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Sample records for affects mitochondrial entrance

  1. Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

    DEFF Research Database (Denmark)

    Philips, Mari-Anne; Kingo, Külli; Karelson, Maire

    2010-01-01

    MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim...

  2. Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

    DEFF Research Database (Denmark)

    Philips, Mari-Anne; Kingo, Külli; Karelson, Maire;

    2010-01-01

    MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to ...

  3. Entrance Qualifications Affect the Performance of Nutrition Students at University: A Pilot Study

    Science.gov (United States)

    Owusu-Apenten, Richard; Xu, Wen Li

    2012-01-01

    This study assessed the effect of admissions qualifications on the subsequent academic performances of BSc nutrition students at a UK university. Entrance qualifications for three groups (Grp01, Grp02, Grp03) reading for a BSc(Hons) degree in, Dietetics, Food & Nutrition or Human Nutrition (n = 105) were determined from their UCAS (Universities…

  4. Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy.

    Science.gov (United States)

    Tigchelaar, Wardit; Yu, Hongjuan; de Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Silljé, Herman H W

    2015-01-15

    Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes. Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs) induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG, however, did not result in loss of mitochondrial DNA integrity. Although EXOG depletion did not induce fetal gene expression and common hypertrophy pathways were not activated, a clear increase in ribosomal S6 phosphorylation was observed, which readily explains increased protein synthesis. With the use of a Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked OCR was 5.2-fold higher. This increase was not explained by mitochondrial biogenesis or alterations in mitochondrial membrane potential. Western blotting confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels. These increased ROS levels could be normalized with specific mitochondrial ROS scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal mitochondrial function resulting in increased mitochondrial respiration, excess ROS production, and cardiomyocyte hypertrophy.

  5. Inherited Mendelian defects of nuclear-mitochondrial communication affecting the stability of mitochondrial DNA.

    Science.gov (United States)

    Limongelli, Anna; Tiranti, Valeria

    2002-11-01

    The presence of mtDNA abnormalities inherited as Mendelian traits indicates the existence of mutations in nuclear genes affecting the integrity of the mitochondrial genome. Two groups of nucleus-driven abnormalities have been described: qualitative alterations of mtDNA, i.e. multiple large-scale deletions of mtDNA, and quantitative decrease of the mtDNA copy number, i.e. tissue-specific depletion of mtDNA. Autosomal dominant or recessive (adPEO), progressive ophthalmoplegia and autosomal-recessive mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), are three neurodegenerative disorders associated with the coexistence of wild-type mtDNA with several deletion-containing mtDNA species. Heterozygous mutations of the genes encoding the muscle-heart isoform of the adenosine diphosphate/adenosine triphosphate mitochondrial translocator (ANT1), the main subunit of polymerase gamma (POLG1), and of the putative mtDNA helicase (Twinkle) have been found in adPEO families linked to three different loci, on chromosomes 4q34-35, 10q24, and 15q25, respectively. Mutations in the gene encoding thymidine phosphorylase have been identified in several MNGIE patients. Severe, tissue-specific depletion of mtDNA is the molecular hallmark of rapidly progressive hepatopathies or myopathies of infancy and childhood. Two genes, deoxyguanosine kinase and thymidine kinase type 2, both involved in the mitochondrion-specific salvage pathways of deoxynucleotide pools, have been associated with depletion syndromes in selected families.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stéphane Demine

    2014-09-01

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

  8. Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS mediated cardiomyocyte hypertrophy

    NARCIS (Netherlands)

    Tigchelaar, Wardit; Yu, Hongjuan; De Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Sillje, Herman H W

    2015-01-01

    Recently, a genetic variant in the mitochondrial exo/endo nuclease EXOG, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrop

  9. COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1.

    Science.gov (United States)

    Ban-Ishihara, Reiko; Tomohiro-Takamiya, Shiho; Tani, Motohiro; Baudier, Jacques; Ishihara, Naotada; Kuge, Osamu

    2015-10-07

    Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology.

  10. Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kowalec, Piotr; Grynberg, Marcin; Pająk, Beata; Socha, Anna; Winiarska, Katarzyna; Fronk, Jan; Kurlandzka, Anna

    2015-09-01

    Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level.

  11. Mitochondrial Haplogroups Affect Severity But Not Prevalence of Diabetic Retinopathy

    Science.gov (United States)

    Bregman, Jana A.; Herren, David J.; Estopinal, Christopher B.; Chocron, Isaac M.; Harlow, Paula A.; Warden, Cassandra; Brantley, Milam A.; Samuels, David C.

    2017-01-01

    Purpose We previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes. Methods Deidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status. Results The percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13–2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79–2.10], P = 0.20). Conclusions Mitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR. PMID:28245487

  12. Drosophila clueless is highly expressed in larval neuroblasts, affects mitochondrial localization and suppresses mitochondrial oxidative damage.

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    Aditya Sen

    Full Text Available Mitochondria are critical for neuronal function due to the high demand of ATP in these cell types. During Drosophila development, neuroblasts in the larval brain divide asymmetrically to populate the adult central nervous system. While many of the proteins responsible for maintaining neuroblast cell fate and asymmetric cell divisions are known, little is know about the role of metabolism and mitochondria in neuroblast division and maintenance. The gene clueless (clu has been previously shown to be important for mitochondrial function. clu mutant adults have severely shortened lifespans and are highly uncoordinated. Part of their lack of coordination is due to defects in muscle, however, in this study we have identified high levels of Clu expression in larval neuroblasts and other regions of the dividing larval brain. We show while mitochondria in clu mutant neuroblasts are mislocalized during the cell cycle, surprisingly, overall brain morphology appears to be normal. This is explained by our observation that clu mutant larvae have normal levels of ATP and do not suffer oxidative damage, in sharp contrast to clu mutant adults. Mutations in two other genes encoding mitochondrial proteins, technical knockout and stress sensitive B, do not cause neuroblast mitochondrial mislocalization, even though technical knockout mutant larvae suffer oxidative damage. These results suggest Clu functions upstream of electron transport and oxidative phosphorylation, has a role in suppressing oxidative damage in the cell, and that lack of Clu's specific function causes mitochondria to mislocalize. These results also support the previous observation that larval development relies on aerobic glycolysis, rather than oxidative phosphorylation. Thus Clu's role in mitochondrial function is not critical during larval development, but is important for pupae and adults.

  13. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells.

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    Matthew E Gegg

    Full Text Available BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD. Impairment of the mitochondrial electron transport chain (ETC and an increased frequency in deletions of mitochondrial DNA (mtDNA, which encodes some of the subunits of the ETC, have been reported in the substantia nigra of PD brains. The identification of mutations in the PINK1 gene, which cause an autosomal recessive form of PD, has supported mitochondrial involvement in PD. The PINK1 protein is a serine/threonine kinase localized in mitochondria and the cytosol. Its precise function is unknown, but it is involved in neuroprotection against a variety of stress signalling pathways. METHODOLOGY/PRINCIPAL FINDINGS: In this report we have investigated the effect of silencing PINK1 expression in human dopaminergic SH-SY5Y cells by siRNA on mtDNA synthesis and ETC function. Loss of PINK1 expression resulted in a decrease in mtDNA levels and mtDNA synthesis. We also report a concomitant loss of mitochondrial membrane potential and decreased mitochondrial ATP synthesis, with the activity of complex IV of the ETC most affected. This mitochondrial dysfunction resulted in increased markers of oxidative stress under basal conditions and increased cell death following treatment with the free radical generator paraquat. CONCLUSIONS: This report highlights a novel function of PINK1 in mitochondrial biogenesis and a role in maintaining mitochondrial ETC activity. Dysfunction of both has been implicated in sporadic forms of PD suggesting that these may be key pathways in the development of the disease.

  14. Apolipoprotein E4 (1–272 fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells

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    Michikawa Makoto

    2009-08-01

    Full Text Available Abstract Background Apolipoprotein E allele ε4 (apoE4 is a strong risk factor for developing Alzheimer's disease (AD. Secreted apoE has a critical function in redistributing lipids among central nervous system cells to maintain normal lipid homeostasis. In addition, previous reports have shown that apoE4 is cleaved by a protease in neurons to generate apoE4(1–272 fragment, which is associated with neurofibrillary tanglelike structures and mitochondria, causing mitochondrial dysfunction. However, it still remains unclear how the apoE fragment associates with mitochondria and induces mitochondrial dysfunction. Results To clarify the molecular mechanism, we carried out experiments to identify intracellular apoE-binding molecules and their functions in modulating mitochondria function. Here, we found that apoE4 binds to ubiquinol cytochrome c reductase core protein 2 (UQCRC2 and cytochrome C1, both of which are components of mitochondrial respiratory complex III, and cytochrome c oxidase subunit 4 isoform 1 (COX IV 1, which is a component of complex IV, in Neuro-2a cells. Interestingly, these proteins associated with apoE4(1–272 more strongly than intact apoE4(1–299. Further analysis showed that in Neuro-2a cells expressing apoE4(1–272, the enzymatic activities of mitochondrial respiratory complexes III and IV were significantly lower than those in Neuro-2a cells expressing apoE4(1–299. Conclusion ApoE4(1–272 fragment expressed in Neuro2a cells is associated with mitochondrial proteins, UQCRC2 and cytochrome C1, which are component of respiratory complex III, and with COX IV 1, which is a member of complex IV. Overexpression of apoE4(1–272 fragment impairs activities of complex III and IV. These results suggest that the C-terminal-truncated fragment of apoE4 binds to mitochondrial complexes and affects their activities, and thereby leading to neurodegeneration.

  15. Common genetic variants of the mitochondrial trafficking system and mitochondrial uncoupling proteins affect the development of two slowly developing demyelinating disorders, leukoaraiosis and multiple sclerosis.

    Science.gov (United States)

    Szolnoki, Z

    2010-01-01

    As the central energy source, the mitochondria are of great importance in the maintenance of the glia cells of the brain. It is presumed that mitochondrial energy production is affected not only by well-characterized genetic mutations of the mitochondria, which are associated with severe malfunctions and resultant acute glia and neuronal cell death, but also by a number of other unfavorable genetic variants. The genetic variants of the kinesin motor proteins and mitochondrial uncoupling proteins (UCPs) are believed to influence the mitochondrial energy production in different distress states of the glia cells. The kinesin motor proteins carry the mitochondria from the central parts to the peripheral parts of the glia cells, where myelin protein synthesis takes place. The UCPs are essential for regulation of the mitochondrial membrane potential under different physiological conditions, thereby finally attuning mitochondrial energy production in environmental states such as cold exposure, fasting or chronic mild hypoxia. While the capacity of the kinesin motor proteins can affect the number of mitochondria in the peripheral parts of the glia cells, the functional features of the UCPs can affect the degree of energy production of the mitochondria by influencing the mitochondrial membrane potential. The different genetic variants may display different activities, and some may result in a slowly developing energy shortage in the glia cells. In this context, this article discusses the roles of genetic variants of the kinesin motor proteins and UCPs in slowly developing diseases of the white matter of the brain as multiple sclerosis and leukoaraiosis.

  16. Cadmium exposure affects mitochondrial bioenergetics and gene expression of key mitochondrial proteins in the eastern oyster Crassostrea virginica Gmelin (Bivalvia: Ostreidae)

    Energy Technology Data Exchange (ETDEWEB)

    Sokolova, Inna M. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)]. E-mail: insokolo@uncc.edu; Sokolov, Eugene P. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Ponnappa, Kavita M. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)

    2005-07-01

    Cadmium is a ubiquitous and extremely toxic metal, which strongly affects mitochondrial function of aquatic organisms in vitro; however, nothing is known about the in vivo effects of sublethal concentrations of this metal on mitochondrial bioenergetics. We have studied the effects of exposure to 0 (control) or 25 {mu}g L{sup -1} (Cd-exposed) Cd{sup 2+} on mitochondrial function and gene expression of key mitochondrial proteins in the eastern oyster Crassostrea virginica. Cadmium exposure in vivo resulted in considerable accumulation of cadmium in oyster mitochondria and in a significant decrease of ADP-stimulated respiration (state 3) by 30% indicating impaired capacity for ATP production. The decrease in state 3 respiration was similar to the level of inhibition expected from the direct effects of cadmium accumulated in oyster mitochondria. On the other hand, while no effect on proton leak was expected based on the mitochondrial accumulation of cadmium, Cd-exposed oysters in fact showed a significant decline of the proton leak rate (state 4 + respiration) by 40%. This suggested a downregulation of proton leak, which correlated with a decrease in mRNA expression of a mitochondrial uncoupling protein UCP6 and two other potential uncouplers, mitochondrial substrate carriers MSC-1 and MSC-2. Expression of other key mitochondrial proteins including cytochrome c oxidase, adenine nucleotide transporter and voltage dependent anion channel was not affected by cadmium exposure. Adenylate energy charge (AEC) was significantly lower in Cd-exposed oysters; however, this was due to higher steady state ADP levels and not to the decrease in tissue ATP levels. Our data show that adjustment of the proton leak in cadmium-exposed oysters may be a compensatory mechanism, which allows them to maintain normal mitochondrial coupling and ATP levels despite the cadmium-induced inhibition of capacity for ATP production.

  17. Do university entrance exams predict academic achievement?

    OpenAIRE

    Häkkinen, Iida

    2004-01-01

    The study examines which factors predict academic performance at university and compares the predictive values of subject-related entrance exams and indicators of past school performance. The results show that in the fields of engineering and social sciences entrance exams predict both graduation and the number of study credits better than past performance. In education past school performance is a better predictor of graduation. Changing the admission rule to school grades would affect the a...

  18. Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle.

    Science.gov (United States)

    Winter, Lilli; Kuznetsov, Andrey V; Grimm, Michael; Zeöld, Anikó; Fischer, Irmgard; Wiche, Gerhard

    2015-08-15

    Plectin, a versatile 500-kDa cytolinker protein, is essential for muscle fiber integrity and function. The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy. Besides displaying pathological desmin-positive protein aggregates and degenerative changes in the myofibrillar apparatus, skeletal muscle specimens of EBS-MD patients and plectin-deficient mice are characterized by massive mitochondrial alterations. In this study, we demonstrate that structural and functional alterations of mitochondria are a primary aftermath of plectin deficiency in muscle, contributing to myofiber degeneration. We found that in skeletal muscle of conditional plectin knockout mice (MCK-Cre/cKO), mitochondrial content was reduced, and mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions and were no longer associated with Z-disks. Additionally, decreased mitochondrial citrate synthase activity, respiratory function and altered adenosine diphosphate kinetics were characteristic of plectin-deficient muscles. To analyze a mechanistic link between plectin deficiency and mitochondrial alterations, we comparatively assessed mitochondrial morphology and function in whole muscle and teased muscle fibers of wild-type, MCK-Cre/cKO and plectin isoform-specific knockout mice that were lacking just one isoform (either P1b or P1d) while expressing all others. Monitoring morphological alterations of mitochondria, an isoform P1b-specific phenotype affecting the mitochondrial fusion-fission machinery and manifesting with upregulated mitochondrial fusion-associated protein mitofusin-2 could be identified. Our results show that the depletion of distinct plectin isoforms affects mitochondrial network organization and function in different ways.

  19. Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver.

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    Anna Picca

    Full Text Available Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18-month-old, 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA content and mitochondrial transcription factor A (TFAM amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1α NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins (PRX-SO3 in the ad libitum-fed animals. An unexpected age-related decrease in the mitochondrial proteins peroxiredoxin III (Prx III and superoxide dismutase 2 (SOD2, usually induced by increased ROS and involved in mitochondrial biogenesis, suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression of these genes with aging. The partial prevention of the decrease in Prx III and SOD2 proteins by CR also supported the preservation of mitochondrial biogenesis in the anti-aging action of CR. To investigate further the age- and CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting

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

    Science.gov (United States)

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

    2016-08-01

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

  1. English for common entrance

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    Kossuth, Kornel

    2013-01-01

    Succeed in the exam with this revision guide, designed specifically for the brand new Common Entrance English syllabus. It breaks down the content into manageable and straightforward chunks with easy-to-use, step-by-step instructions that should take away the fear of CE and guide you through all aspects of the exam. - Gives you step-by-step guidance on how to recognise various types of comprehension questions and answer them. - Shows you how to write creatively as well as for a purpose for the section B questions. - Reinforces and consolidates learning with tips, guidance and exercises through

  2. G alpha12 is targeted to the mitochondria and affects mitochondrial morphology and motility.

    Science.gov (United States)

    Andreeva, Alexandra V; Kutuzov, Mikhail A; Voyno-Yasenetskaya, Tatyana A

    2008-08-01

    G alpha12 constitutes, along with G alpha13, one of the four families of alpha subunits of heterotrimeric G proteins. We found that the N terminus of G alpha12, but not those of other G alpha subunits, contains a predicted mitochondrial targeting sequence. Using confocal microscopy and cell fractionation, we demonstrated that up to 40% of endogenous G alpha12 in human umbilical vein endothelial cells colocalize with mitochondrial markers. N-terminal sequence of G alpha12 fused to GFP efficiently targeted the fusion protein to mitochondria. G alpha12 with mutated mitochondrial targeting sequence was still located in mitochondria, suggesting the existence of additional mechanisms for mitochondrial localization. Lysophosphatidic acid, one of the known stimuli transduced by G alpha12/13, inhibited mitochondrial motility, while depletion of endogenous G alpha12 increased mitochondrial motility. G alpha12Q229L variants uncoupled from RhoGEFs (but not fully functional activated G alpha12Q229L) induced transformation of the mitochondrial network into punctate mitochondria and resulted in a loss of mitochondrial membrane potential. All examined G alpha12Q229L variants reduced phosphorylation of Bcl-2 at Ser-70, while only mutants unable to bind RhoGEFs also decreased cellular levels of Bcl-2. These G alpha12 mutants were also more efficient Hsp90 interactors. These findings are the first demonstration of a heterotrimeric G protein alpha subunit specifically targeted to mitochondria and involved in the control of mitochondrial morphology and dynamics.

  3. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

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    Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

    2016-12-01

    Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca(2+) homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca(2+) uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca(2+) homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss.

  4. Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology

    DEFF Research Database (Denmark)

    Engl, Gertraud; Florian, Stefan; Tranebjærg, Lisbeth

    2012-01-01

    -C66W was overexpressed. Live cell microscopy of primary fibroblasts derived from DDON patients and of DDP1 downregulated HeLa cells displayed alterations of mitochondrial morphology with notable extensions in the length of mitochondrial tubules, whereas overexpression of DDP1 induced the formation...

  5. Mitochondrial DNA Haplogroup Background Affects LHON, but Not Suspected LHON, in Chinese Patients

    Science.gov (United States)

    Bi, Rui; Salas, Antonio; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Kong, Qing-Peng; Zhang, Qingjiong; Yao, Yong-Gang

    2011-01-01

    Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). We analyzed the mitochondrial DNA (mtDNA) variation of 304 Chinese patients with m.11778G>A (sample #1) and of 843 suspected LHON patients who lack the three primary mutations (sample #2) to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3). The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10−17, OR = 0.051, 95% CI: 0.016–0.162; #1 vs. #2, P-value = 4.44×10−17, OR = 0.049, 95% CI: 0.015–0.154; in both cases, adjusted P-value A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor. PMID:22110754

  6. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients.

    Directory of Open Access Journals (Sweden)

    A-Mei Zhang

    Full Text Available Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON. We analyzed the mitochondrial DNA (mtDNA variation of 304 Chinese patients with m.11778G>A (sample #1 and of 843 suspected LHON patients who lack the three primary mutations (sample #2 to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3. The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10(-17, OR = 0.051, 95% CI: 0.016-0.162; #1 vs. #2, P-value = 4.44×10(-17, OR = 0.049, 95% CI: 0.015-0.154; in both cases, adjusted P-value A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.

  7. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients.

    Science.gov (United States)

    Zhang, A-Mei; Jia, Xiaoyun; Bi, Rui; Salas, Antonio; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Kong, Qing-Peng; Zhang, Qingjiong; Yao, Yong-Gang

    2011-01-01

    Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). We analyzed the mitochondrial DNA (mtDNA) variation of 304 Chinese patients with m.11778G>A (sample #1) and of 843 suspected LHON patients who lack the three primary mutations (sample #2) to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3). The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10(-17), OR = 0.051, 95% CI: 0.016-0.162; #1 vs. #2, P-value = 4.44×10(-17), OR = 0.049, 95% CI: 0.015-0.154; in both cases, adjusted P-value LHON in Chinese patients with m.11778G>A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.

  8. Early Exercise Affects Mitochondrial Transcription Factors Expression after Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Yongshan Hu

    2012-02-01

    Full Text Available Increasing evidence shows that exercise training is neuroprotective after stroke, but the underlying mechanisms are unknown. To clarify this critical issue, the current study investigated the effects of early treadmill exercise on the expression of mitochondrial biogenesis factors. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Expression of two genes critical for transcriptional regulation of mitochondrial biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1 and nuclear respiratory factor-1 (NRF-1, were examined by RT-PCR after five days of exercise starting at 24 h after ischemia. Mitochondrial protein cytochrome C oxidase subunit IV (COX IV was detected by Western blot. Neurological status and cerebral infarct volume were evaluated as indices of brain damage. Treadmill training increased levels of PGC-1 and NRF-1 mRNA, indicating that exercise promotes rehabilitation after ischemia via regulation of mitochondrial biogenesis.

  9. miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

    Directory of Open Access Journals (Sweden)

    Maude Giroud

    2016-08-01

    Conclusion: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.

  10. Mitochondrial DNA Alterations and Reduced Mitochondrial Function in Aging

    OpenAIRE

    Hebert, Sadie L.; Lanza, Ian R.; Nair, K. Sreekumaran

    2010-01-01

    Oxidative damage to mitochondrial DNA increases with aging. This damage has the potential to affect mitochondrial DNA replication and transcription which could alter the abundance or functionality of mitochondrial proteins. This review describes mitochondrial DNA alterations and changes in mitochondrial function that occur with aging. Age-related alterations in mitochondrial DNA as a possible contributor to the reduction in mitochondrial function are discussed.

  11. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John S. Abughazaleh; Mushtaq Ahmed; Ashok Anand; John H. Anderson; Charles Benham; Fred D. Brent; Thomas E. Chance; William K. Davis; Raymond F. Drnevich; Larry Hall; Ming He; Stephen A. Lang; Jimmy O. Ong; Sarah J. Patel; George Potoczniak; Adela G. Sanchez; Charles H. Schrader; Lalit S. Shah; Phil J. Shires; Rae Song

    2000-10-26

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which produces at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or other carbonaceous feedstock. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site and to develop a Research, Development, and Testing Plan (RD and T) for implementation in Phase II. The objective of Phase II is to implement the RD and T as outlined in the Phase I RD and T Plan to enhance the development and commercial acceptance of coproduction technology that produces high-value products, particularly those that are critical to our domestic fuel and power requirements. The project will resolve critical knowledge and technology gaps on the integration of gasification and downstream processing to coproduce some combination of power, fuels, and chemicals from coal and other feedstocks. The objective of Phase III is to develop an engineering design package and a financing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information that will be needed to move the EECP forward to detailed design, construction, and operation by industry.

  12. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaq Ahmed; John H. Anderson; Charles Benham; Earl R. Berry; Fred Brent; Belma Demirel; Ming He; Troy Raybold; Manuel E. Quintana; Lalit S. Shah; Kenneth A. Yackly

    2003-06-09

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which produces at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or other carbonaceous feedstocks. The objectives of Phase I were to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan for implementation in Phase II; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology that produces high-value products, particularly those that are critical to our domestic fuel and power requirements. The project will resolve critical knowledge and technology gaps on the integration of gasification and downstream processing to coproduce some combination of power, fuels, and chemicals from coal and/or other carbonaceous feedstocks. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation.

  13. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John S. Abughazaleh; Mushtaq Ahmed; Ashok Anand; John H. Anderson; Charles Benham; Fred D. Brent; Thomas E. Chance; William K. Davis; Raymond F. Drnevich; Larry Hall; Ming He; Stephen A. Lang; David Mintner; Wendy Moore; Jimmy O. Ong; George Potoczniak; Adela G. Sanchez; Charles H. Schrader; Lalit S. Shah; Kalapi D. Sheth; Phil J. Shires; Rae Song

    2001-05-17

    The overall objective of this project is the three-phase development of an Early Entrance Coproduction Plant (EECP) that produces at least one product from at least two of the following three categories: Electric power (or heat); Fuels; and Chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or some other carbonaceous feedstock, such as petroleum coke. The objective of Phase I was to determine the feasibility and define the concept for the EECP located at a specific site and to develop a Research, Development, and Testing (RD and T) Plan for implementation in Phase II. This objective has now been accomplished. A specific site, Motiva Refinery in Port Arthur, Texas, has been selected as the location best suited for the EECP. The accomplishments of Phase I are discussed in detail in this Phase I Concept Report. A RD and T Plan and a preliminary project financing plan have been developed and are submitted separately from this report.

  14. Age affects the contraction-induced mitochondrial redox response in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Dennis R Claflin

    2015-02-01

    Full Text Available Compromised mitochondrial respiratory function is associated with advancing age. Damage due to an increase in reactive oxygen species (ROS with age is thought to contribute to the mitochondrial deficits. The coenzyme nicotinamide adenine dinucleotide in its reduced (NADH and oxidized (NAD+ forms plays an essential role in the cyclic sequence of reactions that result in the regeneration of ATP by oxidative phosphorylation in mitochondria. Monitoring mitochondrial NADH/NAD+ redox status during recovery from an episode of high energy demand thus allows assessment of mitochondrial function. NADH fluoresces when excited with ultraviolet light in the UV-A band and NAD+ does not, allowing NADH/NAD+ to be monitored in real time using fluorescence microscopy. Our goal was to assess mitochondrial function by monitoring the NADH fluorescence response following a brief period of high energy demand in muscle from adult and old wild-type (WT mice. This was accomplished by isolating whole lumbrical muscles from the hind paws of 7- and 28-month-old WT mice and making simultaneous measurements of force and NADH fluorescence responses during and after a 5 s maximum isometric contraction. All muscles exhibited fluorescence oscillations that were qualitatively similar and consisted of a brief transient increase followed by a longer transient period of reduced fluorescence and, finally, an increase that included an overshoot before recovering to resting level. Compared with the adult WT mice, muscles from the 28 mo WT mice exhibited a delayed peak during the first fluorescence transient and an attenuated recovery following the second transient. These findings indicate an impaired mitochondrial capacity to maintain NADH/NAD+ redox homeostasis during contractile activity in skeletal muscles of old mice.

  15. Mitofusin 2 Deficiency Affects Energy Metabolism and Mitochondrial Biogenesis in MEF Cells.

    Directory of Open Access Journals (Sweden)

    Maria Kawalec

    Full Text Available Mitofusin 2 (Mfn2, mitochondrial outer membrane protein which is involved in rearrangement of these organelles, was first described in pathology of hypertension and diabetes, and more recently much attention is paid to its functions in Charcot-Marie-Tooth type 2A neuropathy (CMT2A. Here, cellular energy metabolism was investigated in mouse embryonic fibroblasts (MEF differing in the presence of the Mfn2 gene; control (MEFwt and with Mfn2 gene depleted MEFMfn2-/-. These two cell lines were compared in terms of various parameters characterizing mitochondrial bioenergetics. Here, we have shown that relative rate of proliferation of MEFMfn2-/- cells versus control fibroblasts depend on serum supplementation of the growth media. Moreover, MEFMfn2-/- cells exhibited significantly increased respiration rate in comparison to MEFwt, regardless of serum supplementation of the medium. This effect was correlated with increased level of mitochondrial markers (TOM20 and NAO as well as mitochondrial transcription factor A (TFAM and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α protein levels and unchanged total ATP content. Interestingly, mitochondrial DNA content in MEFMfn2-/- cells was not reduced. Fundamentally, these results are in contrast to a commonly accepted belief that mitofusin 2 deficiency inevitably results in debilitation of mitochondrial energy metabolism. However, we suggest a balance between negative metabolic consequences of mitofusin 2 deficiency and adaptive processes exemplified by increased level of PGC-1α and TFAM transcription factor which prevent an excessive depletion of mtDNA and severe impairment of cell metabolism.

  16. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background.

    NARCIS (Netherlands)

    Hudson, G.; Carelli, V.; Spruijt, L.; Gerards, M.; Mowbray, C.; Achilli, A.; Pyle, A.; Elson, J.; Howell, N.; Morgia, C. La; Valentino, M.L.; Huoponen, K.; Savontaus, M.L.; Nikoskelainen, E.; Sadun, A.A.; Salomao, S.R.; Belfort Jr, R.; Griffiths, P.; Man, P.Y.; Coo, R.F. de; Horvath, R.; Zeviani, M.; Smeets, H.J.M.; Torroni, A.; Chinnery, P.F.

    2007-01-01

    Leber hereditary optic neuropathy (LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder. Both the 11778G-->A and 14484T-->C LHON mutation

  17. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance

    NARCIS (Netherlands)

    Heeman, B.; Haute, C. Van den; Aelvoet, S.A.; Valsecchi, F.; Rodenburg, R.J.T.; Reumers, V.; Debyser, Z.; Callewaert, G.; Koopman, W.J.H.; Willems, P.H.G.M.; Baekelandt, V.

    2011-01-01

    Loss-of-function mutations in the gene encoding the mitochondrial PTEN-induced putative kinase 1 (PINK1) are a major cause of early-onset familial Parkinson's disease (PD). Recent studies have highlighted an important function for PINK1 in clearing depolarized mitochondria by mitophagy. However, the

  18. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    David Storm; Govanon Nongbri; Steve Decanio; Ming He; Lalit Shah; Charles Schrader; Earl Berry; Peter Ricci; Belma Demirel; Charles Benham; Mark Bohn

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several

  19. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John Anderson; Charles Schrader

    2004-01-26

    In 1999, the U. S. Department of Energy (DOE) awarded a Cooperative Agreement to Texaco Energy Systems Inc. to provide a preliminary engineering design of an Early Entrance Coproduction Plant (EECP). Since the award, continuous and diligent work has been undertaken to achieve the design of an economical facility that makes strides toward attaining the goal of DOE's Vision 21 Program. The objective of the EECP is to convert coal and/or petroleum coke to power while coproducing transportation fuels, chemicals, and useful utilities such as steam. This objective is being pursued in a three-phase effort through the partnership of the DOE with prime contractor Texaco Energy Systems, LLC. (TES), the successor to Texaco Energy Systems, Inc. The key subcontractors to TES include General Electric (GE), Praxair, and Kellogg Brown and Root. ChevronTexaco provided gasification technology and Rentech Inc.'s Fischer-Tropsch (F-T) technology that has been developed for non-natural gas sources. GE provided gas turbine technology for the combustion of low energy content gas. Praxair provided air separation technology and KBR provided engineering to integrate the facility. A conceptual design was completed in Phase I and the report was accepted by the DOE in May 2001. The Phase I work identified risks and critical research, development, and testing that would improve the probability of technical success of the EECP. The objective of Phase II was to mitigate the risks by executing research, development, and testing. Results from the Phase II work are the subject of this report. As the work of Phase II concluded, it became evident that sufficient, but not necessarily complete, technical information and data would be available to begin Phase III - Preliminary Engineering Design. Work in Phase II requires additional technical development work to correctly apply technology at a specific site. The project's intended result is to provide the necessary technical, economic, and

  20. Mitochondrial vasculopathy

    Institute of Scientific and Technical Information of China (English)

    Josef Finsterer; Sinda Zarrouk-Mahjoub

    2016-01-01

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

  1. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Charles Benham; Mark Bohn; John Anderson; Earl Berry; Fred Brent; Ming He; Randy Roberts; Lalit Shah; Marjan Roos

    2003-09-15

    The 1999 U. S. Department of Energy (DOE) award to Texaco Energy Systems Inc. (presently Texaco Energy Systems LLC, a subsidiary of ChevronTexaco) was made to provide a Preliminary Engineering Design of an Early Entrance Coproduction Plant (EECP). Since the award presentation, work has been undertaken to achieve an economical concept design that makes strides toward the DOE Vision 21 goal. The objective of the EECP is to convert coal and/or petroleum coke to electric power plus transportation fuels, chemicals and useful utilities such as steam. The use of petroleum coke was added as a fuel to reduce the cost of feedstock and also to increase the probability of commercial implementation of the EECP concept. This objective has been pursued in a three phase effort through the partnership of the DOE with prime contractor Texaco Energy Systems LLC and subcontractors General Electric (GE), Praxair, and Kellogg Brown and Root (KBR). ChevronTexaco is providing gasification technology and Rentech's Fischer-Tropsch technology that has been developed for non-natural gas feed sources. GE is providing gas turbine technology for the combustion of low energy content gas. Praxair is providing air separation technology, and KBR is providing engineering to integrate the facility. The objective of Phase I was to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. Phase I Preliminary Concept Report was completed in 2000. The Phase I Preliminary Concept Report was prepared based on making

  2. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John Anderson; Mark Anselmo; Earl Berry; Mark Bohn; Roko Bujas; Ming He; Ken Kwik; Charles H. Schrader; Lalit Shah; Dennis Slater; Donald Todd; Don Wall

    2003-08-21

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC (TES), a subsidiary of ChevronTexaco, General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc. GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems were assessed for technical risks and barriers. A plan was identified to mitigate the identified risks (Phase II RD&T Plan, October 2000). The RD&T Plan identified catalyst/wax separation as a potential technical and economic risk. To mitigate risks to the proposed EECP, Phase II RD&T included tests of an alternative (to Rentech's Dynamic Settler) primary catalyst

  3. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; Ming He; James F. Stevens; Centha A. Davis; Michael Henley; Jerome Mayer; Harry Tsang; Jimell Erwin; Jennifer Adams; Michael Tillman; Chris Taylor; Marjan J. Roos; Robert F. Earhart

    2004-01-27

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). The potential technical and economic risks to the EECP from Task 2.5 can be mitigated by demonstrating that the end-use products derived from the upgrading of the F-T synthesis total liquid product can meet or exceed current specifications for the

  4. Citral exerts its antifungal activity against Penicillium digitatum by affecting the mitochondrial morphology and function.

    Science.gov (United States)

    Zheng, Shiju; Jing, Guoxing; Wang, Xiao; Ouyang, Qiuli; Jia, Lei; Tao, Nengguo

    2015-07-01

    This work investigated the effect of citral on the mitochondrial morphology and function of Penicillium digitatum. Citral at concentrations of 2.0 or 4.0 μL/mL strongly damaged mitochondria of test pathogen by causing the loss of matrix and increase of irregular mitochondria. The deformation extent of the mitochondria of P. digitatum enhanced with increasing concentrations of citral, as evidenced by a decrease in intracellular ATP content and an increase in extracellular ATP content of P. digitatum cells. Oxygen consumption showed that citral resulted in an inhibition in the tricarboxylic acid cycle (TCA) pathway of P. digitatum cells, induced a decrease in activities of citrate synthetase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinodehydrogenase and the content of citric acid, while enhancing the activity of malic dehydrogenase in P. digitatum cells. Our present results indicated that citral could damage the mitochondrial membrane permeability and disrupt the TCA pathway of P. digitatum.

  5. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

  6. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; J. Erwin; Matthew G. Banks; Terry L. Ullman

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). Phase II RD&T Task 2.6 identified as potential technical risks to the EECP the fuel/engine performance and emissions of the F-T diesel fuel products. Hydrotreating the neat F-T diesel product reduces potentially reactive olefins, oxygenates, and acids

  7. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; J. Erwin; Matthew G. Banks; Terry L. Ullman

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). Phase II RD&T Task 2.6 identified as potential technical risks to the EECP the fuel/engine performance and emissions of the F-T diesel fuel products. Hydrotreating the neat F-T diesel product reduces potentially reactive olefins, oxygenates, and acids

  8. Science for common entrance physics

    CERN Document Server

    Pickering, WR

    2015-01-01

    Cover everything required for the 13+ Common Entrance Physics exam with clearly presented content, lively illustrations and challenging end-of-chapter questions. This challenging and stimulating Science course has been reviewed by the ISEB subject editor and covers the content of both Levels 1 and 2 of the 13+ Physics exam. Designed for pupils in Years 7 and 8, it is an indispensable resource that lays the foundations for Common Entrance success. - Explores every Level 1 and 2 topic with clear explanations and examples - Includes topic-based exercises and extension questions - Builds on p

  9. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells.

    Science.gov (United States)

    Jangamreddy, Jaganmohan Reddy; Ghavami, Saeid; Grabarek, Jerzy; Kratz, Gunnar; Wiechec, Emilia; Fredriksson, Bengt-Arne; Rao Pariti, Rama Krishna; Cieślar-Pobuda, Artur; Panigrahi, Soumya; Łos, Marek J

    2013-09-01

    The molecular mechanism of Salinomycin's toxicity is not fully understood. Various studies reported that Ca(2+), cytochrome c, and caspase activation play a role in Salinomycin-induced cytotoxicity. Furthermore, Salinomycin may target Wnt/β-catenin signaling pathway to promote differentiation and thus elimination of cancer stem cells. In this study, we show a massive autophagic response to Salinomycin (substantially stronger than to commonly used autophagic inducer Rapamycin) in prostrate-, breast cancer cells, and to lesser degree in human normal dermal fibroblasts. Interestingly, autophagy induced by Salinomycin is a cell protective mechanism in all tested cancer cell lines. Furthermore, Salinomycin induces mitophagy, mitoptosis and increased mitochondrial membrane potential (∆Ψ) in a subpopulation of cells. Salinomycin strongly, and in time-dependent manner decreases cellular ATP level. Contrastingly, human normal dermal fibroblasts treated with Salinomycin show some initial decrease in mitochondrial mass, however they are largely resistant to Salinomycin-triggered ATP-depletion. Our data provide new insight into the molecular mechanism of preferential toxicity of Salinomycin towards cancer cells, and suggest possible clinical application of Salinomycin in combination with autophagy inhibitors (i.e. clinically-used Chloroquine). Furthermore, we discuss preferential Salinomycins toxicity in the context of Warburg effect.

  10. Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.

    Science.gov (United States)

    Demetriadou, Anthi; Morales-Sanfrutos, Julia; Nearchou, Marianna; Baba, Otto; Kyriacou, Kyriacos; Tate, Edward W; Drousiotou, Anthi; Petrou, Petros P

    2017-03-01

    Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria.

  11. Metabolic depression during warm torpor in the Golden spiny mouse (Acomys russatus) does not affect mitochondrial respiration and hydrogen peroxide release.

    Science.gov (United States)

    Grimpo, Kirsten; Kutschke, Maria; Kastl, Anja; Meyer, Carola W; Heldmaier, Gerhard; Exner, Cornelia; Jastroch, Martin

    2014-01-01

    Small mammals actively decrease metabolism during daily torpor and hibernation to save energy. Recently, depression of mitochondrial substrate oxidation in isolated liver mitochondria was observed and associated to hypothermic/hypometabolic states in Djungarian hamsters, mice and hibernators. We aimed to clarify whether hypothermia or hypometabolism causes mitochondrial depression during torpor by studying the Golden spiny mouse (Acomys russatus), a desert rodent which performs daily torpor at high ambient temperatures of 32°C. Notably, metabolic rate but not body temperature is significantly decreased under these conditions. In isolated liver, heart, skeletal muscle or kidney mitochondria we found no depression of respiration. Moderate cold exposure lowered torpor body temperature but had minor effects on minimal metabolic rate in torpor. Neither decreased body temperature nor metabolic rate impacted mitochondrial respiration. Measurements of mitochondrial proton leak kinetics and determination of P/O ratio revealed no differences in mitochondrial efficiency. Hydrogen peroxide release from mitochondria was not affected. We conclude that interspecies differences of mitochondrial depression during torpor do not support a general relationship between mitochondrial respiration, body temperature and metabolic rate. In Golden spiny mice, reduction of metabolic rate at mild temperatures is not triggered by depression of substrate oxidation as found in liver mitochondria from other cold-exposed rodents.

  12. Light Intensity Affects Chlorophyll Synthesis During Greening Process by Metabolite Signal from Mitochondrial Alternative Oxidase in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Dawei; YUAN; Shu; 徐飞; ZHU; Feng; YUAN; Ming; YE; Huaxun; GUO; Hongqing; LV; Xin; YIN; Yanhai; 林宏辉

    2015-01-01

    Although mitochondrial alternative oxidase(AOX)has been proposed to play essential roles in high light stress tolerance,the effects of AOX on chlorophyll synthesis are unclear.Previous studies indicated that during greening,chlorophyll accumulation was largely delayed in plants whose mitochondrial cyanide-resistant respiration was inhibited by knocking out nuclear encoded AOX gene.Here we show that this delay of chlorophyll accumulation was more significant under high light condition.Inhibition of cyanide-resistant respiration was also accompanied by the increase of plastid NADPH/NADP~+ratio,especially under high light treatment which subsequently blocked the import of multiple plastidial proteins,such as some components of the photosynthetic electron transport chain,the Calvin-Benson cycle enzymes and malate/oxaloacetate shuttle components.Over expression of AOXla rescued the aoxla mutant phenotype,including the chlorophyll accumulation during greening and plastidial protein import.It thus suggests that light intensity affects chlorophyll synthesis during greening process by a metabolic signal,the AOX-derived plastidial NADPH/NADP~+ratio change.And our results thus revealed a molecular mechanism of chloroplast-mitochondria interactions.

  13. Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance

    DEFF Research Database (Denmark)

    Nguyen, Tammy T; Lewandowska, Agnieszka; Choi, Jae-Yeon;

    2012-01-01

    a primary role for ERMES in mitochondrial association with actin and mitochondrial movement. Finally, we show that ERMES complexes are long-lived, and do not depend on the presence of Gem1. Our findings suggest that the ERMES complex may have primarily a structural role in maintaining mitochondrial...

  14. Caenorhabditis elegans diet significantly affects metabolic profile, mitochondrial DNA levels, lifespan and brood size.

    Science.gov (United States)

    Reinke, S N; Hu, X; Sykes, B D; Lemire, B D

    2010-07-01

    Diet can have profound effects on an organism's health. Metabolic studies offer an effective way to measure and understand the physiological effects of diet or disease. The metabolome is very sensitive to dietary, lifestyle and genetic changes. Caenorhabditis elegans, a soil nematode, is an attractive model organism for metabolic studies because of the ease with which genetic and environmental factors can be controlled. In this work, we report significant effects of diet, mutation and RNA interference on the C.elegans metabolome. Two strains of Escherichia coli, OP50 and HT115 are commonly employed as food sources for maintaining and culturing the nematode. We studied the metabolic and phenotypic effects of culturing wild-type and mutant worms on these two strains of E. coli. We report significant effects of diet on metabolic profile, on mitochondrial DNA copy number and on phenotype. The dietary effects we report are similar in magnitude to the effects of mutations or RNA interference-mediated gene suppression. This is the first critical evaluation of the physiological and metabolic effects on C.elegans of two commonly used culture conditions.

  15. 47 CFR 69.110 - Entrance facilities.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Entrance facilities. 69.110 Section 69.110... Computation of Charges § 69.110 Entrance facilities. (a) A flat-rated entrance facilities charge expressed in... that use telephone company facilities between the interexchange carrier or other person's point...

  16. alpha-Latrotoxin affects mitochondrial potential and synaptic vesicle proton gradient of nerve terminals.

    Science.gov (United States)

    Tarasenko, A S; Storchak, L G; Himmelreich, N H

    2008-02-01

    Ca(2+)-independent [(3)H]GABA release induced by alpha-latrotoxin was found to consist of two sequential processes: a fast initial release realized via exocytosis and more delayed outflow through the plasma membrane GABA transporters [Linetska, M.V., Storchak, L.G., Tarasenko, A.S., Himmelreich, N.H., 2004. Involvement of membrane GABA transporters in alpha-latrotoxin-stimulated [(3)H]GABA release. Neurochem. Int. 44, 303-312]. To characterize the toxin-stimulated events attributable to the transporter-mediated [(3)H]GABA release from rat brain synaptosomes we studied the effect of alpha-latrotoxin on membrane potentials and generation of the synaptic vesicles proton gradient, using fluorescent dyes: potential-sensitive rhodamine 6G and pH-sensitive acridine orange. We revealed that alpha-latrotoxin induced a progressive dose-dependent depolarization of mitochondrial membrane potential and an irreversible run-down of the synaptic vesicle proton gradient. Both processes were insensitive to the presence of cadmium, a potent blocker of toxin-formed transmembrane pores, indicating that alpha-latrotoxin-induced disturbance of the plasma membrane permeability was not responsible to these effects. A gradual dissipation of the synaptic vesicle proton gradient closely coupled with lowering the vesicular GABA transporter activity results in a leakage of the neurotransmitter from synaptic vesicles to cytoplasm. As a consequence, there is an essential increase in GABA concentration in a soluble cytosolic pool that appears to be critical parameter for altering the mode of the plasma membrane GABA transporter operation from inward to outward. Thus, our data allow clarifying what cell processes underlain a recruitment of the plasma membrane transporter-mediated pathway in alpha-LTX-stimulated secretion.

  17. Science for common entrance physics : answers

    CERN Document Server

    Pickering, W R

    2015-01-01

    This book contains answers to all exercises featured in the accompanying textbook Science for Common Entrance: Physics , which covers every Level 1 and 2 topic in the ISEB 13+ Physics Common Entrance exam syllabus. - Clean, clear layout for easy marking. - Includes examples of high-scoring answers with diagrams and workings. - Suitable for ISEB 13+ Mathematics Common Entrance exams taken from Autumn 2017 onwards. Also available to purchase from the Galore Park website www.galorepark.co.uk :. - Science for Common Entrance: Physics. - Science for Common Entrance: Biology. - Science for Common En

  18. Suppression of the External MitochondrialNADPH Dehydrogenase, NDB1, in Arabidopsisthaliana Affects Central Metabolism andVegetative Growth

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Ca2+-dependent oxidation of cytosolic NADPH is mediated by NDB1, which is an external type II NADPHdehydrogenase in the plant mitochondrial electron transport chain. Using RNA interference, the NDB1 transcript wassuppressed by 80% in Arabidopsis thaliana plants, and external Ca2+-dependent NADPH dehydrogenase activity becameundetectable in isolated mitochondria. This was linked to a decreased level of NADP+ in rosettes of the transgenic lines.Sterile-grown transgenic seedlings displayed decreased growth specifically on glucose, and respiratory metabolism of 14C-glucose was increased. On soil, NDBl-suppressing plants had a decreased vegetative biomass, but leaf maximumquantum efficiency of photosystem Ⅱ and CO2 assimilation rates, as well as total respiration, were similar to the wild-type. The in vivo alternative oxidase activity and capacity were also similar in all genotypes. Metabolic profiling revealeddecreased levels of sugars, citric acid cycle intermediates, and amino acids in the transgenic lines. The NDBl-suppressioninduced transcriptomic changes associated with protein synthesis and glucosinolate and jasmonate metabolism. Thetranscriptomic changes also overlapped with changes observed in a mutant lacking ABAINSENSITIVE4 and in A. thalianaoverexpressing stress tolerance genes from rice. The results thus indicate that A. thaliana NDB1 modulates NADP(H)reduction levels, which in turn affect central metabolism and growth, and interact with defense signaling.

  19. Mathematics for common entrance three (extension) answers

    CERN Document Server

    Alexander, Serena

    2015-01-01

    This book contains answers to all exercises featured in the accompanying textbook Mathematics for Common Entrance Three (Extension) , which provides essential preparation for Level 3 of the ISEB 13+ Mathematics exam, as well as for CASE and other scholarship exams. - Clean, clear layout for easy marking. - Includes examples of high-scoring answers with diagrams and workings. Also available to purchase from the Galore Park website www.galorepark.co.uk :. - Mathematics for Common Entrance Three (Extension). - Mathematics for Common Entrance One. - Mathematics for Common Entrance One Answers. - M

  20. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    DEFF Research Database (Denmark)

    Swan, E J; Salem, R M; Sandholm, N;

    2015-01-01

    individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar......AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823...... phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. RESULTS: A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease...

  1. Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy in socially isolated rats: Pros and cons of fluoxetine.

    Science.gov (United States)

    Sonei, Nazanin; Amiri, Shayan; Jafarian, Iman; Anoush, Mahdieh; Rahimi-Balaei, Maryam; Bergen, Hugo; Haj-Mirzaian, Arya; Hosseini, Mir-Jamal

    2017-02-01

    Objectives Depression is tightly associated with cardiovascular comorbidity and accounts for high financial and social burden worldwide. Mitochondrial dysfunction contributes to the pathophysiology of depression and cardiovascular disorders; its contribution to depression-cardiovascular comorbidity has not yet been investigated. Methods Adolescent rats were subjected to 4 weeks of isolation (social isolation stress or SIS) or social conditions (control), and then they were divided into treatment (fluoxetine, 7.5 mg/kg/day for 21 days) and non-treatment groups. After different housing conditions and treatment, animals were evaluated by behavioural tests (n = 6-8) and mitochondrial assessments (n = 3) of brain and cardiac tissues. Results We found that juvenile SIS induced behavioural abnormalities and mitochondrial dysfunction in adulthood. We showed that juvenile SIS was associated with impaired respiratory chain complex, which leads to reactive oxygen species formation, oxidative damage and ATP abatement in both brain and heart. Administration of FLX (7.5 mg/kg/day) during the isolation period attenuated the effects of SIS on the brain mitochondria and behavioural abnormalities, but had little or no effect on SIS-induced mitochondrial dysfunction in cardiac tissue. Conclusions This suggests that juvenile SIS predisposes the co-occurrence of depression and cardiovascular disease through mitochondrial dysfunction and that therapeutic effect of fluoxetine is partly mediated by its effect on mitochondrial function.

  2. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation.

    Science.gov (United States)

    Pérez-Pérez, Rafael; Lobo-Jarne, Teresa; Milenkovic, Dusanka; Mourier, Arnaud; Bratic, Ana; García-Bartolomé, Alberto; Fernández-Vizarra, Erika; Cadenas, Susana; Delmiro, Aitor; García-Consuegra, Inés; Arenas, Joaquín; Martín, Miguel A; Larsson, Nils-Göran; Ugalde, Cristina

    2016-08-30

    Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.

