR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathy, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit.

  4. Ecohydrology of agroecosystems: probabilistic description of yield reduction risk under limited water availability

    Science.gov (United States)

    Vico, Giulia; Porporato, Amilcare

    2013-04-01

    Supplemental irrigation represents one of the main strategies to mitigate the effects of climate variability and stabilize yields. Irrigated agriculture currently provides 40% of food production and its relevance is expected to further increase in the near future, in face of the projected alterations of rainfall patterns and increase in food, fiber, and biofuel demand. Because of the significant investments and water requirements involved in irrigation, strategic choices are needed to preserve productivity and profitability, while maintaining a sustainable water management - a nontrivial task given the unpredictability of the rainfall forcing. To facilitate decision making under uncertainty, a widely applicable probabilistic framework is proposed. The occurrence of rainfall events and irrigation applications are linked probabilistically to crop development during the growing season and yields at harvest. Based on these linkages, the probability density function of yields and corresponding probability density function of required irrigation volumes, as well as the probability density function of yields under the most common case of limited water availability are obtained analytically, as a function of irrigation strategy, climate, soil and crop parameters. The full probabilistic description of the frequency of occurrence of yields and water requirements is a crucial tool for decision making under uncertainty, e.g., via expected utility analysis. Furthermore, the knowledge of the probability density function of yield allows us to quantify the yield reduction hydrologic risk. Two risk indices are defined and quantified: the long-term risk index, suitable for long-term irrigation strategy assessment and investment planning, and the real-time risk index, providing a rigorous probabilistic quantification of the emergence of drought conditions during a single growing season in an agricultural setting. Our approach employs relatively few parameters and is thus easily and

  5. Costs of certified emission reductions under the Clean Development Mechanism of the Kyoto Protocol

    International Nuclear Information System (INIS)

    Rahman, Shaikh M.; Kirkman, Grant A.

    2015-01-01

    This paper examines the cost structure of certified emission reductions (CERs) through various types of projects under the Clean Development Mechanism (CDM) of the Kyoto Protocol. Using the CDM project data, the costs of CERs and their variation across technology and over time and space are estimated by applying alternative functional forms and specifications. Results show that the average cost of CERs decreases with the project scale and duration, scale and duration effects significantly vary across project types, and there is an upward trend in costs. The results also show that the distribution of the projects in the CDM portfolio or a given location does not strictly follow the relative cost structure, nor does the distribution of the CDM projects in different host countries follow the principle of comparative advantage. More than 84% of the CDM portfolio consists of various energy projects with substantially higher costs of CERs than afforestation and reforestation, industrial and landfill gas reduction, and methane avoidance projects, which are only 12% of all projects. While per unit cost of abatement plays an important role in the bottom-up and top-down models to evaluate emission reduction potential and analyze policy alternatives, the findings contradict the presumption of such models that project investors seek out low-cost opportunities. At the aggregate level, the cost of CER by the projects in Asia and Europe is similar but higher than those hosted in Africa, Americas, and Oceania. Yet more than 83% of the projects in the CDM portfolio are located in Asia; more than 69% of the projects are in China and India alone. China appears to have a comparative advantage (i.e., lowest opportunity cost) in energy efficiency projects, while India has a comparative advantage in hydro power projects and Brazil has a comparative advantage in wind power projects. In contrast, energy efficiency category accounts for only 8% of the CDM projects in China, hydro power

  6. Kinetic analysis and modeling of oleate and ethanol stimulated uranium (VI) bio-reduction in contaminated sediments under sulfate reduction conditions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Fan, E-mail: zhangfan@itpcas.ac.cn [Key Laboratory of Tibetan Environment Changes and Land Surface Processes, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085 (China); Wu Weimin [Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305 (United States); Parker, Jack C. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Mehlhorn, Tonia [Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Kelly, Shelly D.; Kemner, Kenneth M. [Biosciences Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Zhang, Gengxin [Key Laboratory of Tibetan Environment Changes and Land Surface Processes, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085 (China); Schadt, Christopher; Brooks, Scott C. [Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Criddle, Craig S. [Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305 (United States); Watson, David B. [Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Jardine, Philip M. [Biosystems Engineering and Soil Science Department, University of Tennessee, Knoxville, TN 37996 (United States)

    2010-11-15

    Microcosm tests with uranium contaminated sediments were performed to explore the feasibility of using oleate as a slow-release electron donor for U(VI) reduction in comparison to ethanol. Oleate degradation proceeded more slowly than ethanol with acetate produced as an intermediate for both electron donors under a range of initial sulfate concentrations. A kinetic microbial reduction model was developed and implemented to describe and compare the reduction of sulfate and U(VI) with oleate or ethanol. The reaction path model considers detailed oleate/ethanol degradation and the production and consumption of intermediates, acetate and hydrogen. Although significant assumptions are made, the model tracked the major trend of sulfate and U(VI) reduction and describes the successive production and consumption of acetate, concurrent with microbial reduction of aqueous sulfate and U(VI) species. The model results imply that the overall rate of U(VI) bioreduction is influenced by both the degradation rate of organic substrates and consumption rate of intermediate products.

  7. Kinetic analysis and modeling of oleate and ethanol stimulated uranium (VI) bio-reduction in contaminated sediments under sulfate reduction conditions

    International Nuclear Information System (INIS)

    Zhang Fan; Wu Weimin; Parker, Jack C.; Mehlhorn, Tonia; Kelly, Shelly D.; Kemner, Kenneth M.; Zhang, Gengxin; Schadt, Christopher; Brooks, Scott C.; Criddle, Craig S.; Watson, David B.; Jardine, Philip M.

    2010-01-01

    Microcosm tests with uranium contaminated sediments were performed to explore the feasibility of using oleate as a slow-release electron donor for U(VI) reduction in comparison to ethanol. Oleate degradation proceeded more slowly than ethanol with acetate produced as an intermediate for both electron donors under a range of initial sulfate concentrations. A kinetic microbial reduction model was developed and implemented to describe and compare the reduction of sulfate and U(VI) with oleate or ethanol. The reaction path model considers detailed oleate/ethanol degradation and the production and consumption of intermediates, acetate and hydrogen. Although significant assumptions are made, the model tracked the major trend of sulfate and U(VI) reduction and describes the successive production and consumption of acetate, concurrent with microbial reduction of aqueous sulfate and U(VI) species. The model results imply that the overall rate of U(VI) bioreduction is influenced by both the degradation rate of organic substrates and consumption rate of intermediate products.

  8. The reduction of petroleum hydrocarbons in soil under saline conditions using ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, D. [SNC-Lavallin, Vancouver, BC (Canada); Northern British Columbia Univ., Prince George, BC (Canada)

    2010-07-01

    Petroleum hydrocarbons (PHCs) and salts are two of the most common soil contaminants found at oil and gas extraction sites. High concentrations of salt from brine spills may amplify the challenges of soil remediation by reducing bioavailability for remediation. This PowerPoint presentation described an ultrasonic soil flushing technology that used sonic cavitation to break down contaminants. Long chain and aromatic hydrocarbons with complex structures were broken down by the direct oxidation under high temperature and pressure environments created by the sonic cavitation process. The cavitation waves broke up the aggregates of solid particles and increased the turbulence and transportation of the contaminants. A laboratory study evaluated the ability of the treatment process to remediate salt and hydrocarbon contaminated soil samples. The adsorption isotherms of the samples were analyzed. Sand, clay, and muskeg samples were treated. Results of the study suggested that the treatment is more effective when treating granular soils with high hydraulic conductivity. Even small amounts of salt were found to have a negative impact on the reduction of hydrocarbon contaminants. tabs., figs.

  9. Mitochondrial Energy and Redox Signaling in Plants

    Science.gov (United States)

    Schwarzländer, Markus

    2013-01-01

    Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467

  10. Constraining the relationships between anaerobic oxidation of methane and sulfate reduction under in situ methane concentrations

    Science.gov (United States)

    Zhuang, G.; Wegener, G.; Joye, S. B.

    2017-12-01

    The anaerobic oxidation of methane (AOM) is an important microbial metabolism in the global carbon cycle. In marine methane seeps sediment, this process is mediated by syntrophic consortium that includes anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB). Stoichiometrically in AOM methane oxidation should be coupled to sulfate reduction (SR) in a 1:1 ratio. However, weak coupling of AOM and SR in seep sediments was frequently observed from the ex situ rate measurements, and the metabolic dynamics of AOM and SR under in situ conditions remain poorly understood. Here we investigated the metabolic activity of AOM and SR with radiotracers by restoring in situ methane concentrations under pressure to constrain the in situ relationships between AOM and SR in the cold seep sediments of Gulf of Mexico as well as the sediment-free AOM enrichments cultivated from cold seep of Italian Island Elba or hydrothermal vent of Guaymas Basin5. Surprisingly, we found that AOM rates strongly exceeded those of SR when high pressures and methane concentrations were applied at seep sites of GC600 and GC767 in Gulf of Mexico. With the addition of molybdate, SR was inhibited but AOM was not affected, suggesting the potential coupling of AOM with other terminal processes. Amendments of nitrate, iron, manganese and AQDS to the SR-inhibited slurries did not stimulate or inhibit the AOM activity, indicating either those electron acceptors were not limiting for AOM in the sediments or AOM was coupled to other process (e.g., organic matter). In the ANME enrichments, higher AOM rates were also observed with the addition of high concentrations of methane (10mM and 50 mM). The tracer transfer of CO2 to methane, i.e., the back reaction of AOM, increased with increasing methane concentrations and accounted for 1%-5% of the AOM rates. AOM rates at 10 mM and 50 mM methane concentration were much higher than the SR rates, suggesting those two processes were not tightly coupled

  11. Environmental TEM investigation of the reduction of α-Fe2O3 nanorods under H2 atmosphere

    DEFF Research Database (Denmark)

    Almeida, Trevor P.; Fay, Michael W.; Zhu, Yanqiu

    2012-01-01

    The thermal reduction of hydrothermally synthesised α-Fe2O3 nanorods (NRs) to Fe3O4 NRs under hydrogen is investigated. Complete reduction of α-Fe2O3 NRs to Fe3O4 NRs was achieved during in situ XRD under 1 bar H2 atmosphere at 360°C. Complementary environmental transmission electron microscope...... investigation at high resolution, during in situ heating under an H2 pressure of 5 mbar at 500°C, provided evidence for the very first stages of transformation, supporting a model for the migration of oxygen along favoured α-Fe2O3 lattice planes during the templated thermal reduction of α-Fe2O3 NRs to Fe3O4 NRs....

  12. Subsurface nitrate reduction under wetlands takes place in narrow superficial zones

    DEFF Research Database (Denmark)

    dos Santos Ribas, Osmar; Calderer, M.; Marti, Vicens

    2017-01-01

    This study aims to investigate the depth distribution of the Nitrate Reduction Potential (NRP) on a natural and a re-established wetland. The obtained NRP provides a valuable data of the driving factors affecting denitrification, the Dissimilatory Nitrate Reduction to Ammonium (DNRA) process and ...... that wetlands can be restored satisfactorily.......This study aims to investigate the depth distribution of the Nitrate Reduction Potential (NRP) on a natural and a re-established wetland. The obtained NRP provides a valuable data of the driving factors affecting denitrification, the Dissimilatory Nitrate Reduction to Ammonium (DNRA) process...... and the performance of a re-established wetland. Intact soil cores were collected and divided in slices for the determination of Organic Matter (OM) through Loss of Ignition (LOI) as well as Dissolved Organic Carbon (DOC) and NRP spiking nitrate in batch tests. The Nitrate Reduction (NR) was fitted as a pseudo...

  13. The reduction of Winterveld chrome spinel at 1300 degrees Celsius under an argon atmosphere in the presence of carbon

    International Nuclear Information System (INIS)

    Kuecuekkaragoz, C.S.; Algie, S.H.; Finn, C.W.P.

    1984-01-01

    The reduction of a mixture of particles of gangue-free spinel in the size range 106 to 90 μm and particles of graphite in the same size range was studied by the use of a recording thermobalance. The partially reduced material was analysed chemically, as well as by X-ray diffraction, optical microscopy, and electron-microprobe analysis. The reaction is shown to be sequential, the ferric iron being reduced to ferrous iron before a metallic reduction product appears. Almost one-half of the iron is reduced before the reduction of chromium becomes significant, and, by the time about one-half of the chromium has been reduced, almost no unreduced iron remains in the oxide. Carbon appears in the reduced material after the reduction of chromium has started. The carbon content rises as the reaction proceeds, and beyond the stage at which all the iron has been reduced, the reduced product is an iron-chromium carbide. The product is therefore in a state of near equilibrium with the partially reduced spinel. This indicates that, up to about 60 per cent reduction, the transfer of carbon to the oxide is a controlling factor in the reduction. This conclusion is supported by the observation that the reduced product is confined to the surface of the chromite particle, which retains its external shape while becoming progressively more porous as reduction proceeds. Under hydrogen, a metallic reduction product is formed within the internal pores as well as on the surface. The second half of the reduction proceeds at a reproducible decreasing rate that can be modelled on the basis of the diffusion of chromium from within the particle to the surface. The initial reduction rate is slow but accelerating, and is not reproducible. Further investigation of this stage of the reduction process is recommended

  14. Reductions in mitochondrial O(2) consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium.

    Science.gov (United States)

    Hu, Qingsong; Suzuki, Gen; Young, Rebeccah F; Page, Brian J; Fallavollita, James A; Canty, John M

    2009-07-01

    We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 +/- 0.2 vs. 5.4 +/- 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37 degrees C). At baseline, ATP (20.1 +/- 1.0 vs. 26.7 +/- 2.1 micromol/g dry wt, P < 0.05), ADP (8.1 +/- 0.4 vs. 10.3 +/- 0.8 micromol/g, P < 0.05), and total adenine nucleotides (31.2 +/- 1.3 vs. 40.1 +/- 2.9 micromol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 +/- 0.9 vs. 13.7 +/- 1.7 micromol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 +/- 13 vs. 187 +/- 11 ng atoms O(2).mg protein(-1).min(-1) in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

  15. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

    Science.gov (United States)

    Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

    2009-07-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.

  16. Antioxidant and oxidative stress parameters in brain of Heteropneustes fossilis under air exposure condition; role of mitochondrial electron transport chain.

    Science.gov (United States)

    Paital, Biswaranjan

    2013-09-01

    Many fishes are exposed to air in their natural habitat or during their commercial handling. In natural habitat or during commercial handling, the cat fish Heteropneustes fossilis is exposed to air for >24h. Data on its oxidative metabolism in the above condition are not available. Oxidative stress (OS) indices (lipid and protein oxidation), toxic reactive oxygen species (ROS: H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of electron transport chain (ETC) enzymes (complex I-IV) were investigated in brain tissue of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25°C). Decreased activities of antioxidant (except catalase) and ETC enzymes (except complex II) with increased H2O2 and OS levels were observed in the tissue under water deprivation condition. Positive correlation was observed for complex II activity and non-protein thiol groups with time period of air exposure. The critical time period to induce OS and to reduce most of the studied antioxidant level in brain was found to be 3-6h air exposure. The data can be useful to minimize the stress generated during commercial handling of the live fishes those exposed to air in general and H. fossilis in particular. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart.

    Science.gov (United States)

    Gong, Guohua; Liu, Xiaoyun; Zhang, Huiliang; Sheu, Shey-Shing; Wang, Wang

    2015-10-01

    Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1 ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions. Copyright © 2015 the American Physiological Society.

  18. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

    Directory of Open Access Journals (Sweden)

    Annalisa Canta

    2015-06-01

    Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.

  19. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

    Science.gov (United States)

    Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

    2015-01-01

    The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

  20. 22 CFR 201.03 - OMB approval under the Paperwork Reduction Act.

    Science.gov (United States)

    2010-04-01

    .... The information is required from suppliers in order to receive payment for commodities or commodity..., and the Office of Management and Budget, Paperwork Reduction Project (0412-0514), Washington, DC 20503...

  1. Achieving 80% greenhouse gas reduction target in Saudi Arabia under low and medium oil prices

    KAUST Repository

    Alshammari, Yousef Mohammad; Sarathy, Mani

    2016-01-01

    meeting the 80% target, and it would also lower costs of transition to low carbon energy system while maintaining cleaner use of hydrocarbons with CCS. Setting very deep GHG reduction targets may be economically uncompetitive in consideration of the energy

  2. Comparisons of receive array interference reduction techniques under erroneous generalized transmit beamforming

    KAUST Repository

    Radaydeh, Redha Mahmoud; Alouini, Mohamed-Slim

    2014-01-01

    information for the desired user spatially uncorrelated transmit channels on the effectiveness of transmit beamforming for different interference reduction techniques is investigated. The case of over-loaded receive array with closely-spaced elements

  3. Kinetics of U(VI) reduction by a dissimilatory Fe(III)-reducing bacterium under non-growth conditions

    International Nuclear Information System (INIS)

    Truex, M.J.; Peyton, B.M.; Valentine, N.B.; Gorby, Y.A.

    1997-01-01

    Dissimilatory metal-reducing microorganisms may be useful in processes designed for selective removal of uranium from aqueous streams. These bacteria can use U(VI) as an electron acceptor and thereby reduce soluble U(VI) to insoluble U(IV). While significant research has been devoted to demonstrating and describing the mechanism of dissimilatory metal reduction, the reaction kinetics necessary to apply this for remediation processes have not been adequately defined. In this study, pure culture Shewanella alga strain BrY reduced U(VI) under non-growth conditions in the presence of excess lactate as the electron donor. Initial U(VI) concentrations ranged from 13 to 1,680microM. A maximum specific U(VI) reduction rate of 2.37 micromole-U(VI)/(mg-biomass h) and Monod half-saturation coefficient of 132 microM-U(VI) were calculated from measured U(VI) reduction rates. U(VI) reduction activity was sustained at 60% of this rate for at least 80 h. The initial presence of oxygen at a concentration equal to atmospheric saturation at 22 C delays but does not prevent U(VI) reduction. The rate of U(VI) reduction by BrY is comparable or better than rates reported for other metal reducing species. BrY reduces U(VI) at a rate that is 30% of its Fe(III) reduction rate

  4. Biomechanical walking mechanisms underlying the metabolic reduction caused by an autonomous exoskeleton.

    Science.gov (United States)

    Mooney, Luke M; Herr, Hugh M

    2016-01-28

    Ankle exoskeletons can now reduce the metabolic cost of walking in humans without leg disability, but the biomechanical mechanisms that underlie this augmentation are not fully understood. In this study, we analyze the energetics and lower limb mechanics of human study participants walking with and without an active autonomous ankle exoskeleton previously shown to reduce the metabolic cost of walking. We measured the metabolic, kinetic and kinematic effects of wearing a battery powered bilateral ankle exoskeleton. Six participants walked on a level treadmill at 1.4 m/s under three conditions: exoskeleton not worn, exoskeleton worn in a powered-on state, and exoskeleton worn in a powered-off state. Metabolic rates were measured with a portable pulmonary gas exchange unit, body marker positions with a motion capture system, and ground reaction forces with a force-plate instrumented treadmill. Inverse dynamics were then used to estimate ankle, knee and hip torques and mechanical powers. The active ankle exoskeleton provided a mean positive power of 0.105 ± 0.008 W/kg per leg during the push-off region of stance phase. The net metabolic cost of walking with the active exoskeleton (3.28 ± 0.10 W/kg) was an 11 ± 4 % (p = 0.019) reduction compared to the cost of walking without the exoskeleton (3.71 ± 0.14 W/kg). Wearing the ankle exoskeleton significantly reduced the mean positive power of the ankle joint by 0.033 ± 0.006 W/kg (p = 0.007), the knee joint by 0.042 ± 0.015 W/kg (p = 0.020), and the hip joint by 0.034 ± 0.009 W/kg (p = 0.006). This study shows that the ankle exoskeleton does not exclusively reduce positive mechanical power at the ankle joint, but also mitigates positive power at the knee and hip. Furthermore, the active ankle exoskeleton did not simply replace biological ankle function in walking, but rather augmented the total (biological + exoskeletal) ankle moment and power. This study

  5. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

    Directory of Open Access Journals (Sweden)

    Carola Stockburger

    2016-01-01

    Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

  6. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

    Science.gov (United States)

    Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

    2016-01-01

    The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

  7. Synthesis of 2-Alkenylquinoline by Reductive Olefination of Quinoline N-Oxide under Metal-Free Conditions.

    Science.gov (United States)

    Xia, Hong; Liu, Yuanhong; Zhao, Peng; Gou, Shaohua; Wang, Jun

    2016-04-15

    Synthesis of 2-alkenylquinoline by reductive olefination of quinoline N-oxide under metal-free conditions is disclosed. Practically, the reaction could be performed with quinoline as starting material via a one-pot, two-step process. A possible mechanism is proposed that involves a sequential 1,3-dipolar cycloaddition and acid-assisted ring opening followed by a dehydration process.

  8. Mitochondrial uncoupling proteins in unicellular eukaryotes.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Antos-Krzeminska, Nina; Sluse, Francis E

    2010-01-01

    Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier protein family that are present in the mitochondrial inner membrane and mediate free fatty acid (FFA)-activated, purine nucleotide (PN)-inhibited proton conductance. Since 1999, the presence of UCPs has been demonstrated in some non-photosynthesising unicellular eukaryotes, including amoeboid and parasite protists, as well as in non-fermentative yeast and filamentous fungi. In the mitochondria of these organisms, UCP activity is revealed upon FFA-induced, PN-inhibited stimulation of resting respiration and a decrease in membrane potential, which are accompanied by a decrease in membranous ubiquinone (Q) reduction level. UCPs in unicellular eukaryotes are able to divert energy from oxidative phosphorylation and thus compete for a proton electrochemical gradient with ATP synthase. Our recent work indicates that membranous Q is a metabolic sensor that might utilise its redox state to release the PN inhibition of UCP-mediated mitochondrial uncoupling under conditions of phosphorylation and resting respiration. The action of reduced Q (QH2) could allow higher or complete activation of UCP. As this regulatory feature was demonstrated for microorganism UCPs (A. castellanii UCP), plant and mammalian UCP1 analogues, and UCP1 in brown adipose tissue, the process could involve all UCPs. Here, we discuss the functional connection and physiological role of UCP and alternative oxidase, two main energy-dissipating systems in the plant-type mitochondrial respiratory chain of unicellular eukaryotes, including the control of cellular energy balance as well as preventive action against the production of reactive oxygen species. Copyright © 2009 Elsevier B.V. All rights reserved.

  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 and organophosphorus compounds

    International Nuclear Information System (INIS)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-01-01

    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

  11. Noise Reduction Evaluation of Multi-Layered Viscoelastic Infinite Cylinder under Acoustical Wave Excitation

    Directory of Open Access Journals (Sweden)

    M.R. Mofakhami

    2008-01-01

    Full Text Available In this paper sound transmission through the multilayered viscoelastic air filled cylinders subjected to the incident acoustic wave is studied using the technique of separation of variables on the basis of linear three dimensional theory of elasticity. The effect of interior acoustic medium on the mode maps (frequency vs geometry and noise reduction is investigated. The effects of internal absorption and external moving medium on noise reduction are also evaluated. The dynamic viscoelastic properties of the structure are rigorously taken into account with a power law technique that models the viscoelastic damping of the cylinder. A parametric study is also performed for the two layered infinite cylinders to obtain the effect of viscoelastic layer characteristics such as thickness, material type and frequency dependency of viscoelastic properties on the noise reduction. It is shown that using constant and frequency dependent viscoelastic material with high loss factor leads to the uniform noise reduction in the frequency domain. It is also shown that the noise reduction obtained for constant viscoelastic material property is subjected to some errors in the low frequency range with respect to those obtained for the frequency dependent viscoelastic material.

  12. Achieving 80% greenhouse gas reduction target in Saudi Arabia under low and medium oil prices

    KAUST Repository

    Alshammari, Yousef Mohammad

    2016-11-10

    COP 21 led to a global agreement to limit the earth\\'s rising temperature to less than 2 °C. This will require countries to act upon climate change and achieve a significant reduction in their greenhouse gas emissions which will play a pivotal role in shaping future energy systems. Saudi Arabia is the World\\'s largest exporter of crude oil, and the 11th largest CO2 emitter. Understanding the Kingdom\\'s role in global greenhouse gas reduction is critical in shaping the future of fossil fuels. Hence, this work presents an optimisation study to understand how Saudi Arabia can meet the CO2 reduction targets to achieve the 80% reduction in the power generation sector. It is found that the implementation of energy efficiency measures is necessary to enable meeting the 80% target, and it would also lower costs of transition to low carbon energy system while maintaining cleaner use of hydrocarbons with CCS. Setting very deep GHG reduction targets may be economically uncompetitive in consideration of the energy supply requirements. In addition, we determine the breakeven price of crude oil needed to make CCS economically viable. Results show important dimension for pricing CO2 and the role of CCS compared with alternative sources of energy.

  13. Reduction of Cr(VI) to Cr(III) using silicon nanowire arrays under visible light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fellahi, Ouarda [Institut d' Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Avenue Poincaré—BP 70478, 59652 Villeneuve d' Ascq Cedex (France); Centre de Recherche en Technologie des Semi-conducteurs pour l' Energétique-CRTSE 02, Bd Frantz Fanon, BP. 140, Alger 7 Merveilles (Algeria); Barras, Alexandre [Institut d' Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Avenue Poincaré—BP 70478, 59652 Villeneuve d' Ascq Cedex (France); Pan, Guo-Hui [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 3888 Dong Nanhu Road, Changchun 130033 (China); Coffinier, Yannick [Institut d' Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Avenue Poincaré—BP 70478, 59652 Villeneuve d' Ascq Cedex (France); Hadjersi, Toufik [Centre de Recherche en Technologie des Semi-conducteurs pour l' Energétique-CRTSE 02, Bd Frantz Fanon, BP. 140, Alger 7 Merveilles (Algeria); Maamache, Mustapha [Laboratoire de Physique Quantique et Systèmes Dynamiques, Département de Physique, Université de Sétif, Sétif 19000 (Algeria); Szunerits, Sabine [Institut d' Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Avenue Poincaré—BP 70478, 59652 Villeneuve d' Ascq Cedex (France); and others

    2016-03-05

    Highlights: • Cr(VI) reduction to Cr(III) using silicon nanowires decorated with Cu nanoparticles. • The reduction takes place at room temperature and neutral pH under visible light. • The photocatalytic reduction was enhanced by addition of adipic or citric acid. - Abstract: We report an efficient visible light-induced reduction of hexavalent chromium Cr(VI) to trivalent Cr(III) by direct illumination of an aqueous solution of potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) in the presence of hydrogenated silicon nanowires (H-SiNWs) or silicon nanowires decorated with copper nanoparticles (Cu NPs-SiNWs) as photocatalyst. The SiNW arrays investigated in this study were prepared by chemical etching of crystalline silicon in HF/AgNO{sub 3} aqueous solution. The Cu NPs were deposited on SiNW arrays via electroless deposition technique. Visible light irradiation of an aqueous solution of K{sub 2}Cr{sub 2}O{sub 7} (10{sup −4} M) in presence of H-SiNWs showed that these substrates were not efficient for Cr(VI) reduction. The reduction efficiency achieved was less than 10% after 120 min irradiation at λ > 420 nm. Addition of organic acids such as citric or adipic acid in the solution accelerated Cr(VI) reduction in a concentration-dependent manner. Interestingly, Cu NPs-SiNWs was found to be a very efficient interface for the reduction of Cr(VI) to Cr(III) in absence of organic acids. Almost a full reduction of Cr(VI) was achieved by direct visible light irradiation for 140 min using this photocatalyst.

  14. 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 ...

  15. Achieving 80% greenhouse gas reduction target in Saudi Arabia under low and medium oil prices

    International Nuclear Information System (INIS)

    Alshammari, Yousef M.; Sarathy, S. Mani

    2017-01-01

    COP 21 led to a global agreement to limit the earth's rising temperature to less than 2 °C. This will require countries to act upon climate change and achieve a significant reduction in their greenhouse gas emissions which will play a pivotal role in shaping future energy systems. Saudi Arabia is the World's largest exporter of crude oil, and the 11th largest CO_2 emitter. Understanding the Kingdom's role in global greenhouse gas reduction is critical in shaping the future of fossil fuels. Hence, this work presents an optimisation study to understand how Saudi Arabia can meet the CO_2 reduction targets to achieve the 80% reduction in the power generation sector. It is found that the implementation of energy efficiency measures is necessary to enable meeting the 80% target, and it would also lower costs of transition to low carbon energy system while maintaining cleaner use of hydrocarbons with CCS. Setting very deep GHG reduction targets may be economically uncompetitive in consideration of the energy supply requirements. In addition, we determine the breakeven price of crude oil needed to make CCS economically viable. Results show important dimension for pricing CO_2 and the role of CCS compared with alternative sources of energy. - Highlights: • Energy efficiency measures are needed to achieve 80% reduction. • Nuclear appears as an important option to achieve deep cuts in CO_2 by 2050. • Technology improvement can enable using heavy fuel oil with CCS until 2050. • IGCC requires lower net CO_2 footprint in order to be competitive. • Nuclear power causes a sharp increase in the CO_2 avoidance costs.

  16. Radical-mediated reduction of the dithiocarbamate group under tin-free conditions.

    Science.gov (United States)

    McMaster, Claire; Bream, Robert N; Grainger, Richard S

    2012-06-28

    Reductive desulfurisation of dithiocarbamates is conveniently achieved using H(3)PO(2)-Et(3)N-ACCN in refluxing dioxane. Fused and spirocyclic β-lactams, prepared through 4-exo trig carbamoyl radical cyclisation-dithiocarbamate group transfer reactions, are reduced without fragmentation of the strained 4-membered ring. Diethyl tetraacetyl-d-glucopyranosyl dithiocarbamate is selectively reduced with or without acyloxy group migration depending on reaction conditions and choice of reductant. Deuterium incorporation from D(3)PO(2)-Et(3)N is observed for a system involving a nucleophilic radical intermediate, but not in the case of the electrophilic radical obtained through acyloxy group migration on a glucose derivative.

  17. Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less ρ0 cells and cybrids carrying MELAS mitochondrial DNA mutation

    International Nuclear Information System (INIS)

    Yoshii, Yukie; Yoneda, Makoto; Ikawa, Masamichi; Furukawa, Takako; Kiyono, Yasushi; Mori, Tetsuya; Yoshii, Hiroshi; Oyama, Nobuyuki; Okazawa, Hidehiko; Saga, Tsuneo; Fujibayashi, Yasuhisa

    2012-01-01

    Objectives: Radiolabeled Cu-diacetyl-bis (N 4 -methylthiosemicarbazone) ( ⁎ Cu-ATSM), including 60/62/64 Cu-ATSM, is a potential imaging agent of hypoxic tumors for positron emission tomography (PET). We have reported that ⁎ Cu-ATSM is trapped in tumor cells under intracellular overreduced states, e.g., hypoxia. Here we evaluated ⁎ Cu-ATSM as an indicator of intracellular overreduced states in mitochondrial disorders using cell lines with mitochondrial dysfunction. Methods: Mitochondrial DNA-less ρ 0 206 cells; the parental 143B human osteosarcoma cells; the cybrids carrying mutated mitochondria from a patient of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (2SD); and that carrying wild-type one (2SA) were used. Cells were treated under normoxia or hypoxia, and 64 Cu-ATSM uptake was examined to compare it with levels of biological reductant NADH and NADPH. Results: ρ 0 206 cells showed higher 64 Cu-ATSM uptake than control 143B cells under normoxia, whereas 64 Cu-ATSM uptake was not significantly increased under hypoxia in ρ 0 206 cells. Additionally, 64 Cu-ATSM uptake showed correlate change to the NADH and NADPH levels, but not oxygenic conditions. 2SD cells showed increased 64 Cu-ATSM uptake under normoxia as compared with the control 2SA, and 64 Cu-ATSM uptake followed NADH and NADPH levels, but not oxygenic conditions. Conclusions: 64 Cu-ATSM accumulated in cells with overreduced states due to mitochondrial dysfunction, even under normoxia. We recently reported that 62 Cu-ATSM-PET can visualize stroke-like episodes maintaining oxygen supply in MELAS patients. Taken together, our data indicate that ⁎ Cu-ATSM uptake reflects overreduced intracellular states, despite oxygenic conditions; thus, ⁎ Cu-ATSM would be a promising marker of intracellular overreduced states for disorders with mitochondrial dysfunction, such as MELAS, Parkinson's disease and Alzheimer's disease.

  18. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging.Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction fol...

  19. Mitochondrial Dynamics in Cardiovascular Health and Disease

    OpenAIRE

    Ong, Sang-Bing; Hall, Andrew R.; Hausenloy, Derek J.

    2013-01-01

    Significance: Mitochondria are dynamic organelles capable of changing their shape and distribution by undergoing either fission or fusion. Changes in mitochondrial dynamics, which is under the control of specific mitochondrial fission and fusion proteins, have been implicated in cell division, embryonic development, apoptosis, autophagy, and metabolism. Although the machinery for modulating mitochondrial dynamics is present in the cardiovascular system, its function there has only recently be...

  20. Diffusive tunneling for alleviating Knudsen-layer reactivity reduction under hydrodynamic mix

    Science.gov (United States)

    Tang, Xianzhu; McDevitt, Chris; Guo, Zehua

    2017-10-01

    Hydrodynamic mix will produce small features for intermixed deuterium-tritium fuel and inert pusher materials. The geometrical characteristics of the mix feature have a large impact on Knudsen layer yield reduction. We considered two features. One is planar structure, and the other is fuel cells segmented by inert pusher material which can be represented by a spherical DT bubble enclosed by a pusher shell. The truly 3D fuel feature, the spherical bubble, has the largest degree of yield reduction, due to fast ions being lost in all directions. The planar fuel structure, which can be regarded as 1D features, has modest amount of potential for yield degradation. While the increasing yield reduction with increasing Knudsen number of the fuel region is straightforwardly anticipated, we also show, by a combination of direct simulation and simple model, that once the pusher materials is stretched sufficiently thin by hydrodynamic mix, the fast fuel ions diffusively tunnel through them with minimal energy loss, so the Knudsen layer yield reduction becomes alleviated. This yield recovery can occur in a chunk-mixed plasma, way before the far more stringent, asymptotic limit of an atomically homogenized fuel and pusher assembly. Work supported by LANL LDRD program.

  1. Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions.

    Directory of Open Access Journals (Sweden)

    Mauro Tiso

    Full Text Available The biological nitrogen cycle involves step-wise reduction of nitrogen oxides to ammonium salts and oxidation of ammonia back to nitrites and nitrates by plants and bacteria. Neither process has been thought to have relevance to mammalian physiology; however in recent years the salivary bacterial reduction of nitrate to nitrite has been recognized as an important metabolic conversion in humans. Several enteric bacteria have also shown the ability of catalytic reduction of nitrate to ammonia via nitrite during dissimilatory respiration; however, the importance of this pathway in bacterial species colonizing the human intestine has been little studied. We measured nitrite, nitric oxide (NO and ammonia formation in cultures of Escherichia coli, Lactobacillus and Bifidobacterium species grown at different sodium nitrate concentrations and oxygen levels. We found that the presence of 5 mM nitrate provided a growth benefit and induced both nitrite and ammonia generation in E.coli and L.plantarum bacteria grown at oxygen concentrations compatible with the content in the gastrointestinal tract. Nitrite and ammonia accumulated in the growth medium when at least 2.5 mM nitrate was present. Time-course curves suggest that nitrate is first converted to nitrite and subsequently to ammonia. Strains of L.rhamnosus, L.acidophilus and B.longum infantis grown with nitrate produced minor changes in nitrite or ammonia levels in the cultures. However, when supplied with exogenous nitrite, NO gas was readily produced independently of added nitrate. Bacterial production of lactic acid causes medium acidification that in turn generates NO by non-enzymatic nitrite reduction. In contrast, nitrite was converted to NO by E.coli cultures even at neutral pH. We suggest that the bacterial nitrate reduction to ammonia, as well as the related NO formation in the gut, could be an important aspect of the overall mammalian nitrate/nitrite/NO metabolism and is yet another way in

  2. Nitrate Reduction to Nitrite, Nitric Oxide and Ammonia by Gut Bacteria under Physiological Conditions

    Science.gov (United States)

    Tiso, Mauro; Schechter, Alan N.

