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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 was to ...

  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 examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility....

  3. Drosophila Porin/VDAC affects mitochondrial morphology.

    Directory of Open Access Journals (Sweden)

    Jeehye Park

    Full Text Available Voltage-dependent anion channel (VDAC has been suggested to be a mediator of mitochondrial-dependent cell death induced by Ca(2+ overload, oxidative stress and Bax-Bid activation. To confirm this hypothesis in vivo, we generated and characterized Drosophila VDAC (porin mutants and found that Porin is not required for mitochondrial apoptosis, which is consistent with the previous mouse studies. We also reported a novel physiological role of Porin. Loss of porin resulted in locomotive defects and male sterility. Intriguingly, porin mutants exhibited elongated mitochondria in indirect flight muscle, whereas Porin overexpression produced fragmented mitochondria. Through genetic analysis with the components of mitochondrial fission and fusion, we found that the elongated mitochondria phenotype in porin mutants were suppressed by increased mitochondrial fission, but enhanced by increased mitochondrial fusion. Furthermore, increased mitochondrial fission by Drp1 expression suppressed the flight defects in the porin mutants. Collectively, our study showed that loss of Drosophila Porin results in mitochondrial morphological defects and suggested that the defective mitochondrial function by Porin deficiency affects the mitochondrial remodeling process.

  4. Analyzing the Factors Affecting the Success in University Entrance Examination through the use of Artificial Neural Networks

    Science.gov (United States)

    Agdelen, Zafer; Haydar, Ali; Kanani, Andisheh

    2007-01-01

    There are many factors that affect the success of students in university entrance examination. These factors can be mainly categorized as follows; social factors, environmental factors, economical factors etc. The main aim of this study is to find whether there is a relation between these factors and the success in the university entrance…

  5. 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…

  6. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

    Directory of Open Access Journals (Sweden)

    Lina M. Ruiz

    2015-01-01

    Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

  7. 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

  8. 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.

  9. 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

  10. Mitochondrial DNA mutations affect calcium handling in differentiated neurons.

    NARCIS (Netherlands)

    Trevelyan, A.J.; Kirby, D.M.; Smulders-Srinivasan, T.K.; Nooteboom, M.; Acin-Perez, R.; Enriquez, J.A.; Whittington, M.A.; Lightowlers, R.N.; Turnbull, D.M.

    2010-01-01

    Mutations in the mitochondrial genome are associated with a wide range of neurological symptoms, but many aspects of the basic neuronal pathology are not understood. One candidate mechanism, given the well-established role of mitochondria in calcium buffering, is a deficit in neuronal calcium homoeo

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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

    In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin......, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from...... the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against...

  14. 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.

  15. 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

    2015-01-01

    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. PMID:26019234

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

    Science.gov (United States)

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

    2016-08-01

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

  17. 影响地方院校大学生考研的因素及其措施%The Factors Affecting Regional Academy Students to Take Postgraduate Entrance Exam and its Countermeasures

    Institute of Scientific and Technical Information of China (English)

    张信练

    2016-01-01

    It's important choice for university students to take graduate entrance exam. But these years the enthusiasm of regional academy students is decreasing. The rate of apply and admission become lower and lower. This should be taken more intention by educators. There are many factors affecting the enthusiasm of regional academy students to take graduate entrance exam. So reasonable countermeasures should be adopted in order to enhance students' enthusiasm and make the postgraduate education develop effectively.%考研是大学生的重要选择,但近年来地方院校大学生考研积极性不高,报考率与录取率持续走低,应当引起教育工作者的重视.影响地方院校大学生考研存在各种因素,针对这些因素采取相应的措施才能提高他们报考的积极性,从而有效地促进研究生教育事业健康发展.

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

    Science.gov (United States)

    Swan, E J; Salem, R M; Sandholm, N; Tarnow, L; Rossing, P; Lajer, M; Groop, P H; Maxwell, A P; McKnight, A J

    2015-01-01

    polymorphisms (SNPs) in nuclear genes affecting mitochondrial function were found to be associated with diabetic kidney disease. The highlighted SNPs were within the genes implicated in regulation of epigenetic processes. Further research to explore the interactions between hyperglycaemia, uraemia and epigenetic modifications of the genome could shed new light on how these nuclear genome SNPs are associated with kidney disease. PMID:25819010

  19. 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.

  20. 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.

  1. English for common entrance

    CERN Document Server

    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. 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.

  3. 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.

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

    OpenAIRE

    Yongshan Hu; Jianhong Zhu; Pengyue Zhang; Jie Jia; Hongying Sha; Yi Wu; Qi Zhang

    2012-01-01

    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 pro...

  5. 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.

  6. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    International Nuclear Information System (INIS)

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H2O2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

  7. Miro GTPase controls mitochondrial behavior affecting stress tolerance and virulence of a fungal insect pathogen.

    Science.gov (United States)

    Guan, Yi; Wang, Ding-Yi; Ying, Sheng-Hua; Feng, Ming-Guang

    2016-08-01

    Miro homologues are small mitochondrial Rho GTPases belonging to the Ras superfamily across organisms and are generally unexplored in filamentous fungi. Here we identified a Miro orthologue (bMiro) in Beauveria bassiana, a filamentous fungal insect pathogen as a classic biological control agent of insect pests. This orthologue was proven to anchor on mitochondrial outer membrane in a manner depending completely upon a short C-terminal transmembrane domain. As a result of bmiro deletion, mitochondria in hyphal cells were largely aggregated, and their mass and mobility were reduced, accompanied with a remarkable decrease in ATP content but little change in mitochondrial morphology. The deletion mutant became 42%, 37%, 19% and 10% more tolerant to Ca(2+), Mn(2+), Zn(2+) and Mg(2+) than wild-type, respectively, during cultivation in a minimal medium under normal conditions. The deletion mutant also showed mild defects in conidial germination, vegetative growth, thermotolerance, UV-B resistance and virulence despite null response to oxidative and osmotic stresses. All these phenotypic changes were restored by targeted gene complementation. Our results indicate that bMiro can control mitochondrial distribution and movement required for the transport of ATP-form energy and metal ions and contributes significantly to the fungal potential against insect pests through the control. PMID:27241960

  8. 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

  9. 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.

  10. 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.

  11. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaq Ahmed; John H. Anderson; Earl R. Berry; Fred Brent; Ming He; Jimmy O. Ong; Mike K. Porter; Randy Roberts; Charles H. Schrader; Lalit S. Shah; Kenneth A. Yackly

    2002-11-22

    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 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 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.

  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. 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.

  14. 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.

  15. 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. PMID:26118693

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

    OpenAIRE

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

    2003-01-01

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

  17. Cromakalin pretreatment affects mitochondrial structure and function in a rat model of ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Peng Wang; Qingxian Chang; Yu Li; Yan Jiang; Shiduan Wang

    2008-01-01

    BACKGROUND: Mitochondrial structural changes and energy dysmetabolism frequently occur subsequent to cerebral ischemia. Adenosine triphosphate (ATP)-sensitive potassium channel openers exhibit protective effects on cerebral ischemia/reperfusion injury. OBJECTIVE: To validate the effects of cromakalin on mitochondrial structure and function in ischemic penumbra brain tissue in a rat model of middle cerebral artery occlusion (MCAO). DESIGN, TIME AND SETTING: The present single-factor analysis of variance, randomized, controlled, animal experiment was performed at the Institute of Brain Science, Affiliated Hospital of Qingdao University Medical College between October 2007 and March 2008. MATERIALS: Forty male, Wistar rats were randomly divided into four groups, with 10 rats per group: sham-operated, MCAO, MCAO+ATP-sensitive potassium channel opener (cromakalin), and MCAO+eromakalin+ATP-sensitive potassium channel blocking agent (glibenclamide). METHODS: Focal cerebral ischemia/reperfusion injury was induced by MCAO in all groups except the sham-operated group. The MCAO cromakalin group was administered 10 mg/kg cromakalin (i.p.) prior to MCAO induction. The MCAO+cromakalin+glibenclamide group received an injection of 10 mg/kg cromakalin (i.v.), and subsequently an injection of 10 mg/kg cromakalin (i.p.) prior to MCAO induction. MAIN OUTCOME MEASURES: At 24 hours after cerebral ischemia/reperfusion injury, cellular apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique. Cytochrome C expression was measured by immunohistochemistry. In addition, mitochondrial swelling, membrane fluidity, membrane phospholipid and malonaldehyde (MDA) contents, as well as Na+-K+-ATPase, Ca2+-ATPase, and superoxide dismutase (SOD) activities were determined. RESULTS: Compared with the sham-operated group, the three ischemia groups exhibited significantly elevated mitochondrial MDA content, reduced membrane

  18. 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

  19. 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

  20. 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

  1. 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

  2. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John H. Anderson; Charles Benham; Earl R. Berry; Ming He; Charles H. Schrader; Lalit S. Shah; O.O. Omatete; T.D. Burchell

    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. During Phase I the team identified several potential methods to reduce or minimize the environmental impact of the proposed EECP. The EECP Project Team identified F-T catalyst disposal, beneficial gasifier slag usage (other than landfill), and carbon dioxide recovery for the gas turbine exhaust for study under this task. Successfully completing the Task 2.10 RD&T provides additional opportunities for the EECP to

  3. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Madsen, Claus Desler; Bøggild, Cecilie Sisse Line;

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear...... and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells....... pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection....

  4. 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

  5. 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

  6. A high-fat diet negatively affects rat sperm mitochondrial respiration.

    Science.gov (United States)

    Ferramosca, A; Conte, A; Moscatelli, N; Zara, V

    2016-05-01

    Recent evidences have linked abdominal obesity, insulin resistance, and dyslipidemia to male infertility. Since a defective energy metabolism may play an important role in the impairment of sperm quality, the aim of this study is to investigate the sperm energetic metabolism in rats fed with a high-fat diet, an animal model associated with metabolic syndrome development. Sexually mature male Sprague-Dawley rats were divided into two groups and fed for 4 weeks a standard diet (control group) or a diet enriched in 35% of fat (high fat group). Liver and adipose tissue weight, plasma glucose, insulin, and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption. The administration of a high-fat diet caused a significant increase in body weight of rats and provoked hyperglycemia, hyperinsulinemia, and dyslipidemia. In these animals, we also observed a reduction in sperm concentration and motility. The investigation of sperm energetic metabolism in animals fed a high-fat diet revealed an impairment in the activity of pyruvate and lactate dehydrogenase, citrate synthase, and respiratory chain complexes. A parallel reduction in the cellular levels of adenosine triphosphate (ATP) and an increase in oxidative damage were also observed. A defective energy metabolism may play an important role in the impairment of sperm quality in the high-fat diet fed rats. PMID:27062222

  7. 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

  8. 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.

  9. 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

    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...... or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of...

  10. 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.

  11. 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

  12. The yeast nuclear gene suv3 affecting mitochondrial post-transcriptional processes encodes a putative ATP-dependent RNA helicase.

    OpenAIRE

    Stepien, P P; Margossian, S P; Landsman, D.; Butow, R A

    1992-01-01

    Mitochondrial gene expression is controlled largely through the action of products of the nuclear genome. The yeast nuclear gene suv3 has been implicated in a variety of mitochondrial posttranscriptional processes and in translation and, thus, represents a key control element in nuclear-mitochondrial interactions. We have exploited a property of a mutant allele of suv3, SUV3-1, that causes, among other effects, a massive increase in the abundance of excised group I introns to clone the wild-t...

  13. Utility service entrance in boreholes

    International Nuclear Information System (INIS)

    This study evaluates alternatives for utility service entrances to the repository. We determined the requirements for a repository utility supply. These requirements were defined as safety, maintainability, flexibility, reliability, cost efficiency, voltage regulation, and simplicity of operation. The study showed that repository shafts can best satisfy all requirements for location of the utility supply without the use of borehole penetrations into the repository. It is recommended that the shafts be utilized for utility distribution to the repository, and that the current NWTS program position to minimize the number of boreholes penetrating the repository horizon be maintained. 42 refs., 2 figs., 3 tabs

  14. 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.

  15. 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

  16. 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.

  17. EARLY ENTRANCE COPRODUCTION PLANT; TOPICAL

    International Nuclear Information System (INIS)

    As part of the Department of Energy's (DOE) Gasification Technologies and Transportation Fuels and Chemicals programs, DOE and Texaco are partners through Cooperative Agreement DE-FC26-99FT40658 to determine the feasibility of developing, constructing and operating an Early Entrance Coproduction Plant (EECP). The overall objective of the project is the three-phase development of an 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 specific work requirements of Phase I included: Prepare an EECP Preliminary Concept Report covering Tasks 2-8 specified in the Cooperative Agreement; Develop a Research, Development, and Testing (RD and T) Plan as specified in Task 9 of the Cooperative Agreement for implementation in Phase II; and Develop a Preliminary Project Financing Plan for the EECP Project as specified in Task 10 of the Cooperative Agreement. This document is the Preliminary Project Financing Plan for the design, construction, and operation of the EECP at the Motiva Port Arthur Refinery

  18. 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.

  19. 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.

  20. Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Moskovitz, Jackob; Du, Fang; Bowman, Connor F; Yan, Shirley S

    2016-03-15

    Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice (APP(+)/MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP(+) mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP(+)/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.

  1. Paternal Genetic Structure of Hainan Aborigines Isolated at the Entrance to East Asia

    OpenAIRE

    Dongna Li; Hui Li; Caiying Ou; Yan Lu; Yuantian Sun; Bo Yang; Zhendong Qin; Zhenjian Zhou; Shilin Li; Li Jin

    2008-01-01

    BACKGROUND: At the southern entrance to East Asia, early population migration has affected most of the Y-chromosome variations of East Asians. METHODOLOGY/PRINCIPAL FINDINGS: To assess the isolated genetic structure of Hainan Island and the original genetic structure at the southern entrance, we studied the Y chromosome diversity of 405 Hainan Island aborigines from all the six populations, who have little influence of the recent mainland population relocations and admixtures. Here we report ...

  2. 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

  3. Affectivity

    OpenAIRE

    Stenner, Paul; Greco, Monica

    2013-01-01

    The concept of affectivity has assumed central importance in much recent scholarship, and many in the social sciences and humanities now talk of an ‘affective turn’. The concept of affectivity at play in this ‘turn’ remains, however, somewhat vague and slippery. Starting with Silvan Tomkins’ influential theory of affect, this paper will explore the relevance of the general assumptions (or ‘utmost abstractions’) that inform thinking about affectivity. The technological and instrumentalist char...

  4. 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

  5. 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.

  6. 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

  7. The University Entrance Examination System in China

    Science.gov (United States)

    Davey, Gareth; De Lian, Chuan; Higgins, Louise

    2007-01-01

    Every year, millions of high school students sit the Chinese national university entrance exam, and their results determine entry into universities or alternatives such as employment. Limited information about the exam is available in the Western literature even though it determines the future of millions of young people, and is increasingly of…

  8. 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)

  9. 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.

  10. 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...

  11. 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.

  12. 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...

  13. 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 ...

  14. Profile of State College Entrance Exam Policies. Delaware

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Delaware's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking…

  15. Profile of State College Entrance Exam Policies. Alabama

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alabama's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking…

  16. Profile of State College Entrance Exam Policies. Idaho

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Idaho's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking college…

  17. Profile of State College Entrance Exam Policies. North Dakota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on North Dakota's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking…

  18. Profile of State College Entrance Exam Policies. Tennessee

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Tennessee's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking…

  19. Profile of State College Entrance Exam Policies. Maine

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Maine's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking college…

  20. Profile of State College Entrance Exam Policies. Kentucky

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Kentucky's college entrance exam standards and polices. Some of the categories presented include: (1) College entrance exam policy; (2) Purpose; (3) Major changes in college entrance exam policy since the 2009-10 school year for financial reasons; (4) Preparation state offers to students taking…

  1. Impeller entrance pre whirl characteristics research

    Science.gov (United States)

    WU, W.; Wang, Y.; Han, Y. W.

    2016-05-01

    In order to study the effect of inlet port on the pump performance, the impeller inlet part, should be analyzed for impeller is able to extend the function of water flow to the front of the impeller for a long distance. Impeller flow of pre swirl flow is due to selection of least resistance into the impeller, but the pre swirl in the flow direction according to the impeller blade entrance angle, and the circumferential velocity of flow. The study found that lies in the external characteristic of the pump will be fell when the off-design, but in the case of large flow impeller and impeller in the direction of the front entrance fluid pre whirl steering is on the contrary, when this with little traffic is quite different .this article will study the occurrence, development, and the mechanism of the influence of flow field.

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Binaural recordings enable us to capture all sound attributes including spatial information, room effect, and source characteristics in a given environment. It has been shown that blocked-entrance binaural recordings provide advantages over open-entrance recordings, primarily because the blocked-...... 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.......Binaural recordings enable us to capture all sound attributes including spatial information, room effect, and source characteristics in a given environment. It has been shown that blocked-entrance binaural recordings provide advantages over open-entrance recordings, primarily because the blocked......-entrance recordings is not influenced by the ear canal acoustics of the individual for which it is recorded. However, blocking the ear canal for recoding imposes an obvious disruption to normal hearing conditions, which may be unacceptable for applications in which binaural audio capturing is desired but without...

  5. Learning (Not) to become a Teacher: A Qualitative Analysis of the Job Entrance Issue

    Science.gov (United States)

    Rots, Isabel; Kelchtermans, Geert; Aelterman, Antonia

    2012-01-01

    Reporting on 12 case studies of student teachers, this paper examines how experiences during teacher education affect graduates' decision on job entrance. Interpretative data-analysis reveals that powerful sources of the shift in motivation to enter teaching concern interactions in which the person of the teacher is at stake. These mainly involve…

  6. 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.

  7. Mitochondrial Myopathy

    Science.gov (United States)

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

  8. Mitochondrial cytopathies.

    Science.gov (United States)

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-09-01

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

  9. 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...

  10. 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

  11. 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...

  12. 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...

  13. 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

  14. 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

  15. Gender Differences in Strategic Behaviour under Competitive Pressure: Evidence on Omission Patterns in University Entrance Examinations

    OpenAIRE

    Pekkarinen, Tuomas

    2014-01-01

    This paper studies gender differences in performance in university entrance examinations. We exploit data from the exams that the nine Finnish universities providing education in economics and business use to choose their students. These exams are multiple choice tests where wrong answers are penalized by minus points and omissions yield zero points. This scoring rule means that the number of omitted items will affect the probability of entry. The strategic setting of the applicants varies de...

  16. 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.

  17. Bezafibrate improves mitochondrial function in the CNS of a mouse model of mitochondrial encephalopathy

    OpenAIRE

    Noe, Natalie; Dillon, Lloye; Lellek, Veronika; Diaz, Francisca; Hida, Aline; Carlos T. Moraes; Wenz, Tina

    2012-01-01

    Mitochondrial dysfunction frequently affects the central nervous system. Here, we investigated the effect of bezafibrate treatment on neuronal mitochondrial function and its impact on the progression of a mitochondrial encephalopathy. We used a murine model with a forebrain-specific cytochrome c oxidase deficiency caused by conditional deletion of the COX10 gene. In this mouse model, bezafibrate-administration improved the phenotype of the mice associated with an increase in mitochondrial pro...

  18. 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.

  19. 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.

  20. 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.

  1. Effect of entrance channel in 16O + 51V interactions

    International Nuclear Information System (INIS)

    The incomplete fusion reactions is a dynamic area of investigation due to complex nature of incomplete mass transfer and its dependence on various entrance channel parameters like type of projectile, energy of projectile, transfer of input angular momentum (ℓ), deformations of the interacting nuclides, mass-asymmetry and α-break up energy (Qα). The aim of this work is to investigate the dependence of ICF on different entrance channel parameters

  2. 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.

  3. A Novel Syndrome Affecting Multiple Mitochondrial Functions, Located by Microcell-Mediated Transfer to Chromosome 2p14-2p13

    Science.gov (United States)

    Seyda, Agnieszka; Newbold, Robert F.; Hudson, Thomas J.; Verner, Andrei; MacKay, Neviana; Winter, Susan; Feigenbaum, Annette; Malaney, Suzann; Gonzalez-Halphen, Diego; Cuthbert, Andrew P.; Robinson, Brian H.

