WorldWideScience

Sample records for preventing mtdna damage

  1. Preventing thefts and wilful damage

    CERN Multimedia

    DG Unit

    2011-01-01

    The best means of preventing crime is to make it difficult to commit. As the summer holidays begin, in everybody’s interest we advise the following precautions: 1. MONEY, VALUABLES & KEYS Never leave money or objects of value unattended in offices or changing rooms, even locked. Keys and spares must always be taken away or kept in a safe place. Supposedly “safe” hiding places such as drawers, even locked, metal boxes and flower pots, are well known to burglars and should be avoided. Change lock codes regularly. 2. DOORS & WINDOWS Offices, workshops and meeting-rooms, etc. should be locked when vacated. Care should also be taken that windows are properly shut, especially if they are easily accessible from the outside. 3. VANDALISM If you witness an act of vandalism of public or private property, please report all the facts and your observations immediately to the CERN Fire Brigade (74444). 4. REPORTING INCIDENTS Every misdemeanour solved increases the chances of others be...

  2. Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells

    DEFF Research Database (Denmark)

    Akbari, Mansour; Sykora, Peter; Bohr, Vilhelm A

    2015-01-01

    is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders the mitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well...

  3. Vitamin C for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Sram, Radim J., E-mail: sram@biomed.cas.cz [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic); Binkova, Blanka; Rossner, Pavel [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic)

    2012-05-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2 Prime -deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 {mu}mol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with {gamma}-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 {mu}mol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 {mu}mol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  4. Vitamin C for DNA damage prevention

    International Nuclear Information System (INIS)

    Sram, Radim J.; Binkova, Blanka; Rossner, Pavel

    2012-01-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2′-deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 μmol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with γ-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 μmol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 μmol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  5. Sulfur Mustard Damage to Cornea: Preventive Studies

    National Research Council Canada - National Science Library

    Varma, Shambhu

    2004-01-01

    .... A preventive effect has been observed at the level of tissue morphology. Studies are in progress at the level of cellular metabolism, Here, CEES has been used as a representative compound simulating the action of sulfur mustard (HD...

  6. Ultraviolet radiation, sun damage and preventing

    International Nuclear Information System (INIS)

    Johnsen, B.; Christensen, T.; Nilsen, L.T.; Hannevik, M.

    2013-01-01

    The report focuses on the large impact of health damages due to excessive UV exposure from natural sun. The first part of the report gives background information on factors significantly affecting the intensity of UV radiation. The second part gives an overview of health effects related to UV exposure, with recommendations on how to avoid excessive UV exposure and still enjoy the positive sides of outdoor activity. The report is intended to contribute to informational activities about sun exposure as recommended by the World Health Organisation and the World Meteorology Organisation. (Author)

  7. Damage preventing measures for wind turbines. Phase 1- Reliability data

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, Fredrik; Eriksson, Emil; Dahlberg, Magnus

    2010-08-15

    The state of existing reliability and failure data in the public sources has been investigated. The prime goal has been to evaluate the data's usefulness for developing damage preventing measures. Some publicly available databases exist, and the data has been presented in several papers in the literature. The results from the investigation can seem quite negative. Detailed data are lacking and the level of detailed reporting has even been decreasing in recent years. Information on the impact of load condition on failures, which is an important question, are lacking throughout in the statistics. Some components dominate the failure statistics. These are for example the gearboxes, where failures lead to long down times. Failures of the electrical system lead to considerably shorter down times but the failure rate is much higher. Severe rotor failures seem to be rare, but they occur and the consequences can be dramatic. Operators and insurance companies are demanding improved insight in damage collection, maintenance and overall damage preventing measures. Closer cooperation with these parties could be a fruitful way of gathering more useful data. Improvements for future databases are suggested. A structure for damage collection is proposed. Comparing experience of damage preventing measures from other industries, knowledge about the nature of the damage mechanism and current practice in the wind industry will be an important tool in the evaluation of different damage preventing measures. This will be done in the following phases of this project

  8. Preventing thefts and damage to property

    CERN Multimedia

    2013-01-01

    The best means of preventing crime is to make it difficult to commit. As the summer holidays begin, in everybody's interest we advise the following precautions.   1. Money, valuables and keys Never leave money or objects of value unattended in offices or changing rooms, even if they are locked. Keys and spares must always be taken away or kept in a safe place. Supposedly "safe" hiding places such as drawers, even locked ones, metal boxes and flower pots, are well known to burglars and should be avoided. Change lock codes regularly. 2. Doors and windows Offices, workshops and meeting rooms, etc. should be locked when vacated. Care should also be taken that windows are properly shut, especially if they are easily accessible from the outside. 3. Vandalism If you witness an act of vandalism of public or private property, please report all the facts and your observations immediately to the CERN Fire Brigade (74444). 4. Reporting incidents Every misdemeanour solved increase...

  9. Preventing thefts and damage to property

    CERN Document Server

    HR Department

    2007-01-01

    Discouraging thieves is the best way of protecting your property. On the eve of CERN's annual end-of-year closure, in your own interest, that of your colleagues and that of the Organization, we would strongly advise you to take the following precautions: MONEY, VALUABLES & KEYS: Do not leave money or valuables in your office or your lockers. Keys and spare keys must be taken away or kept in a safe place (please avoid supposedly 'safe hiding places' such as drawers, even if they are locked, metal boxes and flowers pots, all of which are well-known to burglars). Change lock codes regularly. Be careful if you have to leave your keys with a third party and make sure that they do not pass them on to anyone else. DOORS & WINDOWS: Lock office, workshop and meeting-room doors, etc. when you leave. Also make sure windows are properly shut, especially if they are easily accessible from outside. REPORTING INCIDENTS: Each theft solved could prevent another from be...

  10. PREVENTING THEFTS AND DAMAGE TO PROPERTY

    CERN Document Server

    2006-01-01

    Discouraging thieves is the best way of protecting your property. On the eve of CERN's annual end-of-year closure, in your own interest, that of your colleagues and that of the Organization, we would strongly advise you to take the following precautions: MONEY, VALUABLES & KEYS: Do not leave money or valuables in your office or your lockers. Keys and spare keys must be taken away or kept in a safe place (please avoid supposedly 'safe hiding places' such as drawers, even if they are locked, metal boxes and flowers pots, all of which are well-known to burglars). Change lock codes regularly. Be careful if you have to leave your keys with a third party and make sure that they do not pass them on to anyone else. DOORS & WINDOWS: Lock office, workshop and meeting-room doors, etc. when you leave. Also make sure windows are properly shut, especially if they are easily accessible from outside. REPORTING INCIDENTS: Each theft solved could prevent another from being perpetrated. Please report thef...

  11. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

    Science.gov (United States)

    Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

  12. 77 FR 19799 - Pipeline Safety: Pipeline Damage Prevention Programs

    Science.gov (United States)

    2012-04-02

    ... rates translate to increased public and worker safety and decreased repair and outage costs for pipeline... April 2, 2012 Part III Department of Transportation Pipeline and Hazardous Materials Safety Administration 49 CFR Parts 196 and 198 Pipeline Safety: Pipeline Damage Prevention Programs; Proposed Rule #0;#0...

  13. Preventing organ damage by genetic testing for hereditary ...

    African Journals Online (AJOL)

    Haemochromatosis can be prevented by regular blood donation or phlebotomy and therefore detection of a genetic predisposition at an early age, before irreversible damage to cardiac, hepatic and endocrine tissue occurs, represents an important clinical goal. South African Family Practice Vol. 47(2) 2005: 44-45 ...

  14. Metformin Treatment Prevents Sedentariness Related Damages in Mice

    Directory of Open Access Journals (Sweden)

    Pamela Senesi

    2016-01-01

    Full Text Available Metformin (METF, historical antihyperglycemic drug, is a likely candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance, and obesity. Skeletal muscle is a highly adaptable tissue, capable of hypertrophy response to resistance training and of regeneration after damage. Aims of this work were to investigate METF ability to prevent sedentariness damage and to enhance skeletal muscle function. Sedentary 12-week-old C57BL/6 mice were treated with METF (250 mg/kg per day, in drinking water for 60 days. METF role on skeletal muscle differentiation was studied in vitro using murine C2C12 myoblasts. Muscular performance evaluation revealed that METF enhanced mice physical performance (Estimated VO2max. Biochemical analyses of hepatic and muscular tissues indicated that in liver METF increased AMPK and CAMKII signaling. In contrast, METF inactivated ERKs, the principal kinases involved in hepatic stress. In skeletal muscle, METF activated AKT, key kinase in skeletal muscle mass maintenance. In in vitro studies, METF did not modify the C2C12 proliferation capacity, while it positively influenced the differentiation process and myotube maturation. In conclusion, our novel results suggest that METF has a positive action not only on the promotion of healthy aging but also on the prevention of sedentariness damages.

  15. Communication and preventing damage in the internet use

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Machado

    2013-06-01

    Full Text Available Introduction: The bank communications have done intensive use of new technologies and contents, case of net banking, which creates new possibilities and relationships with the bank customer. He is a consumer who is encouraged to know the services offered by the new channels, to use these attributes, but if he detects restrictions of information or miscommunication, manifests itself in some way. Many consumers are dealing with fraud or damage caused by the virtual access system provided by banks. This context presents innovations in the communication system played by banks and consumers mediated by the internet.Objectives: To describe the bank communication oriented to prevent damage when their websites are used by consumers.Methodology: It was searched websites of banks Bradesco, Itaú and Banco do Brasil, besides an opinion poll with 130 users of these net banking.Results: The banks offer specific and non-standardized spaces on their websites to prevent damage to the consumer in using the net banking, as too customers use such services only partially.Conclusion: The results cannot be generalized, thus this study serves as a step for that the further works might develop the study object presented in order to measure with greater scope and representativeness the management of prevention of damage to the consumer in the net banking context.

  16. Techniques for preventing damage to high power laser components

    International Nuclear Information System (INIS)

    Stowers, I.F.; Patton, H.G.; Jones, W.A.; Wentworth, D.E.

    1977-09-01

    Techniques for preventing damage to components of the LASL Shiva high power laser system were briefly presented. Optical element damage in the disk amplifier from the combined fluence of the primary laser beam and the Xenon flash lamps that pump the cavity was discussed. Assembly and cleaning techniques were described which have improved optical element life by minimizing particulate and optically absorbing film contamination on assembled amplifier structures. A Class-100 vertical flaw clean room used for assembly and inspection of laser components was also described. The life of a disk amplifier was extended from less than 50 shots to 500 shots through application of these assembly and cleaning techniques

  17. Prevention of damage and 'residual risk' in nuclear power laws

    International Nuclear Information System (INIS)

    Greipl, C.

    1992-01-01

    The concept of prevention of damage within the framework of nuclear power laws includes averting danger for the protection of third parties and preventing risks for the partial protection of third parties with the proviso that still a desire to use the concept 'residual risk' in addition, it should be limited, on the grounds of what can be reasonably expected, to those risks which cannot be reduced any further by the government, i.e. to risks which the public in general and third parties ('actually') must accept. In the future, questions regarding safety systems should be taken into account exclusively withing the context of 'what is necessary for protection against damage in keeping with the latest developments in science and technology' and not at the discretion of the law in denying permission according to Article 7 Paragraph 2 Atomic Energy Law. (orig.) [de

  18. Are all phytochemicals useful in the preventing of DNA damage?

    Science.gov (United States)

    Bacanlı, Merve; Aydın, Sevtap; Başaran, A Ahmet; Başaran, Nurşen

    2017-11-01

    Phytochemicals derived from natural plants have been used commonly for the prevention and/or treatment of different diseases due to the belief of their safety. Many plant species synthesize toxic chemicals. New natural chemicals are being discovered but their toxic effects are unknown. Phytochemicals have been regarded as possible antioxidants. But on the other hand it is suggested that various phenolic antioxidants can display pro-oxidant properties at high doses. In this review, the role of some phytochemicals (epigallocathecin gallate, carvacrol, galangin, limonene, lycopene, naringin, puerarin, terpinene, thymol and ursolic acid) on the prevention of DNA damage will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage.

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P; Morales-Nebreda, Luisa; Cheng, Yuan; Hogan, Erin; Yeldandi, Anjana; Chi, Monica; Piseaux, Raul; Ridge, Karen; Michael Hart, C; Chandel, Navdeep; Scott Budinger, G R; Kamp, David W

    2016-12-01

    Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Crocidolite asbestos (100µg/50µL), TiO 2 (negative control), bleomycin (0.025 units/50µL), or PBS was instilled intratracheally in 8-10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role

  20. Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

    Directory of Open Access Journals (Sweden)

    Simón Quetzalcoatl Rodríguez-Lara

    2016-01-01

    Full Text Available Ischemia/reperfusion (I/R lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states.

  1. Bee products prevent agrichemical-induced oxidative damage in fish.

    Directory of Open Access Journals (Sweden)

    Daiane Ferreira

    Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

  2. Bee Products Prevent Agrichemical-Induced Oxidative Damage in Fish

    Science.gov (United States)

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; Santos da Rosa, João Gabriel; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

    2013-01-01

    In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L−1 of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased. PMID:24098336

  3. Skin penetration and UV-damage prevention by nanoberries.

    Science.gov (United States)

    Bucci, Paula; Prieto, María Jimena; Milla, Laura; Calienni, María Natalia; Martinez, Luis; Rivarola, Viviana; Alonso, Silvia; Montanari, Jorge

    2017-10-03

    Ethanolic extract from blueberry (Vaccinium myrtillus) is rich in anthocyanins and thus exhibits antioxidant activity. On the other hand, ultradeformable liposomes are capable of penetrating to the impermeable barrier of skin. Nanoberries are ultradeformable liposomes carrying blueberry extract. In this study, their capacity to penetrate the stratum corneum and photodamage prevention were tested, with the aim of developing a topical formulation for skin protection from environmental damage. Nanoberries were prepared by lipid film resuspension with ethanolic extract from blueberry, followed by sonication and incorporation to a gel. Size, zeta potential, deformability, rheology, and viscoelasticity were determined. Toxicity was assessed in vivo in zebrafish model, while in vitro cytotoxicity assay was performed on HaCaT and HEK-293T cell lines. Skin penetration was evaluated with the Saarbrücken penetration model followed by tape stripping, cryosection, or optical sectioning. UV-damage protection and photoprotection were determined by ad hoc methods with UVA, UVB, and UVC radiation on HaCaT cells. Wound assay was performed on HaCaT cells. Nanoberries of about 100 nm, with differential elastic properties, did penetrate the stratum corneum, with low toxicity. When HaCaT cells were exposed to UV radiation in the presence of nanoberries, their viability was maintained. Nanoberries could be effective to protect the skin from sun photodamage. © 2017 Wiley Periodicals, Inc.

  4. Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

    Science.gov (United States)

    Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

    2016-01-01

    Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

  5. Alphavirus Encephalomyelitis: Mechanisms and Approaches to Prevention of Neuronal Damage.

    Science.gov (United States)

    Griffin, Diane E

    2016-07-01

    Mosquito-borne viruses are important causes of death and long-term neurologic disability due to encephalomyelitis. Studies of mice infected with the alphavirus Sindbis virus have shown that outcome is dependent on the age and genetic background of the mouse and virulence of the infecting virus. Age-dependent susceptibility reflects the acquisition by neurons of resistance to virus replication and virus-induced cell death with maturation. In mature mice, the populations of neurons most susceptible to infection are in the hippocampus and anterior horn of the spinal cord. Hippocampal infection leads to long-term memory deficits in mice that survive, while motor neuron infection can lead to paralysis and death. Neuronal death is immune-mediated, rather than a direct consequence of virus infection, and associated with entry and differentiation of pathogenic T helper 17 cells in the nervous system. To modulate glutamate excitotoxicity, mice were treated with an N-methyl-D-aspartate receptor antagonist, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists or a glutamine antagonist. The N-methyl-D-aspartate receptor antagonist MK-801 protected hippocampal neurons but not motor neurons, and mice still became paralyzed and died. α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists GYKI-52466 and talampanel protected both hippocampal and motor neurons and prevented paralysis and death. Glutamine antagonist 6-diazo-5-l-norleucine protected hippocampal neurons and improved memory generation in mice surviving infection with an avirulent virus. Surprisingly, in all cases protection was associated with inhibition of the antiviral immune response, reduced entry of inflammatory cells into the central nervous system, and delayed virus clearance, emphasizing the importance of treatment approaches that include prevention of immunopathologic damage.

  6. Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

    Science.gov (United States)

    Furda, Amy M.; Marrangoni, Adele M.; Lokshin, Anna; Van Houten, Bennett

    2013-01-01

    Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60 min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60 min treatment with 2 mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. PMID:22766155

  7. Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter

    2012-01-01

    Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence...... indicates that CSB is present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We report an increase in metabolism in the CSB(m/m) mouse model and CSB-deficient cells. Mitochondrial content is increased in CSB-deficient cells, whereas autophagy is down-regulated, presumably as a result...... of defects in the recruitment of P62 and mitochondrial ubiquitination. CSB-deficient cells show increased free radical production and an accumulation of damaged mitochondria. Accordingly, treatment with the autophagic stimulators lithium chloride or rapamycin reverses the bioenergetic phenotype of CSB...

  8. DNA Damage, Fruits and Vegetables and Breast Cancer Prevention

    National Research Council Canada - National Science Library

    Thompson, Henry

    2000-01-01

    The purpose of this project is to evaluate the effect(s) of increasing fruit and vegetable intake on oxidative DNA damage and lipid peroxidation in a population of women at elevated risk for breast cancer...

  9. DNA Damage, Fruits and Vegetables and Breast Cancer Prevention

    National Research Council Canada - National Science Library

    Thompson, Henry

    2003-01-01

    The purpose of this project was to evaluate the effect(s) of increasing fruit and vegetable intake on oxidative DNA damage and lipid peroxidation in a population of women at elevated risk for breast cancer...

  10. DNA Damage, Fruits and Vegetables and Breast Cancer Prevention

    National Research Council Canada - National Science Library

    Thompson, Henry

    2002-01-01

    The purpose of this project is to evaluate the effect(s) of increasing fruit and vegetable intake on oxidative DNA damage and lipid peroxidation in a population of women at elevated risk for breast cancer...

  11. DNA Damage, Fruits and Vegetables and Breast Cancer Prevention

    National Research Council Canada - National Science Library

    Thompson, Henry

    2001-01-01

    The purpose of this project is to evaluate the effect(s) of increasing fruit and vegetable intake on oxidative DNA damage and lipid peroxidation in a population of women at elevated risk for breast cancer...

  12. Vicair Academy Mattress in the prevention of pressure damage.

    Science.gov (United States)

    Collins, Fiona

    There are many costs associated with the development of pressure ulcers, both in terms of the patient experience and those associated with healing. If patients who are deemed to be at risk are identified and suitable preventive equipment is provided, incidence of pressure ulcer development can be reduced significantly. Pressure-reducing mattresses are primarily used to prevent pressure ulcers from occurring, in conjunction with other preventive measures, such as repositioning. The Vicair Academy Mattress, manufactured by Vicair BV and distributed by Gerald Simonds, uses Vicair's 'dry air' flotation system to offer maximum pressure and shear protection to patients who are at high risk of developing pressure ulcers.

  13. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Doudican, Nicole A; Song, Binwei; Shadel, Gerald S; Doetsch, Paul W

    2005-06-01

    Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

  14. Prevent Eye Damage: Protect Yourself from UV Radiation

    Science.gov (United States)

    ... program uses classroom, school, and community components to develop sustained sun-safe behaviors in children. When choosing sunglasses for children, SunWise, in partnership with Prevent Blindness America, recommends that you: ® Read the labels: Always ...

  15. Melanesian mtDNA complexity.

    Directory of Open Access Journals (Sweden)

    Jonathan S Friedlaender

    Full Text Available Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA sequences from hypervariable regions 1 and 2 (HVR1 and HVR2 from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups. Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at approximately 30-50,000 years before present (YBP, and a second important expansion from Island Southeast Asia/Taiwan during the interval approximately 3,500-8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal Austronesian influence in this region remains unresolved.

  16. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, Pdiabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), Pnerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, Pdiabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Tempol prevents genotoxicity induced by vorinostat: role of oxidative DNA damage.

    Science.gov (United States)

    Alzoubi, Karem H; Khabour, Omar F; Jaber, Aya G; Al-Azzam, Sayer I; Mhaidat, Nizar M; Masadeh, Majed M

    2014-05-01

    Vorinostat is a member of histone deacetylase inhibitors, which represents a new class of anticancer agents for the treatment of solid and hematological malignancies. Studies have shown that these drugs induce DNA damage in blood lymphocytes, which is proposed to be due to the generation of oxidative lesions. The increase in DNA damage is sometimes associated with risk of developing secondary cancer. Thus, finding a treatment that limits DNA damage caused by anticancer drugs would be beneficial. Tempol is a potent antioxidant that was shown to prevent DNA damage induced by radiation. In this study, we aimed to investigate the harmful effects of vorinostat on DNA damage, and the possible protective effects of tempol against this damage. For that, the spontaneous frequency of sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels were measured in cultured human lymphocytes treated with vorinostat and/or tempol. The results showed that vorinostat significantly increases the frequency of SCEs, CAs and 8-OHdG levels in human lymphocytes as compared to control. These increases were normalized by the treatment of cells with tempol. In conclusion, vorinostat is genotoxic to lymphocytes, and this toxicity is reduced by tempol. Such results could set the stage for future studies investigating the possible usefulness of antioxidants co-treatment in preventing the genotoxicity of vorinostat when used as anticancer in human.

  18. Nutriomes and personalised nutrition for DNA damage prevention, telomere integrity maintenance and cancer growth control.

    Science.gov (United States)

    Fenech, Michael F

    2014-01-01

    DNA damage at the base sequence and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability, including telomere integrity and functionality and DNA repair. Using nutrient array systems with high-content analysis diagnostics of DNA damage, cell death and cell growth, it is possible to define, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control. This knowledge can also be used to improve culture systems for cells used in therapeutics such as stem cells to ensure that they are not genetically aberrant when returned to the body. Furthermore, this information could be used to design dietary patterns that deliver the micronutrient combinations and concentrations required for preventing DNA damage by micronutrient deficiency or excess. Using this approach, new knowledge could be obtained to identify the dietary restrictions and/or supplementations required to control specific cancers, which is particularly important given that reliable validated advice is not yet available for those diagnosed with cancer.

  19. Micronutrient special issue: Coenzyme Q{sub 10} requirements for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Schmelzer, Constance, E-mail: schmelzer@fbn-dummerstorf.de [Leibniz Institute for Farm Animal Biology (FBN), Nutritional Physiology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf (Germany); Doering, Frank [University of Kiel, Institute of Human Nutrition and Food Science, Molecular Prevention, Heinrich-Hecht-Platz 10, 24118 Kiel (Germany)

    2012-05-01

    Coenzyme Q{sub 10} (CoQ{sub 10}) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ{sub 10} (ubiquinol, Q{sub 10}H{sub 2}) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ{sub 10} supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ{sub 10} on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ{sub 10} provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ{sub 10} on oxidative stress biomarkers, CoQ{sub 10} intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ{sub 10} on prevention of DNA damage.

  20. Micronutrient special issue: Coenzyme Q10 requirements for DNA damage prevention

    International Nuclear Information System (INIS)

    Schmelzer, Constance; Döring, Frank

    2012-01-01

    Coenzyme Q 10 (CoQ 10 ) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ 10 (ubiquinol, Q 10 H 2 ) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ 10 supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ 10 on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ 10 provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ 10 on oxidative stress biomarkers, CoQ 10 intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ 10 on prevention of DNA damage.

  1. Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage

    Directory of Open Access Journals (Sweden)

    Marco Malaguti

    2013-01-01

    Full Text Available Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely.

  2. Preventive effect of Coriandrum sativum on neuronal damages in pentylentetrazole-induced seizure in rats

    Science.gov (United States)

    Pourzaki, Mojtaba; Homayoun, Mansour; Sadeghi, Saeed; Seghatoleslam, Masoumeh; Hosseini, Mahmoud; Ebrahimzadeh Bideskan, Alireza

    2017-01-01

    Objective: Coriandrum sativum (C. sativum) as a medicinal plant has been pointed to have analgesic, hypnotic and anti-oxidant effects. In the current study, a possible preventive effect of the hydro-alcoholic extract of the plant on neuronal damages was examined in pentylenetetrazole (PTZ) rat model of seizure. Materials and Methods: Forty male rats were divided into five main groups and treated by (1) saline, (2) PTZ: 100 mg/kg PTZ (i.p) and (3-5) 50, 100 and 200 mg/kg of hydro-alcoholic extract of C. sativum during seven consecutive days before PTZ injection. After electrocorticography (ECoG), the brains were removed to use for histological examination. Results: All doses of the extract reduced duration, frequency and amplitude of the burst discharges while prolonged the latency of the seizure attacks (psativum, because of its antioxidant properties, prevents from neuronal damages in PTZ rat model of seizure. PMID:28348967

  3. Preventive effect ofCoriandrum sativumon neuronal damages in pentylentetrazole-induced seizure in rats.

    Science.gov (United States)

    Pourzaki, Mojtaba; Homayoun, Mansour; Sadeghi, Saeed; Seghatoleslam, Masoumeh; Hosseini, Mahmoud; Ebrahimzadeh Bideskan, Alireza

    2017-01-01

    Coriandrum sativum ( C. sativum ) as a medicinal plant has been pointed to have analgesic, hypnotic and anti-oxidant effects. In the current study, a possible preventive effect of the hydro-alcoholic extract of the plant on neuronal damages was examined in pentylenetetrazole (PTZ) rat model of seizure. Forty male rats were divided into five main groups and treated by (1) saline, (2) PTZ: 100 mg/kg PTZ (i.p) and (3-5) 50, 100 and 200 mg/kg of hydro-alcoholic extract of C. sativum during seven consecutive days before PTZ injection. After electrocorticography (ECoG), the brains were removed to use for histological examination. All doses of the extract reduced duration, frequency and amplitude of the burst discharges while prolonged the latency of the seizure attacks (psativum , because of its antioxidant properties, prevents from neuronal damages in PTZ rat model of seizure.

  4. Development of hybrid organic-inorganic optical coatings to prevent laser damage

    International Nuclear Information System (INIS)

    Compoint, Francois

    2015-01-01

    The optical devices (lents, mirrors, portholes...) that are set on the chains of the Laser Megajoule (LMJ) may be damaged by the high energy laser beam especially around the UV wavelength of 351 nm. The damages are micronic craters on the rear of the optics that grows exponentially after each laser shots. The study aims at developing some optical thin coatings on the rear of the optical substrates to prevent the growth of the damage by amortizing the laser shock wave, self-healing the craters that has appeared, or repairing the laser hole after the damage occurs. The thin coatings have been prepared by a sol-gel method by using silica precursor and a polydimethylsiloxane (PDMS) elastomer. The two species reacted together to get a hybrid organic-inorganic Ormosil (organically modified silica) material, by creating a silica network linked to the PDMS species with covalent and hydrogen bounds. The thin layers are obtained from the sol-gel solution by using a dip and spin coating method. The coatings have an excellent optical transmission around the UV (351 nm) wavelength. They also have some self-healing properties by using mechanical (viscoelastic) mechanism and chemical reversible hydrogen bounds action in the materials. The silica-PDMS coatings prove to be resistant to the laser beam at 351 nm, despite some optimizations that still need to be done to reach the sought laser damage threshold. (author) [fr

  5. Concurrent Transient Activation of Wnt/β-Catenin Pathway Prevents Radiation Damage to Salivary Glands

    International Nuclear Information System (INIS)

    Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu; Boyer, Arthur; Liu, Fei

    2012-01-01

    Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/β-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/β-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/β-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/β-catenin pathway could prevent radiation-induced salivary gland dysfunction.

  6. Concurrent Transient Activation of Wnt/{beta}-Catenin Pathway Prevents Radiation Damage to Salivary Glands

    Energy Technology Data Exchange (ETDEWEB)

    Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States); Boyer, Arthur [Department of Radiology, Scott and White Hospital, Temple, Texas (United States); Liu, Fei, E-mail: fliu@medicine.tamhsc.edu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States)

    2012-05-01

    Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.

  7. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

    Science.gov (United States)

    Zugno, A I; Chipindo, H L; Volpato, A M; Budni, J; Steckert, A V; de Oliveira, M B; Heylmann, A S; da Rosa Silveira, F; Mastella, G A; Maravai, S G; Wessler, P G; Binatti, A R; Panizzutti, B; Schuck, P F; Quevedo, J; Gama, C S

    2014-02-14

    Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia. Copyright © 2014. Published by Elsevier Ltd.

  8. Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression.

    Science.gov (United States)

    Finckenberg, Piet; Merasto, Saara; Louhelainen, Marjut; Lindgren, Leena; Vapaatalo, Heikki; Müller, Dominik N; Luft, Friedrich C; Mervaala, Eero M A

    2005-02-01

    Magnesium deficiency promotes vasoconstriction and myocardial damage. Recent studies provide evidence that Ang II mobilizes intracellular Mg through AT1 receptor-mediated pathways. We tested the hypothesis of whether magnesium supplementation prevents Ang II-induced myocardial damage and induction of the profibrotic connective tissue growth factor (CTGF). Four-week-old double transgenic rats harboring human renin and angiotensinogen genes (dTGR) were given dietary magnesium supplementation (0.6%) for 3 weeks. Control dTGR and normotensive Sprague-Dawley (SD) rats received normal diet (Mg 0.2%). Histopathological, immunohistochemical and mRNA analysis were used to detect the treatment-related effects of dietary magnesium in dTGR. Magnesium (Mg) supplementation decreased blood pressure, ameliorated cardiac hypertrophy, protected against the development of Ang II-induced myocardial damage and increased serum ionized Mg2+ concentration (all variables P protein expressions were increased by 300% in dTGR (P supplementation prevented Ang II-induced myocardial CTGF overexpression (P supplementation also improved the therapeutic effects of the calcineurin inhibitor tacrolimus, which produced marked hypomagnesemia when given as monotherapy. Our findings suggest a salutary effect for magnesium supplementation in the treatment of Ang II-induced myocardial complications.

  9. Which is the most preventive measure against tail damage in finisher pigs: tail docking, straw provision or lowered stocking density?

    DEFF Research Database (Denmark)

    Larsen, Mona Lilian Vestbjerg; Andersen, Heidi Mai-Lis; Pedersen, Lene Juul

    2018-01-01

    One challenge of intensive pig production is tail damage caused by tail biting, and farmers often decrease the prevalence of tail damage through tail docking. However, tail docking is not an optimal preventive measure against tail damage and thus, it would be preferable to replace it. The aim...... by scoring the tail of each individual pig. A pen was recorded as a tail damage pen and no longer included in the study if at least one pig in a pen had a bleeding tail wound; thus, only the first incidence of tail damage on pen level was recorded. Data were analysed by a Cox regression for survival analysis...

  10. The Dystrophin-Glycoprotein Complex in the Prevention of Muscle Damage

    Directory of Open Access Journals (Sweden)

    Jessica D. Gumerson

    2011-01-01

    Full Text Available Muscular dystrophies are genetically diverse but share common phenotypic features of muscle weakness, degeneration, and progressive decline in muscle function. Previous work has focused on understanding how disruptions in the dystrophin-glycoprotein complex result in muscular dystrophy, supporting a hypothesis that the muscle sarcolemma is fragile and susceptible to contraction-induced injury in multiple forms of dystrophy. Although benign in healthy muscle, contractions in dystrophic muscle may contribute to a higher degree of muscle damage which eventually overwhelms muscle regeneration capacity. While increased susceptibility of muscle to mechanical injury is thought to be an important contributor to disease pathology, it is becoming clear that not all DGC-associated diseases share this supposed hallmark feature. This paper outlines experimental support for a function of the DGC in preventing muscle damage and examines the evidence that supports novel functions for this complex in muscle that when impaired, may contribute to the pathogenesis of muscular dystrophy.

  11. Prevention of device-related tissue damage during percutaneous deployment of tissue-engineered heart valves.

    Science.gov (United States)

    Stock, U A; Degenkolbe, I; Attmann, T; Schenke-Layland, K; Freitag, S; Lutter, G

    2006-06-01

    Endovascular application of pulmonary heart valves has been recently introduced clinically. A tissue-engineering approach was pursued to overcome the current limitations of bovine jugular vein valves (degeneration and limited longevity). However, deployment of the delicate tissue-engineered valves resulted in severe tissue damage. Therefore the objective of this study was to prevent tissue damage during the folding and deployment maneuver. Porcine pulmonary heart valves, small intestinal submucosa, and ovine carotid arteries were obtained from a slaughterhouse. After dissection and antimicrobial incubation, the valves were trimmed (removal of sinus and most of the muscular ring) to fit into the deployment catheter. The inside (in-stent group, n = 6) or outside (out-stent group, n = 6) of a nitinol stent was covered by an acellular small intestinal submucosa, and the valves were sutured into the stent. The valves were folded, tested for placement in the deployment catheter, and decellularized enzymatically. Myofibroblasts were obtained from carotid artery segments and seeded onto the scaffolds. The seeded constructs were placed in a dynamic bioreactor system and cultured for 16 consecutive days. After endothelial cell seeding, the constructs were folded, deployed, and processed for histology and surface electron microscopy. The valves opened and closed competently throughout the entire dynamic culture. Surface electron microscopy revealed an almost completely preserved tissue in the in-stent group. Stents covered with small intestinal submucosa on the outside, however, showed severe damage. This study demonstrates that small intestinal submucosa covering of the inside of a pulmonary valved stent can prevent stent strut-related tissue damage.