    2015-01-01

    The biological nitrogen cycle involves step-wise reduction of nitrogen oxides to ammonium salts and oxidation of ammonia back to nitrites and nitrates by plants and bacteria. Neither process has been thought to have relevance to mammalian physiology; however in recent years the salivary bacterial reduction of nitrate to nitrite has been recognized as an important metabolic conversion in humans. Several enteric bacteria have also shown the ability of catalytic reduction of nitrate to ammonia via nitrite during dissimilatory respiration; however, the importance of this pathway in bacterial species colonizing the human intestine has been little studied. We measured nitrite, nitric oxide (NO) and ammonia formation in cultures of Escherichia coli, Lactobacillus and Bifidobacterium species grown at different sodium nitrate concentrations and oxygen levels. We found that the presence of 5 mM nitrate provided a growth benefit and induced both nitrite and ammonia generation in E.coli and L.plantarum bacteria grown at oxygen concentrations compatible with the content in the gastrointestinal tract. Nitrite and ammonia accumulated in the growth medium when at least 2.5 mM nitrate was present. Time-course curves suggest that nitrate is first converted to nitrite and subsequently to ammonia. Strains of L.rhamnosus, L.acidophilus and B.longum infantis grown with nitrate produced minor changes in nitrite or ammonia levels in the cultures. However, when supplied with exogenous nitrite, NO gas was readily produced independently of added nitrate. Bacterial production of lactic acid causes medium acidification that in turn generates NO by non-enzymatic nitrite reduction. In contrast, nitrite was converted to NO by E.coli cultures even at neutral pH. We suggest that the bacterial nitrate reduction to ammonia, as well as the related NO formation in the gut, could be an important aspect of the overall mammalian nitrate/nitrite/NO metabolism and is yet another way in which the microbiome

  3. SMALL BUSINESS – ALTERNATIVE TO UNEMPLOYMENT REDUCTION IN ECONOMY UNDER RECESSION

    Directory of Open Access Journals (Sweden)

    Trajković Svetlana

    2013-01-01

    Full Text Available The decade long trend of unemployment rate increase, reduction of national income and salaries of the employees and demand reduction implies the necessity for taking urgent measures and counteracting the high inflation rate in order to reduce the unemployment of both the younger population as well as the elderly population (older than 50 which is often considered to be unneeded. More active initiation of small business through entrepreneurship, even self-employment can be an impetus for healing the economy. Education, financial support in the form of favorable loans together with the fiscal policy of new entrepreneurs can initiate entering into business of people with the feeling, awareness and readiness for innovative work and uncertainty, and those who are ready to face the risk of anticipating future developments and market turbulences which are inevitable companions of modern business.

  4. Land-Based Mitigation Strategies under the Mid-Term Carbon Reduction Targets in Indonesia

    Directory of Open Access Journals (Sweden)

    Tomoko Hasegawa

    2016-12-01

    Full Text Available We investigated the key mitigation options for achieving the mid-term target for carbon emission reduction in Indonesia. A computable general equilibrium model coupled with a land-based mitigation technology model was used to evaluate specific mitigation options within the whole economic framework. The results revealed three primary findings: (1 If no climate policy were implemented, Indonesia’s total greenhouse gas emissions would reach 3.0 GtCO2eq by 2030; (2 To reduce carbon emissions to meet the latest Intended Nationally-Determined Contributions (INDC target, ~58% of total reductions should come from the agriculture, forestry and other land use sectors by implementing forest protection, afforestation and plantation efforts; (3 A higher carbon price in 2020 suggests that meeting the 2020 target would be economically challenging, whereas the INDC target for 2030 would be more economically realistic in Indonesia.

  5. Reductive Dechlorination of Trichloroethylene and Tetrachloroethylene under Aerobic Conditions in a Sediment Column

    OpenAIRE

    1994-01-01

    Biodegradation of trichloroethylene and tetrachloroethylene under aerobic conditions was studied in a sediment column. Cumulative mass balances indicated 87 and 90% removal for trichloroethylene and tetrachloroethylene, respectively. These studies suggest the potential for simultaneous aerobic and anaerobic biotransformation processes under bulk aerobic conditions.

  6. Introduction of a computer-based method for automated planning of reduction paths under consideration of simulated muscular forces.

    Science.gov (United States)

    Buschbaum, Jan; Fremd, Rainer; Pohlemann, Tim; Kristen, Alexander

    2017-08-01

    Reduction is a crucial step in the surgical treatment of bone fractures. Finding an optimal path for restoring anatomical alignment is considered technically demanding because collisions as well as high forces caused by surrounding soft tissues can avoid desired reduction movements. The repetition of reduction movements leads to a trial-and-error process which causes a prolonged duration of surgery. By planning an appropriate reduction path-an optimal sequence of target-directed movements-these problems should be overcome. For this purpose, a computer-based method has been developed. Using the example of simple femoral shaft fractures, 3D models are generated out of CT images. A reposition algorithm aligns both fragments by reconstructing their broken edges. According to the criteria of a deduced planning strategy, a modified A*-algorithm searches collision-free route of minimal force from the dislocated into the computed target position. Muscular forces are considered using a musculoskeletal reduction model (OpenSim model), and bone collisions are detected by an appropriate method. Five femoral SYNBONE models were broken into different fracture classification types and were automatically reduced from ten randomly selected displaced positions. Highest mean translational and rotational error for achieving target alignment is [Formula: see text] and [Formula: see text]. Mean value and standard deviation of occurring forces are [Formula: see text] for M. tensor fasciae latae and [Formula: see text] for M. semitendinosus over all trials. These pathways are precise, collision-free, required forces are minimized, and thus regarded as optimal paths. A novel method for planning reduction paths under consideration of collisions and muscular forces is introduced. The results deliver additional knowledge for an appropriate tactical reduction procedure and can provide a basis for further navigated or robotic-assisted developments.

  7. Enhanced selective photocatalytic CO{sub 2} reduction into CO over Ag/CdS nanocomposites under visible light

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zezhou; Qin, Jiani; Jiang, Min; Ding, Zhengxin; Hou, Yidong, E-mail: ydhou@fzu.edu.cn

    2017-01-01

    Highlights: • Ag/CdS nanocomposites were prepared by a facile photodeposition method. • Ag/CdS was more effective as a photocatalyst for CO{sub 2} reduction than CdS. • Ag as cocatalyst served as electron trap as well as active site for CO{sub 2} reduction reaction. - Abstract: Photocatalytic reduction of carbon dioxide can convert chemically inert carbon dioxide into useful chemical fuel in a mild manner. Herein, Ag-CdS nanocomposites were prepared by photodeposition method and examined for photocatalytic CO{sub 2} reduction under visible light. Meanwhile, the nanocomposites were characterized by XRD, SEM, TEM, XPS, DRS and PL in detail. The results show that, the deposition of Ag improves the photocatalytic performance of CdS, especially in the selectivity of CO{sub 2}-to-CO. The highest photocatalytic activity is achieved over 1.0 wt.% Ag/CdS, with an increase by 3 times in comparison to CdS. In this reaction system, Ag can serve as electron trap as well as active site for CO{sub 2} reduction, which is probably responsible for the enhanced activity and selectivity of CO{sub 2} to CO over Ag/CdS. The possible mechanism of CO{sub 2} photoreduction over Ag/CdS was proposed in view of the abovementioned analysis.

  8. Reduction of SO sub 2 emission from a fluidized-bed under staged combustion by coarse limestone

    International Nuclear Information System (INIS)

    Khan, W.Z.; Gibbbs, B.M.

    1998-01-01

    A study was performed to investigate the effect of course limestone on the reduction of SO sub 2 emission from a fluidized-bed under staged combustion. The limestone of 1.2-2.5 mm size was premixed with fine coal of 1-3 mm size and fed under bed. The staging levels, bed height, and Ca/S ratio was fixed at 70:30, 30 cm and 3:1, respectively. A maximum of around 50% reduction in SO sub 2 emissions was achieved at both excess air of 20 and 40% and at 830 deg. C. bed temperature. The SO sub 2 emissions were very sensitive to bed temperature. The course limestone was found better in desulfurization efficiency at lower temperature than fine limestone. (author)

  9. The effect of the adsorbate layer on the work function reduction of gold substrates under external electric fields

    Science.gov (United States)

    He, Xiang; Cheng, Feng; Chen, Zhao-Xu

    2017-12-01

    The interface interaction between the dimethyl sulfide (DMS) molecule and the gold substrate under external electric fields is investigated by density functional theory method. The polarized DMS adsorbate reduces the work function of the gold substrate while the induced substrate dipole upon the adsorption slightly increases the work function. The DMS layer partially shields the Au(111) substrate from the electric fields and the vacuum level of DMS/Au(111) shifts less than of Au(111) in consequence. Under electric fields pointing outward from the Au(111) surface, both the reduction of work function and the adsorption of DMS molecule are enhanced on the surface. We also suggest the possible application of the field-effect transistor (FET) sensor with gold gate for detecting DMS molecule by utilizing the reduction of substrate work function upon adsorption. The effects of coverage and electric field on the theoretical sensitivity of the sensor are also discussed.

  10. Mitochondrial role in cell aging

    Science.gov (United States)

    Miquel, J.; Fleming, J.; Economos, A. C.; Johnson, J. E., Jr.

    1980-01-01

    The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

  11. Mitochondrial Metabolism in Aging Heart

    Science.gov (United States)

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  12. Hexavalent chromium reduction under fermentative conditions with lactate stimulated native microbial communities.

    Science.gov (United States)

    Somenahally, Anil C; Mosher, Jennifer J; Yuan, Tong; Podar, Mircea; Phelps, Tommy J; Brown, Steven D; Yang, Zamin K; Hazen, Terry C; Arkin, Adam P; Palumbo, Anthony V; Van Nostrand, Joy D; Zhou, Jizhong; Elias, Dwayne A

    2013-01-01

    Microbial reduction of toxic hexavalent chromium (Cr(VI)) in-situ is a plausible bioremediation strategy in electron-acceptor limited environments. However, higher [Cr(VI)] may impose stress on syntrophic communities and impact community structure and function. The study objectives were to understand the impacts of Cr(VI) concentrations on community structure and on the Cr(VI)-reduction potential of groundwater communities at Hanford, WA. Steady state continuous flow bioreactors were used to grow native communities enriched with lactate (30 mM) and continuously amended with Cr(VI) at 0.0 (No-Cr), 0.1 (Low-Cr) and 3.0 (High-Cr) mg/L. Microbial growth, metabolites, Cr(VI), 16S rRNA gene sequences and GeoChip based functional gene composition were monitored for 15 weeks. Temporal trends and differences in growth, metabolite profiles, and community composition were observed, largely between Low-Cr and High-Cr bioreactors. In both High-Cr and Low-Cr bioreactors, Cr(VI) levels were below detection from week 1 until week 15. With lactate enrichment, native bacterial diversity substantially decreased as Pelosinus spp., and Sporotalea spp., became the dominant groups, but did not significantly differ between Cr concentrations. The Archaea diversity also substantially decreased after lactate enrichment from Methanosaeta (35%), Methanosarcina (17%) and others, to mostly Methanosarcina spp. (95%). Methane production was lower in High-Cr reactors suggesting some inhibition of methanogens. Several key functional genes were distinct in Low-Cr bioreactors compared to High-Cr. Among the Cr resistant microbes, Burkholderia vietnamiensis, Comamonas testosterone and Ralstonia pickettii proliferated in Cr amended bioreactors. In-situ fermentative conditions facilitated Cr(VI) reduction, and as a result 3.0 mg/L Cr(VI) did not impact the overall bacterial community structure.

  13. Hexavalent chromium reduction under fermentative conditions with lactate stimulated native microbial communities.

    Directory of Open Access Journals (Sweden)

    Anil C Somenahally

    Full Text Available Microbial reduction of toxic hexavalent chromium (Cr(VI in-situ is a plausible bioremediation strategy in electron-acceptor limited environments. However, higher [Cr(VI] may impose stress on syntrophic communities and impact community structure and function. The study objectives were to understand the impacts of Cr(VI concentrations on community structure and on the Cr(VI-reduction potential of groundwater communities at Hanford, WA. Steady state continuous flow bioreactors were used to grow native communities enriched with lactate (30 mM and continuously amended with Cr(VI at 0.0 (No-Cr, 0.1 (Low-Cr and 3.0 (High-Cr mg/L. Microbial growth, metabolites, Cr(VI, 16S rRNA gene sequences and GeoChip based functional gene composition were monitored for 15 weeks. Temporal trends and differences in growth, metabolite profiles, and community composition were observed, largely between Low-Cr and High-Cr bioreactors. In both High-Cr and Low-Cr bioreactors, Cr(VI levels were below detection from week 1 until week 15. With lactate enrichment, native bacterial diversity substantially decreased as Pelosinus spp., and Sporotalea spp., became the dominant groups, but did not significantly differ between Cr concentrations. The Archaea diversity also substantially decreased after lactate enrichment from Methanosaeta (35%, Methanosarcina (17% and others, to mostly Methanosarcina spp. (95%. Methane production was lower in High-Cr reactors suggesting some inhibition of methanogens. Several key functional genes were distinct in Low-Cr bioreactors compared to High-Cr. Among the Cr resistant microbes, Burkholderia vietnamiensis, Comamonas testosterone and Ralstonia pickettii proliferated in Cr amended bioreactors. In-situ fermentative conditions facilitated Cr(VI reduction, and as a result 3.0 mg/L Cr(VI did not impact the overall bacterial community structure.

  14. Hexavalent Chromium Reduction under Fermentative Conditions with Lactate Stimulated Native Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Somenahally, Anil C [ORNL; Mosher, Jennifer J [ORNL; Yuan, Tong [University of Oklahoma; Phelps, Tommy Joe [ORNL; Brown, Steven D [ORNL; Yang, Zamin Koo [ORNL; Hazen, Terry C [ORNL; Arkin, Adam [Lawrence Berkeley National Laboratory (LBNL); Palumbo, Anthony Vito [ORNL; Van Nostrand, Dr. Joy D. [Oklahoma University; Zhou, Jizhong [University of Oklahoma; Elias, Dwayne A [ORNL

    2013-01-01

    Microbial reduction of toxic hexavalent chromium (Cr(VI)) in-situ is a plausible bioremediation strategy in electron-acceptor limited environments. However, higher [Cr(VI)] may impose stress on syntrophic communities and impact community structure and function. The study objectives were to understand the impacts of Cr(VI) concentrations on community structure and on the Cr(VI)-reduction potential of groundwater communities at Hanford, WA. Steady state continuous flow bioreactors were used to grow native communities enriched with lactate (30 mM) and continuously amended with Cr(VI) at 0.0 (No-Cr), 0.1 (Low-Cr) and 3.0 (High-Cr) mg/L. Microbial growth, metabolites, Cr(VI), 16S rRNA gene sequences and GeoChip based functional gene composition were monitored for 15 weeks. Temporal trends and differences in growth, metabolite profiles, and community composition were observed, largely between Low-Cr and High-Cr bioreactors. In both High-Cr and Low-Cr bioreactors, Cr(VI) levels were below detection from week 1 until week 15. With lactate enrichment, native bacterial diversity substantially decreased as Pelosinus spp., and Sporotalea spp., became the dominant groups, but did not significantly differ between Cr concentrations. The Archaea diversity also substantially decreased after lactate enrichment from Methanosaeta (35%), Methanosarcina (17%) and others, to mostly Methanosarcina spp. (95%). Methane production was lower in High-Cr reactors suggesting some inhibition of methanogens. Several key functional genes were distinct in Low-Cr bioreactors compared to High-Cr. Among the Cr resistant microbes, Burkholderia vietnamiensis, Comamonas testosterone and Ralstonia pickettii proliferated in Cr amended bioreactors. In-situ fermentative conditions facilitated Cr(VI) reduction, and as a result 3.0 mg/L Cr(VI) did not impact the overall bacterial community structure.

  15. SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.

    Science.gov (United States)

    Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

    2017-05-01

    Mitochondrial calcium ([Ca 2+ ] m ) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca 2+ ] m uptake upon SK channel activation as detected by time lapse mitochondrial Ca 2+ measurements with the Ca 2+ -binding mitochondria-targeted aequorin and FRET-based [Ca 2+ ] m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca 2+ ] m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.

  16. Optimization of Power Generation Rights Under the Requirements of Energy Conservation and Emission Reduction

    Science.gov (United States)

    Hu-ping, YANY; Chong-wei, ZHONG; Fei-fei, YAN; Cheng-yi, TANG

    2018-03-01

    In recent years, the energy crisis and greenhouse effect problem have caused wide public concern, if these issues cannot be resolved quickly, they will bring troubles to people’s lives.In response, many countries around the world have implemented policies to reduce energy consumption and greenhouse gas emissions. In our country, the electric power industry has made great contribution to the daily life of people and the development of industry, but it is also an industry of high consumption and high emission.In order to realize the sustainable development of society, it is necessary to make energy conservation and emission reduction in the power industry as an important part of the realization of this goal.In this context, power generation trade has become a hot topic in energy conservation and emission reduction.Through the electricity consumption of the units with different power efficiency and coal consumption rate,it can achieve the target of reducing coal consumption, reducing network loss, reducing greenhouse gas emission, and increasing social benefit,and so on. This article put forward a optimal energy model on the basis of guaranteeing safety and environmental protection.In this paper, they used the IEEE30, IEEE39, IEEE57 and IEEE118 node system as an example, and set up the control groups to prove the practicality of the presented model.The solving method of this model was interior-point method.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    and 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....

  18. Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

    Directory of Open Access Journals (Sweden)

    Guang-xing Shui

    2017-01-01

    Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

  19. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Michelle Barbi de Moura

    Full Text Available SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.

  20. Behaviour of the RBMK-1000 plant during reactivity disturbances under part load reduction - completing investigations

    International Nuclear Information System (INIS)

    Clemente, M.; Langenbuch, S.

    1989-01-01

    This report describes investigations of the behavior of a RBMK-1000 reactor core during reactivity initiated accidents and completes earlier studies of the Chernobyl accident. Special questions related to this accident are studied, e.g. the effect of Xenon dynamics during the delayed load reduction and the coarse of the experiment as planned with the coast-down of four main recirculaton pumps at nominal part load conditions. The main interest is the detailed analysis of reactivity initiated accidents in the low power range till 25% during start-up. In the calculations no reactor trip is taken into account. The results confirm the unfavourable effects of the positive void coefficient, which are amplified in the low power range. Finally the results are discussed in comparison to other positive reactivity effects. (orig.) [de

  1. Marketing of Local Public Services under the Reduction of Administrative Expenditures

    Directory of Open Access Journals (Sweden)

    Ani Matei

    2009-03-01

    Full Text Available The concerns for reducing administrative expenditures have been expressed in the last 10-15 years in concrete initiatives. It is worth to remark the occurrence of networks concerning the application of Standard Cost Model (SCM, aimed to reduce administrative expenditures for affairs. Even the European Commission aims to elaborate and implement a strategy to reduce administrative costs for affairs inside the European Union. We find similar initiatives in OECD, several European states, i.e. United Kingdom, Denmark, Netherlands, Sweden, Norway, as well as other countries. An international project “Cross Country Benchmarking” is important in this respect.These concerns have developed and diversified due to the worsening of the economic crisis. The crisis effects, already visible in the public sector too, lessen more and more the possibilities of satisfying the citizen’s needs. The marketing specialists bring up more and more frequently new marketing instruments that, giving the context, should generate products and services meant to satisfy the citizens’ needs. The product and service, in itself, as well as their price, become the main marketing instruments. The present paper proposes an assessment, based on the two instruments of the public marketing mix, of the way in which the reduction of the administrative expenditures can lead to a reduction in the price of the public services or to their diversification with regard to the consumers’ needs. By using elements specific to the production theory, the product management shall be substantiated, as well as the strategies regarding the prices of the public services.

  2. Modeling the reduction of gross lithium erosion observed under high-flux deuterium bombardment

    NARCIS (Netherlands)

    Abrams, T.; Jaworski, M. A.; Kaita, R.; Nichols, J. H.; Stotler, D. P.; De Temmerman, G.; van den Berg, M. A.; van der Meiden, H. J.; Morgan, T. W.

    2015-01-01

    Abstract Both thin (<1 μm) and thick (∼500 μm) lithium films under high-flux deuterium and neon plasma bombardment were studied in the linear plasma device Magnum-PSI at ion fluxes >1024 m−2 s−1 and surface temperatures <700 °C.

  3. Trial of finger contamination reduction of the operator in nerve block treatment. Comparison of over- and under-table systems

    International Nuclear Information System (INIS)

    Saito, Hajime; Okabe, Keigo; Nakazawa, Yasuo

    2004-01-01

    Fluoroscopy-guided intervention of the lumbar spine, such as nerve block, plays an important role in the management of disc hernia patients. However, irradiation of operators' fingers remains a problem even with careful collimation and operation, especially when performed by non-radiologists. We compared the irradiation doses of under-table and over-table fluoroscopy systems, and we discuss the most advantageous method of reducing irradiation. The effectiveness and conditions of use of lead protection gloves were also evaluated. Skin dose was monitored using polymethyl methacrylate (PMMA) and an electronic dose meter. The skin doses of over- and under-table fluoroscopy were compared using C-arm fluoroscopy. Finger irradiation dose with 0.03 mmPb protection gloves was also measured. The under-table method reduced skin dose by 95% compared with the over-table method. Thicker PMMA resulted in a higher rate of irradiation reduction. Protection gloves reduced radiation dose by half, although this reduction was cancelled when automatic brightness control (ABC) was utilized. Under-tube fluoroscopy was superior to over-tube fluoroscopy in reducing irradiation to the fingers. (author)

  4. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

    Science.gov (United States)

    Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

    2015-11-01

    Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Savannah River Site Footprint Reduction Results under the American Recovery and Reinvestment Act - 13302

    Energy Technology Data Exchange (ETDEWEB)

    Flora, Mary [Savannah River Nuclear Solutions Bldg. 730-4B, Aiken, SC 29808 (United States); Adams, Angelia [United States Department of Energy Bldg. 730-B, Aiken, SC 29808 (United States); Pope, Robert [United States Environmental Protection Agency Region IV Atlanta, GA 30303 (United States)

    2013-07-01

    The Savannah River Site (SRS) is an 802 square-kilometer United States Department of Energy (US DOE) nuclear facility located along the Savannah River near Aiken, South Carolina, managed and operated by Savannah River Nuclear Solutions. Construction of SRS began in the early 1950's to enhance the nation's nuclear weapons capability. Nuclear weapons material production began in the early 1950's, eventually utilizing five production reactors constructed to support the national defense mission. Past operations have resulted in releases of hazardous constituents and substances to soil and groundwater, resulting in 515 waste sites with contamination exceeding regulatory thresholds. More than 1,000 facilities were constructed onsite with approximately 300 of them considered radiological, nuclear or industrial in nature. In 2003, SRS entered into a Memorandum of Agreement with its regulators to accelerate the cleanup using an Area Completion strategy. The strategy was designed to focus cleanup efforts on the 14 large industrial areas of the site to realize efficiencies of scale in the characterization, assessment, and remediation activities. This strategy focuses on addressing the contaminated surface units and the vadose zone and addressing groundwater plumes subsequently. This approach streamlines characterization and remediation efforts as well as the required regulatory documentation, while enhancing the ability to make large-scale cleanup decisions. In February 2009, Congress approved the American Reinvestment and Recovery Act (ARRA) to create jobs and promote economic recovery. At SRS, ARRA funding was established in part to accelerate the completion of environmental remediation and facility deactivation and decommissioning (D and D). By late 2012, SRS achieved 85 percent footprint reduction utilizing ARRA funding by accelerating and coupling waste unit remediation with D and D of remnant facilities. Facility D and D activities were sequenced and

  6. NOx reduction over metal-ion exchanged novel zeolite under lean conditions. Activity and hydrothermal stability

    International Nuclear Information System (INIS)

    Subbiah, Ayyappan; Gujar, Amit; Price, Geoffrey L.; Cho, Byong K.; Blint, Richard J.; Yie, Jae E.

    2003-01-01

    Zeolite SUZ-4 was synthesized and tested for its hydrothermal stability using a standard aging procedure coupled with NMR spectroscopy, and was identified as a promising support for lean-NO x catalysts for high temperature applications. Various metals such as Cu, Ag, Fe, Co were ion exchanged onto the SUZ-4 zeolite, and their catalytic activity for NO/NO x conversion was measured in the presence of excess oxygen using ethylene as the reducing agent. Among the metal-ions exchanged, copper proved to be the best metal cation for lean-NO x catalysis with the optimum level of exchange at 29-42%. The optimized, fresh Cu/SUZ-4 catalyst achieved 70-80% of NO/NO x conversion activity over a wide range of temperature from 350 to 600C with the maximum conversion temperature at 450C. The presence of H 2 O and SO 2 reduced the NO/NO x conversion by about 30% of the fresh Cu/SUZ-4 catalyst due possibly to the blocking of active sites for NO/NO x adsorption. Substitution of gasoline vapor for ethylene as the reductant improved the NO x reduction activity of the fresh Cu/SUZ-4 catalyst at high temperatures above 350C. Aging the Cu/SUZ-4 catalyst resulted in a slight shift of activity profile toward higher temperatures, yielding an increase of NO conversion by 16% and a decrease of NO x conversion by 15% at 525C. The effect of H 2 O and SO 2 on the aged catalyst was to reduce the NO activity by 20% and NO x activity by 30% at 500C. The effect of space velocity change was not significant except in the low temperature range where the reaction light-off occurs. Adsorption/desorption measurements indicate that aging Cu/SUZ-4 results in partial migration/agglomeration of Cu particles in the pores thereby reducing the NO/NO x activity. Overall, the NO x conversion efficiency of Cu/SUZ-4, for both fresh and aged, is much better than the benchmark Cu/ZSM-5 in the presence of H 2 O and/or SO 2

  7. Mechanisms of basin-scale nitrogen load reductions under intensified irrigated agriculture.

    Directory of Open Access Journals (Sweden)

    Rebecka Törnqvist

    Full Text Available Irrigated agriculture can modify the cycling and transport of nitrogen (N, due to associated water diversions, water losses, and changes in transport flow-paths. We investigate dominant processes behind observed long-term changes in dissolved inorganic nitrogen (DIN concentrations and loads of the extensive (465,000 km2 semi-arid Amu Darya River basin (ADRB in Central Asia. We specifically considered a 40-year period (1960-2000 of large irrigation expansion, reduced river water flows, increased fertilizer application and net increase of N input into the soil-water system. Results showed that observed decreases in riverine DIN concentration near the Aral Sea outlet of ADRB primarily were due to increased recirculation of irrigation water, which extends the flow-path lengths and enhances N attenuation. The observed DIN concentrations matched a developed analytical relation between concentration attenuation and recirculation ratio, showing that a fourfold increase in basin-scale recirculation can increase DIN attenuation from 85 to 99%. Such effects have previously only been observed at small scales, in laboratory experiments and at individual agricultural plots. These results imply that increased recirculation can have contributed to observed increases in N attenuation in agriculturally dominated drainage basins in different parts of the world. Additionally, it can be important for basin scale attenuation of other pollutants, including phosphorous, metals and organic matter. A six-fold lower DIN export from ADRB during the period 1981-2000, compared to the period 1960-1980, was due to the combined result of drastic river flow reduction of almost 70%, and decreased DIN concentrations at the basin outlet. Several arid and semi-arid regions around the world are projected to undergo similar reductions in discharge as the ADRB due to climate change and agricultural intensification, and may therefore undergo comparable shifts in DIN export as shown here

  8. Recent progress in transition-metal-catalyzed reduction of molecular dinitrogen under ambient reaction conditions.

    Science.gov (United States)

    Nishibayashi, Yoshiaki

    2015-10-05

    This paper describes our recent progress in catalytic nitrogen fixation by using transition-metal-dinitrogen complexes as catalysts. Two reaction systems for the catalytic transformation of molecular dinitrogen into ammonia and its equivalent such as silylamine under ambient reaction conditions have been achieved by the molybdenum-, iron-, and cobalt-dinitrogen complexes as catalysts. Many new findings presented here may provide new access to the development of economical nitrogen fixation in place of the Haber-Bosch process.

  9. Investing in finite-life carbon emissions reduction program under risk and idiosyncratic uncertainty

    International Nuclear Information System (INIS)

    Fouilloux, Jessica; Moraux, Franck; Viviani, Jean-Laurent

    2015-01-01

    This paper aims at emphasizing the ability of new frameworks of real option model to highlight key characteristics of industrial Carbon Emissions Reduction Program investment decision. We develop both theoretical arguments and numerical simulations with structural parameters calibrated on real-life data. We find that both radical uncertainty and risk lead to speed-up green investments, compared to the predictions of real option models that are normally used in green investment literature. The conventional “wait and see” attitude, questioned in recent developments of the real option theory, is not validated. In conclusion, our results should foster companies to implement green investments and help governments to define appropriate incentives to encourage green investments. Of particular note, the paper highlights that finance theory is not necessarily an obstacle to green investment decisions. -- Highlights: •We use real option model to identify key features of CERP investment decision. •We determine the optimal carbon price threshold to undertake a CERP. •Investment decision is a non-monotonic function of idiosyncratic uncertainty. •Increasing uncertainty until a moderate level can accelerate investment decision. •Decreasing idiosyncratic risk can accelerate investment decision

  10. A blood pressure monitor with robust noise reduction system under linear cuff inflation and deflation.

    Science.gov (United States)

    Usuda, Takashi; Kobayashi, Naoki; Takeda, Sunao; Kotake, Yoshifumi

    2010-01-01

    We have developed the non-invasive blood pressure monitor which can measure the blood pressure quickly and robustly. This monitor combines two measurement mode: the linear inflation and the linear deflation. On the inflation mode, we realized a faster measurement with rapid inflation rate. On the deflation mode, we realized a robust noise reduction. When there is neither noise nor arrhythmia, the inflation mode incorporated on this monitor provides precise, quick and comfortable measurement. Once the inflation mode fails to calculate appropriate blood pressure due to body movement or arrhythmia, then the monitor switches automatically to the deflation mode and measure blood pressure by using digital signal processing as wavelet analysis, filter bank, filter combined with FFT and Inverse FFT. The inflation mode succeeded 2440 measurements out of 3099 measurements (79%) in an operating room and a rehabilitation room. The new designed blood pressure monitor provides the fastest measurement for patient with normal circulation and robust measurement for patients with body movement or severe arrhythmia. Also this fast measurement method provides comfortableness for patients.

  11. Analyzing Agricultural Sustainability Indicators,Under Energy Subsidy Reduction Policy(Case Study of Qorveh Plain

    Directory of Open Access Journals (Sweden)

    H. Balali

    2016-03-01

    Full Text Available Introduction: Generally, subsidies are the amounts of government payments in order to provide all society members with minimum well-being. In several countries such as Iran, the agriculture sector is supported by different methods to achieve goals such as increasing farmers' income, supporting domestic producers and eliminating dependence on imports, preserving employment and reducing poverty. A significant part of agriculture subsidies has been allocated to energy resources, chemical fertilizers, seeds, agriculture machines, vaccines, animal toxins, the interest on bank loans, insurance fees, certain airplane services, distributing young saplings, and government guaranteed purchase of products. However, examining the subsidies system in Iran reveals that most government payments are in the agriculture sector and more specifically on energy resources. Recently, the extra low cost of energy in the agriculture sector, which has had certain government supports, has resulted in low productivity and environmental damage, and has resulted in increased demand for agricultural products due to population growth, changes in life pattern, deviation in energy cost in agricultural sector, environment destruction and influences on sustainable agriculture indicators. Moreover, among different production units, agriculture has the closest relationship with the environment. This relationship is a mutual.On the one hand, erosion and destruction of the environment along with pollution growth and shortage of water resources negatively influences the production and efficiency of agricultural products, and on the other hand, agricultural pollutants and irregular use of chemical fertilizers in this sector impose indispensable damages to the environment.This study aims to apply a partial equilibrium model in order to examine direct and indirect effects of reduction of energy subsidies on economic and environmental indicators of agricultural sustainability in the Qorveh

  12. Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

    Science.gov (United States)

    Long, Aaron; Klimova, Nina; Kristian, Tibor

    2017-10-01

    NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.

  13. Effect of Intravenous Infusion of Lidocaine on Pain Reduction after Cesarean Section under General Anesthesia

    Directory of Open Access Journals (Sweden)

    Anahita Hirmanpour

    2018-01-01

    Full Text Available Background: The present study was conducted to evaluate the effect of Lidocaine on pain reduction during and ileus and the need for opioids after caesarean section. Methods: For this randomized double-blind controlled clinical trial, 40 ASA I, II pregnant women who were candidates for caesarean section with general anesthesia, were randomly allocated into two groups of Lidocaine receivers and placebo using randomized block design; the Lidocaine group received 1.5 mg/kg of Lidocaine right before the surgery and then its infusion with a dose of 2 mg/kg.h until the end of the surgery and the placebo group received normal saline with the same volume and application. Patients’ pain intensity was measured using numerical rating scale (NRS, 0 (entering the recovery, 0.5, 1, 4, 12 and 24 hours after the surgery. Results: Lidocaine decreased the systolic and diastolic pressures of the patients only during the first minute after intubation, decreased the mean of arterial blood pressure at the 10th minute after intubation and 40th minute after surgery, and also decreased the mean of patients’ pain intensity, Diclofenac and Pethidine consumption, side effects (nausea and vomiting and reduced the time interval before the first time of tolerating oral liquids; but it had effect on infants’ Apgar score 1 and 5 minutes after delivery. Conclusions: Lidocaine was definitely effective on reducing the intensity of pain, opioid and non-steroidal anti-inflammatory drugs consumption and ileus after surgery with the least occurrence of side effects for mothers and infants.

  14. Effect of Intravenous Infusion of Lidocaine on Pain Reduction after Cesarean Section under General Anesthesia

    Directory of Open Access Journals (Sweden)

    Anahita Hirmanpour

    2018-01-01

    Full Text Available Background: The present study was conducted to evaluate the effect of Lidocaine on pain reduction during and ileus and the need for opioids after caesarean section.Methods: For this randomized double-blind controlled clinical trial, 40 ASA I, II pregnant women who were candidates for caesarean section with general anesthesia, were randomly allocated into two groups of Lidocaine receivers and placebo using randomized block design; the Lidocaine group received 1.5 mg/kg of Lidocaine right before the surgery and then its infusion with a dose of 2 mg/kg.h until the end of the surgery and the placebo group received normal saline with the same volume and application. Patients’ pain intensity was measured using numerical rating scale (NRS, 0 (entering the recovery, 0.5, 1, 4, 12 and 24 hours after the surgery.Results: Lidocaine decreased the systolic and diastolic pressures of the patients only during the first minute after intubation, decreased the mean of arterial blood pressure at the 10th minute after intubation and 40th minute after surgery, and also decreased the mean of patients’ pain intensity, Diclofenac and Pethidine consumption, side effects (nausea and vomiting and reduced the time interval before the first time of tolerating oral liquids; but it had effect on infants’ Apgar score 1 and 5 minutes after delivery.Conclusions: Lidocaine was definitely effective on reducing the intensity of pain, opioid and non-steroidal anti-inflammatory drugs consumption and ileus after surgery with the least occurrence of side effects for mothers and infants.