    2001-01-01

    We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by ∼50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain α-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c1, and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13. PMID

  4. MOLECULAR NEUROGENETICS OF MITOCHONDRIAL DISEASES

    Directory of Open Access Journals (Sweden)

    E. Cardaioli

    2012-01-01

    Full Text Available Mitochondrial diseases are an expanding group of clinically heterogeneous disorders associated with mitochondrial DNA (mtDNA mutations or nuclear gene defects. Whatever the mechanism, the final common step in mitochondrial disorders is a defect of energy production resulting from respiratory chain impairment. The complexity of the biochemical and genetic features of the respiratory chain accounts for the extraordinarily wide range of clinical presentations of mitochondrial disorders. In general, organs with high aerobic demand, such as skeletal muscle, brain and heart, are the most affected. However, virtually any organ or tissue in the body may be affected and the disorders can be multisystemic (mitochondrial encephalomyopathiesor confined to a single tissue. Moreover, mitochondrial diseases can be sporadic or transmitted by mendelian (nuclear genes or maternal inheritance (mutations in mtDNA. Precise diagnosis is often a challenge; we go through the traditional steps of the diagnostic process, starting with study of inheritance in the family, clinical manifestations in the individual,electrophysiology and imaging techniques at organ level, down to biochemistry, pathology and molecular genetics at tissue, cell and DNA level, respectively. In fact the ultimate goal is to reach, whenever possible, a definitive molecular diagnosis, which can permit rational therapeutic approach and a genetic counseling.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Autism Spectrum Disorder and Mitochondrial Disease

    Science.gov (United States)

    ... that the cells need to work. In mitochondrial diseases, the mitochondria cannot efficiently turn sugar and oxygen into energy, so the cells do not work correctly. There are many types of mitochondrial disease, and they can affect different parts of the ...

  10. 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…

  11. 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...

  12. [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

  13. 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.

  14. RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity

    DEFF Research Database (Denmark)

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

    2012-01-01

    in 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...... reserve capacity after lentiviral knockdown of RECQL4 in two different primary cell lines. Additionally, biochemical assays with RECQL4, mitochondrial transcription factor A, and mitochondrial DNA polymerase ¿ showed that the polymerase inhibited RECQL4's helicase activity. RECQL4 is the first 3'-5' Rec...

  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. 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 ...

  17. 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.

  18. Prévessin site – Pedestrian and cycle entrances

    CERN Multimedia

    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.

  19. Mitochondrial Metabolism in Aging Heart.

    Science.gov (United States)

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

    2016-05-13

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

  20. 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.

  1. 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.

  2. Mitochondrial dysfunction and organophosphorus compounds

    International Nuclear Information System (INIS)

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP

  3. 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.

  4. Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy.

    OpenAIRE

    Siciliano, Gabriele; Monzani, Fabio; Manca, Maria Laura; Tessa, Alessandra; Caraccio, Nadia; Tozzi, Giulia; Piemonte, Fiorella; Mancuso, Michelangelo; Santorelli, Filippo Maria; Ferrannini, Eleuterio; Murri, Luigi

    2002-01-01

    BACKGROUND: Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding for regulatory proteins of mitochondrial respiratory function, the mitochondrial transcription factor A (h-mtTFA) has been proposed to be a target of thyroid hormone action. The aim of this study has been to relate h-mtTFA levels in the skeletal muscle of patients affected by Hashimoto's hypoth...

  5. The Cognitive Abilities of Children: Reflections from an Entrance Exam

    Science.gov (United States)

    Cil, Emine; Cepni, Salih

    2012-01-01

    The basic determiner for the school in which the children who completed their primary education will in at an upper education level in Turkey is the entrance exam carried out nationwide. The items of national exam, called as LDE (Level Determination Exam) which the primary education pupils (aged between 12 and 15) will participate in Turkey were…

  6. Early College Entrance: How Will My Child Do?

    Science.gov (United States)

    Chung, Rachel U.; Hertzog, Nancy B.

    2014-01-01

    Early college entrance is a form of acceleration, or the process of advancing students in academic programs faster than their same-aged peers. Many early entrants have demonstrated academic ability to achieve at high levels but they exhibit tremendous variety in their age, specific abilities, social and emotional maturity, family support, and…

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

    DEFF Research Database (Denmark)

    Gulmann, C; Hougen, H P

    1999-01-01

    , 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...

  8. Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.

    Science.gov (United States)

    Wada, Jun; Nakatsuka, Atsuko

    2016-06-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  10. 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...

  11. 30 CFR 75.1403-11 - Criteria-Entrances to shafts and slopes.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Criteria-Entrances to shafts and slopes. 75.1403-11 Section 75.1403-11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 75.1403-11 Criteria—Entrances to shafts and slopes. All open entrances to shafts should be...

  12. 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 p......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...

  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

    International Nuclear Information System (INIS)

    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 ∼ 4-7 MeV/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, the 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. (authors)

  15. 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.

  16. 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.

  17. 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. PMID:27181353

  18. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Blein, Sophie; Bardel, Claire; Danjean, Vincent;

    2015-01-01

    mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter...

  19. 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

  20. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Science.gov (United States)

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

    2016-03-14

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

  1. [Exercise and aging: regulation of mitochondrial function and redox system].

    Science.gov (United States)

    Sun, Li-Juan; Zhang, Yong; Liu, Jian-Kang

    2014-10-01

    Evidence shows that aging is closely related to mitochondrial decay and redox imbalance. With aging, both mitochondrial content and protein synthesis declined and free radicals, the by-products of mitochondrial metabolism and their oxidation to lipids, proteins and nuclear acids increased. The age-related declines in mitochondrial function and redox imbalance affect physical function, induce insulin resistance and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, thus, play a major role in regulation of life span. Therefore, mitochondrion may be the most important determinant of life span. Increasing evidence demonstrates that long-term aerobic exercise could prevent age-related diseases and improve life quality of aged people. Exercise may possibly stimulate mitochondrial biogenesis and phase II antioxidant defense system to regulate mitochondrial function and balance of redox system. Therefore, regular aerobic exercise may prevent age-related diseases, increase life quality and prolong life span through regulation of mitochondrial function and redox balance. PMID:25764789

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Heat transfer to liquid sodium in the thermal entrance region

    International Nuclear Information System (INIS)

    It is well known that the convective heat transfer in the regions of duct systems where the thermal boundary layers are not yet established can be far superior to heat transfer in the fully developed regions. A quantitative understanding of heat transfer in the thermal entrance region is essential in designing high heat-flux nuclear reactors. More specifically, if the thermal boundary layers have not been fully established in the system, the forced-convection relations for the fully developed regions cannot be used to predict the heat transfer characteristics. The present work is characterized by the following: 1. The behaviours in the thermal entrance region have been examined more completely. 2. To obtain a higher accuracy of analyses, in present study the method of SPARROW et al. for pipe was improved for annulus by utilizing a finite difference technique. Furthermore, an asymptotic solution was developed. 3. This is, in our knowledge, the first experimental investigation about the thermal development effect on turbulent heat transfer from rod element to liquid sodium in annulus with fully developed flow. (MDC)

  8. 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...

  9. Effect of entrance channel on dynamics of heavy ions collision

    Science.gov (United States)

    Naderi, D.

    2016-01-01

    A combined dynamical model using concept of dinuclear systems (DNS) and one-dimensional (1D) Langevin equations was applied to investigate the effect of entrance channel on dynamics of heavy ions collision. The 30Si+170Er, 16O+184W and 19F+181Ta reactions which formed the compound nucleus 200Pb have been considered to study this effect. We studied these reactions dynamically and calculated the ratio of evaporation residue cross-section to fusion cross-section (σER/σFus) as a tool for investigation of entrance channel effect. Results of combined model are compared with available experimental data and results of 1D Langevin equations. Obtained results based on combined model are in better agreement with experimental data in comparison with results of Langevin equations. We concluded for 30Si+170Er and 19F+181Ta reactions the results of combined model that support the quasi-fission process are different relative to Langevin dynamical approach, whereas for 16O+184W system the two models give similar results.

  10. Why ions enter the sheath entrance at supersonic speed?

    Science.gov (United States)

    Tang, Xianzhu; Guo, Zehua

    2015-11-01

    In a boundary plasma of a fusion device, the sheath Knudsen number, which is defined as the ratio of the plasma mean-free-path and the plasma Debye length, is much greater than unity, so one anticipates a collisionless sheath, even though the overall boundary plasma in the scrape-off layer is collisional. This is supposed to be the regime for which the Bohm criteria for the ion entry flow at the sheath entrance, v >=cs with cs the sound speed, is usually satisfied at the equal sign. But numerical simulations using first-principles particle-in-cell codes tend to report a supersonic flow. Here we revisit the two-scale and transition layer analysis of the sheath-presheath transition, in tandem with the conventional Bohm criteria analysis, to understand why and how the supersonic sheath entry flow is established at the sheath entrance, which is a few Debye length away from the wall, and its impact on plasma particle and power load at the wall. Works upported by DOE OFES. Work supported by DOE OFES.

  11. 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.

  12. 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.

  13. Scoliosis in Mitochondrial Myopathy

    OpenAIRE

    Li, Zheng; Shen, Jianxiong; Liang, Jinqian

    2015-01-01

    Abstract The mitochondrial myopathies include a diverse group of disorders characterized by morphological abnormalities of muscle mitochondria. Little is reported about spinal deformity associated with this syndrome. This study presents a case of scoliosis occurring in the setting of mitochondrial myopathies and explores the possible mechanisms between the 2 diseases. A previously unreported scoliosis in mitochondrial myopathies is described. The patient was a 16-year-old Chinese adolescent b...

  14. Mitochondrial Gene Therapy Augments Mitochondrial Physiology in a Parkinson's Disease Cell Model

    OpenAIRE

    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.

    2009-01-01

    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-ter...

  15. Laminar pipe flow at the entrance into transverse magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yongqi [Department of Mechanical Engineering, University of Michigan-Dearborn, MI 48128-1491 (United States); Zikanov, Oleg, E-mail: zikanov@umich.edu [Department of Mechanical Engineering, University of Michigan-Dearborn, MI 48128-1491 (United States)

    2013-05-15

    Highlights: ► High fidelity numerical simulations of a liquid metal flow in a pipe entering strong magnetic field are conducted. ► The results are relevant for design of elements of lithium-based liquid metal blankets. ► The main results include analysis of the complex structure of the flow and determining accuracy criteria for numerical simulations of flows in strong magnetic fields. -- Abstract: High-resolution numerical simulations are conducted to analyze transformation of a liquid metal flow in a pipe at the entrance into a transverse magnetic field. The case of laminar flow, perfectly insulating pipe walls, and Hartmann number up to 200 is considered. The simulations reveal detailed structure of velocity and electric current fields and distribution of forces with particular attention given to the flow with an M-shaped velocity profile. They also establish criteria for accurate computations of laminar magnetohydrodynamic flows in strong non-uniform magnetic fields.

  16. Mitochondrial morphology and cardiovascular disease

    OpenAIRE

    Ong, Sang-Bing; Hausenloy, Derek J

    2010-01-01

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

  17. 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.

  18. Reform of the College Entrance Examination: Ideology, Principles, and Policy Recommendations

    Science.gov (United States)

    Liu, Haifeng

    2013-01-01

    Reform of the College Entrance Examination is trending toward simultaneous unification and diversification. The objective of reforming the entrance exam is to establish a college enrollment examination system that is primarily based on a unified test, which would assess students' abilities, appraise them on multiple levels, and classify them.…

  19. On the Rationality of the College Entrance Examination: Analysis of Its Social Foundations, Functions, and Influences

    Science.gov (United States)

    Ruoling, Zheng

    2010-01-01

    Giving everyone an equal opportunity to participate in higher education and to compete for society's resources is the foundation for the existence of the college entrance examination system. Despite the persistent imbalance between the supply of and the demand for higher education, the foundations of the entrance exam system have not been shaken;…

  20. 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).

  1. Mitochondrial Dynamics in Diabetes

    OpenAIRE

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

    2011-01-01

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

  2. Entrance channel effects in fusion reactions near the barrier: Reaction dynamics or nuclear structure?

    International Nuclear Information System (INIS)

    The origin of previously reported entrance channel effects by symmetric and asymmetric fusion reactions leading to rare earth nuclei near the Coulomb barrier is critically reviewed. Possible influences of reaction dynamics or structure effects due to the proximity of superdeformation are discussed using new charged-particle spectra and angular distributions associated with specific axn exit channels. For axn channels, nonstatistical effects in the fusion of the asymmetric entrance channel are responsible for the large difference in the spin distributions in the evaporation residues formed by symmetric and asymmetric entrance channels. Whereas GDR spectra show significant entrance channel effects, the authors find no influence on the subbarrier α spectra from possible elongated shapes associated with early reaction dynamics. New data and analyses of γ-ray multiplicity distributions from the xn exit channels show that previously reported entrance channel effects are due to mapping from l to residue spin and then to γ-ray multiplicity

  3. Determination of Entrance Skin Doses and Organ Doses for Medical X Ray Examinations

    International Nuclear Information System (INIS)

    A national survey of patient doses for diagnostic X ray radiographs is planned in Taiwan. Entrance skin doses and organ doses for all installed X ray machines will be investigated. A pilot study has been carried out for the national survey to develop a protocol for the dose assessment. Entrance skin doses and organ doses were measured by thermoluminescence dosemeters and calculated by Monte Carlo simulations for several X ray examinations. The conversion factor from free air entrance absorbed dose to entrance skin dose was derived. A formula for the computation of entrance skin doses from inputs of kVp, mA.s, source to skin distance, aluminium filtration, and generator rectifying was constructed. Organ doses were measured using a RANDO phantom and calculated using a mathematical phantom. All data will be passed to the Atomic Energy Council for developing a programme of national survey and regulatory controls for diagnostic X ray examinations. (author)

  4. Data on mitochondrial function in skeletal muscle of old mice in response to different exercise intensity

    OpenAIRE

    Kang, Chounghun; Lim, Wonchung

    2016-01-01

    Endurance exercise is securely linked to muscle metabolic adaptations including enhanced mitochondrial function (“Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle” [1], “Effects of exercise on mitochondrial content and function in aging human skeletal muscle” [2]). However, the link between exercise intensity and mitochondrial function in aging muscle has not been fully investigated. In order to understand how strenuous exercise affects mit...

  5. 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.

  6. 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.

  7. 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.

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

    International Nuclear Information System (INIS)

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

  9. Factors Affecting University Entrants' Performance in High-Stakes Tests: A Multiple Regression Analysis

    Science.gov (United States)

    Uy, Chin; Manalo, Ronaldo A.; Cabauatan, Ronaldo R.

    2015-01-01

    In the Philippines, students seeking admission to a university are usually required to meet certain entrance requirements, including passing the entrance examinations with questions on IQ and English, mathematics, and science. This paper aims to determine the factors that affect the performance of entrants into business programmes in high-stakes…

  10. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment.

    Science.gov (United States)

    Niyazov, Dmitriy M; Kahler, Stephan G; Frye, Richard E

    2016-07-01

    Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to abnormal oxidative phosphorylation (oxphos). Primary mitochondrial disease (PMD) is diagnosed clinically and ideally, but not always, confirmed by a known or indisputably pathogenic mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutation. The PMD genes either encode oxphos proteins directly or they affect oxphos function by impacting production of the complex machinery needed to run the oxphos process. However, many disorders have the 'mitochondrial' phenotype without an identifiable mtDNA or nDNA mutation or they have a variant of unknown clinical significance. Secondary mitochondrial dysfunction (SMD) can be caused by genes encoding neither function nor production of the oxphos proteins and accompanies many hereditary non-mitochondrial diseases. SMD may also be due to nongenetic causes such as environmental factors. In our practice, we see many patients with clinical signs of mitochondrial dysfunction based on phenotype, biomarkers, imaging, muscle biopsy, or negative/equivocal mtDNA or nDNA test results. In these cases, it is often tempting to assign a patient's phenotype to 'mitochondrial disease', but SMD is often challenging to distinguish from PMD. Fortunately, rapid advances in molecular testing, made possible by next generation sequencing, have been effective at least in some cases in establishing accurate diagnoses to distinguish between PMD and SMD. This is important, since their treatments and prognoses can be quite different. However, even in the absence of the ability to distinguish between PMD and SMD, treating SMD with standard treatments for PMD can be effective. We review the latest findings regarding mitochondrial disease/dysfunction and give representative examples in which differentiation between PMD and SMD has been crucial for diagnosis and treatment. PMID:27587988

  11. Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division.

    Science.gov (United States)

    Jokinen, Riikka; Marttinen, Paula; Stewart, James B; Neil Dear, T; Battersby, Brendan J

    2016-02-15

    Mitochondria are dynamic organelles that divide and fuse by remodeling an outer and inner membrane in response to developmental, physiological and stress stimuli. These events are coordinated by conserved dynamin-related GTPases. The dynamics of mitochondrial morphology require coordination with mitochondrial DNA (mtDNA) to ensure faithful genome transmission, however, this process remains poorly understood. Mitochondrial division is linked to the segregation of mtDNA but how it affects cases of mtDNA heteroplasmy, where two or more mtDNA variants/mutations co-exist in a cell, is unknown. Segregation of heteroplasmic human pathogenic mtDNA mutations is a critical factor in the onset and severity of human mitochondrial diseases. Here, we investigated the coupling of mitochondrial morphology to the transmission and segregation of mtDNA in mammals by taking advantage of two genetically modified mouse models: one with a dominant-negative mutation in the dynamin-related protein 1 (Drp1 or Dnm1l) that impairs mitochondrial fission and the other, heteroplasmic mice segregating two neutral mtDNA haplotypes (BALB and NZB). We show a tissue-specific response to mtDNA segregation from a defect in mitochondrial fission. Only mtDNA segregation in the hematopoietic compartment is modulated from impaired Dnm1l function. In contrast, no effect was observed in other tissues arising from the three germ layers during development and in mtDNA transmission through the female germline. Our data suggest a robust organization of a heteroplasmic mtDNA segregating unit across mammalian cell types that can overcome impaired mitochondrial division to ensure faithful transmission of the mitochondrial genome. PMID:26681804

  12. Novel spherical hohlraum with cylindrical laser entrance holes and shields

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Ke [Institute of Applied Physics and Computational Mathematics, Beijing 100088 (China); Center for Applied Physics and Technology, Peking University, Beijing 100871 (China); Zheng, Wudi [Institute of Applied Physics and Computational Mathematics, Beijing 100088 (China)

    2014-09-15

    Our recent works [K. Lan et al., Phys. Plasmas 21, 010704 (2014); K. Lan et al., Phys. Plasmas 21, 052704 (2014)] have shown that the octahedral spherical hohlraums are superior to the cylindrical hohlraums in both higher symmetry during the capsule implosion and lower backscatter without supplementary technology. However, both the coupling efficiency from the drive laser energy to the capsule and the capsule symmetry decrease remarkably when larger laser entrance holes (LEHs) are used. In addition, the laser beams injected at angles > 45° transport close to the hohlraum wall, thus the wall blowoff causes the LEH to close faster and results in strong laser plasma interactions inside the spherical hohlraums. In this letter, we propose a novel octahedral hohlraum with LEH shields and cylindrical LEHs to alleviate these problems. From our theoretical study, with the LEH shields, the laser coupling efficiency is significantly increased and the capsule symmetry is remarkably improved in the spherical hohlraums. The cylindrical LEHs take advantage of the cylindrical hohlraum near the LEH and mitigate the influence of the blowoff on laser transport inside a spherical hohlraum. The cylindrical LEHs can also be applied to the rugby and elliptical hohlraums.

  13. 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.

  14. Medical school entrance and career plans of Malaysian medical students.

    Science.gov (United States)

    Razali, S M

    1996-11-01

    This study investigates the reasons for entry to medicine and the career perspectives of phase III medical students of the Universiti Sains Malaysia (USM). The majority of the students were Malays from low socio-economic backgrounds who entered medical school after completing a 2-year matriculation course. An interest in medicine and helping people were the two main stated reasons for entry to medical school. A group of students wishing to work in private practice was identified. In comparison to the rest of the study body, students in the group were: not well prepared to enter medical school; dissatisfied with the course; and subject to family influences. A desire for monetary gain motivated their choice of medicine as a career. Overall, 13% of the students wished to change career because they were dissatisfied with their experience of medicine as undergraduates. The study did not find a significant difference in career intentions between female and male medical students. However, women were less likely to seek entrance into private practice or pursue formal postgraduate education. The choice of surgery as a career was confined to men. About 90% of the students had already decided on their future specialty. Four well-established specialties were their most popular choices. The gender of the students had no significant influences of the decision to continue into postgraduate education. The proportion of female students who wished to marry doctors was significantly higher than for male students. PMID:9217903

  15. Entrance surface dose measurements in mammography using thermoluminescence technique

    International Nuclear Information System (INIS)

    Full text: Of the various techniques that can be used for personnel dosimetry, thermoluminescence dosimetry (TLD) has emerged as a superior technique due to its manifold advantages over other methods of dose estimation. Various phosphors have been therefore investigated regarding their suitability for dosimetry. In this paper, a dosimetry system based on thermally stimulated luminescence (TSL) from zirconium oxide phosphors embedded in polytetrafluorethylene (ZrO2+PTFE) was developed for entrance surface doses (ES) measurements in mammography. Small ZrO2 pellets of 5 mm in diameter and 0.8 mm in thickness were used. The reproducibility of measurements and linearity of ZrO2 were also studied. The results were compared with those obtained from LiF:Mg,Cu,P usually used for the determination of absorbed dose in mammography. Measurements both per unit air kerma and In vivo were performed using a mammography unit model DMR (General Electric). The results showed that ZrO2 TLDs can be used for the same X-ray dosimetry applications as LiF:Mg,Cu,P, with each type having the disadvantage of a response dependent on energy, particularly at low energies. These results indicate a considerable potential for use in routine control and In vivo ES measurements in mammography. (Author)

  16. 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.