  12. IAEA Regional Workshop on Development and Validation of EOP/AMG for Effective Prevention/Mitigation of Severe Core Damage

    International Nuclear Information System (INIS)

    1999-01-01

    Materials of the IAEA Regional Workshop contain 24 presented lectures. Authors deal with development and validation of emergency operating procedures as well as with accident management guidelines (EOP/AMG) for effective prevention and mitigation of severe core damage

  13. Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

    Directory of Open Access Journals (Sweden)

    Tatyana A. Kuznetsova

    2014-01-01

    Full Text Available An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS. The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6, as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice’s resistance to LPS.

  14. [Urinary incontinence and other pelvic floor damages: ethilogy and prevention strategies].

    Science.gov (United States)

    Amóstegui Azcúe, J M; Ferri Morales, A; Lillo De La Quintana, C; Serra Llosa, M L

    2004-01-01

    Urinary incontinence, as well as additional pelvic floor damage, such as third and fourth degree muscular lacerations, as well as fecal incontinence, genital prolapse or dyspareunia, result from obstetric trauma, and are generally linked to the first delivery. The purpose of this study is to analyze, from a physiotherapeutic point of view, and therefore from the perspective of muscular physiology and biomechanics, why this damage occurs, while studying the birth process and the way it is currently performed in most hospitals in our country. Analysis of the birth process and, in short, of the different types of positions used for the first and second stage of labor, as well as of the care provided for women in the puerperium, leads us to propose a global prevention strategy to be carried out in three stages: --Ante-natal prevention: specific preparation of the pelvic floor and abdominal musculature during pregnancy, using massage techniques and manual stretching of the perineum. In addition, the pregnant woman learns these positions and methods of pushing, which makes the first and second stage of labour easier. An osteopathic treatment of the pelvis joints is performed in order to facilitate their mobility or to liberate blockades, if they exist. --Prevention during labour: During this stage, physiology is respected and manual, position-based and breathing techniques are implemented in order to enhance the protection of the baby and of the pelvic floor. --Postpartum prevention: The action is focused on the pelvic floor, through diaphragmatic and abdominal exercises or postures and, if necessary, osteopathic treatment in the early puerperium, in order to facilitate the correct involution of all soft tissues and the pelvic joints involved in labor. Early specific physiotherapeutic treatment will be proposed for women with functional pathology six weeks after delivery.

  15. Dealing with flood damages: will prevention, mitigation, and ex post compensation provide for a resilient triangle?

    Directory of Open Access Journals (Sweden)

    Cathy Suykens

    2016-12-01

    Full Text Available There is a wealth of literature on the design of ex post compensation mechanisms for natural disasters. However, more research needs to be done on the manner in which these mechanisms could steer citizens toward adopting individual-level preventive and protection measures in the face of flood risks. We have provided a comparative legal analysis of the financial compensation mechanisms following floods, be it through insurance, public funds, or a combination of both, with an empirical focus on Belgium, the Netherlands, England, and France. Similarities and differences between the methods in which these compensation mechanisms for flood damages enhance resilience were analyzed. The comparative analysis especially focused on the link between the recovery strategy on the one hand and prevention and mitigation strategies on the other. There is great potential within the recovery strategy for promoting preventive action, for example in terms of discouraging citizens from living in high-risk areas, or encouraging the uptake of mitigation measures, such as adaptive building. However, this large potential has yet to be realized, in part because of insufficient consideration and promotion of these connections within existing legal frameworks. We have made recommendations about how the linkages between strategies can be further improved. These recommendations relate to, among others, the promotion of resilient reinstatement through recovery mechanisms and the removal of legal barriers preventing the establishment of link-inducing measures.

  16. Somatic mtDNA mutations in lung tissues of pesticide-exposed fruit growers.

    Science.gov (United States)

    Wang, Cheng-Ye; Zhao, Zhong-Bao

    2012-01-27

    Some pesticides have been considered potential chemical mutagens and their widespread use involves the assessment of their potentially hazardous effects. The mitochondrial genome is especially prone to DNA damage and thus can serve as a biomarker to monitor the genotoxicity of pesticides to human DNA. We performed a screening for somatic mutations in lung tissues from pesticide-exposed fruit growers, by direct comparing the entire mtDNA sequences of the lung tissue and the matched peripheral blood from the same individual. A phylogenetic approach and a high standard procedure were utilized to avoid potential errors in data generation and analysis. We observed a significantly increased frequency of mtDNA somatic mutations in lung tissues which had been exposed to pesticides multiple times by inhalation, and the potential biological significance of these mutations was further discussed. The samples represented in this observational study, which has multiple exposures to pesticides, experience a significant greater incidence of mtDNA mutations, suggesting that multiple exposures to pesticides could damage human mtDNA and cause somatic mutations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yi [Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning 110001 (China); Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721 (United States); Tao, Shasha [Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721 (United States); Lian, Fangru [Department of Pathology, University of Arizona, 1501 North Campbell Ave, Tucson, AZ 85724 (United States); Chau, Binh T. [Department of Cellular and Molecular Medicine, The University of Arizona, 1501 North Campbell Ave, Tucson, AZ 85724 (United States); Chen, Jie; Sun, Guifan [Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning 110001 (China); Fang, Deyu [Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Lantz, R. Clark [Department of Cellular and Molecular Medicine, The University of Arizona, 1501 North Campbell Ave, Tucson, AZ 85724 (United States); Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724 (United States); Zhang, Donna D., E-mail: dzhang@pharmacy.arizona.edu [Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721 (United States); Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724 (United States)

    2012-12-15

    Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.

  18. Pathophysiology of repetitive head injury in sports. Prevention against catastrophic brain damage

    International Nuclear Information System (INIS)

    Mori, Tatsuro; Kawamata, Tatsuro; Katayama, Yoichi

    2008-01-01

    The most common head injury in sports is concussion and experiencing multiple concussions in a short period of time sometimes can cause severe brain damage. In this paper, we investigate severe brain damage due to repeated head injury in sports and discuss the pathophysiology of repeated sports injury. The majority of these severe cases are usually male adolescents or young adults that suffer a second head injury before they have recovered from the first head injury. All cases that could be confirmed by brain CT scan after the second injury revealed brain swelling associated with a thin subdural hematoma. We suggested that the existence of subdural hematoma is one of the major causes of brain swelling after repeated head injury in sports. Since repeated concussions occurring within a short period may have a risk for severe brain damage, the diagnosis for initial cerebral concussion should be done appropriately. To prevent catastrophic brain damage, the player who suffered from concussion should not engage in any sports before recovery. The american Academy of Neurology and Colorado Medical Society set a guideline to return to play after cerebral concussion. An international conference on concussion in sports was held at Prague in 2004. The summary and agreement of this meeting was published and the Sports Concussion Assessment Tool (SCAT) was introduced to treat sports-related concussion. In addition, a number of computerized cognitive assessment tests and test batteries have been developed to allow athletes to return to play. It is important that coaches, as well as players and trainers, understand the medical issues involved in concussion. (author)

  19. Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

    Directory of Open Access Journals (Sweden)

    Sarit Suissa

    2009-05-01

    Full Text Available Although the functional consequences of mitochondrial DNA (mtDNA genetic backgrounds (haplotypes, haplogroups have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74% and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%. The variant defining Caucasian haplogroup J (C295T increased the binding of TFAM (Electro Mobility Shift Assay and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1, a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mtDNA

  20. Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

    Science.gov (United States)

    Lapshina, Elena A; Zamaraeva, Maria; Cheshchevik, Vitali T; Olchowik-Grabarek, Ewa; Sekowski, Szymon; Zukowska, Izabela; Golovach, Nina G; Burd, Vasili N; Zavodnik, Ilya B

    2015-06-01

    The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7 mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50  = 4.4 ± 0.4 µg/ml), superoxide anion radicals (IC50  = 2.8 ± 0.3 µg/ml) and hydroxyl radicals (IC50  = 53 ± 4 µg/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2 ± 0.3 µg/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression

    Science.gov (United States)

    Cline, Susan D.

    2012-01-01

    How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression. PMID:22728831

  2. Self-Cyclizing Antioxidants to Prevent DNA Damage Caused by Hydroxyl Radical.

    Science.gov (United States)

    AbdulSalam, Safnas F; Gurjar, Purujit N; Zhu, Haizhou; Liu, Jing; Johnson, Emma S; Kadekaro, Ana Luisa; Landero-Figueroa, Julio; Merino, Edward J

    2017-10-18

    Antioxidant therapy is a promising treatment strategy for protecting DNA from the damage caused by reactive oxygen species (ROS). Here, we report new self-cyclizing antioxidant reagents that are selective for the hydroxyl radical. Our mechanistic investigation revealed that the reagents react with three equivalents of oxidant in a cascade reaction to form a bicyclic final product. Among the reagents synthesized, 1 c showed favorable properties in vitro and in cellular studies. Using As 2 O 3 , which triggers ROS production, we showed that 1 c prevents formation of the guanine oxidation product 2,2,4-triamino-2H-oxazol-5-one-2'-deoxyribonucleoside and lowers cellular levels of reactive oxygen. The described self-cyclizing antioxidants are efficient, flexible, and tunable reagents with the potential to limit toxic oxidative stress. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. USE OF DISC SPRINGS IN A PELLET FUEL MACHINE FOR PRESSURE REGULATION AND PREVENTION OF DAMAGE

    Directory of Open Access Journals (Sweden)

    İsmet Çelik

    2017-05-01

    Full Text Available The use of biomass fuel pellets is becoming widespread as a renewable and environment-friendly energy. Pellet fuels are produced in various pellet machine types. Pellet machines encounter problems such as pressure irregularities and choke at the initial start for different kinds of biomass feedstock. In this study, disc springs are integrated into a vertical axis pellet machine for a pressure regulation and design optimization. Force-deformation and stress-deformation relations of disc springs are investigated using analytical and finite element methods. Pelletizing pressures were calculated based on disc spring force values using the Hertzian stress formula. Utilized disc springs ensured the pressure regulation, production efficiency increase and damage prevention on the die-roller mechanism.

  4. Damage on sliding bearings of internal combustion engines. Damage patterns, causes, prevention; Schaeden an Gleitlagern von Verbrennungsmotoren. Erscheinungsbilder, Ursachen, Vermeidung

    Energy Technology Data Exchange (ETDEWEB)

    Ederer, U.G. [Miba Gleitlager GmbH, Laakrichen (Austria)

    2005-07-01

    Bearing failures are consequences of system deficiencies which cause an inadequate function of the hydrodynamic action and, thereby, too high a friction, at least locally. The bearing overheats, what ultimately leads to its destruction and that of adjacent components. These 'consequential damages' are frequently severe. We identify, therefore, early stages of malfunction, already as 'bearing damage'. In this condition, a diagnosis and remedial measures to avoid total destruction are possible. Typical bearing conditions, possible causes and remedies are described herein. (orig.)

  5. Oxidative Stress Induces Mitochondrial DNA Damage and Cytotoxicity through Independent Mechanisms in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yue Han

    2013-01-01

    Full Text Available Intrinsic oxidative stress through increased production of reactive oxygen species (ROS is associated with carcinogenic transformation, cell toxicity, and DNA damage. Mitochondrial DNA (mtDNA is a natural surrogate to oxidative DNA damage. MtDNA damage results in the loss of its supercoiled structure and is readily detectable using a novel, supercoiling-sensitive real-time PCR method. Our studies have demonstrated that mtDNA damage, as measured by DNA strand breaks and copy number depletion, is very sensitive to exogenous H2O2 but independent of endogenous ROS production in both prostate cancer and normal cells. In contrast, aggressive prostate cancer cells exhibit a more than 10-fold sensitivity to H2O2-induced cell toxicity than normal cells, and a cascade of secondary ROS production is a critical determinant to the differential response. We propose a new paradigm to account for different mechanisms governing cellular oxidative stress, cell toxicity, and DNA damage with important ramifications in devising new techniques and strategies in prostate cancer prevention and treatment.

  6. Solar radiation induced skin damage: review of protective and preventive options.

    Science.gov (United States)

    Svobodová, Alena; Vostálová, Jitka

    2010-12-01

    Solar energy has a number of short- and long-term detrimental effects on skin that can result in several skin disorders. The aim of this review is to summarise current knowledge on endogenous systems within the skin for protection from solar radiation and present research findings to date, on the exogenous options for such skin photoprotection. Endogenous systems for protection from solar radiation include melanin synthesis, epidermal thickening and an antioxidant network. Existing lesions are eliminated via repair mechanisms. Cells with irreparable damage undergo apoptosis. Excessive and chronic sun exposure however can overwhelm these mechanisms leading to photoaging and the development of cutaneous malignancies. Therefore exogenous means are a necessity. Exogenous protection includes sun avoidance, use of photoprotective clothing and sufficient application of broad-spectrum sunscreens as presently the best way to protect the skin. However other strategies that may enhance currently used means of protection are being investigated. These are often based on the endogenous protective response to solar light such as compounds that stimulate pigmentation, antioxidant enzymes, DNA repair enzymes, non-enzymatic antioxidants. More research is needed to confirm the effectiveness of new alternatives to photoprotection such as use of DNA repair and antioxidant enzymes and plant polyphenols and to find an efficient way for their delivery to the skin. New approaches to the prevention of skin damage are important especially for specific groups of people such as (young) children, photosensitive people and patients on immunosuppressive therapy. Changes in public awareness on the subject too must be made.

  7. Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation.

    Science.gov (United States)

    Amaro-Ortiz, Alexandra; Yan, Betty; D'Orazio, John A

    2014-05-15

    Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of "realized" solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

  8. Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

    Directory of Open Access Journals (Sweden)

    Alexandra Amaro-Ortiz

    2014-05-01

    Full Text Available Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

  9. mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences

    OpenAIRE

    Zapico, Sara C.; Ubelaker, Douglas H.

    2013-01-01

    Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exp...

  10. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis

    Science.gov (United States)

    Philpott, Holly T.; O'Brien, Melissa; McDougall, Jason J.

    2017-01-01

    Abstract Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P inflammation was reduced by local CBD treatment (P pain at later time points (P pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain. PMID:28885454

  11. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

    Science.gov (United States)

    Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

    2016-09-01

    Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. Copyright © 2016 the American Physiological Society.

  12. Camptosorus sibiricus rupr aqueous extract prevents lung tumorigenesis via dual effects against ROS and DNA damage.

    Science.gov (United States)

    He, Shugui; Ou, Rilan; Wang, Wensheng; Ji, Liyan; Gao, Hui; Zhu, Yuanfeng; Liu, Xiaomin; Zheng, Hongming; Liu, Zhongqiu; Wu, Peng; Lu, Linlin

    2017-12-16

    Camptosorus sibiricus Rupr (CSR) is a widely used herbal medicine with antivasculitis, antitrauma, and antitumor effects. However, the effect of CSR aqueous extract on B[a]P-initiated tumorigenesis and the underlying mechanism remain unclear. Moreover, the compounds in CSR aqueous extract need to be identified and structurally characterized. We aim to investigate the chemopreventive effect of CSR and the underlying molecular mechanism. A B[a]P-stimulated normal cell model (BEAS.2B) and lung adenocarcinoma animal model were established on A/J mice. In B[a]P-treated BEAS.2B cells, the protective effects of CSR aqueous extract on B[a]P-induced DNA damage and ROS production were evaluated through flow cytometry, Western blot, real-time quantitative PCR, single-cell gel electrophoresis, and immunofluorescence. Moreover, a model of B[a]P-initiated lung adenocarcinoma was established on A/J mice to determine the chemopreventive effect of CSR in vivo. The underlying mechanism was analyzed via immunohistochemistry and microscopy. Furthermore, the new compounds in CSR aqueous extract were isolated and structurally characterized using IR, HR-ESI-MS, and 1D and 2D NMR spectroscopy. CSR effectively suppressed ROS production by re-activating Nrf2-mediated reductases HO-1 and NQO-1. Simultaneously, CSR attenuated the DNA damage of BEAS.2B cells in the presence of B[a]P. Moreover, CSR at 1.5 and 3 g/kg significantly suppressed tumorigenesis with tumor inhibition ratios of 36.65% and 65.80%, respectively. The tumor volume, tumor size, and multiplicity of B[a]P-induced lung adenocarcinoma were effectively decreased by CSR in vivo. After extracting and identifying the compounds in CSR aqueous extract, three new triterpene saponins were isolated and characterized structurally. CSR aqueous extract prevents lung tumorigenesis by exerting dual effects against ROS and DNA damage, suggesting that CSR is a novel and effective agent for B[a]P-induced carcinogenesis. Moreover, by isolating

  13. Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

    Science.gov (United States)

    Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

    2016-06-01

    Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. Copyright © 2016 the American Physiological Society.

  14. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM...

  15. Logging damage in thinned, young-growth true fir stands in California and recommendations for prevention.

    Science.gov (United States)

    Paul E. Aho; Gary Fiddler; Mike. Srago

    1983-01-01

    Logging-damage surveys and tree-dissection studies were made in commercially thinned, naturally established young-growth true fir stands in the Lassen National Forest in northern California. Significant damage occurred to residual trees in stands logged by conventional methods. Logging damage was substantially lower in stands thinned using techniques designed to reduce...

  16. Prevention of H2O2 Induced Oxidative Damages of Rat Testis by Thymus algeriensis.

    Science.gov (United States)

    Guesmi, Fatma; Beghalem, Hamida; Tyagi, Amit K; Ali, Manel Ben; Mouhoub, Ramla Ben; Bellamine, Houda; Landoulsi, Ahmed

    2016-04-01

    We evaluate the effects of Thymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats. Rats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg). The results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls. The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity and significant increase (P<0.05) in MDA concentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2 generated oxidative stress. These results were confirmed by histological architecture examinations. H2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  17. Benefits of Prenatal Taurine Supplementation in Preventing the Onset of Acute Damage in the Mdx Mouse.

    Science.gov (United States)

    Barker, Robert G; Horvath, Deanna; van der Poel, Chris; Murphy, Robyn M

    2017-09-22

    Duchenne Muscular Dystrophy (DMD) is a debilitating muscle wasting disorder with no cure. Safer supplements and therapies are needed to improve the severity of symptoms, as severe side effects are associated with the only effective treatment, corticosteroids. The amino acid taurine has shown promise in ameliorating dystrophic symptoms in mdx mice, an animal model of DMD, however little work is in 21-28 (d)ay animals, the period of natural peak damage. This study compares the effect of prenatal taurine supplementation on tibialis anterior (TA) in situ contractile function, histopathological characteristics and the abundance of Ca 2+ -handling as well as pathologically relevant proteins in non-exercised mdx mice at 28 and 70 d. Supplementation elevated TA taurine content by 25% (peffects in SERCA1, calsequestrin 1 (CSQ1), CSQ2, utrophin and myogenin protein abundances were seen between both 28 and 70 d mdx and mdx taurine-supplemented mice. Considering these findings and that taurine is a relatively cost effective, readily accessible and side effect free dietary supplement, we propose further investigation into taurine supplementation during pregnancy in a protective capacity, reminiscent of folate in the prevention of spinal bifida.

  18. N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage.

    Directory of Open Access Journals (Sweden)

    Hee-Jung Kim

    Full Text Available Ubiquitin C-terminal hydrolase-L1 (UCH-L1 has been proposed as one of the Parkinson's disease (PD related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX with tandem mass spectrometry (MS studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.

  19. Toward sensitive graphene nanoribbon-nanopore devices by preventing electron beam-induced damage.

    Science.gov (United States)

    Puster, Matthew; Rodríguez-Manzo, Julio A; Balan, Adrian; Drndić, Marija

    2013-12-23

    Graphene-based nanopore devices are promising candidates for next-generation DNA sequencing. Here we fabricated graphene nanoribbon-nanopore (GNR-NP) sensors for DNA detection. Nanopores with diameters in the range 2-10 nm were formed at the edge or in the center of graphene nanoribbons (GNRs), with widths between 20 and 250 nm and lengths of 600 nm, on 40 nm thick silicon nitride (SiN(x)) membranes. GNR conductance was monitored in situ during electron irradiation-induced nanopore formation inside a transmission electron microscope (TEM) operating at 200 kV. We show that GNR resistance increases linearly with electron dose and that GNR conductance and mobility decrease by a factor of 10 or more when GNRs are imaged at relatively high magnification with a broad beam prior to making a nanopore. By operating the TEM in scanning TEM (STEM) mode, in which the position of the converged electron beam can be controlled with high spatial precision via automated feedback, we were able to prevent electron beam-induced damage and make nanopores in highly conducting GNR sensors. This method minimizes the exposure of the GNRs to the beam before and during nanopore formation. The resulting GNRs with unchanged resistances after nanopore formation can sustain microampere currents at low voltages (∼50 mV) in buffered electrolyte solution and exhibit high sensitivity, with a large relative change of resistance upon changes of gate voltage, similar to pristine GNRs without nanopores.

  20. Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema.

    Science.gov (United States)

    Maugeri, Grazia; D'Amico, Agata Grazia; Rasà, Daniela Maria; La Cognata, Valentina; Saccone, Salvatore; Federico, Concetta; Cavallaro, Sebastiano; D'Agata, Velia

    2017-08-01

    Diabetic macular edema (DME) is the major cause of vision loss in patients affected by diabetic retinopathy. Hyperglycemia and hypoxia represent the key elements in the progression of these pathologies, leading to breakdown of the blood-retinal barrier (BRB). Caffeine, a psychoactive substance largely consumed in the world, is a nonselective antagonist of adenosine receptors (AR) and it possesses a protective effect in various diseases, including eye pathologies. Here, we have investigated the effect of this substance on BRB integrity following exposure to hyperglycemic/hypoxic insult. Retinal pigmented epithelial cells, ARPE-19, have been grown on semi-permeable supports mimicking an experimental model, in vitro, of outer BRB. Caffeine treatment has reduced cell monolayer permeability after exposure to high glucose and desferoxamine as shown by TEER and FITC-dextran permeability assays. This effect is also mediated through the restoration of membrane's tight junction expression, ZO-1. Moreover, we have demonstrated that caffeine is able to prevent outer BRB damage by inhibiting apoptotic cell death induced by hyperglycemic/hypoxic insult since it downregulates the proapoptotic Bax and upregulates the anti-apoptotic Bcl-2 genes. Although further studies are needed to better comprise the beneficial effect of caffeine, we can speculate that it might be used as an innovative drug for DME treatment. J. Cell. Biochem. 118: 2371-2379, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Design retrofit to prevent damage due to heat transport pump operation under conditions of significant void

    International Nuclear Information System (INIS)

    Lam, K.F.

    1991-01-01

    The purpose of this paper is to provide a general review of certain key design areas which address the safety concerns of HT pump operation under conditions of significant void. To illustrate the challenges confronting designers and analysts, some of the highlights during the design of a protective system to prevent damage to HT piping and pump supports at Bruce NGS 'A' are outlined. The effects of this protective system on reactor safety are also discussed. HI pump operation under conditions of significant void offers a major challenge to designers and analysts to ensure that pump induced vibration and its effects on pump and piping are addressed. For an in-service station the search for a practical solution is often limited by existing. station equipment design and Layout. The diversity of design verification process requires a major commitment of engineering resources to ensure all. safety aspects meet the requirements of regulatory body. Work currently undertaken at Ontario Hydro Research Pump Test Complex on two-phase flow in pumps and piping may provide better prediction of vibration characteristics so that inherent conservativeness in fatigue Life prediction of HI system components can be reduced

  2. Effect of mineral oil, sunflower oil, and coconut oil on prevention of hair damage.

    Science.gov (United States)

    Rele, Aarti S; Mohile, R B

    2003-01-01

    Previously published results showed that both in vitro and in vivo coconut oil (CNO) treatments prevented combing damage of various hair types. Using the same methodology, an attempt was made to study the properties of mineral oil and sunflower oil on hair. Mineral oil (MO) was selected because it is extensively used in hair oil formulations in India, because it is non-greasy in nature, and because it is cheaper than vegetable oils like coconut and sunflower oils. The study was extended to sunflower oil (SFO) because it is the second most utilized base oil in the hair oil industry on account of its non-freezing property and its odorlessness at ambient temperature. As the aim was to cover different treatments, and the effect of these treatments on various hair types using the above oils, the number of experiments to be conducted was a very high number and a technique termed as the Taguchi Design of Experimentation was used. The findings clearly indicate the strong impact that coconut oil application has to hair as compared to application of both sunflower and mineral oils. Among three oils, coconut oil was the only oil found to reduce the protein loss remarkably for both undamaged and damaged hair when used as a pre-wash and post-wash grooming product. Both sunflower and mineral oils do not help at all in reducing the protein loss from hair. This difference in results could arise from the composition of each of these oils. Coconut oil, being a triglyceride of lauric acid (principal fatty acid), has a high affinity for hair proteins and, because of its low molecular weight and straight linear chain, is able to penetrate inside the hair shaft. Mineral oil, being a hydrocarbon, has no affinity for proteins and therefore is not able to penetrate and yield better results. In the case of sunflower oil, although it is a triglyceride of linoleic acid, because of its bulky structure due to the presence of double bonds, it does not penetrate the fiber, consequently resulting

  3. A new material to prevent urethral damage after implantation of artificial devices: an experimental study

    Directory of Open Access Journals (Sweden)

    Salvador Vilar Correia Lima

    Full Text Available ABSTRACT Objective To validate the application of the bacterial cellulose (BC membrane as a protecting barrier to the urethra. Materials and Methods Forty female Wistar rats (four groups of 10: Group 1 (sham, the urethra was dissected as in previous groups and nothing applied around; Group 2, received a 0.7cm strip of the BC applied around the urethra just below the bladder neck; Group 3, received a silicon strip with the same dimensions as in group 2; Group 4, had a combination of 2 and 3 groups being the silicon strip applied over the cellulosic material. Half of the animals in each group were killed at 4 and 8 months. Bladder and urethra were fixed in formalin for histological analysis. Results Inflammatory infiltrates were more intense at 4 months at lymphonodes (80% Grade 2, statistically different in the group 2 compared with groups 1 (p=0.0044 and 3 (p=0.0154. At 8 months, all samples were classified as grade 1 indicating a less intense inflammatory reaction in all groups. In group 2, at 8 months, there was a reduction in epithelial thickness (30±1μm when com-pared to groups 1 (p=0.0001 and 3 (p<0.0001. Angiogenesis was present in groups 2 and 4 and absent in group 3. In BC implant, at 4 and 8 months, it was significant when comparing groups 4 with 1 (p=0.0159. Conclusion BC membrane was well integrated to the urethral wall promoting tissue remodeling and strengthening based on morphometric and histological results and may be a future option to prevent urethral damage.

  4. Resolving the Enigma of the Clonal Expansion of mtDNA Deletions

    Directory of Open Access Journals (Sweden)

    Axel Kowald

    2018-02-01

    Full Text Available Mitochondria are cell organelles that are special since they contain their own genetic material in the form of mitochondrial DNA (mtDNA. Damage and mutations of mtDNA are not only involved in several inherited human diseases but are also widely thought to play an important role during aging. In both cases, point mutations or large deletions accumulate inside cells, leading to functional impairment once a certain threshold has been surpassed. In most cases, it is a single type of mutant that clonally expands and out-competes the wild type mtDNA, with different mutant molecules being amplified in different cells. The challenge is to explain where the selection advantage for the accumulation comes from, why such a large range of different deletions seem to possess this advantage, and how this process can scale to species with different lifespans such as those of rats and man. From this perspective, we provide an overview of current ideas, present an update of our own proposal, and discuss the wider relevance of the phenomenon for aging.

  5. Blood flow restriction prevents muscle damage but not protein synthesis signaling following eccentric contractions

    Science.gov (United States)

    Sudo, Mizuki; Ando, Soichi; Poole, David C; Kano, Yutaka

    2015-01-01

    There is a growing body of evidence to suggest that resistance training exercise combined with blood flow restriction (BFR) increases muscle size and strength in humans. Eccentric contraction (ECC) frequently induces severe muscle damage. However, it is not known whether and to what extent muscle damage occurs following ECC + BFR due to the difficulty of conducting definitive invasive studies. The purpose of this study was to examine muscle fiber damage following ECC + BFR at the cellular level. High-intensity ECC was purposefully selected to maximize the opportunity for muscle damage and hypertrophic signaling in our novel in vivo animal model. Male Wistar rats were assigned randomly to the following groups: ECC and ECC + BFR at varying levels of occlusion pressure (140, 160, and 200 Torr). In all conditions, electrical stimulation was applied to the dorsiflexor muscles simultaneously with electromotor-induced plantar flexion. We observed severe histochemical muscle fiber damage (area of damaged fibers/total fiber area analyzed) following ECC (26.4 ± 4.0%). Surprisingly, however, muscle damage was negligible following ECC + BFR140 (2.6 ± 1.2%), ECC+BFR160 (3.0 ± 0.5%), and ECC + BFR200 (0.2 ± 0.1%). Ribosomal S6 kinase 1 (S6K1) phosphorylation, a downstream target of rapamycin (mTOR)-phosphorylation kinase, increased following ECC + BFR200 as well as ECC. In contrast, S6K1 phosphorylation was not altered by BFR alone. The present findings suggest that ECC combined with BFR, even at high exercise intensities, may enhance muscle protein synthesis without appreciable muscle fiber damage. PMID:26149281

  6. Use of grafting to prevent Hypsipyla grandella (Zeller) (Lepidoptera: Pyralidae) damage to new world Meliaceae species.

    Science.gov (United States)

    Perez, Julian; Eigenbrode, Sanford D; Hilje, Luko; Tripepi, Robert R; Aguilar, Maria E; Mesen, Francisco

    2010-01-01

    The susceptible species Cedrela odorata and Swietenia macrophylla to attack by Hypsipyla grandella (Zeller) larvae were grafted onto the resistant species Khaya senegalensis and Toona ciliata. Six-month-old grafted plants were then compared to their reciprocal grafts and to both intact (non-grafted) and autografted plants for damage due to H. grandella larvae and for their effects on larval performance. Two experiments were conducted: one in which the apical bud of the main plant shoot was inoculated with H. grandella eggs, and the other in which the bud was inoculated with third instars. Damage in each experiment was assessed by the number of frass piles, number and length of tunnels, number of damaged leaves, and damage to the apical bud. Larval performance was evaluated in terms of time to reach pupation and pupal weight and length. In both experiments, plant damage differed significantly among treatments (P < 0.03). Resistant rootstocks conferred resistance to susceptible scions. In both experiments, grafting by itself, regardless of the rootstock and scion combination, also reduced damage caused by H. grandella larvae. Scions of autografted susceptible species had similar resistance to susceptible scions grafted on resistant rootstocks. Few larvae reached pupation, and their pupal weight and length were similar.

  7. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

    OpenAIRE

    Hawthorne, A B; Mahida, Y R; Cole, A T; Hawkey, C J

    1991-01-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin...

  8. Preventing Long-Term Cardiac Damage in Pediatric Patients With Kawasaki Disease.

    Science.gov (United States)

    Williams, Kelly

    Kawasaki disease is currently the leading cause of long-term cardiac damage in pediatric patients in the United States. Kawasaki disease is diagnosed based on symptomatology and by ruling out other etiology. There is a significant need for an improved, standardized treatment protocol for patients diagnosed with Kawasaki disease and a more rapid initiation of treatment for these patients. Decreasing the cardiac damage caused by Kawasaki disease with timely diagnosis and treatment needs be a principal goal. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  9. MtDNA mutagenesis impairs elimination of mitochondria during erythroid maturation leading to enhanced erythrocyte destruction

    NARCIS (Netherlands)

    Ahlqvist, K.J.; Leoncini, S.; Pecorelli, A.; Wortmann, S.B.; Ahola, S.; Forsstrom, S.; Guerranti, R.; Felice, C. De; Smeitink, J.; Ciccoli, L.; Hamalainen, R.H.; Suomalainen, A.

    2015-01-01

    Haematopoietic progenitor cells show special sensitivity to mitochondrial DNA (mtDNA) mutagenesis, which suggests that increased mtDNA mutagenesis could underlie anemias. Here we show that elevated mtDNA mutagenesis in mice with a proof-reading deficient mtDNA polymerase (PolG) leads to incomplete

  10. Prevention of Cold Damage to Container-Grown Longleaf Pine Roots

    Science.gov (United States)

    Richard W. Tinus; Mary Anne Sword; James P. Barnett

    2002-01-01

    When longleaf pine (Pinus palustris Mill.) seedlings are container-grown in open fields, their roots may be exposed to damaging, cold temperatures. Major losses in some nurseries have occurred. Between November 1996 and February 1997, we measured the cold hardiness of container-grown longleaf pine roots by measuring electrolyte leakage (a) of...

  11. Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

    Directory of Open Access Journals (Sweden)

    Paolo Durigutto

    2017-09-01

    Full Text Available Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI. As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

  12. Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia

    NARCIS (Netherlands)

    Vodret, Simone; Bortolussi, Giulia; Schreuder, Andrea B.; Jasprova, Jana; Vitek, Libor; Verkade, Henkjan J.; Muro, Andres F.

    2015-01-01

    Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free

  13. Ganoderma extract prevents albumin-induced oxidative damage and chemokines synthesis in cultured human proximal tubular epithelial cells.