  15. Biochemical and anatomical changes and yield reduction in rice (Oryza sativa L.) under varied salinity regimes.

    Science.gov (United States)

    Hakim, M A; Juraimi, Abdul Shukor; Hanafi, M M; Ismail, Mohd Razi; Selamat, Ahmad; Rafii, M Y; Latif, M A

    2014-01-01

    Five Malaysian rice (Oryza sativa L.) varieties, MR33, MR52, MR211, MR219, and MR232, were tested in pot culture under different salinity regimes for biochemical response, physiological activity, and grain yield. Three different levels of salt stresses, namely, 4, 8, and 12 dS m(-1), were used in a randomized complete block design with four replications under glass house conditions. The results revealed that the chlorophyll content, proline, sugar content, soluble protein, free amino acid, and yield per plant of all the genotypes were influenced by different salinity levels. The chlorophyll content was observed to decrease with salinity level but the proline increased with salinity levels in all varieties. Reducing sugar and total sugar increased up to 8 dS m(-1) and decreased up to 12 dS m(-1). Nonreducing sugar decreased with increasing the salinity levels in all varieties. Soluble protein and free amino acid also decreased with increasing salinity levels. Cortical cells of MR211 and MR232 did not show cell collapse up to 8 dS m(-1) salinity levels compared to susceptible checks (IR20 and BRRI dhan29). Therefore, considering all parameters, MR211 and MR232 showed better salinity tolerance among the tested varieties. Both cluster and principal component analyses depict the similar results.

  16. Biochemical and Anatomical Changes and Yield Reduction in Rice (Oryza sativa L. under Varied Salinity Regimes

    Directory of Open Access Journals (Sweden)

    M. A. Hakim

    2014-01-01

    Full Text Available Five Malaysian rice (Oryza sativa L. varieties, MR33, MR52, MR211, MR219, and MR232, were tested in pot culture under different salinity regimes for biochemical response, physiological activity, and grain yield. Three different levels of salt stresses, namely, 4, 8, and 12 dS m−1, were used in a randomized complete block design with four replications under glass house conditions. The results revealed that the chlorophyll content, proline, sugar content, soluble protein, free amino acid, and yield per plant of all the genotypes were influenced by different salinity levels. The chlorophyll content was observed to decrease with salinity level but the proline increased with salinity levels in all varieties. Reducing sugar and total sugar increased up to 8 dS m−1 and decreased up to 12 dS m−1. Nonreducing sugar decreased with increasing the salinity levels in all varieties. Soluble protein and free amino acid also decreased with increasing salinity levels. Cortical cells of MR211 and MR232 did not show cell collapse up to 8 dS m−1 salinity levels compared to susceptible checks (IR20 and BRRI dhan29. Therefore, considering all parameters, MR211 and MR232 showed better salinity tolerance among the tested varieties. Both cluster and principal component analyses depict the similar results.

  17. Microbial reduction of Fe(III) in the presence of oxygen under low pH conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kusel, K.; Roth, U.; Drake, H.L. [University of Bayreuth, Bayreuth (Germany)

    2002-07-01

    In acidic, coal mining lake sediments, facultatively anaerobic Acidiphilium species are probably involved in the reduction of Fe(III). Previous results indicate that these bacteria can co-respire O{sub 2} and Fe(III). In this study, we investigated the capacity of the sediment microbiota to reduce Fe(III) in the presence of O{sub 2} at pH 3. In sediment microcosms with 4% O{sub 2} in the headspace, the concentration of Fe(II) increased at a rate of 1.03 {mu}mol (g wet sediment){sup -1} day{sup -1} within the first 7 days of incubation which was similar to the rate obtained with controls incubated under anoxic conditions. However, in microcosms incubated under air, Fe(II) was consumed after a lag phase of 8 h with a rate of 2.66 {mu}mol (g wet sediment){sup -1} day{sup -1}. Acidiphilium cryptum JF-5, isolated from this sediment, reduced soluble Fe(III) with either 4 or 21% O{sub 2} in the headspace, and concomitantly consumed O{sub 2}. However, the rate of Fe(II) formation normalized for cell density decreased under oxic conditions. Schwertmannite, the predominant Fe(III)-mineral of this sediment, was also reduced by A. cryptum JF-5 under oxic conditions. The rate of Fe(II) formation by A. cryptum JF-5 decreased after transfer from preincubation under air in medium lacking Fe(III). Acidiphilium cryptum JF-5 did not form Fe(II) when preincubated under air and transferred to anoxic medium containing Fe(III) and chloramphenicol, an inhibitor of protein synthesis. These results indicate that: (i) the reduction of Fe(III) can occur at low O{sub 2} concentrations in acidic sediments; (ii) Fe(II) can be oxidized at O{sub 2} concentrations near saturation; and (iii) the enzyme(s) responsible for the reduction of Fe(III) in A. cryptum JF-5 are not constitutive.

  18. Anaerobic reductive dechlorination of tetrachloroethene: how can dual Carbon-Chlorine isotopic measurements help elucidating the underlying reaction mechanism?

    Science.gov (United States)

    Badin, Alice; Buttet, Géraldine; Maillard, Julien; Holliger, Christof; Hunkeler, Daniel

    2014-05-01

    Chlorinated ethenes (CEs) such as tetrachloroethene (PCE) are common persistent groundwater contaminants. Among clean-up strategies applied to sites affected by such pollution, bioremediation has been considered with a growing interest as it represents a cost-effective, environmental friendly approach. This technique however sometimes leads to an incomplete and slow biodegradation of CEs resulting in an accumulation of toxic metabolites. Understanding the reaction mechanisms underlying anaerobic reductive dechlorination would thus help assessing PCE biodegradation in polluted sites. Stable isotope analysis can provide insight into reaction mechanisms. For chlorinated hydrocarbons, carbon (C) and chlorine (Cl) isotope data (δ13C and δ37Cl) tend to show a linear correlation with a slope (m ≡ ɛC/ɛCl) characteristic of the reaction mechanism [1]. This study hence aims at exploring the potential of a dual C-Cl isotope approach in the determination of the reaction mechanisms involved in PCE reductive dechlorination. C and Cl isotope fractionation were investigated during anaerobic PCE dechlorination by two bacterial consortia containing members of the Sulfurospirillum genus. The specificity in these consortia resides in the fact that they each conduct PCE reductive dechlorination catalysed by one different reductive dehalogenase, i.e. PceADCE which yields trichloroethene (TCE) and cis-dichloroethene (cDCE), and PceATCE which yields TCE only. The bulk C isotope enrichment factors were -3.6±0.3 o for PceATCE and -0.7±0.1o for PceADCE. The bulk Cl isotope enrichment factors were -1.3±0.2 o for PceATCE and -0.9±0.1 o for PceADCE. When applying the dual isotope approach, two m values of 2.7±0.1 and 0.7±0.2 were obtained for the reductive dehalogenases PceATCE and PceADCE, respectively. These results suggest that PCE can be degraded according to two different mechanisms. Furthermore, despite their highly similar protein sequences, each reductive dehalogenase seems

  19. Goethite promoted biodegradation of 2,4-dinitrophenol under nitrate reduction condition.

    Science.gov (United States)

    Tang, Ting; Yue, Zhengbo; Wang, Jin; Chen, Tianhu; Qing, Chengsong

    2018-02-05

    Iron oxide may interact with other pollutants in the aquatic environments and further influence their toxicity, transport and fate. The current study was conducted to investigate the biodegradation of 2,4-dinitrophenol (2,4-DNP) in the presence of iron oxide of goethite under anoxic condition using nitrate as the electron acceptor. Experiment results showed that the degradation rate of 2,4-DNP was improved by goethite. High performance liquid chromatography-mass spectra analysis results showed that goethite promoted degradation and transformation of 2,4-diaminophenol and 2-amino-4-nitrophenol (2-nitro-4-aminophenol). Microbial community analysis results showed that the abundance of Actinobacteria, which have the potential ability to degrade PAHs, was increased when goethite was available. This might partially explain the higher degradation of 2,4-DNP. Furthermore, another bacterium of Desulfotomaculum reducens which could reduce soluble Fe(III) and nitrate was also increased. Results further confirmed that nanomaterials in the aquatic environment will influence the microbial community and further change the transformation process of toxic pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Reduction of photosynthetically active radiation under extreme stratospheric-aerosol loads

    International Nuclear Information System (INIS)

    Gerstl, S.A.W.; Zardecki, A.

    1981-01-01

    The recently published hypothesis that the Cretaceous-Tertiary extinctions might be caused by an obstruction of sunlight is tested by model calculations. First we compute the total mass of stratospheric aerosols under normal atmospheric conditions for four different (measured) aerosol size distributions and vertical profiles. For comparison, the stratospheric dust masses after four volcanic eruptions are also evaluated. Detailed solar radiative transfer calculations are then performed for artificially increased aerosol amounts until the postulated darkness scenario is obtained. Thus we find that a total stratospheric aerosol mass between 1 and 4 times 10 16 g is sufficient to reduce photosynthesis to 10 3 of normal. We also infer from this result that the impact of a 0.4- to 3-km-diameter asteroid or a close encounter with a Halley-size comet may deposit that amount of particulates into the stratosphere. The darkness scenario of Alvarez et al., is thus shown to be a possible extinction mechanism, even with smaller size asteroids or comets than previously estimated

  1. A Joint Optimal Decision on Shipment Size and Carbon Reduction under Direct Shipment and Peddling Distribution Strategies

    Directory of Open Access Journals (Sweden)

    Daiki Min

    2017-11-01

    Full Text Available Recently, much research has focused on lowering carbon emissions in logistics. This paper attempts to contribute to the literature on the joint shipment size and carbon reduction decisions by developing novel models for distribution systems under direct shipment and peddling distribution strategies. Unlike the literature that has simply investigated the effects of carbon costs on operational decisions, we address how to reduce carbon emissions and logistics costs by adjusting shipment size and making an optimal decision on carbon reduction investment. An optimal decision is made by analyzing the distribution cost including not only logistics and carbon trading costs but also the cost for adjusting carbon emission factors. No research has explicitly considered the two sources of carbon emissions, but we develop a model covering the difference in managing carbon emissions from transportation and storage. Structural analysis guides how to determine an optimal shipment size and emission factors in a closed form. Moreover, we analytically prove the possibility of reducing the distribution cost and carbon emissions at the same time. Numerical analysis follows validation of the results and demonstrates some interesting findings on carbon and distribution cost reduction.

  2. Effect of addition of organic waste on reduction of Escherichia coli during cattle feces composting under high-moisture condition.

    Science.gov (United States)

    Hanajima, Dai; Kuroda, Kazutaka; Fukumoto, Yasuyuki; Haga, Kiyonori

    2006-09-01

    To ensure Escherichia coli reduction during cattle feces composting, co-composting with a variety of organic wastes was examined. A mixture of dairy cattle feces and shredded rice straw (control) was blended with organic wastes (tofu residue, rice bran, rapeseed meal, dried chicken feces, raw chicken feces, or garbage), and composted using a bench-scale composter under the high-moisture condition (78%). The addition of organic waste except chicken feces brought about maximum temperatures of more than 55 degrees C and significantly reduced the number of E. coli from 10(6) to below 10(2)CFU/g-wet after seven days composting, while in the control treatment, E. coli survived at the same level as that of raw feces. Enhancements of the thermophilic phase and E. coli reduction were related to the initial amount of easily digestible carbon in mass determined as BOD. BOD value more than 166.2 mg O2/DMg brought about significant E. coli reduction.

  3. MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

    Directory of Open Access Journals (Sweden)

    Elisa Balboa

    2017-08-01

    Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

  4. Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy

    Directory of Open Access Journals (Sweden)

    Pasquale Picone

    2014-01-01

    Full Text Available Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ, an important component in Alzheimer’s disease (AD pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed.

  5. Oxidative stress negatively affects human sperm mitochondrial respiration.

    Science.gov (United States)

    Ferramosca, Alessandra; Pinto Provenzano, Sara; Montagna, Daniela Domenica; Coppola, Lamberto; Zara, Vincenzo

    2013-07-01

    To correlate the level of oxidative stress in serum and seminal fluid and the level of sperm deoxyribonucleic acid (DNA) fragmentation with sperm mitochondrial respiratory efficiency. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically treated sperm cells. A possible relationship between sperm mitochondrial respiratory efficiency, the level of oxidative stress, and the level of sperm DNA fragmentation was investigated. Sperm motility was positively correlated with mitochondrial respiration but negatively correlated with oxidative stress and DNA fragmentation. Interestingly, sperm mitochondrial respiratory activity was negatively affected by oxidative stress and DNA fragmentation. Our data indicate that sperm mitochondrial respiration is decreased in patients with high levels of reactive oxygen species by an uncoupling between electron transport and adenosine triphosphate synthesis. This reduction in mitochondrial functionality might be 1 of the reasons responsible for the decrease in spermatozoa motility. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Application of numerical modeling of selective NOx reduction by hydrocarbon under diesel transient conditions in consideration of hydrocarbon adsorption and desorption process

    International Nuclear Information System (INIS)

    Watanabe, Y.; Asano, A.; Banno, K.; Yokota, K.; Sugiura, M.

    2001-01-01

    A model of NO x selective reduction by hydrocarbon (HC) was developed, which takes into account the adsorption and desorption of HC. The model was applied for predicting the performance of a De-NO x catalytic reactor, working under transient conditions such as a legislative driving cycle. Diesel fuel was used as a supplemental reductant. The behavior of HC and NO x reactions and HC adsorption and desorption has been simulated successfully by our numerical approach under the transient conditions of the simulated Japanese 10-15 driving cycle. Our model is expected to optimize the design of selective diesel NO x reduction systems using a diesel fuel as a supplemental reductant

  7. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    International Nuclear Information System (INIS)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M.

    2010-01-01

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1α, NRF-1α and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  8. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

    2010-07-02

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  9. PINK1 regulates mitochondrial trafficking in dendrites of cortical neurons through mitochondrial PKA.

    Science.gov (United States)

    Das Banerjee, Tania; Dagda, Raul Y; Dagda, Marisela; Chu, Charleen T; Rice, Monica; Vazquez-Mayorga, Emmanuel; Dagda, Ruben K

    2017-08-01

    Mitochondrial Protein Kinase A (PKA) and PTEN-induced kinase 1 (PINK1), which is linked to Parkinson's disease, are two neuroprotective serine/threonine kinases that regulate dendrite remodeling and mitochondrial function. We have previously shown that PINK1 regulates dendrite morphology by enhancing PKA activity. Here, we show the molecular mechanisms by which PINK1 and PKA in the mitochondrion interact to regulate dendrite remodeling, mitochondrial morphology, content, and trafficking in dendrites. PINK1-deficient cortical neurons exhibit impaired mitochondrial trafficking, reduced mitochondrial content, fragmented mitochondria, and a reduction in dendrite outgrowth compared to wild-type neurons. Transient expression of wild-type, but not a PKA-binding-deficient mutant of the PKA-mitochondrial scaffold dual-specificity A Kinase Anchoring Protein 1 (D-AKAP1), restores mitochondrial trafficking, morphology, and content in dendrites of PINK1-deficient cortical neurons suggesting that recruiting PKA to the mitochondrion reverses mitochondrial pathology in dendrites induced by loss of PINK1. Mechanistically, full-length and cleaved forms of PINK1 increase the binding of the regulatory subunit β of PKA (PKA/RIIβ) to D-AKAP1 to enhance the autocatalytic-mediated phosphorylation of PKA/RIIβ and PKA activity. D-AKAP1/PKA governs mitochondrial trafficking in dendrites via the Miro-2/TRAK2 complex and by increasing the phosphorylation of Miro-2. Our study identifies a new role of D-AKAP1 in regulating mitochondrial trafficking through Miro-2, and supports a model in which PINK1 and mitochondrial PKA participate in a similar neuroprotective signaling pathway to maintain dendrite connectivity. © 2017 International Society for Neurochemistry.

  10. Excimer laser assisted very fast exfoliation and reduction of graphite oxide at room temperature under air ambient for Supercapacitors electrode

    Science.gov (United States)

    Malek Hosseini, S. M. B.; Baizaee, S. M.; Naderi, Hamid Reza; Dare Kordi, Ali

    2018-01-01

    Excimer laser was used for reduction and exfoliation of graphite oxide (GO) at room temperature under air ambient. The prepared excimer laser reduced graphite oxide (XLRGO) is characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), nitrogen adsorption/desorption (BET method), X-ray diffraction (XRD), X-ray photoemission spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and UV-vis absorption techniques for surface, structural functional groups and band gap analysis. Electrochemical properties are investigated using cyclic voltammetry, galvanostatic charge-discharge, electrochemical impedance spectroscopy (EIS) and continues cyclic voltammetry (CCV) in 0.5 M Na2SO4 as electrolyte. Electrochemical investigations revealed that XLRGO electrode has enhanced supercapacitive performance including specific capacitance of 299 F/g at a scan rate of 2 mV/s. Furthermore, CCV measurement showed that XLRGO electrode kept 97.8% of its initial capacitance/capacity after 4000 cycles. The obtained results from electrochemical investigations confirm that the reduction of GO by using an excimer laser produces high-quality graphene for supercapacitor applications without the need for additional operations.

  11. Isothermal Oxidation of Magnetite to Hematite in Air and Cyclic Reduction/Oxidation Under Carbon Looping Combustion Conditions

    Science.gov (United States)

    Simmonds, Tegan; Hayes, Peter C.

    2017-12-01

    In the carbon looping combustion process the oxygen carrier is regenerated through oxidation in air; this process has been simulated by the oxidation of dense synthetic magnetite for selected temperatures and times. The oxidation of magnetite in air is shown to occur through the formation of dense hematite layers on the particle surface. This dense hematite forms through lath type shear transformations or solid-state diffusion through the product layer. Cyclic reduction in CO-CO2/oxidation in air of hematite single crystals has been carried out under controlled laboratory conditions at 1173 K (900 °C). It has been shown that the initial reduction step is critical to determining the product microstructure, which consists of gas pore dendrites in the magnetite matrix with blocky hematite formed on the pore surfaces. The progressive growth of the magnetite layer with the application of subsequent cycles appears to continue until no original hematite remains, after which physical disintegration of the particles takes place.

  12. Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

    Science.gov (United States)

    Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

    2012-01-01

    Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394

  13. Sleep disorders associated with primary mitochondrial diseases.

    Science.gov (United States)

    Ramezani, Ryan J; Stacpoole, Peter W

    2014-11-15

    Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

  14. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Suzana Gispert

    Full Text Available BACKGROUND: Parkinson's disease (PD is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1 cause the recessive PARK6 variant of PD. METHODOLOGY/PRINCIPAL FINDINGS: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. CONCLUSION: Thus, aging Pink1(-/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.

  15. [Bio-electrochemical effect on hydrogenotrophic sulfate reduction stimulated by electrical field in the presence of H2 under atmospheric pressure].

    Science.gov (United States)

    Xu, Hui-Wei; Zhang, Xu; Yang, Shan-Shan; Li, Guang-He

    2009-07-15

    Microbial sulfate reduction rate is limited with H2 as electron donor. In order to improve hydrogenotrophic sulfate reduction under normal atmospheric H2 pressure, a bio-electrochemical system with direct current was designed and performed in this study. Results indicates that sulfate reduction rate (SRR) increases with the augment of current intensity under lower current intensity (I electric or magnetic field stimulates the proliferation of sulfate-reducing bacteria (SRB) and the activity of the enzymes. When I is higher than 1.50 mA, the activity of SRB is inhibited, resulting in lower reduction rate compared with that at lower current. If controlling the cathode potential lower than -0.69 V and H2 partial pressure 1.01 x 10(5) Pa, electro-catalytic sulfate reduction process takes place with H2 as reductant in this bio-electrochemical system. However, the overall reduction rate is still lower than that when I = 1.50 mA is applied, and additionally the energy consumption is much higher. Therefore, electric field of low intensity can enhance hydrogenotrophic sulfate reduction in the presence of H2 under atmospheric pressure.

  16. Reversible infantile mitochondrial diseases.

    Science.gov (United States)

    Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

    2015-05-01

    Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

  17. Enhanced Sulfate Reduction and Carbon Sequestration in Sediments Underlying the Core of the Arabian Sea Oxygen Minimum Zone

    Science.gov (United States)

    Fernandes, S. Q.; Mazumdar, A.; Peketi, A.; Bhattacharya, S.; Carvalho, M.; Da Silva, R.; Roy, R.; Mapder, T.; Roy, C.; Banik, S. K.; Ghosh, W.

    2017-12-01

    The oxygen minimum zone (OMZ) of the Arabian Sea in the northern Indian Ocean is one of the three major global sites of open ocean denitrification. The functionally anoxic water column between 150 to 1200 mbsl plays host to unique biogeochemical processes and organism interactions. Little is known, however, about the consequence of the low dissolved oxygen on the underlying sedimentary biogeochemical processes. Here we present, for the first time, a comprehensive investigation of sediment biogeochemistry of the Arabian Sea OMZ by coupling pore fluid analyses with microbial diversity data in eight sediment cores collected across a transect off the west coast of India in the Eastern Arabian Sea. We observed that in sediments underlying the core of the OMZ, high organic carbon sequestration coincides with a high diversity of all bacteria (the majority of which are complex organic matter hydrolyzers) and sulfate reducing bacteria (simple organic compound utilizers). Depth-integrated sulfate reduction rate also intensifies in this territory. These biogeochemical features, together with the detected shallowing of the sulfate-methane interface and buildup of pore-water sulfide, are all reflective of heightened carbon-sulfur cycling in the sediments underlying the OMZ core. Our data suggests that the sediment biogeochemistry of the OMZ is sensitive to minute changes in bottom water dissolved oxygen, and is dictated by the potential abundance and bioavailability of complex to simple carbon compounds which can stimulate a cascade of geomicrobial activities pertaining to the carbon-sulfur cycle. Our findings hold implications in benthic ecology and sediment diagenesis.

  18. RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity

    DEFF Research Database (Denmark)

    Croteau, Deborah L; Rossi, Marie L; Canugovi, Chandrika

    2012-01-01

    in premature aging. There is no information about whether any of the RecQ helicases play roles in mitochondrial biogenesis, which is strongly implicated in the aging process. Here, we used microscopy to visualize RECQL4 in mitochondria. Fractionation of human and mouse cells also showed that RECQL4 was present...... in mitochondria. Q-PCR amplification of mitochondrial DNA demonstrated that mtDNA damage accumulated in RECQL4-deficient cells. Microarray analysis suggested that mitochondrial bioenergetic pathways might be affected in RTS. Measurements of mitochondrial bioenergetics showed a reduction in the mitochondrial......Q helicase to be found in both human and mouse mitochondria, and the loss of RECQL4 alters mitochondrial integrity....

  19. Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2011-01-01

    Cellular hypoxia triggers a homeostatic increase in mitochondrial free radical signaling. In this study, blood was obtained from the radial artery and jugular venous bulb in 10 men during normoxia and 9¿ hours hypoxia (12.9% O(2)). Mitochondrial oxygen tension (p(O(2))(mit)) was derived from...... cerebral blood flow and blood gases. The ascorbate radical (A(•-)) was detected by electron paramagnetic resonance spectroscopy and neuron-specific enolase (NSE), a biomarker of neuronal injury, by enzyme-linked immunosorbent assay. Hypoxia increased the cerebral output of A(•-) in proportion...

  20. Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2011-01-01

    Cellular hypoxia triggers a homeostatic increase in mitochondrial free radical signaling. In this study, blood was obtained from the radial artery and jugular venous bulb in 10 men during normoxia and 9  hours hypoxia (12.9% O(2)). Mitochondrial oxygen tension (p(O(2))(mit)) was derived from...... cerebral blood flow and blood gases. The ascorbate radical (A(•-)) was detected by electron paramagnetic resonance spectroscopy and neuron-specific enolase (NSE), a biomarker of neuronal injury, by enzyme-linked immunosorbent assay. Hypoxia increased the cerebral output of A(•-) in proportion...

  1. Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Susana Rovira-Llopis

    2017-04-01

    Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.

  2. Mitochondrial matters: Mitochondrial bottlenecks, self-assembling structures, and entrapment in the female germline

    Directory of Open Access Journals (Sweden)

    Florence L. Marlow

    2017-05-01

    Full Text Available Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility. The procedure may produce an embryo that is free of diseased mitochondria. A recent study addresses important fundamental questions about the mechanisms underlying maternal inheritance and translational questions regarding the transgenerational effectiveness of this promising therapeutic strategy. This review considers recent advances in our understanding of maternal inheritance of mitochondria, implications for fertility and mitochondrial disease, and potential roles for the Balbiani body, an ancient oocyte structure, in mitochondrial selection in oocytes, with emphasis on therapies to remedy mitochondrial disorders.

  3. Protein Carbonylation and Adipocyte Mitochondrial Function*

    Science.gov (United States)

    Curtis, Jessica M.; Hahn, Wendy S.; Stone, Matthew D.; Inda, Jacob J.; Droullard, David J.; Kuzmicic, Jovan P.; Donoghue, Margaret A.; Long, Eric K.; Armien, Anibal G.; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J.; Bernlohr, David A.

    2012-01-01

    Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte. PMID:22822087

  4. Protein carbonylation and adipocyte mitochondrial function.

    Science.gov (United States)

    Curtis, Jessica M; Hahn, Wendy S; Stone, Matthew D; Inda, Jacob J; Droullard, David J; Kuzmicic, Jovan P; Donoghue, Margaret A; Long, Eric K; Armien, Anibal G; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J; Bernlohr, David A

    2012-09-21

    Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte.

  5. Stroke due to mitochondrial disorders in Saudi children

    International Nuclear Information System (INIS)

    Salih, Mustafa A.; Zahraa, Jihad N.; Abdel-Gader, Abdel-Galil M.; Alorainy, Ibrahim A.; Hassan, Hamdy H.; Al-Rayees, Molham; Ruitenbeek, W.; Zeviani, M.

    2006-01-01

    Objective was to report on the clinical and biochemical features of patients who presented with stroke due to mitochondrial disorders amongst a prospective and retrospective cohort of Saudi children. Children, who presented with stroke were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, during the periods July 1992 to February2001 (retrospective study)and February 2001 to March 2003 (prospective study). Open muscle biopsies were obtained from patients suspected to have mitochondrial disorders, and examined using conventional histological and histochemical techniques. Biochemical, molecular pathological investigations, or both, of muscle could be arranged for only some of the patients. Mitochondrial disorders were the underlying risk factor for stroke in 4 (3.8%) of 104 children (aged one month to 12 years). Three patients (one male and 2 females) had Leigh syndromes (LS) and one had mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). At the time of stroke, the 3 children with LS were 11 months, 15 months, and 7 years old. They presented with psychomotor regression and seizures. Muscle histology and histochemistry showed mild non-specific changes but no ragged red fibers. Biochemical analysis of muscle (in one patient) revealed deficiency of pyruvate dehydrogenase complex. Analysis of mitochondrial DNA (mtDNA), [the other 2 patients] was negative for the 2 point mutations (T-G and T-C) at nucleotide position 8993, and for two T-C point mutations (at position 8851 and 9176 of the ATPase 6 gene) that have been described in patients with LS. The girl with MELAS syndrome presented with a stroke-like episode at the age of 29 months and had focal brain lesions in the media aspect of the left occipital and temporal lobes, and in the posteromedial aspect of the left thalamus, which resolved within 7 weeks. She had

  6. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

    Science.gov (United States)

    Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

    2012-03-01

    Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

  7. 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...

  8. Fast and efficient method for reduction of carbonyl compounds with NaBH{sub 4} /wet SiO{sub 2} under solvent free condition

    Energy Technology Data Exchange (ETDEWEB)

    Zeynizadeh, Behzad; Bahyar, Tarifeh [Urmia University, Urmia (Iran, Islamic Republic of). Faculty of Sciences. Dept. of Chemistry]. E-mail: b.zeynizadeh@mail.urmia.ac.ir

    2005-11-15

    Reduction of structurally different carbonyl compounds such as aldehydes, ketones, {alpha},{beta}-unsaturated enals and enones, {alpha}-diketones and acyloins were accomplished efficiently by sodium borohydride in the presence of wet SiO{sub 2} (30% m/m) under solvent free condition. The reactions were performed at room tempere or 75-80 deg C with high to excellent yields of the corresponding products. The chemoselective reduction of aldehydes over ketones was achieved successfully with this reducing system. (author)

  9. Fast and efficient method for reduction of carbonyl compounds with NaBH4 /wet SiO2 under solvent free condition

    International Nuclear Information System (INIS)

    Zeynizadeh, Behzad; Bahyar, Tarifeh

    2005-01-01

    Reduction of structurally different carbonyl compounds such as aldehydes, ketones, α,β-unsaturated enals and enones, α-diketones and acyloins were accomplished efficiently by sodium borohydride in the presence of wet SiO 2 (30% m/m) under solvent free condition. The reactions were performed at room temperature or 75-80 deg C with high to excellent yields of the corresponding products. The chemoselective reduction of aldehydes over ketones was achieved successfully with this reducing system. (author)

  10. Piracetam improves mitochondrial dysfunction following oxidative stress

    Science.gov (United States)

    Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

  11. In situ time-of-flight neutron imaging of NiO-YSZ anode support reduction under influence of stress

    DEFF Research Database (Denmark)

    Makowska, Malgorzata Grazyna; Strobl, Markus; Lauridsen, Erik M.

    2016-01-01

    This article reports on in situ macroscopic scale imaging of NiO-YSZ (YSZ is yttria-stabilized zirconia) reduction under applied stress - a phase transition taking place in solid oxide electrochemical cells in a reducing atmosphere of a hydrogen/nitrogen mixture and at operation temperatures of u...... of applying energy-resolved neutron imaging with both approaches to the NiO-YSZ reduction investigation indicate enhancement of the reduction rate due to applied stress, which is consistent with the results of the authors’ previous research....

  12. Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission.

    Science.gov (United States)

    Tsushima, Kensuke; Bugger, Heiko; Wende, Adam R; Soto, Jamie; Jenson, Gregory A; Tor, Austin R; McGlauflin, Rose; Kenny, Helena C; Zhang, Yuan; Souvenir, Rhonda; Hu, Xiao X; Sloan, Crystal L; Pereira, Renata O; Lira, Vitor A; Spitzer, Kenneth W; Sharp, Terry L; Shoghi, Kooresh I; Sparagna, Genevieve C; Rog-Zielinska, Eva A; Kohl, Peter; Khalimonchuk, Oleh; Schaffer, Jean E; Abel, E Dale

    2018-01-05

    Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes mellitus. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Using a transgenic mouse model of cardiac lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation in isolated mitochondria. Mitochondrial morphological changes and elevated ROS generation are also observed in palmitate-treated neonatal rat ventricular cardiomyocytes. Palmitate exposure to neonatal rat ventricular cardiomyocytes initially activates mitochondrial respiration, coupled with increased mitochondrial polarization and ATP synthesis. However, long-term exposure to palmitate (>8 hours) enhances ROS generation, which is accompanied by loss of the mitochondrial reticulum and a pattern suggesting increased mitochondrial fission. Mechanistically, lipid-induced changes in mitochondrial redox status increased mitochondrial fission by increased ubiquitination of AKAP121 (A-kinase anchor protein 121) leading to reduced phosphorylation of DRP1 (dynamin-related protein 1) at Ser637 and altered proteolytic processing of OPA1 (optic atrophy 1). Scavenging mitochondrial ROS restored mitochondrial morphology in vivo and in vitro. Our results reveal a molecular mechanism by which lipid overload-induced mitochondrial ROS generation causes mitochondrial dysfunction by inducing post-translational modifications of mitochondrial proteins that regulate mitochondrial dynamics. These findings provide a

  13. Developing "Personality" Taxonomies: Metatheoretical and Methodological Rationales Underlying Selection Approaches, Methods of Data Generation and Reduction Principles.

    Science.gov (United States)

    Uher, Jana

    2015-12-01

    Taxonomic "personality" models are widely used in research and applied fields. This article applies the Transdisciplinary Philosophy-of-Science Paradigm for Research on Individuals (TPS-Paradigm) to scrutinise the three methodological steps that are required for developing comprehensive "personality" taxonomies: 1) the approaches used to select the phenomena and events to be studied, 2) the methods used to generate data about the selected phenomena and events and 3) the reduction principles used to extract the "most important" individual-specific variations for constructing "personality" taxonomies. Analyses of some currently popular taxonomies reveal frequent mismatches between the researchers' explicit and implicit metatheories about "personality" and the abilities of previous methodologies to capture the particular kinds of phenomena toward which they are targeted. Serious deficiencies that preclude scientific quantifications are identified in standardised questionnaires, psychology's established standard method of investigation. These mismatches and deficiencies derive from the lack of an explicit formulation and critical reflection on the philosophical and metatheoretical assumptions being made by scientists and from the established practice of radically matching the methodological tools to researchers' preconceived ideas and to pre-existing statistical theories rather than to the particular phenomena and individuals under study. These findings raise serious doubts about the ability of previous taxonomies to appropriately and comprehensively reflect the phenomena towards which they are targeted and the structures of individual-specificity occurring in them. The article elaborates and illustrates with empirical examples methodological principles that allow researchers to appropriately meet the metatheoretical requirements and that are suitable for comprehensively exploring individuals' "personality".

  14. Adhesion Regulating Molecule 1 Mediates HAP40 Overexpression-Induced Mitochondrial Defects

    Science.gov (United States)

    Huang, Zih-Ning; Chung, Her Min; Fang, Su-Chiung; Her, Lu-Shiun

    2017-01-01

    Striatal neuron death in Huntington's disease is associated with abnormal mitochondrial dynamics and functions. However, the mechanisms for this mitochondrial dysregulation remain elusive. Increased accumulation of Huntingtin-associated protein 40 (HAP40) has been shown to be associated with Huntington's disease. However, the link between increased HAP40 and Huntington's disease remains largely unknown. Here we show that HAP40 overexpression causes mitochondrial dysfunction and reduces cell viability in the immortalized mouse striatal neurons. HAP40-associated mitochondrial dysfunction is associated with reduction of adhesion regulating molecule 1 (ADRM1) protein. Consistently, depletion of ADRM1 by shRNAs impaired mitochondrial functions and increased mitochondrial fragmentation in mouse striatal cells. Moreover, reducing ADRM1 levels enhanced activity of fission factor dynamin-related GTPase protein 1 (Drp1) via increased phosphorylation at serine 616 of Drp1 (Drp1Ser616). Restoring ADRM1 protein levels was able to reduce HAP40-induced ROS levels and mitochondrial fragmentation and improved mitochondrial functions and cell viability. Moreover, reducing Drp1 activity by Drp1 inhibitor, Mdivi-1, ameliorates both HAP40 overexpression- and ADRM1 depletion-induced mitochondrial dysfunction. Taken together, our studies suggest that HAP40-mediated reduction of ADRM1 alters the mitochondrial fission activity and results in mitochondrial fragmentation and mitochondrial dysfunction. PMID:29209146

  15. Experimental studies of the mechanisms and the kinetic and thermodynamic aspects of the uranium reduction by sedimentary organic materials from ligneous origin under diagenetic or hydrothermal conditions

    International Nuclear Information System (INIS)

    Nakashima, S.