  17. A Commentary on China's New Curriculum and the Programs to Design Subjects for the College Entrance Examination

    Science.gov (United States)

    Wang, Houxiong

    2013-01-01

    Designing and reforming the subjects on the College Entrance Examination, based on the new curriculum, are the focal point and also the most difficult aspect of entrance exam reform. The entrance exam subject programs instituted in more than ten "subject reform" regions in China, including the provinces of Shandong, Ningxia, Guangdong, Hainan, and…

  18. 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

  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. 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.

  1. Prerotacijski tok na vstopu v radialni rotor: Prerotation flow at the entrance to a radial impeller:

    OpenAIRE

    Biluš, Ignacijo; Predin, Andrej

    2000-01-01

    In the following paper an analysis is given of the prerotation flow in the entrance pipe of a radial turbomachine which occurs at partial load, i.e. during operartion under out-of-design conditions. Theoretically, the prerotation flow appears in the entrance pipe before the entrance in the radial impeller as a result of the real radial impeller operation. The final number of blades creates the impeller channels where the relative whirl flow exists, in addition to the around the the individual...

  2. 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.

  3. 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 ...

  4. Recombinant human growth hormone and insulin-like growth factor-1 do not affect mitochondrial derived highly reactive oxygen species production in peripheral blood mononuclear cells under conditions of substrate saturation in-vitro

    OpenAIRE

    Keane, James; Tajouri, Lotti; Gray, Bon

    2016-01-01

    Background The purpose of this study was to investigate the mitochondrial effects exerted by physiological and supra-physiological concentrations of recombinant human growth hormone (rhGH) and recombinant insulin-like growth factor-1 (rIGF-1) under conditions of substrate saturation in peripheral blood mononuclear cells (PBMCs). Methods PBMCs from healthy male subjects were treated with either rhGH, at concentrations of 0.5, 5 and 50 μg/L, or rIGF-1 at concentrations of 100, 300 and 500 μg/L ...

  5. Antireflection-structured surfaces for mid-infrared entrance windows

    Science.gov (United States)

    Dubreuil, Didier; Harvey, Erol C.; Pigot, Claude; Rizvi, Nadeem H.

    1998-08-01

    SubWavelength Structured Surfaces (SWS), by synthesizing effective index of refraction, offer an attractive way to mimic antireflective coating effects. It is of particular interest for some IR materials of high index of refraction such as CdTe or KRS-5. These material are often used for entrance window in cryogenic IR instrument in the 20 microns band. For these materials, multilayer antireflective coatings provide limited performances in transmission, while expected performances of SWS can be very high even for a wavelength range covering both the N and Q atmospheric windows, from 7 microns to 28 microns. The SWS simulates a gradient index layer. Its main parameters are its pitch and its depth. The pitches required depend on the IR material index. For CdTe and KRS5, they are around 3 microns to work in N-band and Q-band and around 6 microns to work only on Q- band, and the depth required is around 10 microns to work till 28 microns. We have tried a new approach to realize these structures by using excimer laser ablation technique. We describe the used technique and our results for different materials such as CdTe, KRS5, CsBr and CsI. Antireflection structured surfaces on CdTe could offer an increase in transmission better than 25 percent at 24 microns. We measured a transmission efficiency of near 96 percent between 23 micrometers and 35 micrometers on KRS-5, and more than 95 percent between 18.5 micrometers and 35.5 micrometers on CsI.

  6. 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....

  7. Mitochondrial metabolism and diabetes

    OpenAIRE

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

    2010-01-01

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

  8. Mitochondrial dynamics and apoptosis

    OpenAIRE

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

    2008-01-01

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

  9. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

    2008-08-15

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  10. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    International Nuclear Information System (INIS)

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  11. A whole mitochondrial genome screening in a MELAS patient: A novel mitochondrial tRNAVal mutation

    International Nuclear Information System (INIS)

    Highlights: → We report a young Tunisian patient with clinical features of MELAS syndrome. → Reported mitochondrial mutations were absent after a mutational screening of the whole mtDNA. → We described a novel m.1640A>G mutation in the tRNAVal gene which was absent in 150 controls. → Mitochondrial deletions and POLG1 gene mutations were absent. → 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 tRNAVal. 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.

  12. 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.

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

    CERN Document Server

    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...

  14. Distributing of power of signals on the entrance of receiver of height aerial platform

    OpenAIRE

    V. A. Bychkovsky; Yu. Yu. Reutskaya

    2010-01-01

    The method of determination of probability density of power of signal is considered on the entrance of receiver for organization of effective informative exchange between telephone subscriber stations through balloon retransmitting station, located on airship.

  15. 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.

  16. 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.

  17. Distributing of power of signals on the entrance of receiver of height aerial platform.

    Directory of Open Access Journals (Sweden)

    V. A. Bychkovsky

    2010-05-01

    Full Text Available The method of determination of probability density of power of signal is considered on the entrance of receiver for organization of effective informative exchange between telephone subscriber stations through balloon retransmitting station, located on airship.

  18. Distributing of power of signals on the entrance of receiver of height aerial platform

    Directory of Open Access Journals (Sweden)

    V. A. Bychkovsky

    2010-05-01

    Full Text Available The method of determination of probability density of power of signal is considered on the entrance of receiver for organization of effective informative exchange between telephone subscriber stations through balloon retransmitting station, located on airship.

  19. Does China¡¯s National College Entrance Exam Effectively Evaluate Applicants?

    OpenAIRE

    Wei Hu; Feng Li; Li Gan

    2014-01-01

    Based on micro-level student data from one Chinese academic institution, we study the validity of the national college entrance exam from the perspective of student performance in college and employment prospects after graduation. We find that the current college entrance exam could reflect the students¡¯ learning ability to a certain degree, providing a relatively valid evaluation. Demonstration of well-rounded development ability should be an important factor in the evaluation system. Based...

  20. 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.

  1. 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

  2. Effects of mitochondrial dysfunction on the immunological properties of microglia

    Directory of Open Access Journals (Sweden)

    Ferger Annette I

    2010-08-01

    Full Text Available Abstract Background Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells. Methods We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS- induced microglial activation and the alternative, interleukin-4- (IL-4- induced microglial activation in these mitochondrial toxin-treated microglial cells. Results We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β, they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1 and the counteraction of the LPS induced cytokine release. Conclusions Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. 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.

  5. Mitochondrial fusion and inheritance of the mitochondrial genome.

    Science.gov (United States)

    Takano, Hiroyoshi; Onoue, Kenta; Kawano, Shigeyuki

    2010-03-01

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

  6. Cancer: Mitochondrial Origins.

    Science.gov (United States)

    Stefano, George B; Kream, Richard M

    2015-12-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial matrix. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionary fashioned chemiosmotic production of ATP as a high-efficiency biological process. The mechanistic bases of carcinogenesis have demonstrated profound alteration of normative mitochondrial function, notably dysregulated respiratory processes. Accordingly, the classic Warburg effect functionally links aerobic glycolysis, aberrant production and release of lactate, and metabolic down-regulation of mitochondrial oxidative processes with the carcinogenetic phenotype. We surmise, however, that aerobic fermentation by cancer cells may also represent a developmental re-emergence of an evolutionarily conserved early phenotype, which was "sidelined" with the emergence of mitochondrial oxidative phosphorylation as a primary mechanism for ATP production in normal cells. Regardless of state-dependent physiological status in mixed populations of cancer cells, it has been established that mitochondria are functionally linked to the initiation of cancer and its progression. Biochemical, molecular, and physiological differences in cancer cell mitochondria, notably mtDNA heteroplasmy and allele-specific expression of selected nuclear genes, may represent major focal points for novel targeting and elimination of cancer cells in metastatic disease afflicting human populations. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial

  7. 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.

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

    OpenAIRE

    Pasquale Picone; Domenico Nuzzo; Luca Caruana; Valeria Scafidi; Marta Di Carlo

    2014-01-01

    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 dys...

  9. The effect of mitochondrial dysfunction on cytosolic nucleotide metabolism

    DEFF Research Database (Denmark)

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

    2010-01-01

    Several enzymes of the metabolic pathways responsible for metabolism of cytosolic ribonucleotides and deoxyribonucleotides are located in mitochondria. Studies described in this paper suggest dysfunction of the mitochondria to affect these metabolic pathways and limit the available levels 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...

  10. Analysis of mitochondrial transcription factor A SNPs in alcoholic cirrhosis

    OpenAIRE

    Tang, Chun; LIU, HONGMING; TANG, YONGLIANG; Guo, Yong; LIANG, XIANCHUN; GUO, LIPING; Pi, Ruxian; Yang, Juntao

    2013-01-01

    Genetic susceptibility to alcoholic cirrhosis (AC) exists. We previously demonstrated hepatic mitochondrial DNA (mtDNA) damage in patients with AC compared with chronic alcoholics without cirrhosis. Mitochondrial transcription factor A (mtTFA) is central to mtDNA expression regulation and repair; however, it is unclear whether there are specific mtTFA single nucleotide polymorphisms (SNPs) in patients with AC and whether they affect mtDNA repair. In the present study, we screened mtTFA SNPs i...

  11. Mitochondrial Dysfunction and Psychiatric Disorders

    OpenAIRE

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

    2009-01-01

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

  12. 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.

  13. 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.

  14. 体育中考现状与改革研究%Research on Present Situation and Reform of Senior High School Entrance Examination of Sports

    Institute of Scientific and Technical Information of China (English)

    杨雯婧

    2015-01-01

    随着体育作为学生中考的一门考试科目,并且分值逐年增加,体育中考牵动着各方的神经,受到各级教育行政部门、千万家庭、学校和学生的重视。体育站在中考的光环下得到了快速发展,然而要摆脱体育的应试化,达到体育的真正目的还需要不断的改变体育考试的方式方法。%With the development of sports as a student of senior high school entrance examination of the exam scores,and increased year by year,senior high school entrance examination of sports affects all nerves,by the education administrative departments at all levels,tens of thousands of families,schools and students' attention.Sports station in the senior high school entrance examination's aura has been rapid development,but to get rid of physical examination, methods to achieve the real goal of sports also need to constantly change the physical examination of the way.

  15. Analysis on Freshmen Dropping Out of School to Take Entrance Examination%高校新生“退学复读”现象分析

    Institute of Scientific and Technical Information of China (English)

    张信练

    2012-01-01

    One performance of freshmen can' t adapt to the new environment is a point of freshmen want to back to take the entrance examination because of failing in the entrance examination. This would take a little bad affection on students themselves and the management of university. Analysis on the reasons of freshmen dropping out of school to take entrance examination, taking specific measures to solve the phenomenon seasonally to make the freshmen adapt to the university quickly and establish a new goal is very necessary.%高校新生不适应的一个表现是一小部分学生因高考失利而要退学复读,这给学生本人,也给高校管理带来一定的影响。分析新生产生“退学复读”心理的原因,采取有针对性措施,合理解决新生“退学复读”现象,使有“退学复读”心理的新生尽快适应大学生活,建立起新的奋斗目标就显得尤为必要。

  16. 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.

  17. Evaluation of entrance surface air kerma from exposure index in computed radiography

    Science.gov (United States)

    Costa, A. M.; Pelegrino, M. S.

    2014-11-01

    The aim of this study was to establish an indirect method to calculate the values of entrance surface air kerma in patients undergoing diagnostic examinations in X-ray systems with computed radiography based on the exposure index. The entrance surface air kerma values were compared with values obtained also indirectly based on measurements of X-ray tube output. The mean±standard deviation (1σ) and third quartile for entrance surface air kerma calculated from the exposure index were 2.1±1.0 mGy and 3.0 mGy, respectively. For entrance surface air kerma based on measurements of the X-ray tube output, the mean±standard deviation (1σ) and third quartile were respectively 3.1±1.9 mGy and 5.5 mGy. The observed values of entrance surface air kerma are smaller than the reference level adopted in Brazil (10 mGy). The results obtained with both methods were similar when taking into account the estimated uncertainties in the determination of air kerma values, although the reproducibility of the determinations based on the exposure index is better.

  18. 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.

  19. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

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

  20. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number.

    Science.gov (United States)

    Campbell, Christopher T; Kolesar, Jill E; Kaufman, Brett A

    2012-01-01

    Mitochondrial transcription factor A (mtTFA, mtTF1, TFAM) is an essential protein that binds mitochondrial DNA (mtDNA) with and without sequence specificity to regulate both mitochondrial transcription initiation and mtDNA copy number. The abundance of mtDNA generally reflects TFAM protein levels; however, the precise mechanism(s) by which this occurs remains a matter of debate. Data suggest that the usage of mitochondrial promoters is regulated by TFAM dosage, allowing TFAM to affect both gene expression and RNA priming for first strand mtDNA replication. Additionally, TFAM has a non-specific DNA binding activity that is both cooperative and high affinity. TFAM can compact plasmid DNA in vitro, suggesting a structural role for the non-specific DNA binding activity in genome packaging. This review summarizes TFAM-mtDNA interactions and describes an emerging view of TFAM as a multipurpose coordinator of mtDNA transactions, with direct consequences for the maintenance of gene expression and genome copy number. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. PMID:22465614

  1. 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

  2. Multiple Targets for Drug-Induced Mitochondrial Toxicity.

    Science.gov (United States)

    Wallace, Kendall B

    2015-01-01

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

  3. 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.

  4. Entrance channel dependence of back angle yields: orbiting in 24Mg+16O reaction

    International Nuclear Information System (INIS)

    The back-angle yields of the oxygen and carbon particles from the 24Mg+16O reaction have been measured at E/sub Lab/(24Mg) = 79.5 MeV by using reverse kinematics. Comparison with data for the 28Si+12C reaction forming the same compound nucleus at the same excitation energy and with very similar spin distribution, demonstrates a strong entrance channel effect which is favoring the break-up into the entrance channel with large excitation energy. This result qualitatively supports the picture of the formation of a long-lived orbiting complex whose structure and decay are dependent on the entrance channel. The compound nucleus contribution has been inferred to be less than 15% of the measured oxygen cross-section. 9 references

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

    International Nuclear Information System (INIS)

    The decay of hot and rotating 172Yb*, formed in two entrance channels 124Sn + 48Ca and 132Sn + 40Ca, is studied using the dynamical cluster-decay model. The effect of entrance channel, deformations (up to β2), 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 132Sn + 40Ca channel at lower energies as compare to 124Sn + 48Ca. 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

  6. [The entrance to the guild chamber of the Amsterdam Guild of Surgeons].

    Science.gov (United States)

    Ottenhof, Anne; IJpma, Frank A; van Gulik, Thomas M

    2016-01-01

    In the 17th and 18th centuries the entrance to the guild chamber of the Amsterdam Guild of Surgeons was located in the right corner-tower of the Waag on the Nieuwmarkt in Amsterdam. The surgeons entered their guild chamber through this door for guild meetings or to take surgical exams. The entrance also gave access to the anatomy theatre, the 'Theatrum Anatomicum', where anatomical dissections - anatomy lessons - took place. There was a bust of Hippocrates in the facade above the door, and the inscription 'Theatrum Anatomicum'. The series of 'anatomy lessons' reminds us of the famous paintings that were commissioned by the Surgeons' Guild. At the beginning of the 17th century, a skeleton was painted on the door in the gateway, and this marked the entrance to the Surgeons' Guild for almost 200 years. We examined, from a historical perspective, how the gateway to the guild chamber of the Amsterdam Guild of Surgeons was transformed over time. PMID:27122076

  7. 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.

  8. 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.

  9. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    OpenAIRE

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the...

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

    OpenAIRE

    cunha-oliveira, teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J.; Oliveira, Catarina R.; Santos, Maria S.

    2013-01-01

    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 ...

  11. 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

  12. 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.

  13. Distinction between entrance and exit wounds by energy dispersive X-ray fluorescence spectrometry.

    Science.gov (United States)

    Tanaka, Naoko; Kinoshita, Hiroshi; Takakura, Ayaka; Jamal, Mostofa; Ito, Asuka; Kumihashi, Mitsuru; Tsutsui, Kunihiko; Kimura, Shoji; Ameno, Kiyoshi

    2016-09-01

    We investigated gunshot wounds in two autopsy cases using energy dispersive X-ray spectrometry (EDX). Lead and copper were detected in the entrance wound of one case and lead, antimony, and copper were detected in that of the other case. In the exit wounds of both cases, lead, antimony, and copper were below detection limits. These findings indicate that the detection of metallic elements, such as lead, antimony, and copper, which are found in bullets, may be useful for differentiating entrance from exit wounds using EDX. PMID:27591531

  14. Different intensity extension methods and their impact on entrance dose in breast radiotherapy: A study

    Directory of Open Access Journals (Sweden)

    Sankar A

    2009-01-01

    Full Text Available In breast radiotherapy, skin flashing of treatment fields is important to account for intrafraction movements and setup errors. This study compares the two different intensity extension methods, namely, Virtual Bolus method and skin flash tool method, to provide skin flashing in intensity modulated treatment fields. The impact of these two different intensity extension methods on skin dose was studied by measuring the entrance dose of the treatment fields using semiconductor diode detectors. We found no significant difference in entrance dose due to different methods used for intensity extension. However, in the skin flash tool method, selection of appropriate parameters is important to get optimum fluence extension.

  15. Effects of the Czech Propolis on Sperm Mitochondrial Function

    Science.gov (United States)

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

    2014-01-01

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

  16. Dual Effect of Phosphate Transport on Mitochondrial Ca2+ Dynamics.

    Science.gov (United States)

    Wei, An-Chi; Liu, Ting; O'Rourke, Brian

    2015-06-26

    The large inner membrane electrochemical driving force and restricted volume of the matrix confer unique constraints on mitochondrial ion transport. Cation uptake along with anion and water movement induces swelling if not compensated by other processes. For mitochondrial Ca(2+) uptake, these include activation of countertransporters (Na(+)/Ca(2+) exchanger and Na(+)/H(+) exchanger) coupled to the proton gradient, ultimately maintained by the proton pumps of the respiratory chain, and Ca(2+) binding to matrix buffers. Inorganic phosphate (Pi) is known to affect both the Ca(2+) uptake rate and the buffering reaction, but the role of anion transport in determining mitochondrial Ca(2+) dynamics is poorly understood. Here we simultaneously monitor extra- and intra-mitochondrial Ca(2+) and mitochondrial membrane potential (ΔΨm) to examine the effects of anion transport on mitochondrial Ca(2+) flux and buffering in Pi-depleted guinea pig cardiac mitochondria. Mitochondrial Ca(2+) uptake proceeded slowly in the absence of Pi but matrix free Ca(2+) ([Ca(2+)]mito) still rose to ~50 μm. Pi (0.001-1 mm) accelerated Ca(2+) uptake but decreased [Ca(2+)]mito by almost 50% while restoring ΔΨm. Pi-dependent effects on Ca(2+) were blocked by inhibiting the phosphate carrier. Mitochondrial Ca(2+) uptake rate was also increased by vanadate (Vi), acetate, ATP, or a non-hydrolyzable ATP analog (AMP-PNP), with differential effects on matrix Ca(2+) buffering and ΔΨm recovery. Interestingly, ATP or AMP-PNP prevented the effects of Pi on Ca(2+) uptake. The results show that anion transport imposes an upper limit on mitochondrial Ca(2+) uptake and modifies the [Ca(2+)]mito response in a complex manner. PMID:25963147

  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. 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.