    Science.gov (United States)

    Lai, Kar Neng; Chan, Loretta Y Y; Tang, Sydney C W; Leung, Joseph C K

    2006-05-01

    Ganoderma lucidum (Ganoderma or lingzhi) is widely used as an alternative medicine remedy to promote health and longevity. Recent studies have indicated that components extracted from Ganoderma have a wide range of pharmacological actions including suppressing inflammation and scavenging free radicals. We recently reported that tubular secretion of interleukin-8 (IL-8) induced by albumin is important in the pathogenesis of tubulointerstitial injury in the proteinuric state. In this study, we explored the protective effect of Ganoderma extract (LZ) on albumin-induced kidney epithelial injury. Growth arrested human proximal tubular epithelial cells (PTECs) were incubated with 0.625 to 10 mg/ml human serum albumin (HSA) for up to 72 h. HSA induced DNA damage and apoptosis in PTEC in a dose- and time-dependent manner. Co-incubation of PTEC with 4-64 microg/ml LZ significantly reduced the oxidative damage and cytotoxic effect of HSA in a dose-dependent manner (PGanoderma (16 microg/ml). To explore the components of LZ that exhibited most protective effect in HSA-induced PTEC damages, LZ was further separated into two sub-fractions, LZF1 (MW effective in reducing sICAM-1 released from HSA-activated PTEC whereas the high molecular weight LZ (unfractionated LZ) was more effective in diminishing IL-8 production. Our results suggest that Ganoderma significantly reduces oxidative damages and apoptosis in PTEC induced by HSA. The differential reduction of IL-8 or sICAM-1 released from HSA-activated PTEC by different components of the LZ implicates that components of Ganoderma with different molecular weights could play different roles and operate different mechanisms in preventing HSA-induced PTEC damage.

  14. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan

    2003-01-01

    and neuroprotective proteins that are expressed during EAE and MS. We have shown recently that exogenous administration of Zn-MT-II to Lewis rats with EAE significantly reduced clinical symptoms and the inflammatory response, oxidative stress, and apoptosis of the infiltrated central nervous system areas. We show...... for the first time that Zn-MT-II treatment during EAE significantly prevents demyelination and axonal damage and transection, and stimulates oligodendroglial regeneration from precursor cells, as well as the expression of the growth factors basic fibroblast growth factor (bFGF), transforming growth factor (TGF...

  15. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  16. Iron chelation or anti-oxidants prevent renal cell damage in the rewarming phase after normoxic, but not hypoxic cold incubation.

    NARCIS (Netherlands)

    Bartels-Stringer, M.; Verpalen, J.T.M.; Wetzels, J.F.M.; Russel, F.G.M.; Kramers, C.

    2007-01-01

    It has now been firmly established that, not only ischemia/reperfusion, but also cold itself causes damage during kidney transplantation. Iron chelators or anti-oxidants applied during the cold plus rewarming phase are able to prevent this damage. At present, it is unknown if these measures act only

  17. Evaluation of satellite technology for pipeline route surveillance and the prevention of third party interference damage

    Energy Technology Data Exchange (ETDEWEB)

    Palmer-Jones, Roland; Hopkins, Phil [Penspen Integrity, Newcastle upon Tyne (United Kingdom)]. E-mail: r.palmer-jones@penspen.com; p.hopkins@penspen.com; Fraser, Andy [Integrated Statistical Solutions (United States)]. E-mail: andy@issquared.co.uk; Dezobry, Jerome [Gas de France, Paris (France)]. E-mail: jerome.dezobry@gazdefrance.com; Merrienboer, Hugo Van [Gasunie, Groningen (Netherlands)]. E-mail: H.A.M.van.Merrienboer@gasunie.nl

    2003-07-01

    The damage caused by Third Party Interference (TPI) is one of the major causes of pipeline failures. Consequently, new technologies for identifying activities that may cause damage to our pipelines are constantly being developed. A recently completed project sponsored by a number of pipeline operators has investigated the use of high-resolution satellites for the integrity management of onshore transmission pipelines. The sponsors were BG Technology (on behalf of Transco), Dansk Olie NatureGas, Gasunie, BP, Gaz de France, Distrigas, and the Health and Safety Executive. The project started with a general review of the satellite technologies available and their potential. The study was then focussed on the identification of activities that might result in damage to the pipeline and the potential of high-resolution optical satellites in identifying hazardous activities. A key element of the study was a comparison with existing surveillance systems, which generally involve regular aerial patrols of the pipeline route. To achieve this a survey was carried out to try and evaluate the costs and benefits of existing systems. In addition a simple model for analysing the cost benefit of pipeline surveillance was constructed, and a functional specification for a surveillance system drafted. Finally the performance of the IKONOS 2 high-resolution satellite system was tested in a controlled experiment using targets placed along a pipeline route. The results of this test were compared with a similar test of helicopter-based surveillance carried out by one of the sponsors. (author)

  18. Nickel exposure induces oxidative damage to mitochondrial DNA in Neuro2a cells: the neuroprotective roles of melatonin.

    Science.gov (United States)

    Xu, Shang-Cheng; He, Min-Di; Lu, Yong-Hui; Li, Li; Zhong, Min; Zhang, Yan-Wen; Wang, Yuan; Yu, Zheng-Ping; Zhou, Zhou

    2011-11-01

    Recent studies suggest that oxidative stress and mitochondrial dysfunction play important roles in the neurotoxicity of nickel. Because mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and melatonin can efficiently protect mtDNA against oxidative damage in various pathological conditions, the aims of this study were to determine whether mtDNA oxidative damage was involved in the neurotoxicity of nickel and to assay the neuroprotective effects of melatonin in mtDNA. In this study, we exposed mouse neuroblastoma cell lines (Neuro2a) to different concentrations of nickel chloride (NiCl(2), 0.125, 0.25, and 0.5 mm) for 24 hr. We found that nickel significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, nickel exposure increased mitochondrial 8-hydroxyguanine (8-OHdG) content and reduced mtDNA content and mtDNA transcript levels. Consistent with this finding, nickel was found to destroy mtDNA nucleoid structure and decrease protein levels of Tfam, a key protein component for nucleoid organization. However, all the oxidative damage to mtDNA induced by nickel was efficiently attenuated by melatonin pretreatment. Our results suggest that oxidative damage to mtDNA may account for the neurotoxicity of nickel. Melatonin has great pharmacological potential in protecting mtDNA against the adverse effects of nickel in the nervous system. © 2011 John Wiley & Sons A/S.

  19. Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect.

    Science.gov (United States)

    Sun, Hongnan; Mu, Taihua; Liu, Xingli; Zhang, Miao; Chen, Jingwang

    2014-03-19

    This study aimed to investigate the dealcoholic effect and preventive effect of anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic liver damage (ALD). Seven-week-old male inbred mice were grouped into five groups: control group (without PSPAs and ethanol treatments), model group (with ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body weight), and the mice in all groups were administered intragastrically. Biochemical parameters of serum and liver were determined, and the histopathological changes of liver tissue were also analyzed. Results showed that all tested parameters were ameliorated after consumption of PSPAs. Therefore, PSPAs have preventive effect on acute and subacute ALD. It is suggested that PSPAs could be used as a supplementary reagent during prophylactic and curative managements of ALD.

  20. A PILOT STUDY OF HYDROXYUREA TO PREVENT CHRONIC ORGAN DAMAGE IN YOUNG CHILDREN WITH SICKLE CELL ANEMIA

    Science.gov (United States)

    Thornburg, Courtney D.; Dixon, Natalia; Burgett, Shelly; Mortier, Nicole A.; Schultz, William H.; Zimmerman, Sherri A.; Bonner, Melanie; Hardy, Kristina K.; Calatroni, Agustin; Ware, Russell E.

    2016-01-01

    Background Hydroxyurea improves laboratory parameters and prevents acute clinical complications of sickle cell anemia (SCA) in children and adults, but its effects on organ function remain incompletely defined. Methods To assess the safety and efficacy of hydroxyurea in young children with SCA and to prospectively assess kidney and brain function, 14 young children (mean age 35 months) received hydroxyurea at a mean maximum tolerated dose (MTD) of 28 mg/kg/day. Results After a mean of 25 months, expected laboratory effects included significant increases in hemoglobin, MCV and %HbF along with significant decreases in reticulocytes, absolute neutrophil count, and bilirubin. There was no significant increase in glomerular filtration rate by DTPA clearance or Schwartz estimate. Mean transcranial Doppler (TCD) velocity changes were −25.6 cm/sec (phydroxyurea at MTD is well-tolerated by both children and families, and may prevent chronic organ damage in young children with SCA. PMID:19061213

  1. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    Science.gov (United States)

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-06-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.

  2. Ultraviolet radiation, sun damage and preventing; Ultrafiolett straaling, solskader og forebygging

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, B.; Christensen, T.; Nilsen, L.T.; Hannevik, M.

    2013-03-01

    The report focuses on the large impact of health damages due to excessive UV exposure from natural sun. The first part of the report gives background information on factors significantly affecting the intensity of UV radiation. The second part gives an overview of health effects related to UV exposure, with recommendations on how to avoid excessive UV exposure and still enjoy the positive sides of outdoor activity. The report is intended to contribute to informational activities about sun exposure as recommended by the World Health Organisation and the World Meteorology Organisation. (Author)

  3. Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

    Science.gov (United States)

    Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

    2015-01-01

    We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

  4. Dealing with flood damages : will prevention, mitigation, and ex post compensation provide for a resilient triangle?

    NARCIS (Netherlands)

    Suykens, C.B.R.; Priest, Sally; van Doorn - Hoekveld, W.J.; Thuillier, Thomas; van Rijswick, H.F.M.W.

    2016-01-01

    There is a wealth of literature on the design of ex post compensation mechanisms for natural disasters. However, more research needs to be done on the manner in which these mechanisms could steer citizens toward adopting individual-level preventive and protection measures in the face of flood risks.

  5. Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat

    Science.gov (United States)

    Guo, Zikang; Li, Jiang

    2017-01-01

    Abstract The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells. PMID:29318034

  6. Screening of plant resources with anti-ice nucleation activity for frost damage prevention.

    Science.gov (United States)

    Suzuki, Shingo; Fukuda, Satoshi; Fukushi, Yukiharu; Arakawa, Keita

    2017-11-01

    Previous studies have shown that some polyphenols have anti-ice nucleation activity (anti-INA) against ice-nucleating bacteria that contribute to frost damage. In the present study, leaf disk freezing assay, a test of in vitro application to plant leaves, was performed for the screening of anti-INA, which inhibits the ice nucleation activity of an ice-nucleating bacterium Erwinia ananas in water droplets on the leaf surfaces. The application of polyphenols with anti-INA, kaempferol 7-O-β-glucoside and (-)-epigallocatechin gallate, to the leaf disk freezing assay by cooling at -4--6 °C for 3 h, revealed that both the compounds showed anti-INAs against E. ananas in water droplets on the leaf surfaces. Further, this assay also revealed that the extracts of five plant leaves showed high anti-INA against E. ananas in water droplets on leaf surfaces, indicating that they are the candidate resources to protect crops from frost damage.

  7. Failure of Stainless Steel Welds Due to Microstructural Damage Prevented by In Situ Metallography

    Directory of Open Access Journals (Sweden)

    Juan Manuel Salgado Lopez

    Full Text Available Abstract In stainless steels, microstructural damage is caused by precipitation of chromium carbides or sigma phase. These microconstituents are detrimental in stainless steel welds because they lead to weld decay. Nevertheless, they are prone to appear in the heat affected zone (HAZ microstructure of stainless steel welds. This is particularly important for repairs of industrial components made of austenitic stainless steel. Non-destructive metallography can be applied in welding repairs of AISI 304 stainless steel components where it is difficult to ensure that no detrimental phase is present in the HAZ microstructure. The need of microstructural inspection in repairs of AISI 304 is caused because it is not possible to manufacture coupons for destructive metallography, with which the microstructure can be analyzed. In this work, it is proposed to apply in situ metallography as non-destructive testing in order to identify microstructural damage in the microstructure of AISI 304 stainless steel welds. The results of this study showed that the external surface micrographs of the weldment are representative of HAZ microstructure of the stainless steel component; because they show the presence of precipitated metallic carbides in the grain boundaries or sigma phase in the microstructure of the HAZ.

  8. Dendrosomal nanocurcumin prevents morphine self-administration behavior in rats despite CA1 damage.

    Science.gov (United States)

    Noroozi, Jalaleden; Hassanpour-Ezatti, Majid; Alaei, Hojjat A

    2017-12-01

    Dendrosomal nanocurcumin (DNC) is fabricated from esterification of oleic acid and polyethylene glycol residues with curcumin. DNC has shown antioxidant, neuroprotective, and neurogenesis-enhancing effects. In addition, it can attenuate morphine tolerance. Morphine self-administration is associated with neurodegenerative changes of CA1 neurons in the adult hippocampus. The present study evaluated the effect of DNC pretreatment on morphine self-administration and hippocampal damage. Rats were pretreated with DNC (5 and 10 mg/kg, intraperitoneally) 30 min before a morphine self-administration paradigm performed in 2-h/sessions for 12 days under a FR-1 schedule. Pretreatment with both doses of DNC markedly suppressed morphine intake. Morphine self-administration resulted in a 71% reduction in the number of hippocampal CA1 neurons. DNC (5 mg/kg) pretreatment only marginally improved (by 22%) neuronal loss in this area. The data suggest that the effect of DNC on morphine self-administration is largely independent of the CA1 area. A functional restoration and regulation of reward circuit activity by DNC may reduce the motivation for morphine despite CA1 damage.

  9. Date (Phoenix dactylifera) Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy’s Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond

    Science.gov (United States)

    Yasin, Bibi R.; El-Fawal, Hassan A. N.; Mousa, Shaker A.

    2015-01-01

    This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients. PMID:26694370

  10. Date (Phoenix dactylifera) Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy's Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond.

    Science.gov (United States)

    Yasin, Bibi R; El-Fawal, Hassan A N; Mousa, Shaker A

    2015-12-17

    This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients.

  11. Date (Phoenix dactylifera Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy’s Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond

    Directory of Open Access Journals (Sweden)

    Bibi R. Yasin

    2015-12-01

    Full Text Available This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients.

  12. The experimental study of the preventional effects of drugs to lung radiation damage

    International Nuclear Information System (INIS)

    Tomita, Naoaki

    1977-01-01

    The author experimented on effects of Cepharanthin (CR) and Urokinase (UK) on the lung of rabbits to which 60 Co was irradiated by dividing a total dose of 10,000R into 500R a day. The rabbits irradiated were divided into 3 groups: a group administered ''CR'' (Group A), a group administered ''UK'' (Group B) and a control group (Group C). Body weight, leukocytes and chest x-ray findings were examined, and macroscopic and microscopic findings were discussed immediately and 3 months after irradiation. CR was effective in preventing the decrease of leukocytes and body weight. In the case of 5000R irradiation, an abnormal shadow was not recognized, but in the case of 10,000R irradiation, radiation pneumonitis began to appear immediately after the irradiation, and heart dilation and the shift of mediastinum on the side of irradiation were observed 3 months after that. In Group C, adhesion, hydropericardium and bleeding lesion were observed. In Groups A and B, the preventive effects were noted macroscopically. Group A seemed to show more significant results. In this group, the infiltration of the cells, and the appearance of foamy cells and eosinophyl cells which are characteristic of lung radiation disease were less observed than those in the other groups, and therefore, Group A showed more preventive effect upon inflammation than the other groups. In Group B, the thickness of the wall of the blood vessel tended to be improved 3 months after irradiation. Microthrombosis was not recognized, either. From these results, CR was effective in decreasing the infiltration of the cells, and UK was effective in decreasing the thickness of the wall of the blood vessel and in forming thromboses. Thus, these drugs should be used simultaneously because they had different reaction to the prevention of lung radiation disease. (J.P.N.)

  13. To Investigate the Effect of Colchicine in Prevention of Adhesions Caused by Serosal Damage in Rats

    Directory of Open Access Journals (Sweden)

    İhsan Yıldız

    2015-01-01

    Full Text Available Introduction and Aim. Adhesion formation is a process which starts with an inflammation caused by a number of factors and eventually results in fibrosis. Colchicine prevents adhesion formation which is antifibrous process. The effectivity of colchicine in the prevention of adhesions was investigated. Materials and Methods. A total of 36 rats were equally divided into three groups: (I control group 1 (n=12, (II abrasion group 2 (n=12, and (III abrasion + colchicine group 3 (n=12. Group 1 underwent laparotomy and was orally given physiological serum 2 cc/day for 10 days. In Group 2, injury was created in the cecum serosa following laparotomy and they were orally given physiological serum 2 cc/day for 10 days. In Group 3, injury was created in the cecum serosa following laparotomy and the rats were orally given colchicine 50 mcg kg/day mixed with physiological serum 2 cc/day for 10 days. Laparotomy was performed and adhesions were examined both macroscopically and microscopically. Both macroscopic and microscopic examinations were performed using Zühlke’s score. Results. A significant difference was observed among the adhesion scores of the groups both macroscopically and microscopically. Macroscopic score was lower in group 3 than group 2. Microscopic score was lower in group 3 than group 2. Conclusion. Oral administration of colchicine is effective in the prevention of adhesions.

  14. Indirect assessment of economic damages from the Prestige oil spill: consequences for liability and risk prevention.

    Science.gov (United States)

    Garza, María Dolores; Prada, Albino; Varela, Manuel; Rodríguez, María Xosé Vázquez

    2009-03-01

    The social losses arising from the Prestige oil spill exceed the compensation granted under the IOPC (International Oil Pollution Compensation) system, with losses estimated at 15 times more than the applicable limit of compensations. This is far above the level of costs for which those responsible for hydrocarbons spills are liable. The highest market losses correspond to sectors of extraction, elaboration and commercialisation of seafood. However, damages to non-commercial natural resources could constitute an outstanding group of losses for which further primary data are needed: these losses would only be compensable under the current system by means of a refund for cleaning and restoration costs. Results show that, in Europe, the responsibility for oil spills in maritime transport is limited and unclear. The consequence of this is net social losses from recurrent oil spills and internationally accepted incentives for risky strategies in the marine transport of hydrocarbons.

  15. Clinical implications of duplicated mtDNA in Pearson syndrome.

    Science.gov (United States)

    Muraki, K; Sakura, N; Ueda, H; Kihara, H; Goto, Y

    2001-01-22

    We report on a seven-year-old Japanese boy with Pearson syndrome, which is characterized by refractory sideroblastic anemia with vacuolization of marrow precursors and dysfunction of the exocrine pancreas, and caused by mitochondrial (mt) DNA deletions and duplications. Although analysis with Southern hybridization on his bone marrow cells at age one year or on the muscle at age five years did not detect any duplications of mtDNA, an analysis after death at age seven years detected them in the kidney, heart, and even in the bone marrow. Using long PCR to specifically amplify duplicated mtDNA, we found duplications in all biopsy and postmortem samples, indicating that duplications had been present in the patient since his early life, and that the number of duplications increased with age. The results indicate some dynamism in the mtDNA duplication and that the dynamism may imply clinical importance.

  16. MtDNA ancestry of Rio de Janeiro population, Brazil.

    Science.gov (United States)

    Bernardo, Suellen; Hermida, Rose; Desidério, Márcia; Silva, Dayse A; de Carvalho, Elizeu F

    2014-01-01

    Polymorphism studies concerning HVI and HVII regions of mitochondrial DNA (mtDNA) have improved the understanding of the admixture genetic process related to the occupation of the continents by human population groups. We have analyzed the mtDNA lineages of 190 healthy and maternally unrelated individuals born in the metropolitan region of the Rio de Janeiro city, the capital of the State of Rio de Janeiro, southeastern Brazil. The data showing that 57.9, 25.3 and 16.8 % of the matrilineages found in Rio de Janeiro come from African, Amerindian and European population groups. They are, respectively, in close agreement with historical records which indicate that the admixture population of Brazil is the resulting of interethnic asymmetry crosses between individuals from those population groups. The high proportion of African mtDNA lineages in the population of Rio de Janeiro is in accordance with studies related to other Brazilian states.

  17. MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    Science.gov (United States)

    Stumpf, Jeffrey D; Copeland, William C

    2014-10-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  18. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment.

    Science.gov (United States)

    Lanas, Angel; Scheiman, James

    2007-01-01

    Low-dose aspirin (75-325 mg/day) is widely used for the prevention of cardiovascular disease. However, due to its action on cyclo-oxygenase (COX), aspirin is associated with upper gastrointestinal (GI) side effects including ulcers and bleeding. This was a comprehensive review of the literature available on the side effects associated with low-dose aspirin, together with the available treatment and prevention options, which was based on the authors' expertise in the field and a supplementary PubMed search limited to papers published in English during the last 10 years, up to November 2006. Although the risk of upper GI side effects is smaller with low-dose aspirin compared with non-selective, non-steroidal anti-inflammatory drugs (NSAIDs), it is nevertheless a substantial healthcare issue. Factors associated with an increased risk of upper GI complications during low-dose aspirin therapy include aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of NSAIDs (including COX-2-selective NSAIDs), and Helicobacter pylori infection. Co-administration of a gastroprotective agent such as proton pump inhibitors (PPIs) may be useful for alleviating the upper GI side effects associated with use of low-dose aspirin. Eradication of H. pylori also appears to reduce the risk of these side effects, especially in those at high risk. The use of other antiplatelet agents such as clopidogrel does not seem to provide a safer alternative to low-dose aspirin in at-risk patients. Prophylactic low-dose aspirin therapy is associated with an increased risk of developing upper GI side effects. Administration of a PPI seems the most effective therapy for the prevention and/or relief of such side effects in at-risk patients. H. pylori eradication therapy further reduces the risk of upper GI bleeding in these patients.

  19. Tempol prevents cardiac oxidative damage and left ventricular dysfunction in the PPAR-α KO mouse.

    Science.gov (United States)

    Guellich, Aziz; Damy, Thibaud; Conti, Marc; Claes, Victor; Samuel, Jane-Lise; Pineau, Thierry; Lecarpentier, Yves; Coirault, Catherine

    2013-06-01

    Peroxisome proliferator-activated receptor (PPAR)-α deletion induces a profound decrease in MnSOD activity, leading to oxidative stress and left ventricular (LV) dysfunction. We tested the hypothesis that treatment of PPAR-α knockout (KO) mice with the SOD mimetic tempol prevents the heart from pathological remodelling and preserves LV function. Twenty PPAR-α KO mice and 20 age-matched wild-type mice were randomly treated for 8 wk with vehicle or tempol in the drinking water. LV contractile parameters were determined both in vivo using echocardiography and ex vivo using papillary muscle mechanics. Translational and posttranslational modifications of myosin heavy chain protein as well as the expression and activity of major antioxidant enzymes were measured. Tempol treatment did not affect LV function in wild-type mice; however, in PPAR-α KO mice, tempol prevented the decrease in LV ejection fraction and restored the contractile parameters of papillary muscle, including maximum shortening velocity, maximum extent of shortening, and total tension. Moreover, compared with untreated PPAR-α KO mice, myosin heavy chain tyrosine nitration and anion superoxide production were markedly reduced in PPAR-α KO mice after treatment. Tempol also significantly increased glutathione peroxidase and glutathione reductase activities (~ 50%) in PPAR-α KO mice. In conclusion, these findings demonstrate that treatment with the SOD mimetic tempol can prevent cardiac dysfunction in PPAR-α KO mice by reducing the oxidation of contractile proteins. In addition, we show that the beneficial effects of tempol in PPAR-α KO mice involve activation of the glutathione peroxidase/glutathione reductase system.

  20. Elucidation of mechanism of blood-brain barrier damage for prevention and treatment of vascular dementia.

    Science.gov (United States)

    Ueno, Masaki

    2017-03-28

    . These clearance pathways may play a role in maintenance of the barrier in the entire brain. Obstruction of the passage of fluids through the perivascular drainage and glymphatic pathways as well as damage of the BBB and BCSFB may induce several kinds of brain disorders, such as vascular dementia. In this review, we focus on the relationship between damage of the barriers and the pathogenesis of vascular dementia and introduce recent findings including our experimental data using animal models.

  1. Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

    Science.gov (United States)

    García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

    2012-06-07

    Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

  2. Resveratrol attenuates radiation damage in Caenorhabditis elegans by preventing oxidative stress

    International Nuclear Information System (INIS)

    Ye Kan; Gu Guixiong; Ji Chenbo; Ni Yuhui; Chen Xiaohui; Guo Xirong; Lu Xiaowei; Gao Chunlin; Zhao Yaping

    2010-01-01

    Resveratrol, a member of a class of polyphenolic compounds known as flavonols, has been extensively studied for its anticancer, antiviral, anti-inflammatory, and neuroprotective roles. Caenorhabidits elegans is a well-established animal for investigating responses to radiation. We found that resveratrol may provide protection against hazardous radiation. Pre-treatment with resveratrol extended both the maximum and mean life span of irradiated C. elegans. Resveratrol acted as a strong radical scavenger and regulated superoxide dismutase (SOD) expression. In addition, resveratrol was shown to be capable of alleviating γ-ray radiation exposure-induced reduction in mitochondrial SOD expression. Ultimately, a correlation may exist between dietary intake of trace amounts of resveratrol and anti-aging effects. A specific response mechanism may be activated after the administration of resveratrol in irradiated animals. Our results suggest the protective effect of resveratrol is due to its strong ability to protect from oxidative stress and protective effects in mitochondria. Therefore, resveratrol is potentially an effective protecting agent against irradiative damage. (author)

  3. DNA damage induced by hydroquinone can be prevented by fungal detoxification

    Directory of Open Access Journals (Sweden)

    Pedro Pereira

    2014-01-01

    Full Text Available Hydroquinone is a benzene metabolite with a wide range of industrial applications, which has potential for widespread human exposure; however, the toxicity of hydroquinone on human cells remains unclear. The aims of this study are to investigate the cytotoxicity and genotoxicity of hydroquinone in human primary fibroblasts and human colon cancer cells (HCT116. Low doses of hydroquinone (227-454 μM reduce the viability of fibroblasts and HCT116 cells, determined by resazurin conversion, and induce genotoxic damage (DNA strand breaks, as assessed by alkaline comet assays. Bioremediation may provide an excellent alternative to promote the degradation of hydroquinone, however few microorganisms are known that efficiently degrade it. Here we also investigate the capacity of a halotolerant fungus, Penicillium chrysogenum var. halophenolicum, to remove hydroquinone toxicity under hypersaline condition. The fungus is able to tolerate high concentrations of hydroquinone and can reverse these noxious effects via degradation of hydroquinone to completion, even when the initial concentration of this compound is as high as 7265 μM. Our findings reveal that P. chrysogenum var. halophenolicum efficiently degrade hydroquinone under hypersaline conditions, placing this fungus among the best candidates for the detoxification of habitats contaminated with this aromatic compound.

  4. Omega-3 supplementation can restore glutathione levels and prevent oxidative damage caused by prenatal ethanol exposure.

    Science.gov (United States)

    Patten, Anna R; Brocardo, Patricia S; Christie, Brian R

    2013-05-01

    Prenatal ethanol exposure (PNEE) causes long-lasting deficits in brain structure and function. In this study, we have examined the effect of PNEE on antioxidant capacity and oxidative stress in the adult brain with particular focus on four brain regions known to be affected by ethanol: cerebellum, prefrontal cortex and hippocampus (cornu ammonis and dentate gyrus subregions). We have utilized a liquid diet model of fetal alcohol spectrum disorders that is supplied to pregnant Sprague-Dawley rats throughout gestation. To examine the therapeutic potential of omega-3 fatty acid supplementation, a subset of animals were provided with an omega-3-enriched diet from birth until adulthood to examine whether these fatty acids could ameliorate any deficits in antioxidant capacity that occurred due to PNEE. Our results showed that PNEE caused a long-lasting decrease in glutathione levels in all four brain regions analyzed that was accompanied by an increase in lipid peroxidation, a marker of oxidative damage. These results indicate that PNEE induces long-lasting changes in the antioxidant capacity of the brain, and this can lead to a state of oxidative stress. Postnatal omega-3 supplementation was able to increase glutathione levels and reduce lipid peroxidation in PNEE animals, partially reversing the effects of alcohol exposure, particularly in the dentate gyrus and the cerebellum. This is the first study where omega-3 supplementation has been shown to have a beneficial effect in PNEE, reducing oxidative stress and enhancing antioxidant capacity. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1.

    Science.gov (United States)

    Shichita, Takashi; Ito, Minako; Morita, Rimpei; Komai, Kyoko; Noguchi, Yoshiko; Ooboshi, Hiroaki; Koshida, Ryusuke; Takahashi, Satoru; Kodama, Tatsuhiko; Yoshimura, Akihiko

    2017-06-01

    Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.

  6. Prevention of radiation-induced hepatic damage in Swiss albino mice by Aloe Vera leaf extract

    Directory of Open Access Journals (Sweden)

    Gehlot Prashasnika

    2010-01-01

    Full Text Available The radioprotective effect of the Aloe vera leaf extract was studied in Swiss albino mice against radiation-induced changes in the liver. The mice were treated with 1000 mg/kg of body weight orally, once a day for 15 consecutive days, before exposure to a single dose of gamma radiation (6 Gy, half an hour after the last administration. The irradiation of mice caused a significant elevation in lipid peroxidation followed by a decrease in glutathione, acid phosphatase and alkaline phosphatase. The treatment of mice before irradiation elevated the glutathione, acid phosphatase and alkaline phosphatase, and was accompanied by a decline in lipid peroxidation. Recovery and regeneration from radiation damage were faster in pretreated animals than the animals in the irradiation-only group. The data clearly indicate that the Aloe vera leaf extract significantly reduced the deleterious effects of radiation on the liver and it could be a useful agent in reducing the side effects of therapeutic radiation.

  7. VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema.

    Science.gov (United States)

    Maugeri, Grazia; D'Amico, Agata Grazia; Gagliano, Caterina; Saccone, Salvatore; Federico, Concetta; Cavallaro, Sebastiano; D'Agata, Velia

    2017-05-01

    Diabetic macular edema (DME), characterized by an increase of thickness in the eye macular area, is due to breakdown of the blood-retinal barrier (BRB). Hypoxia plays a key role in the progression of this pathology by activating the hypoxia-inducible factors. In the last years, various studies have put their attention on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in retinal dysfunction. However, until now, no study has investigated their protective role against the harmful combined effect of both hyperglycemia and hypoxia on outer BRB. Therefore, in the present study, we have analyzed the role of these peptides on permeability, restoration of tight junctions expression and inhibition of hyperglycemia/hypoxia-induced apoptosis, in an experimental in vitro model of outer BRB. Our results have demonstrated that the peptides' treatment have restored the integrity of outer BRB induced by cell exposure to hyperglycemia/hypoxia. Their effect is mediated through the activation of phosphoinositide 3 kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling pathways. In conclusion, our study further clarifies the mechanism through which PACAP and VIP perform the beneficial effect on retinal damage induced by hyperglycemic/hypoxic insult, responsible of DME progression. J. Cell. Physiol. 232: 1079-1085, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. An Experimental Investigation On Minimum Compressive Strength Of Early Age Concrete To Prevent Frost Damage For Nuclear Power Plant Structures In Cold Climates

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Kyungtaek; Kim, Dogyeum; Park, Chunjin; Ryu, Gumsung; Park, Jungjun; Lee, Janghwa [Korea Institute Construction Technology, Goyang (Korea, Republic of)

    2013-06-15

    Concrete undergoing early frost damage in cold weather will experience significant loss of not only strength, but also of permeability and durability. Accordingly, concrete codes like ACI-306R prescribe a minimum compressive strength and duration of curing to prevent frost damage at an early age and secure the quality of concrete. Such minimum compressive strength and duration of curing are mostly defined based on the strength development of concrete. However, concrete subjected to frost damage at early age may not show a consistent relationship between its strength and durability. Especially, since durability of concrete is of utmost importance in nuclear power plant structures, this relationship should be imperatively clarified. Therefore, this study verifies the feasibility of the minimum compressive strength specified in the codes like ACI-306R by evaluating the strength development and the durability preventing the frost damage of early age concrete for nuclear power plant. The results indicate that the value of 5 MPa specified by the concrete standards like ACI-306R as the minimum compressive strength to prevent the early frost damage is reasonable in terms of the strength development, but seems to be inappropriate in the viewpoint of the resistance to chloride ion penetration and freeze-thaw. Consequently, it is recommended to propose a minimum compressive strength preventing early frost damage in terms of not only the strength development, but also in terms of the durability to secure the quality of concrete for nuclear power plants in cold climates.