    1984-01-01

    This research thesis reports experimental studies of fixation and reduction of the uranyl cation by sedimentary organic materials from ligneous origin in order to understand the mechanisms and quantitative aspects of these processes in diagenetic or hydrothermal conditions. Two fixation mechanisms have been identified. Reduction appears to be governed by the oxidation of hydroxyl functions and the dehydrogenation of aliphatic hydro-carbonated entities. A kinetic study of this reduction process is reported, as well as a simulation of these processes by simple organic compounds (alcohols, aliphatic hydrocarbons). The assessment of thermodynamic parameters of the reduction process is discussed, and the obtained thermodynamic data show that almost the totality of uranium present in natural waters precipitates under the form of uraninite in presence of lignite. The extension of the obtained results to all sedimentary organic materials is finally discussed [fr

  16. Photoassisted reduction of metal ions and organic dye by titanium dioxide nanoparticles in aqueous solution under anoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Doong, Ruey-An, E-mail: radoong@mx.nthu.edu.tw [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2, Kuang Fu Road, Hsinchu, 30013, Taiwan (China); Hsieh, Tien-Chin [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Sec. 2, Kuang Fu Road, Hsinchu, 30013, Taiwan (China); Huang, Chin-Pao [Department of Civil and Environmental Engineering, University of Delaware, Newark, 19716, Delaware (United States)

    2010-07-15

    The photoassisted reduction of metal ions and organic dye by metal-deposited Degussa P25 TiO{sub 2} nanoparticles was investigated. Copper and silver ions were selected as the target metal ions to modify the surface properties of TiO{sub 2} and to enhance the photocatalytic activity of TiO{sub 2} towards methylene blue (MB) degradation. X-ray powder diffraction (XRPD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM) were used to characterize the crystallinity, chemical species and morphology of metal-deposited TiO{sub 2}, respectively. Results showed that the particle size of metal-deposited TiO{sub 2} was larger than that of Degussa P25 TiO{sub 2}. Based on XRPD patterns and XPS spectra, it was observed that the addition of formate promoted the photoreduction of metal ion by lowering its oxidation number, and subsequently enhancing the photodegradation efficiency and rate of MB. The pseudo-first-order rate constant (k{sub obs}) for MB photodegradation by Degussa P25 TiO{sub 2} was 3.94 x 10{sup -2} min{sup -1} and increased by 1.4-1.7 times in k{sub obs} with metal-deposited TiO{sub 2} for MB photodegradation compared to simple Degussa P25 TiO{sub 2}. The increase in mass loading of metal ions significantly enhanced the photodegradation efficiency of MB; the k{sub obs} for MB degradation increased from 3.94 x 10{sup -2} min{sup -1} in the absence of metal ion to 4.64-7.28 x 10{sup -2} min{sup -1} for Ag/TiO{sub 2} and to 5.14-7.61 x 10{sup -2} min{sup -1} for Cu/TiO{sub 2}. In addition, the electrons generated from TiO{sub 2} can effectively reduce metal ions and MB simultaneously under anoxic conditions. However, metal ions and organic dye would compete for electrons from the illuminated TiO{sub 2}.

  17. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  18. Melatonin-induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence.

    Science.gov (United States)

    He, Bin; Yin, Chao; Gong, Yabin; Liu, Jie; Guo, Huiduo; Zhao, Ruqian

    2018-01-01

    Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin-treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence. © 2017 Wiley Periodicals, Inc.

  19. De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction.

    Science.gov (United States)

    Ehmke, Nadja; Graul-Neumann, Luitgard; Smorag, Lukasz; Koenig, Rainer; Segebrecht, Lara; Magoulas, Pilar; Scaglia, Fernando; Kilic, Esra; Hennig, Anna F; Adolphs, Nicolai; Saha, Namrata; Fauler, Beatrix; Kalscheuer, Vera M; Hennig, Friederike; Altmüller, Janine; Netzer, Christian; Thiele, Holger; Nürnberg, Peter; Yigit, Gökhan; Jäger, Marten; Hecht, Jochen; Krüger, Ulrike; Mielke, Thorsten; Krawitz, Peter M; Horn, Denise; Schuelke, Markus; Mundlos, Stefan; Bacino, Carlos A; Bonnen, Penelope E; Wollnik, Bernd; Fischer-Zirnsak, Björn; Kornak, Uwe

    2017-11-02

    Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/P i carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H 2 O 2 ). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H 2 O 2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/P i transport to the development of skeletal and connective tissue. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  20. Mitochondrial dysfunction is responsible for fatty acid synthase inhibition-induced apoptosis in breast cancer cells by PdpaMn.

    Science.gov (United States)

    Wang, Qiang; Du, Xia; Zhou, Bingjie; Li, Jing; Lu, Wenlong; Chen, Qiuyun; Gao, Jing

    2017-12-01

    Targeting cellular metabolism is becoming a hallmark to overcome drug resistance in breast cancer treatment. Activation of fatty acid synthase (FASN) has been shown to promote breast cancer cell growth. However, there is no concrete report underlying the mechanism associated with mitochondrial dysfunction in relation to fatty acid synthase inhibition-induced apoptosis in breast cancer cells. The current study is aimed at exploring the effect of the novel manganese (Mn) complex, labeled as PdpaMn, on lipid metabolism and mitochondrial function in breast cancer cells. Herein, we observed that PdpaMn displayed strong cytotoxicity on breast cancer cell lines and selectively targeted the tumor without affecting the normal organs or cells in vivo. We also observed that PdpaMn could bind to TE domain of FASN and decrease the activity and the level of expression of FASN, which is an indication that FASN could serve as a target of PdpaMn. In addition, we demonstrated that PdpaMn increased intrinsic apoptosis in breast cancer cells relayed by a suppressed the level of expression of FASN, followed by the release of mitochondrial cytochrome c and the activation of caspases-9. Instigated by the above observations, we hypothesized that PdpaMn-induced apoptosis events are dependent on mitochondrial dysfunction. Indeed, we found that mitochondrial membrane potential (MMP) collapse, mitochondrial oxygen consumption reduction and adenosine triphosphate (ATP) release were deeply repressed. Furthermore, our results showed that PdpaMn significantly increased the reactive oxygen species (ROS) production, and the protection conferred by the free radical scavenger N-acetyl-cysteine (NAC) indicates that PdpaMn-induced apoptosis through an oxidative stress-associated mechanism. More so, the above results have demonstrated that mitochondrial dysfunction participated in FASN inhibition-induce apoptosis in breast cancer cells by PdpaMn. Therefore, PdpaMn may be considered as a good candidate

  1. Human skeletal muscle mitochondrial capacity.

    Science.gov (United States)

    Rasmussen, U F; Rasmussen, H N

    2000-04-01

    Under aerobic work, the oxygen consumption and major ATP production occur in the mitochondria and it is therefore a relevant question whether the in vivo rates can be accounted for by mitochondrial capacities measured in vitro. Mitochondria were isolated from human quadriceps muscle biopsies in yields of approximately 45%. The tissue content of total creatine, mitochondrial protein and different cytochromes was estimated. A number of activities were measured in functional assays of the mitochondria: pyruvate, ketoglutarate, glutamate and succinate dehydrogenases, palmitoyl-carnitine respiration, cytochrome oxidase, the respiratory chain and the ATP synthesis. The activities involved in carbohydrate oxidation could account for in vivo oxygen uptakes of 15-16 mmol O2 min-1 kg-1 or slightly above the value measured at maximal work rates in the knee-extensor model of Saltin and co-workers, i.e. without limitation from the cardiac output. This probably indicates that the maximal oxygen consumption of the muscle is limited by the mitochondrial capacities. The in vitro activities of fatty acid oxidation corresponded to only 39% of those of carbohydrate oxidation. The maximal rate of free energy production from aerobic metabolism of glycogen was calculated from the mitochondrial activities and estimates of the DeltaG or ATP hydrolysis and the efficiency of the actin-myosin reaction. The resultant value was 20 W kg-1 or approximately 70% of the maximal in vivo work rates of which 10-20% probably are sustained by the anaerobic ATP production. The lack of aerobic in vitro ATP synthesis might reflect termination of some critical interplay between cytoplasm and mitochondria.

  2. The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.

    Science.gov (United States)

    Tanis, Ross M; Piroli, Gerardo G; Day, Stani D; Frizzell, Norma

    2015-01-01

    While the 3T3-L1 adipocyte model is routinely used for the study of obesity and diabetes, the mitochondrial respiratory profile in normal versus high glucose has not been examined in detail. We matured adipocytes in normal (5mM) or high (30 mM) glucose and insulin and examined the mitochondrial bioenergetics. We also assessed the requirement for the Unfolded Protein Response (UPR) and ER stress under these conditions. Basal respiration was ~1.7-fold greater in adipocytes that had matured in 30 mM glucose; however, their ability to increase oxygen consumption in response to stress was impaired. Adipogenesis proceeded in both normal and high glucose with concomitant activation of the UPR, but only high glucose was associated with increased levels of ER stress and mitochondrial stress as observed by parallel increases in CHOP and protein succination. Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration. Our data suggests that mitochondrial stress, protein succination and ER stress are uniquely linked in adipocytes matured in high glucose. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Science.gov (United States)

    Warren, Emily Booth; Aicher, Aidan Edward; Fessel, Joshua Patrick; Konradi, Christine

    2017-01-01

    Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  4. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Directory of Open Access Journals (Sweden)

    Emily Booth Warren

    Full Text Available Mitochondrial DNA (mtDNA, the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD patients who had developed L-DOPA Induced Dyskinesia (LID, compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  5. Interactive Development-oriented Poverty Reduction Model for Bijie Experimental Region under the Guidance of Scientific Outlook on Development

    Institute of Scientific and Technical Information of China (English)

    Faliang; YU; Lisong; CHEN

    2013-01-01

    Bijie Experimental Region takes the ecological construction as the guarantee and takes population control as the key,to promote development-oriented poverty reduction and explore benign interaction between development-oriented poverty reduction and ecological construction and population control.Development-oriented poverty reduction model includes combination of raising crops and livestock,coordinated development of multiple wealth sources,transferring labor,and partner assistance;ecological construction model includes"Five sons passed imperial examinations",desertification control,agricultural circular economy,and project promotion;population control models includes human-land linkage,combination of favorable policies and propaganda and education,and combination of ambition arousing and education promotion.

  6. Phase Transition Mapping by Means of Neutron Imaging in SOFC Anode Supports During Reduction Under Applied Stress

    DEFF Research Database (Denmark)

    Makowska, Malgorzata; Strobl, M.; Lauridsen, E. M.

    2015-01-01

    Mechanical and electrochemical performance of layers composed of Ni-YSZ cermet in solid oxide fuel and electrolysis cells (SOC) depends on their microstructure and initial internal stresses. After sintering, the manufacturing conditions, i.e. temperature, atmosphere and loads, can influence...... the microstructure and in particular the internal stresses in the Ni-YSZ layer and thereby the cell performance. Spatially resolved observation of the phase transition during reduction can provide information on how parameters like temperature and external load influence the reaction progress. This information...... is crucial for optimization of the SOC performance. In this work the measurements with energy resolved neutron imaging of the phase transition during the NiOYSZ reduction performed at different temperatures with and without applied load, are presented. The results indicate a link between reduction rate...

  7. Epilepsy and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Russell P. Saneto DO, PhD

    2017-10-01

    Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.

  8. The research and application of electricity economic boom model under the constraint of energy conservation and emission reduction

    Science.gov (United States)

    Chen, Guangyan; Xia, Huaijian; Chen, Meiling; Wang, Dong; Jia, Sujin

    2017-10-01

    Energy saving and emission reduction policies affects the development of high power industry, thereby affecting electricity demand, so the study of the electricity industry boom helps to master the national economy. This paper analyses the influence of energy saving and emission reduction on power generation structure and pollutant emission in power industry. Through the construction of electricity market composite boom index to indicate electricity boom, using boom index to study volatility characteristics and trend of electricity market. Here we provide a method for the enterprise and the government, that it can infer the overall operation of the national economy situation from power data.

  9. 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....

  10. Non-electron transfer chain mitochondrial defects differently regulate HIF-1α degradation and transcription

    Directory of Open Access Journals (Sweden)

    Antonina N. Shvetsova

    2017-08-01

    Full Text Available Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS. Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α. While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation. However, studies investigating non-ETC located mitochondrial defects and their effects on HIF-1α regulation are scarce, if at all existing. Thus, in the present study we examined three cell lines with non-ETC mitochondrial defects and focused on HIF-1α degradation and transcription, target gene expression, as well as ROS levels. We found that cells lacking the key enzyme 2-enoyl thioester reductase/mitochondrial enoyl-CoA reductase (MECR, and cells lacking manganese superoxide dismutase (MnSOD showed a reduced induction of HIF-1α under long-term (20 h hypoxia. By contrast, cells lacking the mitochondrial DNA depletion syndrome channel protein Mpv17 displayed enhanced levels of HIF-1α already under normoxic conditions. Further, we show that ROS do not exert a uniform pattern when mediating their effects on HIF-1α, although all mitochondrial defects in the used cell types increased ROS formation. Moreover, all defects caused a different HIF-1α regulation via promoting HIF-1α degradation as well as via changes in HIF-1α transcription. Thereby, MECR- and MnSOD-deficient cells showed a reduction in HIF-1α mRNA levels whereas the Mpv17 lacking cells displayed enhanced HIF-1α mRNA levels under normoxia and hypoxia. Altogether, our study shows for the first time that mitochondrial defects which are not related to the ETC and Krebs cycle

  11. Realizing high-rate sulfur reduction under sulfate-rich conditions in a biological sulfide production system to treat metal-laden wastewater deficient in organic matter.

    Science.gov (United States)

    Sun, Rongrong; Zhang, Liang; Zhang, Zefeng; Chen, Guang-Hao; Jiang, Feng

    2017-12-22

    Biological sulfur reduction can theoretically produce sufficient sulfide to effectively remove and recover heavy metals in the treatment of organics-deficient sulfate-rich metal-laden wastewater such as acid mine drainage and metallurgic wastewater, using 75% less organics than biological sulfate reduction. However, it is still unknown whether sulfur reduction can indeed compete with sulfate reduction, particularly under high-strength sulfate conditions. The aim of this study was to investigate the long-term feasibility of biological sulfur reduction under high sulfate conditions in a lab-scale sulfur-reducing biological sulfide production (BSP) system with sublimed sulfur added. In the 169-day trial, an average sulfide production rate (SPR) as high as 47 ± 9 mg S/L-h was achieved in the absence of sulfate, and the average SPR under sulfate-rich conditions was similar (53 ± 10 mg S/L-h) when 1300 mg S/L sulfate were fed with the influent. Interestingly, sulfate was barely reduced even at such a high strength and contributed to only 1.5% of total sulfide production. Desulfomicrobium was identified as the predominant sulfidogenic bacterium in the bioreactor. Batch tests further revealed that this sulfidogenic bacteria used elemental sulfur as the electron acceptor instead of the highly bioavailable sulfate, during which polysulfide acted as an intermediate, leading to an even higher bioavailability of sulfur than sulfate. The pathway of sulfur to sulfide conversion via polysulfide in the presence of both sulfur and sulfate was discussed. Collectively, when conditions favor polysulfide formation, sulfur reduction can be a promising and attractive technology to realize a high-rate and low-cost BSP process for treating sulfate-rich metal-laden wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Ischemic preconditioning improves mitochondrial tolerance to experimental calcium overload.

    Science.gov (United States)

    Crestanello, Juan A; Doliba, Nicolai M; Babsky, Andriy M; Doliba, Natalia M; Niibori, Koki; Whitman, Glenn J R; Osbakken, Mary D

    2002-04-01

    preserving mitochondrial function during reperfusion and increasing mitochondrial tolerance to Ca(2+) loading at end-RP. Activation of mitochondrial K(ATP) channels by IPC and their improvement in Ca(2+) homeostasis during RP may be the mechanism underlying this protection.

  13. Reduction of excess sludge in a sequencing batch reactor by lysis-cryptic growth using quick lime for disintegration under low temperature.

    Science.gov (United States)

    Lv, Xiao-Mei; Song, Ju-Sheng; Li, Ji; Zhai, Kun

    2017-08-01

    In the present study, quick-lime-based thermal-alkaline sludge disintegration (SD) under low temperature was combined with cryptic growth to investigate the excess sludge reduction efficiency in the sequencing batch reactor (SBR). The optimized condition of SD was as follows: T = 80℃, pH = 11, t = 180 min, and the SD rate was about 42.1%. With 65.6% of excess sludge disintegrated and returned to the SBR, the system achieved sludge reduction rate of about 40.1%. The lysis-cryptic growth still obtained satisfactory sludge reduction efficiency despite the comparative low SD rate, which suggested that disintegration rate might not be the decisive factor for cryptic-growth-based sludge reduction. Lysis-cryptic growth did not impact the effluent quality, yet the phosphorus removal performance was enhanced, with effluent total phosphorus concentration decreased by 0.3 mg/L (33%). Crystal compounds of calcium phosphate precipitate were detected in the system by Fourier transform infrared spectroscopy and X-ray diffraction, which indicated the phosphorus removal potential of SD using lime. Moreover, endogenous dehydrogenase activity of activated sludge in the lysis-cryptic system was enhanced, which was beneficial for sludge reduction. SD and cryptic growth in the present study demonstrates an economical and effective approach for sludge reduction.

  14. Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression.

    Science.gov (United States)

    Boutilier, Robert G; St-Pierre, Julie

    2002-08-01

    The common frog (Rana temporaria) spends the coldest months of each year overwintering in ice-covered ponds where temperatures can vary from 0.5 to 4.0 degrees C. Over the course of a winter season, the animals enter progressively into a state of metabolic depression that relies almost exclusively on aerobic production of ATP. However, if aerobic metabolism is threatened, for example by increasingly hypoxic conditions, decreases in the animal's metabolic rate can reach upwards of 75% compared with the 50% decrease seen during normoxia. Under these conditions, the major proportion of the overall reduction in whole-animal metabolic rate can be accounted for by metabolic suppression of the skeletal muscle (which makes up approximately 40% of body mass). Little is known about the properties of mitochondria during prolonged periods of metabolic depression, so we have examined several aspects of mitochondrial metabolism in the skeletal muscle of frogs over periods of hibernation of up to 4 months. Mitochondria isolated from the skeletal muscle of frogs hibernating in hypoxic water show a considerable reorganisation of function compared with those isolated from normoxic submerged animals at the same temperature (3 degrees C). Both the active (state 3) and resting (state 4) respiration rates of mitochondria decrease during hypoxic, but not normoxic, hibernation. In addition, the affinity of mitochondria for oxygen increases during periods of acute hypoxic stress during normoxic hibernation as well as during long-term hibernation in hypoxic water. The decrease in mitochondrial state 4 respiration rates during hypoxic hibernation evidently occurs through a reduction in electron-transport chain activity, not through a lowered proton conductance of the mitochondrial inner membrane. The reduced aerobic capacity of frog skeletal muscle during hypoxic hibernation is accompanied by lowered activities of key enzymes of mitochondrial metabolism caused by changes in the intrinsic

  15. Mitochondrial signaling in health and disease

    National Research Council Canada - National Science Library

    Orrenius, Sten; Packer, Lester; Cadenas, Enrique

    2012-01-01

    .... The text covers themes essential for the maintenance of mitochondrial activity, including electron transport and energy production, mitochondrial biogenesis and dynamics, mitochondrial signaling...

  16. Bacterial sulphate reduction and the development of alklinity. III. Experiments under natural conditions in the Wadi Natrun

    Energy Technology Data Exchange (ETDEWEB)

    Abd-El-Malek, Y; Rizk, S G

    1963-01-01

    Evidence that microbial sulphate reduction is mainly responsible for the formation of the natron (hydrated Na/sub 2/CO/sub 3/) deposits in Wadi Natrun is presented. The sulphate in the infiltrating water is reduced during passage through the surrounding waterlogged soil and the bicarbonate formed is later concentrated by evaporation in the lakes.

  17. Diagnosing the uncertainty and detectability of emission reductions for REDD + under current capabilities: an example for Panama

    International Nuclear Information System (INIS)

    Pelletier, Johanne; Potvin, Catherine; Ramankutty, Navin

    2011-01-01

    In preparation for the deployment of a new mechanism that could address as much as one fifth of global greenhouse gas emissions by reducing emissions from deforestation and forest degradation (REDD +), important work on methodological issues is still needed to secure the capacity to produce measurable, reportable, and verifiable emissions reductions from REDD + in developing countries. To contribute to this effort, we have diagnosed the main sources of uncertainty in the quantification of emission from deforestation for Panama, one of the first countries to be supported by the Forest Carbon Partnership Facility of the World Bank and by UN-REDD. Performing sensitivity analyses using a land-cover change emissions model, we identified forest carbon stocks and the quality of land-cover maps as the key parameters influencing model uncertainty. The time interval between two land-cover assessments, carbon density in fallow and secondary forest, and the accuracy of land-cover classifications also affect our ability to produce accurate estimates. Further, we used the model to compare emission reductions from five different deforestation reduction scenarios drawn from governmental input. Only the scenario simulating a reduction in deforestation by half succeeds in crossing outside the confidence bounds surrounding the baseline emission obtained from the uncertainty analysis. These results suggest that with current data, real emission reductions in developing countries could be obscured by their associated uncertainties. Ways of addressing the key sources of error are proposed, for developing countries involved in REDD + , for improving the accuracy of their estimates in the future. These new considerations confirm the importance of current efforts to establish forest monitoring systems and enhance capabilities for REDD + in developing countries.

  18. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  19. Involvement of the mitochondrial compartment in human NCL fibroblasts

    International Nuclear Information System (INIS)

    Pezzini, Francesco; Gismondi, Floriana; Tessa, Alessandra; Tonin, Paola; Carrozzo, Rosalba; Mole, Sara E.; Santorelli, Filippo M.; Simonati, Alessandro

    2011-01-01

    Highlights: ► Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. ► Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. ► Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

  20. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects after prolonged culture in a low non-stimulating glucose concentration.

    Science.gov (United States)

    Roma, L P; Pascal, S M; Duprez, J; Jonas, J-C

    2012-08-01

    Pancreatic beta cells chronically exposed to low glucose concentrations show signs of oxidative stress, loss of glucose-stimulated insulin secretion (GSIS) and increased apoptosis. Our aim was to confirm the role of mitochondrial oxidative stress in rat islet cell apoptosis under these culture conditions and to evaluate whether its reduction similarly improves survival and GSIS. Apoptosis, oxidative stress-response gene mRNA expression and glucose-induced stimulation of mitochondrial metabolism, intracellular Ca(2+) concentration and insulin secretion were measured in male Wistar rat islets cultured for 1 week in RPMI medium containing 5-10 mmol/l glucose with or without manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) or N-acetyl-L-: cysteine (NAC). Oxidative stress was measured in islet cell clusters cultured under similar conditions using cytosolic and mitochondrial redox-sensitive green fluorescent protein (roGFP1/mt-roGFP1). Prolonged culture in 5 vs 10 mmol/l glucose increased mt-roGFP1 (but not roGFP1) oxidation followed by beta cell apoptosis and loss of GSIS resulting from reduced insulin content, mitochondrial metabolism, Ca(2+) influx and Ca(2+)-induced secretion. Tolbutamide-induced, but not high K(+)-induced, Ca(2+) influx was also suppressed. Under these conditions, MnTBAP, but not NAC, triggered parallel ~50-70% reductions in mt-roGFP1 oxidation and beta cell apoptosis, but failed to protect against the loss of GSIS despite significant improvement in glucose-induced and tolbutamide-induced Ca(2+) influx. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects during culture in a low glucose concentration. Thus, targeting beta cell survival may not be sufficient to restore insulin secretion when beta cells suffer from prolonged mitochondrial oxidative stress, e.g. in the context of reduced glucose metabolism.

  1. Evolution of gastropod mitochondrial genome arrangements

    Directory of Open Access Journals (Sweden)

    Zardoya Rafael

    2008-02-01

    Full Text Available Abstract Background Gastropod mitochondrial genomes exhibit an unusually great variety of gene orders compared to other metazoan mitochondrial genome such as e.g those of vertebrates. Hence, gastropod mitochondrial genomes constitute a good model system to study patterns, rates, and mechanisms of mitochondrial genome rearrangement. However, this kind of evolutionary comparative analysis requires a robust phylogenetic framework of the group under study, which has been elusive so far for gastropods in spite of the efforts carried out during the last two decades. Here, we report the complete nucleotide sequence of five mitochondrial genomes of gastropods (Pyramidella dolabrata, Ascobulla fragilis, Siphonaria pectinata, Onchidella celtica, and Myosotella myosotis, and we analyze them together with another ten complete mitochondrial genomes of gastropods currently available in molecular databases in order to reconstruct the phylogenetic relationships among the main lineages of gastropods. Results Comparative analyses with other mollusk mitochondrial genomes allowed us to describe molecular features and general trends in the evolution of mitochondrial genome organization in gastropods. Phylogenetic reconstruction with commonly used methods of phylogenetic inference (ME, MP, ML, BI arrived at a single topology, which was used to reconstruct the evolution of mitochondrial gene rearrangements in the group. Conclusion Four main lineages were identified within gastropods: Caenogastropoda, Vetigastropoda, Patellogastropoda, and Heterobranchia. Caenogastropoda and Vetigastropoda are sister taxa, as well as, Patellogastropoda and Heterobranchia. This result rejects the validity of the derived clade Apogastropoda (Caenogastropoda + Heterobranchia. The position of Patellogastropoda remains unclear likely due to long-branch attraction biases. Within Heterobranchia, the most heterogeneous group of gastropods, neither Euthyneura (because of the inclusion of P

  2. Ocean acidification impacts on sperm mitochondrial membrane potential bring sperm swimming behaviour near its tipping point.

    Science.gov (United States)

    Schlegel, Peter; Binet, Monique T; Havenhand, Jonathan N; Doyle, Christopher J; Williamson, Jane E

    2015-04-01

    Broadcast spawning marine invertebrates are susceptible to environmental stressors such as climate change, as their reproduction depends on the successful meeting and fertilization of gametes in the water column. Under near-future scenarios of ocean acidification, the swimming behaviour of marine invertebrate sperm is altered. We tested whether this was due to changes in sperm mitochondrial activity by investigating the effects of ocean acidification on sperm metabolism and swimming behaviour in the sea urchin Centrostephanus rodgersii. We used a fluorescent molecular probe (JC-1) and flow cytometry to visualize mitochondrial activity (measured as change in mitochondrial membrane potential, MMP). Sperm MMP was significantly reduced in ΔpH -0.3 (35% reduction) and ΔpH -0.5 (48% reduction) treatments, whereas sperm swimming behaviour was less sensitive with only slight changes (up to 11% decrease) observed overall. There was significant inter-individual variability in responses of sperm swimming behaviour and MMP to acidified seawater. We suggest it is likely that sperm exposed to these changes in pH are close to their tipping point in terms of physiological tolerance to acidity. Importantly, substantial inter-individual variation in responses of sperm swimming to ocean acidification may increase the scope for selection of resilient phenotypes, which, if heritable, could provide a basis for adaptation to future ocean acidification. © 2015. Published by The Company of Biologists Ltd.

  3. ZnCr2S4: Highly effective photocatalyst converting nitrate into N2 without over-reduction under both UV and pure visible light

    Science.gov (United States)

    Yue, Mufei; Wang, Rong; Cheng, Nana; Cong, Rihong; Gao, Wenliang; Yang, Tao

    2016-08-01

    We propose several superiorities of applying some particular metal sulfides to the photocatalytic nitrate reduction in aqueous solution, including the high density of photogenerated excitons, high N2 selectivity (without over-reduction to ammonia). Indeed, ZnCr2S4 behaved as a highly efficient photocatalyst, and with the assistance of 1 wt% cocatalysts (RuOx, Ag, Au, Pd, or Pt), the efficiency was greatly improved. The simultaneous loading of Pt and Pd led to a synergistic effect. It offered the highest nitrate conversion rate of ~45 mg N/h together with the N2 selectivity of ~89%. Such a high activity remained steady after 5 cycles. The optimal apparent quantum yield at 380 nm was 15.46%. More importantly, with the assistance of the surface plasma resonance effect of Au, the visible light activity achieved 1.352 mg N/h under full arc Xe-lamp, and 0.452 mg N/h under pure visible light (λ > 400 nm). Comparing to the previous achievements in photocatalytic nitrate removal, our work on ZnCr2S4 eliminates the over-reduction problem, and possesses an extremely high and steady activity under UV-light, as well as a decent conversion rate under pure visible light.

  4. ZnCr2S4: Highly effective photocatalyst converting nitrate into N2 without over-reduction under both UV and pure visible light.

    Science.gov (United States)

    Yue, Mufei; Wang, Rong; Cheng, Nana; Cong, Rihong; Gao, Wenliang; Yang, Tao

    2016-08-03

    We propose several superiorities of applying some particular metal sulfides to the photocatalytic nitrate reduction in aqueous solution, including the high density of photogenerated excitons, high N2 selectivity (without over-reduction to ammonia). Indeed, ZnCr2S4 behaved as a highly efficient photocatalyst, and with the assistance of 1 wt% cocatalysts (RuOx, Ag, Au, Pd, or Pt), the efficiency was greatly improved. The simultaneous loading of Pt and Pd led to a synergistic effect. It offered the highest nitrate conversion rate of ~45 mg N/h together with the N2 selectivity of ~89%. Such a high activity remained steady after 5 cycles. The optimal apparent quantum yield at 380 nm was 15.46%. More importantly, with the assistance of the surface plasma resonance effect of Au, the visible light activity achieved 1.352 mg N/h under full arc Xe-lamp, and 0.452 mg N/h under pure visible light (λ > 400 nm). Comparing to the previous achievements in photocatalytic nitrate removal, our work on ZnCr2S4 eliminates the over-reduction problem, and possesses an extremely high and steady activity under UV-light, as well as a decent conversion rate under pure visible light.

  5. Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.

    Directory of Open Access Journals (Sweden)

    Lianggong Ding

    2016-10-01

    Full Text Available As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF. However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions. Because Vimar could co-immunoprecipitate with Miro in vitro, we speculated that Vimar might be the GEF of Miro. In support of this hypothesis, a loss-of-function (LOF vimar mutant rescued mitochondrial enlargement induced by a gain-of-function (GOF Miro transgene; whereas a GOF vimar transgene enhanced Miro function. In addition, vimar lost its effect under the expression of a constitutively GTP-bound or GDP-bound Miro mutant background. These results indicate a genetic dependence of vimar on Miro. Moreover, we found that mitochondrial fission played a functional role in high-calcium induced necrosis, and a LOF vimar mutant rescued the mitochondrial fission defect and cell death. This result can also be explained by vimar's function through Miro, because Miro's effect on mitochondrial morphology is altered upon binding with calcium. In addition, a PINK1 mutant, which induced mitochondrial enlargement and had been considered as a Drosophila model of Parkinson's disease (PD, caused fly muscle defects, and the loss of vimar could rescue these defects. Furthermore, we found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in regulating mitochondrial morphology, suggesting a functional conservation of this GEF member. The Miro/Vimar complex may be a promising drug target for diseases in which mitochondrial fission and fusion are dysfunctional.

  6. Determining the Threshold Value of Basil Yield Reduction and Evaluation of Water Uptake Models under Salinity Stress Condition

    OpenAIRE

    M. Sarai Tabrizi; H. Babazadeh; M. Homaee; F. Kaveh Kaveh; M. Parsinejad

    2016-01-01

    Introduction: Several mathematical models are being used for assessing the plant response to the salinity of the root zone. The salinity of the soil and water resources is a major challenge for agricultural sector in Iran. Several mathematical models have been developed for plant responses to the salinity stress. However, these models are often applicable in particular conditions. The objectives of this study were to evaluate the threshold value of Basil yield reduction, modeling Basil respon...

  7. Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts

    DEFF Research Database (Denmark)

    Guillery, O.; Malka, F.; Frachon, P.

    2008-01-01

    induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under...... basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition. In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked...... to mitochondrial oxidative phosphorylation. Its alteration by glycolysis, inhibition points to a severe oxidative phosphorylation defect. (C) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008/4...

  8. Fault-Tolerant Control of ANPC Three-Level Inverter Based on Order-Reduction Optimal Control Strategy under Multi-Device Open-Circuit Fault.

    Science.gov (United States)

    Xu, Shi-Zhou; Wang, Chun-Jie; Lin, Fang-Li; Li, Shi-Xiang

    2017-10-31

    The multi-device open-circuit fault is a common fault of ANPC (Active Neutral-Point Clamped) three-level inverter and effect the operation stability of the whole system. To improve the operation stability, this paper summarized the main solutions currently firstly and analyzed all the possible states of multi-device open-circuit fault. Secondly, an order-reduction optimal control strategy was proposed under multi-device open-circuit fault to realize fault-tolerant control based on the topology and control requirement of ANPC three-level inverter and operation stability. This control strategy can solve the faults with different operation states, and can works in order-reduction state under specific open-circuit faults with specific combined devices, which sacrifices the control quality to obtain the stability priority control. Finally, the simulation and experiment proved the effectiveness of the proposed strategy.

  9. Atypical mitochondrial inheritance patterns in eukaryotes.

    Science.gov (United States)

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  10. Mitochondrial dysfunction in obesity.

    Science.gov (United States)

    de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

    2018-01-01

    Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Multifunctional Mitochondrial AAA Proteases.

    Science.gov (United States)

    Glynn, Steven E

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

  12. An interdisciplinary approach to volcanic risk reduction under conditions of uncertainty: a case study of Tristan da Cunha

    Science.gov (United States)

    Hicks, A.; Barclay, J.; Simmons, P.; Loughlin, S.

    2014-07-01

    The uncertainty brought about by intermittent volcanic activity is fairly common at volcanoes worldwide. While better knowledge of any one volcano's behavioural characteristics has the potential to reduce this uncertainty, the subsequent reduction of risk from volcanic threats is only realised if that knowledge is pertinent to stakeholders and effectively communicated to inform good decision making. Success requires integration of methods, skills and expertise across disciplinary boundaries. This research project develops and trials a novel interdisciplinary approach to volcanic risk reduction on the remote volcanic island of Tristan da Cunha (South Atlantic). For the first time, volcanological techniques, probabilistic decision support and social scientific methods were integrated in a single study. New data were produced that (1) established no spatio-temporal pattern to recent volcanic activity; (2) quantified the high degree of scientific uncertainty around future eruptive scenarios; (3) analysed the physical vulnerability of the community as a consequence of their geographical isolation and exposure to volcanic hazards; (4) evaluated social and cultural influences on vulnerability and resilience; and (5) evaluated the effectiveness of a scenario planning approach, both as a method for integrating the different strands of the research and as a way of enabling on-island decision makers to take ownership of risk identification and management, and capacity building within their community. The paper provides empirical evidence of the value of an innovative interdisciplinary framework for reducing volcanic risk. It also provides evidence for the strength that comes from integrating social and physical sciences with the development of effective, tailored engagement and communication strategies in volcanic risk reduction.

  13. Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

    Science.gov (United States)

    Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

    2016-01-01

    Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

  14. Is cell aging caused by respiration-dependent injury to the mitochondrial genome

    Science.gov (United States)

    Fleming, J. E.; Yengoyan, L. S.; Miquel, J.; Cottrell, S. F.; Economos, A. C.