  3. The erratic mitochondrial clock: variations of mutation rate, not population size, affect mtDNA diversity across birds and mammals

    Directory of Open Access Journals (Sweden)

    Galtier Nicolas

    2009-03-01

    Full Text Available Abstract Background During the last ten years, major advances have been made in characterizing and understanding the evolution of mitochondrial DNA, the most popular marker of molecular biodiversity. Several important results were recently reported using mammals as model organisms, including (i the absence of relationship between mitochondrial DNA diversity and life-history or ecological variables, (ii the absence of prominent adaptive selection, contrary to what was found in invertebrates, and (iii the unexpectedly large variation in neutral substitution rate among lineages, revealing a possible link with species maximal longevity. We propose to challenge these results thanks to the bird/mammal comparison. Direct estimates of population size are available in birds, and this group presents striking life-history trait differences with mammals (higher mass-specific metabolic rate and longevity. These properties make birds the ideal model to directly test for population size effects, and to discriminate between competing hypotheses about the causes of substitution rate variation. Results A phylogenetic analysis of cytochrome b third-codon position confirms that the mitochondrial DNA mutation rate is quite variable in birds, passerines being the fastest evolving order. On average, mitochondrial DNA evolves slower in birds than in mammals of similar body size. This result is in agreement with the longevity hypothesis, and contradicts the hypothesis of a metabolic rate-dependent mutation rate. Birds show no footprint of adaptive selection on cytochrome b evolutionary patterns, but no link between direct estimates of population size and cytochrome b diversity. The mutation rate is the best predictor we have of within-species mitochondrial diversity in birds. It partly explains the differences in mitochondrial DNA diversity patterns observed between mammals and birds, previously interpreted as reflecting Hill-Robertson interferences with the W

  4. Candidate cave entrances on Mars

    Science.gov (United States)

    Cushing, Glen E.

    2012-01-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visible-wavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  5. Effects of Magnetic Particles Entrance Arrange-ments on Mixing Efficiency of a Magnetic Bead Micromixer

    Institute of Scientific and Technical Information of China (English)

    Reza Kamali∗; Seyed Alireza Shekoohi; Alireza Binesh

    2014-01-01

    In this study, a computer code is developed to numerically investigate a magnetic bead micromixer under different conditions. The micromixer consists of a microchannel and numerous micro magnetic particles which enter the micromixer by fluid flows and are actuated by an alternating magnetic field normal to the main flow. An important feature of micromixer which is not considered before by researchers is the particle entrance arrangement into the micromixer. This parameter could effectively affect the micromixer efficiency. There are two general micro magnetic particle entrance arrangements in magnetic bead micromixers: determined position entrance and random position entrance. In the case of determined position entrances, micro magnetic particles enter the micromixer at specific positions of entrance cross section. However, in a random position entrance, particles enter the microchannel with no order. In this study mixing efficiencies of identical magnetic bead micromixers which only differ in particle entrance arrangement are numerically investigated and compared. The results reported in this paper illustrate that the prepared computer code can be one of the most powerful and beneficial tools for the magnetic bead micromixer performance analysis. In addition, the results show that some features of the magnetic bead micromixer are strongly affected by the entrance arrangement of the particles.

  6. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920)

    Science.gov (United States)

    Velasquez-Vottelerd, P.; Anton, Y.; Salazar-Lugo, R.

    2015-01-01

    The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

  7. Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients.

    Science.gov (United States)

    Polimeno, Lorenzo; Rossi, Roberta; Mastrodonato, Maria; Montagnani, Monica; Piscitelli, Domenico; Pesetti, Barbara; De Benedictis, Leonarda; Girardi, Bruna; Resta, Leonardo; Napoli, Anna; Francavilla, Antonio

    2013-11-01

    Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation. We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu). With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed. The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).

  8. Entrance C - Meyrin site: new access conditions

    CERN Multimedia

    2013-01-01

    Entrance C on the Meyrin site, which drivers of motorised vehicles can use Mondays to Fridays from 7 a.m. to 9 a.m. and from 5 p.m. to 7 p.m., has been altered to include a turnstile to allow cyclists and pedestrians to use their access card to get in and out of the site from 6 a.m. until 10 p.m.   The following video illustrates how to use the new turnstile: A new type of entrance gate fitted with a number plate reader similar to that installed at the entrance to the Prévessin site should, once fully tested, allow drivers of motorised vehicles to access the site. For the time being, the conditions of use of Entrance C remain unchanged. Further information on the entry into force of new arrangements will be issued in due course. For further information about CERN entrances: CERN opening hours CERN control access GS Department

  9. Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability.

    Science.gov (United States)

    Fontanesi, Flavia; Palmieri, Luigi; Scarcia, Pasquale; Lodi, Tiziana; Donnini, Claudia; Limongelli, Anna; Tiranti, Valeria; Zeviani, Massimo; Ferrero, Iliana; Viola, Anna Maria

    2004-05-01

    Autosomal dominant and recessive forms of progressive external ophthalmoplegia (adPEO and arPEO) are mitochondrial disorders characterized by the presence of multiple deletions of mitochondrial DNA in affected tissues. Four adPEO-associated missense mutations have been identified in the ANT1 gene. In order to investigate their functional consequences on cellular physiology, we introduced three of them at equivalent positions in AAC2, the yeast orthologue of human ANT1. We demonstrate here that expression of the equivalent mutations in aac2-defective haploid strains of Saccharomyces cerevisiae results in (a) a marked growth defect on non-fermentable carbon sources, and (b) a concurrent reduction of the amount of mitochondrial cytochromes, cytochrome c oxidase activity and cellular respiration. The efficiency of ATP and ADP transport was variably affected by the different AAC2 mutations. However, irrespective of the absolute level of activity, the AAC2 pathogenic mutants showed a significant defect in ADP versus ATP transport compared with wild-type AAC2. In order to study whether a dominant phenotype, as in humans, could be observed, the aac2 mutant alleles were also inserted in combination with the endogenous wild-type AAC2 gene. The heteroallelic strains behaved as recessive for oxidative growth and petite-negative phenotype. In contrast, reduction in cytochrome content and increased mtDNA instability appeared to behave as dominant traits in heteroallelic strains. Our results indicate that S. cerevisiae is a suitable in vivo model to study the pathogenicity of the human ANT1 mutations and the pathophysiology leading to impairment of oxidative phosphorylation and damage of mtDNA integrity, as found in adPEO.

  10. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation

    Directory of Open Access Journals (Sweden)

    Rafael Pérez-Pérez

    2016-08-01

    Full Text Available Mitochondrial respiratory chain (MRC complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.

  11. Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children.

    Science.gov (United States)

    Mayr, Johannes A; Zimmermann, Franz A; Horváth, Rita; Schneider, Hans-Christian; Schoser, Benedikt; Holinski-Feder, Elke; Czermin, Birgit; Freisinger, Peter; Sperl, Wolfgang

    2011-11-01

    In a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic cardiomyopathy and normal mental development. In a muscle biopsy normal activity of respiratory chain enzymes was found; however the amount of the mitochondrial phosphate carrier was decreased. This protein is expressed in two tissue-specific isoforms generated by mutually exclusive alternative splicing of the SLC25A3 gene transcript. We identified a homozygous mutation c.158-9A>G located in the 5'-intron next to exon 3A specific for heart and skeletal muscle. This creates a novel splice site resulting in a more than 95% decrease of the wild type allele.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    It has been suggested that human mitochondrial variants influence maximal oxygen uptake (VO2max). Whether mitochondrial respiratory capacity per mitochondrion (intrinsic activity) in human skeletal muscle is affected by differences in mitochondrial variants is not known. We recruited 54 males and...

  13. Mathematics for common entrance one answers

    CERN Document Server

    Alexander, Serena

    2015-01-01

    Enables efficient assessment of pupils' performance at Levels 1 and 2 of the ISEB 13+ Common Entrance syllabus. Clear layout saves time marking work and identifies areas requiring further attention. Includes diagrams and working where necessary, to demonstrate how to present high-scoring answers in Level 1 and 2 exams

  14. Mathematics for common entrance two answers

    CERN Document Server

    Alexander, Serena

    2015-01-01

    Enables efficient assessment of pupils' performance at Levels 1 and 2 of the ISEB 13+ Common Entrance syllabus. Clear layout saves time marking work and identifies areas requiring further attention. Includes diagrams and working where necessary, to demonstrate how to present high-scoring answers in Level 1 and 2 exams.

  15. Supercalculators and University Entrance Calculus Examinations.

    Science.gov (United States)

    Hong, Ye Yoon; Thomas, Mike; Kiernan, Christine

    2000-01-01

    Investigates whether the use of computer algebra systems could provide a significant advantage to students taking standard university entrance calculus examinations. Indicates that supercalculators would probably provide a significant advantage, particularly for lower-achieving students. Demonstrates that it is possible to write questions in which…

  16. 30 CFR 18.37 - Lead entrances.

    Science.gov (United States)

    2010-07-01

    ... against loosening. (d) Compressed packing material shall be in contact with the cable jacket for a length... cable jacket and the nominal inside diameter of the packing material shall not exceed 1/32-inch, based... § 18.37 Lead entrances. (a) Insulated cable(s), which must extend through an outside wall of...

  17. An Entrance Region Mass Transfer Experiment.

    Science.gov (United States)

    Youngquist, G. R.

    1979-01-01

    This paper describes an experiment designed to reveal the consequences of the development of a concentration boundary layer. The rate of a mass transfer limited electrochemical reaction is measured and used to obtain the dependence of average Sherwood number on Reynolds number and entrance length. (Author/BB)

  18. Mitochondrial Dynamics in Mitochondrial Diseases

    Directory of Open Access Journals (Sweden)

    Juan M. Suárez-Rivero

    2016-12-01

    Full Text Available Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton’s disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases.

  19. Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells.

    Science.gov (United States)

    Bousquet, Paula A; Sandvik, Joe Alexander; Arntzen, Magnus Ø; Jeppesen Edin, Nina F; Christoffersen, Stine; Krengel, Ute; Pettersen, Erik O; Thiede, Bernd

    2015-01-01

    Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression in response to hypoxia by quantitative proteome analysis using stable isotope labeling with amino acids in cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept either in a hypoxic environment or under normoxic conditions. 125 proteins were found to be regulated, with maximum alteration of 18-fold. In particular, three clusters of differentially regulated proteins were identified, showing significant upregulation of glycolysis and downregulation of mitochondrial ribosomal proteins and translocases. This interaction is likely orchestrated by HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows accumulation in G1 and a prolonged S phase under these conditions. Implications. This work not only improves our understanding of the response to hypoxia, but also reveals proteins important for malignant progression, which may be targeted in future therapies.

  20. 49 CFR 236.534 - Entrance to equipped territory; requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Entrance to equipped territory; requirements. 236... Entrance to equipped territory; requirements. Where trains are not required to stop at the entrance to equipped territory, except when leaving yards and stations and speed until entering equipped territory...

  1. Entrance Effects in Microchannel Gas Flow

    Institute of Scientific and Technical Information of China (English)

    T. Lewandowski; S. Jebauer; J. Czerwinska; P. Doerffer

    2009-01-01

    Motivation of this work has its origin in the boundary layer control for aeronautics and turbomachinery. For that purpose boundary layer can be modified by perforated plates with holes of specific sizes. The questions which rise in such configuration are related to the existence of optimal size of the holes and the influence of microscale phenomena on the global flow patterns. This paper concentrates on the issue of the entrance effects on the micro-channel flow. It is shown that mass flow rate is only insignificantly influenced by slip effects. Global parameters such as pressure difference and geometrical shape in more pronounced way alter flow behavior. In this paper we concentrate on the numerical investigation of the microchannel flow for Kn < 0.01 and Re < 500. The channel length is finite. Hence, entrance and outlet effects on microchannel flow can be studied.

  2. Salicylic acid binding of mitochondrial alpha-ketoglutarate dehydrogenase E2 affects mitochondrial oxidative phosphorylation and electron transport chain components and plays a role in basal defense against tobacco mosaic virus in tomato.

    Science.gov (United States)

    Liao, Yangwenke; Tian, Miaoying; Zhang, Huan; Li, Xin; Wang, Yu; Xia, Xiaojian; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Shi, Kai; Klessig, Daniel F

    2015-02-01

    Salicylic acid (SA) plays a critical role in plant defense against pathogen invasion. SA-induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense and involves a specific pathway mediated by mitochondria; however, the underlying mechanisms remain largely unknown. The SA-binding activity of the recombinant tomato (Solanum lycopersicum) alpha-ketoglutarate dehydrogenase (Slα-kGDH) E2 subunit of the tricarboxylic acid (TCA) cycle was characterized. The biological role of this binding in plant defenses against tobacco mosaic virus (TMV) was further investigated via Slα-kGDH E2 silencing and transient overexpression in plants. Slα-kGDH E2 was found to bind SA in two independent assays. SA treatment, as well as Slα-kGDH E2 silencing, increased resistance to TMV. SA did not further enhance TMV defense in Slα-kGDH E2-silenced tomato plants but did reduce TMV susceptibility in Nicotiana benthamiana plants transiently overexpressing Slα-kGDH E2. Furthermore, Slα-kGDH E2-silencing-induced TMV resistance was fully blocked by bongkrekic acid application and alternative oxidase 1a silencing. These results indicated that binding by Slα-kGDH E2 of SA acts upstream of and affects the mitochondrial electron transport chain, which plays an important role in basal defense against TMV. The findings of this study help to elucidate the mechanisms of SA-induced viral defense.

  3. Adult-onset mitochondrial myopathy.

    Science.gov (United States)

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  4. LHON/MELAS overlap mutation in ND1 subunit of mitochondrial complex I affects ubiquinone binding as revealed by modeling in Escherichia coli NDH-1.

    Science.gov (United States)

    Pätsi, Jukka; Maliniemi, Pilvi; Pakanen, Salla; Hinttala, Reetta; Uusimaa, Johanna; Majamaa, Kari; Nyström, Thomas; Kervinen, Marko; Hassinen, Ilmo E

    2012-02-01

    Defects in complex I due to mutations in mitochondrial DNA are associated with clinical features ranging from single organ manifestation like Leber hereditary optic neuropathy (LHON) to multiorgan disorders like mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. Specific mutations cause overlap syndromes combining several phenotypes, but the mechanisms of their biochemical effects are largely unknown. The m.3376G>A transition leading to p.E24K substitution in ND1 with LHON/MELAS phenotype was modeled here in a homologous position (NuoH-E36K) in the Escherichia coli enzyme and it almost totally abolished complex I activity. The more conservative mutation NuoH-E36Q resulted in higher apparent K(m) for ubiquinone and diminished inhibitor sensitivity. A NuoH homolog of the m.3865A>G transition, which has been found concomitantly in the overlap syndrome patient with the m.3376G>A, had only a minor effect. Consequences of a primary LHON-mutation m.3460G>A affecting the same extramembrane loop as the m.3376G>A substitution were also studied in the E. coli model and were found to be mild. The results indicate that the overlap syndrome-associated m.3376G>A transition in MTND1 is the pathogenic mutation and m.3865A>G transition has minor, if any, effect on presentation of the disease. The kinetic effects of the NuoH-E36Q mutation suggest its proximity to the putative ubiquinone binding domain in 49kD/PSST subunits. In all, m.3376G>A perturbs ubiquinone binding, a phenomenon found in LHON, and decreases the activity of fully assembled complex I as in MELAS.

  5. Mitochondrial dynamics in human NADH:ubiquinone oxidoreductase deficiency.

    NARCIS (Netherlands)

    Willems, P.H.G.M.; Smeitink, J.A.M.; Koopman, W.J.H.

    2009-01-01

    Mitochondrial NADH:ubiquinone oxidoreductase or complex I (CI) is a frequently affected enzyme in cases of mitochondrial disorders. However, the cytopathological mechanism of the associated pediatric syndromes is poorly understood. Evidence in the literature suggests a connection between mitochondri

  6. Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry.

    Science.gov (United States)

    Pla-Martín, David; Rueda, Carlos B; Estela, Anna; Sánchez-Piris, Maribel; González-Sánchez, Paloma; Traba, Javier; de la Fuente, Sergio; Scorrano, Luca; Renau-Piqueras, Jaime; Alvarez, Javier; Satrústegui, Jorgina; Palau, Francesc

    2013-07-01

    GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may participate in the mitochondrial movement within the cell. GDAP1 silencing in the SH-SY5Y cell line induces abnormal distribution of the mitochondrial network, reduces the contact between mitochondria and endoplasmic reticulum (ER) and alters the mobilization of mitochondria towards plasma membrane upon depletion of ER-Ca(2+) stores. GDAP1 silencing does not affect mitochondrial Ca(2+) uptake, ER-Ca(2+), or Ca(2+) flow from ER to mitochondria, but reduces Ca(2+) inflow through store-operated Ca(2+) entry (SOCE) following mobilization of ER-Ca(2+) and SOCE-driven Ca(2+) entry in mitochondria. Our studies suggest that the pathophysiology of GDAP1-related CMT neuropathies may be associated with abnormal distribution and movement of mitochondria throughout cytoskeleton towards the ER and subplasmalemmal microdomains, resulting in a decrease in SOCE activity and impaired SOCE-driven Ca(2+) uptake in mitochondria.

  7. Mitochondrial Diseases

    Science.gov (United States)

    ... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...

  8. Mitochondrial Myopathies

    Science.gov (United States)

    ... which stimulates normal beating of the heart. Cardiac muscle damage also may occur. People with mitochondrial disorders may need to have regular examina- tions by a cardiologist. Other potential health issues Some people with mitochondrial disease experience ...

  9. Mitochondrial haplogroups

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  10. Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: a case report

    Directory of Open Access Journals (Sweden)

    Moggio Maurizio

    2011-07-01

    Full Text Available Abstract Background Leigh Syndrome (LS is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors. Case presentation Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA. Conclusions The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.

  11. Decreasing the mitochondrial synthesis of malate in potato tubers does not affect plastidial starch synthesis, suggesting that the physiological regulation of ADPglucose pyrophosphorylase is context dependent.

    Science.gov (United States)

    Szecowka, Marek; Osorio, Sonia; Obata, Toshihiro; Araújo, Wagner L; Rohrmann, Johannes; Nunes-Nesi, Adriano; Fernie, Alisdair R

    2012-12-01

    Modulation of the malate content of tomato (Solanum lycopersicum) fruit by altering the expression of mitochondrially localized enzymes of the tricarboxylic acid cycle resulted in enhanced transitory starch accumulation and subsequent effects on postharvest fruit physiology. In this study, we assessed whether such a manipulation would similarly affect starch biosynthesis in an organ that displays a linear, as opposed to a transient, kinetic of starch accumulation. For this purpose, we used RNA interference to down-regulate the expression of fumarase in potato (Solanum tuberosum) under the control of the tuber-specific B33 promoter. Despite displaying similar reductions in both fumarase activity and malate content as observed in tomato fruit expressing the same construct, the resultant transformants were neither characterized by an increased flux to, or accumulation of, starch, nor by alteration in yield parameters. Since the effect in tomato was mechanistically linked to derepression of the reaction catalyzed by ADP-glucose pyrophosphorylase, we evaluated whether the lack of effect on starch biosynthesis was due to differences in enzymatic properties of the enzyme from potato and tomato or rather due to differential subcellular compartmentation of reductant in the different organs. The results are discussed in the context both of current models of metabolic compartmentation and engineering.

  12. Entrance Length and Turbulence Transition in Microflows

    Science.gov (United States)

    Wereley, Steve; Lee, Sangyoup; Gui, Lichuan

    2002-11-01

    Since microfabrication techniques are typically planar processes, microchannel flows typically have significant predevelopment due to the upstream reservoir having the same height as the microchannel. The main concerns of the current study are categorized into finding the effects of typical microchannel geometry on the velocity entrance length in the laminar flow regime and providing the turbulence transitional Reynolds number range using the details of the velocity profile rather than global measurements of pressure drop. A rectangular micro-channel of aspect ratio 2.65 and the hydraulic diameter 380 um was used in this study. Micro particle image velocimetry measurement was performed to measure the velocity profiles. The entrance length is found to be reduced by about 45number occurs between 2100 and 2900-comparable to macroscale observations. Finally a new technique is proposed to measure the turbulence intensity of a flow directly from the PIV correlation function peak width. This new technique provides results comparable to traditional means of calculating turbulence intensity but is particularly useful in measuring microflows where the seeding density can be very low.

  13. Mitochondrial genetics

    OpenAIRE

    Chinnery, Patrick Francis; Hudson, Gavin

    2013-01-01

    Introduction In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders. Sources of data In this article, a review of the current mitochondrial genetics literature was con...

  14. LITERACY SENSES: WRITING IN VESTIBULAR (ENTRANCE EXAMS

    Directory of Open Access Journals (Sweden)

    Victoria Wilson da Costa Coelho

    2015-10-01

    Full Text Available The aim of this paper is to pose a reflection on explicit or underlying literacy practices in a literacy event such as the Brazilian university entrance exams (vestibular using, as an object of study, the essays written during that event. We aim to understand the educated writing culture, or Brazilian literacy, in its very extreme, that is, the end of High School, based on Bakhtin’s theory of enunciation. Despite pedagogical measures focused on elaborate (argumentative writing in view of college assessment exams and ENEM (National High School Exam, we know how unsatisfactory its results still are, in terms of the school literacy practices, which still remains to be sufficiently reflected on. It is also worth highlighting that we understand writing (school writing more as a set of social practices than as a set of skills alone.

  15. Capturing blocked-entrance binaural signals from open-entrance recordings

    DEFF Research Database (Denmark)

    Hammershøi, Dorte; Hoffmann, Pablo F.; Olesen, Søren Krarup

    2008-01-01

    interfering the individual's hearing and doing. In this work we propose a strategy for the recording of binaural audio with minimal hearing interference, and for transforming these recordings to blocked-entrance versions that are more suitable for analysis and reproduction of binaural audio in a more general...... context. To this purpose, equalization filters are derived from the ratio between blocked and open ear canal transfer functions. Different transfer-function measuring techniques and inverse filtering methods are evaluated....

  16. Persuasive Ways to Change Entrance Use of Buildings

    NARCIS (Netherlands)

    Boer, de Johannes; Heylen, Dirk K.J.; Teeuw, Wouter B.

    2014-01-01

    People tend to use the same door every time they enter and exit a building. When certain entrances are widely preferred over others, congestion can occur. This paper describes two interventions to persuade visitors to use another entrance. The first intervention used sensory deprivation (darkness),

  17. Effect of University Entrance Exam on Gifted High School Students’ Motivation Scrutinized: An Iranian Perspective

    Directory of Open Access Journals (Sweden)

    Ali Kazemi

    2014-09-01

    Full Text Available Passing University Entrance Exams (UEE successfully has long been a major concern for Iranian high school students. High Schools for the Gifted admit highly intelligent and hardworking students, who reportedly form a remarkable proportion of students admitted in best universities of Iran, through hard entrance exams. This study aimed to investigate attitudes of students educating in High Schools for the Gifted towards learning English, their dominant motivation type (instrumental or integrative, and the likely effect Iranian University Entrance Exam has on their motivation.  For the purpose of this investigation, 166 male and female participants educating in the four grades of high school were selected through Stratified Random Sampling Method from both boys’ and girls’ High Schools for the Gifted. A 26-item questioner previously developed by the researchers, investigating the participants’ attitudes towards English learning, their dominant motivation type, and the likely effect of Iranian UEE on their motivation was administered to them. Descriptive statistics and the analysis of variance were used to analyze the data, and the results revealed that all participants educating in the four grades of high school showed positive attitudes towards English learning, and that 1st and 2nd grade subjects were both instrumentally and integratively motivated, whereas 3rd and 4th graders were instrumentally motivated. The degree of subjects’ concern about the Iranian UEE significantly affected their motivational orientations and prioritization.Keywords: Motivation, Interest, Instrumental, Integrative, University Entrance Exam, Gifted Students

  18. 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...... by a dystrophic morphology. The results add to the complexity of the pathogenesis underlying mitochondrial myopathies, and expand the knowledge about the impact of energy deficiency on another aspect of muscle structure and function....

  19. Low dietary protein intake during pregnancy differentially affects mitochondrial copy number in stromal vascular cells from subcutaneous versus visceral adipose tissue in the offspring

    Science.gov (United States)

    The present study examined the influence of protein intake during pregnancy on mitochondrial metabolism in stromal vascular cells from subcutaneous (SVSu) and visceral (SVVi) adipose tissue of offspring fed a high fat diet. Obese-prone Sprague-Dawley rats were fed diets containing either 8% or 20% p...

  20. 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.

  1. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology.

  2. Mitochondrial disorders.

    Science.gov (United States)

    Zeviani, M; Tiranti, V; Piantadosi, C

    1998-01-01

    Mitochondrial respiration, the most efficient metabolic pathway devoted to energy production, is at the crosspoint of 2 quite different genetic systems, the nuclear genome and the mitochondrial genome (mitochondrial DNA, mtDNA). The latter encodes a few essential components of the mitochondrial respiratory chain and has unique molecular and genetic properties that account for some of the peculiar features of mitochondrial disorders. However, the perpetuation, propagation, and expression of mtDNA, the majority of the subunits of the respiratory complexes, as well as a number of genes involved in their assembly and turnover, are contained in the nuclear genome. Although mitochondrial disorders have been known for more than 30 years, a major breakthrough in their understanding has come much later, with the discovery of an impressive, ever-increasing number of mutations of mitochondrial DNA. Partial deletions or duplications of mtDNA, or maternally inherited point mutations, have been associated with well-defined clinical syndromes. However, phenotypes transmitted as mendelian traits have also been identified. These include clinical entities defined on the basis of specific biochemical defects, and also a few autosomal dominant or recessive syndromes associated with multiple deletions or tissue-specific depletion of mtDNA. Given the complexity of mitochondrial genetics and biochemistry, the clinical manifestations of mitochondrial disorders are extremely heterogenous. They range from lesions of single tissues or structures, such as the optic nerve in Leber hereditary optic neuropathy or the cochlea in maternally inherited nonsyndromic deafness, to more widespread lesions including myopathies, encephalomyopathies, cardiopathies, or complex multisystem syndromes. The recent advances in genetic studies provide both diagnostic tools and new pathogenetic insights in this rapidly expanding area of human pathology.

  3. Historical bathymetric changes near the entrance to Grays Harbor, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Burch, T.L.; Sherwood, C.R. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1992-12-01

    Large changes in the distribution of sediment near the entrance to Grays Harbor, Washington, have occurred since the long rock jetties were built to confine flow. Spits to the north and south of the entrance have grown, the entrance channel has deepened, and the outer bar has eroded and moved offshore. The shorelines of North Beach and South Beach have experienced significant amounts of both erosion and accretion since the jetties were constructed around the turn of the century. Recently, the erosion rate at South Beach has increased and, because Half Moon Bay is growing at the expense of the shoreward side of Point Chehalis, the vegetated portion of the spit is now less than 350 ft wide at the narrowest section. The US Army Corps of Engineers, Seattle District, requested that Battelle/Marine Sciences Laboratory evaluate long-term trends in erosion near the entrance to Grays Harbor.

  4. Crab Orchard National Wildlife Refuge : Entrance Fee Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Emergency Wetlands Resources Act of 1986 authorizes the Fish and Wildlife Service to collect entrance fees within selected units of the National Wildlife Refuge...

  5. COX7A2L is a mitochondrial complex III-binding protein that stabilizes the III2+IV supercomplex without affecting respirasome formation

    OpenAIRE

    Pérez-Pérez, Rafael; Lobo-Jarne, Teresa; Milenkovic, Dusanka; Mourier, Arnaud; Bratic, Ana; García-Bartolomé, Alberto; Fernández-Vizarra, Erika; Cadenas, Susana; Delmiro, Aitor; García-Consuegra, Inés; Arenas, Joaquín; Martín, Miguel A.; Larsson, Nils-Göran; Ugalde, Cristina

    2016-01-01

    Mitochondrial respiratory chain (MRC) complexes I, III and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here we further examine the functional significance of COX7A2L in the structural organization of the mammalian res...

  6. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation

    OpenAIRE

    Rafael Pérez-Pérez; Teresa Lobo-Jarne; Dusanka Milenkovic; Arnaud Mourier; Ana Bratic; Alberto García-Bartolomé; Erika Fernández-Vizarra; Susana Cadenas; Aitor Delmiro; Inés García-Consuegra; Joaquín Arenas; Miguel A. Martín; Nils-Göran Larsson; Cristina Ugalde

    2016-01-01

    Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian r...

  7. Oral administration of fumonisin B1 and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits.

    Science.gov (United States)

    Szabó, A; Szabó-Fodor, J; Fébel, H; Mézes, M; Bajzik, G; Kovács, M

    2016-09-01

    Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B1 (FB1) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition, margaric acid (C17:0) proportion decreased in the separated toxin treatments compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the FB1-treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB1 group's mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation.

  8. Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay.

    Science.gov (United States)

    Smakowska, Elwira; Skibior-Blaszczyk, Renata; Czarna, Malgorzata; Kolodziejczak, Marta; Kwasniak-Owczarek, Malgorzata; Parys, Katarzyna; Funk, Christiane; Janska, Hanna

    2016-08-01

    FTSH4 is one of the inner membrane-embedded ATP-dependent metalloproteases in mitochondria of Arabidopsis (Arabidopsis thaliana). In mutants impaired to express FTSH4, carbonylated proteins accumulated and leaf morphology was altered when grown under a short-day photoperiod, at 22°C, and a long-day photoperiod, at 30°C. To provide better insight into the function of FTSH4, we compared the mitochondrial proteomes and oxyproteomes of two ftsh4 mutants and wild-type plants grown under conditions inducing the phenotypic alterations. Numerous proteins from various submitochondrial compartments were observed to be carbonylated in the ftsh4 mutants, indicating a widespread oxidative stress. One of the reasons for the accumulation of carbonylated proteins in ftsh4 was the limited ATP-dependent proteolytic capacity of ftsh4 mitochondria, arising from insufficient ATP amount, probably as a result of an impaired oxidative phosphorylation (OXPHOS), especially complex V. In ftsh4, we further observed giant, spherical mitochondria coexisting among normal ones. Both effects, the increased number of abnormal mitochondria and the decreased stability/activity of the OXPHOS complexes, were probably caused by the lower amount of the mitochondrial membrane phospholipid cardiolipin. We postulate that the reduced cardiolipin content in ftsh4 mitochondria leads to perturbations within the OXPHOS complexes, generating more reactive oxygen species and less ATP, and to the deregulation of mitochondrial dynamics, causing in consequence the accumulation of oxidative damage.

  9. Cyclophilin D Is Involved in the Regulation of Autophagy and Affects the Lifespan of P. anserina in Response to Mitochondrial Oxidative Stress

    Science.gov (United States)

    Kramer, Piet; Jung, Alexander T.; Hamann, Andrea; Osiewacz, Heinz D.

    2016-01-01

    The mitochondrial permeability transition pore plays a key role in programmed cell death and the induction of autophagy. Opening of the pore is regulated by the mitochondrial peptidyl prolyl-cis, trans-isomerase cyclophilin D (CYPD). Previously it was shown in the aging model organism Podospora anserina that PaCYPD abundance increases during aging and that PaCypD overexpressors are characterized by accelerated aging. Here, we describe a role of PaCYPD in the regulation of autophagy. We found that the accelerated aging phenotype observed in a strain overexpressing PaCypD is not metacaspase-dependent but is accompanied by an increase of general autophagy and mitophagy, the selective autophagic degradation of mitochondria. It thus is linked to what has been defined as “autophagic cell death” or “type II” programmed cell death. Moreover, we found that the previously demonstrated age-related induction of autophagy in wild-type aging depends on the presence of PaCYPD. Deletion of PaCypD leads to a decrease in autophagy in later stages of age and under paraquat-mediated oxidative stress. Finally, we report that PaCYPD is also required for mitohormesis, the beneficial effect of mild mitochondrial stress. Thus, PaCYPD plays a key role in the context-dependent regulation of pathways leading to pro-survival and pro-death effects of autophagy. PMID:27683587

  10. Mitochondrial DNA plasticity is an essential inducer of tumorigenesis.

    Science.gov (United States)

    Lee, W T Y; Cain, J E; Cuddihy, A; Johnson, J; Dickinson, A; Yeung, K-Y; Kumar, B; Johns, T G; Watkins, D N; Spencer, A; St John, J C

    2016-01-01

    Although mitochondrial DNA has been implicated in diseases such as cancer, its role remains to be defined. Using three models of tumorigenesis, namely glioblastoma multiforme, multiple myeloma and osteosarcoma, we show that mitochondrial DNA plays defining roles at early and late tumour progression. Specifically, tumour cells partially or completely depleted of mitochondrial DNA either restored their mitochondrial DNA content or actively recruited mitochondrial DNA, which affected the rate of tumorigenesis. Nevertheless, non-depleted tumour cells modulated mitochondrial DNA copy number at early and late progression in a mitochondrial DNA genotype-specific manner. In glioblastoma multiforme and osteosarcoma, this was coupled with loss and gain of mitochondrial DNA variants. Changes in mitochondrial DNA genotype affected tumour morphology and gene expression patterns at early and late progression. Importantly, this identified a subset of genes that are essential to early progression. Consequently, mitochondrial DNA and commonly expressed early tumour-specific genes provide novel targets against tumorigenesis.

  11. Predicting Siltation in Entrance Channel Based on Wind Conditions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The siltation induced by wind waves in an entrance channel is one of the prime factors influencing the operation efficiency of a port. It is necessary to predict the siltation accurately for dredging and ship operation passing through the entrance of the port. However, it is difficult to apply the traditional method to predicting entrance siltation because of its complex computational procedure and lacking the data of ocean dynamic elements in the specified sea area. From the view of energy conservation, a direct relationship between wind conditions and sediment deposition can be founded. On the basis of the above methodology, an empirical formula expressed by wind conditions for forecasting the siltation in the entrance channel is set up. The wind conditions are easily obtained from the local meteorological stations or weather maps, so the formula established in this paper is more convenient and practical than the traditional method. A case study is provided, in which the emopirical formula is calibrated and verified utilizing the measured wind and siltation conditions in the entrance channel of the port. Comparisons between computed values and measured data show satisfactory agreement.

  12. Optimal shape of entrances for a frictionless nanochannel

    Science.gov (United States)

    Belin, Christophe; Joly, Laurent; Detcheverry, François

    2016-09-01

    The nearly frictionless flow of water in narrow carbon nanotubes is a genuine nanofluidic phenomenon with many prospects of applications in membrane technology. When inner dissipation is vanishing, the limiting factor to high flux lies in the viscous dissipation occurring at the tube mouth. As shown by Gravelle et al. [Gravelle, Joly, Detcheverry, Ybert, Cottin-Bizonne, and Bocquet, Proc. Natl. Acad. Sci. USA 110, 16367 (2013), 10.1073/pnas.1306447110], these so-called end effects can be reduced by adding a conical entrance. In this work, we take a step further and search for the optimal entrance shape. We use finite element calculations to compute the hydrodynamic resistance of a frictionless tube with superellipse-shaped entrances and propose an approximate analytical model. If perfect slip applies on its wall, an optimal entrance which is only 10 tube radii in length is sufficient to reduce end effects by an order of magnitude, a performance almost three times better than the optimal cone. In the case of partial slip, the resistance decreases with the entrance length before reaching a plateau at an optimal length controlled by liquid-solid slip. Our results are discussed in connection with biological and artificial systems.

  13. A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I

    Energy Technology Data Exchange (ETDEWEB)

    Lertrit, P.; Noer, A.S.; Kapsa, R.; Marzuki, S. (Monash Univ., Clayton, Victoria (Australia)); Jean-Francois, M.J.B.; Thyagarajan, D.; Byrne, E. (St. Vincent' s Hospital, Fitzroy, Victoria (Australia)); Dennett, X. (Univ. of Melbourne, Parkville, Victoria (Australia)); Lethlean, K. (Prince Henry Hospital, Sydney (Australia))

    1992-09-01

    The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A[yields]G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA[sup Leu], was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A[yields]G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A[yields]G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation. 49 refs., 7 figs., 1 tab.

  14. The Arabidopsis thaliana RNA Editing FactorSLO2, which Affects the Mitochondrial ElectronTransport Chain, Participates in Multiple Stressand Hormone Resoonses

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Recently, we reported that the novel mitochondrial RNA editing factor SLO2 is essential for mitochondrialelectron transport, and vital for plant growth through regulation of carbon and energy metabolism. Here, we show thatmutation in SL02 causes hypersensitivity to ABA and insensitivity to ethylene, suggesting a link with stress responses.Indeed, slo2 mutants are hypersensitive to salt and osmotic stress during the germination stage, while adult plantsshow increased drought and salt tolerance. Moreover, slo2 mutants are more susceptible to Botrytis cinerea infection.An increased expression of nuclear-encoded stress-responsive genes, as well as mitochondrial-encoded NAD genes ofcomplex I and genes of the alternative respiratory pathway, was observed in slo2 mutants, further enhanced by ABAtreatment. In addition, H202 accumulation and altered amino acid levels were recorded in slo2 mutants. We conclude thatSLO2 is required for plant sensitivity to ABA, ethylene, biotic, and abiotic stress. Although two stress-related RNA editingfactors were reported very recently, this study demonstrates a unique role of SLO2, and further supports a link betweenmitochondrial RNA editing events and stress response.

  15. Traffic disruption at Entrance B -TRAM- related work

    CERN Multimedia

    Infrastructure and General Services Department

    2010-01-01

    Due to work being carried out for the TRAM we inform you that vehicles coming from Geneva will be prohibited from turning left into Entrance B. This restriction will be in place for approx. 10 weeks*) starting from Monday 30 August 2010. You are highly recommended to enter CERN through Entrance A during this period even though a diversion will be put in place to allow access to CERN from Entrance B (as shown in the attached sketch). In addition, approx. 20 car parking spaces will be temporarily unavailable at the western end of the flags car park. We thank you in advance for your kind understanding. ______________ *) The exact end date of the work will be communicated in due course. GS-SEM Group

  16. Prévessin site – Pedestrian and cycle entrances

    CERN Document Server

    GS-IS

    2013-01-01

      A second entrance for pedestrians and cyclists on Route du Maroc will be opened and the existing entrance on Chemin du Moulin des Ponts will be re-opened: - for the period 2 April to 31 October 2013, - from 7.00 a.m. to 9.00 a.m. and from 5.00 p.m. to 7.00 p.m. on working days (Monday to Friday). IMPORTANT: all users must show their access cards to the security guard as a matter of course when passing through the gates, both on entering and leaving the site.

  17. Mitochondrial Myopathy

    Science.gov (United States)

    ... diseases are caused by CoQ10 deficiency, and CoQ10 supplementation is clearly beneficial in these cases. It might provide some relief from other mitochondrial diseases. Creatine, L-carnitine, and CoQ10 supplements often are combined into a “ ...

  18. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    Science.gov (United States)

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.

  19. Principles of the mitochondrial fusion and fission cycle in neurons.

    Science.gov (United States)

    Cagalinec, Michal; Safiulina, Dzhamilja; Liiv, Mailis; Liiv, Joanna; Choubey, Vinay; Wareski, Przemyslaw; Veksler, Vladimir; Kaasik, Allen

    2013-05-15

    Mitochondrial fusion-fission dynamics play a crucial role in many important cell processes. These dynamics control mitochondrial morphology, which in turn influences several important mitochondrial properties including mitochondrial bioenergetics and quality control, and they appear to be affected in several neurodegenerative diseases. However, an integrated and quantitative understanding of how fusion-fission dynamics control mitochondrial morphology has not yet been described. Here, we took advantage of modern visualisation techniques to provide a clear explanation of how fusion and fission correlate with mitochondrial length and motility in neurons. Our main findings demonstrate that: (1) the probability of a single mitochondrion splitting is determined by its length; (2) the probability of a single mitochondrion fusing is determined primarily by its motility; (3) the fusion and fission cycle is driven by changes in mitochondrial length and deviations from this cycle serves as a corrective mechanism to avoid extreme mitochondrial length; (4) impaired mitochondrial motility in neurons overexpressing 120Q Htt or Tau suppresses mitochondrial fusion and leads to mitochondrial shortening whereas stimulation of mitochondrial motility by overexpressing Miro-1 restores mitochondrial fusion rates and sizes. Taken together, our results provide a novel insight into the complex crosstalk between different processes involved in mitochondrial dynamics. This knowledge will increase understanding of the dynamic mitochondrial functions in cells and in particular, the pathogenesis of mitochondrial-related neurodegenerative diseases.

  20. Getting Interpersonal on a University Entrance Exam Impromptu Writing Task

    Science.gov (United States)

    Myskow, Gordon; Gordon, Kana

    2012-01-01

    This article explores the types of audience engagement strategies used by a Japanese secondary school student in an after school course preparing for a high-stakes impromptu academic writing task on a university entrance exam. The study uses appraisal theory--the branch of Systemic Functional Linguistics (SFL) concerned with the patterning of…

  1. Genetic counseling in mitochondrial disease.

    Science.gov (United States)

    Vento, Jodie M; Pappa, Belen

    2013-04-01

    Mitochondrial diseases are a genetically and clinically diverse group of disorders that arise as a result of dysfunction of the mitochondria. Mitochondrial disorders can be caused by alterations in nuclear DNA and/or mitochondrial DNA. Although some mitochondrial syndromes have been described clearly in the literature many others present as challenging clinical cases with multisystemic involvement at variable ages of onset. Given the clinical variability and genetic heterogeneity of these conditions, patients and their families often experience a lengthy and complicated diagnostic process. The diagnostic journey may be characterized by heightened levels of uncertainty due to the delayed diagnosis and the absence of a clear prognosis, among other factors. Uncertainty surrounding issues of family planning and genetic testing may also affect the patient. The role of the genetic counselor is particularly important to help explain these complexities and support the patient and family's ability to achieve effective coping strategies in dealing with increased levels of uncertainty.

  2. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome.

    Directory of Open Access Journals (Sweden)

    Lance H Rodan

    Full Text Available To study the effects of L-arginine (L-Arg on total body aerobic capacity and muscle metabolism as assessed by (31Phosphorus Magnetic Resonance Spectroscopy ((31P-MRS in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes syndrome.We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR in MTTL1 gene with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.At baseline (no L-Arg, MELAS had lower serum Arg (p = 0.001. On 3(1P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr (p = 0.05, decreased ATP (p = 0.018, and decreased intracellular Mg(2+ (p = 0.0002 when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1 increase in mean % maximum work at anaerobic threshold (AT (2 increase in % maximum heart rate at AT (3 small increase in VO(2peak. On (31P-MRS the following mean trends were noted: (1 A blunted decrease in pH after exercise (less acidosis (2 increase in Pi/PCr ratio (ADP suggesting increased work capacity (3 a faster half time of PCr recovery (marker of mitochondrial activity following 5 minutes of moderate intensity exercise (4 increase in torque.These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study.Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.ClinicalTrials.gov NCT01603446.

  3. The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Genipin (GNP effectively inhibits uncoupling protein 2 (UCP2, which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS levels. In this study, the hydroxyls at positions C10 (10-OH and C1 (1-OH of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1 proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP's activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1 and 1-ethyl-genipin (1-GNP2 lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1 and 10-acetic acid-genipin (10-GNP2 exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP's apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.

  4. Emerging Therapeutic Approaches to Mitochondrial Diseases

    Science.gov (United States)

    Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

    2010-01-01

    Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

  5. The Neurologic Manifestations of Mitochondrial Disease

    Science.gov (United States)

    Parikh, Sumit

    2010-01-01

    The nervous system contains some of the body's most metabolically demanding cells that are highly dependent on ATP produced via mitochondrial oxidative phosphorylation. Thus, the neurological system is consistently involved in patients with mitochondrial disease. Symptoms differ depending on the part of the nervous system affected. Although almost…

  6. Mitochondrial accumulation of APP and Abeta

    DEFF Research Database (Denmark)

    Pavlov, Pavel F; Petersen, Anna Camilla Hansson; Glaser, Elzbieta;

    2009-01-01

    mitochondrial function of neurons within specific brain regions. This is accompanied by an elevated production of reactive oxygen species contributing to increased rates of neuronal loss in the AD-affected brain regions. In this review, we will discuss the role of mitochondrial function and dysfunction in AD...

  7. [Mitochondrial diseases; thinking beyond organ specialism necessary

    NARCIS (Netherlands)

    Smits, B.W.; Smeitink, J.A.M.; Engelen, B.G.M. van

    2008-01-01

    Mitochondrial disorders are caused by a defect in intracellular energy production. In general, these are multi-system disorders, predominantly affecting organs with high energy requirements. Due to the fact that mitochondrial disorders are not as rare as is generally assumed, and due to the diversit

  8. Glutathionylation of Pea Chloroplast 2-Cys Prx and Mitochondrial Prx IIF Affects Their Structure and Peroxidase Activity and Sulfiredoxin Deglutathionylates Only the 2-Cys Prx.

    Science.gov (United States)

    Calderón, Aingeru; Lázaro-Payo, Alfonso; Iglesias-Baena, Iván; Camejo, Daymi; Lázaro, Juan J; Sevilla, Francisca; Jiménez, Ana

    2017-01-01

    Together with thioredoxins (Trxs), plant peroxiredoxins (Prxs), and sulfiredoxins (Srxs) are involved in antioxidant defense and redox signaling, while their regulation by post-translational modifications (PTMs) is increasingly regarded as a key component for the transduction of the bioactivity of reactive oxygen and nitrogen species. Among these PTMs, S-glutathionylation is considered a protective mechanism against overoxidation, it also modulates protein activity and allows signaling. This study explores the glutathionylation of recombinant chloroplastic 2-Cys Prx and mitochondrial Prx IIF from Pisum sativum. Glutathionylation of the decameric form of 2-Cys Prx produced a change in the elution volume after FPLC chromatography and converted it to its dimeric glutathionylated form, while Prx IIF in its reduced dimeric form was glutathionylated without changing its oligomeric state. Mass spectrometry demonstrated that oxidized glutathione (GSSG) can glutathionylate resolving cysteine (Cys(174)), but not the peroxidatic equivalent (Cys(52)), in 2-Cys Prx. In contrast, GSSG was able to glutathionylate both peroxidatic (Cys(59)) and resolving (Cys(84)) cysteine in Prx IIF. Glutathionylation was seen to be dependent on the GSH/GSSG ratio, although the exact effect on the 2-Cys Prx and Prx IIF proteins differed. However, the glutathionylation provoked a similar decrease in the peroxidase activity of both peroxiredoxins. Despite growing evidence of the importance of post-translational modifications, little is known about the enzymatic systems that specifically regulate the reversal of this modification. In the present work, sulfiredoxin from P. sativum was seen to be able to deglutathionylate pea 2-Cys Prx but not pea Prx IIF. Redox changes during plant development and the response to stress influence glutathionylation/deglutathionylation processes, which may represent an important event through the modulation of peroxiredoxin and sulfiredoxin proteins.

  9. Role of mitochondrial calcium uniporter in regulating mitochondrial fission in the cerebral cortexes of living rats.

    Science.gov (United States)

    Liang, Nan; Wang, Peng; Wang, Shilei; Li, Shuhong; Li, Yu; Wang, Jinying; Wang, Min

    2014-06-01

    The mitochondrial calcium uniporter (MCU) transports Ca2+ from the cytoplasm to the mitochondrial matrix and thus maintains Ca2+ homeostasis. Previous studies have reported that inhibition of MCU by ruthenium red (RR) protects the brain from ischemia/reperfusion (I/R) injury and that mitochondrial fission plays an important role in I/R injury. However, it is still not known whether MCU affects mitochondrial fission. In the present study, treatment with RR was found to decrease the concentration of free calcium in the mitochondria, calcineurin enzyme activity and dynamin-related protein 1 expression, and treatment with spermine was found to have the opposite effect in organisms subjected to occlusion of the middle cerebral artery lasting 2 h followed by 24 h reperfusion. These results indicate that MCU may be related to mitochondrial fission via modulating mitochondrial Ca2+ uptake and this relationship between MCU and mitochondrial fission may protect the brain from I/R injury.

  10. 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 ...

  11. CFTR activity and mitochondrial function

    Directory of Open Access Journals (Sweden)

    Angel Gabriel Valdivieso

    2013-01-01

    Full Text Available Cystic Fibrosis (CF is a frequent and lethal autosomal recessive disease, caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR. Before the discovery of the CFTR gene, several hypotheses attempted to explain the etiology of this disease, including the possible role of a chloride channel, diverse alterations in mitochondrial functions, the overexpression of the lysosomal enzyme α-glucosidase and a deficiency in the cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse mitochondrial changes found, some authors proposed that the affected gene should codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration of its chloride channel activity turned the mitochondrial, lysosomal and cytosolic hypotheses obsolete. However, in recent years, using new approaches, several investigators reported similar or new alterations of mitochondrial functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria in this disease. Here, we review these CFTR-driven mitochondrial defects, including differential gene expression, alterations in oxidative phosphorylation, calcium homeostasis, oxidative stress, apoptosis and innate immune response, which might explain some characteristics of the complex CF phenotype and reveals potential new targets for therapy.

  12. 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.

  13. Search for entrance channel effects in compound nuclear formation

    CERN Document Server

    Maj, A; Herskind, B; Bracco, A; Camera, F; Hagemann, G; Varmette, P

    1999-01-01

    The entrance channel effect was studied for the decay of sup 1 sup 7 sup 0 W formed in fusion reactions with different beam-target combinations. The average number of emitted neutrons suggest a lower effective excitation energy in the (alpha,xn) decay channel when more mass-symmetric reaction is used, especially at the highest angular momenta. The results are in qualitative agreement with predictions of the dissipative fusion model.

  14. Entrance channel effect in the incomplete fusion reactions

    Directory of Open Access Journals (Sweden)

    Singh B.P.