  19. Calpastatin overexpression reduces oxidative stress-induced mitochondrial impairment and cell death in human neuroblastoma SH-SY5Y cells by decreasing calpain and calcineurin activation, induction of mitochondrial fission and destruction of mitochondrial fusion.

    Science.gov (United States)

    Tangmansakulchai, Kulvadee; Abubakar, Zuroida; Kitiyanant, Narisorn; Suwanjang, Wilasinee; Leepiyasakulchai, Chaniya; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-09-01

    Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that calpain activation and mitochondrial damage are involved in the cell death process; however, recent evidence has not clearly indicated a neuroprotective mechanism of calpastatin against calpain-dependent mitochondrial impairment in the process of neuronal cell death. Therefore, the purpose of this study was to investigate the potential ability of calpastatin to inhibit calpain activation and mitochondrial impairment in oxidative stress-induced neuron degeneration. Calpastatin was stably overexpressed in human neuroblastoma SH-SY5Y cells. In non-calpastatin overexpressing SH-SY5Y cells, hydrogen peroxide significantly decreased cell viability, superoxide dismutase activity, mitochondrial membrane potential, ATP production and mitochondrial fusion protein (Opa1) levels in the mitochondrial fraction but increased reactive oxygen species formation, calpain and calcineurin activation, mitochondrial fission protein (Fis1 and Drp1) levels in the mitochondrial fraction and apoptotic cells. Nevertheless, these toxic effects were abolished in hydrogen peroxide-treated calpastatin-overexpressing SH-SY5Y cells. The results of the present study demonstrate the potential ability of calpastatin to diminish calpain and calcineurin activation and mitochondrial impairment in neurons that are affected by oxidative damage. PMID:27453331

  20. 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…

  1. What’s Behind the Dropping Number Of College Entrance Exam Takers?

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This year, China’s national college entrance examination saw a decrease in can- didates, with some provinces registering a substantial 10-percent drop. For years, the number of candidates had risen steadily. According to statistics from the Ministry of Education, the number of

  2. Three Key Issues in the Reform Programs for the Chinese College Entrance Examination

    Science.gov (United States)

    Liu, Qinghua

    2013-01-01

    The new entrance exam reform programs that have been presented in a number of provinces and regions adhere to the direction of new curriculum reform. Within these programs, comprehensive evaluation serves as the weather vane for quality education. The high school academic proficiency test serves as a firmly fixed benchmark for learning ability,…

  3. 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…

  4. 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…

  5. Research on Micro- and Macroskills for Reading Tested in College Entrance Examination of Tianjin

    Institute of Scientific and Technical Information of China (English)

    张慧玲

    2016-01-01

    Through doing a systematic contrastive research on the part of reading comprehension of the recent five years’ English papers of College Entrance examination, the author attempted to find some teaching and learning guidance on the usage of micro- and macroskills for reading assessment.

  6. Does Large Scale Publicity Benefit College Entrance Exam’s Top Achievers?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Late June in China is the time of year when the national college entrance examination results are announced and the whole country is whipped into a frenzy. Because of the competition and pressure on students for top university openings, those who score t

  7. 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…

  8. Chinese College Entrance Examination: Review of Discussions and the Value Orientation of Reforms

    Science.gov (United States)

    Ruoling, Zheng

    2008-01-01

    The retention or abolition of national college entrance examination (CEE) has triggered a fierce controversy in academe. Although controversial causes and focus vary from time to time, the result remains the same--adopting uniform national examinations and making it innovative all the time. Since CEE has political, social and educational…

  9. 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…

  10. 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.

  11. College Board to Revise Entrance Exam; Says New Version Will Be More Useful.

    Science.gov (United States)

    Evangelauf, Jean

    1990-01-01

    In revisions due to be implemented in 1994, the Scholastic Aptitude Test (SAT) will emphasize critical reading skills and mathematical computation more, and test takers will be allowed to use calculators. The College Entrance Examination Board's Achievement Tests will also be overhauled, with new subject tests added and current test format and…

  12. 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.

  13. 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…

  14. Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

    Science.gov (United States)

    Satory, P R

    2012-03-01

    This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient. PMID:22298238

  15. An Introduction to the System and Culture of the College Entrance Examination of China. Research Notes. RN-28

    Science.gov (United States)

    Wang, Xiang Bo

    2006-01-01

    This report provides an introduction to the system and culture of the college entrance examination (CEE) of China. College entrance examinations in China (and in several other Asian countries such as Korea and Japan) are so important that they are commonly dubbed "once in a lifetime" or a "one-test-to-determine-a-life" for most…

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. A hemagglutinin isolated from Northeast China black beans induced mitochondrial dysfunction and apoptosis in colorectal cancer cells.

    Science.gov (United States)

    Dan, Xiuli; Ng, Tzi Bun; Wong, Jack Ho; Chan, Yau Sang; Cheung, Randy Chi Fai; Chan, Wai Yee

    2016-09-01

    Incidence of colorectal cancer is closely related with the lifestyle, especially the dietary habits of patients. Epidemiological researches have demonstrated a negative correlation between legume consumption and colorectal cancer incidence. Lectins/hemagglutinins are a type of carbohydrate binding proteins which are abundantly stored in legumes. Their eminent pH-stability allows them to survive digestion and remain active in the intestine where they may have direct contact with colorectal tumors. It is therefore interesting to explore the direct interaction between lectins/hemagglutinins and colorectal cancer. In the present research, we reported a detailed research on the interaction between a hemagglutinin isolated from an edible legume with two colorectal cancer cell lines. This hemagglutinin (NCBBH) was found to first bind to tumor cell membrane as early as 30min post treatment and was gradually transported inside the cytoplasm within 3h, with some of it localized in the Golgi apparatus and some in the lysosomes. After its entrance, the hemagglutinin induced aggregation of the Golgi apparatus, which in turn adversely affected the transportation of protein from endoplasmic reticulum (ER) to the Golgi apparatus, resulting in protein accumulation in ER and ER stress. The hemagglutinin-treated cells also manifested severe mitochondrial malformation and membrane depolarization, accompanied by obvious apoptosis characteristics, like chromatin condensation, phosphatidylserine exposure and caspase activation. Collectively, our results indicate that the hemaggltuinin could successfully enter the cytoplasm of colorectal cancer cells and adversely affect their growth, providing a mechanism in support of the application of edible legumes to the prevention and treatment of colorectal cancer. PMID:27235832

  1. Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins.

    Science.gov (United States)

    Birsa, Nicol; Norkett, Rosalind; Higgs, Nathalie; Lopez-Domenech, Guillermo; Kittler, Josef T

    2013-12-01

    Correct mitochondrial dynamics are essential to neuronal function. These dynamics include mitochondrial trafficking and quality-control systems that maintain a precisely distributed and healthy mitochondrial network, so that local energy demands or Ca2+-buffering requirements within the intricate architecture of the neuron can be met. Mitochondria make use of molecular machinery that couples these organelles to microtubule-based transport via kinesin and dynein motors, facilitating the required long-range movements. These motors in turn are associated with a variety of adaptor proteins allowing additional regulation of the complex dynamics demonstrated by these organelles. Over recent years, a number of new motor and adaptor proteins have been added to a growing list of components implicated in mitochondrial trafficking and distribution. Yet, there are major questions that remain to be addressed about the regulation of mitochondrial transport complexes. One of the core components of this machinery, the mitochondrial Rho GTPases Miro1 (mitochondrial Rho 1) and Miro2 have received special attention due to their Ca2+-sensing and GTPase abilities, marking Miro an exceptional candidate for co-ordinating mitochondrial dynamics and intracellular signalling pathways. In the present paper, we discuss the wealth of literature regarding Miro-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration. PMID:24256248

  2. 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.

  3. Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

    Science.gov (United States)

    Machado, Alencar Kolinski; Pan, Alexander Yongshuai; da Silva, Tatiane Morgana; Duong, Angela; Andreazza, Ana Cristina

    2016-08-01

    Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics. PMID:27310240

  4. 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.

  5. 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...

  6. 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.

  7. Biochemical diagnosis of mitochondrial disorders

    NARCIS (Netherlands)

    Rodenburg, R.J.T.

    2011-01-01

    Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patie

  8. 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...

  9. Mitochondrial dysfunction in metabolic syndrome and asthma.

    Science.gov (United States)

    Mabalirajan, Ulaganathan; Ghosh, Balaram

    2013-01-01

    Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma. PMID:23840225

  10. Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

    Directory of Open Access Journals (Sweden)

    Ulaganathan Mabalirajan

    2013-01-01

    Full Text Available Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma.

  11. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. 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

  14. The mitochondrial genome in embryo technologies.

    Science.gov (United States)

    Hiendleder, S; Wolf, E

    2003-08-01

    The mammalian mitochondrial genome encodes for 37 genes which are involved in a broad range of cellular functions. The mitochondrial DNA (mtDNA) molecule is commonly assumed to be inherited through oocyte cytoplasm in a clonal manner, and apparently species-specific mechanisms have evolved to eliminate the contribution of sperm mitochondria after natural fertilization. However, recent evidence for paternal mtDNA inheritance in embryos and offspring questions the general validity of this model, particularly in the context of assisted reproduction and embryo biotechnology. In addition to normal mt DNA haplotype variation, oocytes and spermatozoa show remarkable differences in mtDNA content and may be affected by inherited or acquired mtDNA aberrations. All these parameters have been correlated with gamete quality and reproductive success rates. Nuclear transfer (NT) technology provides experimental models for studying interactions between nuclear and mitochondrial genomes. Recent studies demonstrated (i) a significant effect of mtDNA haplotype or other maternal cytoplasmic factors on the efficiency of NT; (ii) phenotypic differences between transmitochondrial clones pointing to functionally relevant nuclear-cytoplasmic interactions; and (iii) neutral or non-neutral selection of mtDNA haplotypes in heteroplasmic conditions. Mitochondria form a dynamic reticulum, enabling complementation of mitochondrial components and possibly mixing of different mtDNA populations in heteroplasmic individuals. Future directions of research on mtDNA in the context of reproductive biotechnology range from the elimination of adverse effects of artificial heteroplasmy, e.g. created by ooplasm transfer, to engineering of optimized constellations of nuclear and cytoplasmic genes for the production of superior livestock. PMID:12887568

  15. 对立体化大学生入学教育体系的实证研究%The Empirical Study of Three-dimensional College Entrance Education System

    Institute of Scientific and Technical Information of China (English)

    闵婕; 娄洁; 吴伟青

    2014-01-01

    College freshmen entrance education is an important content of new management in colleges, it not only directly affect the students' state of mind, also affects the students' study and life in the future. Through the survey, we found that the affection of the entrance education can be recognized by students, but the content and way in the entrance education needs to be improved.%大学新生入学教育作为我国高校新生管理的重要内容,其不仅直接影响了学生的思想状况,也影响了学生未来的学习、生活。通过调查,我们发现,入学教育的效果能够得到认可,但是入学教育的内容和方式有待进一步完善。

  16. The m.13051G>A mitochondrial DNA mutation results in variable neurology and activated mitophagy

    OpenAIRE

    Dombi, E.; Diot, A.; Morten, K.; Carver, J; Lodge, T.; Fratter, C.; Ng, Y.S.; Liao, C.; Muir, R; Blakely, E.L.; Hargreaves, I; Al-Dosary, M.; Sarkar, G; Hickman, S. J.; Downes, S M

    2016-01-01

    Maternally inherited mitochondrial DNA (mtDNA) mutations cause symptoms of Leber hereditary optic neuropathy (LHON) in -1 in 30,000 individuals. Most of the affected individuals lack respiratory chain defects1 and there is no proven prophylactic treatment.

  17. Altered Mitochondrial Function, Mitochondrial DNA and Reduced Metabolic Flexibility in Patients With Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Anna Czajka

    2015-06-01

    Full Text Available The purpose of this study was to determine if mitochondrial dysfunction plays a role in diabetic nephropathy (DN, a kidney disease which affects >100 million people worldwide and is a leading cause of renal failure despite therapy. A cross-sectional study comparing DN with diabetes patients without kidney disease (DC and healthy controls (HCs; and renal mesangial cells (HMCs grown in normal and high glucose, was carried out. Patients with diabetes (DC had increased circulating mitochondrial DNA (MtDNA, and HMCs increased their MtDNA within 24 h of hyperglycaemia. The increased MtDNA content in DCs and HMCs was not functional as transcription was unaltered/down-regulated, and MtDNA damage was present. MtDNA was increased in DC compared to HC, conversely, patients with DN had lower MtDNA than DC. Hyperglycaemic HMCs had fragmented mitochondria and TLR9 pathway activation, and in diabetic patients, mitophagy was reduced. Despite MtDNA content and integrity changing within 4 days, hyperglycaemic HMCs had a normal bio-energetic profile until 8 days, after which mitochondrial metabolism was progressively impaired. Peripheral blood mononuclear cells (PBMCs from DN patients had reduced reserve capacity and maximal respiration, loss of metabolic flexibility and reduced Bioenergetic Health Index (BHI compared to DC. Our data show that MtDNA changes precede bioenergetic dysfunction and that patients with DN have impaired mitochondrial metabolism compared to DC, leading us to propose that systemic mitochondrial dysfunction initiated by glucose induced MtDNA damage may be involved in the development of DN. Longitudinal studies are needed to define a potential cause–effect relationship between changes in MtDNA and bioenergetics in DN.

  18. 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.

  19. Entrance channel dependence of fission fragment anisotropies - a direct experimental signature of fission before equilibration

    International Nuclear Information System (INIS)

    In several cases of heavy ion induced fusion-fission reactions, the fission fragment angular distributions exhibit much larger anisotropies than predicted by the standard Halpern-Strutinsky theory. Several explanations have been put forward to interpret these anomalous angular distributions. One of them is that a characteristic signature of fission before full K-equilibration will be an entrance channel dependence of the fragment anisotropies for target-projectile combinations across the Businaro-Gallone ridge in the mass/charge asymmetry degree of freedom. To look for any such entrance channel dependence of fragment anisotropies, we have carried out measurements of fragment angular distributions in fission induced by boron, carbon, oxygen ions on thorium and neptunium targets and by fluorine ions on neptunium target at above barrier energies. (author). 7 refs., 1 fig

  20. LAMINAR DEVELOPING FLOW IN THE ENTRANCE REGION OF ROTATING CURVED PIPES

    Institute of Scientific and Technical Information of China (English)

    MA Jian-feng; SHEN Xin-rong; ZHANG Ming-kan; ZHANG Ben-Zhao

    2006-01-01

    Three-dimensional laminar flow in the entrance region of rotating curved pipes was investigated. The governing equations were written in an orthogonal curvilinear coordinate system and solved with a fully three-dimensional numerical method. The development of secondary flow, axial velocity, local and average friction factors for different cases of rotation were given and discussed in detail. The results show that rotation influences the flow structure and friction factor greatly and that the secondary flow is sink-type in the early stage of development and then turns to vortex structure. The average friction factor and the intensity of secondary flow have drastic decrease near the entrance. At some proper rotation, the average friction factor can be noticeably reduced.

  1. Entrance and exit region friction factor models for annular seal analysis. Ph.D. Thesis

    Science.gov (United States)

    Elrod, David Alan

    1988-01-01

    The Mach number definition and boundary conditions in Nelson's nominally-centered, annular gas seal analysis are revised. A method is described for determining the wall shear stress characteristics of an annular gas seal experimentally. Two friction factor models are developed for annular seal analysis; one model is based on flat-plate flow theory; the other uses empirical entrance and exit region friction factors. The friction factor predictions of the models are compared to experimental results. Each friction model is used in an annular gas seal analysis. The seal characteristics predicted by the two seal analyses are compared to experimental results and to the predictions of Nelson's analysis. The comparisons are for smooth-rotor seals with smooth and honeycomb stators. The comparisons show that the analysis which uses empirical entrance and exit region shear stress models predicts the static and stability characteristics of annular gas seals better than the other analyses. The analyses predict direct stiffness poorly.

  2. Spectroscopy of free radicals and radical containing entrance-channel complexes in superfluid helium nanodroplets

    OpenAIRE

    Küpper, J.; Merritt, J.

    2007-01-01

    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 ( ~ 1016 K s-1)provides novel opportunities for the formation and high-resolution st...

  3. On the role of Attitudes and Motivation in students’ performance in Iranian university entrance exam

    OpenAIRE

    ALIAKBARI, Mohamad; ALHOSSEIN, Isar

    2015-01-01

    Abstract. The Iranian University Entrance Exam, Konkoor, is a nation-wide exam used as the criteria to enter higher education in Iran. This exam includes almost all subjects of high school, including English language. This study investigates the effect of Iranian students’ attitudes toward learning English and motivations for learning English on their performance in "Konkoor ". The sample of the study included of 383 male and female students of four high schools in Dehloran west of Iran.  A c...

  4. Average Nusselt number correlation in the thermal entrance region of steady and pulsating turbulent pipe flows

    Science.gov (United States)

    Gbadebo, S. A.; Said, S. A. M.; Habib, M. A.

    Empirical correlation has been developed for local and average Nusselt numbers in the thermal entrance region of steady and pulsating turbulent air-flows in a pipe. The correlation was based on experimental data obtained from experiment carried out on a pipe heated under uniform heat flux conditions. The rate of flow was periodically varied at frequencies ranging from 1Hz to 13Hz while the average Reynolds number varied from 6400 to 42000.

  5. DVD-based distance-learning program for university entrance exams -- RCT experiments in rural Bangladesh

    OpenAIRE

    Kono, Hisaki; Sawada, Yasuyuki; Shonchoy, Abu S.; 高野, 久紀; 澤田, 康幸

    2016-01-01

    In contrast to the remarkable progress in developing countries in improving primary education, access to higher education in many countries remains limited, especially in rural areas where the quality of education is inadequate. We evaluate a DVD-based distance-learning program in rural Bangladesh, targeted at students aiming to take university entrance tests. We conducted two experiments: one to evaluate the effect of the distance-learning program and the second to determine the demand and p...

  6. Entrance surface dose measurement on the thyroid gland in orthopantomography: The need for optimization

    International Nuclear Information System (INIS)

    Background: The anatomic position and proven radiosensitivity of the thyroid make it an organ of concern in dental x-ray examinations. A National Radiation Protection Department sponsored pilot study carried out in the Dental Radiology Department of Rafsanjan University of Medical Sciences, to assess if the radiation dose in panoramic radiographies could be reduced without significant impairment of the subjective image quality. Materials and methods: Thermoluminescent dosimetry is widely acknowledged to be the recommended method for measuring entrance surface doses. In this study, entrance surface doses was measured using LiF thermoluminescent dosimeters (TLD-100) on the thyroid of 40 patients who had referred to the School of Dentistry, Rafsanjan University of Medical Sciences. Patients were no exposed to any additional radiation and the radiographs were used for diagnostic purposes. Thermoluminescent dosimetry were calibrated with radiation energies similar to those commonly used in orthopantomography. Results: The overall mean entrance surface doses on the thyroid in orthopantomography was 0.071±0.012 mGy (ranged from 0.01 to 0.40 mGy). The mean entrance surface doses for radiographies performed with 66 k Vp (20 patients) and 68 k Vp (20 patients) were 0.072± 0.016 respectively. No statistically significant difference was found between these means. Conclusions: The measured surface doses in our study are inconsistent with the only one already reported about the same experiment. However, due to lack of national diagnostic reference levels for orthopantomography, it is not clear whether in case of the Pm 2002 Cc unit used in this experiment, reducing the radiation dose to a level that still keeps a diagnostically acceptable image quality is necessary

  7. 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.

  8. A Bandwidth Control Method Providing Entrance QoS for Multimedia Communication

    Institute of Scientific and Technical Information of China (English)

    LUO Qiang-qiang; ZHU Zhi-xiang; HUANG Ting-xue

    2005-01-01

    With the development of wideband IP network, many new IP-Based multimedia applications appear ceaselessly. The real-time multimedia application requires that the IP network provides QoS. To the end-to-end real-time multimedia communication, the QoS service includes the trunk QoS and the entrance QoS. The trunk QoS has some feasible technologies, such as RSVP and DiffServ. But, the entrance QoS has few technologies at the moment. So, this paper introduces the entrance bandwidth control to get the end-to-end QoS. The design and scheme of bandwidth controller applying to the usual Internet application and real-time media communication is provided in this paper. It distinguishes between the usual Internet applications, such as HTTP and FTP, and the real-time multimedia applications, such as Internet telephony and videoconferencing. Then they will be dealt with in different ways in order to satisfy the QoS requirements of different types of services. In this paper, we propose a new bandwidth control method for real-time multimedia communication. The principle, the implementing flow, the control policy and the application scheme are discussed.