    1982-01-01

    Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article, the hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells is expanded. It is maintained that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

  15. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies

    NARCIS (Netherlands)

    Wang, Gang; McCain, Megan L.; Yang, Luhan; He, Aibin; Pasqualini, Francesco Silvio; Agarwal, Ashutosh; Yuan, Hongyan; Jiang, Dawei; Zhang, Donghui; Zangi, Lior; Geva, Judith; Roberts, Amy E.; Ma, Qing; Ding, Jian; Chen, Jinghai; Wang, Da-Zhi; Li, Kai; Wang, Jiwu; Wanders, Ronald J. A.; Kulik, Wim; Vaz, Frédéric M.; Laflamme, Michael A.; Murry, Charles E.; Chien, Kenneth R.; Kelley, Richard I.; Church, George M.; Parker, Kevin Kit; Pu, William T.

    2014-01-01

    Study of monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying

  16. Tuition reduction is the key factor determining tax burden of graduate students under the Tax Cuts and Job Act.

    Science.gov (United States)

    Lawston, Patricia M; Parker, Michael T

    2017-01-01

    Background : The proposed Tax Cuts and Jobs Act (H.R.1) has stirred significant public debate on the future of American economics.  While supporters of the plan have championed it as a necessity for economic revitalization, detractors have pointed out areas of serious concern, particularly for low- and middle-income Americans.  One particularly alarming facet of the plan is the radical change to education finance programs and taxation of students in higher education.  Methods :  By analyzing actual income and tuition of a public and a private university student, as well as the 'average' graduate student, we investigated the effect of both the House and Senate versions of H.R. 1 on taxation of students of various family structures.  Results :  Our findings indicate that taxable tuition would be the greatest contributor to graduate student tax burden across all four categories of filing status.  However, when tuition reduction is upheld or a student is on sustaining fees rather than full tuition, graduate students would realize decreases in taxation. Conclusions :  Overall, we conclude that removal of tuition reduction would result in enormous tax burdens for graduate students and their families and that these effects are dependent not only on the status of the student in their degree program but also on their tuition and stipend, and therefore the institution they attend.

  17. An interdisciplinary approach to volcanic risk reduction under conditions of uncertainty: a case study of Tristan da Cunha

    Science.gov (United States)

    Hicks, A.; Barclay, J.; Simmons, P.; Loughlin, S.

    2013-12-01

    This research project adopted an interdisciplinary approach to volcanic risk reduction on the remote volcanic island of Tristan da Cunha (South Atlantic). New data were produced that: (1) established no spatio-temporal pattern to recent volcanic activity; (2) quantified the high degree of scientific uncertainty around future eruptive scenarios; (3) analysed the physical vulnerability of the community as a consequence of their geographical isolation and exposure to volcanic hazards; (4) evaluated social and cultural influences on vulnerability and resilience. Despite their isolation and prolonged periods of hardship, islanders have demonstrated an ability to cope with and recover from adverse events. This resilience is likely a function of remoteness, strong kinship ties, bonding social capital, and persistence of shared values and principles established at community inception. While there is good knowledge of the styles of volcanic activity on Tristan, given the high degree of scientific uncertainty about the timing, size and location of future volcanism, a qualitative scenario planning approach was used as a vehicle to convey this information to the islanders. This deliberative, anticipatory method allowed on-island decision makers to take ownership of risk identification, management and capacity building within their community. This paper demonstrates the value of integrating social and physical sciences with development of effective, tailored communication strategies in volcanic risk reduction.

  18. Solid-solution partitioning and thionation of diphenylarsinic acid in a flooded soil under the impact of sulfate and iron reduction

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Meng [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Tu, Chen [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Hu, Xuefeng; Zhang, Haibo [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Lijuan [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Wei, Jing [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Li, Yuan [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Luo, Yongming, E-mail: ymluo@yic.ac.cn [Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Christie, Peter [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China)

    2016-11-01

    Diphenylarsinic acid (DPAA) is a major organic arsenic (As) compound derived from abandoned chemical weapons. The solid-solution partitioning and transformation of DPAA in flooded soils are poorly understood but are of great concern. The identification of the mechanisms responsible for the mobilization and transformation of DPAA may help to develop effective remediation strategies. Here, soil and Fe mineral incubation experiments were carried out to elucidate the partitioning and transformation of DPAA in anoxic (without addition of sulfate or sodium lactate) and sulfide (with the addition of sulfate and sodium lactate) soil and to examine the impact of sulfate and Fe(III) reduction on these processes. Results show that DPAA was more effectively mobilized and thionated in sulfide soil than in anoxic soil. At the initial incubation stages (0–4 weeks), 6.7–74.5% of the total DPAA in sulfide soil was mobilized likely by sorption competition with sodium lactate. At later incubation stage (4–8 weeks), DPAA was almost completely released into the solution likely due to the near-complete Fe(III) reduction. Scanning transmission X-ray microscopy (STXM) results provide further direct evidence of elevated DPAA release coupled with Fe(III) reduction in sulfide environments. The total DPAA fraction decreased significantly to 24.5% after two weeks and reached 3.4% after eight weeks in sulfide soil, whereas no obvious elimination of DPAA occurred in anoxic soil at the initial two weeks and the total DPAA fraction decreased to 10.9% after eight weeks. This can be explained in part by the enhanced mobilization of DPAA and sulfate reduction in sulfide soil compared with anoxic soil. These results suggest that under flooded soil conditions, Fe(III) and sulfate reduction significantly promote DPAA mobilization and thionation, respectively, and we suggest that it is essential to consider both sulfate and Fe(III) reduction to further our understanding of the environmental fate of

  19. Determining the Threshold Value of Basil Yield Reduction and Evaluation of Water Uptake Models under Salinity Stress Condition

    Directory of Open Access Journals (Sweden)

    M. Sarai Tabrizi

    2016-10-01

    Full Text Available Introduction: Several mathematical models are being used for assessing the plant response to the salinity of the root zone. The salinity of the soil and water resources is a major challenge for agricultural sector in Iran. Several mathematical models have been developed for plant responses to the salinity stress. However, these models are often applicable in particular conditions. The objectives of this study were to evaluate the threshold value of Basil yield reduction, modeling Basil response to salinity and to evaluate the effectiveness of available mathematical models for the yield estimation of the Basil . Materials and Methods: The extensive experiments were conducted with 13 natural saline water treatments including 1.2, 1.8, 2, 2.2, 2.5, 2.8, 3, 3.5, 4, 5, 6, 8, and 10 dSm-1. Water salinity treatments were prepared by mixing Shoor River water with fresh water. In order to quantify the salinity effect on Basil yield, seven mathematical models including Maas and Hoffman (1977, van Genuchten and Hoffman (1984, Dirksen and Augustijn (1988, and Homaee et al., (2002 were used. One of the relatively recent methods for soil water content measurements is theta probes instrument. Theta probes instrument consists of four probes with 60 mm long and 3 mm diameter, a water proof container (probe structure, and a cable that links input and output signals to the data logger display. The advantages that have been attributed to this method are high precision and direct and rapid measurements in the field and greenhouse. The range of measurements is not limited like tensiometer and is from saturation to wilting point. In this study, Theta probes instrument was calibrated by weighing method for exact irrigation scheduling. Relative transpiration was calculated using daily soil water content changes. A coarse sand layer with 2 centimeters thick was used to decrease evaporation from the surface soil of the pots. Quantity comparison of the used models was done

  20. Non-sensitized selective photochemical reduction of CO2 to CO under visible light with an iron molecular catalyst.

    Science.gov (United States)

    Rao, Heng; Bonin, Julien; Robert, Marc

    2017-03-02

    A substituted tetraphenyl iron porphyrin, bearing positively charged trimethylammonio groups at the para position of each phenyl ring, demonstrates its ability as a homogeneous molecular catalyst to selectively reduce CO 2 to CO under visible light irradiation in organic media without the assistance of a sensitizer and no competitive hydrogen evolution for several days.

  1. Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Kang, Hyun Tae; Park, Joon Tae; Choi, Kobong; Choi, Hyo Jei Claudia; Jung, Chul Won; Kim, Gyu Ree; Lee, Young-Sam; Park, Sang Chul

    2017-06-01

    Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  2. Effects of improved sanitation on diarrheal reduction for children under five in Idiofa, DR Congo: a cluster randomized trial.

    Science.gov (United States)

    Cha, Seungman; Lee, JaeEun; Seo, DongSik; Park, Byoung Mann; Mansiangi, Paul; Bernard, Kabore; Mulakub-Yazho, Guy Jerome Nkay; Famasulu, Honore Minka

    2017-09-19

    The lack of safe water and sanitation contributes to the rampancy of diarrhea in many developing countries. This study describes the design of a cluster-randomized trial in Idiofa, the Democratic Republic of the Congo, seeking evidence of the impact of improved sanitation on diarrhea for children under four. Of the 276 quartiers, 18 quartiers were randomly allocated to the intervention or control arm. Seven hundred and-twenty households were sampled and the youngest under-four child in each household was registered for this study. The primary endpoint of the study is diarrheal incidence, prevalence and duration in children under five. Material subsidies will be provided only to the households who complete pit digging plus superstructure and roof construction, regardless of their income level. This study employs a Sanitation Calendar so that the mother of each household can record the diarrheal episodes of her under-four child on a daily basis. The diary enables examination of the effect of the sanitation intervention on diarrhea duration and also resolves the limitation of the small number of clusters in the trial. In addition, the project will be monitored through the 'Sanitation Map', on which all households in the study area, including both the control and intervention arms, are registered. To avoid information bias or courtesy bias, photos will be taken of the latrine during the household visit, and a supervisor will determine well-equipped latrine uptake based on the photos. This reduces the possibility of recall bias and under- or over-estimation of diarrhea, which was the main limitation of previous studies. The study was approved by the Institutional Review Board of the School of Public Health, Kinshasa University (ESP/CE/040/15; April 13, 2015) and registered as an International Standard Randomized Controlled Trial (ISRCTN: 10,419,317) on March 13, 2015.

  3. Mechanistic perspective of mitochondrial fusion: tubulation vs. fragmentation.

    Science.gov (United States)

    Escobar-Henriques, Mafalda; Anton, Fabian

    2013-01-01

    Mitochondrial fusion is a fundamental process driven by dynamin related GTPase proteins (DRPs), in contrast to the general SNARE-dependence of most cellular fusion events. The DRPs Mfn1/Mfn2/Fzo1 and OPA1/Mgm1 are the key effectors for fusion of the mitochondrial outer and inner membranes, respectively. In order to promote fusion, these two DRPs require post-translational modifications and proteolysis. OPA1/Mgm1 undergoes partial proteolytic processing, which results in a combination between short and long isoforms. In turn, ubiquitylation of mitofusins, after oligomerization and GTP hydrolysis, promotes and positively regulates mitochondrial fusion. In contrast, under conditions of mitochondrial dysfunction, negative regulation by proteolysis on these DRPs results in mitochondrial fragmentation. This occurs by complete processing of OPA1 and via ubiquitylation and degradation of mitofusins. Mitochondrial fragmentation contributes to the elimination of damaged mitochondria by mitophagy, and may play a protective role against Parkinson's disease. Moreover, a link of Mfn2 to Alzheimer's disease is emerging and mutations in Mfn2 or OPA1 cause Charcot-Marie-Tooth type 2A neuropathy or autosomal-dominant optic atrophy. Here, we summarize our current understanding on the molecular mechanisms promoting or inhibiting fusion of mitochondrial membranes, which is essential for cellular survival and disease control. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Regenerative abilities of mesenchymal stem cells through mitochondrial transfer.

    Science.gov (United States)

    Paliwal, Swati; Chaudhuri, Rituparna; Agrawal, Anurag; Mohanty, Sujata

    2018-03-30

    The past decade has witnessed an upsurge in studies demonstrating mitochondrial transfer as one of the emerging mechanisms through which mesenchymal stem cells (MSCs) can regenerate and repair damaged cells or tissues. It has been found to play a critical role in healing several diseases related to brain injury, cardiac myopathies, muscle sepsis, lung disorders and acute respiratory disorders. Several studies have shown that various mechanisms are involved in mitochondrial transfer that includes tunnel tube formation, micro vesicle formation, gap junctions, cell fusion and others modes of transfer. Few studies have investigated the mechanisms that contribute to mitochondrial transfer, primarily comprising of signaling pathways involved in tunnel tube formation that facilitates tunnel tube formation for movement of mitochondria from one cell to another. Various stress signals such as release of damaged mitochondria, mtDNA and mitochondrial products along with elevated reactive oxygen species levels trigger the transfer of mitochondria from MSCs to recipient cells. However, extensive cell signaling pathways that lead to mitochondrial transfer from healthy cells are still under investigation and the changes that contribute to restoration of mitochondrial bioenergetics in recipient cells remain largely elusive. In this review, we have discussed the phenomenon of mitochondrial transfer from MSCs to neighboring stressed cells, and how this aids in cellular repair and regeneration of different organs such as lung, heart, eye, brain and kidney. The potential scope of mitochondrial transfer in providing novel therapeutic strategies for treatment of various pathophysiological conditions has also been discussed.

  5. [MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].

    Science.gov (United States)

    Murakami, Hidetomo; Ono, Kenjiro

    2017-02-01

    Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse. About 80% of patients with MELAS have an A-to-G transition mutation at the nucleotide pair 3243 in the dihydrouridine loop of mitochondrial tRNALeu(UUR), which causes the absence of posttranscriptional taurine modification at the wobble nucleotide of mitochondrial tRNALeu(UUR) and disrupts protein synthesis. However, the precise pathophysiology of stroke-like episodes is under investigation, with possible hypotheses for these episodes including mitochondrial angiopathy, mitochondrial cytopathy, and neuron-astrocyte uncoupling. With regard to treatment, L-arginine and taurine have recently been suggested for relief of clinical symptoms.

  6. Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging.

    Science.gov (United States)

    Sebastián, David; Palacín, Manuel; Zorzano, Antonio

    2017-03-01

    Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans. Here, we review the link between alterations in mitochondrial dynamics, aging, and age-related impairment. We propose that the dysregulation of mitochondrial dynamics leads to age-induced accumulation of unhealthy mitochondria and contributes to alterations linked to aging, such as diabetes and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. LABORATORY STUDY FOR THE REDUCTION OF CHROME (VI) TO CHROME (III) USING SODIUM METABISULFITE UNDER ACIDIC CONDITIONS

    International Nuclear Information System (INIS)

    DUNCAM JB; GUTHRIE MD; LUECK KJ; AVILA M

    2007-01-01

    This report describes the results from RPP-PLAN-32738, 'Test Plan for the Effluent Treatment Facility to Reduce Chrome(VI) to Chrome(I1I) in the Secondary Waste Stream', using sodium metabisulfite. Appendix A presents the report as submitted by the Center for Laboratory Sciences (CLS) to CH2M HILL Hanford Group, Inc. The CLS carried out the laboratory effort under Contract Number 21065, release Number 30. This report extracts the more pertinent aspects of the laboratory effort

  8. 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

  9. 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

  10. Elastocapillary Instability in Mitochondrial Fission

    Science.gov (United States)

    Gonzalez-Rodriguez, David; Sart, Sébastien; Babataheri, Avin; Tareste, David; Barakat, Abdul I.; Clanet, Christophe; Husson, Julien

    2015-08-01

    Mitochondria are dynamic cell organelles that constantly undergo fission and fusion events. These dynamical processes, which tightly regulate mitochondrial morphology, are essential for cell physiology. Here we propose an elastocapillary mechanical instability as a mechanism for mitochondrial fission. We experimentally induce mitochondrial fission by rupturing the cell's plasma membrane. We present a stability analysis that successfully explains the observed fission wavelength and the role of mitochondrial morphology in the occurrence of fission events. Our results show that the laws of fluid mechanics can describe mitochondrial morphology and dynamics.

  11. The impact of the worldwide Millennium Development Goals campaign on maternal and under-five child mortality reduction: 'Where did the worldwide campaign work most effectively?'

    Science.gov (United States)

    Cha, Seungman

    2017-01-01

    As the Millennium Development Goals campaign (MDGs) came to a close, clear evidence was needed on the contribution of the worldwide MDG campaign. We seek to determine the degree of difference in the reduction rate between the pre-MDG and MDG campaign periods and its statistical significance by region. Unlike the prevailing studies that measured progress in 1990-2010, this study explores by percentage how much MDG progress has been achieved during the MDG campaign period and quantifies the impact of the MDG campaign on the maternal and under-five child mortality reduction during the MDG era by comparing observed values with counterfactual values estimated on the basis of the historical trend. The low accomplishment of sub-Saharan Africa toward the MDG target mainly resulted from the debilitated progress of mortality reduction during 1990-2000, which was not related to the worldwide MDG campaign. In contrast, the other regions had already achieved substantial progress before the Millennium Declaration was proclaimed. Sub-Saharan African countries have seen the most remarkable impact of the worldwide MDG campaign on maternal and child mortality reduction across all different measurements. In sub-Saharan Africa, the MDG campaign has advanced the progress of the declining maternal mortality ratio and under-five mortality rate, respectively, by 4.29 and 4.37 years. Sub-Saharan African countries were frequently labeled as 'off-track', 'insufficient progress', or 'no progress' even though the greatest progress was achieved here during the worldwide MDG campaign period and the impact of the worldwide MDG campaign was most pronounced in this region in all respects. It is time to learn from the success stories of the sub-Saharan African countries. Erroneous and biased measurement should be avoided for the sustainable development goals to progress.

  12. Reductive and oxidative degradation of iopamidol, iodinated X-ray contrast media, by Fe(III)-oxalate under UV and visible light treatment.

    Science.gov (United States)

    Zhao, Cen; Arroyo-Mora, Luis E; DeCaprio, Anthony P; Sharma, Virender K; Dionysiou, Dionysios D; O'Shea, Kevin E

    2014-12-15

    Iopamidol, widely employed as iodinated X-ray contrast media (ICM), is readily degraded in a Fe(III)-oxalate photochemical system under UV (350 nm) and visible light (450 nm) irradiation. The degradation is nicely modeled by pseudo first order kinetics. The rates of hydroxyl radical (OH) production for Fe(III)-oxalate/H2O2/UV (350 nm) and Fe(III)-oxalate/H2O2/visible (450 nm) systems were 1.19 ± 0.12 and 0.30 ± 0.01 μM/min, respectively. The steady-state concentration of hydroxyl radical (OH) for the Fe(III)-oxalate/H2O2/UV (350 nm) conditions was 10.88 ± 1.13 × 10(-14) M and 2.7 ± 0.1 × 10(-14) M for the Fe(III)-oxalate/H2O2/visible (450 nm). The rate of superoxide anion radical (O2(-)) production under Fe(III)-oxalate/H2O2/UV (350 nm) was 0.19 ± 0.02 μM/min with a steady-state concentration of 5.43 ± 0.473 × 10(-10) M. Detailed product studies using liquid chromatography coupled to Q-TOF/MS demonstrate both reduction (multiple dehalogenations) and oxidation (aromatic ring and side chains) contribute to the degradation pathways. The reduction processes appear to be initiated by the carbon dioxide anion radical (CO2(-)) while oxidation processes are consistent with OH initiated reaction pathways. Unlike most advanced oxidation processes the Fe(III)-oxalate/H2O2/photochemical system can initiate to both reductive and oxidative degradation processes. The observed reductive dehalogenation is an attractive remediation strategy for halogenated organic compounds as the process can dramatically reduce the formation of the problematic disinfection by-products often associated with oxidative treatment processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. LABORATORY STUDY FOR THE REDUCTION OF CHROME (VI) TO CHROME (III) USING SODIUM METABISULFITE UNDER ACIDIC CONDITIONS

    Energy Technology Data Exchange (ETDEWEB)

    DUNCAM JB; GUTHRIE MD; LUECK KJ; AVILA M

    2007-07-18

    This report describes the results from RPP-PLAN-32738, 'Test Plan for the Effluent Treatment Facility to Reduce Chrome(VI) to Chrome(I1I) in the Secondary Waste Stream', using sodium metabisulfite. Appendix A presents the report as submitted by the Center for Laboratory Sciences (CLS) to CH2M HILL Hanford Group, Inc. The CLS carried out the laboratory effort under Contract Number 21065, release Number 30. This report extracts the more pertinent aspects of the laboratory effort.

  14. Stocking and price-reduction decisions for non-instantaneous deteriorating items under time value of money

    Directory of Open Access Journals (Sweden)

    Freddy Andrés Pérez

    2019-01-01

    Full Text Available Deteriorating inventory models are used as decision support tools for managers primarily, although not exclusively, in the retail trade. The mathematical modeling of deteriorating items allows managers to analyze their inventory management systems to identify areas that can be improved and to measure the corresponding potential benefits. This study develops an enhanced deteriorating inventory model for optimizing the inventory control strategy of companies operating in sectors with deteriorating products. In contrast with previous studies, our model holistically accounts for the overall financial effect of a company’s policies on product price discounting and on inventory shortages while considering the time value of money (TVM. We aim to find the optimal replenishment strategy and the optimal price reductions that maximize the discounted profit function of this analytical model over a fixed planning horizon. To this end, we use an economic order quantity model to study the effects of the TVM and inflation. The model accounts for pre- and post-deterioration discounts on the selling price for non-instantaneous deteriorating products with the demand rate being a function of time, price-discounts and stock-keeping units. Shortages are allowed and partially backordered, depending on the waiting time until the next replenishment. Additionally, we consider the effect of discounts on the selling price when items have either an instant deterioration or a fixed lifetime. We propose five implementable solutions for obtaining the optimal values, and examine their performance. We present some numerical examples to illustrate the applicability of the models, and carry out a sensitivity analysis. The study reveals that accounting for TVM and inventory shortages is complex and time-consuming; nevertheless, we find that accounting for TVM and shortages can be valuable in terms of increasing the yields of companies. Finally, we provide some important

  15. Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

    Science.gov (United States)

    Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

    2016-10-01

    Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. [Effect of shifting sand burial on evaporation reduction and salt restraint under saline water irrigation in extremely arid region].

    Science.gov (United States)

    Zhang, Jian-Guo; Zhao, Ying; Xu, Xin-Wen; Lei, Jia-Qiang; Li, Sheng-Yu; Wang, Yong-Dong

    2014-05-01

    The Taklimakan Desert Highway Shelterbelt is drip-irrigated with high saline groundwater (2.58-29.70 g x L(-1)), and shifting sand burial and water-salt stress are most common and serious problems in this region. So it is of great importance to study the effect of shifting sand burial on soil moisture evaporation, salt accumulation and their distribution for water saving, salinity restraint, and suitable utilization of local land and water resources. In this study, Micro-Lysimeters (MLS) were used to investigate dynamics of soil moisture and salt under different thicknesses of sand burial (1, 2, 3, 4, and 5 cm), and field control experiments of drip-irrigation were also carried out to investigate soil moisture and salt distribution under different thicknesses of shifting sand burial (5, 10, 15, 20, 25, 30, 35, and 40 cm). The soil daily and cumulative evaporation decreased with the increase of sand burial thickness in MLS, cumulative evaporation decreased by 2.5%-13.7% compared with control. And evaporative inhibiting efficiency increased with sand burial thickness, evaporative inhibiting efficiency of 1-5 cm sand burial was 16.7%-79.0%. Final soil moisture content beneath the interface of sand burial increased with sand burial thickness, and it increased by 2.5%-13.7% than control. The topsoil EC of shifting sand in MLS decreased by 1.19-6.00 mS x cm(-1) with the increasing sand burial thickness, whereas soil salt content beneath the interface in MLS increased and amplitude of the topsoil salt content was higher than that of the subsoil. Under drip-irrigation with saline groundwater, average soil moisture beneath the interface of shifting sand burial increased by 0.4% -2.0% compare with control, and the highest value of EC was 7.77 mS x cm(-1) when the sand burial thickness was 10 cm. The trend of salt accumulation content at shifting sand surface increased firstly, and then decreased with the increasing sand burial thickness. Soil salt contents beneath the

  17. Variation in total sugars and reductive sugars in the moss Pleurozium schreberi (hylocomiaceae) under water deficit conditions

    International Nuclear Information System (INIS)

    Montenegro Ruiz, Luis Carlos; Melgarejo Munoz, Luz Marina.

    2012-01-01

    The structural simplicity of the bryophytes exposed them easily to water stress, forcing them to have physiological and biochemical mechanisms that enable them to survive. This study evaluated the variation of total soluble sugars and reducing sugars in relation to relative water content, in Pleurozium schreberi when faced with low water content in the Paramo de Chingaza (Colombia) and under simulated conditions of water deficit in the laboratory. we found that total sugars increase when the plant is dehydrated and returned to their normal content when re-hydrated moss, this could be interpreted as a possible mechanism of osmotic adjustment and osmoprotection of the cell content and cellular structure. Reducing sugars showed no significant variation, showing that monosaccharides do not have a protective role during dehydration.

  18. A Variationally Formulated Problem of the Stationary Heat Conduction in a Plate with Radiation Reduction Factor Increased under Temperature

    Directory of Open Access Journals (Sweden)

    V. S. Zarubin

    2016-01-01

    dependence of the absorption factor on the local intensity of this radiation. Furthermore, it can be a significant dependence of this factor on the local value of the material temperature, reflecting the above-mentioned relationship between the absorption of electromagnetic wave energy and the excitation of material microparticles. This process can be described by Boltzmann distribution function that comprises the energy to activate microparticles and the local value of temperature.This paper presents a variational formulation of the nonlinear problem of stationary heat conduction in a plate for the case when the radiation reduction factor in relation to the Bouguer law depends on the local temperature. This formulation includes a functional that can have several fixed points corresponding to different steady states of the plate temperature. Analysis of the properties of this functional enabled us to identify the stationary points, which correspond to the realized temperature distribution in the plate.

  19. Understanding D-Ribose and Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Diane E. Mahoney

    2018-02-01

    Full Text Available Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production.  With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production. Without sufficient energy, cells cannot maintain integrity and function. Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction. When individuals take supplemental D-ribose, it can bypass part of the pentose pathway to produce D-ribose-5-phosphate for the production of energy. In this article, we review how energy is produced by cellular respiration, the pentose pathway, and the use of supplemental D-ribose.

  20. Significant reductions in oil quality and lipid content of oilseed rape (Brassica napus L.) under climate change

    DEFF Research Database (Denmark)

    Namazkar, Shahla; Egsgaard, Helge; Frenck, Georg

    2015-01-01

    Despite of the potential importance to food and bioenergy purposes, effects from climate change on plant oil quality have hardly been characterized.On a global basis Brassica napus L., rapeseed or oilseed rape, is the second largest source of vegetable oil after soybean and the predominant oil crop...... in Europe. We found significant changes in oil quality and quantity of four cultivars of oilseed rape grown in five future climate scenarios with elevated [CO2], [O-3] temperature and combinations hereof (similar to RCP8.5,(1)). Populations of the cultivars were grown under ambient and climate change...... conditions in a climate-phytotron. The treatments were ambient (360 ppm CO2, 19/12 degrees C (day/night), 20/20 ppb O-3 (day/night)), all factors elevated (650 ppm CO2, 24/17 degrees C, 60/20 ppb O-3), as well as two- and single-factor treatments with the elevated factors.The overall trend was that oil...

  1. Macrodynamic study and catalytic reduction of NO by ammonia under mild conditions over Pt-La-Ce-O/Al2O3 catalysts

    International Nuclear Information System (INIS)

    Wang, Yanhui; Zhu, Jingli; Ma, Runyu

    2007-01-01

    Catalytic reduction of NO using ammonia upon series prepared catalysts under 423-573 K in a fixed bed reactor was investigated. Results showed that the performance of supported platinum catalyst could be improved by addition of La and Ce to it. Experimental studies indicated that the suitable molar ratio of Pt:La:Ce would be 1.0:3.78:3.56, Pt-La-Ce (c). Results also found Pt-La-Ce (c) catalyst had good stability and tolerance to certain amounts of sulfur compounds under the used experimental conditions. Characterization for the fresh and used catalysts showed the Pt-La-Ce (c) catalyst had a stable structure. In addition, based on experimental data and using a nonlinear regression algorithm method, an empirical macrodynamic equation was obtained in this study

  2. Highly Chemoselective Reduction of Amides (Primary, Secondary, Tertiary) to Alcohols using SmI2/Amine/H2O under Mild Conditions

    Science.gov (United States)

    2014-01-01

    Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C–N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C–O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the nX → π*C=O (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C–N/C–O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions. PMID:24460078

  3. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    2010-01-01

    Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  4. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Science.gov (United States)

    Guo, Rui; Ren, Jun

    2010-01-18

    Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  5. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  6. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

    Science.gov (United States)

    He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

    2012-07-01

    Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

  7. Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution.

    Directory of Open Access Journals (Sweden)

    Valérie Van der Eecken

    Full Text Available In human, the subcellular targeting of peroxiredoxin-5 (PRDX5, a thioredoxin peroxidase, is dependent on the use of multiple alternative transcription start sites and two alternative in-frame translation initiation sites, which determine whether or not the region encoding a mitochondrial targeting sequence (MTS is translated. In the present study, the abolition of PRDX5 mitochondrial targeting in dog is highlighted and the molecular mechanism underlying the loss of mitochondrial PRDX5 during evolution is examined. Here, we show that the absence of mitochondrial PRDX5 is generalized among the extant canids and that the first events leading to PRDX5 MTS abolition in canids involve a mutation in the more 5' translation initiation codon as well as the appearance of a STOP codon. Furthermore, we found that PRDX5 MTS functionality is maintained in giant panda and northern elephant seal, which are phylogenetically closely related to canids. Also, the functional consequences of the restoration of mitochondrial PRDX5 in dog Madin-Darby canine kidney (MDCK cells were investigated. The restoration of PRDX5 mitochondrial targeting in MDCK cells, instead of protecting, provokes deleterious effects following peroxide exposure independently of its peroxidase activity, indicating that mitochondrial PRDX5 gains cytotoxic properties under acute oxidative stress in MDCK cells. Altogether our results show that, although mitochondrial PRDX5 cytoprotective function against oxidative stress has been clearly demonstrated in human and rodents, PRDX5 targeting to mitochondria has been evolutionary lost in canids. Moreover, restoration of mitochondrial PRDX5 in dog MDCK cells, instead of conferring protection against peroxide exposure, makes them more vulnerable.

  8. Synergistic photocatalysis of Cr(VI) reduction and 4-Chlorophenol degradation over hydroxylated α-Fe{sub 2}O{sub 3} under visible light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ji-Chao; Ren, Juan [College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450002 (China); Yao, Hong-Chang, E-mail: yaohongchang@zzu.edu.cn [College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450002 (China); Zhang, Lin; Wang, Jian-She; Zang, Shuang-Quan [College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450002 (China); Han, Li-Feng [Henan Provincial Key Laboratory of Surface & Interface Science, Zhengzhou University of Light Industry, Zhengzhou 450002 (China); Li, Zhong-Jun, E-mail: lizhongjun@zzu.edu.cn [College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450002 (China)

    2016-07-05

    Highlights: • The surface hydroxyl of Fe{sub 2}O{sub 3} influences on the Cr(VI) reduction activity. • The synergistic photocatalysis enhances degradation activity of Cr(VI) and 4-CP. • The Fe{sub 2}O{sub 3} catalyst exhibits good stability and degradation activity after 9 runs. - Abstract: A series of Fe{sub 2}O{sub 3} materials with hydroxyl are synthesized in different monohydric alcohol (C{sub 2} – C{sub 5}) solvents by solvothermal method and characterized by XRD, BET, XPS, TG and EA. The amount of hydroxyl is demonstrated to be emerged on the surface of the as-synthesized Fe{sub 2}O{sub 3} particles and their contents are determined to be from 7.99 to 3.74 wt%. The Cr(VI) reduction experiments show that the hydroxyl content of Fe{sub 2}O{sub 3} samples exacts great influence on the photocatalytic activity under visible light irradiation (λ > 400 nm) and that the Fe{sub 2}O{sub 3} sample synthesized in n-butyl alcohol exhibits the optimal photocatalytic activity. The synergistic photocatalysis for 4-Chlorophenol (4-CP) degradation and Cr(VI) reduction over above Fe{sub 2}O{sub 3} sample is further investigated. The photocatalytic ratio of Cr(VI) reduction are enhanced from 24.8% to 70.2% while that of 4-CP oxidation are increased from 13.5% to 47.8% after 1 h visible light irradiation. The Fe{sub 2}O{sub 3} sample keeps good degradation rates of mixed pollutants after 9 runs. The active oxygen intermediates O{sub 2}{sup −}·, ·OH and H{sub 2}O{sub 2} formed in the photoreaction process are discovered by ESR measurement and UV–vis test. The photocatalytic degradation mechanism is proposed accordingly.

  9. MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY (MNGIE

    Directory of Open Access Journals (Sweden)

    P. Ayatollahi

    2006-06-01

    Full Text Available Mitochondrial neurogastrointestinal encephalo-myopathy (MNGIE is a rare autosomal recessive disease caused by thymidine phosphorylase (TP gene mutation. Here we report a patient with MNGIE in whom sensorimotor polyneuropathy was the first presenting symptom and had a fluctuating course. This 26-year-old female patient developed acute-onset demyelinating polyneuropathy from the age of 6 with two relapses later on. In addition, she had gastrointestinal symptoms (diarrhea, recurrent abdominal pain, progressive weight loss and ophthalmoparesis. Brain magnetic resonance imaging showed white matter abnormalities, and muscle biopsy showed ragged red fibers. This constellation of clinical and laboratory findings raised the diagnosis of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE. This report highlights the uncommon clinical characteristics of this rare disease.

  10. The mitochondrial genome of the ethanol-metabolizing, wine cellar mold Zasmidium cellare is the smallest for a filamentous ascomycete

    Energy Technology Data Exchange (ETDEWEB)

    Goodwin, Stephen; McCorison, Cassandra B.; Cavaletto, Jessica R.; Culley, David E.; LaButti, Kurt M.; Baker, Scott E.; Grigoriev, Igor V.

    2016-05-20

    Fungi in the class Dothideomycetes often live in extreme environments or have unusual physiology. One of these, the wine cellar mold Zasmidium cellare, produces thick curtains of mycelial growth in cellars with high humidity, and its ability to metabolize volatile organic compounds including alcohols, esters and formaldehyde is thought to improve air quality. It grows slowly but appears to outcompete ordinarily faster-growing species under anaerobic conditions.Whether these abilities have affected its mitochondrial genome is not known.To fill this gap, its mitochondrial genome was assembled as part of a whole- genome shotgun-sequencing project.The circular-mapping mitochondrial genome of Z. cellare, at only 23,743 bp, is the smallest yet reported for a filamentous fungus.It contains the complete set of 14 protein-coding genes seen typically in other filamentous fungi, along with genes for large and small ribosomal RNA subunits, 25 predicted tRNA genes capable of decoding all 20 amino acids, and a single open reading frame potentially coding for a protein of unknown function.The Z. cellare mitochondrial genome had genes encoded on both strands with a single change of direction, different from most other fungi but consistent with the Dothideomycetes. The high synteny among mitochondrial genomes of fungi in the Eurotiomycetes broke down almost completely in the Dothideomycetes.Only a low level of microsynteny was observed among protein-coding and tRNA genes in comparison with Mycosphaerella graminicola (synonym Zymoseptoria tritici), the only other fungus in the order Capnodiales with a sequenced mitochondrial genome, involving the three gene pairs atp8-atp9, nad2-nad3, and nad4L-nad5.However, even this low level of microsynteny did not extend to other fungi in the Dothideomycetes and Eurotiomycetes. Phylogenetic analysis of concatenated protein-coding genes confirmed the relationship between Z. cellare and M. graminicola in the Capnodiales, although conclusions were

  11. Financial Performance of Hospitals in the Mississippi Delta Region Under the Hospital Readmissions Reduction Program and Hospital Value-based Purchasing Program.