  9. An Experimental Investigation On Minimum Compressive Strength Of Early Age Concrete To Prevent Frost Damage For Nuclear Power Plant Structures In Cold Climates

    International Nuclear Information System (INIS)

    Koh, Kyungtaek; Kim, Dogyeum; Park, Chunjin; Ryu, Gumsung; Park, Jungjun; Lee, Janghwa

    2013-01-01

    Concrete undergoing early frost damage in cold weather will experience significant loss of not only strength, but also of permeability and durability. Accordingly, concrete codes like ACI-306R prescribe a minimum compressive strength and duration of curing to prevent frost damage at an early age and secure the quality of concrete. Such minimum compressive strength and duration of curing are mostly defined based on the strength development of concrete. However, concrete subjected to frost damage at early age may not show a consistent relationship between its strength and durability. Especially, since durability of concrete is of utmost importance in nuclear power plant structures, this relationship should be imperatively clarified. Therefore, this study verifies the feasibility of the minimum compressive strength specified in the codes like ACI-306R by evaluating the strength development and the durability preventing the frost damage of early age concrete for nuclear power plant. The results indicate that the value of 5 MPa specified by the concrete standards like ACI-306R as the minimum compressive strength to prevent the early frost damage is reasonable in terms of the strength development, but seems to be inappropriate in the viewpoint of the resistance to chloride ion penetration and freeze-thaw. Consequently, it is recommended to propose a minimum compressive strength preventing early frost damage in terms of not only the strength development, but also in terms of the durability to secure the quality of concrete for nuclear power plants in cold climates

  10. The approach of the PREFER project to wildfire prevention and damage assessment in the Mediterranean area

    Science.gov (United States)

    Laneve, Giovanni; Fusilli, Lorenzo; Tampellini, Maria Lucia; Vimercati, Marco; Hirn, Barbara; Sebastian-Lopez, Ana; Diagourtas, Dimitri; Eftychidis, Georgios; Clandillon, Stephen; Caspard, Mathilde; Oliveira, Sandra; Lourenco, Luciano

    2015-04-01

    PREFER is a Copernicus Emergency project funded from the 2012 FP7 Space Work Programme, and it is aimed at developing products and services that will contribute to improve the European capacity to respond to the preparedness, prevention, and recovery management steps in the case of forest fire emergency cycle, with focus on the Mediterranean area. It is well known from the most recent reports on state of Europe's forests that the Mediterranean area is particularly affected by uncontrolled forest fires, with a number of negative consequences on ecosystems, such as desertification and soil erosion, and on the local economy. Most likely, the current risks of forest fires will be exacerbated by climate change. In particular, the climate of Southern Europe and the Mediterranean basin is projected to warm at a rate exceeding the global average. Wild fires will therefore remain the most serious threat to Southern European forests. In this situation, the need to collect better information and more knowledge concerning future risks of forest fires and fire prevention in the Mediterranean area is widely recognized to be a major urgent one. As part of the Copernicus programme (i.e. the European Earth Observation Programme), PREFER is based on advanced geo-information products using in particular the earth observation data acquired and developed in the frame of Copernicus. The objective of the PREFER project, started at the end of 2012, 8 partners (from Italy, Portugal, Spain, France and Greece) involved and three years schedule, is the design, development and demonstration of a pre-operational "end-to-end" information service, fully exploiting satellite sensors data and able to support prevention/ preparedness and recovery phases of the Forest Fires emergency cycle in the EU Mediterranean Region. The PREFER information is as general as to be usable in the different countries of the Mediterranean Region, and acts in full complement to already existing services, such as the EC

  11. Free radicals in alcoholic myopathy: indices of damage and preventive studies.

    Science.gov (United States)

    Preedy, Victor R; Adachi, Junko; Asano, Migiwa; Koll, Michael; Mantle, David; Niemela, Onni; Parkkila, Seppo; Paice, Alistair G; Peters, Timothy; Rajendram, Rajkumar; Seitz, Helmut; Ueno, Yasuhiro; Worrall, Simon

    2002-04-15

    Chronic alcoholic myopathy affects up to two-thirds of all alcohol misusers and is characterized by selective atrophy of Type II (glycolytic, fast-twitch, anaerobic) fibers. In contrast, the Type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Alcohol increases the concentration of cholesterol hydroperoxides and malondialdehyde-protein adducts, though protein-carbonyl concentration levels do not appear to be overtly increased and may actually decrease in some studies. In alcoholics, plasma concentrations of alpha-tocopherol may be reduced in myopathic patients. However, alpha-tocopherol supplementation has failed to prevent either the loss of skeletal muscle protein or the reductions in protein synthesis in alcohol-dosed animals. The evidence for increased oxidative stress in alcohol-exposed skeletal muscle is thus inconsistent. Further work into the role of ROS in alcoholic myopathy is clearly warranted.

  12. Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial damage mediated apoptosis in cardiomyoblasts.

    Science.gov (United States)

    Jadaun, Pratiksha; Yadav, Dhananjay; Bisen, Prakash Singh

    2018-04-01

    The current study was undertaken to study the effect of Spirulina platensis (Spirulina) extract on enhanced oxidative stress during high glucose induced cell death in H9c2 cells. H9c2 cultured under high glucose (33 mM) conditions resulted in a noteworthy increase in oxidative stress (free radical species) accompanied by loss of mitochondrial membrane potential, release of cytochrome c, increase in caspase activity and pro-apoptotic protein (Bax). Spirulina extract (1 μg/mL), considerably inhibited increased ROS and RNS levels, reduction in cytochrome c release, raise in mitochondrial membrane potential, decreased the over expression of proapoptotic protein Bax and suppressed the Bax/Bcl2 ratio with induced apoptosis without affecting cell viability. Overall results suggest that Spirulina extract plays preventing role against enhanced oxidative stress during high glucose induced apoptosis in cardiomyoblasts as well as related dysfunction in H9c2 cells.

  13. Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced peroxynitrite mediated damage in diaphragm.

    Science.gov (United States)

    Ozdülger, Ali; Cinel, Ismail; Unlü, Ali; Cinel, Leyla; Mavioglu, Ilhan; Tamer, Lülüfer; Atik, Ugur; Oral, Ugur

    2002-07-01

    Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P<0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.

  14. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

    KAUST Repository

    Caputo, Fanny

    2015-08-20

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields. © The Royal Society of Chemistry 2015.

  15. Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure.

    Science.gov (United States)

    de Souza Machado, Fernanda; Kuo, Jonnsin; Wohlenberg, Mariane Farias; da Rocha Frusciante, Marina; Freitas, Márcia; Oliveira, Alice S; Andrade, Rodrigo B; Wannmacher, Clovis M D; Dani, Caroline; Funchal, Claudia

    2016-12-01

    Acai has been used by the population due to its high nutritional value and its benefits to health, such as its antioxidant properties. The aim of this study was to evaluate the protective effect of acai frozen pulp on oxidative stress parameters in cerebral cortex, hippocampus and cerebellum of Wistar rats treated with carbon tetrachloride (CCl 4 ). Thirty male Wistar rats (90-day-old) were orally treated with water or acai frozen pulp for 14 days (7 μL/g). On the 15th day, half of the animals received treatment with mineral oil and the other half with CCl 4 (3.0 mL/kg). The cerebral cortex, hippocampus and cerebellum were dissected and used for analysis of creatine kinase activity (CK), thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, and the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Statistical analysis was performed by ANOVA followed by Tukey's post-test. CCl 4 was able to inhibit CK activity in all tissues tested and to provoke lipid damage in cerebral cortex and cerebellum, and protein damage in the three tissues tested. CCl 4 enhanced CAT activity in the cerebral cortex, and inhibited CAT activity in the hippocampus and cerebellum and reduced SOD activity in all tissues studied. Acai frozen pulp prevented the inhibition of CK, TBARS, carbonyl and CAT activity in all brain structures and only in hippocampus for SOD activity. Therefore, acai frozen pulp has antioxidant properties and maybe could be useful in the treatment of some diseases that affect the central nervous system that are associated with oxidative damage.

  16. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

    Science.gov (United States)

    Caputo, Fanny; de Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

    2015-09-01

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

  17. THEOS-2 Orbit Design: Formation Flying in Equatorial Orbit and Damage Prevention Technique for the South Atlantic Magnetic Anomaly (SAMA)

    Science.gov (United States)

    Pimnoo, Ammarin

    2016-07-01

    Geo-Informatics and Space Technology Development Agency (GISTDA) has initiative THEOS-2 project after the THEOS-1 has been operated for more than 7 years which is over the lifetime already. THEOS-2 project requires not only the development of earth observation satellite(s), but also the development of the area-based decision making solution platform comprising of data, application systems, data processing and production system, IT infrastructure improvement and capacity building through development of satellites, engineering model, and infrastructures capable of supporting research in related fields. The developing satellites in THEOS-2 project are THAICHOTE-2 and THAICHOTE-3. This paper focuses the orbit design of THAICHOTE-2 & 3. It discusses the satellite orbit design for the second and third EOS of Thailand. In this paper, both THAICHOTE will be simulated in an equatorial orbit as a formation flying which will be compared the productive to THAICHOTE-1 (THEOS-1). We also consider a serious issue in equatorial orbit design, namely the issue of the geomagnetic field in the area of the eastern coast of South America, called the South Atlantic Magnetic Anomaly (SAMA). The high-energy particles of SAMA comprise a radiation environment which can travel through THAICHOTE-2 & 3 material and deposit kinetic energy. This process causes atomic displacement or leaves a stream of charged atoms in the incident particles' wake. It can cause damage to the satellite including reduction of power generated by solar arrays, failure of sensitive electronics, increased background noise in sensors, and exposure of the satellite devices to radiation. This paper demonstrates the loss of ionizing radiation damage and presents a technique to prevent damage from high-energy particles in the SAMA.

  18. Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

    Science.gov (United States)

    Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

    2016-07-01

    Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

  19. Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa.

    Science.gov (United States)

    Bejarano, Ignacio; Monllor, Fabian; Marchena, Ana María; Ortiz, Agueda; Lozano, Graciela; Jiménez, Maria Isabel; Gaspar, Pilar; García, Juan F; Pariente, Jose A; Rodríguez, Ana B; Espino, Javier

    2014-10-01

    Reactive oxygen species (ROS) are essential for sperm physiological functions such as capacitation, hyperactivation, and acrosome reaction, on the one hand, and for stimulating the apoptotic processes involved in the regulation of spermatogenesis, on the other hand. However, the imbalance between production and removal of ROS leads to oxidative stress, which is referred to as one of the main factors involved in male infertility. The pineal hormone melatonin, given its low toxicity and well-known antioxidant capacity, could be an excellent candidate to improve sperm quality. For this reason, the objective of the present work was to analyze whether long-term supplementation with melatonin to infertile men affects human sperm quality and the quality of the embryos retrieved from their couples. Our findings showed that the daily supplementation of 6 mg melatonin, as early as after 45 days of treatment, produced an increase in melatonin endogenous levels, indirectly measured as urinary 6-sulfatoxymelatonin (aMT6-s), an enhancement of both urinary and seminal total antioxidant capacity, and a consequent reduction in oxidative damage caused in sperm DNA. Moreover, couples whose men were given melatonin showed a statistically significant increase in the percentage of grade A (embryo with blastomeres of equal size; no cytoplasmic fragmentation), B (embryo with blastomeres of equal size; minor cytoplasmic fragmentation), and C (embryo with blastomeres of distinctly unequal size; significant cytoplasmic fragmentation) embryos at the expense of grade D (embryo with blastomeres of equal or unequal size; severe or complete fragmentation.) embryos which were clearly reduced. In summary, melatonin supplementation improves human sperm quality, which is essential to achieve successful natural and/or assisted reproduction outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage.

    Science.gov (United States)

    Maiorana, Arianna; Manganozzi, Lucilla; Barbetti, Fabrizio; Bernabei, Silvia; Gallo, Giorgia; Cusmai, Raffaella; Caviglia, Stefania; Dionisi-Vici, Carlo

    2015-09-24

    Congenital hyperinsulinism (CHI) is the most frequent cause of hypoglycemia in children. In addition to increased peripheral glucose utilization, dysregulated insulin secretion induces profound hypoglycemia and neuroglycopenia by inhibiting glycogenolysis, gluconeogenesis and lipolysis. This results in the shortage of all cerebral energy substrates (glucose, lactate and ketones), and can lead to severe neurological sequelae. Patients with CHI unresponsive to medical treatment can be subjected to near-total pancreatectomy with increased risk of secondary diabetes. Ketogenic diet (KD), by reproducing a fasting-like condition in which body fuel mainly derives from beta-oxidation, is intended to provide alternative cerebral substrates such ketone bodies. We took advantage of known protective effect of KD on neuronal damage associated with GLUT1 deficiency, a disorder of impaired glucose transport across the blood-brain barrier, and administered KD in a patient with drug-unresponsive CHI, with the aim of providing to neurons an energy source alternative to glucose. A child with drug-resistant, long-standing CHI caused by a spontaneous GCK activating mutation (p.Val455Met) suffered from epilepsy and showed neurodevelopmental abnormalities. After attempting various therapeutic regimes without success, near-total pancreatectomy was suggested to parents, who asked for other options. Therefore, we proposed KD in combination with insulin-suppressing drugs. We administered KD for 2 years. Soon after the first six months, the patient was free of epileptic crises, presented normalization of EEG, and showed a marked recover in psychological development and quality of life. KD could represent an effective treatment to support brain function in selected cases of CHI.

  1. Method for assessing damage to mitochondrial DNA caused by radiation and epichlorohydrin

    International Nuclear Information System (INIS)

    Singh, G.; Hauswirth, W.W.; Ross, W.E.; Neims, A.H.

    1985-01-01

    This paper describes a rapid and reliable method for quantification of damage to mitochondrial DNA (mtDNA), especially strand breaks. The degree of damage to mtDNA is assessed by the proportion of physical forms (i.e., supercoiled versus open-circular and linear forms) upon agarose gel electrophoresis, blotting, and visualization by hybridization with [ 32 P]mtDNA probes. The use of a radiolabeled probe is a crucial step in the procedure because it provides both a means to quantify by radioautography and to obtain the mtDNA specificity required to eliminate misinterpretation due to nuclear DNA contamination. To demonstrate the utility of this technique, X-irradiation and epichlorohydrin are shown to damage both isolated mtDNA and mtDNA in whole cells in a dose-dependent fashion

  2. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans. Copyright © 2016. Published by Elsevier Ireland Ltd.

  3. Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease▿

    Science.gov (United States)

    Waghabi, Mariana C.; de Souza, Elen M.; de Oliveira, Gabriel M.; Keramidas, Michelle; Feige, Jean-Jacques; Araújo-Jorge, Tania C.; Bailly, Sabine

    2009-01-01

    Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration. PMID:19738024

  4. Sulforaphane Prevents Testicular Damage in Kunming Mice Exposed to Cadmium via Activation of Nrf2/ARE Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Shu-Hua Yang

    2016-10-01

    Full Text Available Sulforaphane (SFN is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD and glutathione (GSH levels and increases malondialdehyde (MDA concentrations. SFN intervention improved sperm quality, serum testosterone, and antioxidant levels. Both mRNA and protein expression of mouse testicular nuclear factor-erythroid 2-related factor 2 (Nrf2 was reduced in cadmium-treated group. Furthermore, the downstream genes of Nrf2, glutathione peroxidase (GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS, heme oxygenase-1 (HO-1, and NAD(PH:quinone oxidoreductase-1 (NQO1 were also decreased in cadmium-treated group. SFN intervention increases the expression of these genes. Sulforaphane prevents cadmium-induced testicular damage, probably via activation of Nrf2/ARE signaling.

  5. Cactus (Opuntia ficus-indica) cladodes prevent oxidative damage induced by the mycotoxin zearalenone in Balb/C mice.

    Science.gov (United States)

    Zourgui, Lazhar; Golli, Emna El; Bouaziz, Chayma; Bacha, Hassen; Hassen, Wafa

    2008-05-01

    Zearalenone (ZEN) is one of the most widely distributed fusarial mycotoxins which is encountered at high incidence in many foodstuffs. ZEN was associated with different reproductive disorders in animals. Several in vivo studies have shown that ZEN is hepatotoxic, haematotoxic and causes several alterations of immunological parameters. Furthermore, evidence of its cytotoxicity and genotoxicity has recently emerged from several reports. The aim of the current study was (i) to find out whether oxidative stress could be relevant for ZEN induced toxicity in vivo using Balb/c mice and (ii) to evaluate the safety and efficacy of cactus cladodes Opuntia ficus to prevent the deleterious effects of ZEN. To this end, the effect of a single dose of ZEN (40 mg/kg b.w.) alone and with extract of cactus cladodes (25, 50 and 100 mg/kg b.w.) on the induction of oxidative stress was monitored in kidney and liver by measuring the MDA level, the protein carbonyls generation, the catalase activity and the expression of the heat shock proteins (Hsp). Our results clearly showed that ZEN induced significant alterations in all tested oxidative stress markers. Oxidative damage seems to be a key determinant of ZEN induced toxicity in both liver and kidney of Balb/c mice. The combined treatment of ZEN with the lowest tested dose of cactus extracts (25 mg/kg b.w.) showed a total reduction of ZEN induced oxidative damage for all tested markers. It could be concluded that cactus cladodes extract was effective in the protection against ZEN hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental effects of oxidative stress and therefore prevent multiple human diseases.

  6. The role of ketotifen in the prevention of testicular damage in rats with experimental unilateral undescended testes

    Science.gov (United States)

    Acikgoz, Abdullah; Asci, Ramazan; Aydin, Oguz; Çavuş, Hikmet; Donmez, Gamze; Buyukalpelli, Recep

    2014-01-01

    The aims of this study conducted on rats were to determine mast cell (MC) proliferation on undescended testes (UDTs); whether there is a correlation between MC proliferation and testicular damage; and whether testicular damage can be prevented with administration of an MC blocker. Sixty-five newborn male rats were divided into three groups. During the neonatal period, unilateral UDTs were experimentally induced in Group 2 and Group 3. The rats in Group 3 were given 1 mg/kg/day ketotifen orally until the end of the study. Groups 2 (n=30) and 3 (n=15) were divided into groups of ten and five rats, respectively, each of which underwent bilateral orchiectomy in either the prepubertal, pubertal, or adult period. Group 1 (n=15) underwent a sham operation followed by bilateral orchiectomy, with five rats in each of the prepubertal, pubertal, and adult periods. Testicular MCs in the interstitial and subtubular areas, biopsy scores, interstitial connective tissue, seminiferous tubule (ST) diameters, and the basement membrane thickness of STs were evaluated. In Group 2 the ST diameters in the UDTs decreased, the number of MCs in the interstitial and subtubular areas increased, ST basement membranes thickened, and spermatogenesis decreased. The number of MCs in the interstitial and subtubular areas of the descended testes increased and spermatogenesis decreased. In Group 3, the number of MCs in the interstitial and subtubular areas decreased. In unilateral UDTs, the number of MCs in the interstitial and subtubular areas increased in both testes. Fibrosis developed in the ST basement membranes and interstitial areas, and spermatogenesis deteriorated. Testicular fibrosis may be prevented with administration of an MC blocker. PMID:25364234

  7. MtDNA T4216C variation in multiple sclerosis

    DEFF Research Database (Denmark)

    Andalib, Sasan; Emamhadi, Mohammadreza; Yousefzadeh-Chabok, Shahrokh

    2016-01-01

    MtDNA T4216C variation has frequently been investigated in Multiple Sclerosis (MS) patients; nonetheless, controversy has existed about the evidence of association of this variation with susceptibility to MS. The present systematic review and meta-analysis converge the results of the preceding...

  8. Human mitochondrial DNA (mtDNA) types in Malaysia

    International Nuclear Information System (INIS)

    Lian, L.H.; Koh, C.L.; Lim, M.E.

    2000-01-01

    Each human cell contains hundreds of mitochondria and thousands of double-stranded circular mtDNA. The delineation of human mtDNA variation and genetics over the past decade has provided unique and often startling insights into human evolution, degenerative diseases, and aging. Each mtDNA of 16,569 base pairs, encodes 13 polypeptides essential to the enzymes of the mitochondrial energy generating pathway, plus the necessary tRNAs and rRNAs. The highly polymorphic noncoding D-(displacement) loop region, also called the control region, is approximately 1.2 kb long. It contains two well-characterized hypervariable (HV-) regions, HV1 and HV2. MtDNA identification is usually based on these sequence differences. According to the TWTGDAM (Technical Working Group for DNA Analysis Methods), the minimum requirement for a mtDNA database for HV1 is from positions 16024 to 16365 and for HV2, from positions 00073 to 00340. The targeted Malaysian population subgroups for this study were mainly the Malays, Chinese, Indians, and indigenous Ibans, Bidayuhs, Kadazan-Dusuns, and Bajaus. Research methodologies undertaken included DNA extraction of samples from unrelated individuals, amplification of the specific regions via the polymerase chain reaction (PCR), and preparation of template DNA for sequencing by using an automated DNA sequencer. Sufficient nucleotide sequence data were generated from the mtDNA analysis. When the sequences were analyzed, sequence variations were found to be caused by nucleotide substitutions, insertions, and deletions. Of the three causes of the sequence variations, nucleotide substitutions (86.1%) accounted for the vast majority of polymorphism. It is noted that transitions (83.5%) were predominant when compared to the significantly lower frequencies of transversions (2.6%). Insertions (0.9%) and deletions (13.0%) were rather rare and found only in HV2. The data generated will also form the basis of a Malaysian DNA sequence database of mtDNA D

  9. Study of qinolones usage in prevention and therapy of septic complications of radiation damage

    International Nuclear Information System (INIS)

    Petyrek, P.; Spelda, S.

    1994-01-01

    A standard model of experimental sepsis was elaborated at rats in dependence on a gamma irradiation dose and a time interval between irradiation and application infectious agents E. coli O 83:K 24:H 31. For a development of experimental sepsis was proved that it is not decisive in these laboratory animals when infectious agents is i.v. or i.p. applicated. Such amount of organisms (1-20.10 7-8 ) was applicated in particular not to develop sepsis in non-irradiated laboratory animals. Laboratory animals were irradiated with sublethal doses and approximately. LD 50-30 doses of gamma radiation. The laboratory animals were treated only in experiments and qinolone drug ofloxacin was used in the treatment of experimental sepsis. Ofloxacin perorally administrated in the dose of 40 mg/kg in an hour after application of infectious agents and its administration for 5 days in the 24-h intervals confirmed in fact 100% therapeutic effectiveness in irradiated experimental animals. In non-treated experimental groups, animals died in 24-28 hours interval after application of infectious agents and sepsis was a cause of death. In treated experimental groups, animal survived by day 30 after irradiation with sublethal doses or died during the period typical for a bone marrow syndrome of acute radiation injury after irradiation with lethal doses of gamma radiation. Acquired experimental outcomes may suggest that fluorochinolone chemotherapeuticals in the respect of their essential pharmacokinetic properties will be used for a prevention of infectious complications in acute radiation injury. (author)

  10. Galectin-1 Prevents Infection and Damage Induced by Trypanosoma cruzi on Cardiac Cells

    Science.gov (United States)

    Benatar, Alejandro F.; García, Gabriela A.; Bua, Jacqeline; Cerliani, Juan P.; Postan, Miriam; Tasso, Laura M.; Scaglione, Jorge; Stupirski, Juan C.; Toscano, Marta A.

    2015-01-01

    Background Chronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection. Methodology and Principal Findings Here we investigated the contribution of galectin–1 (Gal–1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL–1 cardiac cells to Gal–1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal–1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL–1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal–1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal–1 to the cell surface. Consistent with these data, Gal–1 deficient (Lgals1 -/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain. Conclusion/Significance Our results indicate that Gal–1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions. PMID:26451839

  11. The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

    KAUST Repository

    Blomme, Jonas

    2017-04-19

    In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gainand loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development.

  12. The role of ketotifen in the prevention of testicular damage in rats with experimental unilateral undescended testes

    Directory of Open Access Journals (Sweden)

    Acikgoz A

    2014-10-01

    Full Text Available Abdullah Acikgoz,1 Ramazan Asci,2 Oguz Aydin,3 Hikmet Çavuş,4 Gamze Donmez,5 Recep Buyukalpelli2 1Department of Urology, School of Medicine, Kemerburgaz University, Istanbul, Turkey; 2Department of Urology, 3Department of Pathology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey; 4Department of Urology, Medical Park Samsun Hospital, Samsun, Turkey; 5Department of Pathology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey Abstract: The aims of this study conducted on rats were to determine mast cell (MC proliferation on undescended testes (UDTs; whether there is a correlation between MC proliferation and testicular damage; and whether testicular damage can be prevented with administration of an MC blocker. Sixty-five newborn male rats were divided into three groups. During the neonatal period, unilateral UDTs were experimentally induced in Group 2 and Group 3. The rats in Group 3 were given 1 mg/kg/day ketotifen orally until the end of the study. Groups 2 (n=30 and 3 (n=15 were divided into groups of ten and five rats, respectively, each of which underwent bilateral orchiectomy in either the prepubertal, pubertal, or adult period. Group 1 (n=15 underwent a sham operation followed by bilateral orchiectomy, with five rats in each of the prepubertal, pubertal, and adult periods. Testicular MCs in the interstitial and subtubular areas, biopsy scores, interstitial connective tissue, seminiferous tubule (ST diameters, and the basement membrane thickness of STs were evaluated. In Group 2 the ST diameters in the UDTs decreased, the number of MCs in the interstitial and subtubular areas increased, ST basement membranes thickened, and spermatogenesis decreased. The number of MCs in the interstitial and subtubular areas of the descended testes increased and spermatogenesis decreased. In Group 3, the number of MCs in the interstitial and subtubular areas decreased. In unilateral UDTs, the number of MCs in the interstitial and

  13. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  14. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    International Nuclear Information System (INIS)

    Jiang, Zhenzhou; Bao, Qingli; Sun, Lixin; Huang, Xin; Wang, Tao; Zhang, Shuang; Li, Han; Zhang, Luyong

    2013-01-01

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  15. Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Guan-gui Chen

    2015-01-01

    Full Text Available Polyethyleneimine-polyethylene glycol (PEI-PEG, a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

  16. The materials concept in German light water reactors. A contribution to plant safety, economic performance and damage prevention

    International Nuclear Information System (INIS)

    Ilg, Ulf

    2008-01-01

    Major decisions taken as early as in the planning and construction phases of nuclear power plants may influence overall plant life. Component quality at the beginning of plant life is determined very much also by a balanced inclusion of the 'design, choice of materials, manufacturing and inspection' elements. One example of the holistic treatment of design, choice of material, and manufacture of important safety-related components in pressurized water reactors is the reactor pressure vessel (RPV) in which the ferritic compound tubes, with inside claddings, for the control rod drive nozzles are screwed into the vessel top. Also the choice of Incoloy 800 for the steam generator tubes, and the design of the main coolant pipes with inside claddings as seamless pipe bends / straight pipes with integrated nozzles connected to mixed welds with austenitic pipes are other special design features of the Siemens/KWU plants. A demonstrably high quality standard by international comparison to this day has been exhibited by the austenitic RPV internals of boiling water reactors, which were made of a low-carbon Nb-stabilized austenitic steel grade by optimum manufacturing technologies. The same material is used for backfitting austenitic pipes. Reliable and safe operation of German nuclear power plants has been demonstrated for more than 4 decades. One major element in this performance is the materials concept adopted in Germany also in the interest of damage prevention. (orig.)

  17. Prevention of Dental Damage and Improvement of Difficult Intubation Using a Paraglossal Technique With a Straight Miller Blade

    Directory of Open Access Journals (Sweden)

    Yu-Feng Huang

    2010-10-01

    Full Text Available Patients with diseased teeth, or those who are difficult to intubate, have a higher risk of dental injury during laryngoscopy. We report 3 cases of smooth endotracheal intubation using a paraglossal technique with a straight Miller blade in patients with poor dentition. Three patients with poor dentition were scheduled to undergo surgery under general anesthesia. All patients presented with extremely loose upper central incisors and had lost the other right upper teeth, while micrognathia and prominent, loose upper incisors were noted in 1 case. We elected to use a straight Miller blade using a paraglossal approach. A nasopharyngeal airway was inserted after induction of general anesthesia to facilitate mask ventilation and prevent air leakage from the mask. The Miller blade was then inserted from the right corner of the mouth, avoiding contact with the vulnerable incisors, and advanced along the groove between the tongue and tonsil. The endotracheal tube was subsequently smoothly inserted after obtaining a grade 1 Cormack and Lehane view without dental trauma in all 3 cases. Direct laryngoscopy using the paraglossal straight blade technique avoids dental damage in patients with mobile upper incisors and no right maxillary molars. It is a practical alternative method that differs from the traditional Macintosh laryngoscope in patients with a high risk of dental injury during the procedure. This technique, which provides an improved view of the larynx, might also be helpful with patients in whom intubation is difficult.

  18. Structural damages prevention of the ITER vacuum vessel and ports by elasto-plastic analysis with regards to RCC-MR

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jean-Marc, E-mail: jean-marc.martinez@iter.org [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Jun, Chang Hoon; Portafaix, Christophe; Alekseev, Alexander; Sborchia, Carlo; Choi, Chang-Ho [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Albin, Vincent [SOM Calcul – Groupe ORTEC, 121 ancien Chemin de Cassis – Immeuble Grand Pré, 13009 Marseille (France); Borrelly, Stephane [Sogeti High Tech, RE2, 180 rue René Descartes, Le Millenium – Bat C, 13857 Aix en Provence (France); Cambazar, Magali [Assystem EOS, 117 rue Jacquard, 84120 Pertuis (France); Gaucher, Thomas [SOM Calcul – Groupe ORTEC, 121 ancien Chemin de Cassis – Immeuble Grand Pré, 13009 Marseille (France); Sfarni, Samir; Tailhardat, Olivier [Assystem EOS, 117 rue Jacquard, 84120 Pertuis (France)

    2015-10-15

    Highlights: • ITER vacuum vessel (VV) is a part of the first barrier to confine the plasma. • ITER VV as NPE necessitates a third party organization authorized by the French nuclear regulator to assure design, fabrication, and conformance testing and quality assurance, i.e. ANB. • Several types of damages have to be prevented in order to guarantee the structural integrity with regards to RCC-MR. • It is usual to employ non-linear analysis when the “classical” elastic analysis reaches its limit of linear application. • Several structural analyses were performed with many different global and local models of the whole ITER VV. - Abstract: Several types of damages have to be prevented in order to guarantee the structural integrity of a structure with regards to RCC-MR; the P-type damages which can result from the application to a structure of a steadily and regularly increasing loading or a constant loading and the S-type damages during operational loading conditions which can only result from repeated application of loadings associated to the progressive deformations and fatigue. Following RCC-MR, the S-type damages prevention has to be started only when the structural integrity is guaranteed against P-type damages. The verification of the last one on the ITER vacuum vessel and ports has been performed by limit analysis with elasto-(perfectly)plastic material behavior. It is usual to employ non-linear analysis when the “classical” elastic analysis reaches its limit of linear application. Some elasto-plastic analyses have been performed considering several cyclic loadings to evaluate also more realistic structural margins of the against S-type damages.

  19. Reduced Mtdna Diversity in the Ngobe Amerinds of Panama

    Science.gov (United States)

    Kolman, C. J.; Bermingham, E.; Cooke, R.; Ward, R. H.; Arias, T. D.; Guionneau-Sinclair, F.

    1995-01-01

    Mitochondrial DNA (mtDNA) haplotype diversity was determined for 46 Ngobe Amerinds sampled widely across their geographic range in western Panama. The Ngobe data were compared with mtDNA control region I sequences from two additional Amerind groups located at the northern and southern extremes of Amerind distribution, the Nuu-Chah-Nulth of the Pacific Northwest and the Chilean Mapuche and from one Na-Dene group, the Haida of the Pacific Northwest. The Ngobe exhibit the lowest mtDNA control region sequence diversity yet reported for an Amerind group. Moreover, they carry only two of the four Amerind founding lineages first described by Wallace and coworkers. We posit that the Ngobe passed through a population bottleneck caused by ethnogenesis from a small founding population and/or European conquest and colonization. Dating of the Ngobe population expansion using the HARPENDING et al. approach to the analysis of pairwise genetic differences indicates a Ngobe expansion at roughly 6800 years before present (range: 1850-14,000 years before present), a date more consistent with a bottleneck at Chibcha ethnogenesis than a conquest-based event. PMID:7635293

  20. Analysis of the thermal comfort and impact properties of the neoprene-spacer fabric structure for preventing the joint damages.

    Science.gov (United States)

    Ghorbani, Ehsan; Hasani, Hossein; Rafeian, Homa; Hashemibeni, Batool

    2013-07-01

    Frequent moves at the joint, plus external factors such as trauma, aging, and etc., are all reasons for joint damages. In order to protect and care of joints, the orthopedic textiles are used. To protect the joints, these textiles keep muscles warm to prevent shock. To produce orthopedic textiles, Neoprene foams have been traditionally used. These foams are flexible and resist impact, but are not comfortable enough and might cause problems for the consumer. This study introduces a new structure consisting of perforated Neoprene foam attached to the spacer fabric and also compares the properties of thermal and moisture comfort and impact properties of this structure in comparison with Neoprene foam. In order to measure the factors related to the samples lateral pressure behavior, a tensile tester was used. A uniform pressure is applied to the samples and a force - displacement curve is obtained. The test continues until the maximum compression force is reached to 50 N. The area under the curve is much greater; more energy is absorbed during the impact. In order to investigate the dynamic heat and moisture transfer of fabrics, an experimental apparatus was developed. This device made the simulation of sweating of human body possible and consisted of a controlled environmental chamber, sweating guarded hot plate, and data acquisition system. The findings show that the Neoprene-spacer fabric structure represents higher toughness values compared to other samples (P ≤ 0.001). Neoprene-spacer fabric structure (A3) has higher rate of moisture transport than conventional Neoprene foam; because of undesirable comfort characteristics in Neoprene. Results of the tests indicate full advantage of the new structure compared with the Neoprene foam for use in orthopedic textiles (P ≤ 0.001).