    2011-10-01

    Full Text Available In the present work the effect of various entrance channel parameters on incomplete fusion strength and the reaction dynamics in 12C+159Tb system at energies ≈ 4-7MeV/A have been investigated by measuring the excitation functions of individual reaction channels. Experimental excitation functions have been analyzed in the framework of compound nucleus decay using statistical model code PACE4. Analysis of data suggests the production of xn/pxn-channels via complete fusion of 12C with 159Tb, as these are found to be well reproduced by PACE4 predictions, while, a significant enhancement in the excitation functions of α-emitting channels has been observed over the theoretical ones. This enhancement has been attributed due to incomplete fusion. For better insight into the underlying dynamics, fraction of incomplete fusion to the total fusion has been deduced and compared with 16O+159Tb and other nearby systems as a function of various entrance channel parameters. The fraction of incomplete fusion has been found to be sensitive to the projectile type, energy and entrance-channel mass-asymmetry.

  15. The importance of mitochondrial DNA in aging and cancer

    DEFF Research Database (Denmark)

    Madsen, Claus Desler; Espersen, Maiken Lise Marcker; Singh, Keshav K

    2011-01-01

    Mitochondrial dysfunction has been implicated in premature aging, age-related diseases, and tumor initiation and progression. Alterations of the mitochondrial genome accumulate both in aging tissue and tumors. This paper describes our contemporary view of mechanisms by which alterations...... of the mitochondrial genome contributes to the development of age- and tumor-related pathological conditions. The mechanisms described encompass altered production of mitochondrial ROS, altered regulation of the nuclear epigenome, affected initiation of apoptosis, and a limiting effect on the production...

  16. Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.

    Science.gov (United States)

    Zhang, Cuilin; Shi, Zhun; Zhang, Lingzhi; Zhou, Zehua; Zheng, Xiaoyuan; Liu, Guiying; Bu, Guojun; Fraser, Paul E; Xu, Huaxi; Zhang, Yun-Wu

    2016-03-01

    Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes β-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1(K38A), partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.

  17. 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.

  18. Substation interference on gas entrance of industrial plants

    Energy Technology Data Exchange (ETDEWEB)

    Freire, Paulo Edmundo; Giacommelo, Claudinei [PAIOL Engenharia, Paulinia, SP (Brazil)

    2009-12-19

    Industrial plants often have medium or high voltage electrical power entrance and also gas feeders. Often the main substation is located near the gas entrance, in the utilities area. When the occurrence of a phase to ground short-circuit in the substation, the pipeline and gas entrance that serves the plant may be exposed to high voltage soil potential, of the order of a few kilovolts, due to resistive coupling with the substation ground mesh. The consequences of this situation are reflected in various risks, with emphasis on: damage to the protective coating of the duct, due to the increased soil potential, in excess of its dielectric supportability (typically on the order of 5 kV); spread of potentially hazardous to duct exposed parts (valves, measuring place etc.); and damage to cathodic protection system components, as rectifier and insulating joins at gas entrance. This paper presents the investigations conducted in a factory that has a 69 kV main substation very close to the gas entrance, the order of a few meters away. The substation phase to ground short-circuit current is 7 kA, what causes a 9 kV soil potential near the gas pipe. It is presented the methodology for modeling the various elements involved in this process, the results of simulations made, arrangements been taken to reduce soil potential next to the duct to levels below 5 kV, and the measures for people and insulating joins protection. It is important to note that such problems usually will be solved with measures involving the entire grounding system of the industrial complex and also close to the duct (outside the industrial plant). The gas distribution companies should require from customers where this situation occurs, to ensure safety for people who have access to elements of its network, and for the integrity of their own ducts and cathodic protection components. The computer simulations developed for this work were made with the software Auto Grid, developed by the Canadian company Safe

  19. Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes

    DEFF Research Database (Denmark)

    Jensen, Line; Gejl, Kasper D; Ørtenblad, Niels;

    2015-01-01

    The aim was to determine if the metabolic adaptations, particularly PGC-1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite...... endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also...

  20. EnTranCe to the second life of gas : EnTranCe as source of innovation and human resources

    NARCIS (Netherlands)

    Aué, Jan-jaap; Gemert, Wim van; Martinus, Gerard

    2015-01-01

    The living lab EnTranCe provides a platform for open innovations. Stakeholders from large industry, SME’s, government and the research community team up to work on the future of the European energy system, with gas in a pivotal role. An important element of the innovation strength of EnTranCe is tha

  1. Loads on Entrance Platforms for Offshore Wind Turbines

    DEFF Research Database (Denmark)

    Frigaard, Peter; Andersen, Thomas Lykke; Ramirez, Jorge Robert Rodriguez;

    2010-01-01

    The present paper gives an overview of the performed large scale tests in GWK, Hannover for studying wave run-up generated forces on wind turbine entrance platforms. The run-up height and velocity was measured by use of high speed video recordings supplemented by some wave gauges mounted...... at the pile. Hereafter, the run-up generated impact forces were measured on two types of grates and a solid plate. The pressure distribution was also measured for the solid plate. In addition to this the wave generated backfilling of an initial scour hole and the strength of the backfilling soil was studied...

  2. Prévessin site: Pedestrian and cycle entrance

    CERN Multimedia

    2015-01-01

    The entrance to the Prévessin site for pedestrians and cyclists on Chemin du Moulin des Ponts will be re-opened: from 7 April to 30 October 2015, from 7.00 a.m. to 9.00 a.m. and from 5.00 p.m. to 7.00 p.m. on working days (Monday to Friday).   IMPORTANT: all users must show their access cards to the security guard as a matter of course when passing through the gates, both on entering and leaving the site.

  3. Prévessin site – Pedestrian and cycle entrances

    CERN Multimedia

    GS-DI

    2014-01-01

    Entrances for pedestrians and cyclists on Route du Maroc and on Chemin du Moulin des Ponts, in Prévessin, will be re-opened:   from 7 April to 31 October 2014, from 7.00 a.m. to 9.00 a.m. and from 5.00 p.m. to 7.00 p.m. on working days (Monday to Friday).   IMPORTANT: all users must show their access cards to the security guard as a matter of course when passing through the gates, both on entering and leaving the site.

  4. Mitochondrial abnormalities in the myofibrillar myopathies.

    Science.gov (United States)

    Jackson, S; Schaefer, J; Meinhardt, M; Reichmann, H

    2015-11-01

    Myofibrillar myopathies are a genetically diverse group of skeletal muscle disorders, with distinctive muscle histopathology. Causative mutations have been identified in the genes MYOT, LDB3, DES, CRYAB, FLNC, BAG3, DNAJB6, FHL1, PLEC and TTN, which encode proteins which either reside in the Z-disc or associate with the Z-disc. Mitochondrial abnormalities have been described in muscle from patients with a myofibrillar myopathy. We reviewed the literature to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes. Abnormal mitochondrial distribution is a frequent finding in each of the subtypes, but a high frequency of COX-negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding. Few in vitro studies of mitochondrial function have been performed in affected patients.

  5. Characteristics of mitochondrial calpains.

    Science.gov (United States)

    Ozaki, Taku; Tomita, Hiroshi; Tamai, Makoto; Ishiguro, Sei-Ichi

    2007-09-01

    Calpains are considered to be cytoplasmic enzymes, although several studies have shown that calpain-like protease activities also exist in mitochondria. We partially purified mitochondrial calpain from swine liver mitochondria and characterized. Only one type of mitochondrial calpain was detected by the column chromatographies. The mitochondrial calpain was stained with anti-mu-calpain and calpain small subunit antibodies. The susceptibility of mitochondrial calpain to calpain inhibitors and the optimum pH differ from those of cytosolic mu- and m-calpains. The Ca(2+)-dependency of mitochondrial calpain was similar to that of cytosolic mu-calpain. Therefore, we named the protease mitochondrial mu-like calpain. In zymogram analysis, two types of caseinolytic enzymes existed in mitochondria and showed different mobilities from cytosolic mu- and m-calpains. The upper major band was stained with anti-mu-calpain and calpain small subunit antibodies (mitochondrial calpain I, mitochondrial mu-like calpain). The lower band was stained only with anti-calpain small subunit antibody (mitochondrial calpain II, unknown mitochondrial calpain). Calpastatin was not detected in mitochondrial compartments. The mitochondrial calpain processed apoptosis-inducing factor (AIF) to truncated AIF (tAIF), releasing tAIF into the intermembrane space. These results indicate that mitochondrial calpain, which differs from mu- and m-calpains, seems to be a ubiquitous calpain and may play a role in mitochondrial apoptotic signalling.

  6. Interface Region Imaging Spectrograph (IRIS) entrance aperture design

    Science.gov (United States)

    Cheimets, P.; Park, S.; Bergner, H.; Chou, C.; Gates, R.; Honsa, M.; Podgorski, W.; Yanari, C.

    2014-07-01

    The Interface Region Imaging Spectrograph (IRIS) is a complementary follow-on to Solar Dynamics Observatory Atmospheric Imaging Assembly (SDO-AIA) and funded as a member of the NASA SMEX program. This paper presents the thermal design of the IRIS telescope front end, with a focus on the IRIS door and entrance aperture assembly. The challenge of the IRIS entrance aperture, including the door design, was to manage the solar flux, both before and after the door was opened. This is especially a problem with instruments that are permanently pointed directly at the sun. Though there is an array of effective flux-rejecting coatings, they are expensive, hard to apply, harder to measure, delicate, prone to unpredictable performance decay with exposure, and very often a source of contamination. This paper presents a thermal control and protection method based on robust, inexpensive coatings and materials, combined to produce high thermal and structural isolation. The end result is a first line of thermal protection whose performance is easy to predict and well isolated from the instrument it is protecting.

  7. Entrance C - New Automatic Number Plate Recognition System

    CERN Multimedia

    2013-01-01

    Entrance C (Satigny) is now equipped with a latest-generation Automatic Number Plate Recognition (ANPR) system and a fast-action road gate.   During the month of August, Entrance C will be continuously open from 7.00 a.m. to 7.00 p.m. (working days only). The security guards will open the gate as usual from 7.00 a.m. to 9.00 a.m. and from 5.00 p.m. to 7.00 p.m. For the rest of the working day (9.00 a.m. to 5.00 p.m.) the gate will operate automatically. Please observe the following points:       Stop at the STOP sign on the ground     Position yourself next to the card reader for optimal recognition     Motorcyclists must use their CERN card     Cyclists may not activate the gate and should use the bicycle turnstile     Keep a safe distance from the vehicle in front of you   If access is denied, please check that your vehicle regist...

  8. Evaluation of entrance surface air kerma in pediatric chest radiography

    Science.gov (United States)

    Porto, L.; Lunelli, N.; Paschuk, S.; Oliveira, A.; Ferreira, J. L.; Schelin, H.; Miguel, C.; Denyak, V.; Kmiecik, C.; Tilly, J.; Khoury, H.

    2014-11-01

    The objective of this study was to evaluate the entrance surface air kerma in pediatric chest radiography. An evaluation of 301 radiographical examinations in anterior-posterior (AP) and posterior-anterior (PA) (166 examinations) and lateral (LAT) (135 examinations) projections was performed. The analyses were performed on patients grouped by age; the groups included ages 0-1 y, 1-5 y, 5-10 y, and 10-15 y. The entrance surface air kerma was determined with DoseCal software (Radiological Protection Center of Saint George's Hospital, London) and thermoluminescent dosimeters. Two different exposure techniques were compared. The doses received by patients who had undergone LAT examinations were 40% higher, on average, those in AP/PA examinations because of the difference in tube voltage. A large high-dose “tail” was observed for children up to 5 y old. An increase in tube potential and corresponding decrease in current lead to a significant dose reduction. The difference between the average dose values for different age ranges was not practically observed, implying that the exposure techniques are still not optimal. Exposure doses received using the higher tube voltage and lower current-time product correspond to the international diagnostic reference levels.

  9. Laminar flow in the entrance region of elliptical ducts

    Science.gov (United States)

    Bhatti, M. S.

    1983-06-01

    A closed-form analytical solution is developed to hitherto unsolved problem of steady laminar flow of a Newtonian fluid in the entrance region of elliptical ducts. The analysis is based on the Karman-Pohlhausen integral method and entails solution of the integrated forms of the mass and the momentum balance equations. According to this analysis, the hydrodynamic entrance length based on 99 percent approach to the fully developed flow is equal to 0.5132 lambda/(l + lambda-squared) where lambda is the aspect ratio. Also, the fully developed incremental pressure defect is found to be 7/6 which is independent of the aspect ratio. In the limit when the flow becomes fully developed, the solution converges to the known exact asymptotic solution. Available, wide-ranging velocity measurements for a circular tube agree with the analytical predictions within 7 percent. Also, available pressure drop measurements near the inlet of a circular tube agree with the analytical predictions within 2 percent.

  10. Mitochondrial replacement techniques: egg donation, genealogy and eugenics.

    Science.gov (United States)

    Palacios-González, César

    2016-03-01

    Several objections against the morality of researching or employing mitochondrial replacement techniques have been advanced recently. In this paper, I examine three of these objections and show that they are found wanting. First I examine whether mitochondrial replacement techniques, research and clinical practice, should not be carried out because of possible harms to egg donors. Next I assess whether mitochondrial replacement techniques should be banned because they could affect the study of genealogical ancestry. Finally, I examine the claim that mitochondrial replacement techniques are not transferring mitochondrial DNA but nuclear DNA, and that this should be prohibited on ethical grounds.

  11. Parkin suppresses Drp1-independent mitochondrial division.

    Science.gov (United States)

    Roy, Madhuparna; Itoh, Kie; Iijima, Miho; Sesaki, Hiromi

    2016-07-01

    The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson's disease-associated protein-parkin, which biochemically and genetically interacts with Drp1-in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria-targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division.

  12. Mitochondrial biogenesis and turnover.

    Science.gov (United States)

    Diaz, Francisca; Moraes, Carlos T

    2008-07-01

    Mitochondrial biogenesis is a complex process involving the coordinated expression of mitochondrial and nuclear genes, the import of the products of the latter into the organelle and turnover. The mechanisms associated with these events have been intensively studied in the last 20 years and our understanding of their details is much improved. Mitochondrial biogenesis requires the participation of calcium signaling that activates a series of calcium-dependent protein kinases that in turn activate transcription factors and coactivators such as PGC-1alpha that regulates the expression of genes coding for mitochondrial components. In addition, mitochondrial biogenesis involves the balance of mitochondrial fission-fusion. Mitochondrial malfunction or defects in any of the many pathways involved in mitochondrial biogenesis can lead to degenerative diseases and possibly play an important part in aging.

  13. Impaired mitochondrial trafficking in Huntington's disease

    OpenAIRE

    Li, Xiao-Jiang; Orr, Adam L.; Li, Shihua

    2009-01-01

    Abstract Impaired mitochondrial function has been well documented in Huntington?s disease. Mutant huntingtin is found to affect mitochondria via various mechanisms including the dysregulation of gene transcription and impairment of mitochondrial function or trafficking. The lengthy and highly branched neuronal processes constitute complex neural networks in which there is a large demand for mitochondria-generated energy. Thus, the impaired mitochondria trafficking in neuronal cells...

  14. Entrance, exit, and reentrance of one shot with a shotgun

    DEFF Research Database (Denmark)

    Gulmann, C; Hougen, H P

    1999-01-01

    The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region, and ther......The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region......, and thereafter penetrated the left side of the neck, causing tearing of the left common carotid artery and the right internal carotid artery. The entrance wound in the axilla was larger than the other wounds, and before autopsy it was believed that the shotgun had been fired twice, causing one wound in the neck...

  15. The mitochondrial genome encodes abundant small noncoding RNAs

    Institute of Scientific and Technical Information of China (English)

    Seungil Ro; Hsiu-Yen Ma; Chanjae Park; Nicole Ortogero; Rui Song; Grant W Hennig; Huili Zheng

    2013-01-01

    Small noncoding RNAs identified thus far are all encoded by the nuclear genome.Here,we report that the murine and human mitochondriai genomes encode thousands of small noncoding RNAs,which are predominantly derived from the sense transcripts of the mitochondrial genes (host genes),and we termed these small RNAs mitochondrial genome-encoded small RNAs (mitosRNAs).DICER inactivation affected,but did not completely abolish mitosRNA production.MitosRNAs appear to be products of currently unidentified mitochondrial ribonucleases.Overexpression of mitosRNAs enhanced expression levels of their host genes in vitro,and dysregulated mitosRNA expression was generally associated with aberrant mitochondrial gene expression in vivo.Our data demonstrate that in addition to 37 known mitochondrial genes,the mammalian mitochondrial genome also encodes abundant mitosRNAs,which may play an important regulatory role in the control of mitochondrial gene expression in the cell.

  16. 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.

  17. Strokes in mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    N V Pizova

    2012-01-01

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

  18. 46 CFR 111.83-5 - Bottom entrance and protected enclosures.

    Science.gov (United States)

    2010-10-01

    ... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Shore Connection Boxes § 111.83-5 Bottom entrance and protected enclosures. Each shore connection box must have a bottom entrance for the shore connection cable. The box must provide protection to the shore connection when the connection is in use....

  19. University and the Entrance Examinations in a Greek Provincial Town: A Bottom-Up Perspective.

    Science.gov (United States)

    Benincasa, Luciana

    1998-01-01

    Focuses on the cultural meaning of university education and of participation in the extremely competitive entrance examinations to university, as viewed from a Greek provincial town. Notes that despite high graduate unemployment, university education and sitting for entrance examinations have important social status implications. (DSK)

  20. The effect of mitochondrial dysfunction on cytosolic nucleotide metabolism

    DEFF Research Database (Denmark)

    Madsen, Claus Desler; Lykke, Anne; Rasmussen, Lene Juel

    2010-01-01

    of cytosolic ribonucleotides and deoxyribonucleotides, which in turn can result in aberrant RNA and DNA synthesis. Mitochondrial dysfunction has been linked to genomic instability, and it is possible that the limiting effect of mitochondrial dysfunction on the levels of nucleotides and resulting aberrant RNA...... and DNA synthesis in part can be responsible for this link. This paper summarizes the parts of the metabolic pathways responsible for nucleotide metabolism that can be affected by mitochondrial dysfunction....

  1. Evolutionary implications of mitochondrial genetic variation: mitochondrial genetic effects on OXPHOS respiration and mitochondrial quantity change with age and sex in fruit flies.

    Science.gov (United States)

    Wolff, J N; Pichaud, N; Camus, M F; Côté, G; Blier, P U; Dowling, D K

    2016-04-01

    The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution.

  2. Mitochondrial rejuvenation after induced pluripotency.

    Directory of Open Access Journals (Sweden)

    Steven T Suhr

    Full Text Available BACKGROUND: As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion "resets" some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells. METHODOLOGY/PRINCIPAL FINDINGS: We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1 that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2 the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal. CONCLUSIONS/SIGNIFICANCE: These results - coupled with earlier data from our laboratory - suggest that IPSC conversion not only resets the "biological clock", but can also rejuvenate the energetic capacity of derived cells.

  3. Mitochondria: impaired mitochondrial translation in human disease.

    Science.gov (United States)

    Boczonadi, Veronika; Horvath, Rita

    2014-03-01

    Defects of the mitochondrial protein synthesis cause a subgroup of mitochondrial diseases, which are usually associated with decreased activities of multiple respiratory chain (RC) enzymes. The clinical presentations of these disorders are often disabling, progressive or fatal, affecting the brain, liver, skeletal muscle, heart and other organs. Currently there are no effective cures for these disorders and treatment is at best symptomatic. The diagnosis in patients with multiple respiratory chain complex defects is particularly difficult because of the massive number of nuclear genes potentially involved in intra-mitochondrial protein synthesis. Many of these genes are not yet linked to human disease. Whole exome sequencing rapidly changed the diagnosis of these patients by identifying the primary defect in DNA, and preventing the need for invasive and complex biochemical testing. Better understanding of the mitochondrial protein synthesis apparatus will help us to explore disease mechanisms and will provide clues for developing novel therapies.

  4. Mitochondrial phospholipids: role in mitochondrial function.

    Science.gov (United States)

    Mejia, Edgard M; Hatch, Grant M

    2016-04-01

    Mitochondria are essential components of eukaryotic cells and are involved in a diverse set of cellular processes that include ATP production, cellular signalling, apoptosis and cell growth. These organelles are thought to have originated from a symbiotic relationship between prokaryotic cells in an effort to provide a bioenergetic jump and thus, the greater complexity observed in eukaryotes (Lane and Martin 2010). Mitochondrial processes are required not only for the maintenance of cellular homeostasis, but also allow cell to cell and tissue to tissue communication (Nunnari and Suomalainen 2012). Mitochondrial phospholipids are important components of this system. Phospholipids make up the characteristic outer and inner membranes that give mitochondria their shape. In addition, these membranes house sterols, sphingolipids and a wide variety of proteins. It is the phospholipids that also give rise to other characteristic mitochondrial structures such as cristae (formed from the invaginations of the inner mitochondrial membrane), the matrix (area within cristae) and the intermembrane space (IMS) which separates the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM). Phospholipids are the building blocks that make up these structures. However, the phospholipid composition of the OMM and IMM is unique in each membrane. Mitochondria are able to synthesize some of the phospholipids it requires, but the majority of cellular lipid biosynthesis takes place in the endoplasmic reticulum (ER) in conjunction with the Golgi apparatus (Fagone and Jackowski 2009). In this review, we will focus on the role that mitochondrial phospholipids play in specific cellular functions and discuss their biosynthesis, metabolism and transport as well as the differences between the OMM and IMM phospholipid composition. Finally, we will focus on the human diseases that result from disturbances to mitochondrial phospholipids and the current research being performed to help

  5. Mitochondrial helicases and mitochondrial genome maintenance

    DEFF Research Database (Denmark)

    Aamann, Maria Diget; de Souza-Pinto, Nadja C; Kulikowicz, Tomasz;

    2010-01-01

    Helicases are essential enzymes that utilize the energy of nucleotide hydrolysis to drive unwinding of nucleic acid duplexes. Helicases play roles in all aspects of DNA metabolism including DNA repair, DNA replication and transcription. The subcellular locations and functions of several helicases...... have been studied in detail; however, the roles of specific helicases in mitochondrial biology remain poorly characterized. This review presents important recent advances in identifying and characterizing mitochondrial helicases, some of which also operate in the nucleus....

  6. Entrance surface dose in cerebral interventional radiology procedures

    Energy Technology Data Exchange (ETDEWEB)

    Barrera-Rico, M.; Lopez-Rendon, X.; Rivera-Ordonez, C. E.; Gamboa-deBuen, I. [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, 04510 DF (Mexico); Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, 14269 DF (Mexico); Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, 04510 DF (Mexico)

    2012-10-23

    At the Instituto Nacional de Neurologia y Neurocirugia (INNN) diagnostic as well as therapeutic procedures of interventional radiology are carried out. Since the procedures can last from some minutes to several hours, the absorbed dose for the patient could increase dangerously. An investigation had begun in order to determine the entrance surface dose (ESD) using 25 thermoluminiscent dosimeters TLD-100 and 8 strips of 15 Multiplication-Sign 1 cm{sup 2} of Gafchromic XR-QA2 film bound in a holder of 15 Multiplication-Sign 15 cm{sup 2} in the posteroanterior (PA) and lateral (LAT) positions during all the procedure. The results show that maximum ESD could be from 0.9 to 2.9 Gy for the PA position and between 1.6 and 2.5 Gy for the lateral position. The average ESD was between 0.7 and 1.3 Gy for the PA position, and from 0.44 to 1.1 Gy for the lateral position in a therapeutic procedure.

  7. Mitochondrial transcription factor A (Tfam) gene sequencing and mitochondrial evaluation in inherited retinal dysplasia in miniature schnauzer dogs

    OpenAIRE

    Bauer, Bianca S.; Forsyth, George W.; Sandmeyer, Lynne S.; Grahn, Bruce H.

    2011-01-01

    Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dysplasia in miniature schnauzer dogs and it has been proposed that affected dogs have altered mitochondrial numbers, size, and morphology. To test these hypotheses the Tfam gene of affected and normal miniature schnauzer dogs with retinal dysplasia was sequenced and lymphocyte mitochondria were quantified, measured, and the morphology was compared in normal and affected dogs using transmission elec...

  8. Mitochondrial Biogenesis and Turnover

    OpenAIRE

    Diaz, Francisca; Moraes, Carlos T.

    2008-01-01

    Mitochondrial biogenesis is a complex process involving the coordinated expression of mitochondrial and nuclear genes, the import of the products of the latter into the organelle and turnover. The mechanisms associated with these events have been intensively studied in the last twenty years and our understanding of their details is much improved. Mitochondrial biogenesis requires the participation of calcium signaling that activates a series of calcium dependent protein kinases that in turn a...

  9. The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes.

    Science.gov (United States)

    Diodato, Daria; Ghezzi, Daniele; Tiranti, Valeria

    2014-01-01

    Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations.

  10. The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes

    Directory of Open Access Journals (Sweden)

    Daria Diodato

    2014-01-01

    Full Text Available Mitochondrial respiratory chain (RC disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations.

  11. [Mitochondrial and oocyte development].

    Science.gov (United States)

    Deng, Wei-Ping; Ren, Zhao-Rui

    2007-12-01

    Oocyte development and maturation is a complicated process. The nuclear maturation and cytoplasmic maturation must synchronize which can ensure normal oocyte fertilization and following development. Mitochondrial is the most important cellular organell in cytoplasm, and the variation of its distribution during oocyte maturation, the capacity of OXPHOS generating ATP as well as the content or copy number or transcription level of mitochondrial DNA play an important role in oocyte development and maturation. Therefore, the studies on the variation of mitochondrial distribution, function and mitochondrial DNA could enhance our understanding of the physiology of reproduction and provide new insight to solve the difficulties of assisted reproduction as well as cloning embryo technology.

  12. Progress in mitochondrial epigenetics.

    Science.gov (United States)

    Manev, Hari; Dzitoyeva, Svetlana

    2013-08-01

    Mitochondria, intracellular organelles with their own genome, have been shown capable of interacting with epigenetic mechanisms in at least four different ways. First, epigenetic mechanisms that regulate the expression of nuclear genome influence mitochondria by modulating the expression of nuclear-encoded mitochondrial genes. Second, a cell-specific mitochondrial DNA content (copy number) and mitochondrial activity determine the methylation pattern of nuclear genes. Third, mitochondrial DNA variants influence the nuclear gene expression patterns and the nuclear DNA (ncDNA) methylation levels. Fourth and most recent line of evidence indicates that mitochondrial DNA similar to ncDNA also is subject to epigenetic modifications, particularly by the 5-methylcytosine and 5-hydroxymethylcytosine marks. The latter interaction of mitochondria with epigenetics has been termed 'mitochondrial epigenetics'. Here we summarize recent developments in this particular area of epigenetic research. Furthermore, we propose the term 'mitoepigenetics' to include all four above-noted types of interactions between mitochondria and epigenetics, and we suggest a more restricted usage of the term 'mitochondrial epigenetics' for molecular events dealing solely with the intra-mitochondrial epigenetics and the modifications of mitochondrial genome.

  13. An effect of entrance length on development of velocity profile in channel of millimeter dimensions

    Science.gov (United States)

    Jasikova, D.; Kotek, M.; Kopecky, V.

    2016-06-01

    Here we used modified PIV technique completed with long distance microscope probe for experimental investigation of the flow velocity profile in a rectangular duct. We came from the analytical and numerical prediction of the entrance length for fully developed velocity profile. The results of measurement completed knowledge about the flow stability and velocity profile shape in the channel of 0.00375 hydraulic diameters. There was marked a range of entrance length constant for the transient flow area. The presents of the fluctuating velocities in the transition flow is explained with POD snapshot and modes projection. The minimal entrance length for the laminar, transition, and turbulent flow is set.

  14. Similarity of Heat Transfer on Heat Source Elements in the Entrance Region in Electronic Equipment

    Institute of Scientific and Technical Information of China (English)

    Jane Z. Jiang; Sui Lin

    2001-01-01

    A similarity equation for heat transfer on heat source elements situated in the entrance region in electronic equipment is developed based on the experimental data obtained by Sparrow et al.[4]. The characteristic of the similarity equation is that the ratio of the heat transfer coefficient at the entrance region to that at the fully developed region is independent of the Reynolds number. It depends only on the row number of the elements situated in the entrance region. An example of the usefulness of the similarity equation is presented that determines the heat transfer on heat source elements in a power unit that contains only a small number of the heat source elements.

  15. Drug-induced mitochondrial neuropathy in children: a conceptual framework for critical windows of development.

    Science.gov (United States)

    Wallace, Kendall B

    2014-09-01

    Mitochondrial disease arises from genetic or nongenetic events that interfere either directly or indirectly with the bioenergetic function of the mitochondrion and manifest clinically in some form of metabolic disorder. In primary mitochondrial disease, the critical molecular target is one or more of the individual subunits of the respiratory complexes or their assembly and incorporation into the inner mitochondrial membrane, whereas with secondary mitochondrial disease the bioenergetic deficits are secondary to effects on targets other than the electron transport chain and oxidative phosphorylation. Primary genetic events include mutations to or altered expression of proteins targeted to the mitochondrial compartment, whether they are encoded by the nuclear or mitochondrial genome. In this review, we emphasize the occurrence of nongenetic mitochondrial disease resulting from therapeutic drug administration, review the broad scope of drugs implicated in affecting specific primary mitochondrial targets, and describe evidence demonstrating critical windows of risk for the developing neonate to drug-induced mitochondrial disease and neuropathy.

  16. Mitochondrial Cristae Shape Determines Respiratory Chain Supercomplexes Assembly and Respiratory Efficiency

    OpenAIRE

    Cogliati, Sara; Frezza, Christian; Soriano, Maria Eugenia; Varanita, Tatiana; Quintana-Cabrera, Ruben; Corrado, Mauro; Cipolat, Sara; Costa, Veronica; Casarin, Alberto; Gomes, Ligia C.; Perales-Clemente, Ester; Salviati, Leonardo; Fernandez-Silva, Patricio; Enriquez, Jose A.; Scorrano, Luca

    2013-01-01

    Summary Respiratory chain complexes assemble into functional quaternary structures called supercomplexes (RCS) within the folds of the inner mitochondrial membrane, or cristae. Here, we investigate the relationship between respiratory function and mitochondrial ultrastructure and provide evidence that cristae shape determines the assembly and stability of RCS and hence mitochondrial respiratory efficiency. Genetic and apoptotic manipulations of cristae structure affect assembly and activity o...

  17. Current variability at the Pacific entrance of the Indonesian Throughflow

    Science.gov (United States)

    Kashino, Yuji; Watanabe, Hidetoshi; Herunadi, Bambang; Aoyama, Michio; Hartoyo, Djoko

    1999-05-01

    Current variability at the Pacific entrance of the Indonesian Throughflow is investigated using direct current and hydrographic measurements. Two moorings with three current meters (depths of 350, 550, and 1050 m) and one conductivity-temperature-depth profiler (260 m) were deployed at 4°1'N, 127°31'E and 3°11'N, 128°27'E between Talaud Islands and Morotai Island (Indonesia) from February 1994 to June 1995. Data from four hydrographic surveys conducted mainly between Mindanao and New Guinea from 1994 to 1996 are also used. The onset of a strong northwestward flow was observed at the southern mooring during boreal winter. In contrast, a southwestward flow containing salty South Pacific water was observed there during boreal summer. This current pattern change matched monsoon change around the mooring sites, suggesting that this variability is a seasonal signal in this region. This current change may occur because of the meridional shift of the Halmahera Eddy associated with an enlargement/diminishment of the Mindanao Dome. Our observation result during summer (the southwestward flow with the South Pacific water at the southern mooring) suggests that the Maluku Sea is one of the eastern routes of the Indonesian Throughflow. The current data also revealed that intraseasonal variability occurs in 50-day oscillations. Because the coherence between wind variability in the tropics with a period of 40-50 days (Madden-Julian Oscillation) and current variability with this period are >0.4, it is possible that the 50-day oscillation in the ocean current is induced by wind variability associated with the Madden-Julian Oscillation. The ocean eddy activity with an intrinsic period in this region may also be related to this 50-day oscillation.

  18. Mitochondrial Dysfunction in Lysosomal Storage Disorders

    Directory of Open Access Journals (Sweden)

    Mario de la Mata

    2016-10-01

    Full Text Available Lysosomal storage diseases (LSDs describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS, where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm, diminished ATP production and increased generation of reactive oxygen species (ROS. Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD, the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase. Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer and glucosylsphingosine (GlcSph in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.

  19. Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu.

    Science.gov (United States)

    Valente, Lucia; Tiranti, Valeria; Marsano, Rene Massimiliano; Malfatti, Edoardo; Fernandez-Vizarra, Erika; Donnini, Claudia; Mereghetti, Paolo; De Gioia, Luca; Burlina, Alberto; Castellan, Claudio; Comi, Giacomo P; Savasta, Salvatore; Ferrero, Iliana; Zeviani, Massimo

    2007-01-01

    Mitochondrial protein translation is a complex process performed within mitochondria by an apparatus composed of mitochondrial DNA (mtDNA)-encoded RNAs and nuclear DNA-encoded proteins. Although the latter by far outnumber the former, the vast majority of mitochondrial translation defects in humans have been associated with mutations in RNA-encoding mtDNA genes, whereas mutations in protein-encoding nuclear genes have been identified in a handful of cases. Genetic investigation involving patients with defective mitochondrial translation led us to the discovery of novel mutations in the mitochondrial elongation factor G1 (EFG1) in one affected baby and, for the first time, in the mitochondrial elongation factor Tu (EFTu) in another one. Both patients were affected by severe lactic acidosis and rapidly progressive, fatal encephalopathy. The EFG1-mutant patient had early-onset Leigh syndrome, whereas the EFTu-mutant patient had severe infantile macrocystic leukodystrophy with micropolygyria. Structural modeling enabled us to make predictions about the effects of the mutations at the molecular level. Yeast and mammalian cell systems proved the pathogenic role of the mutant alleles by functional complementation in vivo. Nuclear-gene abnormalities causing mitochondrial translation defects represent a new, potentially broad field of mitochondrial medicine. Investigation of these defects is important to expand the molecular characterization of mitochondrial disorders and also may contribute to the elucidation of the complex control mechanisms, which regulate this fundamental pathway of mtDNA homeostasis.

  20. Infantile Encephalopathy and Defective Mitochondrial DNA Translation in Patients with Mutations of Mitochondrial Elongation Factors EFG1 and EFTu

    Science.gov (United States)

    Valente, Lucia; Tiranti, Valeria; Marsano, René Massimiliano; Malfatti, Edoardo; Fernandez-Vizarra, Erika; Donnini, Claudia; Mereghetti, Paolo; De Gioia, Luca; Burlina, Alberto; Castellan, Claudio; Comi, Giacomo P.; Savasta, Salvatore; Ferrero, Iliana; Zeviani, Massimo

    2007-01-01

    Mitochondrial protein translation is a complex process performed within mitochondria by an apparatus composed of mitochondrial DNA (mtDNA)–encoded RNAs and nuclear DNA–encoded proteins. Although the latter by far outnumber the former, the vast majority of mitochondrial translation defects in humans have been associated with mutations in RNA-encoding mtDNA genes, whereas mutations in protein-encoding nuclear genes have been identified in a handful of cases. Genetic investigation involving patients with defective mitochondrial translation led us to the discovery of novel mutations in the mitochondrial elongation factor G1 (EFG1) in one affected baby and, for the first time, in the mitochondrial elongation factor Tu (EFTu) in another one. Both patients were affected by severe lactic acidosis and rapidly progressive, fatal encephalopathy. The EFG1-mutant patient had early-onset Leigh syndrome, whereas the EFTu-mutant patient had severe infantile macrocystic leukodystrophy with micropolygyria. Structural modeling enabled us to make predictions about the effects of the mutations at the molecular level. Yeast and mammalian cell systems proved the pathogenic role of the mutant alleles by functional complementation in vivo. Nuclear-gene abnormalities causing mitochondrial translation defects represent a new, potentially broad field of mitochondrial medicine. Investigation of these defects is important to expand the molecular characterization of mitochondrial disorders and also may contribute to the elucidation of the complex control mechanisms, which regulate this fundamental pathway of mtDNA homeostasis. PMID:17160893

  1. Mitochondrial divergence between slow- and fast-aging garter snakes.

    Science.gov (United States)

    Schwartz, Tonia S; Arendsee, Zebulun W; Bronikowski, Anne M

    2015-11-01

    Mitochondrial function has long been hypothesized to be intimately involved in aging processes--either directly through declining efficiency of mitochondrial respiration and ATP production with advancing age, or indirectly, e.g., through increased mitochondrial production of damaging free radicals with age. Yet we lack a comprehensive understanding of the evolution of mitochondrial genotypes and phenotypes across diverse animal models, particularly in species that have extremely labile physiology. Here, we measure mitochondrial genome-types and transcription in ecotypes of garter snakes (Thamnophis elegans) that are adapted to disparate habitats and have diverged in aging rates and lifespans despite residing in close proximity. Using two RNA-seq datasets, we (1) reconstruct the garter snake mitochondrial genome sequence and bioinformatically identify regulatory elements, (2) test for divergence of mitochondrial gene expression between the ecotypes and in response to heat stress, and (3) test for sequence divergence in mitochondrial protein-coding regions in these slow-aging (SA) and fast-aging (FA) naturally occurring ecotypes. At the nucleotide sequence level, we confirmed two (duplicated) mitochondrial control regions one of which contains a glucocorticoid response element (GRE). Gene expression of protein-coding genes was higher in FA snakes relative to SA snakes for most genes, but was neither affected by heat stress nor an interaction between heat stress and ecotype. SA and FA ecotypes had unique mitochondrial haplotypes with amino acid substitutions in both CYTB and ND5. The CYTB amino acid change (Isoleucine → Threonine) was highly segregated between ecotypes. This divergence of mitochondrial haplotypes between SA and FA snakes contrasts with nuclear gene-flow estimates, but correlates with previously reported divergence in mitochondrial function (mitochondrial oxygen consumption, ATP production, and reactive oxygen species consequences).

  2. Mitochondrial cytochrome c oxidase deficiency.

    Science.gov (United States)

    Rak, Malgorzata; Bénit, Paule; Chrétien, Dominique; Bouchereau, Juliette; Schiff, Manuel; El-Khoury, Riyad; Tzagoloff, Alexander; Rustin, Pierre

    2016-03-01

    As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.

  3. Safety Evaluation of Highway Tunnel-Entrance Illuminance Transition Based on Eye-Pupil Changes

    Directory of Open Access Journals (Sweden)

    Zhigang Du

    2014-10-01

    Full Text Available Utilizing the EMR-8B eye-tracker system, the pupil changes of eight drivers were monitored when they drove through 26 typical highway tunnels. Based on the test results, the driver’s pupil areas and pupil illuminance were found to be in a power function relationship at tunnel entrances. Furthermore, a quantitative relationship between the pupil area and its critical velocity was established, and the ratio of pupil area’s velocity in relation to its critical velocity was used to evaluate the lighting transitions and to establish the ideal curve of pupil illuminance at tunnel entrances. The results demonstrated that the relationship between the pupil illuminance of the tunnel entrance and the driver’s pupil areas conforms to the Stevens law found in experimental psychology; severe pupil illuminance transition within the range of 10 metres of the existing highway tunnel entrances, which results in great visual load, is in urgent need of improvement.

  4. A numerical solution for the entrance region of non-newtonian flow in annuli

    Directory of Open Access Journals (Sweden)

    Maia M.C.A.

    2003-01-01

    Full Text Available Continuity and momentum equations applied to the entrance region of an axial, incompressible, isothermal, laminar and steady flow of a power-law fluid in a concentric annulus, were solved by a finite difference implicit method. The Newtonian case was solved used for validation of the method and then compared to reported results. For the non-Newtonian case a pseudoplastic power-law model was assumed and the equations were transformed to obtain a pseudo-Newtonian system which enabled its solution using the same technique as that used for the Newtonian case. Comparison of the results for entrance length and pressure drop with those available in the literature showed a qualitative similarity, but significant quantitative differences. This can be attributed to the differences in entrance geometries and the definition of asymptotic entrance length.

  5. Should College Entrance Exam Results Be Made Public,or Kept Private?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The college entrance examination, usually called gaokao in China, is considered the most important test for middle school graduates. It’s the test that makes or breaks the futures of students as the outcome determines who

  6. Alleviating the Entrance to Serious Games by Exploring the Use of Commonly Available Tools

    NARCIS (Netherlands)

    Van Rosmalen, Peter; Klemke, Roland; Westera, Wim

    2011-01-01

    Van Rosmalen, P., Klemke, R., & Westera, W. (2011, 20-21 October). Alleviating the Entrance to Serious Games by Exploring the Use of Commonly Available Tools. Presentation at 5th European Conference on Games Based Learning, Athens, Greece.

  7. Work on the Building 4 car park and closure of Entrance A

    CERN Multimedia

    2015-01-01

    From 6 July to 31 October 2015, the GS department will be carrying out renovation work on the car park next to Buildings 4 and 5. This work is aimed at improving safety on and around the car park for all users, particularly children attending the nursery school, pedestrians and cyclists.   Layout of the upcoming car park.   The work on the car park will be conducted in two stages so that half of the parking spaces will always be available, in order to limit the impact on users as much as possible (the closed-off areas will be clearly indicated). When the work is completed, the car park will have been completely renovated, with new surfacing and road markings, high-quality lighting and more parking spaces (+5%). During the work, part of the car park will be inaccessible, which is likely to make it more difficult to find a parking space. We therefore invite you to park in the Globe car park during this period. The renovation work will also affect Entrance A (Route Bell), which will be fitt...

  8. Experimental study of pedestrian inflow in a room with a separate entrance and exit

    Science.gov (United States)

    Liu, Xiaodong; Song, Weiguo; Fu, Libi; Fang, Zhiming

    2016-01-01

    Pedestrian inflow process frequently occurs in various pedestrian facilities in our daily life. Great importance should be attached to the study of this process. In this paper, we explore the pedestrian inflow process in a room with a separate entrance and exit. Two kinds of experiments are conducted: experiment 1 has no inactive persons and primarily focuses on analyzing the features of the normal pedestrian inflow process and analyzing the representative spatial parameters in the steady state, while experiment 2 involves the influence of the inactive persons. In order to quantitatively discuss the distribution of pedestrians in the steady state, we adopt several analytical methods, such as the Voronoi diagram method, proxemics, and point pattern analysis. Some features of the inflow process are captured. The distribution of pedestrians in the steady state is not uniform. The proxemics and attraction to the exit are both considered to affect pedestrians' distribution in the inflow process. The presence of inactive persons may have an impact on both the inflow and outflow processes. Practical suggestions are provided for the managers of pedestrian facilities.

  9. THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism.

    Science.gov (United States)

    Nguyen, Chi Huu; Krewenka, Christopher; Radad, Khaled; Kranner, Barbara; Huber, Alexandra; Duvigneau, Johanna Catharina; Miller, Ingrid; Moldzio, Rudolf

    2016-12-01

    Aging-related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Δ9-Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate-induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase-3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate-induced neurotoxicity. Moreover, THC significantly counteracted the glutamate-induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration-dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti-apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Mitochondrial DNA response to high altitude: a new perspective on high-altitude adaptation.

    Science.gov (United States)

    Luo, Yongjun; Yang, Xiaohong; Gao, Yuqi

    2013-08-01

    Mitochondria are the energy metabolism centers of the cell. More than 95% of cellular energy is produced by mitochondrial oxidative phosphorylation. Hypoxia affects a wide range of energy generation and consumption processes in animals. The most important mechanisms limiting ATP consumption increase the efficiency of ATP production and accommodate the reduced production of ATP by the body. All of these mechanisms relate to changes in mitochondrial function. Mitochondrial function can be affected by variations in mitochondrial DNA, including polymorphisms, content changes, and deletions. These variations play an important role in acclimatization or adaptation to hypoxia. In this paper, the association between mitochondrial genome sequences and high-altitude adaptation is reviewed.

  11. On the border. Value and function of museum’s entrance hall and its symbolic meaning

    Directory of Open Access Journals (Sweden)

    Lucia Tarantino

    2013-11-01

    Full Text Available The text aims to analyze the museum entrance halls, mainly from the point of view of the growing phenomenon of mass tourism. The entrance space is examined not only for its functional characters but also for its symbolic power in structuring or changing the historical and cultural identity of the entire museum’s building. Both in new projects and in restoration of ancient museum buildings, in fact, contemporary architects seems to be increasingly attracted by this design aspect.

  12. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  13. High endemism at cave entrances: a case study of spiders of the genus Uthina

    Science.gov (United States)

    Yao, Zhiyuan; Dong, Tingting; Zheng, Guo; Fu, Jinzhong; Li, Shuqiang

    2016-01-01

    Endemism, which is typically high on islands and in caves, has rarely been studied in the cave entrance ecotone. We investigated the endemism of the spider genus Uthina at cave entrances. Totally 212 spiders were sampled from 46 localities, from Seychelles across Southeast Asia to Fiji. They mostly occur at cave entrances but occasionally appear at various epigean environments. Phylogenetic analysis of DNA sequence data from COI and 28S genes suggested that Uthina was grouped into 13 well-supported clades. We used three methods, the Bayesian Poisson Tree Processes (bPTP) model, the Bayesian Phylogenetics and Phylogeography (BPP) method, and the general mixed Yule coalescent (GMYC) model, to investigate species boundaries. Both bPTP and BPP identified the 13 clades as 13 separate species, while GMYC identified 19 species. Furthermore, our results revealed high endemism at cave entrances. Of the 13 provisional species, twelve (one known and eleven new) are endemic to one or a cluster of caves, and all of them occurred only at cave entrances except for one population of one species. The only widely distributed species, U. luzonica, mostly occurred in epigean environments while three populations were found at cave entrances. Additionally, eleven new species of the genus are described. PMID:27775081

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

    Energy Technology Data Exchange (ETDEWEB)

    Wills, Lauren P. [MitoHealth Inc., Charleston, SC 29403 (United States); Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Beeson, Craig C. [MitoHealth Inc., Charleston, SC 29403 (United States); Peterson, Yuri K. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

    2013-10-15

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

  15. The Entrance of Pyroclastic Flows into the Sea

    Science.gov (United States)

    Freundt, A.

    2001-12-01

    Explosive volcanoes, especially in subduction-zone and ocean-island settings, can generate pyroclastic flows that enter the sea. Geologic constraints on the interaction mechanisms and hazards are poor since resulting deposits hardly survive coastal erosion. The entrance of hot pyroclastic flows into water has been observed experimentally by letting shooting granular flows of ignimbrite ash heated to up to 420oC run down a chute into a water-filled tank. Flows of relatively cool ash, less than 150oC, impulsively displace some near-shore water generating a tsunami wave and then separate into a fine-ash over-water surge formed near shore and the main, coarser and denser material penetrating the water surface to form a turbulent mixing zone which advances downstream as long as the granular flow is maintained. Pumice floats to the surface, lithics and coarse ash fall out onto the floor, but ash remaining in suspension forms a turbidity current flowing down the tank. At temperatures above 250oC, almost all ash is initially transported along the water surface, rather than immediately penetrating it. Transport over water is facilitated by steam explosions derived from mixing of some of the ash with water across the surface. Ash fountains throw dry ash forward before it contacts the water, triggering the next steam explosion farther away from shore where fountains collapse onto the water surface. Each time ash and heat are consumed by mixing; the distance to where explosions extend thus depends on initial mass flux and temperature. Most fine ash forms an ash-cloud surge travelling over water, loosing sediment plumes that unite on the tank floor to form a turbidity current. Tsunami waves generated by coastal impact appear to be additionally driven by surface-water displacement by massive ash-input from ash fountains. Grain size distribution is also critical in determining interaction processes. Moderately well sorted medium ash generates strong steam explosions and becomes

  16. Engineering geologic conditions at the sinkhole entrance to Logan Cave, Benton County, Arkansas

    Science.gov (United States)

    Schulz, William H.; McKenna, Jonathan P.

    2004-01-01

    Logan Cave, located in Benton County, Arkansas, is inhabited by several endangered and threatened species. The cave and surrounding area was designated a National Wildlife Refuge under the control of the U.S. Fish and Wildlife Service (USFWS) in 1989. Cave researchers access the cave through a steep-sided sinkhole entrance, which also is one of the two access points used by endangered bats. There is evidence of instability of one of the entrance slopes that has raised concerns that the entrance could close if slope failure was to occur. At the request of USFWS, we performed an engineering geologic investigation of the sinkhole to evaluate stability of this slope, which is comprised of soil, and other mechanisms of sediment transport into the cave entrance. The investigation included engineering geologic mapping, sampling and laboratory testing of subsurface geologic materials, and slope-stability analysis. We found that the sinkhole slope that extends into the entrance of the cave is comprised of sandy and gravelly soil to the depths explored (6.4 meters). This soil likely was deposited as alluvium within a previous, larger sinkhole. Based on properties of the alluvium, geometry of the slope, and results of finite-element slope-stability analyses, we conclude that the slope is marginally stable. Future failures of the slope probably would be relatively thin and small, thus several would be required to completely close the cave entrance. However, sediment is accumulating within the cave entrance due to foot traffic of those accessing the cave, surface-water erosion and transport, and shallow slope failures from the other sinkhole slopes. We conclude that the entrance will be closed by sediment in the future, similar to another entrance that we identified that completely closed in the past. Several measures could be taken to reduce the potential for closure of the cave entrance, including periodic sediment removal, installation of materials that reduce erosion by

  17. Involvement of the mitochondrial compartment in human NCL fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Pezzini, Francesco; Gismondi, Floriana [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Tessa, Alessandra [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Tonin, Paola [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Carrozzo, Rosalba [IRCCS Bambino Gesu Hospital-Molecular Medicine Unit, Roma (Italy); Mole, Sara E. [MRC Laboratory for Molecular Cell Biology, Molecular Medicines Unit, UCL Institute of Child Health and Department of Genetics, Evolution and Environment, University College London (United Kingdom); Santorelli, Filippo M. [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Simonati, Alessandro, E-mail: alessandro.simonati@univr.it [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. Black-Right-Pointing-Pointer Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. Black-Right-Pointing-Pointer 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.