    Science.gov (United States)

    Chen, Hsueh-Fen; Karim, Saleema; Wan, Fei; Nevola, Adrienne; Morris, Michael E; Bird, T Mac; Tilford, J Mick

    2017-11-01

    Previous studies showed that the Hospital Readmissions Reduction Program (HRRP) and the Hospital Value-based Purchasing Program (HVBP) disproportionately penalized hospitals caring for the poor. The Mississippi Delta Region (Delta Region) is among the most socioeconomically disadvantaged areas in the United States. The financial performance of hospitals in the Delta Region under both HRRP and HVBP remains unclear. To compare the differences in financial performance under both HRRP and HVBP between hospitals in the Delta Region (Delta hospitals) and others in the nation (non-Delta hospitals). We used a 7-year panel dataset and applied difference-in-difference models to examine operating and total margin between Delta and non-Delta hospitals in 3 time periods: preperiod (2008-2010); postperiod 1 (2011-2012); and postperiod 2 (2013-2014). The Delta hospitals had a 0.89% and 4.24% reduction in operating margin in postperiods 1 and 2, respectively, whereas the non-Delta hospitals had 1.13% and 1% increases in operating margin in postperiods 1 and 2, respectively. The disparity in total margins also widened as Delta hospitals had a 1.98% increase in postperiod 1, but a 0.30% reduction in postperiod 2, whereas non-Delta hospitals had 1.27% and 2.28% increases in postperiods 1 and 2, respectively. The gap in financial performance between Delta and non-Delta hospitals widened following the implementation of HRRP and HVBP. Policy makers should modify these 2 programs to ensure that resources are not moved from the communities that need them most.

  12. MITOCHONDRIAL BKCa CHANNEL

    Directory of Open Access Journals (Sweden)

    Enrique eBalderas

    2015-03-01

    Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

  13. 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.

  14. Chaperone-protease networks in mitochondrial protein homeostasis.

    Science.gov (United States)

    Voos, Wolfgang

    2013-02-01

    As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Peripheral neuropathy associated with mitochondrial disease in children.

    Science.gov (United States)

    Menezes, Manoj P; Ouvrier, Robert A

    2012-05-01

    Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

  16. Mitochondrial functionality in female reproduction

    Directory of Open Access Journals (Sweden)

    Łukasz Gąsior

    2017-01-01

    Full Text Available In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.

  17. Molecular basis for mitochondrial signaling

    CERN Document Server

    2017-01-01

    This book covers recent advances in the study of structure, function, and regulation of metabolite, protein and ion translocating channels, and transporters in mitochondria. A wide array of cutting-edge methods are covered, ranging from electrophysiology and cell biology to bioinformatics, as well as structural, systems, and computational biology. At last, the molecular identity of two important channels in the mitochondrial inner membrane, the mitochondrial calcium uniporter and the mitochondrial permeability transition pore have been established. After years of work on the physiology and structure of VDAC channels in the mitochondrial outer membrane, there have been multiple discoveries on VDAC permeation and regulation by cytosolic proteins. Recent breakthroughs in structural studies of the mitochondrial cholesterol translocator reveal a set of novel unexpected features and provide essential clues for defining therapeutic strategies. Molecular Basis for Mitochondrial Signaling covers these and many more re...

  18. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-09-03

    Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  19. Mitochondrial function in type I cells isolated from rabbit arterial chemoreceptors.

    Science.gov (United States)

    Duchen, M R; Biscoe, T J

    1992-05-01

    1. In this, and the accompanying paper (Duchen & Biscoe, 1992), we test the hypothesis that the oxygen sensitivity of mitochondrial electron transport forms a basis for transduction in the carotid body, the primary peripheral arterial oxygen sensor. We here describe for isolated type I cells the changes in autofluorescence of mitochondrial NAD(P)H that accompany changes in PO2. 2. NAD(P)H autofluorescence (excitation, 340-360 nm; emission peak, 450 nm) increased with anoxia, reflecting a rise in the NAD(P)H/NAD(P) ratio. Graded increases in autofluorescence were seen in response to graded decreases in PO2, suggesting that mitochondrial function is progressively altered below a PO2 of about 60 mmHg. 3. A mitochondrial origin for the NAD(P)H autofluorescence was suggested by the mutual exclusion of the responses to anoxia and cyanide. 4. Oxidized flavoproteins fluoresce when excited at 450 nm with an emission peak at 550 nm. The small signals obtained under these conditions increased with uncoupler and showed a graded decrease with falling PO2 reflecting a rise in the FADH/FAD ratio. 5. Hypoxia raises [Ca2+]i. The hypoxia-induced changes in mitochondrial function were not secondary to this rise. A brief K(+)-induced depolarization leads to a transient increase in [Ca2+]i. At the same time there is a rapid decrease in NAD(P)H autofluorescence followed by an increase that far outlasts the rise in [Ca2+]i. This delayed increase in autofluorescence was smaller than was the increase with anoxia, even though K(+)-induced depolarization raised [Ca2+]i more than does anoxia. In Ca(2+)-free solutions the depolarization-induced changes were abolished, while those associated with hypoxia were maintained. 6. The changes of autofluorescence with K(+)-induced depolarization appear to reflect (i) oxidation of NAD(P)H by stimulation of respiration following mitochondrial Ca2+ uptake and (ii) reduction of NAD(P) by the Ca(2+)-dependent activation of mitochondrial dehydrogenases. This

  20. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

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    Hirotaka Yamamoto

    2016-01-01

    Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

  1. Mitochondrial Dynamics in Diabetic Cardiomyopathy

    Science.gov (United States)

    Galloway, Chad A.

    2015-01-01

    Abstract Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545–1562. PMID

  2. 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...

  3. Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics

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    Zhongbo Liu

    2018-01-01

    Full Text Available One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF that improved glucose utilization in high fat diet (HFD-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle. These data revealed that MGF increased glycolytic metabolites that were further augmented as glycolysis proceeded from the early to the late steps. Consistent with an MGF-stimulation of glycolytic flux there was a concomitant increase in the expression of enzymes catalyzing glycolysis. MGF also increased important metabolites in the tricarboxylic acid (TCA cycle, such as α-ketoglutarate and fumarate. Interestingly however, there was a reduction in succinate, a metabolite that also feeds into the electron transport chain to produce energy. MGF increased succinate clearance by enhancing the expression and activity of succinate dehydrogenase, leading to increased ATP production. At the transcriptional level, MGF induced mRNAs of mitochondrial genes and their transcriptional factors. Together, these data suggest that MGF upregulates mitochondrial oxidative capacity that likely drives the acceleration of glycolysis flux.

  4. Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

    International Nuclear Information System (INIS)

    Velsor, Leonard W.; Kovacevic, Miro; Goldstein, Mark; Leitner, Heather M.; Lewis, William; Day, Brian J.

    2004-01-01

    The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use

  5. Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam.

    Science.gov (United States)

    Stockburger, Carola; Kurz, Christopher; Koch, Konrad A; Eckert, Schamim H; Leuner, Kristina; Müller, Walter E

    2013-10-01

    The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

  6. The Effectiveness of Cognitive-Behavioral Group Therapy on Reduction of Craving, Depression and Anxiety Symptoms among the Opiate Abusers Under MMT

    Directory of Open Access Journals (Sweden)

    Fereshtwh Momeni

    2009-10-01

    Full Text Available Introduction: The aim of this study was to examine the effectiveness of cognitive behavior group therapy on reduction of craving, depression and anxiety symptoms among the Opiate abusers under MMT. Method: In this experimental research, 36 addicts on MMT were selected between the entire opiate addicts referred to Iranian national center for addiction studies (INCAS by convenience sampling and were randomly assigned into experimental and control groups. In experimental group, cognitive behavior group therapy was performed in 8 sessions, one each week. Sessions were performed for craving, depression and anxiety management. Data was gathered by demographic questionnaire, scale of relapse predicts craving assessment, BDI-II and BAI for depression and anxiety symptoms assessment. The data was analyzed, independent and paired samples t test. Results: Data analysis revealed that craving index was decreased in post- test and follow-up and it was statistically significant. Also beck depression and anxiety symptoms were decreased significantly in post-test and follow-up. Conclusion: The results show that cognitive-behavior group therapy was efficient on reduction of drug craving, depression, and anxiety symptoms in post-test and follow-up, and it can apply as a method of treatment.

  7. Activated sludge mass reduction and biodegradability of the endogenous residues by digestion under different aerobic to anaerobic conditions: Comparison and modeling.

    Science.gov (United States)

    Martínez-García, C G; Fall, C; Olguín, M T

    2016-03-01

    This study was performed to identify suitable conditions for the in-situ reduction of excess sludge production by intercalated digesters in recycle-activated sludge (RAS) flow. The objective was to compare and model biological sludge mass reduction and the biodegradation of endogenous residues (XP) by digestion under hypoxic, aerobic, anaerobic, and five intermittent-aeration conditions. A mathematical model based on the heterotrophic endogenous decay constant (bH) and including the biodegradation of XP was used to fit the long-term data from the digesters to identify and estimate the parameters. Both the bH constant (0.02-0.05 d(-1)) and the endogenous residue biodegradation constant (bP, 0.001-0.004 d(-1)) were determined across the different mediums. The digesters with intermittent aeration cycles of 12 h-12 h and 5 min-3 h (ON/OFF) were the fastest, compared to the aerobic reactor. The study provides a basis for rating RAS-digester volumes to avoid the accumulation of XP in aeration tanks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Robust binding between carbon nitride nanosheets and a binuclear ruthenium(II) complex enabling durable, selective CO{sub 2} reduction under visible light in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Kuriki, Ryo; Ishitani, Osamu; Maeda, Kazuhiko [Department of Chemistry, School of Science, Tokyo Institute of Technology (Japan); Yamamoto, Muneaki; Yoshida, Tomoko [Advanced Research Institute for Natural Science and Technology, Osaka City University (Japan); Higuchi, Kimitaka; Yamamoto, Yuta; Akatsuka, Masato; Yagi, Shinya [Institute of Materials and Systems for Sustainability, Nagoya University (Japan); Lu, Daling [Suzukakedai Materials Analysis Division, Technical Department, Tokyo Institute of Technology, Yokohama (Japan)

    2017-04-18

    Carbon nitride nanosheets (NS-C{sub 3}N{sub 4}) were found to undergo robust binding with a binuclear ruthenium(II) complex (RuRu') even in basic aqueous solution. A hybrid material consisting of NS-C{sub 3}N{sub 4} (further modified with nanoparticulate Ag) and RuRu' promoted the photocatalytic reduction of CO{sub 2} to formate in aqueous media, in conjunction with high selectivity (approximately 98 %) and a good turnover number (>2000 with respect to the loaded Ru complex). These represent the highest values yet reported for a powder-based photocatalytic system during CO{sub 2} reduction under visible light in an aqueous environment. We also assessed the desorption of RuRu' from the Ag/C{sub 3}N{sub 4} surface, a factor that can contribute to a loss of activity. It was determined that desorption is not induced by salt additives, pH changes, or photoirradiation, which partly explains the high photocatalytic performance of this material. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  10. 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...

  11. Mitigating Mitochondrial Genome Erosion Without Recombination.

    Science.gov (United States)

    Radzvilavicius, Arunas L; Kokko, Hanna; Christie, Joshua R

    2017-11-01

    Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle promote recombination, but it would also compromise the purifying selection benefits of uniparental inheritance. We assess this tradeoff using a stochastic population-genetic model. In the absence of recombination, uniparental inheritance of freely-segregating genomes mitigates mutational erosion, while paternal leakage exacerbates the ratchet effect. Mitochondrial fusion-fission cycles ensure independent genome segregation, improving purifying selection. Paternal leakage provides opportunity for recombination to slow down the mutation accumulation, but always at a cost of increased steady-state mutation load. Our findings indicate that random segregation of mitochondrial genomes under uniparental inheritance can effectively combat the mutational meltdown, and that homologous recombination under paternal leakage might not be needed. Copyright © 2017 by the Genetics Society of America.

  12. Understanding mitochondrial myopathies: a review

    Directory of Open Access Journals (Sweden)

    Abhimanyu S. Ahuja

    2018-05-01

    Full Text Available Mitochondria are small, energy-producing structures vital to the energy needs of the body. Genetic mutations cause mitochondria to fail to produce the energy needed by cells and organs which can cause severe disease and death. These genetic mutations are likely to be in the mitochondrial DNA (mtDNA, or possibly in the nuclear DNA (nDNA. The goal of this review is to assess the current understanding of mitochondrial diseases. This review focuses on the pathology, causes, risk factors, symptoms, prevalence data, symptomatic treatments, and new research aimed at possible preventions and/or treatments of mitochondrial diseases. Mitochondrial myopathies are mitochondrial diseases that cause prominent muscular symptoms such as muscle weakness and usually present with a multitude of symptoms and can affect virtually all organ systems. There is no cure for these diseases as of today. Treatment is generally supportive and emphasizes symptom management. Mitochondrial diseases occur infrequently and hence research funding levels tend to be low in comparison with more common diseases. On the positive side, quite a few genetic defects responsible for mitochondrial diseases have been identified, which are in turn being used to investigate potential treatments. Speech therapy, physical therapy, and respiratory therapy have been used in mitochondrial diseases with variable results. These therapies are not curative and at best help with maintaining a patient’s current abilities to move and function.

  13. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    Science.gov (United States)

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  14. Mitochondrial DNA repair and aging

    International Nuclear Information System (INIS)

    Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

    2002-01-01

    The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis

  15. Mitochondrial Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    P. C. Keane

    2011-01-01

    Full Text Available 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 proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

  16. Mitochondrial DNA repair and aging

    Energy Technology Data Exchange (ETDEWEB)

    Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

    2002-11-30

    The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.

  17. The effects of fasting and cold exposure on metabolic rate and mitochondrial proton leak in liver and skeletal muscle of an amphibian, the cane toad Bufo marinus.

    Science.gov (United States)

    Trzcionka, M; Withers, K W; Klingenspor, M; Jastroch, M

    2008-06-01

    Futile cycling of protons across the mitochondrial inner membrane contributes significantly to standard metabolic rate in a variety of ectothermic and endothermic animals, but adaptations of the mitochondrial bioenergetics to different environmental conditions have rarely been studied in ectotherms. Changes in ambient temperature and nutritional status have a great effect on the physiological demands of ectothermic amphibians and may require the adjustment of mitochondrial efficiency. In order to investigate the effect of temperature and nutritional status on the mitochondrial level, we exposed male cane toads to either 10 degrees C or 30 degrees C and fasted half of the animals in each group. Cold exposure resulted in a fourfold reduction of the resting metabolic rate whereas nutritional status had only minor effects. The mitochondrial adjustments to each condition were observed by comparing the proton leak kinetics of isolated liver and skeletal muscle mitochondria at 25 degrees C. In response to cold exposure, liver mitochondria showed a decrease in proton conductance while skeletal muscle mitochondria were unchanged. Additional food deprivation had minor effects in skeletal muscle, but in liver we uncovered surprising differences in energy saving mechanisms between the acclimation temperatures: in warm-acclimated toads, fasting resulted in a decrease of the proton conductance whereas in cold-acclimated toads, the activity of the respiratory chain was reduced. To investigate the molecular mechanism underlying mitochondrial proton leakage, we determined the adenine-nucleotide transporter (ANT) content, which explained tissue-specific differences in the basal proton leak, but neither the ANT nor uncoupling protein (UCP) gene expression correlated with alterations of the proton leak in response to physiological stimuli.

  18. Photocatalytic Reduction Activity of 001  TiO2 Codoped with F and Fe under Visible Light for Bromate Removal

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2016-01-01

    Full Text Available The presence of bromate in water is a well-known problem because of its toxic effects on human health, particularly its carcinogenic potential. Photocatalytic reduction is an attractive process for bromate removal. F- and Fe-codoped TiO2 (F-Fe-TiO2 with a {001} facet was successfully prepared, and its bromate-removal activity under visible light was examined. The microstructure, morphology, and chemical state of the doping elements and the optical property of the photocatalysts were examined using transmission electron microscopy (TEM, X-ray photoelectron spectroscopy (XPS, electron paramagnetic resonance (EPR, photoluminescence spectroscopy (PLS, and UV-Vis diffuse reflectance spectra (DRS. The results indicate that the optical properties of F-Fe-TiO2 with the {001} facet and cuboid morphology were obviously improved and its photocatalytic activity was significantly enhanced. The bromate solution of 100 μg/L was thoroughly removed with 0.5 g/L dosage of 1.0% F- and 0.08% Fe-codoped TiO2 composite within 1 hour under visible light.

  19. Numerical investigation of optimal yaw misalignment and collective pitch angle for load imbalance reduction of rigid and flexible HAWT blades under sheared inflow

    International Nuclear Information System (INIS)

    Jeong, Min-Soo; Cha, Myung-Chan; Kim, Sang-Woo; Lee, In

    2015-01-01

    Wind shear can strongly influence the cyclic loading on horizontal axis wind turbine blades. These load fluctuation causes a variation of power output and introduces fatigue load. Thus, individual pitch controllers have been developed that are focused on the load alleviations, however, comes at a price of actuator requirements for control. Moreover, these controllers are unable to apply to already existing wind turbines with active yaw and collective pitch control system. Therefore, the investigations for minimizing load imbalance through the adjustments of yaw misalignment and collective pitch angle are implemented for the rigid and flexible blades under the sheared inflow. By applying the optimization process based on a sequential quadratic programming approach, the optimal yaw and pitch angle can be estimated. Then, the numerical simulations for predicting the performance are performed. The results showed that the fluctuation range of the root flapwise bending moment for the rigid blades can be reduced by 84.5%, whereas the vibratory bending moment for the flexible blades can be reduced by up to approximately 82.4% in the best case. Therefore, the magnitudes of load imbalance can be minimized by the adjustment of the optimal yaw misalignment and collective pitch angle without any power loss. - Highlights: • We propose a novel method for the reduction of load imbalance under sheared inflow. • We estimate optimal yaw misalignment and collective pitch angle through optimization. • Numerical results of performance are predicted for rigid and flexible blades. • By applying optimal angles, load variations are reduced without any power loss

  20. Enhanced selective photocatalytic reduction of CO2 to CH4 over plasmonic Au modified g-C3N4 photocatalyst under UV-vis light irradiation

    Science.gov (United States)

    Li, Hailong; Gao, Yan; Xiong, Zhuo; Liao, Chen; Shih, Kaimin

    2018-05-01

    A series of Au-g-C3N4 (Au-CN) catalysts were prepared through a NaBH4-reduction method using g-C3N4 (CN) from pyrolysis of urea as precursor. The catalysts' surface area, crystal structure, surface morphology, chemical state, functional group composition and optical properties were characterized by X-ray diffraction, transmission electron microscope, X-ray photoelectron spectroscopy, ultraviolet visible (UV-vis) diffuse reflectance spectra, fourier transform infrared, photoluminescence and transient photocurrent analysis. The carbon dioxide (CO2) photoreduction activities under ultraviolet visible (UV-vis) light irradiation were significantly enhanced when gold (Au) was loaded on the surface of CN. 2Au-CN catalyst with Au to CN mole ratio of 2% showed the best catalytic activity. After 2 h UV-vis light irradiation, the methane (CH4) yield over the 2Au-CN catalyst was 9.1 times higher than that over the pure CN. The CH4 selectivity also greatly improved for the 2Au-CN compared to the CN. The deposited Au nanoparticles facilitated the separation of electron-hole pairs on the CN surface. Moreover, the surface plasmon resonance effect of Au further promoted the generation of hot electrons and visible light absorption. Therefore, Au loading significantly improved CO2 photoreduction performance of CN under UV-vis light irradiation.

  1. Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta.

    Directory of Open Access Journals (Sweden)

    Marc Liesa

    Full Text Available There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression.Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1beta is associated with a selective reduction in Mitofusin 2 (Mfn2 expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1beta increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1beta-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1beta increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor alpha (ERRalpha.Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1beta in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.

  2. Similar Efficacies of Selection Shape Mitochondrial and Nuclear Genes in Both Drosophila melanogaster and Homo sapiens.

    Science.gov (United States)

    Cooper, Brandon S; Burrus, Chad R; Ji, Chao; Hahn, Matthew W; Montooth, Kristi L

    2015-08-21

    Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mitochondrial DNA and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes from Drosophila melanogaster and nuclear data available from the same samples, we reexamine the hypothesis that nonrecombining animal mitochondrial DNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction in Ne. Nevertheless, we find that the neutrality index, a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is only weakly significantly different between mitochondrial and nuclear loci. This difference is likely the result of the larger proportion of beneficial mutations in X-linked relative to autosomal loci, and we find little to no difference between mitochondrial and autosomal neutrality indices. Reanalysis of published data from Homo sapiens reveals a similar lack of a difference between the two genomes, although previous studies have suggested a strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci of both flies and humans appear to experience similar efficacies of purifying selection as do loci in the recombining nuclear genome. Copyright © 2015 Cooper et al.

  3. Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

    Science.gov (United States)

    Tan, Dun-Xian; Manchester, Lucien C.; Qin, Lilan; Reiter, Russel J.

    2016-01-01

    Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria. PMID:27999288

  4. Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro.

    Science.gov (United States)

    Casalena, Gabriela; Krick, Stefanie; Daehn, Ilse; Yu, Liping; Ju, Wenjun; Shi, Shaolin; Tsai, Su-yi; D'Agati, Vivette; Lindenmeyer, Maja; Cohen, Clemens D; Schlondorff, Detlef; Bottinger, Erwin P

    2014-06-01

    Mitochondrial dysfunction is increasingly recognized as contributing to glomerular diseases, including those secondary to mitochondrial DNA (mtDNA) mutations and deletions. Mitochondria maintain cellular redox and energy homeostasis and are a major source of intracellular reactive oxygen species (ROS) production. Mitochondrial ROS accumulation may contribute to stress-induced mitochondrial dysfunction and apoptosis and thereby to glomerulosclerosis. In mice, deletion of the gene encoding Mpv17 is associated with glomerulosclerosis, but the underlying mechanism remains poorly defined. Here we report that Mpv17 localizes to mitochondria of podocytes and its expression is reduced in several glomerular injury models and in human focal segmental glomerulosclerosis (FSGS) but not in minimal change disease. Using models of mild or severe nephrotoxic serum nephritis (NTSN) in Mpv17(+/+) wild-type (WT) and Mpv17(-/-) knockout mice, we found that Mpv17 deficiency resulted in increased proteinuria (mild NTSN) and renal insufficiency (severe NTSN) compared with WT. These lesions were associated with increased mitochondrial ROS generation and mitochondrial injury such as oxidative DNA damage. In vitro, podocytes with loss of Mpv17 function were characterized by increased susceptibility to apoptosis and ROS injury including decreased mitochondrial function, loss of mtDNA content, and change in mitochondrial configuration. In summary, the inner mitochondrial membrane protein Mpv17 in podocytes is essential for the maintenance of mitochondrial homeostasis and protects podocytes against oxidative stress-induced injury both in vitro and in vivo. Copyright © 2014 the American Physiological Society.

  5. Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Galloway, Chad A; Lee, Hakjoo; Brookes, Paul S; Yoon, Yisang

    2014-09-15

    Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD. Copyright © 2014 the American Physiological Society.

  6. Altered mitochondrial function and oxidative stress in leukocytes of anorexia nervosa patients.

    Directory of Open Access Journals (Sweden)

    Victor M Victor

    Full Text Available CONTEXT: Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress. OBJECTIVE: The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated. DESIGN AND SETTING: A multi-centre, cross-sectional case-control study was performed. PATIENTS: Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women. MAIN OUTCOME MEASURES: Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells. RESULTS: Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O2 consumption (P<0.05, mitochondrial membrane potential (P<0.01 and GSH levels (P<0.05, and an increase in ROS production (P<0.05 with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05, while the activity of mitochondrial complex I (P<0.001, but not that of complex III, was found to be inhibited in the same population. CONCLUSIONS: Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.

  7. Reduction of chromium (VI) on the hetero-system CuBi2O4/TiO2 under solar light

    Science.gov (United States)

    Lahmar, H.; Benamira, M.; Akika, F. Z.; Trari, M.

    2017-11-01

    The CuBi2O4/TiO2 heterojunction was tested with success for the photo-catalytic reduction of chromate ions under sunlight. CuBi2O4, prepared by nitrate process, was characterised photo-electrochemically. The oxide is stable against photo corrosion by consumption of holes in presence of oxalic acid. The light absorption promotes electrons in the conduction band of the sensitizer (CuBi2O4) with a very negative potential (-1.74 VSCE) to participate in the exchange of the electron with HCrO4-. The enhanced activity is due to electron injection of activated CuBi2O4 into TiO2-CB (-0.97 VSCE). The band gap of the semiconductor CuBi2O4 is 1.50 eV with a direct optical transition. This compound is a p-type semiconductor with a flat band potential of -0.39 VSCE and activation energy of 0.18 eV. The electrochemical impedance spectroscopy was undertaken to study the semiconductor/electrolyte interfacial phenomena. The photoactivity on the heterojunction is strongly enhanced. A remarkable performance is obtained in less than 4 h for a concentration of 30 mg in (Cr (VI)) at pH ∼ 4 and a dose of 1 mg/mL; a 98% reduction has been obtained. The kinetic of chromate photoreduction is well described by the Langmuir-Hinshelwood model. The chromate elimination obeys to a pseudo-first order kinetic with an apparent rate constant of 0.014 min-1.

  8. Photocatalytic reductive dechlorination of 2-chlorodibenzo-p-dioxin by Pd modified g-C3N4 photocatalysts under UV-vis irradiation: Efficacy, kinetics and mechanism.

    Science.gov (United States)

    Ding, Jiafeng; Long, Gaoyuan; Luo, Yang; Sun, Runze; Chen, Mengxia; Li, Yajun; Zhou, Yanfang; Xu, Xinhua; Zhao, Weirong

    2018-05-09

    Polychlorinated dibenzo-p-dioxins (PCDDs), as a group of notorious anthropogenic environmental toxicants, are arguably ubiquitous in nature. In this study, we investigated the photocatalytic reductive dechlorination of 2-chlorodibenzo-p-dioxin (2-CDD) over Pd/g-C 3 N 4 catalysts under UV-vis irradiation. The g-C 3 N 4 and a series of Pd/g-C 3 N 4 catalysts were prepared by thermal polymerization and mechanical mixing-illumination method and characterized by XRD, TEM, BET, SEM and UV-vis DRS analyses. Among all the samples, the Pd/g-C 3 N 4 (5 wt%) yielded the optimal dechlorination activity with a total 2-CDD conversion of 54% within 4 h, and 76% of those converted 2-CDD were evolved to dibenzo-p-dioxin (DD). The kinetics of dechlorination could be described as pseudo-first-order decay model (R 2  > 0.84). Corresponding rate constants (k) increased from 0.052 to 0.17 h -1 with Pd contents up to 5 wt% and decreased to 0.13 h -1 with a 10 wt% of Pd. The enhanced activities originated from the surface plasmonic resonance (SPR) effect of Pd nanoparticles and the formation of Schottky barrier between Pd and g-C 3 N 4 , which extend the spectrum responsive range and suppress the charge recombination of g-C 3 N 4 . This is the first report on the photocatalytic reductive removal of PCDDs and may provide a new approach for PCDDs pollution control. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Synergy of CuO and CeO2 combination for mercury oxidation under low-temperature selective catalytic reduction atmosphere

    KAUST Repository

    Li, Hailong

    2016-07-19

    Synergy for low temperature Hg0 oxidation under selective catalytic reduction (SCR) atmosphere was achieved when copper oxides and cerium oxides were combined in a CuO-CeO2/TiO2 (CuCeTi) catalyst. Hg0 oxidation efficiency as high as 99.0% was observed on the CuCeTi catalyst at 200 °C, even the gas hourly space velocity was extremely high. To analyze the synergistic effect, comparisons of catalyst performance in the presence of different SCR reaction gases were systematically conducted over CuO/TiO2 (CuTi), CeO2/TiO2 (CeTi) and CuCeTi catalysts prepared by sol-gel method. The interactions between copper oxides and cerium oxides in CuCeTi catalyst yielded more surface chemisorbed oxygen, and facilitated the conversion of gas-phase O2 to surface oxygen, which are favorable for Hg0 oxidation. Copper oxides in the combination interacted with NO forming more chemisorbed oxygen for Hg0 oxidation in the absence of gas-phase O2. Cerium oxides in the combination promoted Hg0 oxidation through enhancing the transformations of NO to NO2. In the absence of NO, NH3 exhibited no inhibitive effect on Hg0 oxidation, because enough Lewis acid sites due to the combination of copper oxides and cerium oxides scavenged the competitive adsorption between NH3 and Hg0. In the presence of NO, although NH3 lowered Hg0 oxidation rate through inducing reduction of oxidized mercury, complete recovery of Hg0 oxidation activity over the CuCeTi catalyst was quickly achieved after cutting off NH3. This study revealed the synergistic effect of the combination of copper oxides and cerium oxides on Hg0 oxidation, and explored the involved mechanisms. Such knowledge would help obtaining maximum Hg0 oxidation co-benefit from SCR units in coal-fired power plants.

  10. Adiponectin alleviates genioglossal mitochondrial dysfunction in rats exposed to intermittent hypoxia.

    Directory of Open Access Journals (Sweden)

    Hanpeng Huang

    Full Text Available Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS characterized by nocturnal chronic intermittent hypoxia (CIH. The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks. Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.

  11. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

    Directory of Open Access Journals (Sweden)

    Richard de Boer

    Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

  12. A novel bio-degradable polymer stabilized Ag/TiO2 nanocomposites and their catalytic activity on reduction of methylene blue under natural sun light.

    Science.gov (United States)

    Geetha, D; Kavitha, S; Ramesh, P S

    2015-11-01

    In the present work we defined a novel method of TiO2 doped silver nanocomposite synthesis and stabilization using bio-degradable polymers viz., chitosan (Cts) and polyethylene glycol (PEG). These polymers are used as reducing agents. The instant formation of AgNPs was analyzed by visual observation and UV-visible spectrophotometer. TiO2 nanoparticles doped at different concentrations viz., 0.03, 0.06 and 0.09mM on PEG/Cts stabilized silver (0.04wt%) were successfully synthesized. This study presents a simple route for the in situ synthesis of both metal and polymer confined within the nanomaterial, producing ternary hybrid inorganic-organic nanomaterials. The results reveal that they have higher photocatalytic efficiencies under natural sun light. The synthesized TiO2 doped Ag nanocomposites (NCs) were characterized by SEM/EDS, TEM, XRD, FTIR and DLS with zeta potential. The stability of Ag/TiO2 nanocomposite is due to the high negative values of zeta potential and capping of constituents present in the biodegradable polymer which is evident from zeta potential and FT-IR studies. The XRD and EDS pattern of synthesized Ag/TiO2 NCs showed their crystalline structure, with face centered cubic geometry oriented in (111) plane. AFM and DLS studies revealed that the diameter of stable Ag/TiO2 NCs was approximately 35nm. Moreover the catalytic activity of synthesize Ag/TiO2 NCs in the reduction of methylene blue was studied by UV-visible spectrophotometer. The synthesized Ag/TiO2 NCs are observed to have a good catalytic activity on the reduction of methylene blue by bio-degradable which is confirmed by the decrease in absorbance maximum value of methylene blue with respect to time using UV-vis spectrophotometer. The significant enhancement in the photocatalytic activity of Ag/TiO2 nanocomposites under sun light irradiation can be ascribed to the effect of noble metal Ag by acting as electron traps in TiO2 band gap. Copyright © 2015. Published by Elsevier Inc.

  13. The reactivity of Fe(II) associated with goethite formed during short redox cycles toward Cr(VI) reduction under oxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tomaszewski, Elizabeth J.; Lee, Seungyeol; Rudolph, Jared; Xu, Huifang; Ginder-Vogel, Matthew (UW)

    2017-08-01

    Chromium (Cr) is a toxic metal that causes a myriad of health problems and enters the environment as a result of anthropogenic activities and/or natural processes. The toxicity and solubility of chromium is linked to its oxidation state; Cr(III) is poorly soluble and relatively nontoxic, while Cr(VI) is soluble and a known carcinogen. Solid Fe(II) in iron-bearing minerals, such as pyrite, magnetite, and green rusts, reduce the oxidation state of chromium, reducing its toxicity and mobility. However, these minerals are not the only potential sources of solid-associated Fe(II) available for Cr(VI) reduction. For example, ferric (Fe(III)) (hydr)oxides, such as goethite or hematite, can have Fe(II) in the solid without phase transformation; however, the reactivity of Fe(II) within Fe(III) (hydr)oxides with contaminants, has not been previously investigated. Here, we cyclically react goethite with dissolved Fe(II) followed by dissolved O2, leading to the formation of reactive Fe(II) associated with goethite. In separate reactors, the reactivity of this Fe(II) is probed under oxic conditions, by exposure to chromate (CrO42 -) after either one, two, three or four redox cycles. Cr is not present during redox cycling; rather, it is introduced to a subset of the solid after each oxidation half-cycle. Analysis of X-ray absorption near edge structure (XANES) spectra reveals that the extent of Cr(VI) reduction to Cr(III) depends not only on solid Fe(II) content but also surface area and mean size of ordered crystalline domains, determined by BET surface area analysis and X-ray diffraction (XRD), respectively. Shell-by-shell fitting of the extended X-ray absorption fine structure (EXAFS) spectra demonstrates chromium forms both single and double corner sharing complexes on the surface of goethite, in addition to sorbed Cr(III) species. Finally, transmission electron microscope (TEM) imaging and X-ray energy-dispersive spectroscopy (EDS) illustrate that Cr preferentially

  14. 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.

  15. Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

    Science.gov (United States)

    Mabalirajan, Ulaganathan; Ghosh, Balaram

    2013-01-01

    Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma. PMID:23840225

  16. 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.

  17. Thallium induces hydrogen peroxide generation by impairing mitochondrial function

    International Nuclear Information System (INIS)

    Hanzel, Cecilia E.; Verstraeten, Sandra V.

    2006-01-01

    Thallium (Tl) is highly toxic through yet poorly understood mechanisms. In this study, we comparatively investigated the effects of thallic (Tl(III)) cations on mitochondrial functionality and oxidative stress promotion, and results were compared to those obtained for thallous (Tl(I)) cation. PC12 cells were incubated between 1 and 72 h in the presence of a single dose of Tl(I) or Tl(III) (10-250 μM). A metal concentration- and time-dependent decrease in cell viability was observed evaluated by both MTT reduction and calcein fluorescence. After 24 h in culture, Tl(I) and Tl(III) significantly decreased mitochondrial membrane potential evaluated as the incorporation of rhodamine 123. Along the incubation period assessed, both Tl(I) and Tl(III) (50 and 100 μM) significantly increased mitochondrial H 2 O 2 steady-state levels, being the magnitude of the effect: Tl(III) > Tl(I). Glutathione content, measured by reaction with monochlorobimane, was significantly reduced in Tl-treated cells. Finally, higher oxidant species content in cells cytoplasm was found, which positively correlated with mitochondrial H 2 O 2 content. Together, these results indicate that both ionic species of Tl enhance cells reactive oxygen species production, decreasing mitochondrial functionality. These effects could partially be responsible for the loss of cell viability, and account for the metabolic alterations found in Tl intoxication

  18. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper

    We are testing the hypothesis that oxidized peptides are released from stressed mitochondria and contribute to retrograde signalling (Møller IM & Sweetlove LJ 2010 Trends Plant Sci 15, 370-374). However, there is a large gap between the number of experimentally verified mitochondrial proteins (~450......) 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 mitochondrion. Its...