  1. Sequence and analysis of mtDNA control region in Cnaphalacrocis medinalis Guenée and Marasmia patnalis Bradley (Lepidoptera: Pyralidae).

    Science.gov (United States)

    Yang, Yajun; Wu, Zhihong; Xu, Hongxing; Zheng, Xusong; Tian, Junce; Lu, Zhongxian

    2016-11-01

    Rice leaffolders Cnaphalocrocis medinalis and Marasmia patnalis (Lepidoptera: Pyralidae) are important rice pests and morphologically related with same damage methods. The control region of mitochondrial DNA (mtDNA) in two rice leaffolders C. medinalis and M. patnalis were sequenced and analyzed. The control regions of the two rice leaffolders are located between 12S ribosomal RNA and tRNA Met , and exhibit conserved structural elements. We identified the poly T stretches, (TA)n block, and stem-loop structure. There are no long tandem repeats found in mtDNA control region in the two rice leaffolders studied. Nevertheless, we did not find the GA-rich block in mtDNA control regions of the two rice leaffolders. The molecular-based phylogenies support the traditional morphologically based view of relationships of Pyralidae within the Ditrysia. The addition of the C. medinalis and M. patnalis mtDNA control regions to the literature promotes the understanding of the molecular evolution of Pyralidae in Ditrysia.

  2. Stage-by-stage licensing procedure, prevention of damage, control by administrative courts. Some comments on the Wyhl judgment of the Federal Administrative Court

    International Nuclear Information System (INIS)

    Sellner, D.

    1986-01-01

    The author discusses the three main items of the Wyhl judgment of the Federal Administrative Court, of December 19, 1985 - 7C65/82, which are likely to set trends. The judgment clarifies the function of the socalled preliminary approval of the concept and its delimitation to the preliminary partial licence. According to the judgment, the first is a licensing requirement in substantial law. Precaution for preventing damage according to sec. 7, sub-sec (2) No. 3 Atomic Energy Act is regarded by the Court not as a prevention of hazards, but as the obligation to take every precaution to prevent damage, i.e. types of damage have to be taken into account that cannot be excluded to develop to a real hazard or potential risk. The problem of extent of control by the administrative courts is solved by the approach based on the legal functions of competence and responsibility that are to be drawn from the principle of division of power. (HSCH) [de

  3. Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro

    DEFF Research Database (Denmark)

    Ebert, Regina; Ulmer, Matthias; Zeck, Sabine

    2006-01-01

    signaling, cumulative cell damage, senescence, and tumor development. Selenium-dependent (glutathione peroxidases [GPxs] and thioredoxin reductases [TrxRs]) and selenium-independent (superoxide dismutases [SODs] and catalase [CAT]) enzyme systems regulate cellular ROS steady state levels. SODs process...

  4. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  5. Metabolic rescue in pluripotent cells from patients with mtDNA disease.

    Science.gov (United States)

    Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

    2015-08-13

    Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

  6. Optimized mtDNA Control Region Primer Extension Capture Analysis for Forensically Relevant Samples and Highly Compromised mtDNA of Different Age and Origin

    Directory of Open Access Journals (Sweden)

    Mayra Eduardoff

    2017-09-01

    Full Text Available The analysis of mitochondrial DNA (mtDNA has proven useful in forensic genetics and ancient DNA (aDNA studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR is commonly sequenced using established Sanger-type Sequencing (STS protocols involving fragment sizes down to approximately 150 base pairs (bp. Recent developments include Massively Parallel Sequencing (MPS of (multiplex PCR-generated libraries using the same amplicon sizes. Molecular genetic studies on archaeological remains that harbor more degraded aDNA have pioneered alternative approaches to target mtDNA, such as capture hybridization and primer extension capture (PEC methods followed by MPS. These assays target smaller mtDNA fragment sizes (down to 50 bp or less, and have proven to be substantially more successful in obtaining useful mtDNA sequences from these samples compared to electrophoretic methods. Here, we present the modification and optimization of a PEC method, earlier developed for sequencing the Neanderthal mitochondrial genome, with forensic applications in mind. Our approach was designed for a more sensitive enrichment of the mtDNA CR in a single tube assay and short laboratory turnaround times, thus complying with forensic practices. We characterized the method using sheared, high quantity mtDNA (six samples, and tested challenging forensic samples (n = 2 as well as compromised solid tissue samples (n = 15 up to 8 kyrs of age. The PEC MPS method produced reliable and plausible mtDNA haplotypes that were useful in the forensic context. It yielded plausible data in samples that did not provide results with STS and other MPS techniques. We addressed the issue of contamination by including four generations of negative controls, and discuss the results in the forensic context. We finally offer perspectives for future research to enable the validation and accreditation of the PEC MPS

  7. Using prophylactic antioxidants to prevent noise-induced hearing damage in young adults: a protocol for a double-blind, randomized controlled trial.

    Science.gov (United States)

    Gilles, Annick; Ihtijarevic, Berina; Wouters, Kristien; Van de Heyning, Paul

    2014-04-05

    During leisure activities young people are often exposed to excessive noise levels resulting in an increase of noise-induced symptoms such as hearing loss, tinnitus and hyperacusis. Noise-induced tinnitus is often perceived after loud music exposure and provides an important marker for overexposure as a temporary threshold shift that is often not experienced by the individual itself. As oxidative stress plays an important role in the pathogenesis of noise-induced hearing loss, the use of antioxidants to prevent hearing damage has recently become the subject of research. This study proposes a randomized, double-blind, placebo-controlled crossover trial to assess the effects of a prophylactic combination of N-acetylcysteine (600 mg) and magnesium (200 mg) prior to leisure noise exposure in young adults. The primary outcome measure is the tinnitus loudness scored by a visual analogue scale (VAS). Secondary outcome measures are the differences in audiological measurements for the antioxidant treatments compared to placebo intake. Audiological testing comprising of pure tone audiometry including frequencies up to 16 kHz, distortion product otoacoustic emissions, transient-evoked otoacoustic emissions and speech-in-noise testing will be performed prior to and within 7 hours after noise exposure. By use of a mixed effects statistical model, the effects of antioxidants compared to placebo intake will be assessed. As adolescents and young adults often do not use hearing protection while being exposed to loud music, the use of preventive antioxidant intake may provide a useful and harmless way to prevent noise-induced hearing damage in this population. Furthermore, when exposed to hazardous noise levels the protection provided by hearing protectors might not be sufficient to prevent hearing damage and antioxidants may provide additive otoprotective effects. Previous research mainly focused on occupational noise exposure. The present study provides a protocol to assess the

  8. Prevention of alcohol-induced DNA damage by a proprietary glycyrrhizin/D-mannitol product: A randomized, placebo-controlled, cross-over human study.

    Science.gov (United States)

    Chigurupati, Harsha; Auddy, Biswajit; Biyani, Manish; Chakrabarti, Shrabana; Stohs, Sidney J

    2017-11-06

    The purpose of the present study was to evaluate the ability of a proprietary combination of glycyrrhizin and D-mannitol to protect against oxidative damage to DNA associated with acute alcohol consumption by human subjects in a randomized, placebo-controlled cross-over designed study. Excessive alcohol consumption is associated with numerous diseases. Alcohol has been shown to generate reactive oxygen species that can result in DNA damage, leading to genetic and epigenetic changes. A total of 25 subjects (13 male and 12 female) were enrolled. Alcohol intake in the form of vodka (40% ethanol) was adjusted based on 1.275 g of 100% ethanol/kg body weight for men and 1.020 g/kg body weight for women, which was consumed with and without the study product. Blood samples were drawn at 2 h after alcohol consumption, lymphocytes were isolated, and were subjected to DNA comet electrophoresis on a blinded basis. Acute alcohol consumption increased lymphocyte DNA damage by approximately 8.36%. Co-consumption of the glycyrrhizin/D-mannitol study product with alcohol reduced DNA damage to baseline levels. No adverse effects were associated with use of the study product, and no differences were observed in blood alcohol concentrations in the presence or absence of the study product in males and females. Acute alcohol ingestion resulted in measurable increases in DNA damage, which were prevented by the addition of the proprietary glycyrrhizin/D-mannitol (NTX ® ) study product to the alcohol, suggesting that the tissue-damaging effects of alcohol consumption can be ameliorated. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Hypervariable region polymorphism of mtDNA of recurrent oral ulceration in Chinese.

    Directory of Open Access Journals (Sweden)

    Mao Sun

    Full Text Available BACKGROUND: MtDNA haplogroups could have important implication for understanding of the relationship between the mutations of the mitochondrial genome and diseases. Distribution of a variety of diseases among these haplogroups showed that some of the mitochondrial haplogroups are predisposed to disease. To examine the susceptibility of mtDNA haplogroups to ROU, we sequenced the mtDNA HV1, HV2 and HV3 in Chinese ROU. METHODOLOGY/PRINCIPAL FINDINGS: MtDNA haplogroups were analyzed in the 249 cases of ROU patients and the 237 cases of healthy controls respectively by means of primer extension analysis and DNA sequencing. Haplogroups G1 and H were found significantly more abundant in ROU patients than in healthy persons, while haplogroups D5 and R showed a trend toward a higher frequency in control as compared to those in patients. The distribution of C-stretch sequences polymorphism in mtDNA HV1, HV2 and HV3 regions was found in diversity. CONCLUSIONS/SIGNIFICANCE: For the first time, the relationship of mtDNA haplogroups and ROU in Chinese was investigated. Our results indicated that mtDNA haplogroups G1 and H might constitute a risk factor for ROU, which possibly increasing the susceptibility of ROU. Meanwhile, haplogroups D5 and R were indicated as protective factors for ROU. The polymorphisms of C-stretch sequences might being unstable and influence the mtDNA replication fidelity.

  10. Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells

    International Nuclear Information System (INIS)

    Akimoto, Miho; Niikura, Mamoru; Ichikawa, Masami; Yonekawa, Hiromichi; Nakada, Kazuto; Honma, Yoshio; Hayashi, Jun-Ichi

    2005-01-01

    Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (ρ 0 ) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties

  11. Infantile presentation of the mtDNA A3243G tRNA(Leu (UUR)) mutation.

    NARCIS (Netherlands)

    Okhuijsen-Kroes, E.J.; Trijbels, J.M.F.; Sengers, R.C.A.; Mariman, E.C.M.; Heuvel, L.P.W.J. van den; Wendel, U.A.H.; Koch, G.; Smeitink, J.A.M.

    2001-01-01

    Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, ranging from single organ involvement to severe multisystem disease. One of the most frequently observed mtDNA mutations is the A-to-G transition at position 3243 of the tRNA(Leu (UUR)) gene. This mutation is often related to

  12. Distinct radiation responses after in vitro mtDNA depletion are potentially related to oxidative stress

    NARCIS (Netherlands)

    van Gisbergen, Marike W.; Voets, An M.; Biemans, Rianne; Hoffmann, Roland F.; Drittij-Reijnders, Marie-Jose; Haenen, Guido R. M. M.; Heijink, Irene H.; Rouschop, Kasper M. A.; Dubois, Ludwig J.; Lambin, Philippe

    2017-01-01

    Several clinically used drugs are mitotoxic causing mitochondrial DNA (mtDNA) variations, and thereby influence cancer treatment response. We hypothesized that radiation responsiveness will be enhanced in cellular models with decreased mtDNA content, attributed to altered reactive oxygen species

  13. Replication Errors Made During Oogenesis Lead to Detectable De Novo mtDNA Mutations in Zebrafish Oocytes with a Low mtDNA Copy Number.

    Science.gov (United States)

    Otten, Auke B C; Stassen, Alphons P M; Adriaens, Michiel; Gerards, Mike; Dohmen, Richard G J; Timmer, Adriana J; Vanherle, Sabina J V; Kamps, Rick; Boesten, Iris B W; Vanoevelen, Jo M; Muller, Marc; Smeets, Hubert J M

    2016-12-01

    Of all pathogenic mitochondrial DNA (mtDNA) mutations in humans, ∼25% is de novo, although the occurrence in oocytes has never been directly assessed. We used next-generation sequencing to detect point mutations directly in the mtDNA of 3-15 individual mature oocytes and three somatic tissues from eight zebrafish females. Various statistical and biological filters allowed reliable detection of de novo variants with heteroplasmy ≥1.5%. In total, we detected 38 de novo base substitutions, but no insertions or deletions. These 38 de novo mutations were present in 19 of 103 mature oocytes, indicating that ∼20% of the mature oocytes carry at least one de novo mutation with heteroplasmy ≥1.5%. This frequency of de novo mutations is close to that deducted from the reported error rate of polymerase gamma, the mitochondrial replication enzyme, implying that mtDNA replication errors made during oogenesis are a likely explanation. Substantial variation in the mutation prevalence among mature oocytes can be explained by the highly variable mtDNA copy number, since we previously reported that ∼20% of the primordial germ cells have a mtDNA copy number of ≤73 and would lead to detectable mutation loads. In conclusion, replication errors made during oogenesis are an important source of de novo mtDNA base substitutions and their location and heteroplasmy level determine their significance. Copyright © 2016 by the Genetics Society of America.

  14. Loss of Nek11 Prevents G2/M Arrest and Promotes Cell Death in HCT116 Colorectal Cancer Cells Exposed to Therapeutic DNA Damaging Agents.

    Directory of Open Access Journals (Sweden)

    Sarah R Sabir

    Full Text Available The Nek11 kinase is a potential mediator of the DNA damage response whose expression is upregulated in early stage colorectal cancers (CRCs. Here, using RNAi-mediated depletion, we examined the role of Nek11 in HCT116 WT and p53-null CRC cells exposed to ionizing radiation (IR or the chemotherapeutic drug, irinotecan. We demonstrate that depletion of Nek11 prevents the G2/M arrest induced by these genotoxic agents and promotes p53-dependent apoptosis both in the presence and absence of DNA damage. Interestingly, Nek11 depletion also led to long-term loss of cell viability that was independent of p53 and exacerbated following IR exposure. CRC cells express four splice variants of Nek11 (L/S/C/D. These are predominantly cytoplasmic, but undergo nucleocytoplasmic shuttling mediated through adjacent nuclear import and export signals in the C-terminal non-catalytic domain. In HCT116 cells, Nek11S in particular has an important role in the DNA damage response. These data provide strong evidence that Nek11 contributes to the response of CRC cells to genotoxic agents and is essential for survival either with or without exposure to DNA damage.

  15. Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma

    NARCIS (Netherlands)

    Sauni, Riitta; Uitti, Jukka; Jauhiainen, Merja; Kreiss, Kathleen; Sigsgaard, Torben; Verbeek, Jos H.

    2011-01-01

    Dampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools. To determine the effectiveness of remediating

  16. Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study

    NARCIS (Netherlands)

    H. Schmidt (Helena); F. Fazekas (Franz); G.M. Kostner; R. Schmidt (Reinhold); C.M. van Duijn (Cornelia)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the most important risk factors. We assessed the association between MARCD and sequence

  17. Optimal conditions in (/sup 3/H)-thymidine uptake studies to prevent radiation damage to cells. A scintimetric and cytofluorographic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Arguelles, A.; Llorente, L.; Diaz-Jouanen, E.; Alarcon-Segovia, D. (Instituto Nacional de la Nutricion, Mexico City)

    1981-12-01

    Cells subjected to nucleoside incorporation studies using radiolabelled materials may suffer radiation damage that can alter the results. Scintimetric and cytofluorographic analyses were performed to confirm this and to determine the optimal experimental doses of, and exposure times to, (/sup 3/H)-TdR, in order to prevent or minimize such radiation damage to cells. The results showed that cultures of human mononuclear cells should be pulsed with 0.125 ..mu..Ci for 14 hr when stimulated with phytohaemagglutinin, 0.125 ..mu..Ci for 18 hr when stimulated with pokeweed mitogen, 0.5 ..mu..Ci for 8 hr when stimulated with concanavalin A and 0.5 ..mu..Ci for 8 hr when subjected to allogeneic stimulus, in order to achieve optimal incorporation with minimal disturbances of the cell cycle.

  18. Feather barbs as a good source of mtDNA for bird species identification in forensic wildlife investigations.

    Science.gov (United States)

    Speller, Camilla F; Nicholas, George P; Yang, Dongya Y

    2011-07-28

    The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis. By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl (Glaucidium californicum). The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique. By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis.

  19. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    OpenAIRE

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-01-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in...

  20. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells.

    Science.gov (United States)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Exopolysaccharides Isolated from Milk Fermented with Lactic Acid Bacteria Prevent Ultraviolet-Induced Skin Damage in Hairless Mice.

    Science.gov (United States)

    Morifuji, Masashi; Kitade, Masami; Fukasawa, Tomoyuki; Yamaji, Taketo; Ichihashi, Masamitsu

    2017-01-13

    We studied the mechanism by which fermented milk ameliorates UV-B-induced skin damage and determined the active components in milk fermented with lactic acid bacteria by evaluating erythema formation, dryness, epidermal proliferation, DNA damage and cytokine mRNA levels in hairless mice exposed to acute UV-B irradiation. Nine week-old hairless mice were given fermented milk (1.3 g/kg BW/day) or exopolysaccharide (EPS) concentrate (70 mg/kg BW/day) orally for ten days. Seven days after fermented milk or EPS administration began, the dorsal skin of the mice was exposed to a single dose of UV-B (20 mJ/cm²). Ingestion of either fermented milk or EPS significantly attenuated UV-B-induced erythema formation, dryness and epidermal proliferation in mouse skin. Both fermented milk and EPS were associated with a significant decrease in cyclobutane pyrimidine dimers and upregulated mRNA levels of xeroderma pigmentosum complementation group A (XPA), which is involved in DNA repair. Furthermore, administration of either fermented milk or EPS significantly suppressed increases in the ratio of interleukin (IL)-10/IL-12a and IL-10/interferon-gamma mRNA levels. Together, these results indicate that EPS isolated from milk fermented with lactic acid bacteria enhanced DNA repair mechanisms and modulated skin immunity to protect skin against UV damage.

  2. Exopolysaccharides Isolated from Milk Fermented with Lactic Acid Bacteria Prevent Ultraviolet-Induced Skin Damage in Hairless Mice

    Directory of Open Access Journals (Sweden)

    Masashi Morifuji

    2017-01-01

    Full Text Available Background: We studied the mechanism by which fermented milk ameliorates UV-B-induced skin damage and determined the active components in milk fermented with lactic acid bacteria by evaluating erythema formation, dryness, epidermal proliferation, DNA damage and cytokine mRNA levels in hairless mice exposed to acute UV-B irradiation. Methods: Nine week-old hairless mice were given fermented milk (1.3 g/kg BW/day or exopolysaccharide (EPS concentrate (70 mg/kg BW/day orally for ten days. Seven days after fermented milk or EPS administration began, the dorsal skin of the mice was exposed to a single dose of UV-B (20 mJ/cm2. Results: Ingestion of either fermented milk or EPS significantly attenuated UV-B-induced erythema formation, dryness and epidermal proliferation in mouse skin. Both fermented milk and EPS were associated with a significant decrease in cyclobutane pyrimidine dimers and upregulated mRNA levels of xeroderma pigmentosum complementation group A (XPA, which is involved in DNA repair. Furthermore, administration of either fermented milk or EPS significantly suppressed increases in the ratio of interleukin (IL-10/IL-12a and IL-10/interferon-gamma mRNA levels. Conclusion: Together, these results indicate that EPS isolated from milk fermented with lactic acid bacteria enhanced DNA repair mechanisms and modulated skin immunity to protect skin against UV damage.

  3. Mgm101p is a novel component of the mitochondrial nucleoid that binds DNA and is required for the repair of oxidatively damaged mitochondrial DNA

    International Nuclear Information System (INIS)

    Meeusen, S.; Tieu, Q.; Wong, E.; Weiss, E.; Schieltz, D.; Yates, J.R.; Nunnari, J.

    1999-01-01

    Maintenance of mitochondrial DNA (mtDNA) during cell division is required for progeny to be respiratory competent. Maintenance involves the replication, repair, assembly, segregation, and partitioning of the mitochondrial nucleoid. MGM101 has been identified as a gene essential for mtDNA maintenance in S. cerevisiae, but its role is unknown. Using liquid chromatography coupled with tandem mass spectrometry, we identified Mgm101p as a component of highly enriched nucleoids, suggesting that it plays a nucleoid-specific role in maintenance. Subcellular fractionation, indirect immunofluorescence and GFP tagging show that Mgm101p is exclusively associated with the mitochondrial nucleoid structure in cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part due to this activity. Phenotypic analysis of cells containing a temperature sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging, segregation, partitioning or required for ongoing mtDNA replication. We examined Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells were more sensitive to mtDNA damage induced by UV irradiation and were hypersensitive to mtDNA damage induced by gamma rays and H2O2 treatment. Thus, we propose that Mgm101p performs an essential function in the repair of oxidatively damaged mtDNA that is required for the maintenance of the mitochondrial genome. (author)

  4. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nicolau, L.A.D. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D. [Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Aragão, K.S. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Barbosa, A.L.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Soares, P.M.G.; Souza, M.H.L.P. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Medeiros, J.V.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil)

    2013-08-16

    Our objective was to investigate the protective effect of Lawesson's reagent, an H{sub 2}S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm{sup 2}); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm{sup 2}); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K

  5. Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

    Science.gov (United States)

    Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

    2015-12-01

    It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

  6. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  7. Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

    Science.gov (United States)

    Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

  8. Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection.

    Science.gov (United States)

    Barker, Peter E; Murthy, Mahadev

    2009-11-27

    The anticipated biological and clinical utility of biomarkers has attracted significant interest recently. Aging and early cancer detection represent areas active in the search for predictive and prognostic biomarkers. While applications differ, overlapping biological features, analytical technologies and specific biomarker analytes bear comparison. Mitochondrial DNA (mtDNA) as a biomarker in both biological models has been evaluated. However, it remains unclear whether mtDNA changes in aging and cancer represent biological relationships that are causal, incidental, or a combination of both. This article focuses on evaluation of mtDNA-based biomarkers, emerging strategies for quantitating mtDNA admixtures, and how current understanding of mtDNA in aging and cancer evolves with introduction of new technologies. Whether for cancer or aging, lessons from mtDNA based biomarker evaluations are several. Biological systems are inherently dynamic and heterogeneous. Detection limits for mtDNA sequencing technologies differ among methods for low-level DNA sequence admixtures in healthy and diseased states. Performance metrics of analytical mtDNA technology should be validated prior to application in heterogeneous biologically-based systems. Critical in evaluating biomarker performance is the ability to distinguish measurement system variance from inherent biological variance, because it is within the latter that background healthy variability as well as high-value, disease-specific information reside.

  9. Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection

    Directory of Open Access Journals (Sweden)

    Peter E. Barker

    2009-11-01

    Full Text Available The anticipated biological and clinical utility of biomarkers has attracted significant interest recently. Aging and early cancer detection represent areas active in the search for predictive and prognostic biomarkers. While applications differ, overlapping biological features, analytical technologies and specific biomarker analytes bear comparison. Mitochondrial DNA (mtDNA as a biomarker in both biological models has been evaluated. However, it remains unclear whether mtDNA changes in aging and cancer represent biological relationships that are causal, incidental, or a combination of both. This article focuses on evaluation of mtDNA-based biomarkers, emerging strategies for quantitating mtDNA admixtures, and how current understanding of mtDNA in aging and cancer evolves with introduction of new technologies. Whether for cancer or aging, lessons from mtDNA based biomarker evaluations are several. Biological systems are inherently dynamic and heterogeneous. Detection limits for mtDNA sequencing technologies differ among methods for low-level DNA sequence admixtures in healthy and diseased states. Performance metrics of analytical mtDNA technology should be validated prior to application in heterogeneous biologically-based systems. Critical in evaluating biomarker performance is the ability to distinguish measurement system variance from inherent biological variance, because it is within the latter that background healthy variability as well as high-value, disease-specific information reside.

  10. [Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGM™ Platform].

    Science.gov (United States)

    Cao, Y; Zou, K N; Huang, J P; Ma, K; Ping, Y

    2017-08-01

    To analyze and detect the whole genome sequence of human mitochondrial DNA (mtDNA) by Ion Torrent PGM™ platform and to study the differences of mtDNA sequence in different tissues. Samples were collected from 6 unrelated individuals by forensic postmortem examination, including chest blood, hair, costicartilage, nail, skeletal muscle and oral epithelium. Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer. Libraries were constructed with Ion Shear™ Plus Reagents kit and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed using Ion Torrent PGM™ platform. Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HVⅠ region. The whole genome sequence of mtDNA from all samples were amplified successfully. Six unrelated individuals belonged to 6 different haplotypes. Different tissues in one individual had heteroplasmy difference. The heteroplasmy positions and the mutation positions on HVⅠ region were verified by Sanger sequencing. After a consistency check by the Kappa method, it was found that the results of mtDNA sequence had a high consistency in different tissues. The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues, which have good consistency. The results provide guidance for the further applications of mtDNA in forensic science. Copyright© by the Editorial Department of Journal of Forensic Medicine

  11. Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex.

    Science.gov (United States)

    Zhu, Ben-Zhan; Mao, Li; Fan, Rui-Mei; Zhu, Jun-Ge; Zhang, Ying-Nan; Wang, Jing; Kalyanaraman, Balaraman; Frei, Balz

    2011-01-14

    Ergothioneine (2-mercaptohistidine trimethylbetaine) is a naturally occurring amino acid analogue found in up to millimolar concentrations in several tissues and biological fluids. However, the biological functions of ergothioneine remain incompletely understood. In this study, we investigated the role of ergothioneine in copper-induced oxidative damage to DNA and protein, using two copper-containing systems: Cu(II) with ascorbate and Cu(II) with H(2)O(2) [0.1 mM Cu(II), 1 mM ascorbate, and 1 mM H(2)O(2)]. Oxidative damage to DNA and bovine serum albumin was measured as strand breakage and protein carbonyl formation, respectively. Ergothioneine (0.1-1.0 mM) provided strong, dose-dependent protection against oxidation of DNA and protein in both copper-containing systems. In contrast, only limited protection was observed with the purported hydroxyl radical scavengers, dimethyl sulfoxide and mannitol, even at concentrations as high as 100 mM. Ergothioneine also significantly inhibited copper-catalyzed oxidation of ascorbate and competed effectively with histidine and 1,10-phenanthroline for binding of cuprous copper, but not cupric copper, as demonstrated by UV-visible and low-temperature electron spin resonance techniques. We conclude that ergothioneine is a potent, natural sulfur-containing antioxidant that prevents copper-dependent oxidative damage to biological macromolecules by forming a redox-inactive ergothioneine-copper complex.

  12. Commercialization of a system to prevent the insect damage by termite. Kansai Electric Power Co.; Shiroari shokugai boshi system no jitsuyoka ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, T. [Kansai Electric Power Co. Inc., Osaka (Japan)

    2000-01-10

    The paper studied measures to prevent the underground power cable from insect damage by termite. To search for the termite entering the cable, fiber inspection is good, but the length which fiber reaches and the margin of cable diameter are limited. Moreover, the termite prevention use PFP pipe has been developed, but termite invades inside from the joint in PFP pipe. In AP pipe, termite invades from the place where concrete placing is poor and from cracks. As to the method to search for termite, sounds which termite emit to threaten foreign enemies were gathered by microphone, and the frequency was analyzed. As a result, it was verified that it is possible to judge if there is termite or not by checking levels in the 50-1300Hz zone (the method to let termite emit the threatening sound has been unknown). Since the path of invasion of termite is limited to the joint of cable, a thing in which chemical is put on rubber band of cable joint was developed. The chemical which was a little put on the rubber band is a domestic use insecticide generally commercially available, and adopted pyrethroids base chemical the safety of which was estimated. There is no need for spray of termite prevention agent, and the chemical is lower-priced than a change to the termite prevention cable. (NEDO)

  13. Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease.

    Science.gov (United States)

    Bacman, S R; Williams, S L; Garcia, S; Moraes, C T

    2010-06-01

    Most pathogenic mtDNA mutations are heteroplasmic and there is a clear correlation between high levels of mutated mtDNA in a tissue and pathology. We have found that in vivo double-strand breaks (DSBs) in mtDNA lead to digestion of cleaved mtDNA and replication of residual mtDNA. Therefore, if DSB could be targeted to mutations in mtDNA, mutant genomes could be eliminated and the wild-type mtDNA would repopulate the cells. This can be achieved by using mitochondria-targeted restriction endonucleases as a means to degrade specific mtDNA haplotypes in heteroplasmic cells or tissues. In this work, we investigated the potential of systemic delivery of mitochondria-targeted restriction endonucleases to reduce the proportion of mutant mtDNA in specific tissues. Using the asymptomatic NZB/BALB mtDNA heteroplasmic mouse as a model, we found that a mitochondria-targeted ApaLI (that cleaves BALB mtDNA at a single site and does not cleave NZB mtDNA) increased the proportion of NZB mtDNA in target tissues. This was observed in heart, using a cardiotropic adeno-associated virus type-6 (AAV6) and in liver, using the hepatotropic adenovirus type-5 (Ad5). No mtDNA depletion or loss of cytochrome c oxidase activity was observed in any of these tissues. These results show the potential of systemic delivery of viral vectors to specific organs for the therapeutic application of mitochondria-targeted restriction enzymes in mtDNA disorders.

  14. Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin

    Science.gov (United States)

    Yu, Chia-Chia; Nandrot, Emeline F.; Dun, Ying; Finnemann, Silvia C.

    2011-01-01

    In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5−/− RPE but not neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants grapes or marigold extract containing macular pigments lutein/zeaxanthin was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in β5−/− mice. Acute generation of HNE-adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet. PMID:22178979

  15. Preventive effects of an original combination of grape seed polyphenols with amine fluoride on dental biofilm formation and oxidative damage by oral bacteria.

    Science.gov (United States)

    Furiga, A; Roques, C; Badet, C

    2014-04-01

    To investigate the preventive effects of an original combination of a grape seed extract (GSE) with an amine fluoride (Fluorinol(®) ) on dental plaque formation and oxidative damage caused by oral bacteria. The antibacterial activity of the compounds was assessed using the broth macrodilution method, and their antiplaque activity was evaluated on a multispecies biofilm grown on saliva-coated hydroxyapatite discs. The effect on glucosyltransferases activity was analysed through reductions in the overall reaction and the quantity of insoluble glucan synthesized. The combination of 2000 μg ml(-1) of GSE with 10·2 mg ml(-1) of Fluorinol(®) significantly decreased the biofilm formation (up to 4·76 log10 of reduction) and inhibited by 97·4% the insoluble glucan synthesis by glucosyltransferases. The antioxidant activity of this combination, alone or incorporated into a formulated mouthwash (Eludril daily(®) ), was determined using the Trolox equivalent antioxidant capacity assay (TEAC), and both showed significantly greater antioxidant capacity than vitamin C. The GSE/Fluorinol(®) combination showed both a significant antiplaque activity and an important antioxidant capacity in vitro, without any bactericidal effects. This is, to our knowledge, the first report on the properties of an original combination of a polyphenolic extract with amine fluoride that could be used for the prevention of oral diseases and oxidative damage associated. © 2013 The Society for Applied Microbiology.

  16. The use of nano-quercetin to arrest mitochondrial damage and MMP-9 upregulation during prevention of gastric inflammation induced by ethanol in rat.

    Science.gov (United States)

    Chakraborty, Somsuta; Stalin, Sami; Das, Nirmalendu; Choudhury, Somsubhra Thakur; Ghosh, Swarupa; Swarnakar, Snehasikta

    2012-04-01

    Gastric ulcer is a multifaceted process that involves reactive oxygen species (ROS) generation, extracellular matrix degradation and mitochondrial damage. Mitochondria play a crucial role for homeostasis of ROS and cell survival. In our study, we investigated the efficacy and mechanism of polymeric nanocapsuled quercetin (NQC) over the free quercetin (QC) molecule in prevention of ethanol-induced gastric ulcer in rat. NQC possessed significantly higher efficacy (~20 fold) than free QC while preventing gastric ulcers. Our data show that prior administration of NQC and/or QC significantly blocked synthesis and secretion of matrix metalloproteinase (MMP)-9 as well as infiltration of inflammatory cells and oxidative damage in rat gastric tissues. As compared to free QC, NQC protected much better the mitochondrial integrity and size along with mitochondrial functions by controlling succinate dehydrogenase and NADH oxidase in rat gastric tissues. In addition, both free QC and NQC down regulated PARP-1 as well as apoptosis during protection against ethanol-induced gastric ulcer. Herein, the effect of NQC was greater than QC on expression of enzymes like cyclooxygenase and nitric oxidase synthase (NOS)-2. We conclude that NQC with greater bioavailability offers significantly higher potency in downregulating MMP-9 and NOS-2 as well as oxidative stress in blocking ethanol-induced gastric ulcer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Assessment of mitochondrial DNA damage in little brown bats (Myotis lucifugus) collected near a mercury-contaminated river

    Science.gov (United States)

    Karouna-Renier, Natalie K.; White, Carl; Perkins, Christopher R.; Schmerfeld, John J.; Yates, David

    2014-01-01

    Historical discharges of Hg into the South River near the town of Waynesboro, VA, USA, have resulted in persistently elevated Hg concentrations in sediment, surface water, ground water, soil, and wildlife downstream of the discharge site. In the present study, we examined mercury (Hg) levels in in little brown bats (Myotis lucifugus) from this location and assessed the utility of a non-destructively collected tissue sample (wing punch) for determining mitochondrial DNA (mtDNA) damage in Hg exposed bats. Bats captured 1 and 3 km from the South River, exhibited significantly higher levels of total Hg (THg) in blood and fur than those from the reference location. We compared levels of mtDNA damage using real-time quantitative PCR (qPCR) analysis of two distinct regions of mtDNA. Genotoxicity is among the many known toxic effects of Hg, resulting from direct interactions with DNA or from oxidative damage. Because it lacks many of the protective protein structures and repair mechanisms associated with nuclear DNA, mtDNA is more sensitive to the effects of genotoxic chemicals and therefore may be a useful biomarker in chronically exposed organisms. Significantly higher levels of damage were observed in both regions of mtDNA in bats captured 3 km from the river than in controls. However, levels of mtDNA damage exhibited weak correlations with fur and blood THg levels, suggesting that other factors may play a role in the site-specific differences.