  18. Effects of nonuniform Mach-number entrance on scramjet nozzle flowfield and performance

    Science.gov (United States)

    Zhang, Pu; Xu, Jinglei; Quan, Zhibin; Mo, Jianwei

    2016-12-01

    Considering the non-uniformities of nozzle entrance influenced by the upstream, the effects of nonuniform Mach-number coupled with shock and expansion-wave on the flowfield and performances of single expansion ramp nozzle (SERN) are numerically studied using Reynolds-Averaged Navier-Stokes equations. The adopted Reynolds-averaged Navier-Stokes methodology is validated by comparing the numerical results with the cold experimental data, and the average method used in this paper is discussed. Uniform and nonuniform facility nozzles are designed to generate different Mach-number profile for the inlet of SERN, which is direct-connected with different facility nozzle, and the whole flowfield is simulated. Because of the coupling of shock and expansion-wave, flow direction of nonuniform SERN entrance is distorted. Compared with Mach contour of uniform case, the line is more curved for coupling shock-wave entrance (SWE) case, and flatter for the coupling expansion-wave entrance (EWE) case. Wall pressure distribution of SWE case appears rising region, whereas decreases like stairs of EWE case. The numerical results reveal that the coupled shock and expansion-wave play significant roles on nozzle performances. Compared with the SERN performances of uniform entrance case at the same work conditions, the thrust of nonuniform entrance cases reduces by 3-6%, pitch moment decreases by 2.5-7%. The negative lift presents an incremental trend with EWE while the situation is the opposite with SWE. These results confirm that considering the entrance flow parameter nonuniformities of a scramjet nozzle coupled with shock or expansion-wave from the upstream is necessary.

  19. Keshan disease and mitochondrial cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    YANG Fuyu

    2006-01-01

    Keshan disease (KD) is a potentially fatal form of cardiomyopathy (disease of the heart muscle) endemic in certain areas of China. From 1984 to 1986, a national comprehensive scientific investigation on KD in Chuxiong region of Yunnan Province in the southwest China was conducted. The investigation team was composed of epidemiologists, clinic doctors, pathologists, biochemists, biophysicists and specialists in ecological environment. Results of pathological, biochemical and biophysical as well as clinical studies showed: an obvious increase of enlarged and swollen mitochondria with distended crista membranes in myocardium from patients with KD; significant reductions in the activity of oxidative phosphorylation (succinate dehydrogenase, cytochrome oxidase, succinate oxidase, H+-ATPase) of affected mitochondria; decrease in CoQ, cardiolipin, Se and GSHPx activity, while obvious increase in the Ca2+ content. So, it was suggested that mitochondria are the predominant target of the pathogenic factors of KD. Before Chuxiong KD survey only a few cases of mitochondrial cardiomyopathy were studied. During the multidisciplinary scientific investigation on KD in Chuxiong a large amount of samples from KD cases and the positive controls were examined. On the basis of the results obtained it was suggested that KD might be classified as a "Mitochondrial Cardiomyopathy" endemic in China. This is one of the achievements in the three years' survey in Chuxiong and is valuable not only to the deeper understanding of pathogenic mechanism of KD but also to the study of mitochondrial cardiomyopathy in general.Keshan disease is not a genetic disease, but is closely related to the malnutrition (especially microelement Se deficiency). KD occurs along a low Se belt, and Se supplementation has been effective in prevention of such disease. The incidence of KD has sharply decreased along with the steady raise of living standard and realization of preventive measures. At present, patients of

  20. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

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

  1. Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in mitochondrial myopathy patients.

    Science.gov (United States)

    Nabben, Miranda; Schmitz, Joep P J; Ciapaite, Jolita; Le Clercq, Carlijn M P; van Riel, Natal A; Haak, Harm R; Nicolay, Klaas; de Coo, Irenaeus F; Smeets, Hubert J M; Praet, Stephan F; van Loon, Luc J C; Prompers, Jeanine J

    2017-02-08

    Muscle weakness and exercise intolerance negatively affect the quality of life of mitochondrial myopathy patients. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated if 1 week of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in mitochondrial myopathy patients. Ten mitochondrial myopathy patients (40 ± 5 years, maximal whole-body oxygen uptake = 21.2 ± 3.2 mL/min/kg body weight, maximal workload = 122 ± 26 W) received 8.5 mg/kg body weight/day of inorganic nitrate (~7 mmol) for 8 days. Whole-body oxygen consumption at 50% of the maximal workload, in vivo skeletal muscle oxidative capacity (evaluated from post-exercise phosphocreatine recovery using (31)P magnetic resonance spectroscopy) and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a 6-fold increase in plasma nitrate levels, nitrate supplementation did not affect whole-body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for mitochondrial myopathy patients was evaluated. We conclude that 1 week of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.

  2. The mitochondrial connection in auditory neuropathy.

    Science.gov (United States)

    Cacace, Anthony T; Pinheiro, Joaquim M B

    2011-01-01

    'Auditory neuropathy' (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich's ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.

  3. Investigate Factor Effecting Of Students’ Achievement on High School Entrance Exam-(SBS Respect to the Different Variables

    Directory of Open Access Journals (Sweden)

    Mustafa METİN

    2013-04-01

    Full Text Available The aim of study is to investigate factor affecting of secondary school students’ achievement on high school entrance exam (SBS respect to the different variables. The study was carried out at fall semester of 2012 with 991 students educating primary schools in Artvin. In this study survey method was used and data gathered with questionnaire consists of 40 items. As a result of study, it was determinate that effects of family, educational facilities, teachers and personal characters on students’ achievement are at high level. There is no different between gender and students achievement (p>0.05, although there are different between grade level, family incomes, graduation types of mother and father and students achievement (p<0.05.

  4. United Mitochondrial Disease Foundation

    Science.gov (United States)

    ... to Mitochondrial Disease FAQ's MitoFirst Handbook More Information Mito 101 Symposium Archives Get Connected Find an Event Adult Advisory Council Team Ask The Mito Doc Grand Rounds Kids & Teens Medical Child Abuse ...

  5. 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....

  6. [Mitochondrial diseases and stroke].

    Science.gov (United States)

    Irimia, P; Oliveros-Cid, A; Martínez-Vila, E

    1998-04-01

    We review the mitochondrial diseases in which cerebrovascular changes are seen, such as the MERRF syndrome (myoclonic epilepsy and ragged red fibers) or the Kearns-Sayre syndrome (progressive external ophthalmoplegia, retinitis pigmentaria, cerebellar disorders and disorders of cardiac conduction), focusing on the syndrome involving mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We consider the different clinical aspects, diagnostic methods, pathophysiological mechanisms of the cerebrovascular involvement as well as therapeutic approaches.

  7. Mitochondrial protection by resveratrol.

    Science.gov (United States)

    Ungvari, Zoltan; Sonntag, William E; de Cabo, Rafael; Baur, Joseph A; Csiszar, Anna

    2011-07-01

    Mitochondrial dysfunction and oxidative stress are thought to play important roles in mammalian aging. Resveratrol is a plant-derived polyphenol that exerts diverse antiaging activities, mimicking some of the molecular and functional effects of dietary restriction. This review focuses on the molecular mechanisms underlying the mitochondrial protective effects of resveratrol, which could be exploited for the prevention or amelioration of age-related diseases in the elderly.

  8. Squeezing at entrance of proton transport pathway in proton-translocating pyrophosphatase upon substrate binding.

    Science.gov (United States)

    Huang, Yun-Tzu; Liu, Tseng-Huang; Lin, Shih-Ming; Chen, Yen-Wei; Pan, Yih-Jiuan; Lee, Ching-Hung; Sun, Yuh-Ju; Tseng, Fan-Gang; Pan, Rong-Long

    2013-07-05

    Homodimeric proton-translocating pyrophosphatase (H(+)-PPase; EC 3.6.1.1) is indispensable for many organisms in maintaining organellar pH homeostasis. This unique proton pump couples the hydrolysis of PPi to proton translocation across the membrane. H(+)-PPase consists of 14-16 relatively hydrophobic transmembrane domains presumably for proton translocation and hydrophilic loops primarily embedding a catalytic site. Several highly conserved polar residues located at or near the entrance of the transport pathway in H(+)-PPase are essential for proton pumping activity. In this investigation single molecule FRET was employed to dissect the action at the pathway entrance in homodimeric Clostridium tetani H(+)-PPase upon ligand binding. The presence of the substrate analog, imidodiphosphate mediated two sites at the pathway entrance moving toward each other. Moreover, single molecule FRET analyses after the mutation at the first proton-carrying residue (Arg-169) demonstrated that conformational changes at the entrance are conceivably essential for the initial step of H(+)-PPase proton translocation. A working model is accordingly proposed to illustrate the squeeze at the entrance of the transport pathway in H(+)-PPase upon substrate binding.

  9. RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity

    DEFF Research Database (Denmark)

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

    2012-01-01

    RECQL4 is associated with Rothmund-Thomson Syndrome (RTS), a rare autosomal recessive disorder characterized by premature aging, genomic instability, and cancer predisposition. RECQL4 is a member of the RecQ helicase family, and has many similarities to WRN protein, which is also implicated...... 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...

  10. Mitochondrial gene therapy augments mitochondrial physiology in a Parkinson's disease cell model.

    Science.gov (United States)

    Keeney, Paula M; Quigley, Caitlin K; Dunham, Lisa D; Papageorge, Christina M; Iyer, Shilpa; Thomas, Ravindar R; Schwarz, Kathleen M; Trimmer, Patricia A; Khan, Shaharyar M; Portell, Francisco R; Bergquist, Kristen E; Bennett, James P

    2009-08-01

    Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic function and prevent further cell death. We developed a technology ("ProtoFection") that uses recombinant human mitochondrial transcription factor A (TFAM) engineered with an N-terminal protein transduction domain (PTD) followed by the SOD2 mitochondrial localization signal (MLS) to deliver mtDNA cargo to the mitochondria of living cells. MTD-TFAM (MTD = PTD + MLS = "mitochondrial transduction domain") binds mtDNA and rapidly transports it across plasma membranes to mitochondria. For therapeutic proof-of-principle we tested ProtoFection technology in Parkinson's disease cybrid cells, using mtDNA generated from commercially available human genomic DNA (gDNA; Roche). Nine to 11 weeks after single exposures to MTD-TFAM + mtDNA complex, PD cybrid cells with impaired respiration and reduced mtDNA genes increased their mtDNA gene copy numbers up to 24-fold, mtDNA-derived RNAs up to 35-fold, TFAM and ETC proteins, cell respiration, and mitochondrial movement velocities. Cybrid cells with no or minimal basal mitochondrial impairments showed reduced or no responses to treatment, suggesting the possibility of therapeutic selectivity. Exposure of PD but not control cybrid cells to MTD-TFAM protein alone or MTD-TFAM + mtDNA complex increased expression of PGC-1alpha, suggesting activation of mitochondrial biogenesis. ProtoFection technology for mitochondrial gene therapy holds promise for improving bioenergetic function in impaired PD neurons and needs additional development to define its pharmacodynamics and delineate its molecular mechanisms. It also is unclear whether single-donor gDNA for generating mtDNA would be a preferred therapeutic compared with the pooled

  11. Peripheral neuropathy in mitochondrial disorders.

    Science.gov (United States)

    Pareyson, Davide; Piscosquito, Giuseppe; Moroni, Isabella; Salsano, Ettore; Zeviani, Massimo

    2013-10-01

    Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance.

  12. Ocular manifestations of mitochondrial disease

    Directory of Open Access Journals (Sweden)

    S. D. Mathebula

    2012-12-01

    Full Text Available Mitochondrial disease caused by mutations in mitochondrial DNA is recognized as one of the most common causes of inherited neurological disease. Neuro-ophthalmic manifestations are a common feature of mitochondrial disease.  Optic atrophy causing central visual loss is the dominant feature of mitochondrial DNA diseases. Nystagmus is also encountered in mitochondrial disease.Although optometrists are not involved with the management of mitochondrial disease, they are likely to see more patients with this disease. Oph-thalmic examination forms part of the clinical assessment of mitochondrial disease. Mitochondrial disease should be suspected in any patient with unexplained optic neuropathy, ophthalmoplegia, pigmentary retinopathy or retrochiasmal visual loss. Despite considerable advances in the under-standing of mitochondrial genetics and the patho-genesis of mtDNA diseases, no effective treatment options are currently available for patients withmitochondrial dysfunction. (S Afr Optom 201271(1 46-50

  13. Entrance channel effect with stable and radioactive beams using dynamical cluster decay model

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Raj, E-mail: rajkumarfzr@gmail.com [Dipartimento di Fisica “Galileo Galilei” and INFN, University of Padova, Padova-35131 (Italy); Jain, Deepika [School of Physics and Material Science, Thapar University, Patiala-147004 (India)

    2014-09-15

    The decay of hot and rotating {sup 172}Yb*, formed in two entrance channels {sup 124}Sn + {sup 48}Ca and {sup 132}Sn + {sup 40}Ca, is studied using the dynamical cluster-decay model. The effect of entrance channel, deformations (up to β{sub 2}), barrier modification and fusion enhancement are addressed. The decay pattern of compound system, formed in different channels at comparable energy around the barrier, shows change in magnitude with structure remains almost same. There is an increase in the fusion probability with decrease in barrier modification, which leads to fusion enhancement at low energies. The higher ℓ values are contributing for {sup 132}Sn + {sup 40}Ca channel at lower energies as compare to {sup 124}Sn + {sup 48}Ca. It is inferred that with the use of stable and radioactive beam, forming same compound nucleus, the entrance channel dependence changes with the excitation energy.

  14. Mitochondrial diseases: therapeutic approaches.

    Science.gov (United States)

    DiMauro, Salvatore; Mancuso, Michelangelo

    2007-06-01

    Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. In this review, we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is centered on combating lactic acidosis, but extends to other metabolites. Attempts to bypass blocks in the respiratory chain by administration of electron acceptors have not been successful, but this may be amenable to genetic engineering. Administration of metabolites and cofactors is the mainstay of real-life therapy and is especially important in disorders due to primary deficiencies of specific compounds, such as carnitine or coenzyme Q10. There is increasing interest in the administration of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and improve exercise tolerance in patients with mitochondrial myopathies due to mitochondrial DNA (mtDNA) mutations. Gene therapy is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include, for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes into normal nuclear DNA genes (allotopic expression), importing cognate genes from other species, or correcting mtDNA mutations with specific restriction endonucleases. Germline therapy raises ethical problems but is being considered for prevention of maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is

  15. Wnt Signaling Prevents the Aβ Oligomer-Induced Mitochondrial Permeability Transition Pore Opening Preserving Mitochondrial Structure in Hippocampal Neurons

    Science.gov (United States)

    Arrázola, Macarena S.; Ramos-Fernández, Eva; Cisternas, Pedro; Ordenes, Daniela; Inestrosa, Nibaldo C.

    2017-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through the induction of the mitochondrial permeability transition pore (mPTP). The mPTP is a non-selective pore that is formed under apoptotic conditions, disturbing mitochondrial structure and thus, neuronal viability. In AD, Aβ oligomers (Aβos) favor the opening of the pore, activating mitochondria-dependent neuronal cell death cascades. The Wnt signaling activated through the ligand Wnt3a has been described as a neuroprotective signaling pathway against amyloid-β (Aβ) peptide toxicity in AD. However, the mechanisms by which Wnt signaling prevents Aβos-induced neuronal cell death are unclear. We proposed here to study whether Wnt signaling protects neurons earlier than the late damages in the progression of the disease, through the preservation of the mitochondrial structure by the mPTP inhibition. To study specific events related to mitochondrial permeabilization we performed live-cell imaging from primary rat hippocampal neurons, and electron microscopy to analyze the mitochondrial morphology and structure. We report here that Wnt3a prevents an Aβos-induced cascade of mitochondrial events that leads to neuronal cell death. This cascade involves (a) mPTP opening, (b) mitochondrial swelling, (c) mitochondrial membrane potential loss and (d) cytochrome c release, thus leading to neuronal cell death. Furthermore, our results suggest that the activation of the Wnt signaling prevents mPTP opening by two possible mechanisms, which involve the inhibition of mitochondrial GSK-3β and/or the modulation of mitochondrial hexokinase II levels and activity. This study suggests a possible new approach for the treatment of AD from a mitochondrial perspective, and will also open new lines of study in the field of Wnt signaling in neuroprotection

  16. Determining CO2-brine relative permeability and capillary pressure simultaneously: an insight to capillary entrance and end effects

    Science.gov (United States)

    Chen, X.; Kianinejad, A.; DiCarlo, D. A.

    2014-12-01

    CO2-brine relative permeability relations are important parameters in modeling scenarios such as CO2 sequestration in saline aquifers and CO2 enhanced recovery in oil reservoir. Many steady-state experimental studies on CO2-brine relative permeability showed that the CO2-brine relative permeability differs greatly from typical oil-brine relative permeability. Particularly, they reported a very small endpoint CO2 relative permeability of 0.1~0.2 at a relative high residual water saturation of 0.4~0.6. In this study, we hypothesize the measured low endpoint CO2 relative permeability in previous studies was an experimental artifact that is primary due to low CO2 viscosity. We conducted steady-state CO2 drainage experiments by co-injecting equlibrated CO2 and brine into a long (60.8 cm) and low permeability (116-mD) Berea sandstone core at 20 °C and 1500 psi. During every experiment, both the overall pressure drop across the core and the pressure drops of the five independent and continuous sections of the core were monitored. The in-situ saturation was measured with a medical X-ray Computed Tomography (CT) scanner. In the center three sections where saturation was uniform, we determined the relative permeability to both brine and CO2 phases. In the entrance and exit sections, both measured pressure gradients and saturation were non-uniform. To cope with this, we make several self-consistent assumptions that reveal the nature of capillary entrance and effect in steady-state two-phase core flooding experiments. Based on these assumptions we determined the relative permeability to CO2 and CO2-brine capillary pressure simultaneously using measured pressure drops. We found: (1) a much higher endpoint CO2 relative permeability of 0.58 at a water saturation of 48%, (2) the entrance region with non-uniform saturation expanded CO2 relative permeability data to much lower water saturation, (3) the determined CO2-brine capillary pressure curve is self-consistent and matches

  17. A national perspective on prenatal testing for mitochondrial disease.

    Science.gov (United States)

    Nesbitt, Victoria; Alston, Charlotte L; Blakely, Emma L; Fratter, Carl; Feeney, Catherine L; Poulton, Joanna; Brown, Garry K; Turnbull, Doug M; Taylor, Robert W; McFarland, Robert

    2014-11-01

    Mitochondrial diseases affect >1 in 7500 live births and may be due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Genetic counselling for families with mitochondrial diseases, especially those due to mtDNA mutations, provides unique and difficult challenges particularly in relation to disease transmission and prevention. We have experienced an increasing demand for prenatal diagnostic testing from families affected by mitochondrial disease since we first offered this service in 2007. We review the diagnostic records of the 62 prenatal samples (17 mtDNA and 45 nDNA) analysed since 2007, the reasons for testing, mutation investigated and the clinical outcome. Our findings indicate that prenatal testing for mitochondrial disease is reliable and informative for the nuclear and selected mtDNA mutations we have tested. Where available, the results of mtDNA heteroplasmy analyses from other family members are helpful in interpreting the prenatal mtDNA test result. This is particularly important when the mutation is rare or the mtDNA heteroplasmy is observed at intermediate levels. At least 11 cases of mitochondrial disease were prevented following prenatal testing, 3 of which were mtDNA disease. On the basis of our results, we believe that prenatal testing for mitochondrial disease is an important option for couples where appropriate genetic analyses and pre/post-test counselling can be provided.

  18. Neurological mitochondrial cytopathies.

    Directory of Open Access Journals (Sweden)

    Mehndiratta M

    2002-04-01

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

  19. Mitochondrial fusion and inheritance of the mitochondrial genome.

    Science.gov (United States)

    Takano, Hiroyoshi; Onoue, Kenta; Kawano, Shigeyuki

    2010-03-01

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

  20. Mitochondrial Myopathy with DNA Deletions

    OpenAIRE

    J Gordon Millichap

    1992-01-01

    Deletions of mitochondrial DNA (mtDNA) are reported in 19 of 56 patients with mitochondrial myopathy examined in the Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN.

  1. Mitochondrial calcium uptake.

    Science.gov (United States)

    Williams, George S B; Boyman, Liron; Chikando, Aristide C; Khairallah, Ramzi J; Lederer, W J

    2013-06-25

    Calcium (Ca(2+)) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca(2+) levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca(2+) ([Ca(2+)]i) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca(2+) uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca(2+) uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca(2+) uniporter (MCU) candidate. This quantitative analysis yields four clear results: (i) under physiological conditions, Ca(2+) influx into the mitochondria via the MCU is small relative to other cytosolic Ca(2+) extrusion pathways; (ii) single MCU conductance is ∼6-7 pS (105 mM [Ca(2+)]), and MCU flux appears to be modulated by [Ca(2+)]i, suggesting Ca(2+) regulation of MCU open probability (P(O)); (iii) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (iv) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca(2+) critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca(2+) under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca(2+)]i, mitochondrial Ca(2+) uptake can increase 10- to 1,000-fold and begin to shape [Ca(2+)]i dynamics.

  2. Pharmacologic Effects on Mitochondrial Function

    Science.gov (United States)

    Cohen, Bruce H.

    2010-01-01

    The vast majority of energy necessary for cellular function is produced in mitochondria. Free-radical production and apoptosis are other critical mitochondrial functions. The complex structure, electrochemical properties of the inner mitochondrial membrane (IMM), and genetic control from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) are…

  3. Investigating the Association between Turkish Freshman's Multiple Intelligence Profiles and University Entrance Exam Performance

    Science.gov (United States)

    Atas, Sait; Erisen, Yavuz

    2016-01-01

    Even though curriculum designers in Turkey considered Gardner's multiple intelligence theory as one of the most important theories during the curricula reform in 2005, the university entrance examination system is still on the basis of the two intelligence areas only, mathematical-logical and linguistics intelligence. The aim of this study was to…

  4. Gender Bias and Caste Exclusion in Engineering Admission: Inferences from the Engineering Entrance Examination in Kerala

    Science.gov (United States)

    Rajasenan, D.

    2014-01-01

    The major problem of the engineering entrance examination is the exclusion of certain sections of the society in social, economic, regional and gender dimensions. This has seldom been taken for analysis towards policy correction. To lessen this problem a minor policy shift was prepared in the year 2011 with a 50-50 proportion in academic marks and…

  5. Sleep Patterns and Academic Performance during Preparation for College Entrance Exam in Chinese Adolescents

    Science.gov (United States)

    Wang, Guanghai; Ren, Fen; Liu, Zhijun; Xu, Guangxing; Jiang, Fan; Skora, Elizabeth; Lewin, Daniel S.

    2016-01-01

    Background: Deficient sleep is linked to detrimental outcomes in health and school performance for adolescents. This study characterized sleep patterns in Chinese adolescents preparing for the College Entrance Exam (CEE) and evaluated the association between sleep patterns, self-rated academic performance, and the CEE scores. Methods: A sample of…

  6. Yersinia ruckeri infection of rainbow trout: entrance portals and spread in the host

    DEFF Research Database (Denmark)

    Deshmukh, S.; Khimmakthong, U.; Chettri, J. K.;

    2013-01-01

    The portal of entrance of either formalin inactivated or live Yersinia ruckeri organism in rainbow trout fish was studied by applying immunohistochemistry and in-situ hybridization. The sequential study involved a specific monoclonal antibody and a specific oligonucleotide probe binding to Yersinia...

  7. 33 CFR 334.390 - Atlantic Ocean south of entrance to Chesapeake Bay; firing range.

    Science.gov (United States)

    2010-07-01

    ... to Chesapeake Bay; firing range. 334.390 Section 334.390 Navigation and Navigable Waters CORPS OF....390 Atlantic Ocean south of entrance to Chesapeake Bay; firing range. (a) The danger zone. A section... four (4) nautical miles. (3) Firing on the ranges will be suspended as long as any vessel is within...

  8. Search for entrance-channel dependence in the population of superdeformed bands in {sup 191}Hg

    Energy Technology Data Exchange (ETDEWEB)

    Soramel, F.; Khoo, T.L.; Janssens, R.V.F. [and others

    1995-08-01

    The population intensity of some SD bands in the mass 150 region were observed to depend on the mass symmetry of the entrance channel in the fusion reaction. The authors raised the possibility that the population of SD bands had a memory of the entrance channel. To check this interesting possibility, we made measurements of the population intensities of superdeformed (SD) bands in the {sup 160}Gd({sup 36}S,5n){sup 191}Hg and {sup 130}Te({sup 64}Ni,3n){sup 191}Hg reactions. To ensure that any observed effect was not due to a simple angular momentum difference in the entrance channels, we also measured the average entry points and spin distributions of normal and SD states in {sup 191}Hg in the two reactions. The entry points and spin distributions for {sup 191}Hg are the same and, indeed, so are the SD intensities in the two reactions. Hence, no entrance-channel effect is observed in the population of the SD band in {sup 191}Hg, in contrast with data for SD bands in the mass 150 regions. We suggest that the effect observed previously in the mass 150 region is due to an angular momentum effect. A letter reporting our results was submitted for publication.

  9. The Entrance and Exit Effects in Small Electrochemical Filter-Press Reactors Used in the Laboratory

    Science.gov (United States)

    Frias-Ferrer, Angel; Gonzalez-Garcia, Jose; Saez, Veronica; Exposito, Eduardo; Sanchez-Sanchez, Carlos M.; Mantiel, Vicente; Walsh, Frank C.; Aldaz, Antonio; Walsh, Frank C.

    2005-01-01

    A laboratory experiment designed to examine the entrance and exit effects in small electrochemical filter-press reactors used in the laboratory is presented. The single compartment of the filter-press reactor is filled with different turbulence promoters to study their influence as compared to the empty configuration.

  10. Toward Implementing Computer-Assisted Foreign Language Assessment in the Official Spanish University Entrance Examination

    Science.gov (United States)

    Sanz, Ana Gimeno; Pavón, Ana Sevilla

    2015-01-01

    In 2008 the Spanish Government announced the inclusion of an oral section in the foreign language exam of the National University Entrance Examination during the year 2012 (Royal Decree 1892/2008, of 14 November 2008, Ministerio de Educación, Gobierno de España, 2008). Still awaiting the implementation of these changes, and in an attempt to offer…

  11. Entrance Exam Admission Policies on Ethnic Minorities and Equal Educational Rights for Minorities in China

    Science.gov (United States)

    Weiwei, Lang

    2010-01-01

    In 1977, the Chinese government reinstated the national unified college entrance exam enrollment system. As a part of this system, the government also implemented preferential policies on the enrollment of minorities that authorized the increase or decrease of exam scores and enrollment cutoff points; the policies were therefore seen as…

  12. Family Background and Students' Achievement on a University Entrance Exam in Brazil

    Science.gov (United States)

    Guimaraes, Juliana; Sampaio, Breno

    2013-01-01

    This paper examines the determinants of students' performance on the entrance test at Universidade Federal de Pernambuco, Brazil. Particular attention is paid to the importance of family background variables, such as parents' education and family income, on students' performance and how they relate to the probability of attending public schools…

  13. Spanish Pre-University Students' Use of English: CEA Results from the University Entrance Examination

    Science.gov (United States)

    Diez-Bedmar, Maria Belen

    2011-01-01

    In this paper an updated overview of the main errors that Spanish students make when writing the English exam in the University Entrance Examination is provided. To do so, a Computer-aided Error Analysis (CEA) (Dagneaux, Denness & Granger, 1998) was conducted on a representative sample of the students who took the exam in June 2008 in Jaen,…

  14. Correlation among High School Senior Students' Test Anxiety, Academic Performance and Points of University Entrance Exam

    Science.gov (United States)

    Karatas, Hakan; Alci, Bulent; Aydin, Hasan

    2013-01-01

    Test anxiety seems like a benign problem to some people, but it can be potentially serious when it leads to high levels of distress and academic failure. The aim of this study is to define the correlation among high school senior students' test anxiety, academic performance (GPA) and points of university entrance exam (UEE). The study group of…

  15. Predicting Success Using HESI A2 Entrance Tests in an Associate Degree Nursing Program

    Science.gov (United States)

    Bodman, Susan

    2012-01-01

    A challenge presented to nurse educators is retention of nursing students. This has led nursing faculty to review admission requirements and question how well entrance tests predict success in Associate Degree Nursing Programs. The purpose of this study was to investigate the relationship between the HESI Admission Assessment Exam (HESI A2) and…

  16. Learning beyond graduation: exploring newly qualified specialists' entrance into daily practice from a learning perspective.

    Science.gov (United States)

    Cuyvers, Katrien; Donche, Vincent; Van den Bossche, Piet

    2016-05-01

    The entrance of newly qualified medical specialists into daily practice is considered to be a stressful period in which curriculum support is absent. Although engaging in both personal and professional learning and development activities is recognized fundamental for lifelong professional competence, research on medical professionals' entrance into practice is scarce. This research aims to contribute to the framework of medical professionals' informal learning and outlines the results of an exploratory study on the nature of learning in daily practice beyond postgraduate training. Eleven newly qualified physicians from different specialized backgrounds participated in a phenomenographic study, using a critical incident method and a grounded theory approach. Results demonstrated that learning in the workplace is, to a large extent, informal and associated with a variety of learning experiences. Analysis shows that experiences related to diagnostics and treatments are important sources for learning. Furthermore, incidents related to communication, changing roles, policy and organization offer learning opportunities, and therefore categorized as learning experiences. A broad range of learning activities are identified in dealing with these learning experiences. More specifically, actively engaging in actions and interactions, especially with colleagues of the same specialty, are the most mentioned. Observing others, consulting written sources, and recognizing uncertainties, are also referred to as learning activities. In the study, interaction, solely or combined with other learning activities, are deemed as very important by specialists in the initial entrance into practice. These insights can be used to develop workplace structures to support the entrance into practice following postgraduate training.

  17. Historical Analysis of the Policy on the College Entrance System in South Korea

    Science.gov (United States)

    Choi, Hee Jun; Park, Ji-Hye

    2013-01-01

    The national college admission system has quite frequently been altered in South Korea since Korea was liberated from Japanese colonial rule in 1945. Nonetheless, there are still many ways in which the national college entrance system can be improved. This article initially analysed and synthesized the issues associated with the Korean college…

  18. Personal Well-Being of Gifted Students Following Participation in an Early College-Entrance Program

    Science.gov (United States)

    Boazman, Janette; Sayler, Michael

    2011-01-01

    In this study, life satisfaction and its correlates were explored through analysis of the experiences and psychological traits of highly gifted students who were accelerated into an early college-entrance program. Happiness, fulfillment in life, assuredness, and good dispositions are constructs that point toward positive character development and…

  19. Alleviating the Entrance to Serious Games by Exploring the Use of Commonly Available Tools

    NARCIS (Netherlands)

    Van Rosmalen, Peter; Klemke, Roland; Westera, Wim

    2011-01-01

    Van Rosmalen, P., Klemke, R., & Westera, W. (2011). Alleviating the Entrance to Serious Games by Exploring the Use of Commonly Available Tools. In D. Gouscos, & M. Meimaris (Eds.), Proceedings of the 5th European Conference on Games Based Learning (pp. 613-619), Athens, Greece. 20-21 October 2011.

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

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

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

  1. Wnt Signaling Prevents the Aβ Oligomer-Induced Mitochondrial Permeability Transition Pore Opening Preserving Mitochondrial Structure in Hippocampal Neurons

    OpenAIRE

    Arrázola, Macarena S.; Ramos-Fernández, Eva; Cisternas, Pedro; Ordenes, Daniela; Inestrosa, Nibaldo C.

    2017-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through the induction of the mitochondrial permeability transition pore (mPTP). The mPTP is a non-selective pore that is formed under apoptotic conditions, disturbing mitochondrial structure and thus, neuronal viability. In AD, Aβ oligomers (Aβos) favor the opening of ...

  2. Trichothecene Mycotoxins Inhibit Mitochondrial Translation—Implication for the Mechanism of Toxicity

    Directory of Open Access Journals (Sweden)

    Susan McCormick

    2011-12-01

    Full Text Available Fusarium head blight (FHB reduces crop yield and results in contamination of grains with trichothecene mycotoxins. We previously showed that mitochondria play a critical role in the toxicity of a type B trichothecene. Here, we investigated the direct effects of type A and type B trichothecenes on mitochondrial translation and membrane integrity in Saccharomyces cerevisiae. Sensitivity to trichothecenes increased when functional mitochondria were required for growth, and trichothecenes inhibited mitochondrial translation at concentrations, which did not inhibit total translation. In organello translation in isolated mitochondria was inhibited by type A and B trichothecenes, demonstrating that these toxins have a direct effect on mitochondrial translation. In intact yeast cells trichothecenes showed dose-dependent inhibition of mitochondrial membrane potential and reactive oxygen species, but only at doses higher than those affecting mitochondrial translation. These results demonstrate that inhibition of mitochondrial translation is a primary target of trichothecenes and is not secondary to the disruption of mitochondrial membranes.

  3. Loss of the SIN3 transcriptional corepressor results in aberrant mitochondrial function

    Directory of Open Access Journals (Sweden)

    Hüttemann Maik

    2010-07-01

    Full Text Available Abstract Background SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components. Results By monitoring RNA levels, we find that loss of SIN3 in Drosophila cultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeast sin3 null mutants exhibit very poor growth on non-fermentable carbon sources and show lower levels of ATP and reduced respiration rates. Conclusions The findings that both yeast and Drosophila SIN3 affect mitochondrial activity suggest an evolutionarily conserved role for SIN3 in the control of cellular energy production.

  4. The MLA Survey of Postsecondary Entrance and Degree Requirements for Languages Other Than English, 2009-10

    Science.gov (United States)

    Lusin, Natalia

    2012-01-01

    Since 1953, the MLA has conducted a survey of entrance and degree requirements for languages other than English. The surveys reveal trends over time and show how colleges and universities in the United States have added, dropped, or changed their requirements. Entrance and degree requirements are one measure of the value that an institution…

  5. Preventing Mitochondrial Fission Impairs Mitochondrial Function and Leads to Loss of Mitochondrial DNA

    OpenAIRE

    Parone, Philippe A.; Sandrine Da Cruz; Daniel Tondera; Yves Mattenberger; James, Dominic I.; Pierre Maechler; François Barja; Jean-Claude Martinou

    2008-01-01

    Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS). At t...

  6. Comparative Analysis of Water Quality between the Runoff Entrance and Middle of Recycling Irrigation Reservoirs

    Directory of Open Access Journals (Sweden)

    Haibo Zhang

    2015-07-01

    Full Text Available Recycling irrigation reservoirs (RIRs are an emerging aquatic ecosystem of critical importance, for conserving and protecting increasingly scarce water resources. Here, we compare water quality between runoff entrance and middle of four RIRs in nurseries in Virginia (VA and Maryland (MD. Surface water temperature (T and oxidation-reduction potential (ORP were lower in the middle than at the entrance, while the trend was opposite for dissolved oxygen (DO, pH and chlorophyll a (Chla. The magnitude of these differences between the entrance and middle decreased with increasing depth. These differences were magnified by water stratification from April to October. Minimum differences were observed for electrical conductivity (EC, total dissolved solids (TDS and turbidity (TUR. Cluster analyses were performed on water quality difference data to evaluate whether the differences vary with respect to reservoirs. Two clusters were formed with one consisting primarily of VA reservoirs, and the other consisting mostly of MD reservoirs in both years. Water quality in the middle and at the entrance of RIRs was expected to vary greatly because of runoff inflow. The two-point water quality differences observed here, although statistically significant, are not large enough to cause significant impact on crop health and productivity for most water quality parameters except pH. Additional analysis of outlet data shows that the range and magnitude of water quality difference between the middle and the outlet are comparable to those between the middle and entrance of RIRs. These results indicate that monitoring at a single point is sufficient to obtain reliable water quality estimates for most water quality parameters in RIRs except pH. This is important when considering the cost of labor and equipment necessary for documenting water quality in agricultural production systems. However, additional pH measurements are still necessary to make practical water quality

  7. Melatonin mitigates mitochondrial malfunction.

    Science.gov (United States)

    León, Josefa; Acuña-Castroviejo, Darío; Escames, Germane; Tan, Dun-Xian; Reiter, Russel J

    2005-01-01

    Melatonin, or N-acetyl-5-methoxytryptamine, is a compound derived from tryptophan that is found in all organisms from unicells to vertebrates. This indoleamine may act as a protective agent in disease conditions such as Parkinson's, Alzheimer's, aging, sepsis and other disorders including ischemia/reperfusion. In addition, melatonin has been proposed as a drug for the treatment of cancer. These disorders have in common a dysfunction of the apoptotic program. Thus, while defects which reduce apoptotic processes can exaggerate cancer, neurodegenerative disorders and ischemic conditions are made worse by enhanced apoptosis. The mechanism by which melatonin controls cell death is not entirely known. Recently, mitochondria, which are implicated in the intrinsic pathway of apoptosis, have been identified as a target for melatonin actions. It is known that melatonin scavenges oxygen and nitrogen-based reactants generated in mitochondria. This limits the loss of the intramitochondrial glutathione and lowers mitochondrial protein damage, improving electron transport chain (ETC) activity and reducing mtDNA damage. Melatonin also increases the activity of the complex I and complex IV of the ETC, thereby improving mitochondrial respiration and increasing ATP synthesis under normal and stressful conditions. These effects reflect the ability of melatonin to reduce the harmful reduction in the mitochondrial membrane potential that may trigger mitochondrial transition pore (MTP) opening and the apoptotic cascade. In addition, a reported direct action of melatonin in the control of currents through the MTP opens a new perspective in the understanding of the regulation of apoptotic cell death by the indoleamine.

  8. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    Michelle L Boland

    2013-12-01

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

  9. Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial-localization of tyrosine kinase Src and tyrosine phosphatase SHP2.

    Directory of Open Access Journals (Sweden)

    Qun S Zang

    Full Text Available Our previous research demonstrated that sepsis produces mitochondrial dysfunction with increased mitochondrial oxidative stress in the heart. The present study investigated the role of mitochondria-localized signaling molecules, tyrosine kinase Src and tyrosine phosphatase SHP2, in sepsis-induced cardiac mitochondrial dysfunction using a rat pneumonia-related sepsis model. SD rats were given an intratracheal injection of Streptococcus pneumoniae, 4×10(6 CFU per rat, (or vehicle for shams; heart tissues were then harvested and subcellular fractions were prepared. By Western blot, we detected a gradual and significant decrease in Src and an increase in SHP2 in cardiac mitochondria within 24 hours post-inoculation. Furthermore, at 24 hours post-inoculation, sepsis caused a near 70% reduction in tyrosine phosphorylation of all cardiac mitochondrial proteins. Decreased tyrosine phosphorylation of certain mitochondrial structural proteins (porin, cyclophilin D and cytochrome C and functional proteins (complex II subunit 30kD and complex I subunit NDUFB8 were evident in the hearts of septic rats. In vitro, pre-treatment of mitochondrial fractions with recombinant active Src kinase elevated OXPHOS complex I and II-III activity, whereas the effect of SHP2 phosphatase was opposite. Neither Src nor SHP2 affected complex IV and V activity under the same conditions. By immunoprecipitation, we showed that Src and SHP2 consistently interacted with complex I and III in the heart, suggesting that complex I and III contain putative substrates of Src and SHP2. In addition, in vitro treatment of mitochondrial fractions with active Src suppressed sepsis-associated mtROS production and protected aconitase activity, an indirect marker of mitochondrial oxidative stress. On the contrary, active SHP2 phosphatase overproduced mtROS and deactivated aconitase under the same in vitro conditions. In conclusion, our data suggest that changes in mitochondria

  10. Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Daniel A. Rossignol

    2008-01-01

    Full Text Available Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environ-mental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

  11. Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.

    Science.gov (United States)

    Robb, Ellen L; Moradi, Fereshteh; Maddalena, Lucas A; Valente, Andrew J F; Fonseca, Joao; Stuart, Jeffrey A

    2017-04-01

    Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion. 48 h continuous treatment with 10-20 μM RES stimulated mitochondrial fusion in C2C12 myoblasts, PC3 cancer cells, and mouse embryonic fibroblasts stimulated significant increases in fusion in all instances, resulting in larger and more highly branched mitochondrial networks. Mitofusin-2 (Mfn2) is a key protein facilitating mitochondrial fusion, and its expression was also stimulated by RES. Using Mfn2-null cells we demonstrated that RES's effects on mitochondrial fusion, cellular respiration rates, and cell growth are all dependent upon the presence of Mfn2. Taken together, these results demonstrate that Mfn2 and mitochondrial fusion are affected by RES in ways that appear to relate to RES's known effects on cellular metabolism and growth.

  12. Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics.

    Science.gov (United States)

    Hatakeyama, Hideyuki; Goto, Yu-Ichi

    2016-04-01

    Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics.

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

    Directory of Open Access Journals (Sweden)

    Philippe A Parone

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

  14. 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.

  15. 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.

  16. Mitochondrial Energetics and Therapeutics

    OpenAIRE

    2010-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems app...

  17. Sealing the Mitochondrial Respirasome

    OpenAIRE

    Winge, Dennis R.

    2012-01-01

    The mitochondrial respiratory chain is organized within an array of supercomplexes that function to minimize the generation of reactive oxygen species (ROS) during electron transfer reactions. Structural models of supercomplexes are now known. Another recent advance is the discovery of non-OXPHOS complex proteins that appear to adhere to and seal the individual respiratory complexes to form stable assemblages that prevent electron leakage. This review highlights recent advances in our underst...

  18. Estimation of suspended sediment flux from acoustic Doppler current profiling along the Jinhae Bay entrance

    Institute of Scientific and Technical Information of China (English)

    WANG Yaping; CHU Yong Shik; LEE Hee Jun; HAN Choong Keun; OH Byung Chul

    2005-01-01

    A Nortek acoustic Doppler current profiler (NDP) was installed on a moving vessel to survey the entrance to the Jinhae Bay on August 22~23, 2001. The current velocity and acoustic backscattering signal were collected along two cross-sections; water samples were also collected during the measurement. The acoustic signals were normalized to compensate for the loss incurred by acoustic beam spreading in the seawater. The in situ calibration shows that a significant relationship is present between suspended sediment concentrations (SSC) and normalized acoustic signals. Two acoustic parameters have been determined to construct an acoustic-concentration model.Using this derived model, the SSC patterns along the surveyed cross-sections were obtained by the conversion of acoustic data. Using the current velocity and SSC data, the flux of suspended sediment was estimated. It indicates that the sediment transport into the bay through the entrance has an order of magnitude of 100 t per tidal cycle.

  19. Sphingolipids and mitochondrial apoptosis.

    Science.gov (United States)

    Patwardhan, Gauri A; Beverly, Levi J; Siskind, Leah J

    2016-04-01

    The sphingolipid family of lipids modulate several cellular processes, including proliferation, cell cycle regulation, inflammatory signaling pathways, and cell death. Several members of the sphingolipid pathway have opposing functions and thus imbalances in sphingolipid metabolism result in deregulated cellular processes, which cause or contribute to diseases and disorders in humans. A key cellular process regulated by sphingolipids is apoptosis, or programmed cell death. Sphingolipids play an important role in both extrinsic and intrinsic apoptotic pathways depending on the stimuli, cell type and cellular response to the stress. During mitochondrial-mediated apoptosis, multiple pathways converge on mitochondria and induce mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of intermembrane space proteins such as cytochrome c and Apaf1 into the cytosol where they activate the caspases and DNases that execute cell death. The precise molecular components of the pore(s) responsible for MOMP are unknown, but sphingolipids are thought to play a role. Here, we review evidence for a role of sphingolipids in the induction of mitochondrial-mediated apoptosis with a focus on potential underlying molecular mechanisms by which altered sphingolipid metabolism indirectly or directly induce MOMP. Data available on these mechanisms is reviewed, and the focus and limitations of previous and current studies are discussed to present important unanswered questions and potential future directions.

  20. Mitochondrial ABC transporters.

    Science.gov (United States)

    Lill, R; Kispal, G

    2001-01-01

    In contrast to bacteria, mitochondria contain only a few ATP binding cassette (ABC) transporters in their inner membrane. The known mitochondrial ABC proteins fall into two major classes that, in the yeast Saccharomyces cerevisiae, are represented by the half-transporter Atm1p and the two closely homologous proteins Mdl1p and Mdl2p. In humans two Atm1p orthologues (ABC7 and MTABC3) and two proteins homologous to Mdll/2p have been localized to mitochondria. The Atm1p-like proteins perform an important function in mitochondrial iron homeostasis and in the maturation of Fe/S proteins in the cytosol. Mutations in ABC7 are causative of hereditary X-linked sideroblastic anemia and cerebellar ataxia (XLSA/A). MTABC3 may be a candidate gene for the lethal neonatal syndrome. The function of the mitochondrial Mdl1/2p-like proteins is not clear at present with the notable exception of murine ABC-me that may transport intermediates of heme biosynthesis from the matrix to the cytosol in erythroid tissues.

  1. 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.

  2. 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.

  3. Reductive stress impairs myoblasts mitochondrial function and triggers mitochondrial hormesis.

    Science.gov (United States)

    Singh, François; Charles, Anne-Laure; Schlagowski, Anna-Isabel; Bouitbir, Jamal; Bonifacio, Annalisa; Piquard, François; Krähenbühl, Stephan; Geny, Bernard; Zoll, Joffrey

    2015-07-01

    Even though oxidative stress damage from excessive production of ROS is a well known phenomenon, the impact of reductive stress remains poorly understood. This study tested the hypothesis that cellular reductive stress could lead to mitochondrial malfunction, triggering a mitochondrial hormesis (mitohormesis) phenomenon able to protect mitochondria from the deleterious effects of statins. We performed several in vitro experiments on L6 myoblasts and studied the effects of N-acetylcysteine (NAC) at different exposure times. Direct NAC exposure (1mM) led to reductive stress, impairing mitochondrial function by decreasing maximal mitochondrial respiration and increasing H₂O₂production. After 24h of incubation, the reactive oxygen species (ROS) production was increased. The resulting mitochondrial oxidation activated mitochondrial biogenesis pathways at the mRNA level. After one week of exposure, mitochondria were well-adapted as shown by the decrease of cellular ROS, the increase of mitochondrial content, as well as of the antioxidant capacities. Atorvastatin (ATO) exposure (100μM) for 24h increased ROS levels, reduced the percentage of live cells, and increased the total percentage of apoptotic cells. NAC exposure during 3days failed to protect cells from the deleterious effects of statins. On the other hand, NAC pretreatment during one week triggered mitochondrial hormesis and reduced the deleterious effect of statins. These results contribute to a better understanding of the redox-dependant pathways linked to mitochondria, showing that reductive stress could trigger mitochondrial hormesis phenomenon.

  4. Exploring social patterns of participation in university-entrance level mathematics in England

    OpenAIRE

    Noyes, Andrew

    2009-01-01

    In recent years in England there has been considerable attention given to a range of apparent crises in mathematics education, one of which has been the long term decline of participation in university-entrance level (Advanced or A) mathematics. Given the negative impact upon mathematics participation of Curriculum 2000, together with the government’s emphasis on Science Technology Engineering and Mathematics (STEM) subjects, the political intent to increase participation in Advanced level m...

  5. The Entrance Effect on Gases Flow Characteristics in Micro-tube

    Institute of Scientific and Technical Information of China (English)

    Chengwen Li; Li Jia; Tiantian Zhang

    2009-01-01

    Entrance region may have important effect on gases flow characteristics in micro-channels. It's concluded in the available papers that the entrance effect causes significant difference. An experimental system of single-phase gas flow characteristics in microchannels was set up. Flow characteristics of nitrogen in PEEK polymer micro-tube (hydraulic diameter is 5531am) was studied experimentally. According to the data of nitrogen flow in the mi-cro-tube with the length ranging from 0.1m tol.524m, it is shown that the friction constant becomes higher when the tube becomes shorter. By using pipe cutting methods, it's confirmed that entrance effect is one of the key fac-tors that cause friction constant higher than conventional theory. It's found that friction constant of fully devel-oped flow is lower than the value predicted by conventional theory in turbulent region. The result indicates that the flow transition occurs at Reynolds number ranging from 1600-2000. The phenomenon of obvious early transi-tion is not found.

  6. SIMULATION OF THE PROCESS OF FLOW SEPARATION AT THE ENTRANCE OF SQUARE ASPIRATING PORT

    Directory of Open Access Journals (Sweden)

    Olga A. Averkova

    2014-01-01

    Full Text Available We consider the flow at the inlet to the suction square hole with sharp edges, which is located in an infinite space. The purpose of this study is to construct a mathematical model of flow separation at the entrance to square suction canal with sharp edges, located in infinite space, by using square vortex frameworks. As a part of ideology of the method of discrete vortices in the non-stationary quasi-axisymmetric formulation, we constructed the mathematical model of separated flow at the inlet to the square aspirating pipe and its software-algorithmic implementation. We have determined the velocity field at the entrance to suction channel and a line of flow separation. Determine the velocity field in typical cross-sections of the suction channel, dimensions of the efficient absorption, compression ratio of the jet. Were received analytical formulas for calculating separation surfaces current. Profiling the entrance opening of the suction hole detected on the outlines separation surface will improve the acoustic and aerodynamic properties of the exhaust systems. The obtained results can be useful for designing of local exhaust ventilation of reduced energy consumption.

  7. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using yeast models of OXPHOS deficiencies.

    Science.gov (United States)

    Fontanesi, Flavia; Diaz, Francisca; Barrientos, Antoni

    2009-10-01

    The oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. Several approaches for the assessment of the OXPHOS system enzymes have been developed. Based on the methods described elsewhere, this unit describes the creation and study of yeast models of mitochondrial OXPHOS deficiencies.