  19. Feasibility of biodiesel production and CO2 emission reduction by Monoraphidium dybowskii LB50 under semi-continuous culture with open raceway ponds in the desert area.

    Science.gov (United States)

    Yang, Haijian; He, Qiaoning; Hu, Chunxiang

    2018-01-01

    Compared with other general energy crops, microalgae are more compatible with desert conditions. In addition, microalgae cultivated in desert regions can be used to develop biodiesel. Therefore, screening oil-rich microalgae, and researching the algae growth, CO 2 fixation and oil yield in desert areas not only effectively utilize the idle desertification lands and other resources, but also reduce CO 2 emission. Monoraphidium dybowskii LB50 can be efficiently cultured in the desert area using light resources, and lipid yield can be effectively improved using two-stage induction and semi-continuous culture modes in open raceway ponds (ORPs). Lipid content (LC) and lipid productivity (LP) were increased by 20% under two-stage industrial salt induction, whereas biomass productivity (BP) increased by 80% to enhance LP under semi-continuous mode in 5 m 2 ORPs. After 3 years of operation, M. dybowskii LB50 was successfully and stably cultivated under semi-continuous mode for a month during five cycles of repeated culture in a 200 m 2 ORP in the desert area. This culture mode reduced the supply of the original species. The BP and CO 2 fixation rate were maintained at 18 and 33 g m -2  day -1 , respectively. Moreover, LC decreased only during the fifth cycle of repeated culture. Evaporation occurred at 0.9-1.8 L m -2  day -1 , which corresponded to 6.5-13% of evaporation loss rate. Semi-continuous and two-stage salt induction culture modes can reduce energy consumption and increase energy balance through the energy consumption analysis of life cycle. This study demonstrates the feasibility of combining biodiesel production and CO 2 fixation using microalgae grown as feedstock under culture modes with ORPs by using the resources in the desert area. The understanding of evaporation loss and the sustainability of semi-continuous culture render this approach practically viable. The novel strategy may be a promising alternative to existing technology for CO 2 emission

  20. Mitochondrial-Targeted Antioxidant Maintains Blood Flow, Mitochondrial Function, and Redox Balance in Old Mice Following Prolonged Limb Ischemia

    Directory of Open Access Journals (Sweden)

    Shunsuke Miura

    2017-09-01

    Full Text Available Aging is a major factor in the decline of limb blood flow with ischemia. However, the underlying mechanism remains unclear. We investigated the role of mitochondrial reactive oxygen species (ROS with regard to limb perfusion recovery in aging during ischemia. We performed femoral artery ligation in young and old mice with or without treatment with a scavenger of mitochondrial superoxide, MitoTEMPO (180 μg/kg/day, from pre-operative day 7 to post-operative day (POD 21 infusion using an implanted mini-pump. The recoveries of cutaneous blood flow in the ischemic hind limb were lower in old mice than in young mice but were improved in MitoTEMPO-treated old mice. Mitochondrial DNA damage appeared in ischemic aged muscles but was eliminated by MitoTEMPO treatment. For POD 2, MitoTEMPO treatment suppressed the expression of p53 and the ratio of Bax/Bcl2 and upregulated the expression of hypoxia-inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF in ischemic aged skeletal muscles. For POD 21, MitoTEMPO treatment preserved the expression of PGC-1α in ischemic aged skeletal muscle. The ischemic soleus of old mice showed a lower mitochondrial respiratory control ratio in POD 21 compared to young mice, which was recovered in MitoTEMPO-treated old mice. Scavenging of mitochondrial superoxide attenuated mitochondrial DNA damage and preserved the mitochondrial respiration, in addition to suppression of the expression of p53 and preservation of the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α in ischemic skeletal muscles with aging. Resolution of excessive mitochondrial superoxide could be an effective therapy to recover blood flow of skeletal muscle during ischemia in senescence.

  1. The mitochondrial membrane potential in human platelets: a sensitive parameter for platelet quality

    NARCIS (Netherlands)

    Verhoeven, Arthur J.; Verhaar, Robin; Gouwerok, Eric G. W.; de Korte, Dirk

    2005-01-01

    BACKGROUND: Deterioration of platelet (PLT) quality during storage is accompanied by an increase in lactate production, indicating a decrease in mitochondrial function. In this study, the optimal conditions under which the fluorescent dye JC-1 can be used to detect changes in mitochondrial function

  2. MitBASE : a comprehensive and integrated mitochondrial DNA database. The present status

    NARCIS (Netherlands)

    Attimonelli, M.; Altamura, N.; Benne, R.; Brennicke, A.; Cooper, J. M.; D'Elia, D.; Montalvo, A.; Pinto, B.; de Robertis, M.; Golik, P.; Knoop, V.; Lanave, C.; Lazowska, J.; Licciulli, F.; Malladi, B. S.; Memeo, F.; Monnerot, M.; Pasimeni, R.; Pilbout, S.; Schapira, A. H.; Sloof, P.; Saccone, C.

    2000-01-01

    MitBASE is an integrated and comprehensive database of mitochondrial DNA data which collects, under a single interface, databases for Plant, Vertebrate, Invertebrate, Human, Protist and Fungal mtDNA and a Pilot database on nuclear genes involved in mitochondrial biogenesis in Saccharomyces

  3. MCNP variance reduction overview

    International Nuclear Information System (INIS)

    Hendricks, J.S.; Booth, T.E.

    1985-01-01

    The MCNP code is rich in variance reduction features. Standard variance reduction methods found in most Monte Carlo codes are available as well as a number of methods unique to MCNP. We discuss the variance reduction features presently in MCNP as well as new ones under study for possible inclusion in future versions of the code

  4. Facile Synthesis of g-C3N4 Nanosheets/ZnO Nanocomposites with Enhanced Photocatalytic Activity in Reduction of Aqueous Chromium(VI under Visible Light

    Directory of Open Access Journals (Sweden)

    Xiaoya Yuan

    2016-09-01

    Full Text Available Graphitic-C3N4 nanosheets (CN/ZnO photocatalysts (CN/ZnO with different CN loadings were successfully prepared via a simple precipitation-calcination in the presence of exfoliated C3N4 nanosheets. Their morphology and structure were thoroughly characterized by powder X-ray diffraction (XRD, scanning electron microscopy (SEM, high-resolution transmission electron microscopy (HRTEM, X-ray photoelectron spectroscopy (XPS, UV-Vis diffuse reflectance spectroscopy (DRS and photoluminescence spectra (PL. The results showed that hexagonal wurzite-phase ZnO nanoparticles were randomly distributed onto the CN nanosheets with a well-bonded interface between the two components in the CN/ZnO composites. The performance of the photocatalytic Cr(VI reduction indicated that CN/ZnO exhibited better photocatalytic activity than pure ZnO under visible-light irradiation and the photocatalyst composite with a lower loading of CN sheets eventually displayed higher activity. The enhanced performance of CN/ZnO photocatalysts could be ascribed to the increased absorption of the visible light and the effective transfer and separation of the photogenerated charge carriers.

  5. GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction.

    Directory of Open Access Journals (Sweden)

    Raquel Montero

    Full Text Available We previously described increased levels of growth and differentiation factor 15 (GDF-15 in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21. To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA.Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM relative to healthy (350, 21 and myopathic (350, 32 controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4% and 92.3% (81.5%-97.9%, respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated.Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF

  6. Mitochondrial contribution to lipofuscin formation

    Directory of Open Access Journals (Sweden)

    Jeannette König

    2017-04-01

    Moreover, we observed that Lon protease downregulation is linked to a higher lipofuscinogenesis whereas the application of the mitochondrial-targeted antioxidant mitoTEMPO is able to prevent the accumulation of this protein aggregate.

  7. Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Chong-Chong Xu

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA, characterized by specific degeneration of spinal motor neurons, is caused by mutations in the survival of motor neuron 1, telomeric (SMN1 gene and subsequent decreased levels of functional SMN. How the deficiency of SMN, a ubiquitously expressed protein, leads to spinal motor neuron-specific degeneration in individuals affected by SMA remains unknown. In this study, we examined the role of SMN in mitochondrial axonal transport and morphology in human motor neurons by generating SMA type 1 patient-specific induced pluripotent stem cells (iPSCs and differentiating these cells into spinal motor neurons. The initial specification of spinal motor neurons was not affected, but these SMA spinal motor neurons specifically degenerated following long-term culture. Moreover, at an early stage in SMA spinal motor neurons, but not in SMA forebrain neurons, the number of mitochondria, mitochondrial area and mitochondrial transport were significantly reduced in axons. Knocking down of SMN expression led to similar mitochondrial defects in spinal motor neurons derived from human embryonic stem cells, confirming that SMN deficiency results in impaired mitochondrial dynamics. Finally, the application of N-acetylcysteine (NAC mitigated the impairment in mitochondrial transport and morphology and rescued motor neuron degeneration in SMA long-term cultures. Furthermore, NAC ameliorated the reduction in mitochondrial membrane potential in SMA spinal motor neurons, suggesting that NAC might rescue apoptosis and motor neuron degeneration by improving mitochondrial health. Overall, our data demonstrate that SMN deficiency results in abnormal mitochondrial transport and morphology and a subsequent reduction in mitochondrial health, which are implicated in the specific degeneration of spinal motor neurons in SMA.

  8. Preparation of CdS@CeO{sub 2} core/shell composite for photocatalytic reduction of CO{sub 2} under visible-light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ijaz, Sana [CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190 (China); Institute of Chemical Sciences, Bahauddin Zakaryia University, Multan 60800 (Pakistan); Ehsan, Muhammad Fahad [CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190 (China); Ashiq, Muhammad Naeem, E-mail: naeemashiqqau@yahoo.com [Institute of Chemical Sciences, Bahauddin Zakaryia University, Multan 60800 (Pakistan); Karamat, Nazia [Institute of Chemical Sciences, Bahauddin Zakaryia University, Multan 60800 (Pakistan); He, Tao, E-mail: het@nanoctr.cn [CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

    2016-12-30

    Highlights: • CdS@CeO{sub 2}core(*)/shell composite is fabricated using a two-step method. • CdS@CeO{sub 2} can photoreduce CO{sub 2} into CH{sub 4} and CH{sub 3}OH under visible-light irradiation. • CdS@CeO{sub 2} can enhance photocatalytic activity due to increased charge separation. • Core shell strategy for photocatalyst preparation can improve photostability. - Abstract: Present work demonstrates fabrication of CdS@CeO{sub 2} core/shell composite and its application in the photocatalytic reduction of CO{sub 2} under visible-light irradiation (λ ≥ 420 nm). CdS@CeO{sub 2} composite has been successfully prepared by two-step chemical method, while CeO{sub 2} and CdS have been synthesized by one-step hydrothermal method. X-ray diffraction analysis confirms the formation of fluorite cubic structure of CeO{sub 2} and cubic phase of CdS. High resolution transmission electron microscopy and scanning electron microscopy reveal the microsphere morphology of CdS, while CeO{sub 2} (shell) is in the form of spherical particles that surround the CdS (core) in case of the composite. X-ray photoelectron spectroscopy has been used to confirm the composition, oxidation state of the elements and valance band of the obtained materials. The CdS@CeO{sub 2} core/shell composite and CdS can convert CO{sub 2} into methane and methanol under visible-light irradiation. The CdS@CeO{sub 2} composite shows higher yield for both methane and methanol than CdS due to low recombination rate of photogenerated electron/hole pairs, as well as a larger BET specific surface area. Moreover, the CdS@CeO{sub 2} core/shell composite also shows improved stability upon photocatalysis.

  9. Mitochondrial PKA mediates sperm motility.

    Science.gov (United States)

    Mizrahi, Rashel; Breitbart, Haim

    2014-12-01

    Mitochondria are the major source of ATP to power sperm motility. Phosphorylation of mitochondrial proteins has been proposed as a major regulatory mechanism for mitochondrial bioenergetics. Sperm motility was measured by a computer-assisted analyzer, protein detection by western blotting, membrane potential by tetramethylrhodamine, cellular ATP by luciferase assay and localization of PKA by immuno-electron microscopy. Bicarbonate is essential for the creation of mitochondrial electro-chemical gradient, ATP synthesis and sperm motility. Bicarbonate stimulates PKA-dependent phosphorylation of two 60kDa proteins identified as Tektin and glucose-6-phosphate isomerase. This phosphorylation was inhibited by respiration inhibition and phosphorylation could be restored by glucose in the presence of bicarbonate. However, this effect of glucose cannot be seen when the mitochondrial ATP/ADP exchanger was inhibited indicating that glycolytic-produced ATP is transported into the mitochondria and allows PKA-dependent protein phosphorylation inside the mitochondria. Bicarbonate activates mitochondrial soluble adenylyl cyclase (sAC) which catalyzes cAMP production leading to the activation of mitochondrial PKA. Glucose can overcome the lack of ATP in the absence of bicarbonate but it cannot affect the mitochondrial sAC/PKA system, therefore the PKA-dependent phosphorylation of the 60kDa proteins does not occur in the absence of bicarbonate. Production of CO2 in Krebs cycle, which is converted to bicarbonate is essential for sAC/PKA activation leading to mitochondrial membrane potential creation and ATP synthesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Salvato, Fernanda; Havelund, Jesper Foged; Chen, Mingjie

    2014-01-01

    Mitochondria are called the powerhouses of the cell. To better understand the role of mitochondria in maintaining and regulating metabolism in storage tissues, highly purified mitochondria were isolated from dormant potato tubers (Solanum tuberosum 'Folva') and their proteome investigated. Proteins...... manner using normalized spectral counts including as many as 5-fold more "extreme" proteins (low mass, high isoelectric point, hydrophobic) than previous mitochondrial proteome studies. We estimate that this compendium of proteins represents a high coverage of the potato tuber mitochondrial proteome...

  11. 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.

  12. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  13. Suppression of Cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    So Jung Park

    Full Text Available To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10 interacts with heat shock protein 60 (HSP60 and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.

  14. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

    Science.gov (United States)

    Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

    2017-01-01

    The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

  15. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

    Science.gov (United States)

    Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

    2015-11-01

    Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

  16. Mitochondrial Bioenergetics During Ischemia and Reperfusion.

    Science.gov (United States)

    Consolini, Alicia E; Ragone, María I; Bonazzola, Patricia; Colareda, Germán A

    2017-01-01

    M caffeine-36 mM Na + . The caffeine induced contracture (CIC) was due to SR Ca 2+ release, while relaxation mainly depends on mitochondrial Ca 2+ uptake since neither SL-NCX nor SERCA are functional under this media. The ratio of area-under-curves over ischemic values (AUC-ΔHt/AUC-ΔLVP) estimates the energetical consumption (EC) to maintain CIC. Relaxation of CIC was accelerated by inhibition of mNCX or by adding the aerobic substrate pyruvate, while both increased EC. Contrarily, relaxation was slowed by cardioplegia (high K-low Ca Krebs) and by inhibition of UCam. Thus, Mit regulate the cytosolic [Ca 2+ ] and SR Ca 2+ content. Both, hyperthyroidism (HpT) and hypothyroidism (HypoT) reduced the peak of CIC but increased EC, in spite of improving PICR. Both, CIC and PICR in HpT were also sensitive to inhibition of mNCX or UCam, suggesting that Mit contribute to regulate the SR store and Ca 2+ release. The interaction between mitochondria and SR and the energetic consequences were also analyzed for the effects of genistein in hearts exposed to I/R, and for the hypoxia/reoxygenation process. Our results give evidence about the mitochondrial regulation of both PICR and energetic consumption during stunning, through the Ca 2+ movement.

  17. Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model.

    Science.gov (United States)

    Komulainen, Tuomas; Lodge, Tiffany; Hinttala, Reetta; Bolszak, Maija; Pietilä, Mika; Koivunen, Peppi; Hakkola, Jukka; Poulton, Joanna; Morten, Karl J; Uusimaa, Johanna

    2015-05-04

    Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Risk of VPA-induced hepatotoxicity is increased in patients with mitochondrial diseases and especially in patients with POLG1 gene mutations. We used a HepG2 cell in vitro model to investigate the effect of VPA on mitochondrial activity. Cells were incubated in glucose medium and mitochondrial respiration-inducing medium supplemented with galactose and pyruvate. VPA treatments were carried out at concentrations of 0-2.0mM for 24-72 h. In both media, VPA caused decrease in oxygen consumption rates and mitochondrial membrane potential. VPA exposure led to depleted ATP levels in HepG2 cells incubated in galactose medium suggesting dysfunction in mitochondrial ATP production. In addition, VPA exposure for 72 h increased levels of mitochondrial reactive oxygen species (ROS), but adversely decreased protein levels of mitochondrial superoxide dismutase SOD2, suggesting oxidative stress caused by impaired elimination of mitochondrial ROS and a novel pathomechanism related to VPA toxicity. Increased cell death and decrease in cell number was detected under both metabolic conditions. However, immunoblotting did not show any changes in the protein levels of the catalytic subunit A of mitochondrial DNA polymerase γ, the mitochondrial respiratory chain complexes I, II and IV, ATP synthase, E3 subunit dihydrolipoyl dehydrogenase of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase and glutathione peroxidase. Our results show that VPA inhibits mitochondrial respiration and leads to mitochondrial dysfunction, oxidative stress and increased cell death, thus suggesting an essential role of mitochondria in VPA-induced hepatotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Cumulus cell mitochondrial activity in relation to body mass index in women undergoing assisted reproductive therapy

    Directory of Open Access Journals (Sweden)

    Victoria K. Gorshinova

    2017-06-01

    Full Text Available Most studies have considered the negative influence of obesity on fertility in both genders. In the present study, we assessed mitochondrial activity expressed as the mitochondrial potential index (MPI in cumulus cells from obese women and women with a normal body mass index (BMI during assisted reproductive therapy. The results revealed a significant reduction of MPI with increased body mass. The lower MPI levels in cumulus cells from obese women may reflect mitochondrial dysfunction caused by oxidative stress, which can affect the cumulus-oocyte complex and have an impact on oocyte development.

  19. Heterogeneous photocatalysis using TiO2 modified with hydrotalcite and iron oxide under UV-visible irradiation for color and toxicity reduction in secondary textile mill effluent.

    Science.gov (United States)

    Arcanjo, Gemima Santos; Mounteer, Ann H; Bellato, Carlos Roberto; Silva, Laís Miguelina Marçal da; Brant Dias, Santos Henrique; Silva, Priscila Romana da

    2018-04-01

    The objective of this study was to evaluate ADMI color removal from a biologically treated textile mill effluent by heterogeneous photocatalysis with UV-visible irradiation (UV-vis) using a novel catalyst composed of TiO 2 supported on hydrotalcite and doped with iron oxide (HT/Fe/TiO 2 ). Simulated biological treatment of solutions of the dyes (50 mg/L) used in the greatest amounts at the mill where the textile effluent was collected resulted in no color removal in reactive dye solutions and about 50% color removal in vat dye solutions, after 96 h, indicating that the secondary effluent still contained a large proportion of anionic reactive dyes. Photocatalytic treatments were carried out with TiO 2 and HT/Fe/TiO 2 of Fe:Ti molar ratios of 0.25, 0.5, 0.75 and 1, with varying catalyst doses (0-3 mg/L), initial pH values (4-10) and UV-vis times (0-6 h). The highest ADMI color removal with unmodified TiO 2 was found at a dose of 2 g/L and pH 4, an impractical pH value for industrial application. The most efficient composite was HT/Fe/TiO 2 1 at pH 10, also at a dose of 2 g/L, which provided more complete ADMI color removal, from 303 to 9 ADMI color units (96%), than unmodified TiO 2 , from 303 to 37 ADMI color units (88%), under the same conditions. Hydroxyl radicals were responsible for the color reduction, since when 2-propanol, an OH scavenger, was added color removal was very low. For this reason, the HT/Fe/TiO 2 1 composite performed better at pH 10, because the higher concentration of hydroxide ions present at higher pH favored hydroxyl radical formation. COD reductions were relatively low and similar, approximately 20% for both catalysts after 6 h under UV-vis, because of the low initial COD (78 mg/L). Secondary effluent toxicity to Daphnia similis (EC 50  = 70.7%) was reduced by photocatalysis with TiO 2 (EC 50  = 95.0%) and the HT/Fe/TiO 2 1 composite (EC 50  = 78.6%). HT/Fe/TiO 2 1 was reused five times and still lowered

  20. Lowered iPLA2γ activity causes increased mitochondrial lipid peroxidation and mitochondrial dysfunction in a rotenone-induced model of Parkinson's disease.

    Science.gov (United States)

    Chao, Honglu; Liu, Yinlong; Fu, Xian; Xu, Xiupeng; Bao, Zhongyuan; Lin, Chao; Li, Zheng; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

    2018-02-01

    iPLA 2 γ, calcium-independent phospholipase A 2 γ, discerningly hydrolyses glycerophospholipids to liberate free fatty acids. iPLA 2 γ-deficiency has been associated with abnormal mitochondrial function. More importantly, the iPLA 2 family is causative proteins in mitochondrial neurodegenerative disorders such as parkinsonian disorders. However, the mechanisms by which iPLA 2 γ affects Parkinson's disease (PD) remain unknown. Mitochondrion stress has a key part in rotenone-induced dopaminergic neuronal degeneration. The present evaluation revealed that lowered iPLA 2 γ function provokes the parkinsonian phenotype and leads to the reduction of dopamine and its metabolites, lowered survival, locomotor deficiencies, and organismal hypersensitivity to rotenone-induced oxidative stress. In addition, lowered iPLA 2 γ function escalated the amount of mitochondrial irregularities, including mitochondrial reactive oxygen species (ROS) regeneration, reduced ATP synthesis, reduced glutathione levels, and abnormal mitochondrial morphology. Further, lowered iPLA 2 γ function was tightly linked with strengthened lipid peroxidation and mitochondrial membrane flaws following rotenone treatment, which can cause cytochrome c release and eventually apoptosis. These results confirmed the important role of iPLA 2 γ, whereby decreasing iPLA 2 γ activity aggravates mitochondrial degeneration to induce neurodegenerative disorders in a rotenone rat model of Parkinson's disease. These findings may be useful in the design of rational approaches for the prevention and treatment of PD-associated symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Pseudomonas moraviensis subsp. stanleyae, a bacterial endophyte of hyperaccumulator Stanleya pinnata, is capable of efficient selenite reduction to elemental selenium under aerobic conditions.

    Science.gov (United States)

    Staicu, L C; Ackerson, C J; Cornelis, P; Ye, L; Berendsen, R L; Hunter, W J; Noblitt, S D; Henry, C S; Cappa, J J; Montenieri, R L; Wong, A O; Musilova, L; Sura-de Jong, M; van Hullebusch, E D; Lens, P N L; Reynolds, R J B; Pilon-Smits, E A H

    2015-08-01

    To identify bacteria with high selenium tolerance and reduction capacity for bioremediation of wastewater and nanoselenium particle production. A bacterial endophyte was isolated from the selenium hyperaccumulator Stanleya pinnata (Brassicaceae) growing on seleniferous soils in Colorado, USA. Based on fatty acid methyl ester analysis and multi-locus sequence analysis (MLSA) using 16S rRNA, gyrB, rpoB and rpoD genes, the isolate was identified as a subspecies of Pseudomonas moraviensis (97.3% nucleotide identity) and named P. moraviensis stanleyae. The isolate exhibited extreme tolerance to SeO3(2-) (up to 120 mmol l(-1)) and SeO4(2-) (>150 mmol l(-1)). Selenium oxyanion removal from growth medium was measured by microchip capillary electrophoresis (detection limit 95 nmol l(-1) for SeO3(2-) and 13 nmol l(-1) for SeO4(2-)). Within 48 h, P. moraviensis stanleyae aerobically reduced SeO3(2-) to red Se(0) from 10 mmol l(-1) to below the detection limit (removal rate 0.27 mmol h(-1) at 30 °C); anaerobic SeO3(2-) removal was slower. No SeO4(2-) removal was observed. Pseudomonas moraviensis stanleyae stimulated the growth of crop species Brassica juncea by 70% with no significant effect on Se accumulation. Pseudomonas moraviensis stanleyae can tolerate extreme levels of selenate and selenite and can deplete high levels of selenite under aerobic and anaerobic conditions. Pseudomonas moraviensis subsp. stanleyae may be useful for stimulating plant growth and for the treatment of Se-laden wastewater. © 2015 The Society for Applied Microbiology.

  2. How agro-ecological research helps to address food security issues under new IPM and pesticide reduction policies for global crop production systems.

    Science.gov (United States)

    E Birch, A Nicholas; Begg, Graham S; Squire, Geoffrey R

    2011-06-01

    Drivers behind food security and crop protection issues are discussed in relation to food losses caused by pests. Pests globally consume food estimated to feed an additional one billion people. Key drivers include rapid human population increase, climate change, loss of beneficial on-farm biodiversity, reduction in per capita cropped land, water shortages, and EU pesticide withdrawals under policies relating to 91/414 EEC. IPM (Integrated Pest Management) will be compulsory for all EU agriculture by 2014 and is also being widely adopted globally. IPM offers a 'toolbox' of complementary crop- and region-specific crop protection solutions to address these rising pressures. IPM aims for more sustainable solutions by using complementary technologies. The applied research challenge now is to reduce selection pressure on single solution strategies, by creating additive/synergistic interactions between IPM components. IPM is compatible with organic, conventional, and GM cropping systems and is flexible, allowing regional fine-tuning. It reduces pests below economic thresholds utilizing key 'ecological services', particularly biocontrol. A recent global review demonstrates that IPM can reduce pesticide use and increase yields of most of the major crops studied. Landscape scale 'ecological engineering', together with genetic improvement of new crop varieties, will enhance the durability of pest-resistant cultivars (conventional and GM). IPM will also promote compatibility with semiochemicals, biopesticides, precision pest monitoring tools, and rapid diagnostics. These combined strategies are urgently needed and are best achieved via multi-disciplinary research, including complex spatio-temporal modelling at farm and landscape scales. Integrative and synergistic use of existing and new IPM technologies will help meet future food production needs more sustainably in developed and developing countries, in an era of reduced pesticide availability. Current IPM research gaps are

  3. Mitochondrial Cytochrome c Oxidase Biogenesis Is Regulated by the Redox State of a Heme-Binding Translational Activator.

    Science.gov (United States)

    Soto, Iliana C; Barrientos, Antoni

    2016-02-20

    Mitochondrial cytochrome c oxidase (COX), the last enzyme of the respiratory chain, catalyzes the reduction of oxygen to water and therefore is essential for cell function and viability. COX is a multimeric complex, whose biogenesis is extensively regulated. One type of control targets cytochrome c oxidase subunit 1 (Cox1), a key COX enzymatic core subunit translated on mitochondrial ribosomes. In Saccharomyces cerevisiae, Cox1 synthesis and COX assembly are coordinated through a negative feedback regulatory loop. This coordination is mediated by Mss51, a heme-sensing COX1 mRNA-specific processing factor and translational activator that is also a Cox1 chaperone. In this study, we investigated whether Mss51 hemylation and Mss51-mediated Cox1 synthesis are both modulated by the reduction-oxidation (redox) environment. We report that Cox1 synthesis is attenuated under oxidative stress conditions and have identified one of the underlying mechanisms. We show that in vitro and in vivo exposure to hydrogen peroxide induces the formation of a disulfide bond in Mss51 involving CPX motif heme-coordinating cysteines. Mss51 oxidation results in a heme ligand switch, thereby lowering heme-binding affinity and promoting its release. We demonstrate that in addition to affecting Mss51-dependent heme sensing, oxidative stress compromises Mss51 roles in COX1 mRNA processing and translation. H2O2-induced downregulation of mitochondrial translation has so far not been reported. We show that high H2O2 concentrations induce a global attenuation effect, but milder concentrations specifically affect COX1 mRNA processing and translation in an Mss51-dependent manner. The redox environment modulates Mss51 functions, which are essential for regulation of COX biogenesis and aerobic energy production.

  4. Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome

    Science.gov (United States)

    2017-01-01

    Mitochondria preserve very complex and distinctively unique machinery to maintain and express the content of mitochondrial DNA (mtDNA). Similar to chromosomes, mtDNA is packaged into discrete mtDNA-protein complexes referred to as a nucleoid. In addition to its role as a mtDNA shield, over 50 nucleoid-associated proteins play roles in mtDNA maintenance and gene expression through either temporary or permanent association with mtDNA or other nucleoid-associated proteins. The number of mtDNA(s) contained within a single nucleoid is a fundamental question but remains a somewhat controversial issue. Disturbance in nucleoid components and mutations in mtDNA were identified as significant in various diseases, including carcinogenesis. Significant interest in the nucleoid structure and its regulation has been stimulated in relation to mitochondrial diseases, which encompass diseases in multicellular organisms and are associated with accumulation of numerous mutations in mtDNA. In this review, mitochondrial nucleoid structure, nucleoid-associated proteins, and their regulatory roles in mitochondrial metabolism are briefly addressed to provide an overview of the emerging research field involving mitochondrial biology. PMID:28680532

  5. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  6. Formation and Regulation of Mitochondrial Membranes

    Directory of Open Access Journals (Sweden)

    Laila Cigana Schenkel

    2014-01-01

    Full Text Available Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.

  7. Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Shruti; Amar, Saroj Kumar [Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR — Indian Institute of Toxicology Research (CSIR-IITR), M.G, Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research (AcSIR), CSIR — IITR, Lucknow 226001 (India); Dwivedi, Ashish; Mujtaba, Syed Faiz; Kushwaha, Hari Narayan; Chopra, Deepti; Pal, Manish Kumar; Singh, Dhirendra [Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR — Indian Institute of Toxicology Research (CSIR-IITR), M.G, Marg, Lucknow 226001, Uttar Pradesh (India); Chaturvedi, Rajnish Kumar [Developmental Toxicology Division, CSIR — Indian Institute of Toxicology Research, P. O. Box 80, M.G. Marg, Lucknow 226001 (India); Ray, Ratan Singh, E-mail: ratanray.2011@rediffmail.com [Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR — Indian Institute of Toxicology Research (CSIR-IITR), M.G, Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research (AcSIR), CSIR — IITR, Lucknow 226001 (India)

    2016-04-15

    The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. The role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles. - Highlights: • Photodegradation of A132 and formation of novel photoproduct • Involvement of ROS in A132 phototoxicity • Role of ROS in DNA damage, CPD and micronuclei formation • Release of

  8. Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells

    International Nuclear Information System (INIS)

    Goyal, Shruti; Amar, Saroj Kumar; Dwivedi, Ashish; Mujtaba, Syed Faiz; Kushwaha, Hari Narayan; Chopra, Deepti; Pal, Manish Kumar; Singh, Dhirendra; Chaturvedi, Rajnish Kumar; Ray, Ratan Singh

    2016-01-01

    The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. The role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles. - Highlights: • Photodegradation of A132 and formation of novel photoproduct • Involvement of ROS in A132 phototoxicity • Role of ROS in DNA damage, CPD and micronuclei formation • Release of

  9. Microbial Mn(IV) and Fe(III) reduction in northern Barents Sea sediments under different conditions of ice cover and organic carbon deposition

    DEFF Research Database (Denmark)

    Nickel, Maren; Vandieken, Verona; Brüchert, Volker

    2008-01-01

    station, with seasonally extended ice cover, low organic carbon content and sedimentation rate combined with relatively high concentrations of Mn and Fe(III) oxides favored dissimilatory Fe and Mn reduction (98% of anaerobic carbon oxidation) over sulfate reduction in the top 12 cm of the sediment....... In contrast, in a sediment that had not been ice covered for at least 12 months and with more organic carbon and a higher sedimentation rate, sulfate reduction was the most important anaerobic electron-accepting process (>80% of anaerobic carbon oxidation). In the upper 3 cm, microbial Fe and sulfate...

  10. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  11. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  12. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

    Science.gov (United States)

    Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

    2016-09-01

    Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. Copyright © 2016 the American Physiological Society.

  13. Mitochondrial Protection and Anti-aging Activity of Astragalus Polysaccharides and Their Potential Mechanism

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Xin

    2012-02-01

    Full Text Available The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe2+–Vit C in vitro. Thiobarbituric acid (TBA colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS. Mouse liver mitochondrial permeability transition (PT was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O2•- and hydroxyl radical (•OH, which were produced by reduced nicotinamide adenine dinucleotide (NADH—N-Methylphenazonium methyl sulfate (PMS and hydrogen peroxide (H2O2–Fe2+ system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT reduction and Fenton reaction colorimetry respectively. The Na2S2O3 titration method was used to measure the scavenging activities of APS on H2O2. APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O2•-, •OH and H2O2 significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT, surperoxide dismutase (SOD and glutathione peroxidase (GPx and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS, inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health.

  14. Relationship between mitochondrial dysfunction, oxidative stress and diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Song Yue

    2014-12-01

    Full Text Available As one of the serious complications of diabetes, diabetic retinopathy(DRhas become a main eye disease which causes blindness. The occurrence and development of DR is related to many factors. The pathogenesis is complicated, and the mechanism has not been clear. Early data suggest that the occurrence and development of DR has relations with many factors such as blood sugar level, diabetes duration and the environment. Among the factors, mitochondrial dysfunction and oxidative stress is the important mechanisms of DR and has become research focus in recent years. Consequences of mitochondrial dysfunction within cells include elevation of the rate of reactive oxygen species(ROSproduction due to damage of electron transport chain proteins, mitochondrial DNA(mtDNAdamage, and loss of metabolic capacity. Clear understanding on the mechanism of mitochondrial functional change under high sugar level and oxidative stress response in the occurrence and development of DR is of great significance on prevention and cure of DR. In this article, the development of mitochondrial metabolism and oxidative stress of DR is reviewed.

  15. Age-and Brain Region-Specific Differences in Mitochondrial ...

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  16. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

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

    International Nuclear Information System (INIS)

    Palmeira, Carlos M.; Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.

    2007-01-01

    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

  18. Mitochondrial recessive ataxia syndrome mimicking dominant spinocerebellar ataxia.

    Science.gov (United States)

    Palin, Eino J H; Hakonen, Anna H; Korpela, Mari; Paetau, Anders; Suomalainen, Anu

    2012-04-15

    We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Prospects for therapeutic mitochondrial transplantation.

    Science.gov (United States)

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  20. Resveratrol induces mitochondrial biogenesis in endothelial cells.

    Science.gov (United States)

    Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

    2009-07-01

    Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

  1. Lack of mitochondrial MutS homolog 1 in Toxoplasma gondii disrupts maintenance and fidelity of mitochondrial DNA and reveals metabolic plasticity.