  18. DNA Extraction Procedures Meaningfully Influence qPCR-Based mtDNA Copy Number Determination

    OpenAIRE

    Guo, Wen; Jiang, Lan; Bhasin, Shalender; Khan, Shaharyar M.; Swerdlow, Russell H.

    2009-01-01

    Quantitative real time PCR (qPCR) is commonly used to determine cell mitochondrial DNA (mtDNA) copy number. This technique involves obtaining the ratio of an unknown variable (number of copies of an mtDNA gene) to a known parameter (number of copies of a nuclear DNA gene) within a genomic DNA sample. We considered the possibility that mtDNA: nuclear DNA (nDNA) ratio determinations could vary depending on the method of genomic DNA extraction used, and that these differences could substantively...

  19. Nanocurcumin–pyrroloquinoline formulation prevents hypertrophy–induced pathological damage by relieving mitochondrial stress in cardiomyocytes under hypoxic conditions

    Science.gov (United States)

    Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Chattopadhyay, Pronobesh; Saraswat, Deepika

    2017-01-01

    This study investigates the therapeutic effect of a nanocurcumin formulation (NCF) containing nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) on ameliorating hypoxia-induced stress in hypertrophied primary human ventricular cardiomyocytes (HVCM) under hypoxic conditions, as validated in a Sprague-Dawley rat model of chronic hypobaric hypoxia (cHH)-induced right ventricular hypertrophy (RVH). Based on our previous findings, here, we analyzed the improvement in the protective efficacy of NCF against mitochondrial damage. The electron transport chain Complexes’ activities were analyzed as a chief operational center for mitochondrial homeostasis, along with key gene and protein markers for mitochondrial biogenesis, redox function, fatty acid oxidation, bio-energetic deficit and cell survival. NCF supplementation imparts cyto-protection from hypoxia-induced hypertrophy and damage in both in vitro and in vivo models while maintaining mitochondrial homeostasis better than NC and PQQ alone. This study proposes the use of NCF as a potential candidate molecule for imparting protection from high altitude-induced maladies in ascendants.

  20. Preventing Electromagnetic Pulse Irradiation Damage on Testis Using Selenium-rich Cordyceps Fungi. A Preclinical Study in Young Male Mice.

    Science.gov (United States)

    Miao, Xia; Wang, Yafeng; Lang, Haiyang; Lin, Yanyun; Guo, Qiyan; Yang, Mingjuan; Guo, Juan; Zhang, Yanjun; Zhang, Jie; Liu, Junye; Liu, Yaning; Zeng, Lihua; Guo, Guozhen

    2017-02-01

    Networked 21st century society, globalization, and communications technologies are paralleled by the rise of electromagnetic energy intensity in our environments and the growing pressure of the environtome on human biology and health. The latter is the entire complement of environmental factors, including the electromagnetic energy and the technologies that generate them, enacting on the digital citizen in the new century. Electromagnetic pulse (EMP) irradiation might have serious damaging effects not only on electronic equipment but also in the whole organism and reproductive health, through nonthermal effects and oxidative stress. We sought to determine whether EMP exposure (1) induces biological damage on reproductive health and (2) the extent to which selenium-rich Cordyceps fungi (daily coadministration) offer protection on the testicles and spermatozoa. In a preclinical randomized study, 3-week-old male BALB/c mice were repeatedly exposed to EMP (peak intensity 200 kV/m, pulse edge 3.5 ns, pulse width 15 ns, 0.1 Hz, and 400 pulses/day) 5 days per week for four consecutive weeks, with or without coadministration of daily selenium-rich Cordyceps fungi (100 mg/kg). Testicular index and spermatozoa formation were measured at baseline and 1, 7, 14, 28, and 60 day time points after EMP exposure. The group without Cordyceps cotreatment displayed decreased spermatozoa formation, shrunk seminiferous tubule diameters, and diminished antioxidative capacity at 28 and 60 days after exposure (p digital citizenship.

  1. Assessment of Free Radical Scavenging Potential and Oxidative DNA Damage Preventive Activity of Trachyspermum ammi L. (Carom and Foeniculum vulgare Mill. (Fennel Seed Extracts

    Directory of Open Access Journals (Sweden)

    Nandini Goswami

    2014-01-01

    Full Text Available Oxidation of biomolecules such as carbohydrates, proteins, lipids, and nucleic acids results in generation of free radicals in an organism which is the major cause of onset of various degenerative diseases. Antioxidants scavenge these free radicals, thereby protecting the cell from damage. The present study was designed to examine the free radical scavenging potential and oxidative DNA damage preventive activity of traditionally used spices Trachyspermum ammi L. (carom and Foeniculum vulgare Mill. (fennel. The aqueous, methanolic, and acetonic extracts of T. ammi and F. vulgare seeds were prepared using soxhlet extraction assembly and subjected to qualitative and quantitative estimation of phytochemical constituents. Free radical scavenging potential was investigated using standard methods, namely, DPPH radical scavenging assay and ferric reducing antioxidant power assay along with the protection against oxidative DNA damage. The results stated that acetonic seed extracts (AAcSE and FAcSE of both the spices possessed comparatively high amount of total phenolics whereas methanolic seed extracts (AMSE and FMSE were found to have highest amount of total flavonoids. At 1 mg/mL concentration, highest DPPH radical scavenging activity was shown by FMSE (96.2%, AAcSE was recorded with highest FRAP value (2270.27 ± 0.005 μmol/L, and all the seed extracts have been shown to mitigate the damage induced by Fenton reaction on calf thymus DNA. Therefore, the study suggests that T. ammi and F. vulgare seed extracts could contribute as a highly significant bioresource of antioxidants to be used in our day-to-day life and in food and pharmaceutical industry.

  2. Assessment of free radical scavenging potential and oxidative DNA damage preventive activity of Trachyspermum ammi L. (carom) and Foeniculum vulgare Mill. (fennel) seed extracts.

    Science.gov (United States)

    Goswami, Nandini; Chatterjee, Sreemoyee

    2014-01-01

    Oxidation of biomolecules such as carbohydrates, proteins, lipids, and nucleic acids results in generation of free radicals in an organism which is the major cause of onset of various degenerative diseases. Antioxidants scavenge these free radicals, thereby protecting the cell from damage. The present study was designed to examine the free radical scavenging potential and oxidative DNA damage preventive activity of traditionally used spices Trachyspermum ammi L. (carom) and Foeniculum vulgare Mill. (fennel). The aqueous, methanolic, and acetonic extracts of T. ammi and F. vulgare seeds were prepared using soxhlet extraction assembly and subjected to qualitative and quantitative estimation of phytochemical constituents. Free radical scavenging potential was investigated using standard methods, namely, DPPH radical scavenging assay and ferric reducing antioxidant power assay along with the protection against oxidative DNA damage. The results stated that acetonic seed extracts (AAcSE and FAcSE) of both the spices possessed comparatively high amount of total phenolics whereas methanolic seed extracts (AMSE and FMSE) were found to have highest amount of total flavonoids. At 1 mg/mL concentration, highest DPPH radical scavenging activity was shown by FMSE (96.2%), AAcSE was recorded with highest FRAP value (2270.27 ± 0.005 μmol/L), and all the seed extracts have been shown to mitigate the damage induced by Fenton reaction on calf thymus DNA. Therefore, the study suggests that T. ammi and F. vulgare seed extracts could contribute as a highly significant bioresource of antioxidants to be used in our day-to-day life and in food and pharmaceutical industry.

  3. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  4. Mitochondrial DNA (mtDNA haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Fernandez-Moreno Mercedes

    2011-11-01

    Full Text Available Abstract Background Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2 and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. Methods We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI, age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. Results Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p Conclusions The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase

  5. Mitochondrial DNA (mtDNA haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

    Directory of Open Access Journals (Sweden)

    Juan J. Yunis

    2013-01-01

    Full Text Available The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.

  6. mtDNA point and length heteroplasmy in high- and low radiation areas of Kerala

    International Nuclear Information System (INIS)

    Forster, L.; Forster, P.; Gurney, S.M.; Spencer, M.; Huang, C.; Röhl, A.; Brinkmann, B.

    2010-01-01

    A coastal peninsula in Kerala (India) contains the world's highest level of natural radioactivity in a densely populated area, offering an opportunity to characterize radiation-associated DNA mutations. Here, we focus on mitochondrial DNA (mtDNA) mutations, which are passed exclusively from the mother to her children. To analyse point mutations, we sampled 248 pedigrees (988 individuals) in the high-radiation peninsula and in nearby low-radiation islands as a control population. Then, in an extended sample of 1,172 mtDNA sequences (containing some non-Indians for comparison), we also analysed length mutations, which in mtDNA can lead to the phenomenon of length heteroplasmy, i.e. the existence of different DNA types in the same cell. We wished to find out how fast mtDNA mutates between generations, and whether the mutation rate is increased in radioactive conditions compared to the low-irradiation sample

  7. Searching for doubly uniparental inheritance of mtDNA in the apple snail Pomacea diffusa.

    Science.gov (United States)

    Parakatselaki, Maria Eleni; Saavedra, Carlos; Ladoukakis, Emmanuel D

    2016-11-01

    Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) is an exceptional mode of mtDNA transmission, restricted so far to the class of bivalves. We searched for DUI outside bivalves using the apple snail Pomacea diffusa. It was an appropriate candidate to search for DUI for three reasons; it belongs to gastropods, which is the closest sister group to bivalves, it is gonochoristic and it has a strong sex bias in the progeny of different female individuals. These phenomena (gonochorism and sex-biased progeny) are also found in species with DUI. We searched for heteroplasmy in males and for high sequence divergence among mtDNA sequences obtained from male and female gonads. All sequences examined were identical. These data suggest that the mtDNA in P. diffusa is maternally transmitted and DUI remains an exclusive characteristic of bivalves.

  8. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2014-01-01

    Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

  9. Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

    Directory of Open Access Journals (Sweden)

    Martyn A. Sharpe

    2012-01-01

    Full Text Available Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

  10. Southeast Asian diversity: first insights into the complex mtDNA structure of Laos.

    Science.gov (United States)

    Bodner, Martin; Zimmermann, Bettina; Röck, Alexander; Kloss-Brandstätter, Anita; Horst, David; Horst, Basil; Sengchanh, Sourideth; Sanguansermsri, Torpong; Horst, Jürgen; Krämer, Tanja; Schneider, Peter M; Parson, Walther

    2011-02-18

    Vast migrations and subsequent assimilation processes have shaped the genetic composition of Southeast Asia, an area of close contact between several major ethnic groups. To better characterize the genetic variation of this region, we analyzed the entire mtDNA control region of 214 unrelated donors from Laos according to highest forensic quality standards. To detail the phylogeny, we inspected selected SNPs from the mtDNA coding region. For a posteriori data quality control, quasi-median network constructions and autosomal STR typing were performed. In order to describe the mtDNA setup of Laos more thoroughly, the data were subjected to population genetic comparisons with 16 East Asian groups. The Laos sample exhibited ample mtDNA diversity, reflecting the huge number of ethnic groups listed. We found several new, so far undescribed mtDNA lineages in this dataset and surrounding populations. The Laos population was characteristic in terms of haplotype composition and genetic structure, however, genetic comparisons with other Southeast Asian populations revealed limited, but significant genetic differentiation. Notable differences in the maternal relationship to the major indigenous Southeast Asian ethnolinguistic groups were detected. In this study, we portray the great mtDNA variety of Laos for the first time. Our findings will contribute to clarify the migration history of the region. They encourage setting up regional and subpopulation databases, especially for forensic applications. The Laotian sequences will be incorporated into the collaborative EMPOP mtDNA database http://www.empop.org upon publication and will be available as the first mtDNA reference data for this country.

  11. N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

    Directory of Open Access Journals (Sweden)

    Costa Nicola

    2007-12-01

    Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

  12. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

    2011-01-01

    Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  13. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kukat, Alexandra [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Edgar, Daniel [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Bratic, Ivana [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Maiti, Priyanka [Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany); Trifunovic, Aleksandra, E-mail: aleksandra.trifunovic@ki.se [Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-17171 Stockholm (Sweden); Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Cologne University Clinic, D-50674 Cologne (Germany)

    2011-06-10

    Highlights: {yields} Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. {yields} This process is independent of endogenous ROS production. {yields} Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O{sub 2}) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  14. Multiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans

    Directory of Open Access Journals (Sweden)

    Suraiya Haroon

    2018-03-01

    Full Text Available Summary: Genetic instability of the mitochondrial genome (mtDNA plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could be rescued by intervening in numerous biological pathways, including IGF-1/insulin signaling, mitophagy, and the mitochondrial unfolded protein response, suggesting that it may be possible to ameliorate mtDNA disease through multiple molecular mechanisms. : Haroon et al. describe a genetically engineered C. elegans that carries an error-prone copy of DNA polymerase γ, the enzyme that replicates the mitochondrial genome. This worm recapitulates the major hallmarks of mitochondrial disease in humans. The authors identify multiple biological pathways that could potentially delay disease progression. Keywords: mitochondrial genome, mitophagy, mitochondrial unfolded protein response, IGF-1/insulin signaling, polymerase gamma, mutation, mitochondrial disease, mitochondrial DNA depletion, RNAi, neuromuscular dysfunction

  15. Quality investigation of building structure using ground penetrating radar (GPR) as an early study to prevent severe structural damage

    Science.gov (United States)

    Gumai, M. Fariz; Fernando, Stephen; Nugroho, Gatot; Natania, Kana; Widodo

    2017-07-01

    Many infrastructures in Indonesia suffered damage in a short period of time. It proves that there are still many buildings in Indonesia which have questionable quality so a method is needed for checking the quality of the building. Ground Penetrating Radar (GPR) is a method used to describe the structure of the building on the inside that cannot be seen from the outside in this case Parahyangan Reksa Raga (PASAGA) Bridge was examined with 19.7 m × 3.3 m × 1.5 m dimension. Thismethod uses propagation of electromagnetic wave, which will give Radargram response inside a building based on the characteristics of the medium such as magnetic permeability, electric permittivity and electrical conductivity. GPR method is one of geophysical method which is effective, efficient, and environmentally friendly. The measurements were carried out using MALA RAMAC X3M device with frequency 800 MHz. The results show thatindication of fractures was found at less than 1 m depth in the structure from the Radargram display of PASAGA Bridge and supported by the observation data on the surface.

  16. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang, E-mail: songyangwenrong@hotmail.com

    2014-10-15

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably.

  17. Flow measurement in turbine bearings. A measure to prevent damage; Durchflussmessung an Turbinenlagern. Eine Massnahme zur Verhuetung von Schaeden

    Energy Technology Data Exchange (ETDEWEB)

    Nagler, T. [STEAG AG, Heizkraftwerk Herne (Germany); Schenk, K. [STEAG AG, Essen (Germany)

    1999-10-01

    The temperature of sliding bearings for turbines, pumps, compressors, blowers and motors is normally continually monitored. Depending on the type of construction and size of the aggregates, it has been common practice since the beginning of 1960 to measure the temperature of the bearing metal directly instead of the outflowing oil. Provided measurements are made also in areas of the highest surface compression, any deficiency, i.e. overload due to increasing bearing metal temperatues, are noticed at an early stage. In case of other design types, however, serious damage might result. But also serious maintenance errors due to the closure of bearing oil flow have forced us to implement more suitable measuring measures, one of them being an ultrasonic quantity measurement, that can be refurbished without great expenditure during operation. (orig.) [Deutsch] Gleitlager fuer Turbinen, Pumpen, Verdichter, Geblaese, Getriebe und Motoren werden ueblicherweise kontinuierlich temperaturmaessig ueberwacht. Seit Anfang 1960 werden je nach Bauart und Groesse der Aggregate Temperaturen nicht mehr des ablaufendes Oeles, sondern des Weissmetalls direkt gemessen. Vorausgesetzt, es wird auch im Bereich der hoechsten Flaechenpressung gemessen, werden Maengel, d.h. Ueberbelastung durch ansteigende Weissmetalltemperaturen, schnell erkannt. Bei anderen Konstruktionen hingegen kann es zu schweren Schaeden kommen. Aber auch gravierende Wartungsfehler durch Verschluss der Lageroelzufuhr haben uns gezwungen, geeignetere Messmethoden anzuwenden. Hierzu gehoert eine Mengenmessung mittels Ultraschall, die ohne viel Aufwand waehrend des Betriebes nachgeruestet werden kann. (orig.)

  18. Method to prevent ejecta from damaging the Compact Torus Accelerator driver of an inertial fusion energy power plant

    International Nuclear Information System (INIS)

    Mattingly, S.E.K.; Moir, R.W.

    1992-01-01

    Concern has been expressed about the conceptual design of fusion reactors using a Compact Torus Accelerator (CTA). A CTA accelerates a plasma torus toward a fusion target. When the torus nears the target, it is compressed and focused down to a small volume, creating a very high energy density and initiating a fusion micro explosion. The focusing cone is destroyed with each shot due to the stress from the passage of the torus as well as from the force of the explosion (1 800 MJ of yield, ∼0.5 Ton TNT equivalent). The focusing cone could be made of solidified Li 2 BeF 4 ; the same material used in liquid state to protect the reaction chamber from the micro explosion and to transport heat away to a power plant. The problem with this design is that when the focusing cone is shattered, the resulting small pieces of solid and liquid debris (ejecta) might be carded along by the expanding vapor of the explosion and might enter the CTA itself, causing damage and shortening the life of the CTA. The proposed solution for this possible problem is to bend the focusing cone so that the ejecta no longer have a clear path to the CTA. Calculations show that the plasma torus may be sent through a radius of curvature of less than 0.5 m just after the focusing cone, without significantly disturbing the plasma

  19. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    International Nuclear Information System (INIS)

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang

    2014-01-01

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably

  20. SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing

    Directory of Open Access Journals (Sweden)

    Linlin Chen

    2017-12-01

    Full Text Available Dysregulated alternative splicing events have been implicated in many types of cancer, but the underlying molecular mechanisms remain unclear. Here, we observe that the splicing factor SRSF1 regulates DBF4B exon6 splicing by specifically binding and promoting its inclusion. Knockdown of the exon6-containing isoform (DBF4B-FL significantly inhibits the tumorigenic potential of colon cancer cells in vitro and in mice, and SRSF1 inactivation phenocopies DBF4B-FL depletion. DBF4B-FL and SRSF1 are required for cancer cell proliferation and for the maintenance of genomic stability. Overexpression of DBF4B-FL can protect against DNA damage induced by SRSF1 knockdown and rescues growth defects in SRSF1-depleted cells. Increased DBF4B exon6 inclusion parallels SRSF1 upregulation in clinical colorectal cancer samples. Taken together, our findings identify SRSF1 as a key regulator of DBF4B pre-mRNA splicing dysregulation in colon cancer, with possible clinical implications as candidate prognostic factors in cancer patients.

  1. Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis

    Science.gov (United States)

    Arora, Sumit; Tyagi, Nikhil; Bhardwaj, Arun; Rusu, Lilia; Palanki, Rohan; Vig, Komal; Singh, Shree R.; Singh, Ajay P.; Palanki, Srinivas; Miller, Michael E.; Carter, James E.; Singh, Seema

    2015-01-01

    Ultraviolet (UV)-B radiation from the sun is an established etiological cause of skin cancer, which afflicts more than a million lives each year in the United States alone. Here, we tested the chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-irradiation-induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT). AgNPs were synthesized by reduction-chemistry and characterized for their physicochemical properties. AgNPs were well tolerated by HaCaT cells and their pretreatment protected them from UVB-irradiation-induced apoptosis along with significant reduction in cyclobutane-pyrimidine-dimer formation. Moreover, AgNPs pre-treatment led to G1-phase cell-cycle arrest in UVB-irradiated HaCaT cells. AgNPs were efficiently internalized in UVB-irradiated cells and localized into cytoplasmic and nuclear compartments. Furthermore, we observed an altered expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in HaCaT cells treated with AgNPs prior to UVB-irradiation. Together, these findings provide support for potential utility of AgNPs as novel chemopreventive agents against UVB-irradiation-induced skin carcinogenesis. PMID:25804413

  2. The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

    Directory of Open Access Journals (Sweden)

    Yanjun Zhang

    2014-07-01

    Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

  3. Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

    Science.gov (United States)

    Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

    2014-08-01

    Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage. © 2014 The Authors. Journal of Neurochemistry

  4. Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    H. Milani

    1999-10-01

    Full Text Available In the central nervous system, magnesium ion (Mg2+ acts as an endogenous modulator of N-methyl-D-aspartate (NMDA-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg, either alone or in combination with diazepam (DZ, on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc in single (1x, 2 h post-ischemia or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia. DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34, DZ (10 mg/kg, N = 24, MgCl2 (2.5 mmol/kg, N = 10, MgCl2 (5.0 mmol/kg, N = 17, MgCl2 (7.5 mmol/kg, N = 9 or MgCl2 (5 mmol/kg + DZ (10 mg/kg, N = 14. Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3% and CA1 (88.4% sectors of the hippocampus (P0.05. Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05. No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.

  5. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  6. [The concept of loss of chance: A major evolution in the definition of damage or how to prevent litigation for loss of chance?].

    Science.gov (United States)

    Nguyen, T-D

    2016-07-01

    The concept of medical error in responsibility litigation was based until the past last years on a necessary direct and definite causal link between fault and injury. In France, since the 1960s and increasingly during the last decade, the idea of loss of chance arose, considered as a new and genuine prejudice (practically, a fixable damage); it became the subject of several legal precedents from the Cour de cassation and the Conseil d'État. Thus, plaintiffs may currently demand a compensation for a loss of chance even though a doubt exists on the causal link between the fault and the observed damage. The most frequent litigation circumstances implying a loss of chance are lack of information, lack or delay in diagnosis, delay in action, and default in medical assessment. Based on practical cases, the author presents the most propitious situations where litigation for loss of chance may occur and discusses possible preventive measures. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  7. Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1/Wnt Pathway.

    Science.gov (United States)

    Tulsulkar, Jatin; Glueck, Bryan; Hinds, Terry D; Shah, Zahoor A

    2016-04-01

    It is well known that gender differences exist in experimental or clinical stroke with respect to brain damage and loss of functional outcome. We have previously reported neuroprotective properties of Ginkgo biloba/EGb 761® (EGb 761) in transient and permanent mouse models of brain ischemia using male mice, and the mechanism of action was attributed to the upregulation of the heme oxygenase 1 (HO1)/Wnt pathway. Here, we sought to investigate whether EGb 761's protective effect in ovariectomized female mice following stroke is also mediated by the HO1/Wnt pathway. Female mice were ovariectomized (OVX) to remove the protective effect of estrogen and were treated with EGb 761 for 7 days prior to inducing permanent middle cerebral artery occlusion (pMCAO) and allowed to survive for an additional 7 days. At day 8, animals were sacrificed, and the brains were harvested for infarct volume analysis, western blots, and immunohistochemistry. The OVX female mice treated with EGb 761 showed significantly lower infarct size as compared to Veh/OVX animals. EGb 761 treatment in female mice inhibited apoptosis by preventing caspase-3 cleavage and blocking the extrinsic apoptotic pathway. EGb 761 pretreatment significantly enhanced neurogenesis in OVX mice as compared to the Veh/OVX group and significantly upregulated androgen receptor expression with no changes in HO1/Wnt signaling. These results suggest that EGb 761 prevented brain damage in OVX female mice by improving grip strength and neurological deficits, and the mechanism of action is not through HO1/Wnt but via blocking the extrinsic apoptotic pathway.

  8. An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2013-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia. Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications, the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction. This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

  9. Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

    Science.gov (United States)

    Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

    2014-01-01

    Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

  10. Prevention of UV-induced damage to the anterior segment using class I UV-absorbing hydrogel contact lenses.

    Science.gov (United States)

    Chandler, Heather L; Reuter, Kathleen S; Sinnott, Loraine T; Nichols, Jason J

    2010-01-01

    To determine whether class I ultraviolet (UV) light-blocking contact lenses prevent UV-induced pathologic changes in a rabbit model. Twelve rabbits were assigned to 1 of 3 treatment groups (n = 4), as follows: senofilcon A (class I UV blocking) contact lenses; lotrafilcon A contact lenses (no reported UV blocking); no contact lens. The contralateral eye was patched without a contact lens. Animals received UV-B (1.667 J/cm(2)) exposure daily for 5 days. Postmortem tissue was examined as follows: in the cornea, the expression of matrix-metalloproteinases (MMPs) was evaluated by zymography, and apoptosis was evaluated by TUNEL and caspase-3 ELISA; ascorbate in the aqueous humor was evaluated by nuclear magnetic resonance spectroscopy; crystalline lens apoptosis was evaluated by TUNEL and caspase-3 ELISA. Exposed corneas showed a significant increase in MMP-2 and -9, TUNEL-positive cells, and caspase-3 activity in the lotrafilcon A group compared with the senofilcon A group (all P = 0.03). A significant decrease in aqueous humor ascorbate was observed in the exposed lotrafilcon A lens-wearing group compared with the exposed senofilcon A lens-wearing group (P = 0.03). Exposed crystalline lenses had significantly increased caspase-3 activity in the lotrafilcon A group compared with the senofilcon A group (P = 0.03). Increased numbers of TUNEL-positive cells were noted in both the lotrafilcon A and the non-contact lens groups. The authors show that senofilcon A class I UV-blocking contact lenses are capable of protecting the cornea, aqueous humor, and crystalline lens of rabbits from UV-induced pathologic changes.

  11. Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways.

    Science.gov (United States)

    Fowler, Robert G; White, Steven J; Koyama, Carol; Moore, Sean C; Dunn, Ronnie L; Schaaper, Roel M

    2003-02-03

    We have investigated in detail the interactions between the Escherichia coli mutT, mutM, and mutY error-prevention systems. Jointly, these systems protect the cell against the effects of the oxidative stress product, 8-oxoguanine (8-oxoG), a base analog with ambiguous base-pairing properties, pairing with either A or C during DNA synthesis. mutT mutator strains display a specific increase in A.T-->C.G transversions, while mutM and mutY mutator strains show specific G.C-->T.A increases. To study in more detail the in vivo processing of the various mutational intermediates leading to A.T-->C.G and G.C-->T.A transversions, we analyzed defined A.T-->C.G and G.C-->T.A events in strains containing all possible combinations of these mutator alleles. We report three major findings. First, we do not find evidence that the mutT allele significantly increases G.C-->T.A transversions in either mut(+), mutM, mutY or mutMmutY backgrounds. We interpret this result to indicate that incorporation of 8-oxodGTP opposite template C may not be frequent relative to incorporation opposite template A. Second, we show that mutT-induced A.T-->C.G transversions are significantly reduced in strains carrying mutY and mutMmutY deficiencies suggesting that 8-oxoG, when present in DNA, preferentially mispairs with dATP. Third, the mutY and mutMmutY deficiencies also decrease A.T-->C.G transversions in the mutT(+) background, suggesting that, even in the presence of functional MutT protein, A.T-->C.G transversions may still result from 8-oxodGTP misincorporation.

  12. Hyperglycemia, oxidative stress, liver damage and dysfunction in alloxan-induced diabetic rat are prevented by Spirulina supplementation.

    Science.gov (United States)

    Gargouri, Manel; Magné, Christian; El Feki, Abdelfattah

    2016-11-01

    Medicinal plants have long been used against life-threatening diseases including diabetes, with more or less success. Some of these plants have been shown to possess antioxidant activities, which could help improving diabetes inconveniences. In that context, we investigated the effects of spirulina supplementation on alloxan-induced diabetic rats, hypothesizing that co-administration of spirulina with rat diet could ameliorate diabetes complications and provide as benefits as the common antidiabetic insulin. Following alloxan treatment, male Wistar rats were fed daily with 5% spirulina-enriched diet or treated with insulin (0.5 IU/rat) for 21 days. Both spirulina and insulin treatments of diabetic rats resulted in a significant reduction in fasting blood glucose and an increase of glycogen level. Spirulina supplementation also impeded loss of body weight and ameliorated hepatic toxicity indices, i.e. alkaline phosphatases and transaminases activities, bilirubin levels and lipid peroxidation. Besides, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels decreased in the serum. Moreover, diabetic rats fed with spirulina exhibited sig changes in antioxidant enzyme activities in the liver (ie, decrease in superoxide dismutase and increase in catalase and glutathione peroxidase activities). The beneficial effects of spirulina or insulin were confirmed by histological study of the liver of diabetic rats. Overall, this study indicates that treatment with spirulina decreased hyperglycemia and oxidative stress in diabetic rats, this amelioration being even more pronounced than that provided by insulin injection. Therefore, administration of this alga would be very helpful in the prevention of diabetic complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Taurine: A Potential Ergogenic Aid for Preventing Muscle Damage and Protein Catabolism and Decreasing Oxidative Stress Produced by Endurance Exercise.

    Science.gov (United States)

    De Carvalho, Flávia G; Galan, Bryan S M; Santos, Priscila C; Pritchett, Kelly; Pfrimer, Karina; Ferriolli, Eduardo; Papoti, Marcelo; Marchini, Júlio S; de Freitas, Ellen C

    2017-01-01

    not improve aerobic parameters, but was effective in increasing taurine plasma levels and decreasing oxidative stress markers, which suggests that taurine may prevent oxidative stress in triathletes.

  14. Taurine: A Potential Ergogenic Aid for Preventing Muscle Damage and Protein Catabolism and Decreasing Oxidative Stress Produced by Endurance Exercise

    Directory of Open Access Journals (Sweden)

    Flávia G. De Carvalho

    2017-09-01

    did not improve aerobic parameters, but was effective in increasing taurine plasma levels and decreasing oxidative stress markers, which suggests that taurine may prevent oxidative stress in triathletes.

  15. Variable copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in advanced gastric cancer patients.

    Science.gov (United States)

    Zhang, Guanjun; Qu, Yiping; Dang, Siwen; Yang, Qi; Shi, Bingyin; Hou, Peng

    2013-10-21

    Change of mitochondrial DNA (mtDNA) copy number is widely reported in various human cancers, including gastric cancer, and is considered to be an important hallmark of cancers. However, there is remarkably little consensus on the value of variable mtDNA content in the prognostic evaluation of this cancer. Using real-time quantitative PCR approach, we examined mtDNA copy number in a cohort of gastric cancers and normal gastric tissues, and explored the association of variable mtDNA content with clinical outcomes of gastric cancer patients. Our data showed that the majority of gastric cancer patients had low mtDNA content as compared to control subjects although the relative mean mtDNA content was higher in the former than the latter. Moreover, we found that variable mtDNA content was strongly associated with lymph node metastasis and cancer-related death of the patients with late-stage tumors. Notably, variable mtDNA content did not affect overall survival of gastric cancer patients, however, we found that increased mtDNA content was associated with poor survival in the patients with late-stage tumors. In this study, we demonstrated that variable mtDNA content markedly increased the risk of lymph node metastasis and high mortality of the patients with late-stage tumors. Additionally, we found a strong link between increased mtDNA content and worse survival of the patients with late-stage tumors. Taken together, variable mtDNA content may be a valuable poor prognostic factor for advanced gastric cancer patients. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1344721463103353.

  16. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mtDNA

  17. Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization.

    Science.gov (United States)

    Li, H; Ruan, Y; Zhang, K; Jian, F; Hu, C; Miao, L; Gong, L; Sun, L; Zhang, X; Chen, S; Chen, H; Liu, D; Song, Z

    2016-03-01

    The MICOS complex (mitochondrial contact site and cristae organizing system) is essential for mitochondrial inner membrane organization and mitochondrial membrane contacts, however, the molecular regulation of MICOS assembly and the physiological functions of MICOS in mammals remain obscure. Here, we report that Mic60/Mitofilin has a critical role in the MICOS assembly, which determines the mitochondrial morphology and mitochondrial DNA (mtDNA) organization. The downregulation of Mic60/Mitofilin or Mic19/CHCHD3 results in instability of other MICOS components, disassembly of MICOS complex and disorganized mitochondrial cristae. We show that there exists direct interaction between Mic60/Mitofilin and Mic19/CHCHD3, which is crucial for their stabilization in mammals. Importantly, we identified that the mitochondrial i-AAA protease Yme1L regulates Mic60/Mitofilin homeostasis. Impaired MICOS assembly causes the formation of 'giant mitochondria' because of dysregulated mitochondrial fusion and fission. Also, mtDNA nucleoids are disorganized and clustered in these giant mitochondria in which mtDNA transcription is attenuated because of remarkable downregulation of some key mtDNA nucleoid-associated proteins. Together, these findings demonstrate that Mic60/Mitofilin homeostasis regulated by Yme1L is central to the MICOS assembly, which is required for maintenance of mitochondrial morphology and organization of mtDNA nucleoids.