  8. Mesencephalic complex I deficiency does not correlate with parkinsonism in mitochondrial DNA maintenance disorders.

    Science.gov (United States)

    Palin, Eino J H; Paetau, Anders; Suomalainen, Anu

    2013-08-01

    Genetic evidence from recessively inherited Parkinson's disease has indicated a clear causative role for mitochondrial dysfunction in Parkinson's disease. This role has long been discussed based on findings that toxic inhibition of mitochondrial respiratory complex I caused parkinsonism and that tissues of patients with Parkinson's disease show complex I deficiency. Disorders of mitochondrial DNA maintenance are a common cause of inherited neurodegenerative disorders, and lead to mitochondrial DNA deletions or depletion and respiratory chain defect, including complex I deficiency. However, parkinsonism associates typically with defects of catalytic domain of mitochondrial DNA polymerase gamma. Surprisingly, however, not all mutations affecting DNA polymerase gamma manifest as parkinsonism, but, for example, spacer region mutations lead to spinocerebellar ataxia and/or severe epilepsy. Furthermore, defective Twinkle helicase, a close functional companion of DNA polymerase gamma in mitochondrial DNA replication, results in infantile-onset spinocerebellar ataxia, epilepsy or adult-onset mitochondrial myopathy, but not typically parkinsonism. Here we sought for clues for this specificity in the neurological manifestations of mitochondrial DNA maintenance disorders by studying mesencephalic neuropathology of patients with DNA polymerase gamma or Twinkle defects, with or without parkinsonism. We show here that all patients with mitochondrial DNA maintenance disorders had neuronopathy in substantia nigra, most severe in DNA polymerase gamma-associated parkinsonism. The oculomotor nucleus was also affected, but less severely. In substantia nigra, all patients had a considerable decrease of respiratory chain complex I, but other respiratory chain enzymes were not affected. Complex I deficiency did not correlate with parkinsonism, age, affected gene or inheritance. We conclude that the cell number in substantia nigra correlated well with parkinsonism in DNA polymerase gamma

  9. The Potato Tuber Mitochondrial Proteome

    DEFF Research Database (Denmark)

    Salvato, Fernanda; Havelund, Jesper F; Chen, Mingjie;

    2014-01-01

    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...... that more than 50% of the identified proteins harbor at least one modification. The most prominently observed class of posttranslational modifications was oxidative modifications. This study reveals approximately 500 new or previously unconfirmed plant mitochondrial proteins and outlines a facile strategy...... for unbiased, near-comprehensive identification of mitochondrial proteins and their modified forms....

  10. Multiple major increases and decreases in mitochondrial substitution rates in the plant family Geraniaceae

    Directory of Open Access Journals (Sweden)

    Shirk Andrew J

    2005-12-01

    history. Conclusion The existence of major, mitochondrial-specific changes in rates of synonymous substitutions in the Geraniaceae implies major and reversible underlying changes in the mitochondrial mutation rate in this family. Together with the recent report of a similar pattern of rate heterogeneity in Plantago, these findings indicate that the mitochondrial mutation rate is a more plastic character in plants than previously realized. Many molecular factors could be responsible for these dramatic changes in the mitochondrial mutation rate, including nuclear gene mutations affecting the fidelity and efficacy of mitochondrial DNA replication and/or repair and – consistent with the lack of RNA editing – exceptionally high levels of "mutagenic" retroprocessing. That the mitochondrial mutation rate has returned to normally low levels in many Geraniaceae raises the possibility that, akin to the ephemerality of mutator strains in bacteria, selection favors a low mutation rate in plant mitochondria.

  11. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.

    Science.gov (United States)

    Holmström, Kira M; Pan, Xin; Liu, Julia C; Menazza, Sara; Liu, Jie; Nguyen, Tiffany T; Pan, Haihui; Parks, Randi J; Anderson, Stasia; Noguchi, Audrey; Springer, Danielle; Murphy, Elizabeth; Finkel, Toren

    2015-08-01

    Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.

  12. TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression.

    Directory of Open Access Journals (Sweden)

    Hironori Takamura

    Full Text Available Mitochondria are dynamic organelles that change in response to extracellular stimuli. These changes are essential for normal mitochondrial/cellular function and are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Although some molecules have been identified to mediate the mitochondrial fusion and fission process, the underlying mechanisms remain unclear. Tumor necrosis factor receptor-associated protein 1 (TRAP1 is a mitochondrial molecule that regulates a variety of mitochondrial functions. Here, we examined the role of TRAP1 in the regulation of morphology. Stable TRAP1 knockdown cells showed abnormal mitochondrial morphology, and we observed significant decreases in dynamin-related protein 1 (Drp1 and mitochondrial fission factor (Mff, mitochondrial fission proteins. Similar results were obtained by transient knockdown of TRAP1 in two different cell lines, SH-SY5Y neuroblastoma cells and KNS-42 glioma cells. However, TRAP1 knockdown did not affect expression levels of fusion proteins. The reduction in Drp1 and Mff protein levels was rescued following treatment with the proteasome inhibitor MG132. These results suggest that TRAP1 regulates the expression of fission proteins and controls mitochondrial fusion/fission, which affects mitochondrial/cellular function.

  13. Pressure drop measurements in the transition region for a circular tube with a square-edged entrance

    Science.gov (United States)

    Ghajar, Afshin J.; Augustine, Jody R.

    1990-06-01

    Pressure drop measurements were made in a horizontal circular straight tube with a square-edged entrance under isothermal flow conditions. The experiments covered a Reynolds number range from 512 to 14,970. A total of thirty-three sets of experimental data for the twenty pressure tap locations along the 20 ft length of the test section were gathered. For the square-edged entrance the range of Reynolds number for which transition flow exists was determined to be between 2070 to 2840. A correlation for prediction of fully developed skin friction coefficient in this region is recommended. In the entrance region the length required for the friction factor to become fully developed in both the laminar and turbulent regions was found to be inversely proportional to the Reynolds number, with the turbulent data showing a stronger dependency. A correlation for prediction of entrance length in the turbulent region is offered.

  14. Mitochondrial gene mutations and type 2 diabetes in Chinese families

    Institute of Scientific and Technical Information of China (English)

    LI Ming-zhen; YU De-min; YU Pei; LIU De-min; WANG Kun; TANG Xin-zhi

    2008-01-01

    Background Numerous mitochondrial DNA mutations are significantly correlated with development of diabetes. This study investigated mitochondrial gene, point mutations in patients with type 2 diabetes and their families. Methods Unrelated patients with type 2 diabetes(n=826)were randomly recruited; unrelated and nondiabetic subjects (n=637)served as controls. The clinical and biochemical data of the participants were collected. Total genome was extracted from peripheral leucocytes. Polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP)and clonig techniques were used to screen mitochondrial genes including np3316,np3394 and np3426 in the ND1 region and np3243 in the tRNALeu (UUR). Results In 39 diabetics with one or more mitochondrial gene point mutations, the prevalence(4.7%,39/826)of mtDNA mutations was higher than that(0.7%,5/637)in the controls. The identical mutation was found in 23 of 43 tested members from three pedigrees. Affected family members presented with variable clinical features ranging from normal glucose tolerance to impaired glucose tolerance (IGT)(n=2),impaired fasting glucose(IFG)(n=1)to type 2 diabetes (n=13)with 3 family members suffering from hearing loss. Conclusions Type 2 diabetes in China is associated with several mitochondrial gene mutations. Aged patients with diabetic family history had a higher prevalence of mutation and various clinical pictures. Mitochondrial gene mutation might be one of the genetic factors contributing to diabetic familial clustering.

  15. Mitochondrial fission protein Drp1 regulates mitochondrial transport and dendritic arborization in cerebellar Purkinje cells.

    Science.gov (United States)

    Fukumitsu, Kansai; Hatsukano, Tetsu; Yoshimura, Azumi; Heuser, John; Fujishima, Kazuto; Kengaku, Mineko

    2016-03-01

    Mitochondria dynamically change their shape by repeated fission and fusion in response to physiological and pathological conditions. Recent studies have uncovered significant roles of mitochondrial fission and fusion in neuronal functions, such as neurotransmission and spine formation. However, the contribution of mitochondrial fission to the development of dendrites remains controversial. We analyzed the function of the mitochondrial fission GTPase Drp1 in dendritic arborization in cerebellar Purkinje cells. Overexpression of a dominant-negative mutant of Drp1 in postmitotic Purkinje cells enlarged and clustered mitochondria, which failed to exit from the soma into the dendrites. The emerging dendrites lacking mitochondrial transport remained short and unstable in culture and in vivo. The dominant-negative Drp1 affected neither the basal respiratory function of mitochondria nor the survival of Purkinje cells. Enhanced ATP supply by creatine treatment, but not reduced ROS production by antioxidant treatment, restored the hypomorphic dendrites caused by inhibition of Drp1 function. Collectively, our results suggest that Drp1 is required for dendritic distribution of mitochondria and thereby regulates energy supply in growing dendritic branches in developing Purkinje cells.

  16. The United States Military Entrance Processing Command (USMEPCOM) Uses Six Sigma Process to Develop and Improve Data Quality

    Science.gov (United States)

    2007-06-01

    mecpom.army.mil Original title on 712 A/B: The United States Military Entrance Processing Command (USMEPCOM) uses Six Sigma process to develop and...Entrance Processing Command (USMEPCOM) uses Six Sigma Process to Develop and Improve Data Quality 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...Processing Command (USMEPCOM) uses Six Sigma Process to Develop and Improve Data Quality 3 • USMEPCOM Overview/History • Purpose • Define: What is Important

  17. 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...

  18. Sealing the mitochondrial respirasome.

    Science.gov (United States)

    Winge, Dennis R

    2012-07-01

    The mitochondrial respiratory chain is organized within an array of supercomplexes that function to minimize the generation of reactive oxygen species (ROS) during electron transfer reactions. Structural models of supercomplexes are now known. Another recent advance is the discovery of non-OXPHOS complex proteins that appear to adhere to and seal the individual respiratory complexes to form stable assemblages that prevent electron leakage. This review highlights recent advances in our understanding of the structures of supercomplexes and the factors that mediate their stability.

  19. Evidence for mitochondrial genetic control of autosomal gene expression.

    Science.gov (United States)

    Kassam, Irfahan; Qi, Tuan; Lloyd-Jones, Luke; Holloway, Alexander; Jan Bonder, Marc; Henders, Anjali K; Martin, Nicholas G; Powell, Joseph E; Franke, Lude; Montgomery, Grant W; Visscher, Peter M; McRae, Allan F

    2016-10-18

    The mitochondrial and nuclear genomes coordinate and co-evolve in eukaryotes in order to adapt to environmental changes. Variation in the mitochondrial genome is capable of affecting expression of genes on the nuclear genome. Sex-specific mitochondrial genetic control of gene expression has been demonstrated in Drosophila melanogaster, where males were found to drive most of the total variation in gene expression. This has potential implications for male-related health and disease resulting from variation in mtDNA solely inherited from the mother. We used a family-based study comprised of 47,323 gene expression probes and 78 mitochondrial SNPs (mtSNPs) from n = 846 individuals to examine the extent of mitochondrial genetic control of gene expression in humans. This identified 15 significant probe-mtSNP associations (P[Formula: see text]) corresponding to 5 unique genes on the mitochondrial and nuclear genomes, with three of these genes corresponding to mitochondrial genetic control of gene expression in the nuclear genome. The associated mtSNPs for three genes (one cis and two trans associations) were replicated (P expression in any of these five probes. Sex-specific effects were examined by applying our analysis to males and females separately and testing for differences in effect size. The MEST gene was identified as having the most significantly different effect sizes across the sexes (P [Formula: see text]). MEST was similarly expressed in males and females with the G allele; however, males with the C allele are highly expressed for MEST, while females show no expression of the gene. This study provides evidence for the mitochondrial genetic control of expression of several genes in humans, with little evidence found for sex-specific effects.

  20. A whole mitochondrial genome screening in a MELAS patient: A novel mitochondrial tRNA{sup Val} mutation

    Energy Technology Data Exchange (ETDEWEB)

    Mezghani, Najla [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Mnif, Mouna [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Kacem, Maha [Service de Medecine interne, C.H.U. Fattouma Bourguiba de Monastir (Tunisia); Mkaouar-Rebai, Emna, E-mail: emna_mkaouar@mail2world.com [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Hadj Salem, Ikhlass [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Kallel, Nozha; Charfi, Nadia; Abid, Mohamed [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Fakhfakh, Faiza [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)

    2011-04-22

    Highlights: {yields} We report a young Tunisian patient with clinical features of MELAS syndrome. {yields} Reported mitochondrial mutations were absent after a mutational screening of the whole mtDNA. {yields} We described a novel m.1640A>G mutation in the tRNA{sup Val} gene which was absent in 150 controls. {yields} Mitochondrial deletions and POLG1 gene mutations were absent. {yields} The m.1640A>G mutation could be associated to MELAS syndrome. -- Abstract: Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA{sup Val}. This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.

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

    Science.gov (United States)

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

    2014-09-09

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

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

    Directory of Open Access Journals (Sweden)

    I. Golic

    2014-09-01

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

  3. Molecular Genetics of Mitochondrial Disorders

    Science.gov (United States)

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  4. Redox Homeostasis and Mitochondrial Dynamics

    NARCIS (Netherlands)

    Willems, P.H.G.M.; Rossignol, R.; Dieteren, C.E.J.; Murphy, M.P.; Koopman, W.J.H.

    2015-01-01

    Within living cells, mitochondria are considered relevant sources of reactive oxygen species (ROS) and are exposed to reactive nitrogen species (RNS). During the last decade, accumulating evidence suggests that mitochondrial (dys)function, ROS/RNS levels, and aberrations in mitochondrial morphology

  5. Mitochondrial disorders and the eye

    Directory of Open Access Journals (Sweden)

    O’Neill EC

    2011-09-01

    Full Text Available Nicole J Van Bergen, Rahul Chakrabarti, Evelyn C O'Neill, Jonathan G Crowston, Ian A TrounceCentre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Victoria, AustraliaAbstract: The clinical significance of disturbed mitochondrial function in the eye has emerged since mitochondrial DNA (mtDNA mutation was described in Leber's hereditary optic neuropathy. The spectrum of mitochondrial dysfunction has become apparent through increased understanding of the contribution of nuclear and somatic mtDNA mutations to mitochondrial dynamics and function. Common ophthalmic manifestations of mitochondrial dysfunction include optic atrophy, pigmentary retinopathy, and ophthalmoplegia. The majority of patients with ocular manifestations of mitochondrial disease also have variable central and peripheral nervous system involvement. Mitochondrial dysfunction has recently been associated with age-related retinal disease including macular degeneration and glaucoma. Therefore, therapeutic targets directed at promoting mitochondrial biogenesis and function offer a potential to both preserve retinal function and attenuate neurodegenerative processes.Keywords: mitochondria, disease, retina, eye, aging, neuroprotection

  6. 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.

  7. Mitochondrial dynamics and peripheral neuropathy.

    Science.gov (United States)

    Baloh, Robert H

    2008-02-01

    Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics--the fusion, fission, and movement of mitochondria--as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases.

  8. 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.

  9. Mechanisms of Mitochondrial Defects in Gulf War Syndrome

    Science.gov (United States)

    2014-10-01

    GWS) is associated with increased incidences of amyotrophic lateral sclerosis, pain syndromes, muscle complaints that include fatigue and myalgias, as...expression in genes affecting mitochondrial function, and mtDNA mutations (inherited, somatic , and sporadic during embryogenesis). Gene expression...incidences of amyotrophic lateral sclerosis, pain syndromes, muscle complaints that include fatigue and myalgias, as well as other neurological symptoms

  10. Preliminary Tests of Nose- and Side- Entrance Blower Cooling Systems for Radial Engines, Special Report

    Science.gov (United States)

    Biermann, David; Valentine, E. Floyd

    1939-01-01

    Two cowling systems intended to reduce the drag and improve the low-speed cooling characteristics of conventional radial engine cowlings were tested in model form to determine the practicability of the methods. One cowling included a blower mounted on the rear face of a large propeller spinner which drew cooling air in through side entrance ducts located behind the equivalent engine orifice plate. The air was passed through the equivalent engine orifice plate from rear to front and out through a slot between the spinner and the engine plate. The blower produced substantially all the power necessary to circulate the cooling air in some cases, so the quantity of air flowing was independent of the air speed, Two types of blowers were used, a centrifugal type and one using airfoil blades which forced the air outward from the center of rotation. The other cowling was similar to the conventional N.A.C.A. cowling except for the addition of a large propeller spinner nose. The spinner was provided with a hole in the nose to admit cooling air and blower blades to increase the pressure for cooling at low speeds. The tests show that with both cowling types the basic drag of the nacelle was reduced substantially below that for the N.A.C.A. cowling by virtue of the better nose shape made possible by the spinner . The drag due to the side-entrance ducts was nearly zero when the openings were closed or when the blower was drawing in a certain quantity of air in proportion to the air speed. The drag increased, however, when air mas allowed to spill from the openings. The nose-entrance blower showed considerable promise as a cooling means although the blower tested was relatively inefficient, owing to the fact that the blower compartments evidently were expanded too rapidly under the conditions imposed. by the design.

  11. Empirical models for liquid metal heat transfer in the entrance region of tubes and rod bundles

    Science.gov (United States)

    Jaeger, Wadim

    2016-10-01

    Experiments focusing on liquid metals heat transfer in pipes and rod bundles with thermally and hydraulically developing flow are reviewed. Empirical heat transfer correlations are developed for engineering applications. In the developing regions the heat transfer is in-stationary. The heat transfer at the entrance is around 100 % higher due to the developing process including the lateral exchange of energy and momentum than for developed flow. Developing flow is not physically considered in the framework of system codes, which are used for thermal-hydraulic analysis of power and process plants with a multitude of components like pipes, tanks, valves and heat exchangers. Therefore, the application to liquid metal flows is limited to developed flow, which is independent of the distance from the flow entrance. The heat transfer enhancement in developing flows is important for the optimization of components like heat exchangers and helps to reduce unnecessary conservatism. In this work, empirical models are developed to account for developing flows in pipes and rod bundles. A literature review is performed to collect available experimental data for developing flow in liquid metal heat transfer. The evaluation shows that the length for pure thermally developing pipe flow is much larger (20-30 hydraulic diameters) than for combined thermally and hydraulically developing flow (10-15 hydraulic diameters). In rod bundles, fully combined developed flow is established after 30-40 hydraulic diameters downstream of the entrance. The derived empirical models for the heat transfer enhancement in the developing regions are implemented into a best estimate system code. The validation of these models by means of post-test analyses of 16 experiments shows that they are very well able to represent the heat transfer in developing regions.

  12. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N; D'Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F; Zeviani, Massimo; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A; Tancredi, Andrea; Mancini, Massimiliano; d'Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro; Carelli, Valerio

    2014-02-01

    Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.

  13. L1 Writing Experiences and L2 Writing Instruction : University Entrance Exams in Japan

    OpenAIRE

    Ross, Paul; Paul, ROSS

    2005-01-01

    This poper examines an L1 learning experience shared by many EFL students in Japan: writing an essay in Japanese on university entrance exams. The main purpose is to identify the features of the experience that L2 writing teachers need to address in their classrooms. The major issues that are investigated are 1) what kind of writing students are expected to do on the exams, 2) what the purpose of the essay question is, and 3) what kind of training students receive to improve their writing ski...

  14. Researches on evaluation of smooth entrance in cutting using electrical current. A case study

    Directory of Open Access Journals (Sweden)

    Diţu Valentin

    2017-01-01

    Full Text Available At metal drilling, at the beginning of the process, the cutting tool in the chisel edge zone, frictions and plastically deforms the material, and then enters in cutting. If the drill is entered smoothly in cutting with a special device, its life is increased. The paper presents how the electrical current at cutting is used for the evaluation of smooth entrance in cutting in comparison with classical cutting. These are demonstrated for 41MoC11 steel drilled with a set of 30 tools having 8 mm diameter.

  15. Researches on evaluation of smooth entrance in cutting using electrical current. A case study

    OpenAIRE

    Diţu Valentin; Oancea Gheorghe; Daicu Raluca

    2017-01-01

    At metal drilling, at the beginning of the process, the cutting tool in the chisel edge zone, frictions and plastically deforms the material, and then enters in cutting. If the drill is entered smoothly in cutting with a special device, its life is increased. The paper presents how the electrical current at cutting is used for the evaluation of smooth entrance in cutting in comparison with classical cutting. These are demonstrated for 41MoC11 steel drilled with a set of 30 tools having 8 mm d...

  16. Mitochondrial Mechanisms in Septic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    María Cecilia Cimolai

    2015-08-01

    Full Text Available Sepsis is the manifestation of the immune and inflammatory response to infection that may ultimately result in multi organ failure. Despite the therapeutic strategies that have been used up to now, sepsis and septic shock remain a leading cause of death in critically ill patients. Myocardial dysfunction is a well-described complication of severe sepsis, also referred to as septic cardiomyopathy, which may progress to right and left ventricular pump failure. Many substances and mechanisms seem to be involved in myocardial dysfunction in sepsis, including toxins, cytokines, nitric oxide, complement activation, apoptosis and energy metabolic derangements. Nevertheless, the precise underlying molecular mechanisms as well as their significance in the pathogenesis of septic cardiomyopathy remain incompletely understood. A well-investigated abnormality in septic cardiomyopathy is mitochondrial dysfunction, which likely contributes to cardiac dysfunction by causing myocardial energy depletion. A number of mechanisms have been proposed to cause mitochondrial dysfunction in septic cardiomyopathy, although it remains controversially discussed whether some mechanisms impair mitochondrial function or serve to restore mitochondrial function. The purpose of this review is to discuss mitochondrial mechanisms that may causally contribute to mitochondrial dysfunction and/or may represent adaptive responses to mitochondrial dysfunction in septic cardiomyopathy.

  17. Redox regulation of mitochondrial biogenesis.

    Science.gov (United States)

    Piantadosi, Claude A; Suliman, Hagir B

    2012-12-01

    The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bigenomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species production. This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell, with an emphasis on the responses to oxidative stress and inflammation. The cell's energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and coactivators also involved in the elimination of defective mitochondria and the expression of counterinflammatory and antioxidant genes, such as IL10 and SOD2, as part of a unified damage-control network. The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell's metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress.

  18. Mitochondrial dysfunction in heart failure.

    Science.gov (United States)

    Rosca, Mariana G; Hoppel, Charles L

    2013-09-01

    Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction.

  19. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    Science.gov (United States)

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  20. Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta.

    Directory of Open Access Journals (Sweden)

    Marc Liesa

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  1. Autofluorescence microscopy: a non-destructive tool to monitor mitochondrial toxicity.

    Science.gov (United States)

    Rodrigues, Robim M; Macko, Peter; Palosaari, Taina; Whelan, Maurice P

    2011-10-30

    Visualization of NADH by fluorescence microscopy makes it possible to distinguish mitochondria inside living cells, allowing structure analysis of these organelles in a non-invasive way. Mitochondrial morphology is determined by the occurrence of mitochondrial fission and fusion. During normal cell function mitochondria appear as elongated tubular structures. However, cellular malfunction induces mitochondria to fragment into punctiform, vesicular structures. This change in morphology is associated with the generation of reactive oxygen species (ROS) and early apoptosis. The aim of this study is to demonstrate that autofluorescence imaging of mitochondria in living eukaryotic cells provides structural and morphological information that can be used to assess mitochondrial health. We firstly established the illumination conditions that do not affect mitochondrial structure and calculated the maximum safe light dose to which the cells can be exposed. Subsequently, sequential recording of mitochondrial fluorescence was performed and changes in mitochondrial morphology were monitored in a continuous non-destructive way. This approach was then used to assess mitochondrial toxicity induced by potential toxicants exposed to mammalian cells. Both mouse and human cells were used to evaluate mitochondrial toxicity of different compounds with different toxicities. This technique constitutes a novel and promising approach to explore chemical induced toxicity because of its reliability to monitor mitochondrial morphology changes and corresponding toxicity in a non-invasive way.

  2. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy

    DEFF Research Database (Denmark)

    Elo, Jenni M; Yadavalli, Srujana S; Euro, Liliya

    2012-01-01

    Next-generation sequencing has turned out to be a powerful tool to uncover genetic basis of childhood mitochondrial disorders. We utilized whole-exome analysis and discovered novel compound heterozygous mutations in FARS2 (mitochondrial phenylalanyl transfer RNA synthetase), encoding the mitochon......Next-generation sequencing has turned out to be a powerful tool to uncover genetic basis of childhood mitochondrial disorders. We utilized whole-exome analysis and discovered novel compound heterozygous mutations in FARS2 (mitochondrial phenylalanyl transfer RNA synthetase), encoding...... the mitochondrial phenylalanyl transfer RNA (tRNA) synthetase (mtPheRS) in two patients with fatal epileptic mitochondrial encephalopathy. The mutations affected highly conserved amino acids, p.I329T and p.D391V. Recently, a homozygous FARS2 variant p.Y144C was reported in a Saudi girl with mitochondrial...... was impaired. Our results imply that the three FARS2 mutations directly impair aminoacylation function and stability of mtPheRS, leading to a decrease in overall tRNA charging capacity. This study establishes a new genetic cause of infantile mitochondrial Alpers encephalopathy and reports a new mitochondrial...

  3. Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

    Science.gov (United States)

    Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

    2016-06-01

    Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

  4. Role and Treatment of Mitochondrial DNA-Related Mitochondrial Dysfunction in Sporadic Neurodegenerative Diseases

    OpenAIRE

    Swerdlow, Russell H.

    2011-01-01

    Several sporadic neurodegenerative diseases display phenomena that directly or indirectly relate to mitochondrial function. Data suggesting altered mitochondrial function in these diseases could arise from mitochondrial DNA (mtDNA) are reviewed. Approaches for manipulating mitochondrial function and minimizing the downstream consequences of mitochondrial dysfunction are discussed.

  5. Mitochondrial dysfunction in myofibrillar myopathy.

    Science.gov (United States)

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  6. Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Pfeiffer Ronald F

    2010-04-01

    Full Text Available Abstract Background Mitochondrial function is impaired in Parkinson's disease (PD and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results The frequency of affected mothers of the proband with PD (83/167, 49.4% was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4% (Odds Ratio 1.22; 95%CI 0.83 - 1.81. After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic m

  7. 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.

  8. Respiratory active mitochondrial supercomplexes.

    Science.gov (United States)

    Acín-Pérez, Rebeca; Fernández-Silva, Patricio; Peleato, Maria Luisa; Pérez-Martos, Acisclo; Enriquez, Jose Antonio

    2008-11-21

    The structural organization of the mitochondrial respiratory complexes as four big independently moving entities connected by the mobile carriers CoQ and cytochrome c has been challenged recently. Blue native gel electrophoresis reveals the presence of high-molecular-weight bands containing several respiratory complexes and suggesting an in vivo assembly status of these structures (respirasomes). However, no functional evidence of the activity of supercomplexes as true respirasomes has been provided yet. We have observed that (1) supercomplexes are not formed when one of their component complexes is absent; (2) there is a temporal gap between the formation of the individual complexes and that of the supercomplexes; (3) some putative respirasomes contain CoQ and cytochrome c; (4) isolated respirasomes can transfer electrons from NADH to O(2), that is, they respire. Therefore, we have demonstrated the existence of a functional respirasome and propose a structural organization model that accommodates these findings.

  9. Automated quantification and integrative analysis of 2D and 3D mitochondrial shape and network properties.

    Directory of Open Access Journals (Sweden)

    Julie Nikolaisen

    Full Text Available Mitochondrial morphology and function are coupled in healthy cells, during pathological conditions and (adaptation to endogenous and exogenous stress. In this sense mitochondrial shape can range from small globular compartments to complex filamentous networks, even within the same cell. Understanding how mitochondrial morphological changes (i.e. "mitochondrial dynamics" are linked to cellular (patho physiology is currently the subject of intense study and requires detailed quantitative information. During the last decade, various computational approaches have been developed for automated 2-dimensional (2D analysis of mitochondrial morphology and number in microscopy images. Although these strategies are well suited for analysis of adhering cells with a flat morphology they are not applicable for thicker cells, which require a three-dimensional (3D image acquisition and analysis procedure. Here we developed and validated an automated image analysis algorithm allowing simultaneous 3D quantification of mitochondrial morphology and network properties in human endothelial cells (HUVECs. Cells expressing a mitochondria-targeted green fluorescence protein (mitoGFP were visualized by 3D confocal microscopy and mitochondrial morphology was quantified using both the established 2D method and the new 3D strategy. We demonstrate that both analyses can be used to characterize and discriminate between various mitochondrial morphologies and network properties. However, the results from 2D and 3D analysis were not equivalent when filamentous mitochondria in normal HUVECs were compared with circular/spherical mitochondria in metabolically stressed HUVECs treated with rotenone (ROT. 2D quantification suggested that metabolic stress induced mitochondrial fragmentation and loss of biomass. In contrast, 3D analysis revealed that the mitochondrial network structure was dissolved without affecting the amount and size of the organelles. Thus, our results demonstrate

  10. 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.

  11. Lactobacillus paracasei CBA L74 interferes with gliadin peptides entrance in Caco-2 cells.

    Science.gov (United States)

    Sarno, Marco; Lania, Giuliana; Cuomo, Marialaura; Nigro, Federica; Passannanti, Francesca; Budelli, Andrea; Fasano, Francesca; Troncone, Riccardo; Auricchio, Salvatore; Barone, Maria Vittoria; Nigro, Roberto; Nanayakkara, Merlin

    2014-12-01

    Several recent reports describe a role of probiotics as a therapeutic approach for celiac disease (CD). Two undigested A-gliadin peptides, P31-43 and P57-68, are central to CD pathogenesis, inducing an innate and an adaptive immune response, respectively. They enter enterocytes and localize to vesicular compartment to induce their toxic/immunogenics effects. In this article, we tested the effect of probiotic Lactobacillus paracasei (LP) CBA L74 (International Depository Accession Number LMG P-24778), its supernatant and LP-fermented cereals on gliadin peptides, P31-43 and P57-68, entrance in Caco-2 cells. Both LP CBA L74 and its supernatant inhibit P31-43 (intensity of fluorescence; FI: 75%) and P57-68 (FI: 50%) entrance in Caco2 cells, indicating that this biological effect is due to some product included in LP CBA L74 supernatant. This effect was present also after fermentation of cereals. This study describes a novel effect of probiotics in the prevention of undigested gliadin peptides toxic effects.

  12. Effects of Wavy Channel Entrance Design on Streamwise Counter-rotating Vortices: a Visualization Study

    Directory of Open Access Journals (Sweden)

    Alexander Christantho Budiman

    2016-01-01

    Full Text Available Two different channel entrance designs, code named Valley First (VF and Peak First (PF, were experimentally visualized by means of smoke-wire visualization technique to observe their effects towards the streamwise counter-rotating vortices generated. The spanwise wavelength of the vortices was pre-set by modifying the leading edge. The investigation was carried out on the laminar boundary-layer flow in a rectangular channel with one-sided wavy surface that has amplitude a and wavelength λ of 7.5 mm and 76 mm, respectively. The vortices in the channel with VF design preserve farther downstream than those on the PF design, which might be caused by the large favorable pressure gradient between the entrance flat plate and the first peak location. The counter-rotating vortices could still be observed at non-dimensionalized streamwise distance χ (= x/λ = 2.47 for Reynolds number Re (= UH/ν = 9900 in channel with VF design. For lower Re, the vortices could preserve further downstream. In contrast, in channel with PF design, the structures were only visible clearly up to approximately χ = 1.32 for Re = 4700 and χ = 0.39 for Re = 5200.

  13. In Rio de Janeiro public entrance areas disappeared behind railings out of fear of crime

    Directory of Open Access Journals (Sweden)

    Katja Friedrich

    2013-05-01

    Full Text Available The need for safety leads to an increasing fencing of entrance areas and to a structural spatial segregation in Rio de Janeiro. Today’s passerby moves along high grids instead of walking on lavishly planted ways along noble entrance areas. In the scale of urban development the stronger variant of spatial demarcation is taking place. Gated communities arise as a total spatial exclusion, in a safe distance to existing favelas and disposing of abundant safety equipment.Precisely because the need for safety is important in dwelling, both trends are problematic from the urban perspective. The increasing fencing and demarcating destroys pleasant urban atmospheres and fosters the spreading of mono-functional resp. mono-social areas. However, trust and a peaceful togetherness are required for a socially and functionally mixed and spatially diversified public space. But these conditions can only be realised in the context of the entire society.

  14. Skin tears away from the entrance wound in gunshots to the head.

    Science.gov (United States)

    Faller-Marquardt, M; Pollak, S

    2002-10-01

    The present investigation covers 116 contact shots to the head and shots into the mouth from the Freiburg forensic autopsy material including 20 gunshot wounds which showed stretchmark-like tears of the facial skin away from the entrance wound. In these cases the gunshot entrance wounds were localised either in the mouth, the forehead, or the submental region. The stretchmark-like tears were found in the region of the eyes and the nasolabial folds. Radial tears were seen on the lips and in the vicinity of the corners of the mouth, particularly in cases involving shots into the mouth. The stretchmark-like tears essentially followed the skin tension lines and the expression-related lines of the face. They were apparently caused by the subcutaneous or intraoral expansion of the muzzle gases and/or the radial forces of the bullet resulting in ballooning and overextension of the facial soft tissues. The weapons used were not only rifles and shotguns, but also revolvers and pistols.

  15. Influence of thermoluminescent dosimeters energy dependence on the measurement of entrance skin dose in radiographic procedures

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Mercia Liane de; Galindo, Renata Sales; Hazin, Clovis Abrahao, E-mail: mercial@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN/NE-CNEN/PE), Recife, PE (Brazil); Maia, Ana Figueiredo [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Dept. de Fisica; Nascimento, Natalia Cassia do Espirito Santo; Fragoso, Maria da Conceicao de Farias [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2010-04-15

    Objective: this study was aimed at evaluating the influence of the energy dependence of thermoluminescent materials on the determination of entrance skin dose in patients submitted to conventional radiographic studies (general radiology, mammography and dental radiology). Materials and methods: three different thermoluminescent materials were utilized: LiF:Mg,Ti, LiF:Mg,Cu,P and CaSO{sub 4}:Dy. These materials were exposed to standardized sources of X and gamma radiation and clinical X-ray beams. Results: calibration and energy dependence curves were obtained. All the materials showed a linear response as a function of the air kerma. As far as energy dependence is concerned, the CaSO{sub 4}:Dy and LiF:Mg,Ti samples showed the greatest variation on thermoluminescent responses as a function of the effective radiation beam. Conclusion: the tested materials showed an appropriate performance for detecting X radiation on standard and clinical X-ray beams. Although CaSO{sub 4}:Dy and LiF:Mg,Ti samples present a significant energy dependence in the considered energy range, these materials can be utilized for measuring entrance skin doses, provided appropriate correction factors are applied (author)

  16. Reactive oxygen species act remotely to cause synapse loss in a Drosophila model of developmental mitochondrial encephalopathy

    OpenAIRE

    2008-01-01

    Mitochondrial dysfunction is a hallmark of many neurodegenerative diseases, yet its precise role in disease pathology remains unclear. To examine this link directly, we subtly perturbed electron transport chain function in the Drosophila retina, creating a model of Leigh Syndrome, an early-onset neurodegenerative disorder. Using mutations that affect mitochondrial complex II, we demonstrate that mild disruptions of mitochondrial function have no effect on the initial stages of photoreceptor d...

  17. Mitochondrial Genetic Variation in Iranian Infertile Men with Varicocele

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Heidari

    2016-09-01

    Full Text Available Background: Several recent studies have shown that mitochondrial DNA mutations lead to major disabilities and premature death in carriers. More than 150 mutations in human mitochondrial DNA (mtDNA genes have been associated with a wide spectrum of disorders. Varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observed within spermatic cord, can increase reactive oxygen species (ROS production in semen and cause oxidative stress and sperm dysfunction in patients. Given that mitochondria are the source of ROS production in cells, the aim of this study was to scan nine mitochondrial genes (MT-COX2, MT-tRNALys, MT-ATP8, MT-ATP6, MT-COX3, MT-tRNAGly, MT-ND3, MT-tRNAArg and MT-ND4L for mutations in infertile patients with varicocele. Materials and Methods: In this cross-sectional study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP and DNA sequencing were used to detect and identify point mutations respectively in 9 mitochondrial genes in 72 infertile men with varicocele and 159 fertile men. In brief, the samples showing altered electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to identify the exact nucleotide variation. Results: Ten type nucleotide variants were detected exclusively in mitochondrial DNA of infertile men. These include six novel nucleotide changes and four variants previously reported for other disorders. Conclusion: Mutations in mitochondrial genes may affect respiratory complexes in combination with environmental risk factors. Therefore these nucleotide variants probably lead to impaired ATP synthesis and mitochondrial function ultimately interfering with sperm motility and infertility.

  18. Mouse models of age-related mitochondrial neurosensory hearing loss.

    Science.gov (United States)

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  19. The causes and functions of mitochondrial proton leak.

    Science.gov (United States)

    Brand, M D; Chien, L F; Ainscow, E K; Rolfe, D F; Porter, R K

    1994-08-30

    The non-linear relationship between respiration rate and protonmotive force in isolated mitochondria is explained entirely by delta p-dependent changes in the proton conductance of the mitochondrial inner membrane and is not caused by redox slip in the proton pumps. Mitochondrial proton leak occurs in intact cells and tissues: the futile cycle of proton pumping and proton leak accounts for 26% +/- 7% of the total oxygen consumption rate or 33% +/- 7% of the mitochondrial respiration rate of isolated hepatocytes (mean +/- S.D. for 43 rats); 52% of the oxygen consumption rate of resting perfused muscle and up to 38% of the basal metabolic rate of a rat, suggesting that heat production may be an important function in the proton leak in homeotherms. Together with non-mitochondrial oxygen consumption, it lowers the effective P/O ratio in cells from maximum possible values of 2.33 (palmitate oxidation) or 2.58 (glucose oxidation) to as low as 1.1 in liver or 0.8 in muscle. The effective P/O ratio increases in response to ATP demand; the ability to allow rapid switching of flux from leak to ATP turnover may be an even more important function of the leak reaction than heat production. The mitochondrial proton conductance in isolated mitochondria and in hepatocytes is greatly modulated by thyroid hormones, by phylogeny and by body mass. Usually the reactions of ATP turnover change in parallel so that the coupling ratio is not greatly affected. Changes in proton leak in tissues are brought about in the short term by changes in mitochondrial protonmotive force and in the longer term by changes in the surface area and proton permeability of the mitochondrial inner membrane. Permeability changes are probably caused by changes in the fatty acid composition of the membrane phospholipids.

  20. Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole;

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM....... Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446......>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM....

  1. Mitochondrial protein import and human health and disease.

    Science.gov (United States)

    MacKenzie, James A; Payne, R Mark

    2007-05-01

    The targeting and assembly of nuclear-encoded mitochondrial proteins are essential processes because the energy supply of humans is dependent upon the proper functioning of mitochondria. Defective import of mitochondrial proteins can arise from mutations in the targeting signals within precursor proteins, from mutations that disrupt the proper functioning of the import machinery, or from deficiencies in the chaperones involved in the proper folding and assembly of proteins once they are imported. Defects in these steps of import have been shown to lead to oxidative stress, neurodegenerative diseases, and metabolic disorders. In addition, protein import into mitochondria has been found to be a dynamically regulated process that varies in response to conditions such as oxidative stress, aging, drug treatment, and exercise. This review focuses on how mitochondrial protein import affects human health and disease.

  2. The mitochondrial uniporter controls fight or flight heart rate increases.

    Science.gov (United States)

    Wu, Yuejin; Rasmussen, Tyler P; Koval, Olha M; Joiner, Mei-Ling A; Hall, Duane D; Chen, Biyi; Luczak, Elizabeth D; Wang, Qiongling; Rokita, Adam G; Wehrens, Xander H T; Song, Long-Sheng; Anderson, Mark E

    2015-01-20

    Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

  3. Hematological manifestations of primary mitochondrial disorders.

    Science.gov (United States)

    Finsterer, Josef

    2007-01-01

    At onset mitochondrial disorders (MID) frequently manifest as a mono-organic problem but turn into multisystem disease during the disease course in most of the cases. Organs/tissues most frequently affected in MID are the cerebrum, peripheral nerves, and the skeletal muscle. Additionally, most of the inner organs may be affected alone or in combination. Hematological manifestations of MID include aplastic, megaloblastic, or sideroblastic anemia, leukopenia, neutropenia, thrombocytopenia, or pancytopenia. In single cases either permanent or recurrent eosinophilia has been observed. Hematological abnormalities may occur together with syndromic or nonsyndromic MIDs. Syndromic MIDs, in which hematological manifestations predominate, are the Pearson syndrome (pancytopenia), Kearns-Sayre syndrome (anemia), Barth syndrome (neutropenia), and the autosomal recessive mitochondrial myopathy, lactic acidosis and sideroblastic anemia syndrome. In single cases with Leigh's syndrome, MERRF (myoclonic epilepsy and ragged-red fiber) syndrome, Leber's hereditary optic neuropathy, and Friedreich's ataxia anemia has been described. Anemia, leukopenia, thrombocytopenia, eosinophilia, or pancytopenia can frequently also be found in nonsyndromic MIDs with or without involvement of other tissues. Therapy of blood cell involvement in MID comprises application of antioxidants, vitamins, iron, bone marrow-stimulating factors, or substitution of cells.

  4. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.

    Science.gov (United States)

    Amato, Paula; Tachibana, Masahito; Sparman, Michelle; Mitalipov, Shoukhrat

    2014-01-01

    The exchange of nuclear genetic material between oocytes and embryos offers a novel reproductive option for the prevention of inherited mitochondrial diseases. Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multiorgan diseases. Tissues with a high metabolic demand, such as brain, heart, muscle, and central nervous system, are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Because mitochondrial DNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes, resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application.

  5. The influence of laser clipped by the laser entrance hole on hohlraum radiation measurement on Shenguang-III prototype

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dong [Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China); CAS Key Laboratory of Basic Plasma Physics and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Li, Zhichao; Guo, Liang; Li, Sanwei; Yi, Rongqing; Song, Tianming; Zhang, Huan; Wang, Zhebin; Jiang, Xiaohua; Jiang, Shaoen; Ding, Yongkun [Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China)

    2014-03-15

    Measuring the x-ray flux exiting the target's laser entrance hole (LEH) is the most common diagnostic that quantifies the x-ray intensity inside the laser-driven hohlraum. However, this signal accounts for only a small portion of the incident laser power and thus is likely to be affected by unwanted x-ray background from non-target area, leading to an overestimation of the hohlraum drive. Unwanted emission might be produced when the laser light is clipped by the LEH (LEH clipping) because of a lack of clearance for laser spot, or with a laser spot comprising of discrete structure, or even with a poor pointing accuracy. Its influence on the hohlraum radiation diagnostic is investigated on Shenguang-III prototype laser facility with the typical 1 ns square pulse. The experiment employed three types of targets to excite the unwanted x-ray background from LEH clipping, unconverted light, and both effects, respectively. This work gives an absolute evaluation of x-ray produced by the LEH clipping, which is measured by flat-response x-ray detectors (FXRD) at multiple view angles. The result indicates that there is little variation in measured emission to various view angles, because the unwanted x-rays are mainly generated at the side face of the LEH lip when laser is obliquely incident. Therefore, the LEH clipping brings more overestimation in hohlraum radiation measurement at larger view angle since the hohlraum LEH as an emitting source viewed by FXRD is decreased as the view angle increases. In our condition, the LEH clipping contributes 2%–3.5% overestimation to the hohlraum flux measurement.

  6. Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases

    Science.gov (United States)

    Amato, Paula; Tachibana, Masahito; Sparman, Michelle; Mitalipov, Shoukhrat

    2014-01-01

    Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multi-organ diseases. Tissues with a high metabolic demand such as brain, heart, muscle, CNS are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA (mtDNA) or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Since mtDNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review, we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application. PMID:24382342

  7. Mitochondrial Replacement: Ethics And Identity

    OpenAIRE

    Wrigley, Anthony; Wilkinson, Stephen; Appleby, John B

    2015-01-01

    Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life-threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Mat...

  8. Computed tomography in mitochondrial cytopathy

    Energy Technology Data Exchange (ETDEWEB)

    Egger, J.; Kendall, B.E.

    1981-10-01

    The clinical and computed tomographic (CT) findings in 11 proven cases of mitochondrial cytopathy (mitochondrial myopathy, Kearns Sayre syndrome, ophthalmoplegia plus) were studied. The CT changes included focal low density lesions in the basal ganglia and white matter and atrophy which could be slight or diffuse and severe. Calcification has been described in the basal ganglia, but did not occur in our series. Serial CT showed progression of the abnormalities. The differential diagnosis is discussed.

  9. Mitochondrial diseases: advances and issues

    Science.gov (United States)

    Scarpelli, Mauro; Todeschini, Alice; Volonghi, Irene; Padovani, Alessandro; Filosto, Massimiliano

    2017-01-01

    Mitochondrial diseases (MDs) are a clinically heterogeneous group of disorders caused by a dysfunction of the mitochondrial respiratory chain. They can be related to mutation of genes encoded using either nuclear DNA or mitochondrial DNA. The advent of next generation sequencing and whole exome sequencing in studying the molecular bases of MDs will bring about a revolution in the field of mitochondrial medicine, also opening the possibility of better defining pathogenic mechanisms and developing novel therapeutic approaches for these devastating disorders. The canonical rules of mitochondrial medicine remain milestones, but novel issues have been raised following the use of advanced diagnostic technologies. Rigorous validation of the novel mutations detected using deep sequencing in patients with suspected MD, and a clear definition of the natural history, outcome measures, and biomarkers that could be usefully adopted in clinical trials, are mandatory goals for the scientific community. Today, therapy is often inadequate and mostly palliative. However, important advances have been made in treating some clinical entities, eg, mitochondrial neuro-gastrointestinal encephalomyopathy, for which approaches using allogeneic hematopoietic stem cell transplantation, orthotopic liver transplantation, and carrier erythrocyte entrapped thymidine phosphorylase enzyme therapy have recently been developed. Promising new treatment methods are being identified so that researchers, clinicians, and patients can join forces to change the history of these untreatable disorders. PMID:28243136

  10. Entrance-channel Mass-asymmetry Dependence of Compound-nucleus Formation Time in Light Heavy-ion Reactions

    CERN Document Server

    Szanto de Toledo, A; Beck, C; Thoennessen, M

    1996-01-01

    The entrance-channel mass-asymmetry dependence of the compound nucleus formation time in light heavy-ion reactions has been investigated within the framework of semiclassical dissipative collision models. the model calculations have been succesfully applied to the formation of the $^{38}$Ar compound nucleus as populated via the $^{9}$Be+$^{29}$Si, $^{11}$B+$^{27}$Al, $^{12}$C+$^{26}$Mg and $^{19}$F+$^{19}$F entrance channels. The shape evolution of several other light composite systems appears to be consistent with the so-called "Fusion Inhibition Factor" which has been experimentally observed. As found previously in more massive systems for the fusion-evaporation process, the entrance-channel mass-asymmetry degree of freedom appears to determine the competition between the different mechanisms as well as the time scales involved.

  11. Mitochondrial DNA variant m.15218A > G in Finnish epilepsy patients who have maternal relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus

    OpenAIRE

    Soini, Heidi K; Moilanen, Jukka S; Vilmi-Kerälä, Tiina; Finnilä, Saara; Majamaa, Kari

    2013-01-01

    Background Mitochondrial diseases caused by mutations in mitochondrial DNA (mtDNA) affect tissues with high energy demand. Epilepsy is one of the manifestations of mitochondrial dysfunction when the brain is affected. We have studied here 79 Finnish patients with epilepsy and who have maternal first- or second-degree relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus. Methods The entire mtDNA was studied by using conformation sensitive gel electrophoresis and PCR f...

  12. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity.

    Science.gov (United States)

    Szeto, H H; Birk, A V

    2014-12-01

    The mitochondrial electron transport chain (ETC) plays a central role in energy generation in the cell. Mitochondrial dysfunctions diminish adenosine triphosphate (ATP) production and result in insufficient energy to maintain cell function. As energy output declines, the most energetic tissues are preferentially affected. To satisfy cellular energy demands, the mitochondrial ETC needs to be able to elevate its capacity to produce ATP at times of increased metabolic demand or decreased fuel supply. This mitochondrial plasticity is reduced in many age-associated diseases. In this review, we describe the serendipitous discovery of a novel class of compounds that selectively target cardiolipin on the inner mitochondrial membrane to optimize efficiency of the ETC and thereby restore cellular bioenergetics in aging and diverse disease models, without any effect on the normal healthy organism. The first of these compounds, SS-31, is currently in multiple clinical trials.

  13. Low metabolic rates in salamanders are correlated with weak selective constraints on mitochondrial genes.

    Science.gov (United States)

    Chong, Rebecca A; Mueller, Rachel Lockridge

    2013-03-01

    Mitochondria are the site for the citric acid cycle and oxidative phosphorylation (OXPHOS), the final steps of ATP synthesis via cellular respiration. Each mitochondrion contains its own genome; in vertebrates, this is a small, circular DNA molecule that encodes 13 subunits of the multiprotein OXPHOS electron transport complexes. Vertebrate lineages vary dramatically in metabolic rates; thus, functional constraints on mitochondrial-encoded proteins likely differ, potentially impacting mitochondrial genome evolution. Here, we examine mitochondrial genome evolution in salamanders, which have the lowest metabolic requirements among tetrapods. We show that salamanders experience weaker purifying selection on protein-coding sequences than do frogs, a comparable amphibian clade with higher metabolic rates. In contrast, we find no evidence for weaker selection against mitochondrial genome expansion in salamanders. Together, these results suggest that different aspects of mitochondrial genome evolution (i.e., nucleotide substitution, accumulation of noncoding sequences) are differently affected by metabolic variation across tetrapod lineages.