    Directory of Open Access Journals (Sweden)

    Tamila Garbuz

    Full Text Available The importance of maintaining the fidelity of the mitochondrial genome is underscored by the presence of various repair pathways within this organelle. Presumably, the repair of mitochondrial DNA would be of particular importance in organisms that possess only a single mitochondrion, like the human pathogens Plasmodium falciparum and Toxoplasma gondii. Understanding the machinery that maintains mitochondrial DNA in these parasites is of particular relevance, as mitochondrial function is a validated and effective target for anti-parasitic drugs. We previously determined that the Toxoplasma MutS homolog TgMSH1 localizes to the mitochondrion. MutS homologs are key components of the nuclear mismatch repair system in mammalian cells, and both yeast and plants possess MutS homologs that localize to the mitochondria where they regulate DNA stability. Here we show that the lack of TgMSH1 results in accumulation of single nucleotide variations in mitochondrial DNA and a reduction in mitochondrial DNA content. Additionally, parasites lacking TgMSH1 function can survive treatment with the cytochrome b inhibitor atovaquone. While the Tgmsh1 knockout strain has several missense mutations in cytochrome b, none affect amino acids known to be determinants of atovaquone sensitivity and atovaquone is still able to inhibit electron transport in the Tgmsh1 mutants. Furthermore, culture of Tgmsh1 mutant in the presence atovaquone leads to parasites with enhanced atovaquone resistance and complete shutdown of respiration. Thus, parasites lacking TgMSH1 overcome the disruption of mitochondrial DNA by adapting their physiology allowing them to forgo the need for oxidative phosphorylation. Consistent with this idea, the Tgmsh1 mutant is resistant to mitochondrial inhibitors with diverse targets and exhibits reduced ability to grow in the absence of glucose. This work shows TgMSH1 as critical for the maintenance and fidelity of the mitochondrial DNA in Toxoplasma

  2. Diaphragm atrophy and weakness in the absence of mitochondrial dysfunction in the critically Ill

    NARCIS (Netherlands)

    Van den Berg, Marloes; Hooijman, Pleuni E.; Beishuizen, Albertus; De Waard, Monique C.; Paul, Marinus A.; Hartemink, Koen J.; Van Hees, Hieronymus W.H.; Lawlor, Michael W.; Brocca, Lorenza; Bottinelli, Roberto; Pellegrino, Maria A.; Stienen, Ger J.M.; Heunks, Leo M.A.; Wüst, Rob C.I.; Ottenheijm, Coen A.C.

    2017-01-01

    Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency and increases morbidity, duration of hospital stay, and health care costs. The mechanisms underlying diaphragm weakness are unknown, but might include mitochondrial

  3. Life-stage and organ specific changes in mitochondrial bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identical ...

  4. The mitochondrial genome of the legume Vigna radiata and the analysis of recombination across short mitochondrial repeats.

    Directory of Open Access Journals (Sweden)

    Andrew J Alverson

    2011-01-01

    Full Text Available The mitochondrial genomes of seed plants are exceptionally fluid in size, structure, and sequence content, with the accumulation and activity of repetitive sequences underlying much of this variation. We report the first fully sequenced mitochondrial genome of a legume, Vigna radiata (mung bean, and show that despite its unexceptional size (401,262 nt, the genome is unusually depauperate in repetitive DNA and "promiscuous" sequences from the chloroplast and nuclear genomes. Although Vigna lacks the large, recombinationally active repeats typical of most other seed plants, a PCR survey of its modest repertoire of short (38-297 nt repeats nevertheless revealed evidence for recombination across all of them. A set of novel control assays showed, however, that these results could instead reflect, in part or entirely, artifacts of PCR-mediated recombination. Consequently, we recommend that other methods, especially high-depth genome sequencing, be used instead of PCR to infer patterns of plant mitochondrial recombination. The average-sized but repeat- and feature-poor mitochondrial genome of Vigna makes it ever more difficult to generalize about the factors shaping the size and sequence content of plant mitochondrial genomes.

  5. Redox Regulation of Mitochondrial Function

    Science.gov (United States)

    Handy, Diane E.

    2012-01-01

    Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

  6. Long-term optimization of the transport sector to address greenhouse gas reduction targets under rapid growth. Application of an energy system model for Gauteng province, South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Tomaschek, Jan

    2013-12-11

    -GEECO, the other demand sectors (such as residential or industry) are also represented. In this thesis, a comprehensive analysis was conducted of alternative fuels, vehicle technologies as well as transport infrastructure for the transport sector of Gauteng. As a result, there are many possibilities of reducing GHG emissions and/or of increasing energy efficiency in the transport sector by using alternative fuels or vehicle technologies. In scenario analysis, it was recognized that under current policies significant growth in both energy consumption and climate emissions can be expected in Gauteng. Marginal GHG abatement cost curves have been calculated, which permit the identification of least-cost mitigation measures for the transport sector under consideration of the whole energy system. It was shown that biofuels from waste cooking oil and cellulosic biomass as well as the substitution of fossil synthetic fuels with crude oil products could result in significant GHG emission reductions. Moreover, hybrid vehicles offer prospects for increasing energy efficiency and reducing GHG emissions at low marginal mitigation costs, where, it was identified that measures should first be applied for vehicles with high annual mileages such as buses, minibuses and heavy-duty vehicles (HDVs). However, the analysis also showed that the transport sector is not the first sector to address for GHG mitigation as significant mitigation potentials with low associated costs lie in the provision of electricity and in the supply of fuels.

  7. Long-term optimization of the transport sector to address greenhouse gas reduction targets under rapid growth. Application of an energy system model for Gauteng province, South Africa

    International Nuclear Information System (INIS)

    Tomaschek, Jan

    2013-01-01

    -GEECO, the other demand sectors (such as residential or industry) are also represented. In this thesis, a comprehensive analysis was conducted of alternative fuels, vehicle technologies as well as transport infrastructure for the transport sector of Gauteng. As a result, there are many possibilities of reducing GHG emissions and/or of increasing energy efficiency in the transport sector by using alternative fuels or vehicle technologies. In scenario analysis, it was recognized that under current policies significant growth in both energy consumption and climate emissions can be expected in Gauteng. Marginal GHG abatement cost curves have been calculated, which permit the identification of least-cost mitigation measures for the transport sector under consideration of the whole energy system. It was shown that biofuels from waste cooking oil and cellulosic biomass as well as the substitution of fossil synthetic fuels with crude oil products could result in significant GHG emission reductions. Moreover, hybrid vehicles offer prospects for increasing energy efficiency and reducing GHG emissions at low marginal mitigation costs, where, it was identified that measures should first be applied for vehicles with high annual mileages such as buses, minibuses and heavy-duty vehicles (HDVs). However, the analysis also showed that the transport sector is not the first sector to address for GHG mitigation as significant mitigation potentials with low associated costs lie in the provision of electricity and in the supply of fuels.

  8. Genetics of mitochondrial dysfunction and infertility.

    Science.gov (United States)

    Demain, L A M; Conway, G S; Newman, W G

    2017-02-01

    Increasingly, mitochondria are being recognized as having an important role in fertility. Indeed in assisted reproductive technologies mitochondrial function is a key indicator of sperm and oocyte quality. Here, we review the literature regarding mitochondrial genetics and infertility. In many multisystem disorders caused by mitochondrial dysfunction death occurs prior to sexual maturity, or the clinical features are so severe that infertility may be underreported. Interestingly, many of the genes linked to mitochondrial dysfunction and infertility have roles in the maintenance of mitochondrial DNA or in mitochondrial translation. Studies on populations with genetically uncharacterized infertility have highlighted an association with mitochondrial DNA deletions, whether this is causative or indicative of poor functioning mitochondria requires further examination. Studies on the impact of mitochondrial DNA variants present conflicting data but highlight POLG as a particularly interesting candidate gene for both male and female infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Mitochondrial DNA and Cancer Epidemiology Workshop

    Science.gov (United States)

    A workshop to review the state-of-the science in the mitochondrial DNA field and its use in cancer epidemiology, and to develop a concept for a research initiative on mitochondrial DNA and cancer epidemiology.

  10. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage

    OpenAIRE

    Bachmann, Rosilla F.; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K.

    2009-01-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially media...

  11. Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

    Directory of Open Access Journals (Sweden)

    Boa Kim

    Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

  12. Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status.

    Directory of Open Access Journals (Sweden)

    Gregory M Enns

    Full Text Available Mitochondrial disorders are associated with decreased energy production and redox imbalance. Glutathione plays a central role in redox signaling and protecting cells from oxidative damage. In order to understand the consequences of mitochondrial dysfunction on in vivo redox status, and to determine how this varies by mitochondrial disease subtype and clinical severity, we used a sensitive tandem mass spectrometry assay to precisely quantify whole blood reduced (GSH and oxidized (GSSG glutathione levels in a large cohort of mitochondrial disorder patients. Glutathione redox potential was calculated using the Nernst equation. Compared to healthy controls (n = 59, mitochondrial disease patients (n = 58 as a group showed significant redox imbalance (redox potential -251 mV ± 9.7, p<0.0001 with an increased level of oxidation by ∼ 9 mV compared to controls (-260 mV ± 6.4. Underlying this abnormality were significantly lower whole blood GSH levels (p = 0.0008 and GSH/GSSG ratio (p = 0.0002, and significantly higher GSSG levels (p<0.0001 in mitochondrial disease patients compared to controls. Redox potential was significantly more oxidized in all mitochondrial disease subgroups including Leigh syndrome (n = 15, electron transport chain abnormalities (n = 10, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (n = 8, mtDNA deletion syndrome (n = 7, mtDNA depletion syndrome (n = 7, and miscellaneous other mitochondrial disorders (n = 11. Patients hospitalized in metabolic crisis (n = 7 showed the greatest degree of redox imbalance at -242 mV ± 7. Peripheral whole blood GSH and GSSG levels are promising biomarkers of mitochondrial dysfunction, and may give insights into the contribution of oxidative stress to the pathophysiology of the various mitochondrial disorders. In particular, evaluation of redox potential may be useful in monitoring of clinical status or response to redox-modulating therapies in clinical trials.

  13. Disruption of mitochondrial electron transport chain function potentiates the pro-apoptotic effects of MAPK inhibition.

    Science.gov (United States)

    Trotta, Andrew P; Gelles, Jesse D; Serasinghe, Madhavika N; Loi, Patrick; Arbiser, Jack L; Chipuk, Jerry E

    2017-07-14

    The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma arising from the V600E mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAF V600E ), oncogenic signaling enhances glucose-dependent metabolism while reducing mitochondrial ATP production. Likewise, when BRAF V600E is pharmacologically inhibited by targeted therapies ( e.g. PLX-4032/vemurafenib), glucose metabolism is reduced, and cells increase mitochondrial ATP production to sustain survival. Therefore, collateral inhibition of oncogenic signaling and mitochondrial respiration may help enhance the therapeutic benefit of targeted therapies. Honokiol (HKL) is a well tolerated small molecule that disrupts mitochondrial function; however, its underlying mechanisms and potential utility with targeted anticancer therapies remain unknown. Using wild-type BRAF and BRAF V600E melanoma model systems, we demonstrate here that HKL administration rapidly reduces mitochondrial respiration by broadly inhibiting ETC complexes I, II, and V, resulting in decreased ATP levels. The subsequent energetic crisis induced two cellular responses involving cyclin-dependent kinases (CDKs). First, loss of CDK1-mediated phosphorylation of the mitochondrial division GTPase dynamin-related protein 1 promoted mitochondrial fusion, thus coupling mitochondrial energetic status and morphology. Second, HKL decreased CDK2 activity, leading to G 1 cell cycle arrest. Importantly, although pharmacological inhibition of oncogenic MAPK signaling increased ETC activity, co-treatment with HKL ablated this response and vastly enhanced the rate of apoptosis. Collectively, these findings integrate HKL action with mitochondrial respiration and shape and substantiate a pro-survival role of mitochondrial function in melanoma cells after oncogenic MAPK inhibition.

  14. Mitochondrial respiratory complex I probed by delayed luminescence spectroscopy

    Science.gov (United States)

    Baran, Irina; Ionescu, Diana; Privitera, Simona; Scordino, Agata; Mocanu, Maria Magdalena; Musumeci, Francesco; Grasso, Rosaria; Gulino, Marisa; Iftime, Adrian; Tofolean, Ioana Teodora; Garaiman, Alexandru; Goicea, Alexandru; Irimia, Ruxandra; Dimancea, Alexandru; Ganea, Constanta

    2013-12-01

    The role of mitochondrial complex I in ultraweak photon-induced delayed photon emission [delayed luminescence (DL)] of human leukemia Jurkat T cells was probed by using complex I targeting agents like rotenone, menadione, and quercetin. Rotenone, a complex I-specific inhibitor, dose-dependently increased the mitochondrial level of reduced nicotinamide adenine dinucleotide (NADH), decreased clonogenic survival, and induced apoptosis. A strong correlation was found between the mitochondrial levels of NADH and oxidized flavin mononucleotide (FMNox) in rotenone-, menadione- and quercetin-treated cells. Rotenone enhanced DL dose-dependently, whereas quercetin and menadione inhibited DL as well as NADH or FMNox. Collectively, the data suggest that DL of Jurkat cells originates mainly from mitochondrial complex I, which functions predominantly as a dimer and less frequently as a tetramer. In individual monomers, both pairs of pyridine nucleotide (NADH/reduced nicotinamide adenine dinucleotide phosphate) sites and flavin (FMN-a/FMN-b) sites appear to bind cooperatively their specific ligands. Enhancement of delayed red-light emission by rotenone suggests that the mean time for one-electron reduction of ubiquinone or FMN-a by the terminal Fe/S center (N2) is 20 or 284 μs, respectively. All these findings suggest that DL spectroscopy could be used as a reliable, sensitive, and robust technique to probe electron flow within complex I in situ.

  15. A case of mitochondrial cardiomyopathy with restrictive transmitral filling pattern

    Directory of Open Access Journals (Sweden)

    Otsui K

    2012-04-01

    Full Text Available Kazunori Otsui, Nobutaka Inoue, Anna Tamagawa, Kazuo OnishiDepartment of Cardiovascular Medicine, Kobe Rosai Hospital, Kobe, JapanAbstract: A 61-year-old diabetic woman with a mitochondrial A3243G mutation was hospitalized for evaluation of breathlessness, general fatigue, and leg edema. Chest radiography revealed cardiomegaly with massive pleural effusion. Serum lactate, pyruvate, and brain natriuretic peptide concentrations were elevated. Transthoracic echocardiography revealed a restrictive pattern of transmitral flow, although systolic function of the left ventricle was only mildly impaired. Based on these findings and her clinical course, the patient was diagnosed with right-sided heart failure caused by mitochondrial cardiomyopathy associated with a restrictive transmitral filling pattern. Treatment with furosemide, enalapril, and eplerenone was effective, and improvement in her symptoms was associated with amelioration of transthoracic echocardiographic findings and a reduction in serum brain natriuretic peptide levels. Previous reports have indicated heterogeneity in the clinical features of mitochondrial cardiomyopathy in patients carrying the A3243G mutation; the present case highlights the substantial variability in the clinical features of this disease.Keywords: mitochondrial disease, A3243G mutation, diastolic dysfunction, transmitral flow

  16. Cost-Sharing Contracts for Energy Saving and Emissions Reduction of a Supply Chain under the Conditions of Government Subsidies and a Carbon Tax

    Directory of Open Access Journals (Sweden)

    Yi Yuyin

    2018-03-01

    Full Text Available To study the cooperation of upstream and downstream enterprises of a supply chain in energy saving and emissions reduction, we establish a Stackelberg game model. The retailer moves first to decide a cost-sharing contract, then the manufacturer determines the energy-saving level, carbon-emission level, and wholesale price successively. In the end, the retailer determines the retail price. As a regulation, the government provides subsidies for energy-saving products, while imposing a carbon tax on the carbon emitted. The results show that (1 both the energy-saving cost-sharing (ECS and the carbon emissions reduction cost-sharing (CCS contracts are not the dominant strategy of the two parties by which they can facilitate energy savings and emissions reductions; (2 compared with single cost-sharing contracts, the bivariate cost-sharing (BCS contract for energy saving and emissions reduction is superior, although it still cannot realise prefect coordination of the supply chain; (3 government subsidy and carbon tax policies can promote the cooperation of both the upstream and downstream enterprises of the supply chain—a subsidy policy can always drive energy saving and emissions reductions, while a carbon tax policy does not always exert positive effects, as it depends on the initial level of pollution and the level of carbon tax; and (4 the subsidy policy reduces the coordination efficiency of the supply chain, while the influences of carbon tax policy upon the coordination efficiency relies on the initial carbon-emission level.

  17. Mitochondrial quality control in cardiac diseases.

    Directory of Open Access Journals (Sweden)

    Juliane Campos

    2016-10-01

    Full Text Available Disruption of mitochondrial homeostasis is a hallmark of cardiac diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for cardiomyocyte survival. In this review, we discuss the most recent findings on the central role of mitochondrial quality control processes including regulation of mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics and clearance in cardiac diseases, highlighting their potential as therapeutic targets.

  18. Mitochondrial fusion through membrane automata.

    Science.gov (United States)

    Giannakis, Konstantinos; Andronikos, Theodore

    2015-01-01

    Studies have shown that malfunctions in mitochondrial processes can be blamed for diseases. However, the mechanism behind these operations is yet not sufficiently clear. In this work we present a novel approach to describe a biomolecular model for mitochondrial fusion using notions from the membrane computing. We use a case study defined in BioAmbient calculus and we show how to translate it in terms of a P automata variant. We combine brane calculi with (mem)brane automata to produce a new scheme capable of describing simple, realistic models. We propose the further use of similar methods and the test of other biomolecular models with the same behaviour.

  19. Mitochondrial respiration is sensitive to cytoarchitectural breakdown.

    Science.gov (United States)

    Kandel, Judith; Angelin, Alessia A; Wallace, Douglas C; Eckmann, David M

    2016-11-07

    An abundance of research suggests that cellular mitochondrial and cytoskeletal disruption are related, but few studies have directly investigated causative connections between the two. We previously demonstrated that inhibiting microtubule and microfilament polymerization affects mitochondrial motility on the whole-cell level in fibroblasts. Since mitochondrial motility can be indicative of mitochondrial function, we now further characterize the effects of these cytoskeletal inhibitors on mitochondrial potential, morphology and respiration. We found that although they did not reduce mitochondrial inner membrane potential, cytoskeletal toxins induced significant decreases in basal mitochondrial respiration. In some cases, basal respiration was only affected after cells were pretreated with the calcium ionophore A23187 in order to stress mitochondrial function. In most cases, mitochondrial morphology remained unaffected, but extreme microfilament depolymerization or combined intermediate doses of microtubule and microfilament toxins resulted in decreased mitochondrial lengths. Interestingly, these two particular exposures did not affect mitochondrial respiration in cells not sensitized with A23187, indicating an interplay between mitochondrial morphology and respiration. In all cases, inducing maximal respiration diminished differences between control and experimental groups, suggesting that reduced basal respiration originates as a largely elective rather than pathological symptom of cytoskeletal impairment. However, viability experiments suggest that even this type of respiration decrease may be associated with cell death.

  20. Mitochondrial mutations drive prostate cancer aggression

    DEFF Research Database (Denmark)

    Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

    2017-01-01

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

  1. 26 CFR 301.9100-6T - Time and manner of making certain elections under the Deficit Reduction Act of 1984.

    Science.gov (United States)

    2010-04-01

    ... for alcohol used as fuel. The election under section 40(f) (as added by section 474(k) of the Act) not... election under such section 102(d)(3), guidelines for making such an election are not provided in this...

  2. Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Graham P. Holloway

    2018-03-01

    Full Text Available Summary: It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H2O2 emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2 emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2 and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2 emission rates in the presence of ADP, the fraction of electron leak to H2O2, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2 emission and contributes to age-associated redox stress. : Holloway et al. show that an inability of ADP to decrease mitochondrial reactive oxygen species emission contributes to redox stress in skeletal muscle tissue of older individuals and that this process is not recovered following prolonged resistance-type exercise training, despite the general benefits of resistance training for muscle health. Keywords: mitochondria, aging, muscle, ROS, H2O2, ADP, respiration, bioenergetics, exercise, resistance training

  3. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

    Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

  4. Clueless, a protein required for mitochondrial function, interacts with the PINK1-Parkin complex in Drosophila

    Directory of Open Access Journals (Sweden)

    Aditya Sen

    2015-06-01

    Full Text Available Loss of mitochondrial function often leads to neurodegeneration and is thought to be one of the underlying causes of neurodegenerative diseases such as Parkinson's disease (PD. However, the precise events linking mitochondrial dysfunction to neuronal death remain elusive. PTEN-induced putative kinase 1 (PINK1 and Parkin (Park, either of which, when mutated, are responsible for early-onset PD, mark individual mitochondria for destruction at the mitochondrial outer membrane. The specific molecular pathways that regulate signaling between the nucleus and mitochondria to sense mitochondrial dysfunction under normal physiological conditions are not well understood. Here, we show that Drosophila Clueless (Clu, a highly conserved protein required for normal mitochondrial function, can associate with Translocase of the outer membrane (TOM 20, Porin and PINK1, and is thus located at the mitochondrial outer membrane. Previously, we found that clu genetically interacts with park in Drosophila female germ cells. Here, we show that clu also genetically interacts with PINK1, and our epistasis analysis places clu downstream of PINK1 and upstream of park. In addition, Clu forms a complex with PINK1 and Park, further supporting that Clu links mitochondrial function with the PINK1-Park pathway. Lack of Clu causes PINK1 and Park to interact with each other, and clu mutants have decreased mitochondrial protein levels, suggesting that Clu can act as a negative regulator of the PINK1-Park pathway. Taken together, these results suggest that Clu directly modulates mitochondrial function, and that Clu's function contributes to the PINK1-Park pathway of mitochondrial quality control.

  5. Assessment of mitochondrial functions in Daphnia pulex clones using high-resolution respirometry.

    Science.gov (United States)

    Kake-Guena, Sandrine A; Touisse, Kamal; Vergilino, Roland; Dufresne, France; Blier, Pierre U; Lemieux, Hélène

    2015-06-01

    The objectives of our study were to adapt a method to measure mitochondrial function in intact mitochondria from the small crustacean Daphnia pulex and to validate if this method was sensitive enough to characterize mitochondrial metabolism in clones of the pulex complex differing in ploidy levels, mitochondrial DNA haplotypes, and geographic origins. Daphnia clones belonging to the Daphnia pulex complex represent a powerful model to delineate the link between mitochondrial DNA evolution and mitochondrial phenotypes, as single genotypes with divergent mtDNA can be grown under various experimental conditions. Our study included two diploid clones from temperate environments and two triploid clones from subarctic environments. The whole animal permeabilization and measurement of respiration with high-resolution respirometry enabled the measurement of the functional capacity of specific mitochondrial complexes in four clones. When expressing the activity as ratios, our method detected significant interclonal variations. In the triploid subarctic clone from Kuujjurapik, a higher proportion of the maximal physiological oxidative phosphorylation (OXPHOS) capacity of mitochondria was supported by complex II, and a lower proportion by complex I. The triploid subarctic clone from Churchill (Manitoba) showed the lowest proportion of the maximal OXPHOS supported by complex II. Additional studies are required to determine if these differences in mitochondrial functions are related to differences in mitochondrial haplotypes or ploidy level and if they might be associated with fitness divergences and therefore selective value. © 2015 Wiley Periodicals, Inc.

  6. Molecular Mechanisms for Age-Associated Mitochondrial Deficiency in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Akira Wagatsuma

    2012-01-01

    Full Text Available The abundance, morphology, and functional properties of mitochondria decay in skeletal muscle during the process of ageing. Although the precise mechanisms remain to be elucidated, these mechanisms include decreased mitochondrial DNA (mtDNA repair and mitochondrial biogenesis. Mitochondria possess their own protection system to repair mtDNA damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes. However, mtDNA mutations have shown to be accumulated with age in skeletal muscle. When damaged mitochondria are eliminated by autophagy, mitochondrial biogenesis plays an important role in sustaining energy production and physiological homeostasis. The capacity for mitochondrial biogenesis has shown to decrease with age in skeletal muscle, contributing to progressive mitochondrial deficiency. Understanding how these endogenous systems adapt to altered physiological conditions during the process of ageing will provide a valuable insight into the underlying mechanisms that regulate cellular homeostasis. Here we will summarize the current knowledge about the molecular mechanisms responsible for age-associated mitochondrial deficiency in skeletal muscle. In particular, recent findings on the role of mtDNA repair and mitochondrial biogenesis in maintaining mitochondrial functionality in aged skeletal muscle will be highlighted.

  7. Multiple independent origins of mitochondrial control region duplications in the order Psittaciformes

    Science.gov (United States)

    Schirtzinger, Erin E.; Tavares, Erika S.; Gonzales, Lauren A.; Eberhard, Jessica R.; Miyaki, Cristina Y.; Sanchez, Juan J.; Hernandez, Alexis; Müeller, Heinrich; Graves, Gary R.; Fleischer, Robert C.; Wright, Timothy F.

    2012-01-01

    Mitochondrial genomes are generally thought to be under selection for compactness, due to their small size, consistent gene content, and a lack of introns or intergenic spacers. As more animal mitochondrial genomes are fully sequenced, rearrangements and partial duplications are being identified with increasing frequency, particularly in birds (Class Aves). In this study, we investigate the evolutionary history of mitochondrial control region states within the avian order Psittaciformes (parrots and cockatoos). To this aim, we reconstructed a comprehensive multi-locus phylogeny of parrots, used PCR of three diagnostic fragments to classify the mitochondrial control region state as single or duplicated, and mapped these states onto the phylogeny. We further sequenced 44 selected species to validate these inferences of control region state. Ancestral state reconstruction using a range of weighting schemes identified six independent origins of mitochondrial control region duplications within Psittaciformes. Analysis of sequence data showed that varying levels of mitochondrial gene and tRNA homology and degradation were present within a given clade exhibiting duplications. Levels of divergence between control regions within an individual varied from 0–10.9% with the differences occurring mainly between 51 and 225 nucleotides 3′ of the goose hairpin in domain I. Further investigations into the fates of duplicated mitochondrial genes, the potential costs and benefits of having a second control region, and the complex relationship between evolutionary rates, selection, and time since duplication are needed to fully explain these patterns in the mitochondrial genome. PMID:22543055

  8. The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action.

    Science.gov (United States)

    Griveau, A; Devailly, G; Eberst, L; Navaratnam, N; Le Calvé, B; Ferrand, M; Faull, P; Augert, A; Dante, R; Vanacker, J M; Vindrieux, D; Bernard, D

    2016-09-22

    Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

  9. Pathophysiology of mitochondrial lipid oxidation: Role of 4-hydroxynonenal (4-HNE) and other bioactive lipids in mitochondria.

    Science.gov (United States)

    Xiao, Mengqing; Zhong, Huiqin; Xia, Lin; Tao, Yongzhen; Yin, Huiyong

    2017-10-01

    Mitochondrial lipids are essential for maintaining the integrity of mitochondrial membranes and the proper functions of mitochondria. As the "powerhouse" of a cell, mitochondria are also the major cellular source of reactive oxygen species (ROS). Oxidative stress occurs when the antioxidant system is overwhelmed by overproduction of ROS. Polyunsaturated fatty acids in mitochondrial membranes are primary targets for ROS attack, which may lead to lipid peroxidation (LPO) and generation of reactive lipids, such as 4-hydroxynonenal. When mitochondrial lipids are oxidized, the integrity and function of mitochondria may be compromised and this may eventually lead to mitochondrial dysfunction, which has been associated with many human diseases including cancer, cardiovascular diseases, diabetes, and neurodegenerative diseases. How mitochondrial lipids are oxidized and the underlying molecular mechanisms and pathophysiological consequences associated with mitochondrial LPO remain poorly defined. Oxidation of the mitochondria-specific phospholipid cardiolipin and generation of bioactive lipids through mitochondrial LPO has been increasingly recognized as an important event orchestrating apoptosis, metabolic reprogramming of energy production, mitophagy, and immune responses. In this review, we focus on the current understanding of how mitochondrial LPO and generation of bioactive lipid mediators in mitochondria are involved in the modulation of mitochondrial functions in the context of relevant human diseases associated with oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Laila R.B. Santos

    2017-06-01

    Full Text Available Objective: The glucose stimulation of insulin secretion (GSIS by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets. Methods: Islets were isolated from female C57BL/6J mice (J-islets, which lack functional NNT, and genetically close C57BL/6N mice (N-islets. Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures. Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification. Conclusion: These

  11. Catalytic role of Cu(II) in the reduction of Cr(VI) by citric acid under an irradiation of simulated solar light.

    Science.gov (United States)

    Li, Ying; Chen, Cheng; Zhang, Jing; Lan, Yeqing

    2015-05-01

    The catalytic role of Cu(II) in the reduction of Cr(VI) by citric acid with simulated solar light was investigated. The results demonstrated that Cu(II) could significantly accelerate Cr(VI) reduction and the reaction obeyed to pseudo zero-order kinetics with respect to Cr(VI). The removal of Cr(VI) was related to the initial concentrations of Cu(II), citric acid, and the types of organic acids. The optimal removal of Cr(VI) was achieved at pH 4, and the rates of Cu(II) photocatalytic reduction of Cr(VI) by organic acids were in the order: tartaric acid (two α-OH groups, two -COOH groups)>citric acid (one α-OH group, three -COOH groups)>malic acid (one α-OH group, two -COOH groups)>lactic acid (one α-OH group, one -COOH group)≫succinic acid (two -COOH groups), suggesting that the number of α-OH was the key factor for the reaction, followed by the number of -COOH. The formation of Cu(II)-citric acid complex could generate Cu(I) and radicals through a pathway of metal-ligand-electron transfer, promoting the reduction of Cr(VI). This study is helpful to fully understanding the conversion of Cr(VI) in the existence of both organic acids and Cu(II) with solar light in aquatic environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The role of transport sector within the German energy system under greenhouse gas reduction constraints and effects on other exhaust gases

    Energy Technology Data Exchange (ETDEWEB)

    Walbeck, M; Martinsen, D [Research Center Juelich (Germany)

    1996-12-01

    The German Federal Government pledged itself to make a 25% reduction in national CO{sub 2} emissions by 2005 on the basis of 1990 CO{sub 2} emissions. This reduction target is valid for the entire Federal Republic. Within that context the Federal Ministry of Education, Science, Research and Technology initiated the IKARUS project (Instruments for Greenhouse Gas Reduction Strategies) in 1990. The aim of the project is to provide tools for developing strategies to reduce energy-related emissions of greenhouse gases in Germany. A range of instruments has been developed consisting of models, a data base and various tools with the aid of which different action sequences can be simulated and evaluated until the year 2020. By using the database and mainly one of the models of the project a scenario in terms of energy and carbon dioxide emissions will be sown as it could be expected for the year 2005. For this scenario as base two different strategies that hit the 25% reduction target will be discussed. Special attention is given to the transport sector. (au)

  13. Influence of Th(NO3)4, KCl and pH on the reduction of HgCl2 under X- and UV-radiations

    International Nuclear Information System (INIS)

    Prashad, Jagdish; Suri, Ranjana

    2000-01-01

    The yield of Hg 2 Cl 2 is maximum at relatively high pH, diminished progressively with decrease of pH and is completely inhibited beyond a critical pH. In the presence of Th(NO 3 ) 4 , slight reduction is observed. The results are explicable by assuming the existence of hydrated molecular ion H 2 + (hydr.). (author)

  14. Wet SiO2 As a Suitable Media for Fast and Efficient Reduction of Carbonyl Compounds with NaBH3CN under Solvent-Free and Acid-Free Conditions

    International Nuclear Information System (INIS)

    Kouhkan, Mehri; Zeynizadeh, Behzad

    2010-01-01

    Reduction of carbonyl compounds such as aldehydes, ketones, α,β-unsaturated enals and enones, α-diketones and acyloins was carried out readily with NaBH 3 CN in the presence of wet SiO 2 as a neutral media. The reactions were performed at solvent-free conditions in oil bath (70 - 80 .deg. C) or under microwave irradiation (240 W) to give the product alcohols in high to excellent yields. Regioselective 1,2-reduction of conjugated carbonyl compounds took place in a perfect selectivity without any side product formation

  15. Wet SiO{sub 2} As a Suitable Media for Fast and Efficient Reduction of Carbonyl Compounds with NaBH{sub 3}CN under Solvent-Free and Acid-Free Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kouhkan, Mehri; Zeynizadeh, Behzad [Urmia University, Urmia (Iran, Islamic Republic of)

    2010-10-15

    Reduction of carbonyl compounds such as aldehydes, ketones, α,β-unsaturated enals and enones, α-diketones and acyloins was carried out readily with NaBH{sub 3}CN in the presence of wet SiO{sub 2} as a neutral media. The reactions were performed at solvent-free conditions in oil bath (70 - 80 .deg. C) or under microwave irradiation (240 W) to give the product alcohols in high to excellent yields. Regioselective 1,2-reduction of conjugated carbonyl compounds took place in a perfect selectivity without any side product formation.

  16. Reduction redux.

    Science.gov (United States)

    Shapiro, Lawrence

    2018-04-01

    Putnam's criticisms of the identity theory attack a straw man. Fodor's criticisms of reduction attack a straw man. Properly interpreted, Nagel offered a conception of reduction that captures everything a physicalist could want. I update Nagel, introducing the idea of overlap, and show why multiple realization poses no challenge to reduction so construed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Carbothermic Reduction Kinetics of Phosphorous Vaporization from Tri-calcium Phosphate (TCP) Under Microwave Rapid Heating With/Without the Presence of Fe3O4

    Science.gov (United States)

    Yoshikawa, Noboru; Sunako, Manami; Kawahira, Keita; Suzuki, Koki; Miyamoto, Kazunori; Taniguchi, Shoji

    2018-03-01

    The kinetics of vapor phase dephosphorization from tri-calcium phosphate (TCP) by carbothermic reduction was studied with and without the presence of Fe3O4. Microwave heating was utilized to obtain large variations in the heating rate (HR). In the reduction of TCP alone, the phosphorous removal fraction (RF; equal to ΔP2O5/P2O5 0 , where ΔP2O5 is the weight change and P2O5 0is the P2O5 weight before heating) decreased as the HR increased. In other words, a shorter residence time at a high temperature resulted in a smaller reduction fraction of TCP. An apparently third-order reaction was postulated to account for the kinetics using a fitting simulation based on the additive law of the reaction progress. On the other hand, the phosphorous removal (dephosphorization) rate (RR; equal to ΔP2O3/t MW, where tMW is the microwave heating time period) increased as the HR increased above 1200 °C. The reduction ratio of Fe3O4 above 1100 °C is higher than 97 pct regardless of the heating rate. The reduction of TCP in the presence of Fe3O4 showed that RF increased slightly with increasing HR despite a shorter residence time at a high temperature. The RR also increased with the HR even though RF decreased to half of the values observed in the cases without Fe3O4 for temperatures above 1200 °C. The practicality and optimal operation conditions of phosphorus vapor removal were discussed.

  18. Carbothermic Reduction Kinetics of Phosphorous Vaporization from Tri-calcium Phosphate (TCP) Under Microwave Rapid Heating With/Without the Presence of Fe3O4

    Science.gov (United States)

    Yoshikawa, Noboru; Sunako, Manami; Kawahira, Keita; Suzuki, Koki; Miyamoto, Kazunori; Taniguchi, Shoji

    2018-06-01

    The kinetics of vapor phase dephosphorization from tri-calcium phosphate (TCP) by carbothermic reduction was studied with and without the presence of Fe3O4. Microwave heating was utilized to obtain large variations in the heating rate (HR). In the reduction of TCP alone, the phosphorous removal fraction (RF; equal to ΔP2O5/P2O 5 0 , where ΔP2O5 is the weight change and P2O 5 0 is the P2O5 weight before heating) decreased as the HR increased. In other words, a shorter residence time at a high temperature resulted in a smaller reduction fraction of TCP. An apparently third-order reaction was postulated to account for the kinetics using a fitting simulation based on the additive law of the reaction progress. On the other hand, the phosphorous removal (dephosphorization) rate (RR; equal to ΔP2O3/ t MW, where tMW is the microwave heating time period) increased as the HR increased above 1200 °C. The reduction ratio of Fe3O4 above 1100 °C is higher than 97 pct regardless of the heating rate. The reduction of TCP in the presence of Fe3O4 showed that RF increased slightly with increasing HR despite a shorter residence time at a high temperature. The RR also increased with the HR even though RF decreased to half of the values observed in the cases without Fe3O4 for temperatures above 1200 °C. The practicality and optimal operation conditions of phosphorus vapor removal were discussed.

  19. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.