  9. 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.

  10. 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.

  11. 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. PMID:26712328

  12. 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.

  13. Heat stress enhances the accumulation of polyadenylated mitochondrial transcripts in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Alessio Adamo

    Full Text Available BACKGROUND: Polyadenylation of RNA has a decisive influence on RNA stability. Depending on the organisms or subcellular compartment, it either enhances transcript stability or targets RNAs for degradation. In plant mitochondria, polyadenylation promotes RNA degradation, and polyadenylated mitochondrial transcripts are therefore widely considered to be rare and unstable. We followed up a surprising observation that a large number of mitochondrial transcripts are detectable in microarray experiments that used poly(A-specific RNA probes, and that these transcript levels are significantly enhanced after heat treatment. METHODOLOGY/PRINCIPAL FINDINGS: As the Columbia genome contains a complete set of mitochondrial genes, we had to identify polymorphisms to differentiate between nuclear and mitochondrial copies of a mitochondrial transcript. We found that the affected transcripts were uncapped transcripts of mitochondrial origin, which were polyadenylated at multiple sites within their 3'region. Heat-induced enhancement of these transcripts was quickly restored during a short recovery period. CONCLUSIONS/SIGNIFICANCE: Our results show that polyadenylated transcripts of mitochondrial origin are more stable than previously suggested, and that their steady-state levels can even be significantly enhanced under certain conditions. As many microarrays contain mitochondrial probes, due to the frequent transfer of mitochondrial genes into the genome, these effects need to be considered when interpreting microarray data.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper;

    We are testing the hypothesis that oxidized peptides are released from stressed mitochondria and contribute to retrograde signalling (Møller IM & Sweetlove LJ 2010 Trends Plant Sci 15, 370-374). However, there is a large gap between the number of experimentally verified mitochondrial proteins (~450......) and in silico-predicted mitochondrial proteins (2000-3000). Thus, before starting to look for oxidized peptides, we wanted to expand the current compendium of plant mitochondrial proteins while obtaining what could be termed the "baseline proteome" from our model organelle, the potato tuber mitochondrion. Its...

  19. 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.

  20. Mitochondrial Stress: A Bridge between Mitochondrial Dysfunction and Metabolic Diseases?

    OpenAIRE

    Hu, Fang; Liu, Feng

    2011-01-01

    Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPRmt) and initiation of a retrograde stress signaling pathway. Defects in the UPRmt and the retrograde signaling pathways may disrupt the integrity and homeostasis of the mitochondria, resulting endoplasmic reticulum stress and insulin resistance. Improving the capacity of mitochondria to reduce stress may be an effective a...

  1. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    Science.gov (United States)

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle. PMID:27184881

  2. Numerical Simulation Study of Influence of Nozzle Entrance Diameter on Jet Performance of Pre-mixed Abrasive Water Jet

    Science.gov (United States)

    Guan, Jinfa; Deng, Songsheng; Jiao, Guangwei; Chen, Ming; Hua, Weixing

    Physical model of cone-cylinder nozzle was established. Based on the CFD software of FLUENT, the flow field about abrasive water jet in cone-cylinder nozzle was simulated by use of standard k-ɛ turbulent model, Lagrange Discrete Phase Model and SIMPLE algorithm. The simulation results show that axial velocity of abrasive particle is always smaller than axial velocity of abrasive particle and increases gradually with the increase of axial distance. Axial static pressure of water decreases gradually with the increase of axial distance. Axial velocity of abrasive particle at the exit of cone-cylinder nozzle decreases with the increase of nozzle entrance diameter. And axial static pressure of water at the entrance of cone-cylinder nozzle decreases with the increase of nozzle entrance diameter. 8mm is selected as an optimal nozzle entrance diameter.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Bioenergetic roles of mitochondrial fusion.

    Science.gov (United States)

    Silva Ramos, Eduardo; Larsson, Nils-Göran; Mourier, Arnaud

    2016-08-01

    Mitochondria are bioenergetic hotspots, producing the bulk of ATP by the oxidative phosphorylation process. Mitochondria are also structurally dynamic and undergo coordinated fusion and fission to maintain their function. Recent studies of the mitochondrial fusion machinery have provided new evidence in detailing their role in mitochondrial metabolism. Remarkably, mitofusin 2, in addition to its role in fusion, is important for maintaining coenzyme Q levels and may be an integral player in the mevalonate synthesis pathway. Here, we review the bioenergetic roles of mitochondrial dynamics and emphasize the importance of the in vitro growth conditions when evaluating mitochondrial respiration. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016,' edited by Prof. Paolo Bernardi. PMID:27060252

  8. Higher Education Access Policies and Issues in Georgia before and after the Introduction of Unified National Entrance Examinations in 2005

    OpenAIRE

    Orkodashvili, Mariam

    2007-01-01

    The paper discusses the implications of Unified National Entrance Examinations (UNEEs) for higher education access in Georgia. Increased participation of ethnic minorities and low-SES students in higher education could be regarded as one of the major achievements of the UNEEs. More transparency and decreased corruption in higher education access procedures might be regarded as additional assets of the new policy. However, due to its early stage of implementation, the entrance policy needs fu...

  9. THE RELATIONSHIP BETWEEN THE POINTS OF UNIVERSITY ENTRANCE EXAMINATION AND EXPOSE OF DOMESTIC VIOLENCE AND ATTITUDES TOWARDS VIOLENCE OF STUDENTS

    OpenAIRE

    MAYDA, Atilla Senih; Karacor, Kayihan; Gokmen Umut ERDEM; Necla KIRCA; Utku URGAN

    2006-01-01

    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 ...

  10. The assembly of mitochondrial complex I : a product of nuclear-mitochondrial synergy

    NARCIS (Netherlands)

    Vogel, Rutger Oscar

    2007-01-01

    Mitochondria are essential to cellular energy production. Embedded in the mitochondrial inner membrane, the engine of the mitochondrial powerhouse is formed by the five enzymatic complexes of the oxidative phosphorylation (OXPHOS) system. Dysfunction of this system results in mitochondrial disease,

  11. Mitochondrial transplantation for therapeutic use

    OpenAIRE

    McCully, James Donald; Levitsky, Sidney; del Nido, Pedro J.; Cowan, Douglas Burr

    2016-01-01

    Mitochondria play a key role in the homeostasis of the vast majority of the body’s cells. In the myocardium where mitochondria constitute 30 % of the total myocardial cell volume, temporary attenuation or obstruction of blood flow and as a result oxygen delivery to myocardial cells (ischemia) severely alters mitochondrial structure and function. These alterations in mitochondrial structure and function occur during ischemia and continue after blood flow and oxygen delivery to the myocardium i...

  12. Mitochondrial Dysfunction in Neurodegenerative Diseases

    OpenAIRE

    Johri, Ashu; Beal, M. Flint

    2012-01-01

    Neurodegenerative diseases are a large group of disabling disorders of the nervous system, characterized by the relative selective death of neuronal subtypes. In most cases, there is overwhelming evidence of impaired mitochondrial function as a causative factor in these diseases. More recently, evidence has emerged for impaired mitochondrial dynamics (shape, size, fission-fusion, distribution, movement etc.) in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, amyo...

  13. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  14. Mitochondrial efficiency and insulin resistance.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2014-01-01

    Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle. PMID:25601841

  15. Mitochondrial Epigenetics and Environmental Exposure.

    Science.gov (United States)

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  16. Mitochondrial dysfunction in Parkinson's disease.

    Science.gov (United States)

    Hu, Qingsong; Wang, Guanghui

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta and the formation of Lewy bodies and Lewy neurites in surviving DA neurons in most cases. Although the cause of PD is still unclear, the remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. Numerous studies showed that dysfunction of mitochondria may play key roles in DA neuronal loss. Both genetic and environmental factors that are associated with PD contribute to mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provides direct evidence linking mitochondrial dysfunction to PD. Decrease of mitochondrial complex I activity is present in PD brain and in neurotoxin- or genetic factor-induced PD cellular and animal models. Moreover, PINK1 and parkin, two autosomal recessive PD gene products, have important roles in mitophagy, a cellular process to clear damaged mitochondria. PINK1 activates parkin to ubiquitinate outer mitochondrial membrane proteins to induce a selective degradation of damaged mitochondria by autophagy. In this review, we summarize the factors associated with PD and recent advances in understanding mitochondrial dysfunction in PD. PMID:27453777

  17. Mitochondrial function in human skeletal muscle following high-altitude exposure

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Boushel, Robert; Wright-Paradis, Cynthia;

    2013-01-01

    Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial...... characteristics. The aim of this study, therefore, was to investigate mitochondrial function in response to high-altitude acclimatization through measurements of respiratory control in the vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland natives prior to and again after a total of 9......-11 days of exposure to 4559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, because high-altitude exposure did not affect the capacity...

  18. 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. PMID:25188726

  19. 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...

  20. 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.

  1. The impacts of the presence of sociology on public university entrance exams: what teachers say

    OpenAIRE

    Alexandre Barbosa Fraga; Thiago Oliveira Lima Matiolli

    2015-01-01

    This paper is a outspread from previous researches in which we were concerned to analyze the ways in which sociology was and has been charged in the university entrance exams and in the ENEM. It also corresponds to the current stage of research, where we held the first incursions in school settings in order to understand the specific effects of Sociology presence in these exams in everyday practice of teaching the discipline. Were interviewed within the city of Rio de Janeiro teachers from th...

  2. An annular gas seal analysis using empirical entrance and exit region friction factors

    Science.gov (United States)

    Elrod, D. A.; Childs, D. W.; Nelson, C. C.

    1990-01-01

    Wall shear stress results from stationary-rotor flow tests of five annular gas seals are used to develop entrance and exit region friction factor models. The friction factor models are used in a bulk-flow seal analysis which predicts leakage and rotor-dynamic coefficients. The predictions of the analysis are compared to experimental results and to the predictions of Nelson's analysis (1985). The comparisons are for smooth-rotor seals with smooth and honeycomb-stators. The present analysis predicts the destabilizing cross-coupled stiffness of a seal better than Nelson's analysis. Both analyses predict direct damping well and direct stiffness poorly.

  3. Entrance Channel Dynamics of Hot and Cold Fusion Reactions Leading to Superheavy Elements

    CERN Document Server

    Umar, A S; Maruhn, J A; Reinhard, P -G

    2010-01-01

    We investigate the entrance channel dynamics for the reactions $\\mathrm{^{70}Zn}+\\mathrm{^{208}Pb}$ and $\\mathrm{^{48}Ca}+\\mathrm{^{238}U}$ using the fully microscopic time-dependent Hartree-Fock (TDHF) theory coupled with a density constraint. We calculate excitation energies and capture cross-sections relevant for the study of superheavy formations. We discuss the deformation dependence of the ion-ion potential for the $\\mathrm{^{48}Ca}+\\mathrm{^{238}U}$ system and perform an alignment angle averaging for the calculation of the capture cross-section. The results show that this parameter-free approach can generate results in good agreement with experiment and other theories.

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Cagalinec, Michal; Liiv, Mailis; Hodurova, Zuzana; Hickey, Miriam Ann; Vaarmann, Annika; Mandel, Merle; Zeb, Akbar; Choubey, Vinay; Kuum, Malle; Safiulina, Dzhamilja; Vasar, Eero; Veksler, Vladimir; Kaasik, Allen

    2016-07-01

    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. PMID:27434582

  8. 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.

  9. 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

  10. 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.

  11. 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

    2013-06-01

    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. PMID:23542814

  12. 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.

  13. Middle school teachers’ and students’ view about the secondary school entrance examinations (OKS and SBS

    Directory of Open Access Journals (Sweden)

    Semiha Şahin

    2012-08-01

    Full Text Available The purpose of this study was to explore middle school teachers’ and students’ view about the secondary school entrance examinations (OKS and SBS. With this respect, the students’ and the teachers’ opinions about the necessity of the examinations, process of preparing for the examination, the students’ reactions to the others’ approaches to the examination, and the effects of the examinations on the students’ personal, social and academic lives were investigated. Qualitative research method was used in this descriptive study. The sample of the study included 24 middle school teachers and 65 middle school students from 6th to 8th grades. The data was collected by a semi-structured interview form. According to the results approximately half of both students and teachers reported that the secondary school entrance examinations (OKS were necessary, whereas this rate was very low during the period of SBS. Majority of the students reported that they were listening to the lessons during school hours and were taking educational tests outside school hours in order to prepare for the exams. Finally majority of both students and teachers reported that test taking is a major source of stress and have a negative impact on the students’ social lives.

  14. Study of enhanced entrance pressure losses in a rod bundle experiment employing heavy liquid metal coolant

    International Nuclear Information System (INIS)

    Innovative nuclear reactor concepts like accelerator driven systems (ADS) or the lead cooled fast reactor LFR employ lead bismuth eutectic (LBE) as a coolant. Within the framework of the EU project THINS (thermalhydraulics of innovative nuclear systems) a rod bundle experiment in LBE is performed employing characteristic dimensions at the Karlsruhe Liquid Metal Laboratory (KALLA)l of Karlsruhe Institute of Technology (KIT). In a first measurement campaign it is observed that the pressure drop across the first spacer in the rod bundle experiment is noticeable larger than at the subsequent spacers. We speculate that this is due to blockage of the very narrow spacer channels and numerically investigate whether there are substantially enhanced entrance effects. The present numerical study investigates the whole rod bundle including the entrance region in order to show possible mechanisms which can increase the pressure drop of the first spacer even if no blockage is present. The extra pressure loss compared to simulations with uniform inflow is found to be very small which supports the speculation of blockage. Since rod bundle flow is known to depend very sensitive on turbulence models and mesh resolution we carefully verify that our simulations use an adequate computation domain, mesh resolution and turbulence model. (author)

  15. Aortic dissection with the entrance tear in transverse aorta: analysis of 12 autopsy patients.

    Science.gov (United States)

    Roberts, C S; Roberts, W C

    1990-11-01

    Clinical and autopsy findings are described in 12 patients who had fatal aortic dissection with the entrance tear in the transverse aorta. The 12 patients represent 7% of 182 autopsies of spontaneous aortic dissection studied by us. The ages of the 12 patients at death ranged from 37 to 87 years (mean, 67 years). Eight were men; 8 had a history of systemic hypertension, and 10 had hearts of increased weight. Diagnosis of aortic dissection was made during life in only 4 of the 12 patients. All 12 patients died of rupture of the false channel within 2 weeks of onset of signs or symptoms compatible with dissection. The direction of aortic dissection from the entrance tear was entirely retrograde in 4 patients, entirely anterograde in 4 patients, and in both directions in 4 patients. Hemopericardium occurred in the first group, left hemothorax in the second group, and either in the last group. Of the 8 patients in whom the ascending aorta was involved, the retrograde dissection in each extended to the aortic root, 6 had pulmonary adventitial hemorrhage, and 4 had involvement of the arch arteries by dissection. In the 4 patients with strictly anterograde dissection, none had dissection in the arch arteries. Thus, tear in the transverse aorta causes a dissection that is usually fata, that often dissects retrogradely, and that may mimic dissection from a tear in ascending aorta. Aortic dissection from a tear in transverse aorta requires early operative intervention. PMID:2241339

  16. 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.

  17. Analysis of long-range bullet entrance holes by atomic absorption spectrophotometry and scanning electron microscopy.

    Science.gov (United States)

    Ravreby, M

    1982-01-01

    Bullet residue and primer particles were analyzed by scanning electron microscopy with energy dispersive analysis (SEM-EDA) and by flame and flameless atomic absorption spectrophotometry (AAS). The residue and particles were on cloth targets around entrance holes produced by bullets fired at distances of 10 to 200 m. Primer particles and their chemical constituents were almost always detected by SEM-EDA around the holes produced by rifles and pistols fired at long ranges, and in many cases the barium and antimony associated with primer particles were detected by flameless AAS. Particles were also detected by SEM-EDA on the rear of bullets fired into and recovered from wooden blocks. Usually a hole caused by a bullet jacketed with gilding metal could be distinguished from one caused by a bullet jacketed with yellow brass alloy. Paint from bullet tips of military tracers was also detected. Analysis of the various residues around entrance holes provides a means for identifying the type of ammunition used. PMID:7097199

  18. Evaluation of radiological protection and dose of skin entrance in paediatric dentistry examinations

    International Nuclear Information System (INIS)

    In this work the radiological protection conditions and dose at the entrance of pediatric patients undergoing dental intraoral radiographs were evaluated. The study was conducted in two clinics of the dentistry course at the Federal University of Pernambuco, Recife, PB, Brazil, equipped with conventional X-ray apparatus, with 60 and 70 kV. 254 exams of 113 patients between the ages of 3 to 12 years were evaluated. The skin entrance dose was estimated using TLD-100 thermoluminescent dosemeters. During the examination were also recorded information regarding the time of exposure, radiographic technique used, use of thyroid protectors and lead apron, angle and distance of the cone Locator to the patient's skin. The results showed that the input skin doses ranged from 0.3 mGy to 10mGy. The lead apron was used in 71% of exams while the thyroid shield was only used in 58% of the exams. The exposure times ranged from 0,5s to 1,5s. From the results it can be concluded that the radiological procedures are not optimized and that in some cases the patient dose is high.

  19. 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.

  20. 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.

  1. Mitochondrial Stress Tests Using Seahorse Respirometry on Intact Dictyostelium discoideum Cells.

    Science.gov (United States)

    Lay, Sui; Sanislav, Oana; Annesley, Sarah J; Fisher, Paul R

    2016-01-01

    Mitochondria not only play a critical and central role in providing metabolic energy to the cell but are also integral to the other cellular processes such as modulation of various signaling pathways. These pathways affect many aspects of cell physiology, including cell movement, growth, division, differentiation, and death. Mitochondrial dysfunction which affects mitochondrial bioenergetics and causes oxidative phosphorylation defects can thus lead to altered cellular physiology and manifest in disease. The assessment of the mitochondrial bioenergetics can thus provide valuable insights into the physiological state, and the alterations to the state of the cells. Here, we describe a method to successfully use the Seahorse XF(e)24 Extracellular Flux Analyzer to assess the mitochondrial respirometry of the cellular slime mold Dictyostelium discoideum. PMID:27271893

  2. 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.

  3. Nanodelivery System for Mitochondrial Targeting

    Science.gov (United States)

    Yoong, Sia Lee; Pastorin, Giorgia

    2014-02-01

    Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.

  4. In EXOG-depleted cardiomyocytes cell death is marked by a decreased mitochondrial reserve capacity of the electron transport chain.

    Science.gov (United States)

    Tigchelaar, Wardit; De Jong, Anne Margreet; van Gilst, Wiek H; De Boer, Rudolf A; Silljé, Herman H W

    2016-07-01

    Depletion of mitochondrial endo/exonuclease G-like (EXOG) in cultured neonatal cardiomyocytes stimulates mitochondrial oxygen consumption rate (OCR) and induces hypertrophy via reactive oxygen species (ROS). Here, we show that neurohormonal stress triggers cell death in endo/exonuclease G-like-depleted cells, and this is marked by a decrease in mitochondrial reserve capacity. Neurohormonal stimulation with phenylephrine (PE) did not have an additive effect on the hypertrophic response induced by endo/exonuclease G-like depletion. Interestingly, PE-induced atrial natriuretic peptide (ANP) gene expression was completely abolished in endo/exonuclease G-like-depleted cells, suggesting a reverse signaling function of endo/exonuclease G-like. Endo/exonuclease G-like depletion initially resulted in increased mitochondrial OCR, but this declined upon PE stimulation. In particular, the reserve capacity of the mitochondrial respiratory chain and maximal respiration were the first indicators of perturbations in mitochondrial respiration, and these marked the subsequent decline in mitochondrial function. Although pathological stimulation accelerated these processes, prolonged EXOG depletion also resulted in a decline in mitochondrial function. At early stages of endo/exonuclease G-like depletion, mitochondrial ROS production was increased, but this did not affect mitochondrial DNA (mtDNA) integrity. After prolonged depletion, ROS levels returned to control values, despite hyperpolarization of the mitochondrial membrane. The mitochondrial dysfunction finally resulted in cell death, which appears to be mainly a form of necrosis. In conclusion, endo/exonuclease G-like plays an essential role in cardiomyocyte physiology. Loss of endo/exonuclease G-like results in diminished adaptation to pathological stress. The decline in maximal respiration and reserve capacity is the first sign of mitochondrial dysfunction that determines subsequent cell death. PMID:27417117

  5. Unexplained gastrointestinal symptoms: Think mitochondrial disease

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic.We describe the clinical, histopathol...