  14. Mitochondrial Cristae Shape Determines Respiratory Chain Supercomplexes Assembly and Respiratory Efficiency

    Science.gov (United States)

    Cogliati, Sara; Frezza, Christian; Soriano, Maria Eugenia; Varanita, Tatiana; Quintana-Cabrera, Ruben; Corrado, Mauro; Cipolat, Sara; Costa, Veronica; Casarin, Alberto; Gomes, Ligia C.; Perales-Clemente, Ester; Salviati, Leonardo; Fernandez-Silva, Patricio; Enriquez, Jose A.; Scorrano, Luca

    2013-01-01

    Summary Respiratory chain complexes assemble into functional quaternary structures called supercomplexes (RCS) within the folds of the inner mitochondrial membrane, or cristae. Here, we investigate the relationship between respiratory function and mitochondrial ultrastructure and provide evidence that cristae shape determines the assembly and stability of RCS and hence mitochondrial respiratory efficiency. Genetic and apoptotic manipulations of cristae structure affect assembly and activity of RCS in vitro and in vivo, independently of changes to mitochondrial protein synthesis or apoptotic outer mitochondrial membrane permeabilization. We demonstrate that, accordingly, the efficiency of mitochondria-dependent cell growth depends on cristae shape. Thus, RCS assembly emerges as a link between membrane morphology and function. PMID:24055366

  15. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery.

    Science.gov (United States)

    Yang, Yufeng; Ouyang, Yingshi; Yang, Lichuan; Beal, M Flint; McQuibban, Angus; Vogel, Hannes; Lu, Bingwei

    2008-05-13

    Mitochondria form dynamic tubular networks that undergo frequent morphological changes through fission and fusion, the imbalance of which can affect cell survival in general and impact synaptic transmission and plasticity in neurons in particular. Some core components of the mitochondrial fission/fusion machinery, including the dynamin-like GTPases Drp1, Mitofusin, Opa1, and the Drp1-interacting protein Fis1, have been identified. How the fission and fusion processes are regulated under normal conditions and the extent to which defects in mitochondrial fission/fusion are involved in various disease conditions are poorly understood. Mitochondrial malfunction tends to cause diseases with brain and skeletal muscle manifestations and has been implicated in neurodegenerative diseases such as Parkinson's disease (PD). Whether abnormal mitochondrial fission or fusion plays a role in PD pathogenesis has not been shown. Here, we show that Pink1, a mitochondria-targeted Ser/Thr kinase linked to familial PD, genetically interacts with the mitochondrial fission/fusion machinery and modulates mitochondrial dynamics. Genetic manipulations that promote mitochondrial fission suppress Drosophila Pink1 mutant phenotypes in indirect flight muscle and dopamine neurons, whereas decreased fission has opposite effects. In Drosophila and mammalian cells, overexpression of Pink1 promotes mitochondrial fission, whereas inhibition of Pink1 leads to excessive fusion. Our genetic interaction results suggest that Fis1 may act in-between Pink1 and Drp1 in controlling mitochondrial fission. These results reveal a cell biological role for Pink1 and establish mitochondrial fission/fusion as a paradigm for PD research. Compounds that modulate mitochondrial fission/fusion could have therapeutic value in PD intervention.

  16. 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.

  17. Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy.

    Science.gov (United States)

    Xu, Chong-Chong; Denton, Kyle R; Wang, Zhi-Bo; Zhang, Xiaoqing; Li, Xue-Jun

    2016-01-01

    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.

  18. Entrance Channel Stereospecificity of Photoinitiated H-Atom Reactions in Weakly Bonded Complexes

    Science.gov (United States)

    Shin, Seung Koo; Chen, Y.; Oh, D.; Wittig, C.

    1990-08-01

    Hot H-atom reactions photoinitiated in T-shaped CO2-HBr and nearly-linear CO2-HCl complexes show remarkably different reaction probabilities. Broadside H-atom approaches in CO2-HBr complexes are greatly favoured over the relatively endon approaches of CO2-HCl complexes, a striking steric effect. Photoinitiated hot H-atom reactions with N2O result in a much lower [NH]/[OH] ratio with N2O-HI complexes than under single-collision conditions at the same photolysis wavelength. In addition, OH rotational distributions differ markedly between bulk and complexed conditions, while NH rotational distributions are similar. These results can be interpreted in terms of entrance channel stereospecificity influencing chemically distinct product channels.

  19. Integral throat entrance development, qualification and production for the Antares 3 nozzle

    Science.gov (United States)

    Clayton, F. I.; Dirling, R. B.; Eitman, D. A.; Loomis, W. C.

    1982-01-01

    Although design analyses of a G-90 graphite integral throat entrance for the Antares 3 solid rocket motor nozzle indicated acceptable margins of safety, the nozzle throat insert suffered a thermostructural failure during the first development firing. Subsequent re-analysis using properties measured on material from the same billet as the nozzle throat insert showed negative margins. Carbon-carbon was investigated and found to result in large positive margins of safety. The G-90 graphite was replaced by SAI fast processed 4-D material which uses Hercules HM 10000 fiber as the reinforcement. Its construction allows powder filling of the interstices after preform fabrication which accelerates the densification process. Allied 15V coal tar pitch is then used to complete densification. The properties were extensively characterized on this material and six nozzles were subjected to demonstration, development and qualification firings.

  20. Washback Effect of University Entrance exams in Applied Mathematics to Social Sciences

    Science.gov (United States)

    Díaz, Patricia; Mier, Verónica; Alonso, Pedro

    2016-01-01

    Curricular issues of subject Applied Mathematics to Social Sciences are studied in relation to university entrance exams performed in several Spanish regions between 2009–2014. By using quantitative and qualitative analyses, it has been studied how these exams align with curriculum and how they produce a washback on curriculum and teachers’ work. Additionally, one questionnaire about teachers’ practices has been performed, in order to find out how the exams are influencing teaching methodology development. Main results obtained show that evaluation is producing a bias on the official curriculum, substantially simplifying the specific orientation that should guide applied mathematics. Furthermore, teachers’ practices are influenced by the exams, and they usually approach their teaching methodology to the frequent types of exams. Also, slight differences among the teachers lead to distinguish two behavioral subgroups. Results can also be useful in an international context, because of the importance of standardized exit exams in OECD countries. PMID:27936103

  1. Images of the laser entrance hole from the static x-ray imager at NIF.

    Science.gov (United States)

    Schneider, M B; Jones, O S; Meezan, N B; Milovich, J L; Town, R P; Alvarez, S S; Beeler, R G; Bradley, D K; Celeste, J R; Dixit, S N; Edwards, M J; Haugh, M J; Kalantar, D H; Kline, J L; Kyrala, G A; Landen, O L; MacGowan, B J; Michel, P; Moody, J D; Oberhelman, S K; Piston, K W; Pivovaroff, M J; Suter, L J; Teruya, A T; Thomas, C A; Vernon, S P; Warrick, A L; Widmann, K; Wood, R D; Young, B K

    2010-10-01

    The static x-ray imager at the National Ignition Facility is a pinhole camera using a CCD detector to obtain images of Hohlraum wall x-ray drive illumination patterns seen through the laser entrance hole (LEH). Carefully chosen filters, combined with the CCD response, allow recording images in the x-ray range of 3-5 keV with 60 μm spatial resolution. The routines used to obtain the apparent size of the backlit LEH and the location and intensity of beam spots are discussed and compared to predictions. A new soft x-ray channel centered at 870 eV (near the x-ray peak of a 300 eV temperature ignition Hohlraum) is discussed.

  2. In-Tunnel Blast Pressure Empirical Formulas for Detonations External, Internal and at the Tunnel Entrance

    Institute of Scientific and Technical Information of China (English)

    LI Xiudi; ZHENG Yingren

    2006-01-01

    In order to define the loading on protective doors of an underground tunnel,the exact knowledge of the blast propagation through tunnels is needed.Thirty-three scale high-explosive tests are conducted to obtain in-tunnel blast pressure for detonations external,internal and at the tunnel entrance.The cross section of the concrete model tunnel is 0.67 m2.Explosive charges of TNT,ranging in mass from 400 g to 4 600 g,are detonated at various positions along the central axis of the model tunnel.Blast gages are flush-installed in the interior surface of the tunnel to record side-on blast pressure as it propagates down the tunnel.The engineering empirical formulas for predicting blast peak pressure are evaluated,and are found to be reasonably accurate for in-tunnel pressure prediction.

  3. Dose-area product and entrance surface dose in paediatric radiography

    Energy Technology Data Exchange (ETDEWEB)

    Servomaa, A.; Komppa, T.; Parviainen, T.; Heikkilae, M. [STUK - Radiation and Nuclear Safety Authority, Helsinki (Finland)

    2003-06-01

    Dose-area products (DAP) in paediatric radiography were measured in four university hospitals in Finland. The entrance surface dose (ESD) was calculated from the measured DAP value for each radiographic projection. The purpose was to combine the results with other European studies for development of diagnostic reference levels for paediatric X-ray examinations. The study included 740 paediatric patients, and a total of 1500 single projections were recorded, including 660 projections from extremities. Results were compared with recommended best practices and diagnostic reference levels for ESD. Ratios of DAP to ESD were studied to estimate the levels of DAP corresponding to recommended ESD reference levels. It is desirable for practical purposes that diagnostic reference levels for radiographic projections are also expressed in terms of dose-area product. (orig.)

  4. Application of Variational Methods to the Thermal Entrance Region of Ducts

    Science.gov (United States)

    Sparrow, E. M.; Siegel. R.

    1960-01-01

    A variational method is presented for solving eigenvalue problems which arise in connection with the analysis of convective heat transfer in the thermal entrance region of ducts. Consideration is given, to both situations where the temperature profile depends upon one cross-sectional coordinate (e.g. circular tube) or upon two cross-sectional coordinates (e.g. rectangular duct). The variational method is illustrated and verified by application to laminar heat transfer in a circular tube and a parallel-plate channel, and good agreement with existing numerical solutions is attained. Then, application is made to laminar heat transfer in a square duct as a check, an alternate computation for the square duct is made using a method indicated by Misaps and Pohihausen. The variational method can, in principle, also be applied to problems in turbulent heat transfer.

  5. A numerical study of entrance region in a curved annulus with an inward and outward eccentricity

    Directory of Open Access Journals (Sweden)

    M.R.H. Nobari

    2016-09-01

    Full Text Available In this article, developing incompressible fluid flow in a curved annulus with inward and outward eccentricities is studied numerically. To do so, a second order finite difference method based on the projection algorithm is employed to solve the governing equations written in a general bipolar–toroidal coordinate system using a three-dimensional staggered uniform grid. The effects of the governing dimensionless parameters such as the Dean number, Reynolds number, curvature ratio, aspect ratio, and eccentricity on the flow field pattern and friction factor are studied in the entrance region. The numerical results obtained indicate that the outward eccentricity significantly deforms the secondary flows and axial velocity profiles. Furthermore, as the eccentricity increases, the friction factor decreases due to the reduction of secondary flow intensity.

  6. Effect of ethidium bromide on transmission of mitochondrial genomes and DNA synthesis in the petite negative yeast Schizosaccharomyces pomhe.

    Science.gov (United States)

    Wolf, K; Del Giudice, L

    1980-04-01

    Treatment of haploid strains of the petite negative yeast Schizosaccharomyces pomhe with ethidium bromide prior to mating with untreated cells reduces transmission of mitochondrial markers from the treated strains. This effect is fully reversible after 20 generations of growth in drug free medium before mating. In contrast to the petite positive yeast Saccharomyces cerevisiae, where nuclear DNA synthesis is not affected but mitochondrial DNA is degraded in the presence of 20 μg/ml ethidium bromide, the same concentration decreases both nuclear and mitochondrial DNA synthesis in Schizosaccharomyces pomhe. After removal of the drug, nuclear DNA synthesis increases faster than its mitochondrial counterpart in Schizosaccharomyces pomhe.

  7. Measurement of entrance skin dose and estimation of organ dose during pediatric chest radiography.

    Science.gov (United States)

    Kumaresan, M; Kumar, Rajesh; Biju, K; Choubey, Ajay; Kantharia, S

    2011-06-01

    Entrance skin dose (ESD) was measured to calculate the organ doses from the anteroposterior (AP) and posteroanterior (PA) chest x-ray projections for pediatric patients in an Indian hospital. High sensitivity tissue-equivalent thermoluminescent dosimeters (TLD, LiF: Mg, Cu, P chips) were used for measuring entrance skin dose. The respective organ doses were calculated using the Monte Carlo method (MCNP 3.1) to simulate the examination set-up and a three-dimensional mathematical phantom for representing an average 5-y-old Indian child. Using this method, conversion coefficients were derived for translating the measured ESD to organ doses. The average measured ESDs for the chest AP and PA projections were 0.305 mGy and 0.171 mGy, respectively. The average calculated organ doses in the AP and the PA projections were 0.196 and 0.086 mSv for the thyroid, 0.167 and 0.045 mSv for the trachea, 0.078 and 0.043 mSv for the lungs, 0.110 and 0.013 mSv for the liver, 0.002 and 0.016 mSv for the bone marrow, 0.024 and 0.002 mSv for the kidneys, and 0.109 and 0.023 mSv for the heart, respectively. The ESD and organ doses can be reduced significantly with the proper radiological technique. According to these results, the chest PA projection should be preferred over the AP projection in pediatric patients. The estimated organ doses for the chest AP and PA projections can be used for the estimation of the associated risk.

  8. Mitochondrial diseases: advances and issues

    Directory of Open Access Journals (Sweden)

    Scarpelli M

    2017-02-01

    Full Text Available Mauro Scarpelli,1 Alice Todeschini,2 Irene Volonghi,2 Alessandro Padovani,2 Massimiliano Filosto2 1Department of Neuroscience, Unit of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy; 2Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST “Spedali Civili”, University of Brescia, Brescia, Italy Abstract: Mitochondrial diseases (MDs are a clinically heterogeneous group of disorders caused by a dysfunction of the mitochondrial respiratory chain. They can be related to mutation of genes encoded using either nuclear DNA or mitochondrial DNA. The advent of next generation sequencing and whole exome sequencing in studying the molecular bases of MDs will bring about a revolution in the field of mitochondrial medicine, also opening the possibility of better defining pathogenic mechanisms and developing novel therapeutic approaches for these devastating disorders. The canonical rules of mitochondrial medicine remain milestones, but novel issues have been raised following the use of advanced diagnostic technologies. Rigorous validation of the novel mutations detected using deep sequencing in patients with suspected MD, and a clear definition of the natural history, outcome measures, and biomarkers that could be usefully adopted in clinical trials, are mandatory goals for the scientific community. Today, therapy is often inadequate and mostly palliative. However, important advances have been made in treating some clinical entities, eg, mitochondrial neuro-gastrointestinal encephalomyopathy, for which approaches using allogeneic hematopoietic stem cell transplantation, orthotopic liver transplantation, and carrier erythrocyte entrapped thymidine phosphorylase enzyme therapy have recently been developed. Promising new treatment methods are being identified so that researchers, clinicians, and patients can join forces to change the history of these untreatable disorders. Keywords: mitochondrial diseases

  9. Mitochondrial drug targets in neurodegenerative diseases.

    Science.gov (United States)

    Lee, Jiyoun

    2016-02-01

    Growing evidence suggests that mitochondrial dysfunction is the main culprit in neurodegenerative diseases. Given the fact that mitochondria participate in diverse cellular processes, including energetics, metabolism, and death, the consequences of mitochondrial dysfunction in neuronal cells are inevitable. In fact, new strategies targeting mitochondrial dysfunction are emerging as potential alternatives to current treatment options for neurodegenerative diseases. In this review, we focus on mitochondrial proteins that are directly associated with mitochondrial dysfunction. We also examine recently identified small molecule modulators of these mitochondrial targets and assess their potential in research and therapeutic applications.

  10. 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.

  11. Effects of hydrogen peroxide on mitochondrial gene expression of intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Ming Li; Qian Cai; Hong Zhou; Guang-Xia Xiao

    2002-01-01

    AIM: To study the effects of hydrogen peroxide on mitochondrial gene expression of intestinal epithelial cells in in vitro model of hydrogen peroxide-stimulated SW-480 cells.METHODS: RNA of hydrogen peroxide-induced SW-480 cells was isolated, and reverse-transcriptional polymerase chain reaction was performed to study gene expression of ATPase subunit 6, ATPase subunit 8, cytochrome c oxidase subunit Ⅰ (COⅠ), cytochrome coxidase subuit Ⅱ (COⅡ) and cytochrome c oxidase subunit Ⅲ (COⅢ). Mitochondria were isolated and activities of mitochondrial cytochrome c oxidase and ATPase were also measured simultaneously.RESULTS: Hydrogen peroxide led to differential expression of mitochondrial genes with some genes up-regulated or down-regulated in a dose dependent manner. Differences were very obvious in expressions of mitochondrial genes of cells treated with hydrogen peroxide in a concentration of 400 μmol/L or 4 mmol/L. In general, differential expression of mitochondrial genes was characterized by up-regulation of mitochondrial genes in the concentration of 400 μmol/L and down-regulation in the concentration of 4 mmol/L. In consistence with changes in mitochondrial gene expressions, hydrogen peroxide resulted in decreased activities of cytochrome c oxidase and ATPase.CONCLUSIONS: The differential expression of mitochondrial genes encoding cytochrome c oxidase and ATPase is involved in apoptosis of intestinal epithelial cells by affecting activities of cytochorme c oxidase and ATPase.

  12. Pim-1 preserves mitochondrial morphology by inhibiting dynamin-related protein 1 translocation.

    Science.gov (United States)

    Din, Shabana; Mason, Matthew; Völkers, Mirko; Johnson, Bevan; Cottage, Christopher T; Wang, Zeping; Joyo, Anya Y; Quijada, Pearl; Erhardt, Peter; Magnuson, Nancy S; Konstandin, Mathias H; Sussman, Mark A

    2013-04-09

    Mitochondrial morphological dynamics affect the outcome of ischemic heart damage and pathogenesis. Recently, mitochondrial fission protein dynamin-related protein 1 (Drp1) has been identified as a mediator of mitochondrial morphological changes and cell death during cardiac ischemic injury. In this study, we report a unique relationship between Pim-1 activity and Drp1 regulation of mitochondrial morphology in cardiomyocytes challenged by ischemic stress. Transgenic hearts overexpressing cardiac Pim-1 display reduction of total Drp1 protein levels, increased phosphorylation of Drp1-(S637), and inhibition of Drp1 localization to the mitochondria. Consistent with these findings, adenoviral-induced Pim-1 neonatal rat cardiomyocytes (NRCMs) retain a reticular mitochondrial phenotype after simulated ischemia (sI) and decreased Drp1 mitochondrial sequestration. Interestingly, adenovirus Pim-dominant negative NRCMs show increased expression of Bcl-2 homology 3 (BH3)-only protein p53 up-regulated modulator of apoptosis (PUMA), which has been previously shown to induce Drp1 accumulation at mitochondria and increase sensitivity to apoptotic stimuli. Overexpression of the p53 up-regulated modulator of apoptosis-dominant negative adenovirus attenuates localization of Drp1 to mitochondria in adenovirus Pim-dominant negative NRCMs promotes reticular mitochondrial morphology and inhibits cell death during sI. Therefore, Pim-1 activity prevents Drp1 compartmentalization to the mitochondria and preserves reticular mitochondrial morphology in response to sI.

  13. Role of Mitochondrial Dynamics in Neuronal Development: Mechanism for Wolfram Syndrome.

    Directory of Open Access Journals (Sweden)

    Michal Cagalinec

    2016-07-01

    Full Text Available Deficiency of the protein Wolfram syndrome 1 (WFS1 is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations in mitochondrial dynamics. The aim of this study was to examine the hypothesis that WFS1 deficiency affects neuronal function via mitochondrial abnormalities. We show that down-regulation of WFS1 in neurons leads to dramatic changes in mitochondrial dynamics (inhibited mitochondrial fusion, altered mitochondrial trafficking, and augmented mitophagy, delaying neuronal development. WFS1 deficiency induces endoplasmic reticulum (ER stress, leading to inositol 1,4,5-trisphosphate receptor (IP3R dysfunction and disturbed cytosolic Ca2+ homeostasis, which, in turn, alters mitochondrial dynamics. Importantly, ER stress, impaired Ca2+ homeostasis, altered mitochondrial dynamics, and delayed neuronal development are causatively related events because interventions at all these levels improved the downstream processes. Our data shed light on the mechanisms of neuronal abnormalities in Wolfram syndrome and point out potential therapeutic targets. This work may have broader implications for understanding the role of mitochondrial dynamics in neuropsychiatric diseases.

  14. Modes of metabolic compensation during mitochondrial disease using the Drosophila model of ATP6 dysfunction.

    Directory of Open Access Journals (Sweden)

    Alicia M Celotto

    Full Text Available Numerous mitochondrial DNA mutations cause mitochondrial encephalomyopathy: a collection of related diseases for which there exists no effective treatment. Mitochondrial encephalomyopathies are complex multisystem diseases that exhibit a relentless progression of severity, making them both difficult to treat and study. The pathogenic and compensatory metabolic changes that are associated with chronic mitochondrial dysfunction are not well understood. The Drosophila ATP6(1 mutant models human mitochondrial encephalomyopathy and allows the study of metabolic changes and compensation that occur throughout the lifetime of an affected animal. ATP6(1animals have a nearly complete loss of ATP synthase activity and an acute bioenergetic deficit when they are asymptomatic, but surprisingly we discovered no chronic bioenergetic deficit in these animals during their symptomatic period. Our data demonstrate dynamic metabolic compensatory mechanisms that sustain normal energy availability and activity despite chronic mitochondrial complex V dysfunction resulting from an endogenous mutation in the mitochondrial DNA. ATP6(1animals compensate for their loss of oxidative phosphorylation through increases in glycolytic flux, ketogenesis and Kreb's cycle activity early during pathogenesis. However, succinate dehydrogenase activity is reduced and mitochondrial supercomplex formation is severely disrupted contributing to the pathogenesis seen in ATP6(1 animals. These studies demonstrate the dynamic nature of metabolic compensatory mechanisms and emphasize the need for time course studies in tractable animal systems to elucidate disease pathogenesis and novel therapeutic avenues.

  15. Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization.

    Science.gov (United States)

    Lam, M; Oleinick, N L; Nieminen, A L

    2001-12-14

    Photodynamic therapy (PDT), a novel and promising cancer treatment that employs a combination of a photosensitizing chemical and visible light, induces apoptosis in human epidermoid carcinoma A431 cells. However, the precise mechanism of PDT-induced apoptosis is not well characterized. To dissect the pathways of PDT-induced apoptosis, we investigated the involvement of mitochondrial damage by examining a second generation photosensitizer, the silicon phthalocyanine 4 (Pc 4). By using laser-scanning confocal microscopy, we found that Pc 4 localized to cytosolic membranes primarily, but not exclusively, in mitochondria. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes when cells were exposed to Pc 4 and 670-675 nm light. This was followed by mitochondrial inner membrane permeabilization, depolarization and swelling, cytochrome c release, and apoptotic death. Desferrioxamine prevented mitochondrial ROS production and the events thereafter. Cyclosporin A plus trifluoperazine, blockers of the mitochondrial permeability transition, inhibited mitochondrial inner membrane permeabilization and depolarization without affecting mitochondrial ROS generation. These data indicate that the mitochondrial ROS are critical in initiating mitochondrial inner membrane permeabilization, which leads to mitochondrial swelling, cytochrome c release to the cytosol, and apoptotic death during PDT with Pc 4.

  16. 消极完美主义对学业成败归因与考研焦虑的影响%Influence of negative perfectionism on achievement attribution and the post-graduate entrance test anxiety

    Institute of Scientific and Technical Information of China (English)

    申鲁军; 杨磊; 罗艳艳; 邱智超

    2012-01-01

    目的 考察消极完美主义在大学生考研焦虑与学业成败归因中的作用.方法 采用随机整群抽样法选择500名考研大学生为被试对象,采用考研焦虑问卷、学业成败归因问卷及消极完美主义问卷进行测试.结果 考研焦虑、学业成败归因与消极完美主义之间存在显著正相关(r1 =0.464,P<0.01;r2 =0.519,P<0.01);消极完美主义作为中介变量调节着学业成败归因与考研焦虑之间的关系,中介效应量为0.138.结论 考研焦虑受消极完美主义与学业成败归因的影响,而学业成败归因可能是更本质的影响因素.%Objective To investigate the effect of negative perfectionism on achievement attribution and the post-graduate entrance test anxiety. Methods Five hundred students were selected by random cluster sampling method. The post-graduate entrance test anxiety scale, achievement attribution scale and negative perfectionism scale were used to test the students. Results There was a significant positive relationship between the graduate entrance test anxiety, negative perfectionism and achievement attribution(r1=0.464,P <0. 01 ;r2 =0. 519,P <0. 01). Negative perfectionism as intervening variable adjusted the relationship between achievement attribution and the graduate entrance test anxiety, the intermediary effect was about 0. 138. Conclusion The graduate entrance test anxiety is affected by negative perfectionism and achievement attribution, and achievement attribution may be a more essential influential factor.

  17. Overview of mitochondrial bioenergetics.

    Science.gov (United States)

    Madeira, Vitor M C

    2012-01-01

    Bioenergetic Science started in seventh century with the pioneer works by Joseph Priestley and Antoine Lavoisier on photosynthesis and respiration, respectively. New developments were implemented by Pasteur in 1860s with the description of fermentations associated to microorganisms, further documented by Buchner brothers who discovered that fermentations also occurred in cell extracts in the absence of living cells. In the beginning of twentieth century, Harden and Young demonstrated that orthophosphate and other heat-resistant compounds (cozymase), later identified as NAD, ADP, and metal ions, were mandatory in the fermentation of glucose. The full glycolysis pathway has been detailed in 1940s with the contributions of Embden, Meyeroff, Parnas, Warburg, among others. Studies on the citric acid cycle started in 1910 (Thunberg) and were elucidated by Krebs et al. in the 1940s. Mitochondrial bioenergetics gained emphasis in the late 1940s and 1950s with the works of Lenhinger, Racker, Chance, Boyer, Ernster, and Slater, among others. The prevalent "chemical coupling hypothesis" of energy conservation in oxidative phosphorylation was challenged and replaced by the "chemiosmotic hypothesis" originally formulated in 1960s by Mitchell and later substantiated and extended to energy conservation in bacteria and chloroplasts, besides mitochondria, with clear-cut identification of molecular proton pumps. After identification of most reactive mechanisms, emphasis has been directed to structure resolution of molecular complex clusters, e.g., cytochrome c oxidase, complex III, complex II, ATP synthase, photosystem I, photosynthetic water splitting center, and energy collecting antennæ of several photosynthetic systems. Modern trends concern to the reactivity of radical and other active species in association with bioenergetic activities. A promising trend concentrates on the cell redox status quantified in terms of redox potentials. In spite of significant development and

  18. Hypoxamirs and Mitochondrial Metabolism

    Science.gov (United States)

    Cottrill, Katherine A.; Chan, Stephen Y.

    2014-01-01

    Abstract Significance: Chronic hypoxia can drive maladaptive responses in numerous organ systems, leading to a multitude of chronic mammalian diseases. Oxygen homeostasis is intimately linked with mitochondrial metabolism, and dysfunction in these systems can combine to form the backbone of hypoxic-ischemic injury in multiple tissue beds. Increased appreciation of the crucial roles of hypoxia-associated miRNA (hypoxamirs) in metabolism adds a new dimension to our understanding of the regulation of hypoxia-induced disease. Recent Advances: Myriad factors related to glycolysis (e.g., aldolase A and hexokinase II), tricarboxylic acid cycle function (e.g., glutaminase and iron-sulfur cluster assembly protein 1/2), and apoptosis (e.g., p53) have been recently implicated as targets of hypoxamirs. In addition, several hypoxamirs have been implicated in the regulation of the master transcription factor of hypoxia, hypoxia-inducible factor-1α, clarifying how the cellular program of hypoxia is sustained and resolved. Critical Issues: Central to the discussion of metabolic change in hypoxia is the Warburg effect, a shift toward anaerobic metabolism that persists after normal oxygen levels have been restored. Many newly discovered targets of hypoxia-driven microRNA converge on pathways known to be involved in this pathological phenomenon and the apoptosis-resistant phenotype associated with it. Future Directions: The often synergistic functions of miRNA may make them ideal therapeutic targets. The use of antisense inhibitors is currently being considered in diseases in which hypoxia and metabolic dysregulation predominate. In addition, exploration of pleiotripic miRNA functions will likely continue to offer unique insights into the mechanistic relationships of their downstream target pathways and associated hypoxic phenotypes. Antioxid. Redox Signal. 21, 1189–1201. PMID:24111795

  19. Mitochondrial genetics and hearing loss: the missing link between genotype and phenotype.

    Science.gov (United States)

    Fischel-Ghodsian, N

    1998-05-01

    Mitochondrial DNA mutations have been implicated in a great variety of diseases, including such common ones as diabetes, Parkinson's disease and Alzheimer's, but the pathophysiological pathway leading from a specific mutation to a specific phenotype has remained elusive. Individuals with the same mutation can fall along a clinical spectrum ranging from asymptomatic to severely affected, and can even have completely different diseases. Much of this phenotypic heterogeneity has been attributed to the heteroplasmic nature of mitochondrial mutations, with both normal and mutated mitochondrial chromosomes being present in different proportions and tissue distributions. Isolated hearing loss is one of the only mitochondrial disorders that can be caused by homoplasmic mutations (e.g., only mutated mitochondrial mutations are present in all tissues). This review will outline the relationship between mitochondrial mutations and hearing loss while showing that even in a homoplasmic model, the two basic questions of mitochondrial genetics, penetrance and tissue specificity, remain unanswered: Why does the same mutation cause severe hearing loss in some family members but not in others, and why is the ear the only organ affected?

  20. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-07

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

  1. Hsp90 inhibition decreases mitochondrial protein turnover.

    Directory of Open Access Journals (Sweden)

    Daciana H Margineantu

    Full Text Available BACKGROUND: Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis. FINDINGS: We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP. CONCLUSIONS: Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors.

  2. Recombinant Mitochondrial Transcription Factor A with N-terminal Mitochondrial Transduction Domain Increases Respiration and Mitochondrial Gene Expression

    OpenAIRE

    Iyer, Shilpa; Thomas, Ravindar R.; Portell, Francisco R.; Dunham, Lisa D.; Quigley, Caitlin K.; Bennett, James P

    2009-01-01

    We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its “mitochondrial transduction domain” (MTD=PTD+MLS). Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment of cybrid cells carrying the G11778A LHON mutation. MTD-TFAM reversibly increased respiration and levels ...

  3. The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes.

    Science.gov (United States)

    Karaa, Amel; Goldstein, Amy

    2015-02-01

    Primary mitochondrial diseases refer to a group of heterogeneous and complex genetic disorders affecting 1:5000 people. The true prevalence is anticipated to be even higher because of the complexity of achieving a diagnosis in many patients who present with multisystemic complaints ranging from infancy to adulthood. Diabetes is a prominent feature of several of these disorders which might be overlooked by the endocrinologist. We here review mitochondrial disorders and describe the phenotypic and pathogenetic differences between mitochondrial diabetes mellitus (mDM) and other more common forms of diabetes mellitus.

  4. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress.

    Science.gov (United States)

    Naudi, Alba; Jove, Mariona; Ayala, Victoria; Cassanye, Anna; Serrano, Jose; Gonzalo, Hugo; Boada, Jordi; Prat, Joan; Portero-Otin, Manuel; Pamplona, Reinald

    2012-01-01

    Oxidative stress has been implicated in diabetes long-term complications. In this paper, we summarize the growing evidence suggesting that hyperglycemia-induced overproduction of superoxide by mitochondrial electron transport chain triggers a maladaptive response by affecting several metabolic and signaling pathways involved in the pathophysiology of cellular dysfunction and diabetic complications. In particular, it is our goal to describe physiological mechanisms underlying the mitochondrial free radical production and regulation to explain the oxidative stress derived from a high intracellular glucose concentration and the resulting maladaptive response that leads to a cellular dysfunction and pathological state. Finally, we outline potential therapies for diabetes focused to the prevention of mitochondrial oxidative damage.

  5. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays.

    Science.gov (United States)

    Barrientos, Antoni; Fontanesi, Flavia; Díaz, Francisca

    2009-10-01

    The oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. For this reason, several approaches for the assessment of the OXPHOS system enzymes have been developed. Based on the methods described elsewhere, the assays describe methods that form a biochemical characterization of the OXPHOS system in cells and mitochondria isolated from cultured cells or tissues.

  6. Mitochondrial ribosome assembly in health and disease.

    Science.gov (United States)

    De Silva, Dasmanthie; Tu, Ya-Ting; Amunts, Alexey; Fontanesi, Flavia; Barrientos, Antoni

    2015-01-01

    The ribosome is a structurally and functionally conserved macromolecular machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which synthesize a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. High-resolution cryo-EM structures of the yeast, porcine and human mitoribosomal subunits and of the entire human mitoribosome have uncovered a wealth of new information to illustrate their evolutionary divergence from their bacterial ancestors and their adaptation to synthesis of highly hydrophobic membrane proteins. With such structural data becoming available, one of the most important remaining questions is that of the mitoribosome assembly pathway and factors involved. The regulation of mitoribosome biogenesis is paramount to mitochondrial respiration, and thus to cell viability, growth and differentiation. Moreover, mutations affecting the rRNA and protein components produce severe human mitochondrial disorders. Despite its biological and biomedical significance, knowledge on mitoribosome biogenesis and its deviations from the much-studied bacterial ribosome assembly processes is scarce, especially the order of rRNA processing and assembly events and the regulatory factors required to achieve fully functional particles. This article focuses on summarizing the current available information on mitoribosome assembly pathway, factors that form the mitoribosome assembly machinery, and the effect of defective mitoribosome assembly on human health.

  7. High-frequency vibration effects on hole entrance chipping in rotary ultrasonic drilling of BK7 glass.

    Science.gov (United States)

    Lv, Dongxi; Zhang, Yuanming; Peng, Yunfeng

    2016-12-01

    This present investigation exhibited some fundamental information about the influence of the high-frequency vibration on the hole entrance chipping formation involved in rotary ultrasonic drilling (RUD) of BK7 glass process. The entrance chipping morphologies, produced with and without ultrasonic, were observed and evaluated with respect to the fracture mechanics of brittle material. Giving consideration to the variation characteristics of the plastic deformation region in the interior material induced by the specific kinematics principles of the abrasive, the ultrasonic effects on the chipping formation mechanisms were investigated by assessing the groove morphologies obtained in the scratching experiment utilizing the formation mechanisms of the lateral cracking. Furthermore, the formal confirmatory tests with and without ultrasonic were performed to validate these chipping formation mechanisms. It was found that the plastic deformed region reached its maximum at the trajectory bottom. Moreover, the propagation of the lateral cracking initially nucleated at the bottom of the ductile deformation zone resulted in the formation of the entrance chipping in formal RUD process. The slight deformation of the material at the two terminals of each groove produced with ultrasonic would provide the inhibitory effects to the further extending of the lateral cracks, which would shrink with the increased spindle speed, and the inhibitory effect dominated in determining the improvement effects on the hole entrance quality. Additionally, a theoretical relationship between the nucleation depth and the propagation length of the lateral cracking was developed for the conventional drilling (CD) process.

  8. Gender Gap in the National College Entrance Exam Performance in China: A Case Study of a Typical Chinese Municipality

    Science.gov (United States)

    Zhang, Yu; Tsang, Mun

    2015-01-01

    This is one of the first studies to investigate gender achievement gap in the National College Entrance Exam in a typical municipality in China, which is the crucial examination for the transition from high school to higher education in that country. Using ordinary least square model and quantile regression model, the study consistently finds that…

  9. Experiencing the Change and Continuity of the College Entrance Examination: A Case Study of "Gaokao" County, 1996-2010

    Science.gov (United States)

    Wang, Yimin; Ross, Heidi

    2010-01-01

    Employing data from three encounters, during 1996, 2001, and 2010, with students and teachers in Huining, gansu, China's "Gaokao county," known for its striking contrast between poverty and the remarkable achievements of its College Entrance Examination (CEE) candidates, we explore the lived experiences of Huining students and teachers…

  10. Comparison of experimental hut entrance and exit behavior between Anopheles darlingi from the Cayo District, Belize, and Zungarococha, Peru.

    Science.gov (United States)

    Sachs, Paige; Diaz Rodriguez, Gloria Alicia; Briceno, Ireneo; King, Russell; Achee, Nicole L; Grieco, John P

    2013-12-01

    Anopheles darlingi is a major vector for malaria in Central and South America. Behavioral, ecological, genetic, and morphologic variability has been observed across its wide distribution. Recent studies have documented that 2 distinct genotypes exist for An. darlingi: a northern lineage (Belize, Guatemala, Colombia, Venezuela, and Panama) and a southern lineage (Amazonia and southern Brazil). In order to determine if these genotypes exhibited different behavioral traits, entrance and exit movement patterns between 2 field populations of An. darlingi that represented each genotype were evaluated using experimental huts. The Belize population exhibited bimodal entrance, with peak entry occurring between 7:00-8:00 p.m. and 5:00-6:00 a.m. and peak exiting occurring between 7:00-8:00 p.m. The Peru population exhibited unimodal entrance, with peak entry occurring between 10:00-11:00 p.m. and peak exiting occurring between 11:00-12:00 a.m. with a secondary smaller peak at 2:30 a.m. Entrance and exit behavioral patterns were significantly different between the Belize and Peru populations of An. darlingi (log-rank [Mantel-Cox] P < 0.001). Information from the present study will be used in the future to determine if there is a correlation between genotype and host-seeking behavior and can be used in the present for regional vector risk assessment.

  11. A Comparative Study of the College Entrance Examination Board Validity Study Service and Freshmen Cumulative Point Averages.

    Science.gov (United States)

    Bukowski, Joseph E.

    The success with which freshmen cumulative point averages may be predicted from a combination of a student's high school rank, Scholastic Aptitude Test (SAT) score (Verbal) and SAT score (Mathematics) was investigated. A multiple regression formula developed by the College Entrance Examination Board was used to combine the three predictors into a…

  12. Identifying challenges and opportunities for residents in upernavik as oil companies are making a first entrance into baffin bay

    DEFF Research Database (Denmark)

    Hansen, Anne Merrild; Tejsner, Pelle

    2016-01-01

    While oil industry is making its first entrance offshore in Baffin Bay the Inuit hunters on the northwest coast of Greenland are struggling to uphold a traditional way of living. The oil industry is encouraged by the Government of Greenland to secure a high degree of local content in projects...

  13. Challenges and opportunities for residents in the Upernavik District while oil companies are making a first entrance in Baffin Bay

    DEFF Research Database (Denmark)

    Hansen, Anne Merrild; Tejsner, Pelle

    2016-01-01

    While oil industry is making its first entrance offshore in Baffin Bay the Inuit hunters on the northwest coast of Greenland are struggling to uphold a traditional way of living. The oil industry is encouraged by the Government of Greenland to secure a high degree of local content in projects...

  14. An Investigation of the Combined Assessments Used as Entrance Criteria for a Gifted English Middle School Program

    Science.gov (United States)

    Lindsey, Colleen D.

    2012-01-01

    The purpose of this study was to determine if the four assessments for entrance into an academic middle school gifted English program were accurately predicting success, as measured by students' grades each nine-week grading period. Some students were dismissed from the program each year because they could not maintain the required minimum average…

  15. Differential Predictive Validity of High School GPA and College Entrance Test Scores for University Students in Yemen

    Science.gov (United States)

    Al-Hattami, Abdulghani Ali Dawod

    2012-01-01

    High school grade point average and college entrance test scores are two admission criteria that are currently used by most colleges in Yemen to select their prospective students. Given their widespread use, it is important to investigate their predictive validity to ensure the accuracy of the admission decisions in these institutions. This study…

  16. Challenges and opportunities for residents in the Upernavik District while oil companies are making a first entrance in Baffin Bay

    DEFF Research Database (Denmark)

    Tejsner, Pelle; Merrild, Anne

    2016-01-01

    The oil industry is making its first entrance offshore in Baffin Bay in a time where Inuit residents on the northwest coast of Greenland are struggling to uphold a traditional way of living. The operating oil companies are encouraged by the Government of Greenland to promote a high degree of local...... companies....

  17. Autism Spectrum Disorder and Mitochondrial Disease

    Science.gov (United States)

    ... Is there a relationship between mitochondrial disease and autism? A: A child with a mitochondrial disease: may ... something else. Q: Is there a relationship between autism and encephalopathy? A: Most children with an autism ...

  18. 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.

  19. Vitelliform macular degeneration associated with mitochondrial myopathy.

    OpenAIRE

    Modi, G; Heckman, J M; Saffer, D

    1992-01-01

    A patient with mitochondrial myopathy is described. Examination of his fundus revealed bilateral vitelliform degeneration of the maculae. This lesion is a focal abnormality of the retinal pigment epithelium and may be a manifestation of the underlying mitochondrial disease.

  20. Mitochondrial maintenance failure in aging and role of sexual dimorphism

    OpenAIRE

    Tower, John

    2014-01-01

    Gene expression changes during aging are partly conserved across species, and suggest that oxidative stress, inflammation and proteotoxicity result from mitochondrial malfunction and abnormal mitochondrial-nuclear signaling. Mitochondrial maintenance failure may result from trade-offs between mitochondrial turnover versus growth and reproduction, sexual antagonistic pleiotropy and genetic conflicts resulting from uni-parental mitochondrial transmission, as well as mitochondrial and nuclear mu...

  1. Mitochondrial calcium-activated potassium channel:another potential target for neuroprotection?

    Institute of Scientific and Technical Information of China (English)

    FangSHEN; Li-pingWU; QianSHEN; QiangXIA

    2004-01-01

    AIM: It has recently been reported that large-conductance Ca2+activated potassium channel is present in the inner mitochondrial membrane (mitoKCa) of the neuron cell, which has been reported to have cardioprotective effect similar to that of mitochondrial ATP-sensitive K+ channel (mitoKATP). Hence the aim of this study was to clarify if mitoKCa is neuroprotective and compare thisnotantial affect with that of mitoK METHODS: Male

  2. Ethics of mitochondrial therapy for deafness.

    Science.gov (United States)

    Legge, Michael; Fitzgerald, Ruth P

    2014-11-07

    Mitochondrial therapy may provide the relief to many families with inherited mitochondrial diseases. However, it also has the potential for use in non-fatal disorders such as inherited mitochondrial deafness, providing an option for correction of the deafness using assisted reproductive technology. In this paper we discuss the potential for use in correcting mitochondrial deafness and consider some of the issues for the deaf community.

  3. Mitochondrial myopathy and myoclonic epilepsy

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1990-03-01

    Full Text Available The authors describe a family (mother, son and two daughters with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.

  4. Mitochondrial dysfunction in autism.

    Science.gov (United States)

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  5. Efficiency of mitochondrially targeted gallic acid in reducing brain mitochondrial oxidative damage.

    Science.gov (United States)

    Parihar, P; Jat, D; Ghafourifar, P; Parihar, M S

    2014-07-03

    Oxidative stress is associated with mitochondrial impairments. Supplying mitochondria with potent antioxidants can reduce oxidative stress—induced mitochondrial impairment. Gallic acid can be used to reduce oxidative burden in mitochondria. In order to increase the bioavailability of gallic acid inside the mitochondria we synthesized mitochondrially targeted gallic acid and explored its preventive effects against sodium nitroprusside induced oxidative stress in isolated mitochondria. Our observations revealed an increase in oxidative stress,decrease in reduced glutathione in mitochondria and increase in the mitochondrial permeability pore transition due to sodium nitroprusside treatment. Pre—treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference. Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid. We conclude that mitochondrially targeted gallic acid can be used for preventing mitochondrial impairment caused by oxidative stress.

  6. An Analysis of Factors Affecting Population Genetic Structure of Oligonychus ununguis Based on the Mitochondrial COI Gene Sequences%基于mtDNA-COI基因序列的针叶小爪螨种群遗传结构影响因素分析

    Institute of Scientific and Technical Information of China (English)

    尹淑艳; 李波; 郭慧玲; 李会; 李杨; 孙绪艮

    2012-01-01

    寄主植物、地理距离、农药胁迫、生境片段化等是影响种群遗传结构和进化的重要因素( Harrison et al.,1996;Hutchinson et al.,1999;Knutsen et al.,2000;罗育发等,2006;褚栋等,2008). 许多有关昆虫与植物间关系的研究发现植食性昆虫具有通过缩小或扩大其寄主范围或转移到新寄主上的进化潜力(Via,1990),这种现象可能使种群间产生完全的生殖隔离进而导致与寄主有关的物种形成.寄主型已在多种植食性节肢动物中有报道(Berlocher et al.,2002).%In order to understand effects of host plant, geographical distance and pesticide stress on the genetic structure of the spruce spider mite ( Oligonychus ununguis) , different populations of the mite were used for analyzing the sequence variation of the mitochondrial cytochrome oxidase I gene (COI) segment. Genetic differentiation was very small in the mites collected from different species of Castanea mollissima, Quercus acutissima, Q. Variabilis, Q. Dentate, which distributed in a narrow range (3 -500 m) , and in the mites from the same species of host plants that distributed in a larger area(25 km). These populations were clustered in the same branch of the NJ phylogenetic tree and the genetic distance between them was 0-0. 001. There was significant genetic differentiation of the mites collected on Q. Variabilis from two different districts, Taian district of Shandong Province and Jiaozuo district of Henan Province. The mites from these two provinces were distributed in two different branches of the NJ phylogenetic tree. The population suffered long period pesticide stress had significant genetic differentiation from the population that had not experienced the pesticide stress, although they were collected from the same host species of Q. Acutissima away from about 500 m. Genetic distance between the two populations was 0.015, and they were clustered in the different branch, of the NJ phylogenetic tree. Results showed

  7. Air bubble contact with endothelial cells causes a calcium-independent loss in mitochondrial membrane potential.

    Directory of Open Access Journals (Sweden)

    Peter Sobolewski

    Full Text Available OBJECTIVE: Gas microembolism remains a serious risk associated with surgical procedures and decompression. Despite this, the signaling consequences of air bubbles in the vasculature are poorly understood and there is a lack of pharmacological therapies available. Here, we investigate the mitochondrial consequences of air bubble contact with endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells were loaded with an intracellular calcium indicator (Fluo-4 and either a mitochondrial calcium indicator (X-Rhod-1 or mitochondrial membrane potential indicator (TMRM. Contact with 50-150 µm air bubbles induced concurrent rises in intracellular and mitochondrial calcium, followed by a loss of mitochondrial membrane potential. Pre-treating cells with 1 µmol/L ruthenium red, a TRPV family calcium channel blocker, did not protect cells from the mitochondrial depolarization, despite blocking the intracellular calcium response. Mitigating the interactions between the air-liquid interface and the endothelial surface layer with 5% BSA or 0.1% Pluronic F-127 prevented the loss of mitochondrial membrane potential. Finally, inhibiting protein kinase C-α (PKCα, with 5 µmol/L Gö6976, protected cells from mitochondrial depolarization, but did not affect the intracellular calcium response. CONCLUSIONS: Our results indicate that air bubble contact with endothelial cells activates a novel, calcium-independent, PKCα-dependent signaling pathway, which results in mitochondrial depolarization. As a result, mitochondrial dysfunction is likely to be a key contributor to the pathophysiology of gas embolism injury. Further, this connection between the endothelial surface layer and endothelial mitochondria may also play an important role in vascular homeostasis and disease.

  8. Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene.

    Directory of Open Access Journals (Sweden)

    Izabella Baranowska

    2009-05-01

    Full Text Available Sensory ataxic neuropathy (SAN is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr gene is the causative mutation for SAN.

  9. Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

    Science.gov (United States)

    Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

    2014-01-01

    Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to

  10. Clinical and ethical implications of mitochondrial gene transfer.

    Science.gov (United States)

    Mitalipov, Shoukhrat; Wolf, Don P

    2014-01-01

    Inherited diseases caused by mitochondrial gene (mtDNA) mutations affect at least 1 in 5000-10,000 children and are associated with severe clinical symptoms. Novel reproductive techniques designed to replace mutated mtDNA in oocytes or early embryos have been proposed to prevent transmission of disease from parents to their children. Here we review the efficacy and safety of these approaches and their associated ethical and regulatory issues.

  11. THE MEASUREMENT AND STUDY OF BLASTING VIBRATION AFFECTING IN SITU CAST CONCRETE LINING OF VERTICAL SHAFT

    Institute of Scientific and Technical Information of China (English)

    黄琦; 李玉民

    1997-01-01

    Vertical shaft is main form of drivage in deep mineral depoist. They also serve as the entrance into and the exit from the underground mine. The main problems in shaft and tunnel engineering is to solve the contradiction between drivage and lining. The measurement of blasting vibration affecting concrete lining strength of vertical shaft is carried out in experiment and theory in this paper.

  12. Mitochondrial aminoacyl-tRNA synthetases in human disease.

    Science.gov (United States)

    Konovalova, Svetlana; Tyynismaa, Henna

    2013-04-01

    Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential in the process of transferring genetic information from mitochondrial DNA to the complexes of the oxidative phosphorylation system. These synthetases perform an integral step in the initiation of mitochondrial protein synthesis by charging tRNAs with their cognate amino acids. All mtARSs are encoded by nuclear genes, nine of which have recently been described as disease genes for mitochondrial disorders. Unexpectedly, the clinical presentations of these diseases are highly specific to the affected synthetase. Encephalopathy is the most common manifestation but again with gene-specific outcomes. Other clinical presentations include myopathy with anemia, cardiomyopathy, tubulopathy and hearing loss with female ovarian dysgenesis. Here we review the described mutation types and the associated patient phenotypes. The identified mutation spectrum suggests that only mutation types that allow some residual tRNA-charging activity can result in the described mtARS diseases but the molecular mechanisms behind the selective tissue involvement are not currently understood.