  18. No evidence of Neandertal mtDNA contribution to early modern humans.

    Directory of Open Access Journals (Sweden)

    David Serre

    2004-03-01

    Full Text Available The retrieval of mitochondrial DNA (mtDNA sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution.

  19. Gamma ray induced oxidative damage to human red blood cells proteins under hypotonic conditions and its prevention by natural phenolic malabaricone compounds

    International Nuclear Information System (INIS)

    Meenakshi, K.; Chattopadhyay, Subrata

    2015-01-01

    As an oxygen shuttle, Human RBCs must continue to perform the task while being exposed to a wide range of environments for each vascular circuit and to a variety of xenobiotics across its life time. The inability to synthesise new protein makes them uniquely vulnerable to oxidative stress. Antioxidants can help in protecting the RBCs from oxidative insults. Currently herbal antioxidants gained worldwide popularity as drugs and food/drug supplements for the treatment of various diseases. The present effort was aimed at formulating some natural phenolic compounds isolated from M.malabarica (mal B and mal C) to prevent the biochemical parameters which are considered as biomarkers of redox balance primarily contribute to alterations in red blood cells proteins during gamma radiation induced oxidative stress. Compared to control gamma ray treatment with hypotonic stress resulted in significant haemolysis, associated with increased MDA (3.3 fold, p<0.001) and met-haemoglobin (7.0 fold, p<0.001). The structural deformation due to membrane damage was confirmed from SEM images and Heinz body formation, while the cell permeability was evident from the K + efflux (30.4%, p<0.05) and increased intracellular Na + concentration (5.2%, p<0.05). The membrane damage, due to the reduction of the cholesterol/phospholipids ratio and depletion (p<0.001) of ATP, 2,3-DPG by 54.7% and Na + -K + ATPase activity (48.%) indicated loss of RBC functionally. Pre-treatment of the RBCs with mal B (5μM), mal C (2.5 μM) or vitamin E (50 μM) for 1 h reversed these adverse effects of gamma radiation under hypotonic conditions on all these parameters and provided significant protection against oxidative haemolysis. (author)

  20. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes.

    Science.gov (United States)

    Karachalias, N; Babaei-Jadidi, R; Rabbani, N; Thornalley, P J

    2010-07-01

    The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg(-1) day(-1)) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. There were two- to fourfold increases in fructosyl-lysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven- to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. AGEs, particularly arginine-derived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

  1. Statistical analysis of post mortem DNA damage-derived miscoding lesions in Neandertal mitochondrial DNA

    DEFF Research Database (Denmark)

    Vives, Sergi; Gilbert, M Thomas; Arenas, Conchita

    2008-01-01

    ABSTRACT: BACKGROUND: We have analysed the distribution of post mortem DNA damage derived miscoding lesions from the datasets of seven published Neandertal specimens that have extensive cloned sequence coverage over the mitochondrial DNA (mtDNA) hypervariable region 1 (HVS1). The analysis......-->A miscoding lesions (observed ratio of 67:2 compared to an expected ratio of 7:2), implying that the mtDNA Light strand molecule suffers proportionally more damage-derived miscoding lesions than the Heavy strand. CONCLUSION: The clustering of Cs in the Light strand as opposed to the singleton pattern of Cs...

  2. A novel mtDNA deletion in an infant with Pearson syndrome.

    Science.gov (United States)

    Kapsa, R; Thompson, G N; Thorburn, D R; Dahl, H H; Marzuki, S; Byrne, E; Blok, R B

    1994-01-01

    Pearson syndrome is a multisystem mitochondrial disorder of infancy that is associated with deletions in the mitochondrial DNA (mtDNA) genome. We report a study on a male infant with Pearson syndrome. Assessment of oxidative phosphorylation activity indicated combined respiratory-chain defects in muscle, liver and fibroblasts; in particular, activity of complex I was reduced. Analysis of the patient's mtDNA identified a novel heteroplasmic 2.461 kb deletion, present at levels greater than 50% of the total mtDNA in the tissues examined. The deletion spanned nucleotides 10368 to 12828 and was flanked by a 3 bp GCC direct repeat sequence. Gene sequences affected are subunits 3, 4, 4L and 5 of complex I, and tRNAs for arginine, histidine, serine and leucine. Our findings correlate with the multiorgan involvement observed in Pearson syndrome.

  3. Lingering immune dysregulation of inflammatory dermatoses, particularly psoriasis, probably drives metabolic syndrome culminating in cardiovascular damage and needs preventive public health guidelines as well as comprehensive management

    Directory of Open Access Journals (Sweden)

    Yugal Kishor Sharma

    2016-01-01

    Full Text Available Metabolic syndrome, a constellation of interrelated risk factors of metabolic origin namely, abdominal obesity, insulin resistance, dyslipidemia and hypertension, confers greater risk of cardiovascular disease on its patients than the sum of the individual components. It is increasingly being associated with inflammatory dermatoses, especially psoriasis. Determination of the diagnostic criteria of this syndrome is conditioned by the changing views regarding its pathogenesis. Approximately, a quarter of the world′s population harbors this syndrome, whose reported prevalence in India (5-30% has escalated with an increase in urbanization and socioeconomic status. Due to, up to 3 times, the risk of cardiovascular mortality and up to 24 times risk of diabetes mellitus, the epidemiological significance of metabolic syndrome ideally necessitates formulation of preventive guidelines by public health authorities. Chronic inflammation, involving several cytokines and adipokines, forms the bridge between this syndrome and psoriasis and underlies the formation of atherosclerotic plaque, the primary lesion of coronary artery disease, in whose pathogenesis oxidative stress and genetic factors also play a role. Up to 4-fold increase in the prevalence of metabolic syndrome and 3-fold increased risk of cardiovascular mortality is reported globally in psoriatics. Increasing index of suspicion of this syndrome by the dermatologists, prevention of cardiovascular damage by lifestyle modifications, smoking cessation and redressal of the inherent depression in these patients is as imperative in management as is the specific therapy of the skin lesions of this systemic, rather than "just a skin," disease as well as the lipid-lowering, antihypertensive and antidiabetic agents.

  4. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As

  5. Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Rα-independent alternative differentiation of macrophages.

    Directory of Open Access Journals (Sweden)

    Julia Esser-von Bieren

    Full Text Available Approximately one-third of the world's population suffers from chronic helminth infections with no effective vaccines currently available. Antibodies and alternatively activated macrophages (AAM form crucial components of protective immunity against challenge infections with intestinal helminths. However, the mechanisms by which antibodies target these large multi-cellular parasites remain obscure. Alternative activation of macrophages during helminth infection has been linked to signaling through the IL-4 receptor alpha chain (IL-4Rα, but the potential effects of antibodies on macrophage differentiation have not been explored. We demonstrate that helminth-specific antibodies induce the rapid trapping of tissue migrating helminth larvae and prevent tissue necrosis following challenge infection with the natural murine parasite Heligmosomoides polygyrus bakeri (Hp. Mice lacking antibodies (JH (-/- or activating Fc receptors (FcRγ(-/- harbored highly motile larvae, developed extensive tissue damage and accumulated less Arginase-1 expressing macrophages around the larvae. Moreover, Hp-specific antibodies induced FcRγ- and complement-dependent adherence of macrophages to larvae in vitro, resulting in complete larval immobilization. Antibodies together with helminth larvae reprogrammed macrophages to express wound-healing associated genes, including Arginase-1, and the Arginase-1 product L-ornithine directly impaired larval motility. Antibody-induced expression of Arginase-1 in vitro and in vivo occurred independently of IL-4Rα signaling. In summary, we present a novel IL-4Rα-independent mechanism of alternative macrophage activation that is antibody-dependent and which both mediates anti-helminth immunity and prevents tissue disruption caused by migrating larvae.

  6. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

    International Nuclear Information System (INIS)

    Wang Chengye; Kong Qingpeng; Yao Yonggang; Zhang Yaping

    2006-01-01

    Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL

  7. Low copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in early-stage laryngeal cancer patients.

    Science.gov (United States)

    Dang, Siwen; Qu, Yiping; Wei, Jing; Shao, Yuan; Yang, Qi; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2014-02-05

    Alterations in mitochondrial DNA (mtDNA) copy number have been widely reported in various human cancers, and been considered to be an important hallmark of cancers. However, little is known about the value of copy number variations of mtDNA in the prognostic evaluation of laryngeal cancer. Using real-time quantitative PCR method, we investigated mtDNA copy number in a cohort of laryngeal cancers (n =204) and normal laryngeal tissues (n =40), and explored the association of variable mtDNA copy number with clinical outcomes of laryngeal cancer patients. Our data showed that the relative mean mtDNA content was higher in the laryngeal cancer patients (11.91 ± 4.35 copies) than the control subjects (4.72 ± 0.70 copies). Moreover, we found that mtDNA content was negatively associated with cigarette smoking (pack-years), tumor invasion, and TNM stage. Notably, variable mtDNA content did not affect overall survival of laryngeal cancer patients. However, when the patients were categorized into early-stage and late-stage tumor groups according to TNM stage, we found that low mtDNA content was strongly associated with poor survival in the former, but not in the latter. The present study demonstrated that low mtDNA content was strongly correlated with some of clinicopathological characteristics, such as cigarette smoking, tumor invasion and TNM stage. In addition, we found a strong link between low mtDNA content and worse survival of the patients with early-stage tumors. Taken together, low copy number of mtDNA may be a useful poor prognostic factor for early-stage laryngeal cancer patients. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1841771572115955.

  8. Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

    Science.gov (United States)

    Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

    2017-06-26

    Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

  9. Prunella vulgaris extract and rosmarinic acid prevent UVB-induced DNA damage and oxidative stress in HaCaT keratinocytes.

    Science.gov (United States)

    Vostálová, Jitka; Zdarilová, Adéla; Svobodová, Alena

    2010-04-01

    Solar radiation is a very important exogenous factor in skin pathogenesis and can lead to the development of a number of skin disorders. UVB irradiation is known to induce oxidative stress, inflammation and especially DNA lesions in exposed cells. It is important, therefore, to identify agents that can offer protection against UVB-caused skin damage. Natural compounds have been studied for their possible ability to control/modulate various lifestyle-related diseases. The application of plant compounds/extracts with screening, antioxidant and anti-inflammatory activities may also successfully protect the skin against UV-caused injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295-315 nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and post-treatment of HaCaT cells with PVE (5-50 mg/l) and RA (0.18-1.8 mg/l) reduced breakage together with the apoptotic process. PVE and RA also significantly eliminated ROS production and diminished IL-6 release. Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs to be demonstrated in vivo.

  10. Improved estimates of separation distances to prevent unacceptable damage to nuclear power plant structures from hydrogen detonation for gaseous hydrogen storage. Technical report

    International Nuclear Information System (INIS)

    1994-05-01

    This report provides new estimates of separation distances for nuclear power plant gaseous hydrogen storage facilities. Unacceptable damage to plant structures from hydrogen detonations will be prevented by having hydrogen storage facilities meet separation distance criteria recommended in this report. The revised standoff distances are based on improved calculations on hydrogen gas cloud detonations and structural analysis of reinforced concrete structures. Also, the results presented in this study do not depend upon equivalencing a hydrogen detonation to an equivalent TNT detonation. The static and stagnation pressures, wave velocity, and the shock wave impulse delivered to wall surfaces were computed for several different size hydrogen explosions. Separation distance equations were developed and were used to compute the minimum separation distance for six different wall cases and for seven detonating volumes (from 1.59 to 79.67 lbm of hydrogen). These improved calculation results were compared to previous calculations. The ratio between the separation distance predicted in this report versus that predicted for hydrogen detonation in previous calculations varies from 0 to approximately 4. Thus, the separation distances results from the previous calculations can be either overconservative or unconservative depending upon the set of hydrogen detonation parameters that are used. Consequently, it is concluded that the hydrogen-to-TNT detonation equivalency utilized in previous calculations should no longer be used

  11. Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells

    Directory of Open Access Journals (Sweden)

    Auke B.C. Otten

    2016-07-01

    Full Text Available We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 × 106 mtDNA molecules with high variation between oocytes. During embryogenesis, the mtDNA copy number decreases to ∼170 mtDNA molecules per primordial germ cell (PGC, a number similar to that in mammals, and to ∼50 per non-PGC. These occur at the same developmental stage, implying considerable variation in mtDNA copy number in (non-PGCs of the same female, dictated by variation in the mature oocyte. The presence of oocytes with low mtDNA numbers, if similar in humans, could explain how (de novo mutations can reach high mutation loads within a single generation. High mtDNA copy numbers in mature oocytes are established by mtDNA replication during oocyte development. Bottleneck differences between germline and non-germline cells, due to early differentiation of PGCs, may account for different distribution patterns of familial mutations.

  12. Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

    Science.gov (United States)

    Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

    2005-01-01

    AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

  13. Pleistocene-Holocene boundary in Southern Arabia from the perspective of human mtDNA variation

    Czech Academy of Sciences Publication Activity Database

    Al-Abri, A.-R.; Podgorná, E.; Rose, J. I.; Pereira, L.; Mulligan, C. J.; Silva, N. M.; Bayoumi, R.; Soares, P.; Černý, Viktor

    2012-01-01

    Roč. 149, č. 2 (2012), s. 291-298 ISSN 0002-9483 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.481, year: 2012

  14. Investigation of yeast genes possibly involved in mtDNA stability ...

    African Journals Online (AJOL)

    Screening of Caenorhabditis elegans genes possibly involved in the mitochondrial genome maintenance was performed using our previous validated method of RNAi combined with ethidium bromide. This was to knock down C. elegans genes homologous to yeast genes known to be involved in mtDNA stability but of ...

  15. Pearson syndrome and the role of deletion dimers and duplications in the mtDNA

    NARCIS (Netherlands)

    Jacobs, L. J. A. M.; Jongbloed, R. J. E.; Wijburg, F. A.; de Klerk, J. B. C.; Geraedts, J. P. M.; Nijland, J. G.; Scholte, H. R.; de Coo, I. F. M.; Smeets, H. J. M.

    2004-01-01

    Pearson syndrome is an often fatal multisystem disease associated with mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with deletion dimers. The mutation percentage in different tissues (blood,

  16. To study the relationship between cadmium, zinc and mtDNA copy ...

    African Journals Online (AJOL)

    Objective: To examine the variation of cadmium (Cd), zinc (Zn) and mitochondrial DNA (mtDNA) copy number in prostate cancer (PCa) patients and their age match controls and correlations with clinicopathological parameters. Subjects and methods: This study was conducted between January 2012 and January 2015.

  17. Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

    Science.gov (United States)

    Peñaloza-Espinosa, Rosenda I; Arenas-Aranda, Diego; Cerda-Flores, Ricardo M; Buentello-Malo, Leonor; González-Valencia, Gerardo; Torres, Javier; Alvarez, Berenice; Mendoza, Irma; Flores, Mario; Sandoval, Lucila; Loeza, Francisco; Ramos, Irma; Muñoz, Leopoldo; Salamanca, Fabio

    2007-06-01

    In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.

  18. Forensic and phylogeographic characterization of mtDNA lineages from northern Thailand (Chiang Mai).

    Science.gov (United States)

    Zimmermann, Bettina; Bodner, Martin; Amory, Sylvain; Fendt, Liane; Röck, Alexander; Horst, David; Horst, Basil; Sanguansermsri, Torpong; Parson, Walther; Brandstätter, Anita

    2009-11-01

    The immigration of diverse ethnic groups over the past centuries from surrounding countries into Thailand left footprints in the genetic composition of Thai mitochondrial DNA (mtDNA) lineages. The entire mtDNA control region (1,122 bp) was typed in 190 unrelated male volunteers from the northern Thailand province of Chiang Mai following highest quality standards. For a more precise haplogroup classification, selected single nucleotide polymorphisms from the mtDNA coding region were genotyped. We found several new, so far undescribed mtDNA lineages. Quasi-median networks were constructed for visualisation of character conflicts. The data were put into population-genetic relationships with other Southeast Asian populations. Although the frequencies of the Thai haplogroups were characteristic for Southeast Asia in terms of haplotype composition and genetic structure, the Thai population was significantly different from other Southeast Asian populations. This necessitates establishing regional databases, especially for forensic applications. The population data have been submitted to the EMPOP database (www.empop.org) and will be available on publication.

  19. Investigation of yeast genes possibly involved in mtDNA stability ...

    African Journals Online (AJOL)

    Phelim Isichei

    large number of possible candidate genes, these approaches most often remains laborious (De Lonlay et ... RNA interference of genes involved in mtDNA replication such as polg-1, encoding the mitochondrial DNA .... adult worms were independently picked up and transferred to fresh. RNAi plates with or without different ...

  20. The Expansion of mtDNA Haplogroup L3 within and out of Africa

    Czech Academy of Sciences Publication Activity Database

    Soares, P.; Alshamali, F.; Pereira, J. B.; Fernandes, V.; Silva, N. M.; Afonso, C.; Costa, M. D.; Musilová, E.; Macaulay, V.; Richards, M. B.; Černý, Viktor; Pereira, L.

    2012-01-01

    Roč. 29, č. 3 (2012), s. 915-927 ISSN 0737-4038 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA * complete genomes * haplogroup L3 * out of Africa * modern human expansions Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 10.353, year: 2012

  1. Comprehensive view of the population history of Arabia as inferred by mtDNA variation

    Czech Academy of Sciences Publication Activity Database

    Černý, Viktor; Čížková, M.; Poloni, E. S.; Al-Meeri, A.; Mulligan, C. J.

    2016-01-01

    Roč. 159, č. 4 (2016), s. 607-616 ISSN 0002-9483 R&D Projects: GA ČR GA13-37998S Institutional support: RVO:67985912 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.552, year: 2016

  2. Genetic divergence between Auxis thazard and A. rochei based on PCR-RFLP analysis of mtDNA D-loop region

    Digital Repository Service at National Institute of Oceanography (India)

    GirishKumar; Kunal, S.P.; Menezes, R.M.; Kocour, M.

    is mitochondrial DNA (mtDNA); because of its predominantly maternal inheritance, relatively rapid rate of base substitution, and lack of recombination (Avise et al., 1987). MtDNA sequence differences can either be measured directly through restriction site...

  3. Insertion of a self-splicing intron into the mtDNA of atriploblastic animal

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Y.; Halanych, K.; Boore, J.L.

    2006-04-14

    Nephtys longosetosa is a carnivorous polychaete worm that lives in the intertidal and subtidal zones with worldwide distribution (pleijel&rouse2001). Its mitochondrial genome has the characteristics typical of most metazoans: 37 genes; circular molecule; almost no intergenic sequence; and no significant gene rearrangements when compared to other annelid mtDNAs (booremoritz19981995). Ubiquitous features as small intergenic regions and lack of introns suggested that metazoan mtDNAs are under strong selective pressures to reduce their genome size allowing for faster replication requirements (booremoritz19981995Lynch2005). Yet, in 1996 two type I introns were found in the mtDNA of the basal metazoan Metridium senile (FigureX). Breaking a long-standing rule (absence of introns in metazoan mtDNA), this finding was later supported by the further presence of group I introns in other cnidarians. Interestingly, only the class Anthozoa within cnidarians seems to harbor such introns. Although several hundreds of triploblastic metazoan mtDNAs have been sequenced, this study is the first evidence of mitochondrial introns in triploblastic metazoans. The cox1 gene of N. longosetosa has an intron of almost 2 kbs in length. This finding represents as well the first instance of a group II intron (anthozoans harbor group I introns) in all metazoan lineages. Opposite trends are observed within plants, fungi and protist mtDNAs, where introns (both group I and II) and other non-coding sequences are widespread. Plant, fungal and protist mtDNA structure and organization differ enormously from that of metazoan mtDNA. Both, plant and fungal mtDNA are dynamic molecules that undergo high rates of recombination, contain long intergenic spacer regions and harbor both group I and group II introns. However, as metazoans they have a conserved gene content. Protists, on the other hand have a striking variation of gene content and introns that account for the genome size variation. In contrast to

  4. Role of Ocimum basilicum L. in prevention of ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice brain.

    Science.gov (United States)

    Bora, Kundan Singh; Arora, Shruti; Shri, Richa

    2011-10-11

    The genus Ocimum (Lamiaceae) has a long history of use as culinary and medicinal herbs. Many species are used for their antioxidant and neuroprotective activity in various parts of the world. Ocimum basilicum Linn. has been used traditionally for the treatment of anxiety, diabetes, cardiovascular diseases, headaches, nerve pain, as anticonvulsant and anti-inflammatory, and used in a variety of neurodegenerative disorders. The present study is designed to investigate the effect of ethyl acetate extract of Ocimum basilicum leaves on ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice. Global cerebral ischemia was induced by bilateral carotid artery occlusion for 15 min followed by reperfusion for 24h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. The concentration of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content was determined by colorimetric assay. Short-term memory was evaluated using elevated plus-maze. Inclined beam walking was employed to assess motor coordination. Bilateral carotid artery occlusion followed by reperfusion produced significant increase in cerebral infarct size and lipid peroxidation (TBARS), and reduced GSH content, and impaired short-term memory and motor coordination. Pre-treatment with standardized ethyl acetate extract of Ocimum basilicum (100 and 200mg/kg, p.o.) markedly reduced cerebral infarct size and lipid peroxidation, restored GSH content, and attenuated impairment in short-term memory and motor coordination. The results of the study suggest that Ocimum basilicum could be useful clinically in the prevention of stroke. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Managing Occupational Irritant Contact Dermatitis Using a Two-Step Skincare Regimen Designed to Prevent Skin Damage and Support Skin Recovery.

    Science.gov (United States)

    von Grote, Erika C; Palaniswarmy, Kiruthi; Meckfessel, Matthew H

    2016-12-01

    Occupational irritant contact dermatitis (ICD) affecting the hands is a common and difficult-to-manage condition. Occupations that necessitate contact with harsh chemicals, use of alcohol-based disinfectants, and frequent hand washing elevate the risk of ICD. Management strategies that do not adequately prevent accumulated damage and repair skin, can develop into chronic dermatoses which negatively impact work productivity and quality of life. A 2-step skin-care regimen (Excipial Daily Protection Hand Cream (EP) and Excipial Rapid Repair Hand Cream (ER), Galderma Laboratories, L.P.) has been developed as a daily-use management strategy to protect and repair vulnerable hands. The protective barrier cream is formulated with aluminum chlorohydrate and designed for pre-exposure application to enhance the skin's natural protective barrier and minimize excessive moisture while wearing protective gloves. The repair cream, a lipid-rich formulation, is intended for post-exposure application to rehydrate and facilitate the skin's natural healing process. The results of 3 clinical studies highlighted in this review demonstrate how the use of a 2-step skin-care regimen offers a greater protective effect against ICD than the use of barrier cream alone, and also how the formulation of the barrier cream used in these studies helps minimize the occlusion effect caused by gloves and does not interfere with the antibacterial efficacy of an alcohol-based hand sanitizer. This 2-step skin-care regimen is effectively designed to manage and minimize the risk of ICD development in a variety of patients and provides clinicians an additional tool for helping patients manage ICD. J Drugs Dermatol. 2016;15(12):1504-1510.

  6. Evolutionary neutrality of mtDNA introgression: evidence from complete mitogenome analysis in roe deer.

    Science.gov (United States)

    Matosiuk, M; Sheremetyeva, I N; Sheremetyev, I S; Saveljev, A P; Borkowska, A

    2014-11-01

    Introgressive hybridization offers a unique platform for studying the molecular basis of natural selection acting on mitogenomes. Most of the mtDNA protein-coding genes are extremely conserved; however, some of the observed variations have potentially adaptive significance. Here, we evaluated whether the evolution of mtDNA in closely related roe deer species affected by widespread mtDNA introgression is neutral or adaptive. We characterized and compared 16 complete mitogenomes of European (Capreolus capreolus) and Siberian (C. pygargus) roe deer, including four of Siberian origin introgressed into European species. The average sequence divergence of species-specific lineages was estimated at 2.8% and varied across gene classes. Only 21 of 315 fixed differences identified in protein-coding genes represented nonsynonymous changes. Only three of them were determined to have arisen in the C. pygargus lineage since the time to the most recent common ancestor (TMRCA) of both Capreolus species, reflecting a decelerated evolutionary ratio. The almost four-fold higher dN /dS ratio described for the European roe deer lineage is constrained by overall purifying selection, especially pronounced in the ND4 and ND5 genes. We suggest that the highly divergent C. capreolus lineage could have maintained a capability for genomic incorporation of the well-preserved and almost ancestral type of mtDNA present in C. pygargus. Our analyses did not indicate any signs of positive selection for Siberian roe deer mtDNA, suggesting that the present widespread introgression is evolutionarily neutral. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  7. Second generation sequencing allows for mtDNA mixture deconvolution and high resolution detection of heteroplasmy.

    Science.gov (United States)

    Holland, Mitchell M; McQuillan, Megan R; O'Hanlon, Katherine A

    2011-06-01

    To use parallel array pyrosequencing to deconvolute mixtures of mitochondrial DNA (mtDNA) sequence and provide high resolution analysis of mtDNA heteroplasmy. The hypervariable segment 1 (HV1) of the mtDNA control region was analyzed from 30 individuals using the 454 GS Junior instrument. Mock mixtures were used to evaluate the system's ability to deconvolute mixtures and to reliably detect heteroplasmy, including heteroplasmic differences between 5 family members of the same maternal lineage. Amplicon sequencing was performed on polymerase chain reaction (PCR) products generated with primers that included multiplex identifiers (MID) and adaptors for pyrosequencing. Data analysis was performed using NextGENe® software. The analysis of an autosomal short tandem repeat (STR) locus (D18S51) and a Y-STR locus (DYS389 I/II) was performed simultaneously with a portion of HV1 to illustrate that multiplexing can encompass different markers of forensic interest. Mixtures, including heteroplasmic variants, can be detected routinely down to a component ratio of 1:250 (20 minor variant copies with a coverage rate of 5000 sequences) and can be readily detected down to 1:1000 (0.1%) with expanded coverage. Amplicon sequences from D18S51, DYS389 I/II, and the second half of HV1 were successfully partitioned and analyzed. The ability to routinely deconvolute mtDNA mixtures down to a level of 1:250 allows for high resolution analysis of mtDNA heteroplasmy, and for differentiation of individuals from the same maternal lineage. The pyrosequencing approach results in poor resolution of homopolymeric sequences, and PCR/sequencing artifacts require a filtering mechanism similar to that for STR stutter and spectral bleed through. In addition, chimeric sequences from jumping PCR must be addressed to make the method operational.

  8. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a ‘differential multiple cleavage-site’ model

    Science.gov (United States)

    Bacman, SR; Williams, SL; Hernandez, D; Moraes, CT

    2009-01-01

    The ability to manipulate mitochondrial DNA (mtDNA) heteroplasmy would provide a powerful tool to treat mitochondrial diseases. Recent studies showed that mitochondria-targeted restriction endonucleases can modify mtDNA heteroplasmy in a predictable and efficient manner if it recognizes a single site in the mutant mtDNA. However, the applicability of such model is limited to mutations that create a novel cleavage site, not present in the wild-type mtDNA. We attempted to extend this approach to a ‘differential multiple cleavage site’ model, where an mtDNA mutation creates an extra restriction site to the ones normally present in the wild-type mtDNA. Taking advantage of a heteroplasmic mouse model harboring two haplotypes of mtDNA (NZB/BALB) and using adenovirus as a gene vector, we delivered a mitochondria-targeted Scal restriction endonuclease to different mouse tissues. Scal recognizes five sites in the NZB mtDNA but only three in BALB mtDNA. Our results showed that changes in mtDNA heteroplasmy were obtained by the expression of mitochondria-targeted ScaI in both liver, after intravenous injection, and in skeletal muscle, after intramuscular injection. Although mtDNA depletion was an undesirable side effect, our data suggest that under a regulated expression system, mtDNA depletion could be minimized and restriction endonucleases recognizing multiple sites could have a potential for therapeutic use. PMID:17597792

  9. Initiation of mtDNA transcription is followed by pausing, and diverges across human cell types and during evolution.

    Science.gov (United States)

    Blumberg, Amit; Rice, Edward J; Kundaje, Anshul; Danko, Charles G; Mishmar, Dan

    2017-03-01

    Mitochondrial DNA (mtDNA) genes are long known to be cotranscribed in polycistrones, yet it remains impossible to study nascent mtDNA transcripts quantitatively in vivo using existing tools. To this end, we used deep sequencing (GRO-seq and PRO-seq) and analyzed nascent mtDNA-encoded RNA transcripts in diverse human cell lines and metazoan organisms. Surprisingly, accurate detection of human mtDNA transcription initiation sites (TISs) in the heavy and light strands revealed a novel conserved transcription pausing site near the light-strand TIS. This pausing site correlated with the presence of a bacterial pausing sequence motif, with reduced SNP density, and with a DNase footprinting signal in all tested cells. Its location within conserved sequence block 3 (CSBIII), just upstream of the known transcription-replication transition point, suggests involvement in such transition. Analysis of nonhuman organisms enabled de novo mtDNA sequence assembly, as well as detection of previously unknown mtDNA TIS, pausing, and transcription termination sites with unprecedented accuracy. Whereas mammals ( Pan troglodytes , Macaca mulatta , Rattus norvegicus , and Mus musculus ) showed a human-like mtDNA transcription pattern, the invertebrate pattern ( Drosophila melanogaster and Caenorhabditis elegans ) profoundly diverged. Our approach paves the path toward in vivo, quantitative, reference sequence-free analysis of mtDNA transcription in all eukaryotes. © 2017 Blumberg et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

    Directory of Open Access Journals (Sweden)

    Scalais Emmanuel

    2009-06-01

    Full Text Available Abstract Background In muscle cytochrome oxidase (COX negative fibers (mitochondrial mosaics have often been visualized. Methods COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis. Results Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Conclusion Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent

  11. Mitochondrial mosaics in the liver of 3 infants with mtDNA defects.

    Science.gov (United States)

    Roels, Frank; Verloo, Patrick; Eyskens, François; François, Baudouin; Seneca, Sara; De Paepe, Boel; Martin, Jean-Jacques; Meersschaut, Valerie; Praet, Marleen; Scalais, Emmanuel; Espeel, Marc; Smet, Joél; Van Goethem, Gert; Van Coster, Rudy

    2009-06-05

    In muscle cytochrome oxidase (COX) negative fibers (mitochondrial mosaics) have often been visualized. COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis. Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent than observed until now. A novel pathogenic mutation in POLG is

  12. Seventeen new complete mtDNA sequences reveal extensive mitochondrial genome evolution within the Demospongiae.

    Directory of Open Access Journals (Sweden)

    Xiujuan Wang

    Full Text Available Two major transitions in animal evolution--the origins of multicellularity and bilaterality--correlate with major changes in mitochondrial DNA (mtDNA organization. Demosponges, the largest class in the phylum Porifera, underwent only the first of these transitions and their mitochondrial genomes display a peculiar combination of ancestral and animal-specific features. To get an insight into the evolution of mitochondrial genomes within the Demospongiae, we determined 17 new mtDNA sequences from this group and analyzing them with five previously published sequences. Our analysis revealed that all demosponge mtDNAs are 16- to 25-kbp circular molecules, containing 13-15 protein genes, 2 rRNA genes, and 2-27 tRNA genes. All but four pairs of sampled genomes had unique gene orders, with the number of shared gene boundaries ranging from 1 to 41. Although most demosponge species displayed low rates of mitochondrial sequence evolution, a significant acceleration in evolutionary rates occurred in the G1 group (orders Dendroceratida, Dictyoceratida, and Verticillitida. Large variation in mtDNA organization was also observed within the G0 group (order Homosclerophorida including gene rearrangements, loss of tRNA genes, and the presence of two introns in Plakortis angulospiculatus. While introns are rare in modern-day demosponge mtDNA, we inferred that at least one intron was present in cox1 of the common ancestor of all demosponges. Our study uncovered an extensive mitochondrial genomic diversity within the Demospongiae. Although all sampled mitochondrial genomes retained some ancestral features, including a minimally modified genetic code, conserved structures of tRNA genes, and presence of multiple non-coding regions, they vary considerably in their size, gene content, gene order, and the rates of sequence evolution. Some of the changes in demosponge mtDNA, such as the loss of tRNA genes and the appearance of hairpin-containing repetitive elements

  13. A collaborative EDNAP exercise on SNaPshot™-based mtDNA control region typing

    DEFF Research Database (Denmark)

    Weiler, NEC; Baca, K; Ballard, D

    2017-01-01

    A collaborative European DNA Profiling (EDNAP) Group exercise was undertaken to assess the performance of an earlier described SNaPshot™-based screening assay (denoted mini-mtSNaPshot) (Weiler et al., 2016) [1] that targets 18 single nucleotide polymorphism (SNP) positions in the mitochondrial (mt......) DNA control region and allows for discrimination of major European mtDNA haplogroups. Besides the organising laboratory, 14 forensic genetics laboratories were involved in the analysis of 13 samples, which were centrally prepared and thoroughly tested prior to shipment. The samples had a variable......, the participants compared the SNP typing data of all 13 samples to a set of eight mtDNA reference profiles that were described according to standard nomenclature (Parson et al., 2014) [2], and indicated whether these references matched each sample or not. Incorrect scorings were obtained for 2% of the comparisons...