  6. Unexplained gastrointestinal symptoms: think mitochondrial disease.

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic. We describe the clinical, histopatho...

  7. Platelet mitochondrial membrane potential in Parkinson's disease

    OpenAIRE

    Antony, P.M.; Boyd, O.; Trefois, C.; Ammerlaan, W; Ostaszewski, M.; Baumuratov, A.S.; Longhino, L.; Antunes, L; Koopman, W.J.H.; Balling, R; Diederich, N.J.

    2014-01-01

    OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. METHODS: Twenty-five IPD pati...

  8. Unexplained gastrointestinal symptoms: think mitochondrial disease.

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic.We describe the clinical, histopathol...

  9. 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.

  10. Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, and Management

    OpenAIRE

    Meyers, Deborah E.; Basha, Haseeb Ilias; Koenig, Mary Kay

    2013-01-01

    Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specifi...

  11. 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.

  12. Drosophila Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin

    OpenAIRE

    Ziviani, E.; Tao, R.N.; Whitworth, A. J.

    2010-01-01

    Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology. Parkin has been linked to multiple cellular processes including protein degradation, mitochondrial homeostasis, and autophagy; however, its precise role in pathogenesis is unclear. Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover. The precise mechan...

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

    OpenAIRE

    Keller, Amy C.; Knaub, Leslie A; P. Mason McClatchey; Chelsea A. Connon; Ron Bouchard; Miller, Matthew W.; Kate E. Geary; 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. ...

  14. 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

  15. 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.

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

    Science.gov (United States)

    Yang, Dong; Li, Zhichao; Guo, Liang; Li, Sanwei; Yi, Rongqing; Song, Tianming; Zhang, Huan; Wang, Zhebin; Jiang, Xiaohua; Jiang, Shaoen; Ding, Yongkun

    2014-03-01

    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.

  17. 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

  18. Resources, challenges and way forward in rare mitochondrial diseases research

    OpenAIRE

    Neeraj Kumar Rajput; Vipin Singh; Anshu Bhardwaj

    2015-01-01

    Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major c...

  19. 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

  20. Natural Compounds Modulating Mitochondrial Functions

    Directory of Open Access Journals (Sweden)

    Lara Gibellini

    2015-01-01

    Full Text Available Mitochondria are organelles responsible for several crucial cell functions, including respiration, oxidative phosphorylation, and regulation of apoptosis; they are also the main intracellular source of reactive oxygen species (ROS. In the last years, a particular interest has been devoted to studying the effects on mitochondria of natural compounds of vegetal origin, quercetin (Qu, resveratrol (RSV, and curcumin (Cur being the most studied molecules. All these natural compounds modulate mitochondrial functions by inhibiting organelle enzymes or metabolic pathways (such as oxidative phosphorylation, by altering the production of mitochondrial ROS and by modulating the activity of transcription factors which regulate the expression of mitochondrial proteins. While Qu displays both pro- and antioxidant activities, RSV and Cur are strong antioxidant, as they efficiently scavenge mitochondrial ROS and upregulate antioxidant transcriptional programmes in cells. All the three compounds display a proapoptotic activity, mediated by the capability to directly cause the release of cytochrome c from mitochondria or indirectly by upregulating the expression of proapoptotic proteins of Bcl-2 family and downregulating antiapoptotic proteins. Interestingly, these effects are particularly evident on proliferating cancer cells and can have important therapeutic implications.

  1. 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,…

  2. 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…

  3. 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.

  4. 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.

  5. 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.

  6. Changes in liver mitochondrial plasticity induced by brain tumor

    Directory of Open Access Journals (Sweden)

    Debien Emilie

    2006-10-01

    Full Text Available Abstract Background Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. Methods Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H2Ost were calculated from Nuclear Magnetic Resonance (NMR measurements. Results The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. Conclusion This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation.

  7. Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options.

    Science.gov (United States)

    Tarnopolsky, Mark A; Raha, Sandeep

    2005-12-01

    Mitochondrial myopathies are caused by genetic mutations that directly influence the functioning of the electron transport chain (ETC). It is estimated that 1 of 8,000 people have pathology inducing mutations affecting mitochondrial function. Diagnosis often requires a multifaceted approach with measurements of serum lactate and pyruvate, urine organic acids, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement. Exercise intolerance is a common but often an overlooked hallmark of mitochondrial myopathies. The muscle consequences of ETC dysfunction include increased reliance on anaerobic metabolism (lactate generation, phosphocreatine degradation), enhanced free radical production, reduced oxygen extraction and electron flux through ETC, and mitochondrial proliferation or biogenesis (see article by Hood in current issue). Treatments have included antioxidants (vitamin E, alpha lipoic acid), electron donors and acceptors (coenzyme Q10, riboflavin), alternative energy sources (creatine monohydrate), lactate reduction strategies (dichloroacetate) and exercise training. Exercise is a particularly important modality in diagnosis as well as therapy (see article by Taivassalo in current issue). Increased awareness of these disorders by exercise physiologists and sports medicine practitioners should lead to more accurate and more rapid diagnosis and the opportunity for therapy and genetic counseling. PMID:16331134

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

    Directory of Open Access Journals (Sweden)

    L. A. Egorova

    2013-01-01

    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.

  9. Opening up in the classroom: effects of expressive writing on graduate school entrance exam performance.

    Science.gov (United States)

    Frattaroli, Joanne; Thomas, Michael; Lyubomirsky, Sonja

    2011-06-01

    Our study sought to determine whether experimental disclosure could improve exam performance and psychological health in students taking a graduate school entrance exam. Students preparing for the GRE, MCAT, LSAT, or PCAT were randomly assigned to write expressively about their upcoming exam or to a neutral writing condition. Participants completed measures of depressive symptoms and test anxiety before and after writing, and exam scores were collected. The experimental disclosure group had significantly higher test scores and significantly lower pre-exam depressive symptoms than the neutral writing group. Although benefits for depressive symptoms were found in expressive writers regardless of exam type, the advantage of expressive writing for test performance was only observed in students taking the MCAT or LSAT. PMID:21517162

  10. A conserved chloramphenicol binding site at the entrance to the ribosomal peptide exit tunnel

    DEFF Research Database (Denmark)

    Long, Katherine S; Porse, Bo T

    2003-01-01

    The antibiotic chloramphenicol produces modifications in 23S rRNA when bound to ribosomes from the bacterium Escherichia coli and the archaeon Halobacterium halobium and irradiated with 365 nm light. The modifications map to nucleotides m(5)U747 and C2611/C2612, in domains II and V, respectively......, of E.coli 23S rRNA and G2084 (2058 in E.coli numbering) in domain V of H.halobium 23S rRNA. The modification sites overlap with a portion of the macrolide binding site and cluster at the entrance to the peptide exit tunnel. The data correlate with the recently reported chloramphenicol binding site on...

  11. 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.

  12. 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.

  13. Shell correction energy and the entrance channel effect on the formation of superheavy nuclei

    International Nuclear Information System (INIS)

    Based on the improved isospin dependent molecular dynamics model in which the shell correction energy of the system is calculated by using deformed two-center shell model and the surface energy of the system is improved by introducing a switch function that combines the surface energies of projectile and target with the one of the compound nucleus. The effects of the shell correction energy on synthesis of superheavy nuclei and the fusion cross sections in asymmetric and nearly symmetric reaction systems leading to the same compound nuclei 62Zn, 76Kr, and 202Pb are studied. The entrance channel mass asymmetry dependence of compound nucleus formation is found by analyzing the shell correction energies, Coulomb barriers and fusion cross sections. The experimental data are described quantitatively by the present model. It is found that the compound nucleus formation is favorable for the systems with larger mass asymmetry. (author)

  14. 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.

  15. Images of the Laser Entrance Hole from the Static X-ray Imager at NIF

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-05-04

    The Static X-ray Imager (SXI) at the National Ignition Facility (NIF) 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 allows recording images in the x-ray range of 3 to 5 keV with 60 {micro}m 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.

  16. Measurements of entrance surface dose using a fiber-optic dosimeter in diagnostic radiology

    Science.gov (United States)

    Yoo, Wook Jae; Seo, Jeong Ki; Shin, Sang Hun; Han, Ki-Tek; Jeon, Dayeong; Jang, Kyoung Won; Sim, Hyeok In; Lee, Bongsoo; Park, Jang-Yeon

    2013-03-01

    In this study, a fiber-optic dosimeter (FOD) was developed to measure entrance surface dose (ESD) in diagnostic radiology. We measured the scintillating lights in order to obtain ESDs, which changed with the various exposure parameters of a digital radiography (DR) system, such as tube potential, current-time product, focus-surface distance (FSD), and field size, using the fabricated FOD system. From the experimental results, the output light signals of the FOD were similar to the ESDs of the conventional semiconductor dosimeter. In conclusion, we characterized the measured ESDs as functions of exposure parameters by using two different types of dosimeters and demonstrated that the proposed FOD using a plastic scintillating fiber and a plastic optical fiber (POF) makes it possible to measure ESDs in the energy range of diagnostic radiology. From the results of this study, it is anticipated that the FOD will be a useful dosimeter in low-energy photon applications including diagnostic radiology.

  17. 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.

  18. 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.)

  19. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

    Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

  20. Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source.

    Science.gov (United States)

    Putti, Rosalba; Migliaccio, Vincenzo; Sica, Raffaella; Lionetti, Lillà

    2015-01-01

    It has been suggested that skeletal muscle mitochondria play a key role in high fat (HF) diet induced insulin resistance (IR). Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle IR. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to IR. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of IR. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift toward mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and IR development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle IR and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle IR, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance. PMID:26834644

  1. 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.

  2. Investigating complex I deficiency in Purkinje cells and synapses in patients with mitochondrial disease

    Science.gov (United States)

    Chrysostomou, Alexia; Grady, John P.; Laude, Alex; Taylor, Robert W.; Turnbull, Doug M.

    2015-01-01

    Aims Cerebellar ataxia is common in patients with mitochondrial disease, and despite previous neuropathological investigations demonstrating vulnerability of the olivocerebellar pathway in patients with mitochondrial disease, the exact neurodegenerative mechanisms are still not clear. We use quantitative quadruple immunofluorescence to enable precise quantification of mitochondrial respiratory chain protein expression in Purkinje cell bodies and their synaptic terminals in the dentate nucleus. Methods We investigated NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 protein expression in 12 clinically and genetically defined patients with mitochondrial disease and ataxia and 10 age‐matched controls. Molecular genetic analysis was performed to determine heteroplasmy levels of mutated mitochondrial DNA in Purkinje cell bodies and inhibitory synapses. Results Our data reveal that complex I deficiency is present in both Purkinje cell bodies and their inhibitory synapses which surround dentate nucleus neurons. Inhibitory synapses are fewer and enlarged in patients which could represent a compensatory mechanism. Mitochondrial DNA heteroplasmy demonstrated similarly high levels of mutated mitochondrial DNA in cell bodies and synapses. Conclusions This is the first study to use a validated quantitative immunofluorescence technique to determine complex I expression in neurons and presynaptic terminals, evaluating the distribution of respiratory chain deficiencies and assessing the degree of morphological abnormalities affecting synapses. Respiratory chain deficiencies detected in Purkinje cell bodies and their synapses and structural synaptic changes are likely to contribute to altered cerebellar circuitry and progression of ataxia. PMID:26337858

  3. 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.

  4. Uncoupling protein-4 (UCP4 increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Philip Wing-Lok Ho

    Full Text Available Mitochondrial uncoupling protein-4 (UCP4 protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP(+, but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01, with 20% greater proton leak than vector controls (p<0.01. Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05. Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05, associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05. ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  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. 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…

  12. 33 CFR 165.501 - Chesapeake Bay entrance and Hampton Roads, VA and adjacent waters-Regulated Navigation Area.

    Science.gov (United States)

    2010-07-01

    ... Hampton Roads, VA and adjacent waters-Regulated Navigation Area. 165.501 Section 165.501 Navigation and... Areas Fifth Coast Guard District § 165.501 Chesapeake Bay entrance and Hampton Roads, VA and adjacent... Sector Hampton Roads. Designated representative of the Captain of the Port means a person, including...

  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. 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…

  15. 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…

  16. Entrance radiation doses during paediatric cardiac catheterizations performed for diagnosis or the treatment of congenital heart disease

    International Nuclear Information System (INIS)

    The purpose of this study was to estimate the radiation exposure of children, during cardiac catheterizations for the diagnosis or treatment of congenital heart disease. Radiation doses were estimated for 45 children aged from 1 d to 13 y old. Thermoluminescent dosemeters (TLDs) were used to estimate the posterior entrance dose (DP), the lateral entrance dose (DLAT), the thyroid dose and the gonads dose. A dose-area product (DAP) meter was also attached externally to the tube of the angiographic system and gave a direct value in mGy cm2 for each procedure. Posterior and lateral entrance dose values during cardiac catheterizations ranged from 1 to 197 mGy and from 1.1 to 250.3 mGy, respectively. Radiation exposure to the thyroid and the gonads ranged from 0.3 to 8.4 mGy to 0.1 and 0.7 mGy, respectively. Finally, the DAP meter values ranged between 360 and 33,200 mGy cm2. Radiation doses measured in this study are comparable with those reported to previous studies. Moreover, strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs. (authors)

  17. Polyethylenimine-mediated impairment of mitochondrial membrane potential, respiration and membrane integrity

    DEFF Research Database (Denmark)

    Larsen, Anna Karina; Malinska, Dominika; Koszela-Piotrowska, Izabela;

    2012-01-01

    The 25 kDa branched polyethylenimine (PEI) is a highly efficient synthetic polycation used in transfection protocols, but also triggers mitochondrial-mediated apoptotic cell death processes where the mechanistic issues are poorly understood. We now demonstrate that PEI in a concentration- and time......-dependent manner can affect functions (membrane potential, swelling and respiration) and ultrastructural integrity of freshly isolated rat liver mitochondria. The threshold concentration for detection of PEI-mediated impairment of rat liver mitochondrial functions is 3 µg/mL, however, lower PEI levels still exert...... some effects on mitochondrial morphology and respiration, and these may be related to the inherent membrane perturbing properties of this polycation. The PEI-mediated mitochondrial swelling phase is biphasic, with a fast decaying initial period (most prominent from 4 µg/mL PEI) followed by a slower...

  18. 33 CFR 334.680 - Gulf of Mexico, southeast of St. Andrew Bay East Entrance, small-arms firing range, Tyndall Air...

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Gulf of Mexico, southeast of St... AND RESTRICTED AREA REGULATIONS § 334.680 Gulf of Mexico, southeast of St. Andrew Bay East Entrance... the Gulf of Mexico, southeast of St. Andrew Bay East Entrance within a rectangular area beginning at...

  19. 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

  20. Role of mitochondrial function in cell death and body metabolism.

    Science.gov (United States)

    Lee, Myung-Shik

    2016-01-01

    Mitochondria are the key players in apoptosis and necrosis. Mitochondrial DNA (mtDNA)-depleted r0 cells were resistant to diverse apoptosis inducers such as TNF-alpha, TNFSF10, staurosporine and p53. Apoptosis resistance was accompanied by the absence of mitochondrial potential loss or cytochrome c translocation. r0 cells were also resistant to necrosis induced by reactive oxygen species (ROS) donors due to upregulation of antioxidant enzymes such as manganese superoxide dismutase. Mitochondria also has a close relationship with autophagy that plays a critical role in the turnover of senescent organelles or dysfunctional proteins and may be included in 'cell death' category. It was demonstrated that autophagy deficiency in insulin target tissues such as skeletal muscle induces mitochondrial stress response, which leads to the induction of FGF21 as a 'mitokine' and affects the whole body metabolism. These results show that mitochondria are not simply the power plants of cells generating ATP, but are closely related to several types of cell death and autophagy. Mitochondria affect various pathophysiological events related to diverse disorders such as cancer, metabolic disorders and aging. PMID:27100503

  1. 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.

  2. Mitochondrial plasticity in pathophysiological conditions

    OpenAIRE

    Padrão, Ana Isabel Martins Novais

    2013-01-01

    Both skeletal and cardiac muscles daily burn tremendous amounts of ATP to meet the energy requirements for contraction. So, it is not surprising that the maintenance of mitochondrial morphology, number, distribution and functionality in striated muscle are important for muscle homeostasis. In these tissues mitochondria present the added dimension of two populations, the intermyofibrillar (IMF) and the subsarcolemmal (SS) mitochondria, being IMF the most abundant one. In the present thesis, th...

  3. Impaired Cellular Bioenergetics Causes Mitochondrial Calcium Handling Defects in MT-ND5 Mutant Cybrids

    Science.gov (United States)

    Duchen, Michael R.

    2016-01-01

    Mutations in mitochondrial DNA (mtDNA) can cause mitochondrial disease, a group of metabolic disorders that affect both children and adults. Interestingly, individual mtDNA mutations can cause very different clinical symptoms, however the factors that determine these phenotypes remain obscure. Defects in mitochondrial oxidative phosphorylation can disrupt cell signaling pathways, which may shape these disease phenotypes. In particular, mitochondria participate closely in cellular calcium signaling, with profound impact on cell function. Here, we examined the effects of a homoplasmic m.13565C>T mutation in MT-ND5 on cellular calcium handling using transmitochondrial cybrids (ND5 mutant cybrids). We found that the oxidation of NADH and mitochondrial membrane potential (Δψm) were significantly reduced in ND5 mutant cybrids. These metabolic defects were associated with a significant decrease in calcium uptake by ND5 mutant mitochondria in response to a calcium transient. Inhibition of glycolysis with 2-deoxy-D-glucose did not affect cytosolic calcium levels in control cybrids, but caused an increase in cytosolic calcium in ND5 mutant cybrids. This suggests that glycolytically-generated ATP is required not only to maintain Δψm in ND5 mutant mitochondria but is also critical for regulating cellular calcium homeostasis. We conclude that the m.13565C>T mutation in MT-ND5 causes defects in both mitochondrial oxidative metabolism and mitochondrial calcium sequestration. This disruption of mitochondrial calcium handling, which leads to defects in cellular calcium homeostasis, may be an important contributor to mitochondrial disease pathogenesis. PMID:27110715

  4. Uncoupling Mitochondrial Respiration for Diabesity.

    Science.gov (United States)

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

    2016-08-01

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

  5. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration.

    Science.gov (United States)

    Detaille, D; Vial, G; Borel, A-L; Cottet-Rouselle, C; Hallakou-Bozec, S; Bolze, S; Fouqueray, P; Fontaine, E

    2016-01-01

    Imeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of β-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert-butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death. These events were fully prevented by Imeglimin treatment. This protective effect on cell death occurred without any effect on oxygen consumption rate, on lactate production and on cytosolic redox or phosphate potentials. Imeglimin also dramatically decreased reactive oxygen species production, inhibiting specifically reverse electron transfer through complex I. We conclude that Imeglimin prevents hyperglycemia-induced cell death in HMEC-1 through inhibition of PTP opening without inhibiting mitochondrial respiration nor affecting cellular energy status. Considering the high prevalence of macrovascular and microvascular complications in type 2 diabetic subjects, these results together suggest a potential benefit of Imeglimin in diabetic angiopathy. PMID:27551496

  6. 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.

  7. 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.

  8. 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

  9. Mitochondrial disease heterogeneity: a prognostic challenge.

    Science.gov (United States)

    Moggio, Maurizio; Colombo, Irene; Peverelli, Lorenzo; Villa, Luisa; Xhani, Rubjona; Testolin, Silvia; Di Mauro, Salvatore; Sciacco, Monica

    2014-10-01

    Mitochondrial diseases are a heterogeneous group of progressive, genetically transmitted, multisystem disorders caused by impaired mitochondrial function. The disease course for individuals with mitochondrial myopathies varies greatly from patient to patient because disease progression largely depends on the type of disease and on the degree of involvement of various organs which makes the prognosis unpredictable both within the same family and among families with the same mutation. This is particularly, but not exclusively, true for mitochondrial disorders caused by mtDNA point mutations, which are maternally inherited and subject to the randomness of the heteroplasmy. For this reason, the prognosis cannot be given by single mitochondrial disease, but should be formulated by any single mitochondrial disease-related event or complication keeping in mind that early recognition and treatment of symptoms are crucial for the prognosis. The following approach can help prevent severe organ dysfunctions or at least allow early diagnosis and treatment of disease-related complications. PMID:25709378

  10. Mitochondrial dysfunction and risk of cancer

    DEFF Research Database (Denmark)

    Lund, M; Melbye, M; Diaz, L J;

    2015-01-01

    BACKGROUND: Mitochondrial mutations are commonly reported in tumours, but it is unclear whether impaired mitochondrial function per se is a cause or consequence of cancer. To elucidate this, we examined the risk of cancer in a nationwide cohort of patients with mitochondrial dysfunction. METHODS......: We used nationwide results on genetic testing for mitochondrial disease and the Danish Civil Registration System, to construct a cohort of 311 patients with mitochondrial dysfunction. A total of 177 cohort members were identified from genetic testing and 134 genetically untested cohort members were...... mDNA mutation, cases=13. CONCLUSIONS: Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population....