  13. Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Enrico Desideri

    2012-01-01

    Full Text Available Mitochondria are cellular energy generators whose activity requires a continuous supply of oxygen. Recent genetic analysis has suggested that defects in mitochondrial quality control may be key factors in the development of Parkinson’s disease (PD. Mitochondria have a crucial role in supplying energy to the brain, and their deterioration can affect the function and viability of neurons, contributing to neurodegeneration. These organelles can sow the seeds of their own demise because they generate damaging oxygen-free radicals as a byproduct of their intrinsic physiological functions. Mitochondria have therefore evolved specific molecular quality control mechanisms to compensate for the action of damaging agents such as oxygen-free radicals. PTEN-induced putative kinase 1 (PINK1 and high-temperature-regulated A2 (HTRA2, a mitochondrial protease, have recently been proposed to be key modulators of mitochondrial molecular quality control. Here, we review some of the most recent advances in our understanding of mitochondria stress-control pathways, focusing on how signalling by the p38 stress kinase pathway may regulate mitochondrial stress by modulating the activity of HTRA2 via PINK1 and cyclin-dependent kinase 5 (CDK5. We also propose how defects in this pathway may contribute to PD.

  14. Mitochondrial gene replacement in primate offspring and embryonic stem cells.

    Science.gov (United States)

    Tachibana, Masahito; Sparman, Michelle; Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Woodward, Joy; Li, Ying; Ramsey, Cathy; Kolotushkina, Olena; Mitalipov, Shoukhrat

    2009-09-17

    Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.

  15. POSSIBLE ROLE OF MITOCHONDRIAL GENOME MUTATIONS IN CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    L. A. Egorova

    2014-07-01

    Full Text Available Mitochondria are not only the major producers of adenosine triphosphate, but also an endogenous source of reactive oxygen species. Mitochondrialdysfunction plays a key role in the trigger and progression of atherosclerotic lesion. Impaired function in the mitochondria due to their elevated level of oxidized oxygen species, the accumulation of mitochondrial DNA damages, and the exhaustion of respiratory chains induces dysfunction and apoptosis in the endothelial cells; activation of matrix metalloproteinases; growth of vascular smooth muscle cells and their migration into the intima; expression of adhesion molecules, and oxidation of low-density lipoproteins. Mitochondrial dysfunction may be an important unifying mechanism that accounts for the atherogenic effect of major cardiovascular risk factors. Small clinical pilot studies have shown an association of different mitochondrial genome mutations with atherosclerotic lesion in the artery. Taking into account the available data on the possible role of mitochondria in atherogenesis, novel drugs are now being designed to affect mitochondrial function.

  16. Coenzyme Q and Mitochondrial Disease

    Science.gov (United States)

    Quinzii, Catarina M.; Hirano, Michio

    2010-01-01

    Coenzyme Q[subscript 10] (CoQ[subscript 10]) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ[subscript 10] is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ[subscript…

  17. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  18. Historical Perspective on Mitochondrial Medicine

    Science.gov (United States)

    DiMauro, Salvatore; Garone, Caterina

    2010-01-01

    In this review, we trace the origins and follow the development of mitochondrial medicine from the premolecular era (1962-1988) based on clinical clues, muscle morphology, and biochemistry into the molecular era that started in 1988 and is still advancing at a brisk pace. We have tried to stress conceptual advances, such as endosymbiosis,…

  19. Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: implications for selective neuronal damage.

    Science.gov (United States)

    Shirendeb, Ulziibat; Reddy, Arubala P; Manczak, Maria; Calkins, Marcus J; Mao, Peizhong; Tagle, Danilo A; Reddy, P Hemachandra

    2011-04-01

    oligomers in the nucleus of HD neurons and in mitochondria may disrupt neuronal functions. Based on these findings, we propose that mutant Htt in association with mitochondria imbalance and mitochondrial dynamics impairs axonal transport of mitochondria, decreases mitochondrial function and damages neurons in affected brain regions of HD patients.

  20. Traffic restrictions: Meyrin site and entrance of Prévessin site

    CERN Multimedia

    GS Department

    2010-01-01

    Between 10 April and 19 April 2010 a number of roads on the Meyrin site and at the entrance of the Prévessin site will be resurfaced. The work will be done by zones, as shown below: 12-14 April Intersection of Route Fermi and Route Gregory. Route Fermi, between Building 268 and Route Jentschke Route Fermi, Route Jentschke and Route Einstein, up to Building 593 and between Buildings 194 and 555. Plus Route Oppenheimer. 15 April Intersection of Route Bloch and Route Maxwell, and Route Maxwell itself. Route Sherrer between the overhead walkway (Building 50) and the exit from the carpark behind Building 4. 16 April and 19 April Route Fermi, Route Jentschke and Route Einstein, up to Building 593 and between Buildings 194 and 555. Prévessin site: from Route Adams to the access control Building. The construction works may result in some disruption to traffic. Users are requested to comply with the temporary traffic signs and arrangements.  Thank you for your understanding. GS/...

  1. EARLY ENTRANCE CO-PRODUCTION PLANT - DECENTRALIZED GASIFICATION COGENERATION TRANSPORTATION FUELS AND STEAM FROM AVAILABLE FEEDSTOCKS

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2003-01-01

    Waste Processors Management, Inc. (WMPI), along with its subcontractors Texaco Power & Gasification (now ChevronTexaco), SASOL Technology Ltd., and Nexant Inc. entered into a Cooperative Agreement DE-FC26-00NT40693 with the U. S. Department of Energy (DOE), National Energy Technology Laboratory (NETL) to assess the technoeconomic viability of building an Early Entrance Co-Production Plant (EECP) in the United States to produce ultra clean Fischer-Tropsch (FT) transportation fuels with either power or steam as the major co-product. The EECP design includes recovery and gasification of low-cost coal waste (culm) from physical coal cleaning operations and will assess blends of the culm with coal or petroleum coke. The project has three phases. Phase I is the concept definition and engineering feasibility study to identify areas of technical, environmental and financial risk. Phase II is an experimental testing program designed to validate the coal waste mixture gasification performance. Phase III updates the original EECP design based on results from Phase II, to prepare a preliminary engineering design package and financial plan for obtaining private funding to build a 5,000 barrel per day (BPD) coal gasification/liquefaction plant next to an existing co-generation plant in Gilberton, Schuylkill County, Pennsylvania. The current report covers the period performance from July 1, 2002 through September 30, 2002.

  2. The entrance system laboratory prototype for an advanced mass and ionic charge composition experiment.

    Science.gov (United States)

    Allegrini, F; Desai, M I; Livi, R; Livi, S; McComas, D J; Randol, B

    2009-10-01

    Electrostatic analyzers (ESA) have been used extensively for the characterization of plasmas in a variety of space environments. They vary in shape, geometry, and size and are adapted to the specific particle population to be measured and the configuration of the spacecraft. Their main function is to select the energy per charge of the particles within a passband. An energy-per-charge range larger than that of the passband can be sampled by varying the voltage difference between the ESA electrodes. The voltage sweep takes time and reduces the duty cycle for a particular energy-per-charge passband. Our design approach for an advanced mass and ionic charge composition experiment (AMICCE) has a novel electrostatic analyzer that essentially serves as a spectrograph and selects ions simultaneously over a broad range of energy-per-charge (E/q). Only three voltage settings are required to cover the entire range from approximately 10 to 270 keV/q, thus dramatically increasing the product of the geometric factor times the duty cycle when compared with other instruments. In this paper, we describe the AMICCE concept with particular emphasis on the prototype of the entrance system (ESA and collimator), which we designed, developed, and tested. We also present comparisons of the laboratory results with electrostatic simulations.

  3. Adaptive Beam Smoothing with Plasma-Pinholes for Laser-Entrance-Hole Transmission Studies

    Science.gov (United States)

    Geissel, Matthias; Ruggles, Lawrence E.; Smith, Ian C.; Shores, Jonathn E.; Speas, C. Shane; Porter, John L.

    2014-10-01

    The concept of Magnetized Liner Inertial Fusion (MagLIF) requires the deposition of laser energy into a fuel-filled cylinder that is exposed to a magnetic field. To improve process, it is essential to optimize transmission through the foil covered laser entrance hole (LEH), which involves minimizing laser-plasma-instabilities (LPI). Laser beam smoothing is the most common approach to minimize LPI. It typically involves a Random-Phase-Plate (RPP) and smoothing by spectral dispersion (SSD). This approach can still cause LPI issues due to intensity ``hot-spots'' on a ps-time scale, and it inconveniently fixes the usable spot size. Changing laser spot sizes requires multiple dedicated RPPs. To study ideal spot sizes on a MagLIF LEH, the RPP/SSD approach gets cost prohibitive. As alternative, we use sacrificial thin foils (500 nm or less) at the laser focus, which instantly turn into a plasma-pinhole, acting as spatial filter. The smoothed laser spot size grows linearly with distance from best focus. We present experimental data for smoothing performance and resulting LEH transmission. Sandia is a multiprogram laboratory managed and operated by Sandia Corp., a wholly owned subsidiary of Lockheed Martin Corp., for the U.S. DOE's Nat'l Nucl. Sec. Admin. under Contract DE-AC04-94AL85000.

  4. X-ray tube output based calculation of patient entrance surface dose: validation of the method

    Energy Technology Data Exchange (ETDEWEB)

    Harju, O.; Toivonen, M.; Tapiovaara, M.; Parviainen, T. [Radiation and Nuclear Safety Authority, Helsinki (Finland)

    2003-06-01

    X-ray departments need methods to monitor the doses delivered to the patients in order to be able to compare their dose level to established reference levels. For this purpose, patient dose per radiograph is described in terms of the entrance surface dose (ESD) or dose-area product (DAP). The actual measurement is often made by using a DAP-meter or thermoluminescent dosimeters (TLD). The third possibility, the calculation of ESD from the examination technique factors, is likely to be a common method for x-ray departments that do not have the other methods at their disposal or for examinations where the dose may be too low to be measured by the other means (e.g. chest radiography). We have developed a program for the determination of ESD by the calculation method and analysed the accuracy that can be achieved by this indirect method. The program calculates the ESD from the current time product, x-ray tube voltage, beam filtration and focus- to-skin distance (FSD). Additionally, for calibrating the dose calculation method and thereby improving the accuracy of the calculation, the x-ray tube output should be measured for at least one x-ray tube voltage value in each x-ray unit. The aim of the present work is to point out the restrictions of the method and details of its practical application. The first experiences from the use of the method will be summarised. (orig.)

  5. Optimal Coordinated Control of Power Extraction in LES of a Wind Farm with Entrance Effects

    Directory of Open Access Journals (Sweden)

    Jay P. Goit

    2016-01-01

    Full Text Available We investigate the use of optimal coordinated control techniques in large eddy simulations of wind farm boundary layer interaction with the aim of increasing the total energy extraction in wind farms. The individual wind turbines are considered as flow actuators, and their energy extraction is dynamically regulated in time, so as to optimally influence the flow field. We extend earlier work on wind farm optimal control in the fully-developed regime (Goit and Meyers 2015, J. Fluid Mech. 768, 5–50 to a ‘finite’ wind farm case, in which entrance effects play an important role. For the optimal control, a receding horizon framework is employed in which turbine thrust coefficients are optimized in time and per turbine. Optimization is performed with a conjugate gradient method, where gradients of the cost functional are obtained using adjoint large eddy simulations. Overall, the energy extraction is increased 7% by the optimal control. This increase in energy extraction is related to faster wake recovery throughout the farm. For the first row of turbines, the optimal control increases turbulence levels and Reynolds stresses in the wake, leading to better wake mixing and an inflow velocity for the second row that is significantly higher than in the uncontrolled case. For downstream rows, the optimal control mainly enhances the sideways mean transport of momentum. This is different from earlier observations by Goit and Meyers (2015 in the fully-developed regime, where mainly vertical transport was enhanced.

  6. New hadron discovered at Entrance B (mother and baby doing fine)

    CERN Multimedia

    James Gillies

    2013-01-01

    Hadron: A heavy, strongly interacting particle. So say the dictionaries, and the definition seems entirely appropriate for the latest addition to a particular family that was passing CERN’s Entrance B on Monday afternoon en route for the Hôpital de la Tour.   The father of the baby (left) and the members of the CERN Fire Brigade and Medical Service dealing with the unexpected happy event. (Photo by D. Pagnani, CERN Fireman. The photo is reproduced by the CERN Bulletin with the agreement of the di Castro family.) The new "hadron" certainly showed the strength of its desire to interact with the world in arriving a little earlier than expected, causing its fraught parents to pull up the car and seek help at the first port of call. Luckily for them, that turned out to be CERN. Our medical service and ambulance personnel proved to be entirely up to the task. The fire brigade provided first aid, and was soon joined by the medical service, which ensured that mot...

  7. Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

    Science.gov (United States)

    Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

    2016-01-01

    One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

  8. On Implementation of Psychological Counseling of Students for College Entrance Exam or High School Entrance Exam%中高考学生考前心理辅导的实施

    Institute of Scientific and Technical Information of China (English)

    李玉荣

    2015-01-01

    Based on the research and practical work of psychological counseling of students for college entrance exam or high school entrance exam,and on the constructive elements of counseling contents,the paper analyzes the application of multi measures and puts forward several issues to be aware of during counseling practice,aimed at improving counseling quality.%基于中高考学生考前心理辅导的研究与实践工作,依据中高考学生考前心理辅导内容的构成要素,分析了考前心理辅导多元手段的应用,并提出了辅导实践中应注意的事项,以提升辅导质量。

  9. Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.

    Science.gov (United States)

    Schüll, S; Günther, S D; Brodesser, S; Seeger, J M; Tosetti, B; Wiegmann, K; Pongratz, C; Diaz, F; Witt, A; Andree, M; Brinkmann, K; Krönke, M; Wiesner, R J; Kashkar, H

    2015-03-12

    Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the specific alteration of the cytochrome c oxidase (COX), representing a common defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in response to oxidative stress. Our data identified an increased ceramide synthase 6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction induced either by chemical or genetic approaches. The elevated CerS6 activity resulted in accumulation of the pro-apoptotic C16 : 0 ceramide, which facilitates the mitochondrial apoptosis in response to oxidative stress. Accordingly, inhibition of CerS6 or its specific knockdown diminished the increased susceptibility of COX-deficient cells to oxidative stress. Our results provide new insights into how mitochondrial RC dysfunction mechanistically interferes with the apoptotic machinery. On the basis of its pivotal role in regulating cell death upon COX dysfunction, CerS6 might potentially represent a novel target for therapeutic intervention in mitochondrial diseases caused by COX dysfunction.

  10. Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction.

    Science.gov (United States)

    Wang, Fengyue; Yang, Jing; Sun, Junfeng; Dong, Yanli; Zhao, Hong; Shi, Hui; Fu, Lu

    2015-05-01

    Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

  11. Mitochondrial swinger replication: DNA replication systematically exchanging nucleotides and short 16S ribosomal DNA swinger inserts.

    Science.gov (United States)

    Seligmann, Hervé

    2014-11-01

    Assuming systematic exchanges between nucleotides (swinger RNAs) resolves genomic 'parenthood' of some orphan mitochondrial transcripts. Twenty-three different systematic nucleotide exchanges (bijective transformations) exist. Similarities between transcription and replication suggest occurrence of swinger DNA. GenBank searches for swinger DNA matching the 23 swinger versions of human and mouse mitogenomes detect only vertebrate mitochondrial swinger DNA for swinger type AT+CG (from five different studies, 149 sequences) matching three human and mouse mitochondrial genes: 12S and 16S ribosomal RNAs, and cytochrome oxidase subunit I. Exchange AT+CG conserves self-hybridization properties, putatively explaining swinger biases for rDNA, against protein coding genes. Twenty percent of the regular human mitochondrial 16S rDNA consists of short swinger repeats (from 13 exchanges). Swinger repeats could originate from recombinations between regular and swinger DNA: duplicated mitochondrial genes of the parthenogenetic gecko Heteronotia binoei include fewer short AT+CG swinger repeats than non-duplicated mitochondrial genomes of that species. Presumably, rare recombinations between female and male mitochondrial genes (and in parthenogenetic situations between duplicated genes), favors reverse-mutations of swinger repeat insertions, probably because most inserts affect negatively ribosomal function. Results show that swinger DNA exists, and indicate that swinger polymerization contributes to the genesis of genetic material and polymorphism.

  12. Mitochondrial structure, function and dynamics are temporally controlled by c-Myc.

    Directory of Open Access Journals (Sweden)

    J Anthony Graves

    Full Text Available Although the c-Myc (Myc oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS, the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored. We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion. A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC are not entirely normalized. Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter. The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell.

  13. Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

    Directory of Open Access Journals (Sweden)

    Giuseppina Barrera

    2016-02-01

    Full Text Available In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS, produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE and malondialdehyde (MDA, which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.

  14. Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

    Science.gov (United States)

    Barrera, Giuseppina; Gentile, Fabrizio; Pizzimenti, Stefania; Canuto, Rosa Angela; Daga, Martina; Arcaro, Alessia; Cetrangolo, Giovanni Paolo; Lepore, Alessio; Ferretti, Carlo; Dianzani, Chiara; Muzio, Giuliana

    2016-01-01

    In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations. PMID:26907355

  15. Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Zhongmin Alex Ma

    2012-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS produced by β-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead to β-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced β-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA phospholipase A2 (iPLA2β appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects on β-cell mitochondrial phospholipids might prevent or retard development of T2DM.

  16. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play, expe...... affects can be choreographed and designed intentionally or whether it arises from unpredictable circumstances within urbanity itself....

  17. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  18. Training Skills of English Listening in College Entrance Examination%高考英语听力训练技巧

    Institute of Scientific and Technical Information of China (English)

    孙佳辉

    2011-01-01

    本文就高考英语的听力训练以及解题技巧进行探析,学生在具备了一定的听力知识的基础上还应该掌握一些解题技巧。听力训练技巧的培养能让学生在高考英语的听力测试中得心应手。%In this paper, the author analyzes English listening and problem-solving skills training in college entrance examination, students have a certain knowledge on the basis of the hearing should also have some problem-solving skills. Listening skills training allows students to develop English listening test in the entrance examination in handy.

  19. Oil droplet behavior at a pore entrance in the presence of crossflow: Implications for microfiltration of oil-water dispersions

    CERN Document Server

    Darvishzadeh, Tohid; Priezjev, Nikolai V

    2013-01-01

    The behavior of an oil droplet pinned at the entrance of a micropore and subject to clossflow-induced shear is investigated numerically by solving the Navier-Stokes equation. We found that in the absence of crossflow, the critical transmembrane pressure required to force the droplet into the pore is in excellent agreement with a theoretical prediction based on the Young-Laplace equation. With increasing shear rate, the critical pressure of permeation increases, and at sufficiently high shear rates the oil droplet breaks up into two segments. The results of numerical simulations indicate that droplet breakup at the pore entrance is facilitated at lower surface tension, higher oil-to-water viscosity ratio and larger droplet size but is insensitive to the value of the contact angle. Using simple force and torque balance arguments, an estimate for the increase in critical pressure due to crossflow and the breakup capillary number is obtained and validated for different viscosity ratios, surface tension coefficien...

  20. Spectroscopy of free radicals and radical containing entrance-channel complexes in superfluid helium nano-droplets

    CERN Document Server

    K"upper, J; K\\"upper, Jochen; Merritt, Jeremy M.

    2006-01-01

    The spectroscopy of free radicals and radical containing entrance-channel complexes embedded in superfluid helium nano-droplets is reviewed. The collection of dopants inside individual droplets in the beam represents a micro-canonical ensemble, and as such each droplet may be considered an isolated cryo-reactor. The unique properties of the droplets, namely their low temperature (0.4 K) and fast cooling rates ($\\sim10^{16}$ K s$^{-1}$) provides novel opportunities for the formation and high-resolution studies of molecular complexes containing one or more free radicals. The production methods of radicals are discussed in light of their applicability for embedding the radicals in helium droplets. The spectroscopic studies performed to date on molecular radicals and on entrance / exit-channel complexes of radicals with stable molecules are detailed. The observed complexes provide new information on the potential energy surfaces of several fundamental chemical reactions and on the intermolecular interactions pres...

  1. Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter.

    Science.gov (United States)

    Lee, Youngjin; Min, Choon Kee; Kim, Tae Gyun; Song, Hong Ki; Lim, Yunki; Kim, Dongwook; Shin, Kahee; Kang, Moonkyung; Kang, Jung Youn; Youn, Hyung-Seop; Lee, Jung-Gyu; An, Jun Yop; Park, Kyoung Ryoung; Lim, Jia Jia; Kim, Ji Hun; Kim, Ji Hye; Park, Zee Yong; Kim, Yeon-Soo; Wang, Jimin; Kim, Do Han; Eom, Soo Hyun

    2015-10-01

    The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca(2+) uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

  2. Analysis of Mitochondrial Network Morphology in Cultured Myoblasts from Patients with Mitochondrial Disorders.

    Science.gov (United States)

    Sládková, J; Spáčilová, J; Čapek, M; Tesařová, M; Hansíková, H; Honzík, T; Martínek, J; Zámečník, J; Kostková, O; Zeman, J

    2015-01-01

    Mitochondrial morphology was studied in cultivated myoblasts obtained from patients with mitochondrial disorders, including CPEO, MELAS and TMEM70 deficiency. Mitochondrial networks and ultrastructure were visualized by fluorescence microscopy and transmission electron microscopy, respectively. A heterogeneous picture of abnormally sized and shaped mitochondria with fragmentation, shortening, and aberrant cristae, lower density of mitochondria and an increased number of "megamitochondria" were found in patient myoblasts. Morphometric Fiji analyses revealed different mitochondrial network properties in myoblasts from patients and controls. The small number of cultivated myoblasts required for semiautomatic morphometric image analysis makes this tool useful for estimating mitochondrial disturbances in patients with mitochondrial disorders.

  3. Efficient Mitochondrial Genome Editing by CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Areum Jo

    2015-01-01

    Full Text Available The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9 system has been widely used for nuclear DNA editing to generate mutations or correct specific disease alleles. Despite its flexible application, it has not been determined if CRISPR/Cas9, originally identified as a bacterial defense system against virus, can be targeted to mitochondria for mtDNA editing. Here, we show that regular FLAG-Cas9 can localize to mitochondria to edit mitochondrial DNA with sgRNAs targeting specific loci of the mitochondrial genome. Expression of FLAG-Cas9 together with gRNA targeting Cox1 and Cox3 leads to cleavage of the specific mtDNA loci. In addition, we observed disruption of mitochondrial protein homeostasis following mtDNA truncation or cleavage by CRISPR/Cas9. To overcome nonspecific distribution of FLAG-Cas9, we also created a mitochondria-targeted Cas9 (mitoCas9. This new version of Cas9 localizes only to mitochondria; together with expression of gRNA targeting mtDNA, there is specific cleavage of mtDNA. MitoCas9-induced reduction of mtDNA and its transcription leads to mitochondrial membrane potential disruption and cell growth inhibition. This mitoCas9 could be applied to edit mtDNA together with gRNA expression vectors without affecting genomic DNA. In this brief study, we demonstrate that mtDNA editing is possible using CRISPR/Cas9. Moreover, our development of mitoCas9 with specific localization to the mitochondria should facilitate its application for mitochondrial genome editing.

  4. Mitochondrial diabetes in children: seek and you will find it.

    Directory of Open Access Journals (Sweden)

    Cristina Mazzaccara

    Full Text Available Maternally Inherited Diabetes and Deafness (MIDD is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA. 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1 maculopathy; 2 hearing impairment; 3 maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected. We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91% and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75-98% and macular dystrophy (54% vs 86% was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants.

  5. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

    Science.gov (United States)

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.

  6. Mitochondrial diabetes in children: seek and you will find it.

    Science.gov (United States)

    Mazzaccara, Cristina; Iafusco, Dario; Liguori, Rosario; Ferrigno, Maddalena; Galderisi, Alfonso; Vitale, Domenico; Simonelli, Francesca; Landolfo, Paolo; Prisco, Francesco; Masullo, Mariorosario; Sacchetti, Lucia

    2012-01-01

    Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75-98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants.

  7. Mitochondria: mitochondrial OXPHOS (dys) function ex vivo--the use of primary fibroblasts.

    Science.gov (United States)

    Saada, Ann

    2014-03-01

    Mitochondria are intracellular organelles present in all nucleated cells. They perform a number of vital metabolic processes but their main function is to generate energy in the form of ATP by oxidative phosphorylation (OXPHOS), performed by the mitochondrial respiratory chain. Mitochondrial diseases affecting oxidative phosphorylation are a common group of inherited disorders with variable clinical manifestations. They are caused by mutations either in the mitochondrial or the nuclear genome. In order to study this group of heterogeneous diseases, they are often modeled in animal and microbial systems. However, these are complex, time consuming and unavailable for each specific mutation. Conversely, skin fibroblasts derived from patients provide a feasible alternative. The usefulness of fibroblasts in culture to verify and study the pathomechanism of new mitochondrial diseases and to evaluate the efficacy of individual treatment options is summarized in this review.

  8. Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes.

    Science.gov (United States)

    Chowdhury, Subir K Roy; Dobrowsky, Rick T; Fernyhough, Paul

    2011-11-01

    Diabetic neuropathy is a major complication of diabetes that results in the progressive deterioration of the sensory nervous system. Mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of the neurodegeneration observed in diabetic neuropathy. Our recent work has shown that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory neurons in streptozotocin (STZ) induced diabetic rodents. In neurons, the nutrient excess associated with prolonged diabetes may trigger a switching off of AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling leading to impaired peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression/activity and diminished mitochondrial activity. This review briefly summarizes the alterations of mitochondrial function and proteome in sensory neurons of STZ-diabetic rodents. We also discuss the possible involvement of AMPK/SIRT/PGC-1α pathway in other diabetic models and different tissues affected by diabetes.

  9. The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage

    Science.gov (United States)

    Varanita, Tatiana; Soriano, Maria Eugenia; Romanello, Vanina; Zaglia, Tania; Quintana-Cabrera, Rubén; Semenzato, Martina; Menabò, Roberta; Costa, Veronica; Civiletto, Gabriele; Pesce, Paola; Viscomi, Carlo; Zeviani, Massimo; Di Lisa, Fabio; Mongillo, Marco; Sandri, Marco; Scorrano, Luca

    2015-01-01

    Summary Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo. PMID:26039448

  10. Learning from Our Students' Previous L2 Writing Experiences : The English Composition Question on University Entrance Exams

    OpenAIRE

    Ross, Paul; Paul, ROSS

    2003-01-01

    This article attempts to help EFL writing teachers in Japan become more aware of the previous L2 writing experiences that their students may have had. Specifically, it discusses students' experiences preparing for the English composition question on university entrance exams and compares these with the writing experiences they are likely to encounter in a university-level EFL writing classroom. It will be shown that these two different writing experiences share some basic characteristics in c...

  11. Bolsa Bay, California, Proposed Ocean Entrance System Study. Report 2. Comprehensive Shoreline Response Computer Simulation, Bolsa Bay, California

    Science.gov (United States)

    1990-04-01

    1980). 27. The success of the inlet channel at Agua Hedionda indicates that a stable non-navigable entrance at Bolsa Chica could be feasible provided a...dual jetty system similar to Agua Hedionda is incorporated into the design. However, structures that penetrate into the active surf zone are expected...and from the south in the summer months. i. The surfbreak rarely closes out. j. Surfing is best in the morning before the sea breeze becomes strong. 13

  12. The validity of Iran’s national university entrance examination (Konkoor) for predicting medical students’ academic performance

    OpenAIRE

    Farrokhi-Khajeh-Pasha Yasin; Nedjat Saharnaz; Mohammadi Aeen; Rad Elaheh; Majdzadeh Reza; Monajemi Farshid; Jamali Ehsan; Yazdani Shahryar

    2012-01-01

    Abstract Background In Iran, admission to medical school is based solely on the results of the highly competitive, nationwide Konkoor examination. This paper examines the predictive validity of Konkoor scores, alone and in combination with high school grade point averages (hsGPAs), for the academic performance of public medical school students in Iran. Methods This study followed the cohort of 2003 matriculants at public medical schools in Iran from entrance through internship. The predictor ...

  13. THE RELATIONSHIP BETWEEN THE POINTS OF UNIVERSITY ENTRANCE EXAMINATION AND EXPOSE OF DOMESTIC VIOLENCE AND ATTITUDES TOWARDS VIOLENCE OF STUDENTS

    Directory of Open Access Journals (Sweden)

    Atilla Senih MAYDA

    2006-06-01

    Full Text Available The aim of this cross-sectional study is to explore certain factors effecting the points of university entrance examination of first class students, the relationship between the points and domestic violence the have been exposed last year and the attitudes of students towards domestic violence. Total 316 students were included in the study. The mean points of university entrance examination was found higher in girl students, students who do not smoke and graduated from Anatolian, Science and Private High Schools. 1/3rd of the the students included to the study was found that they were experienced or exposed domestic violence within last year and the violence was most often between parents and kids. It was determined that the students whose parents experienced domestic violence in the past has been exposed domestic violence more frequently. The students who think violence as a child education method were the students whose parents experienced domestic violence in the past, boy students and the students who somoke. The hypothesis “students exposed to domestic violence may have low points from the university entrance examination” can not be supported. Domestic violence in the students who smoke must be researched because of they think that violence may be a method in child education. This study reveals that who experiences domestic violence puts it in practice at later ages as if violence were a normal behaviour. [TAF Prev Med Bull 2006; 5(3.000: 176-186

  14. Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Yuki [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Eguchi, Takahiro [The Institute of Medical Science, The University of Tokyo, Minato, Tokyo 108-8639 (Japan); Kawahara, Kazuko [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Hasegawa, Nanami [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Nakamura, Kazuaki [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Funakoshi-Tago, Megumi [Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Tanoue, Akito [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Tamura, Hiroomi [Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Yamauchi, Junji, E-mail: yamauchi-j@ncchd.go.jp [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510 (Japan)

    2015-07-03

    Myelin-forming glial cells undergo dynamic morphological changes in order to produce mature myelin sheaths with multiple layers. In the central nervous system (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but their related disorders lead not only to dismyelination and repeated demyelination but also to severe neuropathies. Hereditary hypomyelinating leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes and are often caused by missense mutations of the respective responsible genes. Despite increasing identification of gene mutations through advanced nucleotide sequencing technology, studies on the relationships between gene mutations and their effects on cellular and subcellular aberrance have not followed at the same rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly) mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length morphologies and increases the numbers of mitochondria due to their aberrant fission and fusion cycles. In experiments using a fluorescent dye probe, this mutation decreases the mitochondrial membrane potential. Also, mitochondria accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This study constitutes a first finding concerning the relationship between disease-associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the relationship between another disease-associated HSPD1 mutation (MitCHAP-60 disease) and aberrant mitochondrial dynamics. - Highlights: • The HLD4 mutant of HSPD1 decreases mitochondrial fission frequency. • The HLD4 mutant decreases mitochondrial fusion frequency. • Mitochondria harboring the HLD4 mutant exhibit slow motility. • The HLD4 mutant of HSPD1 decreases mitochondrial membrane potential. • HLD4-related diseases may

  15. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death.

    Science.gov (United States)

    Cha, Moon-Yong; Han, Sun-Ho; Son, Sung Min; Hong, Hyun-Seok; Choi, Young-Ju; Byun, Jayoung; Mook-Jung, Inhee

    2012-01-01

    Mitochondria are best known as the essential intracellular organelles that host the homeostasis required for cellular survival, but they also have relevance in diverse disease-related conditions, including Alzheimer's disease (AD). Amyloid β (Aβ) peptide is the key molecule in AD pathogenesis, and has been highlighted in the implication of mitochondrial abnormality during the disease progress. Neuronal exposure to Aβ impairs mitochondrial dynamics and function. Furthermore, mitochondrial Aβ accumulation has been detected in the AD brain. However, the underlying mechanism of how Aβ affects mitochondrial function remains uncertain, and it is questionable whether mitochondrial Aβ accumulation followed by mitochondrial dysfunction leads directly to neuronal toxicity. This study demonstrated that an exogenous Aβ(1-42) treatment, when applied to the hippocampal cell line of mice (specifically HT22 cells), caused a deleterious alteration in mitochondria in both morphology and function. A clathrin-mediated endocytosis blocker rescued the exogenous Aβ(1-42)-mediated mitochondrial dysfunction. Furthermore, the mitochondria-targeted accumulation of Aβ(1-42) in HT22 cells using Aβ(1-42) with a mitochondria-targeting sequence induced the identical morphological alteration of mitochondria as that observed in the APP/PS AD mouse model and exogenous Aβ(1-42)-treated HT22 cells. In addition, subsequent mitochondrial dysfunctions were demonstrated in the mitochondria-specific Aβ(1-42) accumulation model, which proved indistinguishable from the mitochondrial impairment induced by exogenous Aβ(1-42)-treated HT22 cells. Finally, cellular toxicity was directly induced by mitochondria-targeted Aβ(1-42) accumulation, which mimics the apoptosis process in exogenous Aβ(1-42)-treated HT22 cells. Taken together, these results indicate that mitochondria-targeted Aβ(1-42) accumulation is the necessary and sufficient condition for Aβ-mediated mitochondria impairments, and leads

  16. Effect of mitochondrial calcium uniporter blocking on human spermatozoa.

    Science.gov (United States)

    Bravo, A; Treulen, F; Uribe, P; Boguen, R; Felmer, R; Villegas, J V

    2015-08-01

    Calcium (Ca(2+) ) regulates a number of essential processes in spermatozoa. Ca(2+) is taken up by mitochondria via the mitochondrial calcium uniporter (mCU). Oxygen-bridged dinuclear ruthenium amine complex (Ru360) has been used to study mCU because it is a potent and specific inhibitor of this channel. In bovine spermatozoa, it has been demonstrated that mitochondrial calcium uptake inhibition adversely affects the capacitation process. It has been demonstrated in human spermatozoa that mCU blocking, through Ru360, prevents apoptosis; however, the contribution of the mCU to normal human sperm function has not been studied. Therefore, the aim of this study was to evaluate the effect of mCU blocking on human sperm function. Spermatozoa obtained from apparently healthy donors were incubated with 5 and 10 μm Ru360 for 4 h at 37 °C. Viability was assessed using propidium iodide staining; motility was determined by computer-aided sperm analysis, adenosine triphosphate (ATP) levels using a luminescence-based method, mitochondrial membrane potential (ΔΨm) using JC-1 staining and reactive oxygen species (ROS) production using dihydroethidium dye. Our results show that mCU blocking significantly reduced total sperm motility and ATP levels without affecting sperm viability, ΔΨm and ROS production. In conclusion, mCU contributes to the maintenance of sperm motility and ATP levels in human spermatozoa.

  17. Nearshore bedform instability in the eastern entrance to the Qiongzhou Strait,South China Sea

    Institute of Scientific and Technical Information of China (English)

    Heqin CHENG; Jiufa LI; Daowei YIN; Maotian LI; Baocan WANG

    2008-01-01

    Six bathymetric transect profiles were drawn from the nautical charts of 1942,1962 and 1992 to show that the nearshore seabed remained unstable during the recent 50 Vears in the middie channel of the eastern entrance to the Oiongzhou Strait,South China Sea.Our results dem onstrate that the multi-year averaged seabed aggradational rate was 25 cm/a and erosion rate was 12.5 cm/a.Lateral migration rate of the sea bedform identified from the his torical contours was about 100 m/a in the SE direction. Bedform measurements were made using GPY Shallow Seismic Profiler in 1994 in the study area.The records revealed four types of distinctive bedforins that were com.Posed of fine and medium sands.The average spacing of large and small-scale sand dunes is 416 m and 144 m and the average height remains 8.8 m and 4.9 m.The spatial and temporal equilibrium-range spectra of numerical bedform records were applied to estimate short term celerity of bed form movement.Results indicate that large and small dunes migrated at an average celerity of 0.02 cm/hr eastward and 0.09 cm/hr westward in the calm sea weather,while their celerity can reach 53 cm/hr eastward during typhoon season and iS only 0.008 cm/hr westward when NNE winds prevail.The results also show that the larger the temporal and spa tial scale is.the smaller the bedform movement celerity appears.On the other hand,the smaller-scale bedform celerity of the present study is much greater than that of flume,empirical and theoretical data,but close to the wind tunnel and field-measured data of similar grain size.

  18. Nearshore bedform instability in the eastern entrance to the Qiongzhou Strait,South China Sea

    Institute of Scientific and Technical Information of China (English)

    Barendra PURKAIT; Amitava MUKHERJEE

    2008-01-01

    Six bathymetric transect profiles were drawn from the nautical charts of 1942,1962 and 1992 to show that the nearshore seabed remained unstable during the recent 50 Vears in the middie channel of the eastern entrance to the Oiongzhou Strait,South China Sea.Our results dem onstrate that the multi-year averaged seabed aggradational rate was 25 cm/a and erosion rate was 12.5 cm/a.Lateral migration rate of the sea bedform identified from the his torical contours was about 100 m/a in the SE direction. Bedform measurements were made using GPY Shallow Seismic Profiler in 1994 in the study area.The records revealed four types of distinctive bedforins that were com. Posed of fine and medium sands.The average spacing of large and small-scale sand dunes is 416 m and 144 m and the average height remains 8.8 m and 4.9 m.The spatial and temporal equilibrium-range spectra of numerical bedform records were applied to estimate short term celerity of bed form movement.Results indicate that large and small dunes migrated at an average celerity of 0.02 cm/hr eastward and 0.09 cm/hr westward in the calm sea weather,while their celerity can reach 53 cm/hr eastward during typhoon season and iS only 0.008 cm/hr westward when NNE winds prevail. The results also show that the larger the temporal and spa tial scale is.the smaller the bedform movement celerity appears.On the other hand,the smaller-scale bedform celer ity of the present study is much greater than that of flume, empirical and theoretical data,but close to the wind tunnel and field-measured data of similar grain size.

  19. Entrance and survival of Brucella pinnipedialis hooded seal strain in human macrophages and epithelial cells.

    Directory of Open Access Journals (Sweden)

    Anett K Larsen

    Full Text Available Marine mammal Brucella spp. have been isolated from pinnipeds (B. pinnipedialis and cetaceans (B. ceti from around the world. Although the zoonotic potential of marine mammal brucellae is largely unknown, reports of human disease exist. There are few studies of the mechanisms of bacterial intracellular invasion and multiplication involving the marine mammal Brucella spp. We examined the infective capacity of two genetically different B. pinnipedialis strains (reference strain; NTCT 12890 and a hooded seal isolate; B17 by measuring the ability of the bacteria to enter and replicate in cultured phagocytes and epithelial cells. Human macrophage-like cells (THP-1, two murine macrophage cell lines (RAW264.7 and J774A.1, and a human malignant epithelial cell line (HeLa S3 were challenged with bacteria in a gentamicin protection assay. Our results show that B. pinnipedialis is internalized, but is then gradually eliminated during the next 72-96 hours. Confocal microscopy revealed that intracellular B. pinnipedialis hooded seal strain colocalized with lysosomal compartments at 1.5 and 24 hours after infection. Intracellular presence of B. pinnipedialis hooded seal strain was verified by transmission electron microscopy. By using a cholesterol-scavenging lipid inhibitor, entrance of B. pinnipedialis hooded seal strain in human macrophages was significantly reduced by 65.8 % (± 17.3, suggesting involvement of lipid-rafts in intracellular entry. Murine macrophages invaded by B. pinnipedialis do not release nitric oxide (NO and intracellular bacterial presence does not induce cell death. In summary, B. pinnipedialis hooded seal strain can enter human and murine macrophages, as well as human epithelial cells. Intracellular entry of B. pinnipedialis hooded seal strain involves, but seems not to be limited to, lipid-rafts in human macrophages. Brucella pinnipedialis does not multiply or survive for prolonged periods intracellulary.

  20. Regulation and quantification of cellular mitochondrial morphology and content.

    Science.gov (United States)

    Tronstad, Karl J; Nooteboom, Marco; Nilsson, Linn I H; Nikolaisen, Julie; Sokolewicz, Maciek; Grefte, Sander; Pettersen, Ina K N; Dyrstad, Sissel; Hoel, Fredrik; Willems, Peter H G M; Koopman, Werner J H

    2014-01-01

    Mitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

  1. 三个携带线粒体ND1 T3866C的中国汉族Leber遗传性视神经病变家系%Identification of mitochondrial DNA ND1 T3866C mutation in three ethnic Han Chinese families affected with Leber's hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    张赛; 高敏; 张增君; 刘晓玲; 管敏鑫

    2015-01-01

    目的 分析3个中国Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系的临床和分子遗传学特点.方法 收集临床诊断为LHON的3个中国汉族家系.对3个家系的先证者进行眼科相关检查,PCR扩增3个原发位点G3460A、G11778A、T14484C所在的线粒体ND1、ND4、ND6基因.并对3个先证者线粒体基因组全序列进行PCR扩增.结果 3个家系先证者的视力损伤程度不同,外显率分别12.5%、11.1%和33.3%.3个家系先证者及母系成员均未携带ND1 G3460A、ND4G11778A、ND6 T14484C这3个常见原发位点,但均携带同质性ND1 T3866C突变.线粒体ND1 3866位点T>C碱基的改变使线粒体复合体Ⅰ ND1亚基跨膜区的第187位进化高度保守的非极性异亮氨酸转变为极性苏氨酸.结论 线粒体ND1 T3866C突变可能与LHON相关.%Objective To report on the clinical,genetic and molecular characteristics of three ethnic Han Chinese families affected with Leber's hereditary optic neuropathy (LHON).Methods The three families were all diagnosed with LHON.Ophthalmologic examinations were conducted on the probands.The ND1,ND4 and ND6 genes of the mitochondrial DNA (mtDNA) were amplified with PCR respectively for the screening of three primary mutations G3460A,G11778A and T14484C.The entire mtDNA of the probands were also amplified by PCR.Results Analysis of mtDNA in the three pedigrees has failed to find the presence of the three LHON associated mutations but presence of a homoplastic ND1 T3866C mutation in all probands and their matrilineal relatives.The probands had different levels of visual impairment.The penetrance in the three families has been calculated as 12.5%,11.1% and 33.3%,respectively.The T3866C mutation has resulted in replacement of isoleucine at position 187 with theronine.The isoleucine at position 187 is located at one of the transmembrane domains of ND1 polypeptide.Conclusion Above results have suggested that the ND1 T3866C

  2. Mitochondrial cytopathies and cardiovascular disease.

    Science.gov (United States)

    Dominic, Elizabeth A; Ramezani, Ali; Anker, Stefan D; Verma, Mukesh; Mehta, Nehal; Rao, Madhumathi

    2014-04-01

    The global epidemic of cardiovascular disease remains the leading cause of death in the USA and across the world. Functional and structural integrity of mitochondria are essential for the physiological function of the cardiovascular system. The metabolic adaptation observed in normal heart is lost in the failing myocardium, which becomes progressively energy depleted leading to impaired myocardial contraction and relaxation. Uncoupling of electron transfer from ATP synthesis leads to excess generation of reactive species, leading to widespread cellular injury and cardiovascular disease. Accumulation of mitochondrial DNA mutation has been linked to ischaemic heart disease, cardiomyopathy and atherosclerotic vascular disease. Mitochondria are known to regulate apoptotic and autophagic pathways that have been shown to play an important role in the development of cardiomyopathy and atherosclerosis. A number of pharmacological and non-pharmacological treatment options have been explored in the management of mitochondrial diseases with variable success.

  3. Mitochondrial genomes of parasitic flatworms.

    Science.gov (United States)

    Le, Thanh H; Blair, David; McManus, Donald P

    2002-05-01

    Complete or near-complete mitochondrial genomes are now available for 11 species or strains of parasitic flatworms belonging to the Trematoda and the Cestoda. The organization of these genomes is not strikingly different from those of other eumetazoans, although one gene (atp8) commonly found in other phyla is absent from flatworms. The gene order in most flatworms has similarities to those seen in higher protostomes such as annelids. However, the gene order has been drastically altered in Schistosoma mansoni, which obscures this possible relationship. Among the sequenced taxa, base composition varies considerably, creating potential difficulties for phylogeny reconstruction. Long non-coding regions are present in all taxa, but these vary in length from only a few hundred to approximately 10000 nucleotides. Among Schistosoma spp., the long non-coding regions are rich in repeats and length variation among individuals is known. Data from mitochondrial genomes are valuable for studies on species identification, phylogenies and biogeography.

  4. DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?

    Directory of Open Access Journals (Sweden)

    Alessandra eMaresca

    2015-03-01

    Full Text Available Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN and Hereditary sensory neuropathy with dementia and hearing loss (HSN1E are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic dominant pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5-methyltransferase 1. DNMT1 is the enzyme responsible for maintaining the nuclear genome methylation patterns during the DNA replication and repair, thus regulating gene expression. The mutations responsible for ADCA-DN and HSN1E affect the replication foci targeting sequence domain, which regulates DNMT1 binding to chromatin. DNMT1 dysfunction is anticipated to lead to a global alteration of the DNA methylation pattern with predictable downstream consequences on gene expression. Interestingly, ADCA-DN and HSN1E phenotypes share some clinical features typical of mitochondrial diseases, such as optic atrophy, peripheral neuropathy and deafness, and some biochemical evidence of mitochondrial dysfunction. The recent discovery of a mitochondrial isoform of DNMT1 and its proposed role in methylating mitochondrial DNA (mtDNA suggests that DNMT1 mutations may directly affect mtDNA and mitochondrial physiology. On the basis of this latter finding the link between DNMT1 abnormal activity and mitochondrial dysfunction in ADCA-DN and HSN1E appears intuitive, however mtDNA methylation remains highly debated. In the last years several groups demonstrated the presence of 5-methylcytosine in mtDNA by different approaches, but, on the other end, the opposite evidence that mtDNA is not methylated has also been published. Since over 1500 mitochondrial proteins are encoded by the nuclear genome, the altered methylation of these genes may well have a critical role in leading to the mitochondrial impairment observed in ADCA-DN and HSN1E. Thus, many open questions still remain unanswered, such as why mtDNA should be methylated, and how this process is

  5. Rapidly evolving mitochondrial genome and directional selection in mitochondrial genes in the parasitic wasp nasonia (hymenoptera: pteromalidae).

    Science.gov (United States)

    Oliveira, Deodoro C S G; Raychoudhury, Rhitoban; Lavrov, Dennis V; Werren, John H

    2008-10-01

    We sequenced the nearly complete mtDNA of 3 species of parasitic wasps, Nasonia vitripennis (2 strains), Nasonia giraulti, and Nasonia longicornis, including all 13 protein-coding genes and the 2 rRNAs, and found unusual patterns of mitochondrial evolution. The Nasonia mtDNA has a unique gene order compared with other insect mtDNAs due to multiple rearrangements. The mtDNAs of these wasps also show nucleotide substitution rates over 30 times faster than nuclear protein-coding genes, indicating among the highest substitution rates found in animal mitochondria (normally mitochondrial genes of Nasonia, atp6 and atp8, indicating directional selection. Consistent with this interpretation, the Ka/Ks (nonsynonymous/synonymous substitution rates) ratios are higher between species than within species. In contrast, cox1 shows a signature of purifying selection for amino acid sequence conservation, although rates of amino acid substitutions are still higher than for comparable insects. The mitochondrial-encoded polypeptides atp6 and atp8 both occur in F0F1ATP synthase of the electron transport chain. Because malfunction in this fundamental protein severely affects fitness, we suggest that the accelerated accumulation of replacements is due to beneficial mutations necessary to compensate mild-deleterious mutations fixed by random genetic drift or Wolbachia sweeps in the fast evolving mitochondria of Nasonia. We further propose that relatively high rates of amino acid substitution in some mitochondrial genes can be driven by a "Compensation-Draft Feedback"; increased fixation of mildly deleterious mutations results in selection for compensatory mutations, which lead to fixation of additional deleterious mutations in nonrecombining mitochondrial genomes, thus accelerating the process of amino acid substitutions.

  6. Rapidly Evolving Mitochondrial Genome and Directional Selection in Mitochondrial Genes in the Parasitic Wasp Nasonia (Hymenoptera: Pteromalidae)

    Science.gov (United States)

    Raychoudhury, Rhitoban; Lavrov, Dennis V.; Werren, John H.

    2008-01-01

    We sequenced the nearly complete mtDNA of 3 species of parasitic wasps, Nasonia vitripennis (2 strains), Nasonia giraulti, and Nasonia longicornis, including all 13 protein-coding genes and the 2 rRNAs, and found unusual patterns of mitochondrial evolution. The Nasonia mtDNA has a unique gene order compared with other insect mtDNAs due to multiple rearrangements. The mtDNAs of these wasps also show nucleotide substitution rates over 30 times faster than nuclear protein-coding genes, indicating among the highest substitution rates found in animal mitochondria (normally <10 times faster). A McDonald and Kreitman test shows that the between-species frequency of fixed replacement sites relative to silent sites is significantly higher compared with within-species polymorphisms in 2 mitochondrial genes of Nasonia, atp6 and atp8, indicating directional selection. Consistent with this interpretation, the Ka/Ks (nonsynonymous/synonymous substitution rates) ratios are higher between species than within species. In contrast, cox1 shows a signature of purifying selection for amino acid sequence conservation, although rates of amino acid substitutions are still higher than for comparable insects. The mitochondrial-encoded polypeptides atp6 and atp8 both occur in F0F1ATP synthase of the electron transport chain. Because malfunction in this fundamental protein severely affects fitness, we suggest that the accelerated accumulation of replacements is due to beneficial mutations necessary to compensate mild-deleterious mutations fixed by random genetic drift or Wolbachia sweeps in the fast evolving mitochondria of Nasonia. We further propose that relatively high rates of amino acid substitution in some mitochondrial genes can be driven by a “Compensation-Draft Feedback”; increased fixation of mildly deleterious mutations results in selection for compensatory mutations, which lead to fixation of additional deleterious mutations in nonrecombining mitochondrial genomes, thus

  7. Sulfite disrupts brain mitochondrial energy homeostasis and induces mitochondrial permeability transition pore opening via thiol group modification.

    Science.gov (United States)

    Grings, Mateus; Moura, Alana P; Amaral, Alexandre U; Parmeggiani, Belisa; Gasparotto, Juciano; Moreira, José C F; Gelain, Daniel P; Wyse, Angela T S; Wajner, Moacir; Leipnitz, Guilhian

    2014-09-01

    Sulfite oxidase (SO) deficiency is biochemically characterized by the accumulation of sulfite, thiosulfate and S-sulfocysteine in tissues and biological fluids of the affected patients. The main clinical symptoms include severe neurological dysfunction and brain abnormalities, whose pathophysiology is still unknown. The present study investigated the in vitro effects of sulfite and thiosulfate on mitochondrial homeostasis in rat brain mitochondria. It was verified that sulfite per se, but not thiosulfate, decreased state 3, CCCP-stimulated state and respiratory control ratio in mitochondria respiring with glutamate plus malate. In line with this, we found that sulfite inhibited the activities of glutamate and malate (MDH) dehydrogenases. In addition, sulfite decreased the activity of a commercial solution of MDH, that was prevented by antioxidants and dithiothreitol. Sulfite also induced mitochondrial swelling and reduced mitochondrial membrane potential, Ca(2+) retention capacity, NAD(P)H pool and cytochrome c immunocontent when Ca(2+) was present in the medium. These alterations were prevented by ruthenium red, cyclosporine A (CsA) and ADP, supporting the involvement of mitochondrial permeability transition (MPT) in these effects. We further observed that N-ethylmaleimide prevented the sulfite-elicited swelling and that sulfite decreased free thiol group content in brain mitochondria. These findings indicate that sulfite acts directly on MPT pore containing thiol groups. Finally, we verified that sulfite reduced cell viability in cerebral cortex slices and that this effect was prevented by CsA. Therefore, it may be presumed that disturbance of mitochondrial energy homeostasis and MPT induced by sulfite could be involved in the neuronal damage characteristic of SO deficiency.

  8. Neurodegenerative stress related mitochondrial proteostasis

    OpenAIRE

    Fang, Lei

    2015-01-01

    1.1 Background: Mitochondria are the main site of energy production in most cells. Furthermore, they are involved in a multitude of other essential cellular processes, such as regulating the cellular calcium pool, lipid metabolism and programmed cell death. Healthy and functional mitochondria are critical to meet the fundamental needs for almost all cell types, which makes mitochondrial quality control (QC) very important. Given the high energy demand of neuronal cells, their vulnerability...

  9. A novel mitochondrial tRNA gene mutation in a chinese family with dilated cardiomyopathy and sensorineural deafness

    Institute of Scientific and Technical Information of China (English)

    Xianghong Wu; Xiumei Xie; Guotian Ma; Guoju Sun; Xiaobin Chen

    2006-01-01

    Objective: To determine whether a mutation of mitochondrial DNA induces familial dilated cardiomyopathy in Chinese families with cardiomyopathy, and analyzed the correlation between the genotype and phenotype. Methods: Affected members in three Chinese families of the familial dilated cardiomyopathy underwent clinical evaluation and DNA analysis. Polymerase chain reaction and direct DNA sequencing were used to screen for mitochondrial DNA mutation. The type of mtDNA vairations and clinical situation were analysed on the patients with mitochondrial DNA mutation. Results: The mitochondrial A3434G mutation was identified in one of the three families,the 3434 th nucleotide A was replaced by G, which led to change of amino acid. No mutations were identified in the clinically unaffected members of the family and all members of the other two families.Conclusion: This study indicates that the mitochondrial A3434G mutation maybe related with familial dilated cardiomyopathy and deafness.

  10. Mitochondrial Sensorineural Hearing Loss: A Retrospective Study and a Description of Cochlear Implantation in a MELAS Patient

    Directory of Open Access Journals (Sweden)

    Mauro Scarpelli

    2012-01-01

    Full Text Available Hearing impairment is common in patients with mitochondrial disorders, affecting over half of all cases at some time in the course of the disease. In some patients, deafness is only part of a multisystem disorder. By contrast, there are also a number of “pure” mitochondrial deafness disorders, the most common probably being maternally inherited. We retrospectively analyzed the last 60 genetically confirmed mitochondrial disorders diagnosed in our Department: 28 had bilateral sensorineural hearing loss, whereas 32 didn't present ear's abnormalities, without difference about sex and age of onset between each single group of diseases. We reported also a case of MELAS patient with sensorineural hearing loss, in which cochlear implantation greatly contributed to the patient's quality of life. Our study suggests that sensorineural hearing loss is an important feature in mitochondrial disorders and indicated that cochlear implantation can be recommended for patients with MELAS syndrome and others mitochondrial disorders.

  11. Mitochondrial DNA maintenance: an appraisal.

    Science.gov (United States)

    Akhmedov, Alexander T; Marín-García, José

    2015-11-01

    Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS), and Ca(2+) handling to stress responses, cell survival, and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular disorders, cancer, premature aging, and cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Mitochondria are unique as they contain their own genome organized into DNA-protein complexes, so-called mitochondrial nucleoids, along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription, and repair. Although the organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair, and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to oxidative stress and other types of mtDNA damage. Defects in the components of these highly organized machineries, which mediate mtDNA maintenance (replication and repair), may result in accumulation of point mutations and/or deletions in mtDNA and decreased mtDNA copy number impairing mitochondrial function. This review will focus on the mechanisms of mtDNA maintenance with emphasis on the proteins implicated in these processes and their functional role in various disease conditions and aging.

  12. Assessing mitochondrial dysfunction in cells.

    Science.gov (United States)

    Brand, Martin D; Nicholls, David G

    2011-04-15

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

  13. Mitochondrial DNA inheritance after SCNT.

    Science.gov (United States)

    Hiendleder, Stefan

    2007-01-01

    Mitochondrial biogenesis and function is under dual genetic control and requires extensive interaction between biparentally inherited nuclear genes and maternally inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes' mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require it to interact with an entirely foreign nucleus that is again interacting with foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and -offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can escape the selective mechanism that targets and eliminates intraspecific sperm mitochondria in the fertilized oocyte to maintain homoplasmy. However, the factors responsible for the large intra- and interindividual differences in heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably confounded with mtDNA recombination. Considering the essential roles of mitochondria in cellular metabolism, cell signalling, and programmed cell death, future experiments will need to assess the true extent and impact of unorthodox mtDNA transmission on various aspects of SCNT success.

  14. Cardiolipin and mitochondrial cristae organization.

    Science.gov (United States)

    Ikon, Nikita; Ryan, Robert O

    2017-03-20

    A fundamental question in cell biology, under investigation for over six decades, is the structural organization of mitochondrial cristae. Long known to harbor electron transport chain proteins, crista membrane integrity is key to establishment of the proton gradient that drives oxidative phosphorylation. Visualization of cristae morphology by electron microscopy/tomography has provided evidence that cristae are tube-like extensions of the mitochondrial inner membrane (IM) that project into the matrix space. Reconciling ultrastructural data with the lipid composition of the IM provides support for a continuously curved cylindrical bilayer capped by a dome-shaped tip. Strain imposed by the degree of curvature is relieved by an asymmetric distribution of phospholipids in monolayer leaflets that comprise cristae membranes. The signature mitochondrial lipid, cardiolipin (~18% of IM phospholipid mass), and phosphatidylethanolamine (34%) segregate to the negatively curved monolayer leaflet facing the crista lumen while the opposing, positively curved, matrix-facing monolayer leaflet contains predominantly phosphatidylcholine. Associated with cristae are numerous proteins that function in distinctive ways to establish and/or maintain their lipid repertoire and structural integrity. By combining unique lipid components with a set of protein modulators, crista membranes adopt and maintain their characteristic morphological and functional properties. Once established, cristae ultrastructure has a direct impact on oxidative phosphorylation, apoptosis, fusion/fission as well as diseases of compromised energy metabolism.

  15. A randomized trial of coenzyme Q10 in mitochondrial disorders.

    Science.gov (United States)

    Glover, Elisa I; Martin, Joan; Maher, Amy; Thornhill, Rebecca E; Moran, Gerald R; Tarnopolsky, Mark A

    2010-11-01

    Case reports and open-label studies suggest that coenzyme Q(10) (CoQ(10)) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ(10) for 60 days in a randomized, double-blind, cross-over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ(10) treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO(2)/kg lean mass after 5 minutes of cycling (P exercise aerobic capacity and post-exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate.

  16. Oxidative stress and mitochondrial dysfunction in infected pregnant

    Directory of Open Access Journals (Sweden)

    Нана Мерабівна Пасієшвілі

    2015-04-01

    Full Text Available The infected pregnant women have been various perinatal complications. The aim of the work was to clarify the role of oxidative stress and mitochondrial dysfunction in the development of perinatal complications in infected pregnant.Methods. The study included 68 pregnant women with signs of maternal-fetal infection (MFI and 30 pregnant women who were found infected (control group. Later pregnant with MFI were divided into 2 groups: the first included 30 women who received traditional antibacterial and antiviral therapy, the second group consisted of 28 women who were additionally given an immunomodulator in combination with ozone therapy.Results. During pregnancy with MFI it is characterized the thrombophilic disorders, break immune homeostasis pregnant, endothelial dysfunction, which adversely affects perinatal indicators.Conclusions. The use of immunomodulators and ozone therapy in the complex treatment of MFI is pathogenetically substantiated effective treatment of oxidative stress and mitochondrial toxicity in the prevention of perinatal complications in infected women

  17. Wheat Mitochondrial Proteomes Reveal Links between Mitochondrial Respiration, Antioxidant Defence and Plant Salinity Tolerance

    Institute of Scientific and Technical Information of China (English)

    Richard P.Jacoby; A.Harvey Millar; Nicolas L.Taylor

    2012-01-01

    Mitochondrial respiration extracts chemical energy from carbon-containing molecules,and converts that energy into ATP,the cellular energy currency.The ATP produced by respiration fuels biochemical and physiological processes that enable the plant to survive and grow.Several studies have observed a negative correlation between respiration rate and growth rate,indicating that respiratory properties might influence biomass accumulation.Furthermore,there is evidence that salinity-sensitive wheat varieties display a higher respiration rate under salt treatment,while salt-tolerant varieties maintains similar a respiration rate under both control and salt treatments.However,the molecular basis of such results remains unexplored.Here we have investigated the mitochondrial proteome and differences associated with salt tolerance in two Australian commercial varieties of wheat.Using 2D-DIGE we have found quantitative differences in the shoot mitochondrial proteomes of Triticum aestivum v.Wyalkatchem and v.Janz,two commercially important wheat varieties that are known from a range of experiments to have differing salinity tolerance.These proteins included Mn-superoxide dismutase (Mn-SOD),cysteine synthase,nucleotide diphosphate kinase and the voltage dependent anion channel (VDAC).Antibodies to the mitochondrial alternative oxidase (AOX),previously linked to reduced reactive oxygen species (ROS) formation from the electron transport chain and salt tolerance in Arabidopsis,also showed a commensurate higher abundance in v.Wyakatchem in both control and salt-treated conditions.To further investigate this intial observation we screened 24 west australian wheat varieties for biomass retention when subjected to salt stress in a hydroponic system in a growth cabinet,with v.Krichauff and v.Westonia being the top performers.In addition we have investigated the the biomass and respiration rates in a subset of these varieties grown in a salt-affected field in the WA wheatbelt

  18. VARIATION IN MITOCHONDRIAL-DNA LEVELS IN MUSCLE FROM NORMAL CONTROLS - IS DEPLETION OF MTDNA IN PATIENTS WITH MITOCHONDRIAL MYOPATHY A DISTINCT CLINICAL SYNDROME

    NARCIS (Netherlands)

    POULTON, J; SEWRY, C; POTTER, CG; BOUGERON, T; CHRETIEN, D; WIJBURG, FA; MORTEN, KJ; BROWN, G

    1995-01-01

    Recent studies have identified a group of patients with cytochrome oxidase (COX) deficiency presenting in infancy associated with a deficiency of mtDNA in muscle or other affected tissue (Moraes et al 1991). We used a navel approach to compare the level of mitochondrial (mtDNA) compared to nuclear D

  19. Co segregation of the m.1555A>G mutation in the MT-RNR1 gene and mutations in MT-ATP6 gene in a family with dilated mitochondrial cardiomyopathy and hearing loss: A whole mitochondrial genome screening.

    Science.gov (United States)

    Alila-Fersi, Olfa; Chamkha, Imen; Majdoub, Imen; Gargouri, Lamia; Mkaouar-Rebai, Emna; Tabebi, Mouna; Tlili, Abdelaziz; Keskes, Leila; Mahfoudh, Abdelmajid; Fakhfakh, Faiza

    2017-02-26

    Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to dysfunction of the mitochondrial respiratory chain, which is responsible for the generation of most cellular energy. Because cardiac muscles are one of the high energy demanding tissues, mitochondrial cardiomyopathies is one of the most frequent mitochondria disorders. Mitochondrial cardiomyopathy has been associated with several point mutations of mtDNA in both genes encoded mitochondrial proteins and mitochondrial tRNA and rRNA. We reported here the first description of mutations in MT-ATP6 gene in two patients with clinical features of dilated mitochondrial cardiomyopathy. The mutational analysis of the whole mitochondrial DNA revealed the presence of m.1555A>G mutation in MT-RNR1 gene associated to the m.8527A>G (p.M>V) and the m.8392C>T (p.136P>S) variations in the mitochondrial MT-ATP6 gene in patient1 and his family members with variable phenotype including hearing impairment. The second patient with isolated mitochondrial cardiomyopathy presented the m.8605C>T (p.27P>S) mutation in the MT-ATP6 gene. The three mutations p.M1V, p.P27S and p.P136S detected in MT-ATP6 affected well conserved residues of the mitochondrial protein ATPase 6. In addition, the substitution of proline residue at position 27 and 136 effect hydrophobicity and structure flexibility conformation of the protein.

  20. Mitochondrial small conductance SK2 channels prevent glutamate-induced oxytosis and mitochondrial dysfunction.

    Science.gov (United States)

    Dolga, Amalia M; Netter, Michael F; Perocchi, Fabiana; Doti, Nunzianna; Meissner, Lilja; Tobaben, Svenja; Grohm, Julia; Zischka, Hans; Plesnila, Nikolaus; Decher, Niels; Culmsee, Carsten

    2013-04-12

    Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K(+) currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction.

  1. The ins and outs of mitochondrial calcium.

    Science.gov (United States)

    Finkel, Toren; Menazza, Sara; Holmström, Kira M; Parks, Randi J; Liu, Julia; Sun, Junhui; Liu, Jie; Pan, Xin; Murphy, Elizabeth

    2015-05-22

    Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.

  2. Oxidative stress, mitochondrial damage and neurodegenerative diseases****

    Institute of Scientific and Technical Information of China (English)

    Chunyan Guo; Li Sun; Xueping Chen; Danshen Zhang

    2013-01-01

    Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. Al these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive thera-peutic interventions for the treatment of various neurodegenerative diseases.

  3. Mitochondrial morphology-emerging role in bioenergetics.

    Science.gov (United States)

    Galloway, Chad A; Lee, Hakjoo; Yoon, Yisang

    2012-12-15

    Dynamic change in mitochondrial shape is a cellular process mediated mainly by fission and fusion of mitochondria. Studies have shown that mitochondrial fission and fusion are directly and indirectly associated with mitochondrial maintenance, bioenergetic demand, and cell death. Changes in mitochondrial morphology are frequently observed in response to changes in the surrounding cellular milieu, such as metabolic flux, that influence cellular bioenergetics. Connections between morphological regulation and the bioenergetic status of mitochondria are emerging as reciprocally responsive processes, though the nature of the signaling remains to be defined. Given the pivotal role mitochondria play in cellular fate, tight regulation of fission and fusion is therefore critical to preserving normal cellular physiology. Here we describe recent advancements in the understanding of the mechanisms governing mitochondrial morphology and their emerging role in mitochondrial bioenergetics.

  4. Coal Mines, Abandoned - COAL_MINE_ENTRIES_IN: Underground Coal Mine Entrances in Indiana (Indiana Geological Survey, 1:24,000, Point Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — SW_COAL_ENTRY, the predecessor of COAL_MINE_ENTRIES_IN, is a point- based ESRI ArcView shapefile that shows the locations of underground coal mine entrances in the...

  5. HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome.

    Science.gov (United States)

    Mouzakis, Kathryn D; Lang, Andrew L; Vander Meulen, Kirk A; Easterday, Preston D; Butcher, Samuel E

    2013-02-01

    The human immunodeficiency virus (HIV) requires a programmed -1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem-loop structure. Here we investigate the role of the RNA structure in promoting the -1 frameshift. The stem-loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3-4 bp in the stem-loop, which are predicted to reside at the opening of the mRNA entrance channel when the ribosome is paused at the slippery site. Insertion or deletions in the spacer region appear to correspondingly change the identity of the base pairs encountered 8 nt downstream of the slippery site. Finally, the role of the surrounding genomic secondary structure was investigated and found to have a modest impact on frameshift efficiency, consistent with the hypothesis that the genomic secondary structure attenuates frameshifting by affecting the overall rate of translation.

  6. 体育纳入高考制度的理性思考%Rational thinking about including physical education in the National College Entrance Examination system

    Institute of Scientific and Technical Information of China (English)

    周茗

    2012-01-01

      我国高考的目的是选拔德、智、体全面发展的社会主义建设者和接班人。将体育纳入高考的改革,有利于落实国家相关政策,保持基础教育阶段学生健康教育的连续性,加强素质教育,促进学校体育地位的提高和体育活动的开展,但也受到政治、经济、社会、技术等因素的制约。%  The purpose of National College Entrance Examination (NCEE) in China is to select morally, intellectu-ally and physically developed socialist constructors and successors. Including physical education in the reform of NCEE is conducive to implementing related state policies, maintaining the continuity of student health education at the basic education stage, enhancing makings education, and boosting the promotion of school physical education status and the development of physical education activities, but also affected and restricted by factors such as poli-tics, economy, society, technology etc.

  7. Acute and perinatal-programming effects of a fat-rich diet on rat muscle mitochondrial function and hepatic lipid accumulation

    DEFF Research Database (Denmark)

    Hellgren, Lars; Jensen, Runa I.; Waterstradt, Michelle S. G.

    2014-01-01

    Objective. Maternal high-fat intake during pregnancy may have long-term consequences in the offspring. Since this might relate to the capacity of mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated how maternal high-fat intake affected mitochondrial function and hepat...

  8. 谈高校内高考招生专网安全保障措施%Analysis on Security Mechanism in the Enrollment Network of College Entrance Examination

    Institute of Scientific and Technical Information of China (English)

    黄向农; 王海源; 徐彧

    2012-01-01

    The practice of college entrance examination enrollment online admission can upgrade its quality and efficiency, but those many security weaknesses and threats existing in campus network will affect the security of online admission. By understanding the security risks that components of the network may face and applying network security technology, security threats can be especially reduced, and smooth college entrance examination enrollment online admission can be ensured.%实行高考招生网上录取,可以提高工作质量和效率,但由于校园网中存在许多安全弱点和安全威胁,将会影响到网上录取的安全性。通过了解构成学校高考招生专网的各个组成部分可能面临的安全风险,利用网络安全技术,可以有针对性地降低阏络安全风险,确保高考招生网上录取工作的顺利进行。

  9. Habitual physical activity in mitochondrial disease.

    Directory of Open Access Journals (Sweden)

    Shehnaz Apabhai

    Full Text Available PURPOSE: Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype. METHODS: Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. RESULTS: Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001. 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001 and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001. After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s = -0.49; 95% CI -0.33, -0.63, P<0.01. There were no systematic differences in physical activity between different genotypes mitochondrial disease. CONCLUSIONS: These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.

  10. Mitochondrial Diseases: Clinical Features- Management of Patients

    Directory of Open Access Journals (Sweden)

    Filiz Koc

    2003-02-01

    Full Text Available Mitochondria are unique organells which their own DNA in cells. Human mitochondrial DNA is circular, double-stranded molecule and small. Because all mitochondria are contributed by the ovum during the formation of the zygote, the mitochondrial genom is transmitted by maternal inheritance. Multisystem disorders such as deafness, cardiomyopathy, miyopathy can be seen in mitochondrial diseases. [Archives Medical Review Journal 2003; 12(0.100: 14-31

  11. Mitochondrial Diseases: Clinical Features- Management of Patients

    OpenAIRE

    Filiz Koc; Yakup Sarica

    2003-01-01

    Mitochondria are unique organells which their own DNA in cells. Human mitochondrial DNA is circular, double-stranded molecule and small. Because all mitochondria are contributed by the ovum during the formation of the zygote, the mitochondrial genom is transmitted by maternal inheritance. Multisystem disorders such as deafness, cardiomyopathy, miyopathy can be seen in mitochondrial diseases. [Archives Medical Review Journal 2003; 12(0.100): 14-31

  12. Mitochondrial Replacement Therapy in Reproductive Medicine

    OpenAIRE

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2014-01-01

    Mitochondrial dysfunction is implicated in disease and in age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes such as pronuclear (PNT), spindle (ST) or polar body (PBT) transfer could prevent second generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal d...

  13. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-15

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

  15. Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression

    Institute of Scientific and Technical Information of China (English)

    Weiwei Huang; Min Yu; Yang Jiao; Jie Ma; Mingxing Ma; Zehua Wang; Hong Wu; Deyong Tan

    2011-01-01

    Mitochondrial transcription termination factor 2 (mTERF2) is a mitochondriai matrix protein that binds to the mitochondriai DNA.Previous studies have shown that overexpression of mTERF2 can inhibit cell proliferation, but the mechanism has not been well defined so far.This study aimed to present the binding pattern of mTERF2 to the mitochondrial DNA (mtDNA) in vivo, and investigated the biological function of mTERF2 on the replication of mtDNA, mRNA transcription, and protein translation.The mTERF2 binding to entire mtDNA was identified via the chromatin immunoprecipitation analysis.The mtDNA replication efficiency and expression levels of mitochondria genes were significantly inhibited when the mTERF2 was overexpressed in HeLa cells.The inhibition level of mtDNA content was the same with the decreased levels of mRNA and mitochondrial protein expression.Overall, the mTERF2 might be a cell growth inhibitor based on its negative effect on mtDNA replication, which eventually own-regulated all of the oxidative phosphorylation components in the mitochondria that were essential for the cell's energy metabolism.

  16. Parkinson's disease and mitochondrial gene variations

    DEFF Research Database (Denmark)

    Andalib, Sasan; Vafaee, Manouchehr Seyedi; Gjedde, Albert

    2014-01-01

    Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations...... and mutations. More recently, a particular role of mitochondrial dysfunction has been suggested, arising from mitochondrial DNA variations or acquired mutations in PD pathogenesis. The present review summarizes and weighs the evidence in support of mitochondrial DNA (mtDNA) variations as important contributors...

  17. Mitochondrial Cristae: Where Beauty Meets Functionality.

    Science.gov (United States)

    Cogliati, Sara; Enriquez, Jose A; Scorrano, Luca

    2016-03-01

    Mitochondrial cristae are dynamic bioenergetic compartments whose shape changes under different physiological conditions. Recent discoveries have unveiled the relation between cristae shape and oxidative phosphorylation (OXPHOS) function, suggesting that membrane morphology modulates the organization and function of the OXPHOS system, with a direct impact on cellular metabolism. As a corollary, cristae-shaping proteins have emerged as potential modulators of mitochondrial bioenergetics, a concept confirmed by genetic experiments in mouse models of respiratory chain deficiency. Here, we review our knowledge of mitochondrial ultrastructural organization and how it impacts mitochondrial metabolism.

  18. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei, E-mail: wshlei@aliyun.com; Yu, Ning; Liu, Jia

    2015-06-05

    The mitochondrial calcium uniporter (MCU) transports free Ca{sup 2+} into the mitochondrial matrix, maintaining Ca{sup 2+} homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca{sup 2+} concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca{sup 2+} transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. - Highlights: • We study MCU with primary neuron culture. • MCU induces mitochondrial fission. • MCU reverses MIEF1 effect.

  19. Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency.

    Science.gov (United States)

    Cagnone, Gael L M; Tsai, Te-Sha; Makanji, Yogeshwar; Matthews, Pamela; Gould, Jodee; Bonkowski, Michael S; Elgass, Kirstin D; Wong, Ashley S A; Wu, Lindsay E; McKenzie, Matthew; Sinclair, David A; St John, Justin C

    2016-03-18

    An increasing number of women fail to achieve pregnancy due to either failed fertilization or embryo arrest during preimplantation development. This often results from decreased oocyte quality. Indeed, reduced mitochondrial DNA copy number (mitochondrial DNA deficiency) may disrupt oocyte quality in some women. To overcome mitochondrial DNA deficiency, whilst maintaining genetic identity, we supplemented pig oocytes selected for mitochondrial DNA deficiency, reduced cytoplasmic maturation and lower developmental competence, with autologous populations of mitochondrial isolate at fertilization. Supplementation increased development to blastocyst, the final stage of preimplantation development, and promoted mitochondrial DNA replication prior to embryonic genome activation in mitochondrial DNA deficient oocytes but not in oocytes with normal levels of mitochondrial DNA. Blastocysts exhibited transcriptome profiles more closely resembling those of blastocysts from developmentally competent oocytes. Furthermore, mitochondrial supplementation reduced gene expression patterns associated with metabolic disorders that were identified in blastocysts from mitochondrial DNA deficient oocytes. These results demonstrate the importance of the oocyte's mitochondrial DNA investment in fertilization outcome and subsequent embryo development to mitochondrial DNA deficient oocytes.

  20. The mitochondrial transcription factor A functions in mitochondrial base excision repair

    DEFF Research Database (Denmark)

    Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V

    2010-01-01

    Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected i...

  1. Early onset cardiomyopathy associated with the mitochondrial tRNALeu((UUR)) 3271T>C MELAS mutation.

    Science.gov (United States)

    Brisca, Giacomo; Fiorillo, Chiara; Nesti, Claudia; Trucco, Federica; Derchi, Maria; Andaloro, Antonio; Assereto, Stefania; Morcaldi, Guido; Pedemonte, Marina; Minetti, Carlo; Santorelli, Filippo M; Bruno, Claudio

    2015-03-13

    Mitochondrial disorders are a heterogeneous group of diseases sharing a defect of the oxidative phosphorylation system. Point mutations in the mitochondrial DNA are a common cause of mitochondrial disorders and frequently affect the sequences encoding mitochondrial transfer RNAs. The m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) is traditionally reported in patients with clinical features of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and in mitochondrial diabetes. Here we describe the clinical, pathological, and molecular features of an Italian child and his asymptomatic mother, carrying the m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) gene, in association with an unusual clinical phenotype dominated by hypertrophic cardiomyopathy and provide review literature of cases with this mutation. To the best of our knowledge, there are no reports describing the association of this mutation with cardiomyopathy, and our cases suggest that the m.3271T>C mutation has to be taken into account in the diagnostic approach of maternally inherited cardiomyopathies.

  2. p-Bromophenacyl bromide prevents cumene hydroperoxide-induced mitochondrial permeability transition by inhibiting pyridine nucleotide oxidation.

    Science.gov (United States)

    Zhukova, A; Gogvadze, G; Gogvadze, V

    2004-01-01

    Mitochondrial permeability transition is commonly characterized as a Ca2+ -dependent non-specific increase in inner membrane permeability that results in swelling of mitochondria and their de-energization. In the present study, the effect of different inhibitors of phospholipase A2--p-bromophenacyl bromide, dibucaine, and aristolochic acid--on hydroperoxide-induced permeability transitions in rat liver mitochondria was tested. p-Bromophenacyl bromide completely prevented the hydroperoxide-induced mitochondrial permeability transition while the effects of dibucaine or aristolochic acid were negligible. Organic hydroperoxides added to mitochondria undergo reduction to corresponding alcohols by mitochondrial glutathione peroxidase. This reduction occurs at the expense of GSH which, in turn, can be reduced by glutathione reductase via oxidation of mitochondrial pyridine nucleotides. The latter is considered a prerequisite step for mitochondrial permeability transition. Among all the inhibitors tested, only p-bromophenacyl bromide completely prevented hydroperoxide-induced oxidation of mitochondrial pyridine nucleotides. Interestingly, p-bromophenacyl bromide had no affect on mitochondrial glutathione peroxidase, but reacted with mitochondrial glutathione that prevented pyridine nucleotides from being oxidized. Our data suggest that p-bromophenacyl bromide prevents hydroperoxide-induced deterioration of mitochondria via interaction with glutathione rather than through inhibition of phospholipase A2.

  3. Staphylococcus aureus entrance into the dairy chain: Tracking S. aureus from dairy cow to cheese

    Directory of Open Access Journals (Sweden)

    Judith Kümmel

    2016-10-01

    Full Text Available Staphylococcus aureus is one of the most important contagious mastitis pathogens in dairy cattle. Due to its zoonotic potential, control of S. aureus is not only of great economic importance in the dairy industry but also a significant public health concern. The aim of this study was to decipher the potential of bovine udder associated S. aureus as reservoir for S. aureus contamination in dairy production and processing. From 18 farms, delivering their milk to an alpine dairy plant for the production of smeared semi-hard and hard cheese. 1176 quarter milk (QM samples of all cows in lactation (n = 294 and representative samples form bulk tank milk (BTM of all farms were surveyed for coagulase positive (CPS and coagulase negative Staphylococci (CNS. Furthermore, samples from different steps of the cheese manufacturing process were tested for CPS and CNS. As revealed by chemometric-assisted FTIR spectroscopy and molecular subtyping (spa typing and multi locus sequence typing, dairy cattle represent indeed an important, yet underreported, entrance point of S. aureus into the dairy chain. Our data clearly show that certain S. aureus subtypes are present in primary production as well as in the cheese processing at the dairy plant. However, although a considerable diversity of S. aureus subtypes was observed in QM and BTM at the farms, only certain S. aureus subtypes were able to enter and persist in the cheese manufacturing at the dairy plant and could be isolated from cheese until day fourteen of ripening. Farm strains belonging to the FTIR cluster B1 and B3, which show genetic characteristics (t2953, ST8, enterotoxin profile: sea/sed/sej of the recently described S. aureus genotype B, most successfully contaminated the cheese production at the dairy plant. Thus our study fosters the hypothesis that genotype B S. aureus represent a specific challenge in control of S. aureus in the dairy chain that requires effective clearance strategies and hygienic

  4. Staphylococcus aureus Entrance into the Dairy Chain: Tracking S. aureus from Dairy Cow to Cheese

    Science.gov (United States)

    Kümmel, Judith; Stessl, Beatrix; Gonano, Monika; Walcher, Georg; Bereuter, Othmar; Fricker, Martina; Grunert, Tom; Wagner, Martin; Ehling-Schulz, Monika

    2016-01-01

    Staphylococcus aureus is one of the most important contagious mastitis pathogens in dairy cattle. Due to its zoonotic potential, control of S. aureus is not only of great economic importance in the dairy industry but also a significant public health concern. The aim of this study was to decipher the potential of bovine udder associated S. aureus as reservoir for S. aureus contamination in dairy production and processing. From 18 farms, delivering their milk to an alpine dairy plant for the production of smeared semi-hard and hard cheese. one thousand hundred seventy six one thousand hundred seventy six quarter milk (QM) samples of all cows in lactation (n = 294) and representative samples form bulk tank milk (BTM) of all farms were surveyed for coagulase positive (CPS) and coagulase negative Staphylococci (CNS). Furthermore, samples from different steps of the cheese manufacturing process were tested for CPS and CNS. As revealed by chemometric-assisted FTIR spectroscopy and molecular subtyping (spa typing and multi locus sequence typing), dairy cattle represent indeed an important, yet underreported, entrance point of S. aureus into the dairy chain. Our data clearly show that certain S. aureus subtypes are present in primary production as well as in the cheese processing at the dairy plant. However, although a considerable diversity of S. aureus subtypes was observed in QM and BTM at the farms, only certain S. aureus subtypes were able to enter and persist in the cheese manufacturing at the dairy plant and could be isolated from cheese until day 14 of ripening. Farm strains belonging to the FTIR cluster B1 and B3, which show genetic characteristics (t2953, ST8, enterotoxin profile: sea/sed/sej) of the recently described S. aureus genotype B, most successfully contaminated the cheese production at the dairy plant. Thus, our study fosters the hypothesis that genotype B S. aureus represent a specific challenge in control of S. aureus in the dairy chain that requires

  5. EARLY ENTRANCE CO-PRODUCTION PLANT - DECENTRALIZED GASIFICATION COGENERATION TRANSPORTATION FUELS AND STEAM FROM AVAILABLE FEEDSTOCKS

    Energy Technology Data Exchange (ETDEWEB)

    John W. Rich

    2003-12-01

    Waste Processors Management, Inc. (WMPI), along with its subcontractors Texaco Power & Gasification (now ChevronTexaco), SASOL Technology Ltd., and Nexant Inc. entered into a Cooperative Agreement DE-FC26-00NT40693 with the U. S. Department of Energy (DOE), National Energy Technology Laboratory (NETL) to assess the techno-economic viability of building an Early Entrance Co-Production Plant (EECP) in the United States to produce ultra clean Fischer-Tropsch (FT) transportation fuels with either power or steam as the major co-product. The EECP design includes recovery and gasification of low-cost coal waste (culm) from physical coal cleaning operations and will assess blends of the culm with coal or petroleum coke. The project has three phases. Phase I is the concept definition and engineering feasibility study to identify areas of technical, environmental and financial risk. Phase II is an experimental testing program designed to validate the coal waste mixture gasification performance. Phase III updates the original EECP design based on results from Phase II, to prepare a preliminary engineering design package and financial plan for obtaining private funding to build a 5,000 barrel per day (BPD) coal gasification/liquefaction plant next to an existing co-generation plant in Gilberton, Schuylkill County, Pennsylvania. The current report covers the period performance from July 1, 2003 through September 30, 2003. The DOE/WMPI Cooperative Agreement was modified on May 2003 to expand the project team to include Shell Global Solutions, U.S. and Uhde GmbH as the engineering contractor. The addition of Shell and Uhde strengthen both the technical capability and financing ability of the project. Uhde, as the prime EPC contractor, has the responsibility to develop a LSTK (lump sum turnkey) engineering design package for the EECP leading to the eventual detailed engineering, construction and operation of the proposed concept. Major technical activities during the reporting

  6. Spanish pre-university students' use of English: CEA results from the University Entrance Examination

    Directory of Open Access Journals (Sweden)

    María Belén Díez Bedmar

    2011-12-01

    Full Text Available In this paper an updated overview of the main errors that Spanish students make when writing the English exam in the University Entrance Examination is provided. To do so, a Computer-aided Error Analysis (CEA (Dagneaux, Denness & Granger, 1998 was conducted on a representative sample of the students who took the exam in June 2008 in Jaén, and wrote a composition on the same topic. The use of the most widely-used error taxonomy, the Error Tagging Manual version 1.1. (Dagneaux, Denness, Granger & Meunier, 1996, and the analysis of the results by means of descriptive statistics foster the possibility to replicate this study and move forward in the description of the students’ written command in the foreign language at this stage. The comparison of the findings obtained in this study and those from previous (CEAs on the English exam reveals that some common tendencies may be shown.Este artículo aporta una visión general actualizada de los errores más importantes que los alumnos españoles cometen cuando escriben el examen de inglés de la Prueba de Acceso a la Universidad. Con este fin, se realizó un Análisis de Errores Informatizado (Dagneaux, Denness & Granger, 1998 en una muestra representativa de los estudiantes que realizaron el examen en Junio de 2008 en la Universidad de Jaén, y que escribieron sobre un mismo tema. El uso de la taxonomía de errores más usada, el Error Tagging Manual version 1.1. (Dagneaux, Denness, Granger & Meunier, 1996, y de la estadística descriptiva para analizar los resultados, favorecen la réplica de este estudio y la posibilidad de mejorar la descripción de la destreza escrita en la lengua extranjera. La comparación de los resultados en este artículo y otros Análisis de Errores (Informatizados previos muestran que se pueden exponer algunas tendencias comunes.

  7. Study of angular momentum variation due to entrance channel effect in heavy ion fusion reactions

    Science.gov (United States)

    Kumar, Ajay

    2014-05-01

    A systematic investigation of the properties of hot nuclei may be studied by detecting the evaporated particles. These emissions reflect the behavior of the nucleus at various stages of the deexcitation cascade. When the nucleus is formed by the collision of a heavy nucleus with a light particle, the statistical model has done a good job of predicting the distribution of evaporated particles when reasonable choices were made for the level densities and yrast lines. Comparison to more specific measurements could, of course, provide a more severe test of the model and enable one to identify the deviations from the statistical model as the signature of other effects not included in the model. Some papers have claimed that experimental evaporation spectra from heavy-ion fusion reactions at higher excitation energies and angular momenta are no longer consistent with the predictions of the standard statistical model. In order to confirm this prediction we have employed two systems, a mass-symmetric (31P+45Sc) and a mass-asymmetric channel (12C+64Zn), leading to the same compound nucleus 76Kr* at the excitation energy of 75 MeV. Neutron energy spectra of the asymmetric system (12C+64Zn) at different angles are well described by the statistical model predictions using the normal value of the level density parameter a = A/8 MeV-1. However, in the case of the symmetric system (31P+45Sc), the statistical model interpretation of the data requires the change in the value of a = A/10 MeV-1. The delayed evolution of the compound system in case of the symmetric 31P+45Sc system may lead to the formation of a temperature equilibrated dinuclear complex, which may be responsible for the neutron emission at higher temperature, while the protons and alpha particles are evaporated after neutron emission when the system is sufficiently cooled down and the higher g-values do not contribute in the formation of the compound nucleus for the symmetric entrance channel in case of charged

  8. Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Fabian A. Cabezas-Opazo

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disease that affects millions of people worldwide. Currently, there is no effective treatment for AD, which indicates the necessity to understand the pathogenic mechanism of this disorder. Extracellular aggregates of amyloid precursor protein (APP, called Aβ peptide and neurofibrillary tangles (NFTs, formed by tau protein in the hyperphosphorylated form are considered the hallmarks of AD. Accumulative evidence suggests that tau pathology and Aβ affect neuronal cells compromising energy supply, antioxidant response, and synaptic activity. In this context, it has been showed that mitochondrial function could be affected by the presence of tau pathology and Aβ in AD. Mitochondria are essential for brain cells function and the improvement of mitochondrial activity contributes to preventing neurodegeneration. Several reports have suggested that mitochondria could be affected in terms of morphology, bioenergetics, and transport in AD. These defects affect mitochondrial health, which later will contribute to the pathogenesis of AD. In this review, we will discuss evidence that supports the importance of mitochondrial injury in the pathogenesis of AD and how studying these mechanisms could lead us to suggest new targets for diagnostic and therapeutic intervention against neurodegeneration.

  9. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  10. Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi; Hidaka, Makoto; Masaki, Haruhiko, E-mail: amasaki@mail.ecc.u-tokyo.ac.jp

    2014-08-15

    Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.

  11. Etiology and pathogenesis of Parkinson’s disease: role of mitochondrial pathology

    Directory of Open Access Journals (Sweden)

    Ottolini D

    2013-05-01

    Full Text Available Denis Ottolini, Tito Calì, Marisa BriniDepartment of Comparative Biomedicine and Food Science, University of Padova, Padova, ItalyAbstract: Neurons critically rely on mitochondrial activity: they are characterized by high energy demand and they are totally dependent on the process of oxidative phosphorylation to produce adenosine triphosphate. Thus, any impairment in mitochondrial function results in neuronal damage and degeneration. Some particular neuronal populations are more susceptible to mitochondrial damage, as it has been recently proposed for the ventral midbrain dopaminergic neurons, the degeneration of which represents a clinical sign of Parkinson’s disease. Different cellular pathways are involved in the pathogenesis of this neurodegenerative disease, but intriguingly both sporadic and familial forms share common features that essentially recapitulate mitochondrial dysfunction. Mitochondrial biogenesis, bioenergetics, mitochondria dynamics, and quality-control process are the main affected pathways. General consensus agrees on the possibility that deficiency in these processes may represent the cause rather than the consequence of neurodegeneration. In this review, we will discuss these aspects and the substantial achievements that have been reached in recent years in identifying specific defects in precise biological processes, eg, mitochondrial quality control. The development of cell and animal genetic models has been an important tool to dissect numerous molecular details; for this reason, we will mainly refer to experiments performed on them.Keywords: mitochondria, Parkinson’s disease, α-synuclein, PINK1/parkin, DJ-1, LRRK2

  12. The Psm locus controls paternal sorting of the cucumber mitochondrial genome.

    Science.gov (United States)

    Havey, M J; Park, Y H; Bartoszewski, G

    2004-01-01

    The mitochondrial genome of cucumber shows paternal transmission and there are no reports of variation for mitochondrial transmission in cucumber. We used a mitochondrially encoded mosaic (MSC) phenotype to reveal phenotypic variation for mitochondrial-genome transmission in cucumber. At least 10 random plants from each of 71 cucumber plant introductions (PIs) were crossed as the female with an inbred line (MSC16) possessing the MSC phenotype. Nonmosaic F1 progenies were observed at high frequencies (greater than 50%) in F1 families from 10 PIs, with the greatest proportions being from PI 401734. Polymorphisms near the mitochondrial cox1 gene and JLV5 region revealed that nonmosaic hybrid progenies from crosses of PI 401734 with MSC16 as the male possessed the nonmosaic-inducing mitochondrial DNA (mtDNA) from the paternal parent. F2) F3, and backcross progenies from nonmosaic F1 plants from PI 401734 x MSC16 were testcrossed with MSC16 as the male parent to reveal segregation of a nuclear locus (Psm for Paternal sorting of mitochondria) controlling sorting of mtDNA from the paternal parent. Psm is a unique locus at which the maternal genotype affects sorting of paternally transmitted mtDNA.

  13. Mutant Huntingtin and Elusive Defects in Oxidative Metabolism and Mitochondrial Calcium Handling.

    Science.gov (United States)

    Brustovetsky, Nickolay

    2016-07-01

    Elongation of a polyglutamine (polyQ) stretch in huntingtin protein (Htt) is linked to Huntington's disease (HD) pathogenesis. The mutation in Htt correlates with neuronal dysfunction in the striatum and cerebral cortex and eventually leads to neuronal cell death. The exact mechanisms of the injurious effect of mutant Htt (mHtt) on neurons are not completely understood but might include aberrant gene transcription, defective autophagy, abnormal mitochondrial biogenesis, anomalous mitochondrial dynamics, and trafficking. In addition, deficiency in oxidative metabolism and defects in mitochondrial Ca(2+) handling are considered essential contributing factors to neuronal dysfunction in HD and, consequently, in HD pathogenesis. Since the discovery of the mutation in Htt, the questions whether mHtt affects oxidative metabolism and mitochondrial Ca(2+) handling and, if it does, what mechanisms could be involved were in focus of numerous investigations. However, despite significant research efforts, the detrimental effect of mHtt and the mechanisms by which mHtt might impair oxidative metabolism and mitochondrial Ca(2+) handling remain elusive. In this paper, I will briefly review studies aimed at clarifying the consequences of mHtt interaction with mitochondria and discuss experimental results supporting or arguing against the mHtt effects on oxidative metabolism and mitochondrial Ca(2+) handling.

  14. Mitochondrial deficiency: a double-edged sword for ageing and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Daniele eBano

    2012-11-01

    Full Text Available For decades, ageing was considered the inevitable result of the accumulation of damaged macromolecules due to environmental factors and intrinsic processes. Our current knowledge clearly supports that ageing is a complex biological process influenced by multiple evolutionary conserved molecular pathways. With the advanced age, loss of cellular homeostasis severely affects the structure and function of various tissues, especially those highly sensitive to stressful conditions like the central nervous system. In this regard, the age-related regression of neural circuits and the consequent poor neuronal plasticity have been associated with metabolic dysfunctions, in which the decline of mitochondrial activity significantly contributes. Interestingly, while mitochondrial lesions promote the onset of degenerative disorders, mild mitochondrial manipulations delay some of the age-related phenotypes and, more importantly, increase the lifespan of organisms ranging from invertebrates to mammals. Here, we survey the insulin/IGF-1 and the TOR signaling pathways and review how these two important longevity determinants regulate mitochondrial activity. Furthermore, we discuss the contribution of slight mitochondrial dysfunction in the engagement of pro-longevity processes and the opposite role of strong mitochondrial dysfunction in neurodegeneration.

  15. Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion.

    Science.gov (United States)

    Quarrie, Ricardo; Lee, Daniel S; Reyes, Levy; Erdahl, Warren; Pfeiffer, Douglas R; Zweier, Jay L; Crestanello, Juan A

    2014-10-01

    Cardiac ischemia-reperfusion (IR) leads to myocardial dysfunction by increasing production of reactive oxygen species (ROS). Mitochondrial H(+) leak decreases ROS formation; it has been postulated that increasing H(+) leak may be a mechanism of decreasing ROS production after IR. Ischemic preconditioning (IPC) decreases ROS formation after IR, but the mechanism is unknown. We hypothesize that pharmacologically increasing mitochondrial H(+) leak would decrease ROS production after IR. We further hypothesize that IPC would be associated with an increase in the rate of H(+) leak. Isolated male Sprague-Dawley rat hearts were subjected to either control or IPC. Mitochondria were isolated at end equilibration, end ischemia, and end reperfusion. Mitochondrial membrane potential (mΔΨ) was measured using a tetraphenylphosphonium electrode. Mitochondrial uncoupling was achieved by adding increasing concentrations of FCCP. Mitochondrial ROS production was measured by fluorometry using Amplex-Red. Pyridine dinucleotide levels were measured using HPLC. Before IR, increasing H(+) leak decreased mitochondrial ROS production. After IR, ROS production was not affected by increasing H(+) leak. H(+) leak increased at end ischemia in control mitochondria. IPC mitochondria showed no change in the rate of H(+) leak throughout IR. NADPH levels decreased after IR in both IPC and control mitochondria while NADH increased. Pharmacologically, increasing H(+) leak is not a method of decreasing ROS production after IR. Replenishing the NADPH pool may be a means of scavenging the excess ROS thereby attenuating oxidative damage after IR.

  16. Polychlorinated Biphenyls Induce Mitochondrial Dysfunction in SH-SY5Y Neuroblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Stefania Cocco

    Full Text Available Chronic exposure to polychlorinated biphenyls (PCBs, ubiquitous environmental contaminants, can adversely affect the development and function of the nervous system. Here we evaluated the effect of PCB exposure on mitochondrial function using the PCB mixture Aroclor-1254 (A1254 in SH-SY5Y neuroblastoma cells. A 6-hour exposure to A1254 (5 μg/ml reduced cellular ATP production by 45%±7, and mitochondrial membrane potential, detected by TMRE, by 49%±7. Consistently, A1254 significantly decreased oxidative phosphorylation and aerobic glycolysis measured by extracellular flux analyzer. Furthermore, the activity of mitochondrial protein complexes I, II, and IV, but not V (ATPase, measured by BN-PAGE technique, was significantly reduced after 6-hour exposure to A1254. The addition of pyruvic acid during exposure to A1254 significantly prevent A1254-induced cell injury, restoring resting mitochondrial membrane potential, ATP levels, oxidative phosphorylation and aerobic glycolysis. Furthermore, pyruvic acid significantly preserved the activity of mitochondrial complexes I, II and IV and increased basal activity of complex V. Collectively, the present results indicate that the neurotoxicity of A1254 depends on the impairment of oxidative phosphorylation, aerobic glycolysis, and mitochondrial complexes I, II, and IV activity and it was counteracted by pyruvic acid.

  17. Exercise Training Alleviates Hypoxia-induced Mitochondrial Dysfunction in the Lymphocytes of Sedentary Males

    Science.gov (United States)

    Tsai, Hsing-Hua; Chang, Shao-Chiang; Chou, Cheng-Hsien; Weng, Tzu-Pin; Hsu, Chih-Chin; Wang, Jong-Shyan

    2016-01-01

    This study elucidates how interval and continuous exercise regimens affect the mitochondrial functionality of lymphocytes under hypoxic stress. Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3 min intervals at 80% and 40% VO2max, n = 20) or moderate-intensity continuous training (MICT, sustained 60% VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks or were assigned to a control group that did not receive exercise intervention (n = 20). Lymphocyte phenotypes/mitochondrial functionality under hypoxic exercise (HE, 100 W under 12% O2) were determined before and after the various interventions. Before the intervention, HE (i) increased the mobilization of senescent (CD57+/CD28−) lymphocytes into the blood, (ii) decreased the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the citrate synthase activity in the mitochondria, and (iii) lowered the mitochondrial membrane potential (MP) and elevated the matrix oxidant burden (MOB) of lymphocytes. However, both HIIT and MICT significantly (i) decreased blood senescent lymphocyte counts, (ii) enhanced the mitochondrial OCR with increased citrate synthase and succinate dehydrogenase activities, (iii) increased mitochondrial MP and decreased MOB and (iv) increased the ratio of mitofusin to DRP-1 in lymphocytes after HE. Thus, we concluded that either HIIT or MICT effectively improves lymphocyte mitochondrial functionality by enhancing oxidative phosphorylation and suppressing oxidative damage under hypoxic conditions. PMID:27731374

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

    Science.gov (United States)

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

    2016-01-01

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

  19. 33 CFR 334.1210 - Admiralty Inlet, entrance; naval restricted area.

    Science.gov (United States)

    2010-07-01

    ..., and such agencies as he/she may designate. Editorial Note: For Federal Register citations affecting § 334.1210, see the List of CFR Sections Affected, which appears in the Finding Aids section of the.... Beginning at Point Wilson Light thence southwesterly along the coast line to latitude 48°07′ N.;...

  20. Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic Agents

    Directory of Open Access Journals (Sweden)

    Bodil Bjørndal

    2011-01-01

    Full Text Available Adipose tissue metabolism is closely linked to insulin resistance, and differential fat distributions are associated with disorders like hypertension, diabetes, and cardiovascular disease. Adipose tissues vary in their impact on metabolic risk due to diverse gene expression profiles, leading to differences in lipolysis and in the production and release of adipokines and cytokines, thereby affecting the function of other tissues. In this paper, the roles of the various adipose tissues in obesity are summarized, with particular focus on mitochondrial function. In addition, we discuss how a functionally mitochondrial-targeted compound, the modified fatty acid tetradecylthioacetic acid (TTA, can influence mitochondrial function and decrease the size of specific fat depots.