  11. 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.

  12. 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

  13. 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

  14. Renal manifestations of genetic mitochondrial disease

    OpenAIRE

    O’Toole JF

    2014-01-01

    John F O'Toole Department of Internal Medicine, Division of Nephrology, MetroHealth Medical System, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant...

  15. Mitochondrial Dynamics in Cardiovascular Health and Disease

    OpenAIRE

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

    2013-01-01

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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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. PMID:26857402

  1. Complete mitochondrial genome of Drosophila albomicans.

    Science.gov (United States)

    Kang, Xiongbin; Luo, Xiao; Zhang, Zhi; Zhang, Zhen; Yang, Junqing; Bi, Guiqi

    2016-09-01

    Drosophila albomicans has been widely used as an important animal model for chromosome evolution. In this study, the mitochondrial genome sequence of this species is determined and described for the first time. The mitochondrial genome (15 849 bp) encompasses two rRNA, 22 tRNA, and 13 protein-coding genes. Genome content and structure are similar to those reported from other Drosophila mitochondrial genomes. Phylogeny analysis indicates that D. albomicans have a closer genetic relationship with Drosophil aincompta and Drosophil alittoralis. This mitochondrial genome is potentially important for studying molecular evolution and conservation genetics in Drosophila genus. PMID:26358579

  2. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    . Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...... and cultural festivals, both practices indicate that design is implemented as means of creating affective spaces in the city. Both cases show how immaterial production of affects and emotions in the city can be seen in relation to economic potential and urban development. Finally, I will discuss whether urban......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...

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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/...

  9. Search for entrance channel effects in the decay of compound nucleus

    CERN Document Server

    Govil, I M; Kumar, A; Datta, S K; Kataria, S K

    2000-01-01

    The alpha-particle energy spectra have been measured at different laboratory angles from the fusion reaction sup 1 sup 2 C+ sup 4 sup 5 Sc at 83 and 97 MeV incident energies. These spectra are consistent with the predictions of the statistical model calculations using the Rotating Liquid Drop Model (RLDM) values of the moment of inertia and the optical model transmission coefficients for the respective inverse absorption channels. The results of sup 1 sup 2 C+ sup 4 sup 5 Sc asymmetric system were compared with the sup 2 sup 8 Si+ sup 2 sup 7 Al symmetric system at 140 MeV studied earlier as both the systems lead to the formation of nearly same compound nucleus (Z=27) with the same angular momentum and the excitation energy. The comparison was made in order to understand the symmetric and the asymmetric entrance channel effects in the formation and the decay of the compound system. In the case of sup 2 sup 8 Si+ sup 2 sup 7 Al symmetric system, the experimental spectra deviate at higher as well as at lower en...

  10. 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.

  11. 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.

  12. Evaluation of a Model for Predicting the Tidal Velocity in Fjord Entrances

    Directory of Open Access Journals (Sweden)

    Paul Thomassen

    2013-04-01

    Full Text Available Sufficiently accurate and low-cost estimation of tidal velocities is of importance when evaluating a potential site for a tidal energy farm. Here we suggest and evaluate a model to calculate the tidal velocity in fjord entrances. The model is compared with tidal velocities from Acoustic Doppler Current Profiler (ADCP measurements in the tidal channel Skarpsundet in Norway. The calculated velocity value from the model corresponded well with the measured cross-sectional average velocity, but was shown to underestimate the velocity in the centre of the channel. The effect of this was quantified by calculating the kinetic energy of the flow for a 14-day period. A numerical simulation using TELEMAC-2D was performed and validated with ADCP measurements. Velocity data from the simulation was used as input for calculating the kinetic energy at various locations in the channel. It was concluded that the model presented here is not accurate enough for assessing the tidal energy resource. However, the simplicity of the model was considered promising in the use of finding sites where further analyses can be made.

  13. Evaluation of a Model for Predicting the Tidal Velocity in Fjord Entrances

    Energy Technology Data Exchange (ETDEWEB)

    Lalander, Emilia [The Swedish Centre for Renewable Electric Energy Conversion, Division of Electricity, Uppsala Univ. (Sweden); Thomassen, Paul [Team Ashes, Trondheim (Norway); Leijon, Mats [The Swedish Centre for Renewable Electric Energy Conversion, Division of Electricity, Uppsala Univ. (Sweden)

    2013-04-15

    Sufficiently accurate and low-cost estimation of tidal velocities is of importance when evaluating a potential site for a tidal energy farm. Here we suggest and evaluate a model to calculate the tidal velocity in fjord entrances. The model is compared with tidal velocities from Acoustic Doppler Current Profiler (ADCP) measurements in the tidal channel Skarpsundet in Norway. The calculated velocity value from the model corresponded well with the measured cross-sectional average velocity, but was shown to underestimate the velocity in the centre of the channel. The effect of this was quantified by calculating the kinetic energy of the flow for a 14-day period. A numerical simulation using TELEMAC-2D was performed and validated with ADCP measurements. Velocity data from the simulation was used as input for calculating the kinetic energy at various locations in the channel. It was concluded that the model presented here is not accurate enough for assessing the tidal energy resource. However, the simplicity of the model was considered promising in the use of finding sites where further analyses can be made.

  14. Soft x-ray images of the Laser Entrance Hole of NIC Hohlraums (paper, HTPD2012)

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M B; Meezan, N B

    2012-04-30

    Hohlraums at the National Ignition Facility convert laser energy into a thermal x-radiation drive, which implodes the capsule, thus compressing the fuel. The x-radiation drive is measured with a low resolution, time-resolved x-ray spectrometer that views the hohlraum's laser entrance hole (LEH) at 37{sup o} to the hohlraum axis. This measurement has no spatial resolution. To convert this to the drive inside the hohlraum, the area and fraction of the measured x-radiation which comes from the region inside the hohlraum must be known. The size of the LEH is measured with the time integrated Static X-ray Imager (SXI) which view the LEH at 18{sup o} to the hohlraum axis. A soft x-ray image has been added to the SXI to measure the fraction of x-radiation inside the LEH's Clear Aperture in order to correct the measured radiation. A multilayer mirror plus filter selects an x-ray band centered at 870 eV, near the x-ray energy peak of a 300 eV blackbody. Results from this channel and corrections to the x-radiation drive are discussed.

  15. 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.)

  16. [The forensic medical characteristics of the entrance bullet holes created by the shots from pneumatic rifles].

    Science.gov (United States)

    Legin, G A; Bondarchuk, A O; Perebetiuk, A N

    2015-01-01

    The objective of the present study was to compare the injurious action of three types of the bullets for the pneumatic weapons shot from different distances using the Gamo pump air pistol and the BAM B22-1 pneumatic rifle. The following four kinds of the bullets were tested: "the fireball", "Luman cap 0.3", "Luman Field Target 0.68" and "DIABOLO". It was experimentally shown that the injurious action of the bullets fired from the same distance from the pneumatic weapons depends on the type of both the bullet and the weapon, as well as the properties of the target material. Specifically, the action of bullets fired from the piston pneumatic rifle remained stable whereas that of the bullets shot from the gas-balloon air pistol decreased as the gas was exhausted. The studies by the contact-diffusion method have demonstrated that the entrance bullet holes created by the shots from pneumatic weapons are surrounded by dispersed metal particles which makes it possible to estimate the shooting distance. Moreover, the bullets fired from the pneumatic weapons leave the muzzle face imprint on certain target materials. PMID:26036066

  17. 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。

  18. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... 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...

  19. 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.

  20. Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

    International Nuclear Information System (INIS)

    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 ρ0 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Amy C. Keller

    2016-01-01

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

  6. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    Science.gov (United States)

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-12-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson’s disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the retrieval of mitochondrial ribosome protected fragments (RPFs) we show that the size distribution of wild-type mitochondrial RPFs follows a bimodal distribution peaking at 27 and 33 nucleotides, which is distinct from the 30-nucleotide peak of nuclear RPFs. Their cross-correlation suggests generation of mitochondrial RPFs during ribosome progression. In contrast, RPFs from patient-derived mitochondria mutated in tRNA-Tryptophan are centered on tryptophan codons and reduced downstream, indicating ribosome stalling. Intriguingly, long RPFs are enriched in mutated mitochondria, suggesting they characterize stalled ribosomes. Our findings provide the first model for translation in wild-type and disease-triggering mitochondria.

  7. 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.

  8. 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.

  9. Transcription-independent role for human mitochondrial RNA polymerase in mitochondrial ribosome biogenesis

    OpenAIRE

    Surovtseva, Yulia V; Shadel, Gerald S.

    2013-01-01

    Human mitochondrial RNA polymerase, POLRMT, is required for mitochondrial DNA (mtDNA) transcription and forms initiation complexes with human mitochondrial transcription factor B2 (h-mtTFB2). However, POLRMT also interacts with the paralogue of h-mtTFB2, h-mtTFB1, which is a 12S ribosomal RNA methyltransferase required for small (28S) mitochondrial ribosome subunit assembly. Herein, we show that POLRMT associates with h-mtTFB1 in 28S mitochondrial ribosome complexes that are stable in the abs...

  10. 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.

  11. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Young Sang [College of Natural Sciences, Chungnam National University, Daejeon (Korea, Republic of)

    2011-09-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated {beta}-galactosidase (SA-{beta}-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H{sub 2}O{sub 2}-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H{sub 2}O{sub 2}-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-{beta}-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

  12. Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Shane L Rea

    2007-10-01

    Full Text Available Prior studies have shown that disruption of mitochondrial electron transport chain (ETC function in the nematode Caenorhabditis elegans can result in life extension. Counter to these findings, many mutations that disrupt ETC function in humans are known to be pathologically life-shortening. In this study, we have undertaken the first formal investigation of the role of partial mitochondrial ETC inhibition and its contribution to the life-extension phenotype of C. elegans. We have developed a novel RNA interference (RNAi dilution strategy to incrementally reduce the expression level of five genes encoding mitochondrial proteins in C. elegans: atp-3, nuo-2, isp-1, cco-1, and frataxin (frh-1. We observed that each RNAi treatment led to marked alterations in multiple ETC components. Using this dilution technique, we observed a consistent, three-phase lifespan response to increasingly greater inhibition by RNAi: at low levels of inhibition, there was no response, then as inhibition increased, lifespan responded by monotonically lengthening. Finally, at the highest levels of RNAi inhibition, lifespan began to shorten. Indirect measurements of whole-animal oxidative stress showed no correlation with life extension. Instead, larval development, fertility, and adult size all became coordinately affected at the same point at which lifespan began to increase. We show that a specific signal, initiated during the L3/L4 larval stage of development, is sufficient for initiating mitochondrial dysfunction-dependent life extension in C. elegans. This stage of development is characterized by the last somatic cell divisions normally undertaken by C. elegans and also by massive mitochondrial DNA expansion. The coordinate effects of mitochondrial dysfunction on several cell cycle-dependent phenotypes, coupled with recent findings directly linking cell cycle progression with mitochondrial activity in C. elegans, lead us to propose that cell cycle checkpoint control

  13. Lamin Mutations Accelerate Aging via Defective Export of Mitochondrial mRNAs through Nuclear Envelope Budding.

    Science.gov (United States)

    Li, Yihang; Hassinger, Linda; Thomson, Travis; Ding, Baojin; Ashley, James; Hassinger, William; Budnik, Vivian

    2016-08-01

    Defective RNA metabolism and transport are implicated in aging and degeneration [1, 2], but the underlying mechanisms remain poorly understood. A prevalent feature of aging is mitochondrial deterioration [3]. Here, we link a novel mechanism for RNA export through nuclear envelope (NE) budding [4, 5] that requires A-type lamin, an inner nuclear membrane-associated protein, to accelerated aging observed in Drosophila LaminC (LamC) mutations. These LamC mutations were modeled after A-lamin (LMNA) mutations causing progeroid syndromes (PSs) in humans. We identified mitochondrial assembly regulatory factor (Marf), a mitochondrial fusion factor (mitofusin), as well as other transcripts required for mitochondrial integrity and function, in a screen for RNAs that exit the nucleus through NE budding. PS-modeled LamC mutations induced premature aging in adult flight muscles, including decreased levels of specific mitochondrial protein transcripts (RNA) and progressive mitochondrial degradation. PS-modeled LamC mutations also induced the accelerated appearance of other phenotypes associated with aging, including a progressive accumulation of polyubiquitin aggregates [6, 7] and myofibril disorganization [8, 9]. Consistent with these observations, the mutants had progressive jumping and flight defects. Downregulating marf alone induced the above aging defects. Nevertheless, restoring marf was insufficient for rescuing the aging phenotypes in PS-modeled LamC mutations, as other mitochondrial RNAs are affected by inhibition of NE budding. Analysis of NE budding in dominant and recessive PS-modeled LamC mutations suggests a mechanism by which abnormal lamina organization prevents the egress of these RNAs via NE budding. These studies connect defects in RNA export through NE budding to progressive loss of mitochondrial integrity and premature aging. PMID:27451905

  14. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

    Directory of Open Access Journals (Sweden)

    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  15. Prohibitin 1 modulates mitochondrial stress-related autophagy in human colonic epithelial cells.

    Directory of Open Access Journals (Sweden)

    Arwa S Kathiria

    Full Text Available INTRODUCTION: Autophagy is an adaptive response to extracellular and intracellular stress by which cytoplasmic components and organelles, including damaged mitochondria, are degraded to promote cell survival and restore cell homeostasis. Certain genes involved in autophagy confer susceptibility to Crohn's disease. Reactive oxygen species and pro-inflammatory cytokines such as tumor necrosis factor α (TNFα, both of which are increased during active inflammatory bowel disease, promote cellular injury and autophagy via mitochondrial damage. Prohibitin (PHB, which plays a role in maintaining normal mitochondrial respiratory function, is decreased during active inflammatory bowel disease. Restoration of colonic epithelial PHB expression protects mice from experimental colitis and combats oxidative stress. In this study, we investigated the potential role of PHB in modulating mitochondrial stress-related autophagy in intestinal epithelial cells. METHODS: We measured autophagy activation in response to knockdown of PHB expression by RNA interference in Caco2-BBE and HCT116 WT and p53 null cells. The effect of exogenous PHB expression on TNFα- and IFNγ-induced autophagy was assessed. Autophagy was inhibited using Bafilomycin A(1 or siATG16L1 during PHB knockdown and the affect on intracellular oxidative stress, mitochondrial membrane potential, and cell viability were determined. The requirement of intracellular ROS in siPHB-induced autophagy was assessed using the ROS scavenger N-acetyl-L-cysteine. RESULTS: TNFα and IFNγ-induced autophagy inversely correlated with PHB protein expression. Exogenous PHB expression reduced basal autophagy and TNFα-induced autophagy. Gene silencing of PHB in epithelial cells induces mitochondrial autophagy via increased intracellular ROS. Inhibition of autophagy during PHB knockdown exacerbates mitochondrial depolarization and reduces cell viability. CONCLUSIONS: Decreased PHB levels coupled with dysfunctional

  16. 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...

  17. 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...

  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. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury.

    Science.gov (United States)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei; Yu, Ning; Liu, Jia

    2015-06-01

    The mitochondrial calcium uniporter (MCU) transports free Ca(2+) into the mitochondrial matrix, maintaining Ca(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(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(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.

  20. Platelet mitochondrial membrane potential in Parkinson's disease

    NARCIS (Netherlands)

    Antony, P.M.; Boyd, O.; Trefois, C.; Ammerlaan, W.; Ostaszewski, M.; Baumuratov, A.S.; Longhino, L.; Antunes, L.; Koopman, W.J.H.; Balling, R.; Diederich, N.J.

    2015-01-01

    OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced confli

  1. Mitochondrial transcription: How does it end

    Energy Technology Data Exchange (ETDEWEB)

    J Byrnes; M Garcia-Diaz

    2011-12-31

    The structure of the mitochondrial transcription termination factor (MTERF1) provides novel insight into the mechanism of binding, recognition of the termination sequence and the conformational changes involved in mediating termination. Besides its functional implications, this structure provides a framework to understand the consequences of numerous diseases associated with mitochondrial DNA mutations.

  2. Mitochondrial dynamics in mammalian health and disease.

    Science.gov (United States)

    Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

    2009-07-01

    The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

  3. Mitochondrial Fusion Proteins and Human Diseases

    Directory of Open Access Journals (Sweden)

    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  4. Exercise training improves vascular mitochondrial function.

    Science.gov (United States)

    Park, Song-Young; Rossman, Matthew J; Gifford, Jayson R; Bharath, Leena P; Bauersachs, Johann; Richardson, Russell S; Abel, E Dale; Symons, J David; Riehle, Christian

    2016-04-01

    Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels ofperoxisome proliferative activated receptor-γ coactivator-1αand the downstream targetscytochrome c oxidase subunit IV isoform 1,isocitrate dehydrogenase(Idh)2, andIdh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser(1177)), and suppressed reactive oxygen species generation (allPrespiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID:26825520

  5. Mitochondrial mutations and polymorphisms in psychiatric disorders

    NARCIS (Netherlands)

    V. Sequeira (Vasco); M.V. Martin (Maureen); S.M. Rollins; E.A. Moon (Emily); W.E. Bunney (William E); F. MacCiardi (Fabio); S. Lupoli (Sara); G.D. Smith; J. Kelsoe (John); C.N. Magnan (Christophe); M. van Oven (Mannis); P. Baldi (Pierre); D.C. Wallace; M.P. Vawter (Marquis)

    2012-01-01

    textabstractMitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of m

  6. Mitochondrial transcription: how does it end?

    Science.gov (United States)

    Byrnes, James; Garcia-Diaz, Miguel

    2011-01-01

    The structure of the mitochondrial transcription termination factor (MTERF1) provides novel insight into the mechanism of binding, recognition of the termination sequence and the conformational changes involved in mediating termination. Besides its functional implications, this structure provides a framework to understand the consequences of numerous diseases associated with mitochondrial DNA mutations.

  7. Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.

    Science.gov (United States)

    Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D

    2016-06-01

    Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans. PMID:26567514

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

    Directory of Open Access Journals (Sweden)

    Christian M Hagen

    Full Text Available 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 variants. After elimination of 312 (69.9% non-coding and synonymous variants, a further 109 (24.4% with a global prevalence > 0.1%, three (0.7% haplogroup associated and 19 (2.0% variants with a low predicted in silico likelihood of pathogenicity, three variants: MT-TC: m.5772G>A, MT-TF: m.644A>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.

  9. Measurement of Entrance Skin Dose and Calculation of Effective Dose for Common Diagnostic X-Ray Examinations in Kashan, Iran

    OpenAIRE

    Aliasgharzadeh, Akbar; Mihandoost, Ehsan; Masoumbeigi, Mahboubeh; Salimian, Morteza; Mohseni, Mehran

    2015-01-01

    The knowledge of the radiation dose received by the patient during the radiological examination is essential to prevent risks of exposures. The aim of this work is to study patient doses for common diagnostic radiographic examinations in hospitals affiliated to Kashan University of Medical sciences, Iran. The results of this survey are compared with those published by some national and international values. Entrance surface dose (ESD) was measured based on the exposure parameters used for the...

  10. Causal Effects of Single-Sex Schools on College Entrance Exams and College Attendance: Random Assignment in Seoul High Schools

    OpenAIRE

    Park, Hyunjoon; Behrman, Jere R.; Choi, Jaesung

    2013-01-01

    Despite the voluminous literature on the potentials of single-sex schools, there is no consensus on the effects of single-sex schools because of student selection of school types. We exploit a unique feature of schooling in Seoul—the random assignment of students into single-sex versus coeducational high schools—to assess causal effects of single-sex schools on college entrance exam scores and college attendance. Our validation of the random assignment shows comparable socioeconomic backgroun...

  11. A CASE STUDY IN HUNGARIAN EDUCATION POLITICS: THE 2005 REFORM OF MIDDLE SCHOOL FINAL EXAM AND UNIVERSITY ENTRANCE EXAM

    OpenAIRE

    Lilla BAUER

    2012-01-01

    This study attempts to show how a public policy issue can contribute to abandoning the traditional model of public administration and government in favour of what has been called the model of public administration management and the theory of good governance. The chosen issue is the Hungarian reform of Middle School Final Exam and University Entrance Exam that took place in the course of overarching governments from the initial steps in 1993 until its realization in 2005. As we follow the pro...

  12. An entrance region friction factor model applied to annular seal analysis - Theory versus experiment for smooth and honeycomb seals

    Science.gov (United States)

    Elrod, D.; Nelson, C.; Childs, D.

    1989-01-01

    A friction factor model is developed for the entrance-region of a duct. The model is used in an annular gas seal analysis similar to Nelson's (1984). Predictions of the analysis are compared to experimental results for a smooth-stator/smooth-rotor seal and three honeycomb-stator/smooth-rotor seals. The model predicts a leakage and direct damping well. The model overpredicts the dependence of cross-coupled stiffness on fluid prerotation. The model predicts direct stiffness poorly.

  13. Effect of the heat transfer on the laminar flow in the entrance region of a circular tube

    OpenAIRE

    Mík, Václav

    2003-01-01

    An analytical-numerical model of the velocity and temperature field was created, whose parameters are expressed as functions of the thickness of the hydrodynamic and thermal boundary layers. This model converts the set of specific partial differential equations to a set of ordinary differential equations that are always valid in one of three regions into which the entrance region is divided by above mentioned boundary layers.

  14. Mutant p53 exhibits trivial effects on mitochondrial functions which can be reactivated by ellipticine in lymphoma cells

    OpenAIRE

    Wang, Fei; Liu, Jianfeng; Robbins, Delira; Morris, Kerri; Sit, Amos; Liu, Yong-Yu; Zhao, Yunfeng

    2011-01-01

    Increasing evidence has shown that a fraction of the wild-type (wt) form of the tumor suppressor p53, can translocate to mitochondria due to genotoxic stress. The mitochondrial targets of wt p53 have also been studied. However, whether mutant p53, which exists in 50% of human cancers, translocates to mitochondria and affects mitochondrial functions is unclear. In this study, we used doxorubicin, a chemotherapeutic drug, to treat five human lymphoma cell lines with wt, mutant or deficient in p...

  15. Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

    OpenAIRE

    Tang, Yan; Luo, Binping; Deng, Zhili; Wang, Ben; Liu, Fangfen; Li, Jinmao; SHI, Wei; Xie, Hongfu; Hu, Xingwang; Li, Ji

    2016-01-01

    Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect ...

  16. A numerical investigation of entropy generation in the entrance region of curved pipes at constant wall temperature

    International Nuclear Information System (INIS)

    In this study, developing incompressible viscous flow and heat transfer in the curved pipes are studied numerically to analyze the entropy generation and thermodynamic optimization in the entrance region at a constant wall temperature. The governing equations including continuity, momentum and energy equations are solved using a second order finite difference method based on the projection algorithm. Entropy generation and optimal Reynolds number calculation based on the entropy generation minimization are carried out for two cases considering the two groups of non-dimensional parameters both numerically and analytically. The comparison of the numerical results in the entrance region with the analytical ones in the fully developed region indicates that both solutions predict nearly the same optimal Reynolds numbers, specially, for the first group of the non-dimensional parameters. -- Highlights: → Numerical study of a three dimensional developing incompressible viscous flow in curved pipes with a constant wall temperature. → Entropy generation and optimal Reynolds number calculation based on the entropy generation minimization. → Entrance region are compared with the analytical prediction in the fully developed region. → Prediction of nearly the same optimal Reynolds for developing and fully developed region in curved pipe flows.

  17. 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

  18. The inhibitory effect of cromolyn sodium and ketotifen on Toxoplasma gondii entrance into host cells in vitro and in vivo.

    Science.gov (United States)

    Rezaei, Fatemeh; Ebrahimzadeh, Mohammad Ali; Daryani, Ahmad; Sharif, Mehdi; Ahmadpour, Ehsan; Sarvi, Shahabeddin

    2016-09-01

    Toxoplasma gondii is a protozoan with worldwide distribution and in spite of increasing information about its biology, treatment of toxoplasmosis is restricted to a few drugs and unfortunately using of each of drugs is associated with significant side effects in patients. This study was designed to evaluate the efficacy of cromolyn sodium and ketotifen as alternative drugs for the treatment of toxoplasmosis. In vitro; in case group, concentrations of 1, 5, 10 and 15 µg/ml of ketotifen and cromolyn sodium were added to RPMI medium containing peritoneal macrophages. After 1 h incubation and adding tachyzoites to medium, efficacy rate of these drugs in entrance inhibition of Toxoplasma tachyzoites into macrophages were evaluated after 30 and 60 min. In vivo; case groups received ketotifen and cromolyn sodium with different concentrations at various times. Control groups received none of drugs. We found that in vitro; after 60 min the best efficacy of these drugs in inhibition of cell entrance of Toxoplasma was observed at 15 µg/ml (78.9 ± 1.70 and 91.97 ± 0.37 %, respectively) (P Toxoplasma entry into the cells (P < 0.05). Our findings show that ketotifen and cromolyn sodium are suitable drugs for entrance inhibition of tachyzoites into nucleated cells in vitro and in vivo. PMID:27605827

  19. Potentially diagnostic electron paramagnetic resonance spectra elucidate the underlying mechanism of mitochondrial dysfunction in the deoxyguanosine kinase deficient rat model of a genetic mitochondrial DNA depletion syndrome.

    Science.gov (United States)

    Bennett, Brian; Helbling, Daniel; Meng, Hui; Jarzembowski, Jason; Geurts, Aron M; Friederich, Marisa W; Van Hove, Johan L K; Lawlor, Michael W; Dimmock, David P

    2016-03-01

    A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunction. It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool. PMID:26773591

  20. LHON: Mitochondrial Mutations and More.

    Science.gov (United States)

    Kirches, E

    2011-03-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the 'primary LHON mutations' to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs.

  1. 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.

  2. 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.

  3. Patient entrance skin doses in diagnostic radiology at Groote Schuur Hospital

    International Nuclear Information System (INIS)

    Full text: Assessment and optimization of the radiation dose received by patients in diagnostic radiology are important tasks in radiological protection. Patient exposure assessment is necessary to keeping an awareness of exposure, to establish guidance levels by means of surveys, to use guidance levels as reference to compare with at individual facilities, to apply methods of dose reductions and optimizations of protection and to assess population doses. This survey of patient doses at Groote Schuur Hospital served the following purpose: a) To establish guidance levels; b) To compare doses for the same type of examination, done with different exposure parameters or with different equipment; c) To compare patient exposures for different types of examinations; and d) To assess relative contributions to collective doses from various types of examinations. The need to optimize the protection of patients results from the fact that medical exposures are by far the largest source of radiation exposure. One aid in minimizing unnecessary exposure in diagnostic imaging is through the use of patient exposure guidelines. Radiation protection of patients is based on the application of the two major radiation protection principles, i.e. justification and optimisation. In order to evaluate that procedures are effectively optimised and remain optimised as time passes, it is necessary to establish quantitative indicators regarding the doses delivered. Entrance skin doses were measured for a number of diagnostic examinations. When compared with similar studies in other countries, a large variation in dose was observed, particularly for chest and abdomen examinations. Actions taken in other countries which led to a significant dose reduction will also be presented. In summary, it seems that it is possible to develop reference values for a wide range of common examinations and use them as investigation levels. (author)

  4. Assessment of entrance surface dose and health risk from common radiology examinations in Iran

    International Nuclear Information System (INIS)

    Medical X-ray exposures are the largest man-made source of population exposure to ionising radiation in many countries. Although information on medical exposure is already incorporated into national legislative documents, in Isfahan there is no data on the assessment of patient's entrance surface dose (ESD) and the health risk from conventional radiography in daily clinical practice. The aim of this study was to investigate ESDs and the consequent health risk for the patients undergoing routine X-ray procedures in hospitals under the control of Isfahan University of Medical Sciences, Iran, in year 2011. The values of ESDs were measured for common radiographical examinations with the highest absorbed dose to the patient in seven hospitals (Alzahra, Ashrafi-Khomeini-shahr, Feyz, Isabne-Maryam, Kashani, Nour-Aliasghar and Seyed-Al Shohada) and six stationary X-ray machines (General Electric, USA; Phillips, The Netherlands; Siemens, Germany; Shimadzu (Japan)); Toshiba (Japan)) and Varian, USA). The results of the ESD measurements as well as the calculated effective dose values between different X-ray examinations showed values significantly greater than those recorded in some other countries especially for the high tube potential technique (such as the skull) by factors of 2.5-5.0. Based on the fatality risk of 5 % per sievert, it was estimated that, for chest and skull examinations approximately two (40.18 person-Sv x 5 % per sievert) and one (2.53 person-Sv x 5 % per sievert) cases of health risk, respectively, may in the future be attributable to diagnostic X rays done in year 2011 in Isfahan. Efforts should be taken to further lower patient doses while securing image quality. The need to provide relevant education and training to staff in the radiology sections is of utmost importance. (authors)

  5. Mitochondrial uptake of thiamin pyrophosphate: physiological and cell biological aspects.

    Directory of Open Access Journals (Sweden)

    Veedamali S Subramanian

    Full Text Available Mammalian cells obtain vitamin B1 (thiamin from their surrounding environment and convert it to thiamin pyrophosphate (TPP in the cytoplasm. Most of TPP is then transported into the mitochondria via a carrier-mediated process that involves the mitochondrial thiamin pyrophosphate transporter (MTPPT. Knowledge about the physiological parameters of the MTPP-mediated uptake process, MTPPT targeting and the impact of clinical mutations in MTPPT in patients with Amish lethal microcephaly and neuropathy and bilateral striatal necrosis are not fully elucidated, and thus, were addressed in this study using custom-made (3H-TPP as a substrate and mitochondria isolated from mouse liver and human-derived liver HepG2 cells. Results showed (3H-TPP uptake by mouse liver mitochondria to be pH-independent, saturable (Km = 6.79±0.53 µM, and specific for TPP. MTPPT protein was expressed in mouse liver and HepG2 cells, and confocal images showed a human (hMTPPT-GFP construct to be targeted to mitochondria of HepG2 cells. A serial truncation analysis revealed that all three modules of hMTPPT protein cooperated (although at different levels of efficiency in mitochondrial targeting rather than acting autonomously as independent targeting module. Finally, the hMTPPT clinical mutants (G125S and G177A showed proper mitochondrial targeting but displayed significant inhibition in (3H-TPP uptake and a decrease in level of expression of the MTPPT protein. These findings advance our knowledge of the physiology and cell biology of the mitochondrial TPP uptake process. The results also show that clinical mutations in the hMTPPT system impair its functionality via affecting its level of expression with no effect on its targeting to mitochondria.

  6. Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

    2011-01-21

    Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

  7. Complex Mutation and Weak Selection together Determined the Codon Usage Bias in Bryophyte Mitochondrial Genomes

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Jing Liu; Liang Jin; Xue-Ying Feng; Jian-Qun Chen

    2010-01-01

    Mutation and selection are two major forces causing codon usage biases. How these two forces influence the codon usages in green plant mitochondrial genomes has not been well investigated. In the present study, we surveyed five bryophyte mitochondrial genomes to reveal their codon usagepatterns as well as the determining forces. Three interesting findings were made. First, comparing to Chara vulgaris, an algal species sister to all extant land plants, bryophytes have more G, C-ending codon usages in their mitochondrial genes. This is consistent with the generally higher genomic GC content in bryophyte mitochondria, suggesting an increased mutational pressure toward GC. Second, as indicated by Wright's Nc-GC3s plot, mutation, not selection, is the major force affecting codon usages of bryophyte mitochondrial genes. However, the real mutational dynamics seem very complex. Context-dependent analysis indicated that nucleotide at the 2nd codon position would slightly affect synonymous codon choices. Finally, in bryophyte mitochondria, tRNA genes would apply a weak selection force to finetune the synonymous codon frequencies, as revealed by data of Ser4-Pro-Thr-Val families. In summary,complex mutation and weak selection together determined the codon usages in bryophyte mitochondrial genomes.

  8. Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Lamiaa A Ahmed

    Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

  9. Strategy to factors from the investigation on clinical practice and entrance examination for admission to postgraduate of medical students%医学本科生临床实习与考研的现状调查及对策

    Institute of Scientific and Technical Information of China (English)

    李萍; 任佰玲; 王德斌

    2011-01-01

    Objective To analysis attitude on clinical practice and Entrance examination for admission to postgraduate of medical students , then discuss how to deal with the relationship between clinical practice and entrance examination for admission to postgraduate, aim to improve the quality of clinical practice. Methods Data came by anonymous questionnaire,using EXCEL to processing the data. Results 76% medical students want to get admission to postgraduate , 74% medical students think equally important between clinical practice and Entrance examination for admission to postgraduate, in order to get admission to postgraduate 62% medical students would be abandon clinical practice , 61% medical students think that the greatest harvest was that the practicing ability and clinical skills was improved through clinical practice. Conclusion quality of clinical practice quality is seriously affected by the conflict between clinical practice and Entrance examination for admission to postgraduate, and to get the strategy is in need of social multi-sectoral cooperation.%目的 分析正在实习的医学本科生对考研的态度以及对实习的重视程度,从而进一步探讨如何处理好考研与实习的关系,提高实习质量.方法 采取不记名问卷调查,数据采用EXCEL软件进行处理.结果 76%的医学实习生打算考研,74%的医学实习生认为考研与实习都重要,62%的医学实习生认为为了考研可以放弃一部分临床实习或完全放弃实习,61%的医学实习生认为通过实习,收获最大的是提高临床技能操作能力.结论 考研与实习的冲突严重影响了实习质量,需要社会多部门合作提出对策.

  10. Diagnosing Mitochondrial Disorder without Sophisticated Means

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2015-10-01

    Full Text Available Mitochondrial disorders (MIDs require biochemical or genetic investigations for being diagnosed. In some cases, however, the diagnosis can be suspected upon the syndromic phenotype or upon clinical presentation and family history, as in the following case. The patient was a 74-year-old male admitted for worsening of pre-existing left-sided ptosis and ophthalmoparesis after a birthday party. The history was positive for arterial hypertension, hypertrophic cardiomyopathy with systolic dysfunction, diabetes-type 2, mild renal insufficiency, thyroiditis, and polyneuropathy. Instrumental investigations additionally revealed hepatopathy, hyperlipidemia, hyperuricemia, bifascicular block, white matter lesions, and subacute stroke. Systolic dysfunction resolved upon adequate cardiac treatment. On hospital day 11 the patient suddenly developed asystole. He was successfully resuscitated but died a few hours later from acute myocardial infarction. Surprisingly, a more extensive family history was positive for myopathy (patient, brother, daughter, neuropathy (patient, hypoacusis (patient, Parkinson syndrome (mother, spasticity (son, diabetes (patient, son, renal failure (patient, and generalized atherosclerosis (patient. The individual and family history was strongly suggestive of an MID. In conclusion, individual and family history may strongly suggest MID. Phenotypic variability may be high between family members affected by an MID. MID may be associated with an increasing atherosclerotic risk lastly resulting in coronary heart disease and death.

  11. Hereditary optic neuropathies share a common mitochondrial coupling defect.

    Science.gov (United States)

    Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

    2008-06-01

    Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.

  12. Effects of Wolbachia on mitochondrial DNA variation in populations of Athetis lepigone (Lepidoptera: Noctuidae) in China

    Science.gov (United States)

    Wolbachia are endosymbiotic bacteria that infect arthropods and incompatibility among strains can affect gene flow within host insect populations, that can result in significant host mitochondrial DNA (MtD) variation. The effects of Wolbachia infection on mtDNA variation was studied in Athetis lepi...

  13. In vivo mitochondrial oxygen tension measured by a delayed fluorescence lifetime technique

    NARCIS (Netherlands)

    E.G. Mik (Egbert); T. Johannes (Tanja); C.J. Zuurbier (Coert Jozef); A. Heinen (Andre); J.H.P.M. Houben-Weerts (Judith); G.M. Balestra (Gianmarco); J. Stap (Jan); J.F. Beek (Johan); C. Ince (Can)

    2008-01-01

    textabstractMitochondrial oxygen tension (mitoPO2) is a key parameter for cellular function, which is considered to be affected under various pathophysiological circumstances. Although many techniques for assessing in vivo oxygenation are available, no technique for measuring mitoPO2in vivo exists.

  14. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

    DEFF Research Database (Denmark)

    Widlund, Anne Lykkegaard; Vang, Ole; Ye, Lan;

    2013-01-01

    compromise the function of mitochondria in cultured muscle cells, implying that defects in bioenergetics might be an unavoidable consequence of targeting mTORC1 in vivo. Therefore, we tested whether rapamycin, at the same doses used to extend lifespan, affects mitochondrial function in skeletal muscle. While...

  15. 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...

  16. 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.

  17. 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...

  18. Complete mitochondrial DNA diversity in Iranians.

    Science.gov (United States)

    Derenko, Miroslava; Malyarchuk, Boris; Bahmanimehr, Ardeshir; Denisova, Galina; Perkova, Maria; Farjadian, Shirin; Yepiskoposyan, Levon

    2013-01-01

    Due to its pivotal geographical location and proximity to transcontinental migratory routes, Iran has played a key role in subsequent migrations, both prehistoric and historic, between Africa, Asia and Europe. To shed light on the genetic structure of the Iranian population as well as on the expansion patterns and population movements which affected this region, the complete mitochondrial genomes of 352 Iranians were obtained. All Iranian populations studied here exhibit similarly high diversity values comparable to the other groups from the Caucasus, Anatolia and Europe. The results of AMOVA and MDS analyses did not associate any regional and/or linguistic group of populations in the Anatolia/Caucasus and Iran region pointing to close genetic positions of Persians and Qashqais to each other and to Armenians, and Azeris from Iran to Georgians. By reconstructing the complete mtDNA phylogeny of haplogroups R2, N3, U1, U3, U5a1g, U7, H13, HV2, HV12, M5a and C5c we have found a previously unexplored genetic connection between the studied Iranian populations and the Arabian Peninsula, India, Near East and Europe, likely the result of both ancient and recent gene flow. Our results for Persians and Qashqais point to a continuous increase of the population sizes from ∼24 kya to the present, although the phase between 14-24 kya is thought to be hyperarid according to the Gulf Oasis model. Since this would have affected hunter-gatherer ranges and mobility patterns and forced them to increasingly rely on coastal resources, this transition can explain the human expansion across the Persian Gulf region. PMID:24244704

  19. Complete mitochondrial DNA diversity in Iranians.

    Directory of Open Access Journals (Sweden)

    Miroslava Derenko

    Full Text Available Due to its pivotal geographical location and proximity to transcontinental migratory routes, Iran has played a key role in subsequent migrations, both prehistoric and historic, between Africa, Asia and Europe. To shed light on the genetic structure of the Iranian population as well as on the expansion patterns and population movements which affected this region, the complete mitochondrial genomes of 352 Iranians were obtained. All Iranian populations studied here exhibit similarly high diversity values comparable to the other groups from the Caucasus, Anatolia and Europe. The results of AMOVA and MDS analyses did not associate any regional and/or linguistic group of populations in the Anatolia/Caucasus and Iran region pointing to close genetic positions of Persians and Qashqais to each other and to Armenians, and Azeris from Iran to Georgians. By reconstructing the complete mtDNA phylogeny of haplogroups R2, N3, U1, U3, U5a1g, U7, H13, HV2, HV12, M5a and C5c we have found a previously unexplored genetic connection between the studied Iranian populations and the Arabian Peninsula, India, Near East and Europe, likely the result of both ancient and recent gene flow. Our results for Persians and Qashqais point to a continuous increase of the population sizes from ∼24 kya to the present, although the phase between 14-24 kya is thought to be hyperarid according to the Gulf Oasis model. Since this would have affected hunter-gatherer ranges and mobility patterns and forced them to increasingly rely on coastal resources, this transition can explain the human expansion across the Persian Gulf region.

  20. The Diversity Evaluation Model of the College Entrance Exam and the Implement Countermeasures about Hunan in New Curriculum Based on Secondary School Education Reform

    OpenAIRE

    Peilin Liu; Xiuying Shen; Huabai Bu

    2014-01-01

    The institution of the college entrance exam has been suffered criticisms and it partly reflects its disadvantages. It’s a desiderate problem that thinking about how to develop the institution which needs to be solved quickly by the administrator. The primary topic of this research is that analyze the fundamental theory of the diversity evaluation model and some successful experience happened in foreign countries. In addition, the research analyzes the structure model of the college entrance ...