  14. Two distinct mtDNA lineages among captive African penguins in Japan.

    Science.gov (United States)

    Murata, Michiko; Murakami, Masaru

    2014-04-01

    The African penguin (Spheniscus demersus) is one of the world's most endangered seabirds. In Japan, although the number of African penguins in captivity continues to increase, genetic data have not been collected for either wild or captive populations. To reveal genetic diversity and characterization in captive African penguins, we analyzed the nucleotide sequences of mitochondrial DNA (mtDNA) from a sample of 236 African penguins. Analysis of 433 bp of the control region and 1,140 bp of cytochrome b sequences revealed the existence of two mtDNA clades. Control region haplotypes were much more divergent (d=3.39%) between the two clades than within each clade. The divergence of these clades may reflect differences at the subspecies or geographical population level in African penguins. These findings suggest that at least two distinct maternal lineages exist in the wild populations of the African penguin.

  15. Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA.

    OpenAIRE

    McShane, M A; Hammans, S R; Sweeney, M; Holt, I J; Beattie, T J; Brett, E M; Harding, A E

    1991-01-01

    A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDN...

  16. Does aerobic exercises induce mtDNA mutation in human blood ...

    African Journals Online (AJOL)

    The aim of this study was to determine the effect of eight weeks aerobic training on mitochondrial DNA (mtDNA) mutation in human blood leucocytes. Twenty untrained healthy students (training group: n =10, age = 20.7±1.5 yrs, weight = 67.7±10 kg, BF% = 17.5±7.35 & control group: n =10, age = 21±1.3 yrs, weight ...

  17. The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

    Directory of Open Access Journals (Sweden)

    Aoi Noda

    Full Text Available Aurochs (Bos primigenius were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle.We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region.We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181. Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity.

  18. Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

    OpenAIRE

    Li, H; Ruan, Y; Zhang, K; Jian, F; Hu, C; Miao, L; Gong, L; Sun, L; Zhang, X; Chen, S; Chen, H; Liu, D; Song, Z

    2015-01-01

    The MICOS complex (mitochondrial contact site and cristae organizing system) is essential for mitochondrial inner membrane organization and mitochondrial membrane contacts, however, the molecular regulation of MICOS assembly and the physiological functions of MICOS in mammals remain obscure. Here, we report that Mic60/Mitofilin has a critical role in the MICOS assembly, which determines the mitochondrial morphology and mitochondrial DNA (mtDNA) organization. The downregulati...

  19. mtDNA of Fulani Nomads and Their Genetic Relationships to Neighboring Sedentary Populations

    Czech Academy of Sciences Publication Activity Database

    Černý, Viktor; Hájek, Martin; Bromová, Markéta; Čmejla, R.; Diallo, I.; Brdička, R.

    2006-01-01

    Roč. 78, č. 1 (2006), s. 9-27 ISSN 0018-7143 R&D Projects: GA ČR(CZ) GA404/03/0318 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * HVS-I * Fulani nomads * sub - Saharan populations * Chad * Cameroon * Burkina Faso Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 1.132, year: 2006

  20. Rapid deployment of the five founding Amerind mtDNA haplogroups via coastal and riverine colonization.

    Science.gov (United States)

    Fix, Alan G

    2005-10-01

    Numerous studies of variation in mtDNA in Amerindian populations established that four haplogroups are present throughout both North and South America. These four haplogroups (A, B, C, and D) and perhaps a fifth (X) in North America are postulated to be present in the initial founding migration to the Americas. Furthermore, studies of ancient mtDNA in North America suggested long-term regional continuity of the frequencies of these founding haplogroups. Present-day tribal groups possess high frequencies of private mtDNA haplotypes (variants within the major haplogroups), consistent with early establishment of local isolation of regional populations. Clearly these patterns have implications for the mode of colonization of the hemisphere. Recently, the earlier consensus among archaeologists for an initial colonization by Clovis hunters arriving through an ice-free corridor and expanding in a "blitzkrieg " wave was shown to be inconsistent with extensive genetic variability in Native Americans; a coastal migration route avoids this problem. The present paper demonstrates through a computer simulation model how colonization along coasts and rivers could have rapidly spread the founding lineages widely through North America.

  1. Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution

    Directory of Open Access Journals (Sweden)

    Carlos Y Valenzuela

    2010-01-01

    Full Text Available Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA, the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9 was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

  2. Genetic diversity of native chicken based on analysis of D-Loop mtDNA marker

    Directory of Open Access Journals (Sweden)

    Tike Sartika

    2000-06-01

    Full Text Available Production was carried out using control region/D-loop mtDNA marker. The base population of native chicken was selected from subpopulation at Cianjur, Jatiwangi, Depok, Bogor I, and Bogor 2. Samples from each population was 10 heads and 2 samples Green Jungle Fowl (Gallus various from East Java as out Group samples. Two primers binding conserved tRNA Phenylalanine gene and tRNA Glutamine gene were DNA Heavy stranded HI255 (5'-CATCTTGGCATCTTCAGTGCC-3' and DNA Light stranded Ll6750 (5'-AGGACTACGGCTTGAAAAGC-3' was used to amplify D-Ioop mtDNA chicken. PCR-RFLP methods with 6 restriction enzymes 4 cutter such as, Alul (AG↓CT, Hpall (C↓CGG, Mbol (↓GATC, Rsal (GT↓AC, NlaIII (CATG↓ and HaeIII (GG↓CC were used to detect polymorphism within and between subpopulation. Result of experiment show that mtDNA which was amplified by PCR was 1320 bp, consist of 1227 bp control region/D-loop, 45 bp tRNA Glutamine gene and 48 bp tRNA Phenylalananine gene. PCR product which were digested from 6 endonucleases enzyme show that native chicken within and between population was monomorphic and if its compare with Green Jungle Fowl was polymorphic.

  3. Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity.

    Science.gov (United States)

    Babayev, Elnur; Wang, Tianren; Szigeti-Buck, Klara; Lowther, Katie; Taylor, Hugh S; Horvath, Tamas; Seli, Emre

    2016-11-01

    Mitochondria affect numerous aspects of mammalian reproduction. We investigated whether the decrease in oocyte quality associated with aging is related to altered mitochondria. Oocytes from old (12 months) and young (9 weeks) C57BL/6J mice were compared in relation to: mitochondria morphology and dynamics (mitochondria density, coverage, size and shape) throughout folliculogenesis; levels of mitochondrial DNA (mtDNA); mitochondrial stress reflected in the expression of mitochondrial unfolded protein response (mt-UPR) genes; and levels of reactive oxygen species (ROS) under baseline conditions and following H 2 O 2 treatment. In old mice, mitochondria of primary follicle-enclosed oocytes were smaller, with lower mitochondria coverage (total mitochondria μm 2 /μm 2 cytosol area) (pchanges were not significant. Mature oocytes (Metaphase II-MII) from old mice had significantly less mtDNA (paged MII oocytes were also higher following pretreatment with H 2 O 2 (pAging is associated with altered mitochondrial morphological parameters and decreased mtDNA levels in oocytes, as well as an increase in ROS under stressful conditions and elevated expression of mitochondrial stress response gene Hspd1. Delineation of the mechanisms underlying mitochondrial changes associated with ageing may help in the development of diagnostic and therapeutic tools in reproductive medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card.

    Science.gov (United States)

    Tóth, T; Bókay, J; Szönyi, L; Nagy, B; Papp, Z

    1998-03-01

    Pearson syndrome is a multisystem juvenile condition associated with deletions in the mitochondrial genome. The most common 4977 bp deletion of mitochondrial DNA (mtDNA) can mainly be detected in the patients' peripheral blood. Here we report a child with a clinically unclarified diagnosis where molecular genetic results proved Pearson syndrome from stored dried blood sample 6 months after the patient's death. PCR amplification around the breakpoint of the most common mtDNA deletion could detect the presence of mutated mtDNA. Another polymerase chain reaction (PCR) assay indicated the low level of wild type mtDNA in patients' blood. We believe that this case shows the importance of storing Guthrie card and the availability of detection of Pearson syndrome from dried blood sample.

  5. Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences.

    Science.gov (United States)

    Lippold, Sebastian; Xu, Hongyang; Ko, Albert; Li, Mingkun; Renaud, Gabriel; Butthof, Anne; Schröder, Roland; Stoneking, Mark

    2014-01-01

    Comparisons of maternally-inherited mitochondrial DNA (mtDNA) and paternally-inherited non-recombining Y chromosome (NRY) variation have provided important insights into the impact of sex-biased processes (such as migration, residence pattern, and so on) on human genetic variation. However, such comparisons have been limited by the different molecular methods typically used to assay mtDNA and NRY variation (for example, sequencing hypervariable segments of the control region for mtDNA vs. genotyping SNPs and/or STR loci for the NRY). Here, we report a simple capture array method to enrich Illumina sequencing libraries for approximately 500 kb of NRY sequence, which we use to generate NRY sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). We also obtained complete mtDNA genome sequences from the same individuals, allowing us to compare maternal and paternal histories free of any ascertainment bias. We identified 2,228 SNPs in the NRY sequences and 2,163 SNPs in the mtDNA sequences. Our results confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA, although the differences are not as large as previously suggested. More importantly, we find substantial regional variation in patterns of mtDNA versus NRY variation. Model-based simulations indicate very small ancestral effective population sizes (<100) for the out-of-Africa migration as well as for many human populations. We also find that the ratio of female effective population size to male effective population size (Nf/Nm) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in Nf than Nm. The NRY and mtDNA sequences provide new insights into the paternal and maternal histories of human populations, and the methods we introduce here should be widely applicable for further such studies.

  6. mtDNA phylogeny of Japanese ant crickets (Orthoptera : Myrmecophilidae): Diversification in host specificity and habitat use

    OpenAIRE

    Komatsu, Takashi; Maruyama, Munetoshi; Ueda, Shouhei; Itino, Takao

    2008-01-01

    Ant crickets (Myrmecophilidae, Orthoptera) are typical ant guests. Although ten species (all belonging to genus Myrmecophilus) have recently been described from Japan, their phylogeny and the extent of host specificity are not known. Here, we reconstruct mtDNA phylogeny of 48 individuals from six species to examine their host specificity, habitat use, and congruence of mtDNA lineages with the morphological species. The cytb phylogeny reveals seven well-supported lineages that in part do not c...

  7. MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

    Directory of Open Access Journals (Sweden)

    Santa-Rita Pedro

    2005-06-01

    Full Text Available Abstract Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143 of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a breeds tend to display haplotypes belonging to different haplogroups; (b haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the

  8. How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models.

    Science.gov (United States)

    van Gisbergen, M W; Voets, A M; Starmans, M H W; de Coo, I F M; Yadak, R; Hoffmann, R F; Boutros, P C; Smeets, H J M; Dubois, L; Lambin, P

    2015-01-01

    Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized

  9. CDK5-mediated phosphorylation of p19INK4d avoids DNA damage-induced neurodegeneration in mouse hippocampus and prevents loss of cognitive functions.

    Science.gov (United States)

    Ogara, María Florencia; Belluscio, Laura M; de la Fuente, Verónica; Berardino, Bruno G; Sonzogni, Silvina V; Byk, Laura; Marazita, Mariela; Cánepa, Eduardo T

    2014-07-01

    DNA damage, which perturbs genomic stability, has been linked to cognitive decline in the aging human brain, and mutations in DNA repair genes have neurological implications. Several studies have suggested that DNA damage is also increased in brain disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise mechanisms connecting DNA damage with neurodegeneration remain poorly understood. CDK5, a critical enzyme in the development of the central nervous system, phosphorylates a number of synaptic proteins and regulates dendritic spine morphogenesis, synaptic plasticity and learning. In addition to these physiological roles, CDK5 has been involved in the neuronal death initiated by DNA damage. We hypothesized that p19INK4d, a member of the cell cycle inhibitor family INK4, is involved in a neuroprotective mechanism activated in response to DNA damage. We found that in response to genotoxic injury or increased levels of intracellular calcium, p19INK4d is transcriptionally induced and phosphorylated by CDK5 which provides it with greater stability in postmitotic neurons. p19INK4d expression improves DNA repair, decreases apoptosis and increases neuronal survival under conditions of genotoxic stress. Our in vivo experiments showed that decreased levels of p19INK4d rendered hippocampal neurons more sensitive to genotoxic insult resulting in the loss of cognitive abilities that rely on the integrity of this brain structure. We propose a feedback mechanism by which the neurotoxic effects of CDK5-p25 activated by genotoxic stress or abnormal intracellular calcium levels are counteracted by the induction and stabilization of p19INK4d protein reducing the adverse consequences on brain functions. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effects of a sex-ratio distorting endosymbiont on mtDNA variation in a global insect pest

    Directory of Open Access Journals (Sweden)

    Cook James M

    2009-03-01

    Full Text Available Abstract Background Patterns of mtDNA variation within a species reflect long-term population structure, but may also be influenced by maternally inherited endosymbionts, such as Wolbachia. These bacteria often alter host reproductive biology and can drive particular mtDNA haplotypes through populations. We investigated the impacts of Wolbachia infection and geography on mtDNA variation in the diamondback moth, a major global pest whose geographic distribution reflects both natural processes and transport via human agricultural activities. Results The mtDNA phylogeny of 95 individuals sampled from 10 countries on four continents revealed two major clades. One contained only Wolbachia-infected individuals from Malaysia and Kenya, while the other contained only uninfected individuals, from all countries including Malaysia and Kenya. Within the uninfected group was a further clade containing all individuals from Australasia and displaying very limited sequence variation. In contrast, a biparental nuclear gene phylogeny did not have infected and uninfected clades, supporting the notion that maternally-inherited Wolbachia are responsible for the mtDNA pattern. Only about 5% (15/306 of our global sample of individuals was infected with the plutWB1 isolate and even within infected local populations, many insects were uninfected. Comparisons of infected and uninfected isofemale lines revealed that plutWB1 is associated with sex ratio distortion. Uninfected lines have a 1:1 sex ratio, while infected ones show a 2:1 female bias. Conclusion The main correlate of mtDNA variation in P. xylostella is presence or absence of the plutWB1 infection. This is associated with substantial sex ratio distortion and the underlying mechanisms deserve further study. In contrast, geographic origin is a poor predictor of moth mtDNA sequences, reflecting human activity in moving the insects around the globe. The exception is a clade of Australasian individuals, which may

  11. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  12. Potential contribution of mitochondrial DNA damage associated molecular patterns in transfusion products to the development of acute respiratory distress syndrome after multiple transfusions.

    Science.gov (United States)

    Simmons, Jon D; Lee, Yann-Leei L; Pastukh, Viktor M; Capley, Gina; Muscat, Cherry A; Muscat, David C; Marshall, Michael L; Brevard, Sidney B; Gillespie, Mark N

    2017-06-01

    Massive transfusions are accompanied by an increased incidence of a particularly aggressive and lethal form of acute lung injury (delayed transfusion-related acute lung injury) which occurs longer than 24 hours after transfusions. In light of recent reports showing that mitochondrial (mt)DNA damage-associated molecular patterns (DAMPs) are potent proinflammatory mediators, and that their abundance in the sera of severely injured or septic patients is predictive of clinical outcomes, we explored the idea that mtDNA DAMPs are present in transfusion products and are associated with the occurrence of delayed transfusion-related acute lung injury. We prospectively enrolled fourteen consecutive severely injured patients that received greater than three units of blood transfusion products and determined if the total amount of mtDNA DAMPs delivered during transfusion correlated with serum mtDNA DAMPs measured after the last transfusion, and whether the quantity of mtDNA DAMPs in the serum-predicted development of acute respiratory distress syndrome (ARDS). We found detectable levels of mtDNA DAMPs in packed red blood cells (3 ± 0.4 ng/mL), fresh frozen plasma (213.7 ± 65 ng/mL), and platelets (94.8 ± 69.2), with the latter two transfusion products containing significant amounts of mtDNA fragments. There was a linear relationship between the mtDNA DAMPs given during transfusion and the serum concentration of mtDNA fragments (R = 0.0.74, p DAMPs in serum measured at 24 hours after transfusion predicted the occurrence of ARDS (9.9 ± 1.4 vs. 3.3 ± 0.9, p DAMPs administered during transfusion may be a determinant of serum mtDNA DAMP levels, and that serum levels of mtDNA DAMPs after multiple transfusions may predict the development of ARDS. Collectively, these findings support the idea that mtDNA DAMPs in transfusion products significantly contribute to the incidence of ARDS after massive transfusions. Prognostic study, level II; therapeutic study, level II.

  13. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  14. Comparative analysis of the relative potential of silver, Zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis.

    Science.gov (United States)

    Tyagi, Nikhil; Srivastava, Sanjeev K; Arora, Sumit; Omar, Yousef; Ijaz, Zohaib Mohammad; Al-Ghadhban, Ahmed; Deshmukh, Sachin K; Carter, James E; Singh, Ajay P; Singh, Seema

    2016-12-01

    Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO 2 ) nanoparticles (NPs) have been developed to limit the exposure of human skin to UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO 2 - and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO 2 -NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO 2 -NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO 2 -NPs and establish superior protective efficacy of Ag-NPs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Protective effect of sanguinarine on ultraviolet B-mediated damages in SKH-1 hairless mouse skin: implications for prevention of skin cancer.

    Science.gov (United States)

    Ahsan, Haseeb; Reagan-Shaw, Shannon; Eggert, David M; Tan, Thomas C; Afaq, Farrukh; Mukhtar, Hasan; Ahmad, Nihal

    2007-01-01

    Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280-320 nm), to human skin is the major cause of skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 micromol 0.3 mL(-1) ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer. However, further detailed studies are needed to support this suggestion.

  16. Pleistocene-Holocene boundary in Southern Arabia from the perspective of human mtDNA variation.

    Science.gov (United States)

    Al-Abri, Abdulrahim; Podgorná, Eliška; Rose, Jeffrey I; Pereira, Luísa; Mulligan, Connie J; Silva, Nuno M; Bayoumi, Riad; Soares, Pedro; Cerný, Viktor

    2012-10-01

    It is now known that several population movements have taken place at different times throughout southern Arabian prehistory. One of the principal questions under debate is if the Early Holocene peopling of southern Arabia was mainly due to input from the Levant during the Pre-Pottery Neolithic B, to the expansion of an autochthonous population, or some combination of these demographic processes. Since previous genetic studies have not been able to include all parts of southern Arabia, we have helped fill this lacuna by collecting new population datasets from Oman (Dhofar) and Yemen (Al-Mahra and Bab el-Mandab). We identified several new haplotypes belonging to haplogroup R2 and generated its whole genome mtDNA tree with age estimates undertaken by different methods. R2, together with other considerably frequent southern Arabian mtDNA haplogroups (R0a, HV1, summing up more than 20% of the South Arabian gene pool) were used to infer the past effective population size through Bayesian skyline plots. These data indicate that the southern Arabian population underwent a large expansion already some 12 ka. A founder analysis of these haplogroups shows that this expansion is largely attributed to demographic input from the Near East. These results support thus the spread of a population coming from the north, but at a significantly earlier date than presently considered by archaeologists. Our data suggest that some of the mtDNA lineages found in southern Arabia have persisted in the region since the end of the Last Ice Age. Copyright © 2012 Wiley Periodicals, Inc.

  17. Major Population Expansion of East Asians Began before Neolithic Time: Evidence of mtDNA Genomes

    Science.gov (United States)

    Qin, Zhen-Dong; Wang, Yi; Tan, Jing-Ze; Li, Hui; Jin, Li

    2011-01-01

    It is a major question in archaeology and anthropology whether human populations started to grow primarily after the advent of agriculture, i.e., the Neolithic time, especially in East Asia, which was one of the centers of ancient agricultural civilization. To answer this question requires an accurate estimation of the time of lineage expansion as well as that of population expansion in a population sample without ascertainment bias. In this study, we analyzed all available mtDNA genomes of East Asians ascertained by random sampling, a total of 367 complete mtDNA sequences generated by the 1000 Genome Project, including 249 Chinese (CHB, CHD, and CHS) and 118 Japanese (JPT). We found that major mtDNA lineages underwent expansions, all of which, except for two JPT-specific lineages, including D4, D4b2b, D4a, D4j, D5a2a, A, N9a, F1a1'4, F2, B4, B4a, G2a1 and M7b1'2'4, occurred before 10 kya, i.e., before the Neolithic time (symbolized by Dadiwan Culture at 7.9 kya) in East Asia. Consistent to this observation, the further analysis showed that the population expansion in East Asia started at 13 kya and lasted until 4 kya. The results suggest that the population growth in East Asia constituted a need for the introduction of agriculture and might be one of the driving forces that led to the further development of agriculture. PMID:21998705

  18. mtDNA variation in caste populations of Andhra Pradesh, India.

    Science.gov (United States)

    Bamshad, M; Fraley, A E; Crawford, M H; Cann, R L; Busi, B R; Naidu, J M; Jorde, L B

    1996-02-01

    Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p caste populations of Andhra Pradesh cluster more often with Africans than with Asians or Europeans. This is suggestive of admixture with African populations.

  19. Defining mtDNA origins and population stratification in Rio de Janeiro.

    Science.gov (United States)

    Simão, Filipa; Ferreira, Ana Paula; de Carvalho, Elizeu Fagundes; Parson, Walther; Gusmão, Leonor

    2018-02-06

    The genetic composition of the Brazilian population was shaped by interethnic admixture between autochthonous Native Americans, Europeans settlers and African slaves. This structure, characteristic of most American populations, implies the need for large population forensic databases to capture the high diversity that is usually associated with admixed populations. In the present work, we sequenced the control region of mitochondrial DNA from 205 non-related individuals living in the Rio de Janeiro metropolitan region. Overall high haplotype diversity (0.9994 ± 0.0006) was observed, and pairwise comparisons showed a high proportion of haplotype pairs with more than one-point differences. When ignoring homopolymeric tracts, pairwise comparisons showed no differences 0.18% of the time, and differences in a single position were found with a frequency of 0.32%. A high percentage of African mtDNA was found (42%), with lineages showing a major South West origin. For the West Eurasian and Native American haplogroups (representing 32% and 26%, respectively) it was not possible to evaluate a clear geographic or linguistic affiliation. When grouping the mtDNA lineages according to their continental origin (Native American, European and African), differences were observed for the ancestry proportions estimated with autosomal ancestry-informative markers, suggesting some level of genetic substructure. The results from this study are in accordance with historical data where admixture processes are confirmed with a strong maternal contribution of African maternal ancestry and a relevant contribution of Native American maternal ancestry. Moreover, the evidence for some degree of association between mtDNA and autosomal information should be considered when combining these types of markers in forensic analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. mtDNA structure: the women who formed the Brazilian Northeast.

    Science.gov (United States)

    Schaan, Ana Paula; Costa, Lorenna; Santos, Diego; Modesto, Antonio; Amador, Marcos; Lopes, Camile; Rabenhorst, Sílvia Helena; Montenegro, Raquel; Souza, Bruno D A; Lopes, Thayson; Yoshioka, France Keiko; Pinto, Giovanny; Silbiger, Vivian; Ribeiro-Dos-Santos, Ândrea

    2017-08-09

    The distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization. Unexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups. Our findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the

  1. Phylogenetic analysis of Sicilian goats reveals a new mtDNA lineage.

    Science.gov (United States)

    Sardina, M T; Ballester, M; Marmi, J; Finocchiaro, R; van Kaam, J B C H M; Portolano, B; Folch, J M

    2006-08-01

    The mitochondrial hypervariable region 1 (HVR1) sequence of 67 goats belonging to the Girgentana, Maltese and Derivata di Siria breeds was partially sequenced in order to present the first phylogenetic characterization of Sicilian goat breeds. These sequences were compared with published sequences of Indian and Pakistani domestic goats and wild goats. Mitochondrial lineage A was observed in most of the Sicilian goats. However, three Girgentana haplotypes were highly divergent from the Capra hircus clade, indicating that a new mtDNA lineage in domestic goats was found.

  2. Three reciprocally monophyletic mtDNA lineages elucidate the taxonomic status of Grant's gazelles

    DEFF Research Database (Denmark)

    Lorenzen, Eline Deidre; Arctander, Peter; Siegismund, Hans Redlef

    2008-01-01

    are discussed in reference to the four currently recognised subspecies. We suggest Grant's gazelles be raised to the superspecies Nanger (granti) comprising three taxonomic units corresponding to the three mtDNA lineages. There was no evidence of gene flow between the notata and granti lineages, despite...... their geographic proximity, suggesting reproductive isolation. These constitute evolutionary significant units within the adaptive evolutionary framework. Due to its restricted geographic distribution and genetic and morphological distinctiveness, we suggest the petersii lineage be raised to the species Nanger...

  3. mtDNA copy number in oocytes of different sizes from individual pre- and post-pubertal pigs

    DEFF Research Database (Denmark)

    Pedersen, Hanne Skovsgaard; Løvendahl, Peter; Larsen, Knud Erik

    2014-01-01

    Reproduction 131, 233–245). However, the correlation between size and mtDNA copy number in single oocytes has not been determined. This study describes the relation between oocytes of defined diameters from individual pre- and postpubertal pigs and mtDNA copy number. Cumulus-oocyte complexes were aspirated......Oocyte competence has been related to mtDNA copy number, but a large variation in mtDNA copy number between oocytes has been observed, caused by, e.g. oocyte donor and oocyte size (Sato et al. 2014 PLOS ONE 9, e94488; Cotterill et al. 2013 Mol. Hum. Reprod. 19, 444–450; El Shourbagy et al. 2006...... from ovaries of 10 pre- and 10 post-pubertal pigs. Cumulus cells were removed and the oocytes were measured (inside-ZP-diameter). Oocytes were transferred to DNAase-free tubes, snap-frozen, and stored at –80°C. The genes ND1 and COX1 were used to determine the mtDNA copy number. Plasmid preparations...

  4. Identification of West Eurasian mitochondrial haplogroups by mtDNA SNP screening: results of the 2006-2007 EDNAP collaborative exercise

    DEFF Research Database (Denmark)

    Parson, Walther; Fendt, Liane; Ballard, David

    2008-01-01

    The European DNA Profiling (EDNAP) Group performed a collaborative exercise on a mitochondrial (mt) DNA screening assay that targeted 16 nucleotide positions in the coding region and allowed for the discrimination of major west Eurasian mtDNA haplogroups. The purpose of the exercise was to evaluate...... no previous experience with the technology and/or mtDNA analysis. The results of this collaborative exercise stimulate the expansion of screening methods in forensic laboratories to increase efficiency and performance of mtDNA typing, and thus demonstrates that mtDNA SNP typing is a powerful tool for forensic...

  5. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a ‘differential multiple cleavage-site’ model

    OpenAIRE

    Bacman, SR; Williams, SL; Hernandez, D; Moraes, CT

    2007-01-01

    The ability to manipulate mitochondrial DNA (mtDNA) heteroplasmy would provide a powerful tool to treat mitochondrial diseases. Recent studies showed that mitochondria-targeted restriction endonucleases can modify mtDNA heteroplasmy in a predictable and efficient manner if it recognizes a single site in the mutant mtDNA. However, the applicability of such model is limited to mutations that create a novel cleavage site, not present in the wild-type mtDNA. We attempted to extend this approach t...

  6. Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

    International Nuclear Information System (INIS)

    Topcu-Tarladacalisir, Yeter; Kanter, Mehmet; Uzal, Mustafa Cem

    2009-01-01

    The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (γ)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal γ-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal γ-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of γ-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

  7. Prevention of UVA-induced oxidative damage in human dermal fibroblasts by new UV filters, assessed using a novel in vitro experimental system.

    Directory of Open Access Journals (Sweden)

    Francesca Brugè

    Full Text Available BACKGROUND: UVA rays present in sunlight are able to reach the dermal skin layer generating reactive oxygen species (ROS responsible for oxidative damage, alterations in gene expression, DNA damage, leading to cell inflammation, photo-ageing/-carcinogenesis. Sunscreens contain UV filters as active ingredients that absorb/reflect/dissipate UV radiation: their efficiency depends on their spectral profile and photostability which should then be reflected in biological protection of underlying skin. METHODS: A set of new UV filters was synthesized, and the most photostable one was compared to BMDBM, a widely used UVA filter. Cultured human dermal fibroblasts were exposed to UVA radiation which was filtered by a base cream containing or not UV filters placed above cell culture wells. The endpoints measured were: cell viability (MTT assay, ROS generation (DCFH-DA assay, mitochondrial function (JC-1 assay, DNA integrity (Comet assay and gene expression (MMP-1, COL1A1 by RT-qPCR. RESULTS: The new UV filter resulted more efficient than BMDBM in preserving cell viability, mitochondrial functionality and oxidative DNA damage, despite similar inhibition levels of intracellular ROS. Moreover, expression of genes involved in dermal photoageing were positively affected by the filtering action of the tested molecules. CONCLUSIONS: The experimental model proposed was able to validate the efficacy of the new UV filter, taking into account important cellular events related to UV-induced intracellular oxidative stress, often underestimated in the assessments of these compounds. GENERAL SIGNIFICANCE: The model may be used to compare the actual biological protection of commercial sunscreens and suncare products aside from their SPF and UVA-PF values.

  8. Prevention of UVA-induced oxidative damage in human dermal fibroblasts by new UV filters, assessed using a novel in vitro experimental system.

    Science.gov (United States)

    Brugè, Francesca; Tiano, Luca; Astolfi, Paola; Emanuelli, Monica; Damiani, Elisabetta

    2014-01-01

    UVA rays present in sunlight are able to reach the dermal skin layer generating reactive oxygen species (ROS) responsible for oxidative damage, alterations in gene expression, DNA damage, leading to cell inflammation, photo-ageing/-carcinogenesis. Sunscreens contain UV filters as active ingredients that absorb/reflect/dissipate UV radiation: their efficiency depends on their spectral profile and photostability which should then be reflected in biological protection of underlying skin. A set of new UV filters was synthesized, and the most photostable one was compared to BMDBM, a widely used UVA filter. Cultured human dermal fibroblasts were exposed to UVA radiation which was filtered by a base cream containing or not UV filters placed above cell culture wells. The endpoints measured were: cell viability (MTT assay), ROS generation (DCFH-DA assay), mitochondrial function (JC-1 assay), DNA integrity (Comet assay) and gene expression (MMP-1, COL1A1) by RT-qPCR. The new UV filter resulted more efficient than BMDBM in preserving cell viability, mitochondrial functionality and oxidative DNA damage, despite similar inhibition levels of intracellular ROS. Moreover, expression of genes involved in dermal photoageing were positively affected by the filtering action of the tested molecules. The experimental model proposed was able to validate the efficacy of the new UV filter, taking into account important cellular events related to UV-induced intracellular oxidative stress, often underestimated in the assessments of these compounds. The model may be used to compare the actual biological protection of commercial sunscreens and suncare products aside from their SPF and UVA-PF values.

  9. Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Topcu-Tarladacalisir, Yeter; Kanter, Mehmet [Trakya University, Department of Histology and Embryology, Faculty of Medicine, Edirne (Turkey); Uzal, Mustafa Cem [Trakya University, Department of Radiation Oncology, Faculty of Medicine, Edirne (Turkey)

    2009-08-15

    The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma ({gamma})-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal {gamma}-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal {gamma}-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of {gamma}-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

  10. Air exposure behavior of the semiterrestrial crab Neohelice granulata allows tolerance to severe hypoxia but not prevent oxidative damage due to hypoxia-reoxygenation cycle.

    Science.gov (United States)

    de Lima, Tábata Martins; Geihs, Márcio Alberto; Nery, Luiz Eduardo Maia; Maciel, Fábio Everton

    2015-11-01

    The air exposure behavior of the semi-terrestrial crab Neohelice granulata during severe hypoxia was studied. This study also verified whether this behavior mitigates possible oxidative damage, namely lipoperoxidation, caused by hypoxia and reoxygenation cycles. The lethal time for 50% of the crabs subjected to severe hypoxia (0.5 mgO2 · L(-1)) with free access to air was compared to that of crabs subjected to severe hypoxia without access to air. Crabs were placed in aquaria divided into three zones: water (when the animal was fully submersed), land (when the animal was completely emerged) and intermediate (when the animal was in contact with both environments) zones. Then the crabs were held in this condition for 270 min, and the time spent in each zone was recorded. Lipid peroxidation (LPO) damage to the walking leg muscles was determined for the following four experimental conditions: a--normoxic water with free access to air; b--hypoxic water without access to air; c--hypoxic water followed by normoxic water without air access; and d--hypoxic water with free access to air. When exposed to hypoxic water, N. granulata spent significantly more time on land, 135.3 ± 17.7 min, whereas control animals (exposed to normoxic water) spent more time submerged, 187.4 ± 20.2 min. By this behavior, N. granulata was able to maintain a 100% survival rate when exposed to severe hypoxia. However, N. granulata must still return to water after periods of air exposure (~ 14 min), causing a sequence of hypoxia/reoxygenation events. Despite increasing the survival rate, hypoxia with air access does not decrease the lipid peroxidation damage caused by the hypoxia and reoxygenation cycle experienced by these crabs.

  11. Phenotypic and mtDNA variation in Philippine Kappaphycus cottonii (Gigartinales, Rhodophyta).

    Science.gov (United States)

    Dumilag, Richard V; Gallardo, William George M; Garcia, Christian Philip C; You, YeaEun; Chaves, Alyssa Keren G; Agahan, Lance

    2017-11-09

    Members of the carrageenan-producing seaweeds of the genus Kappapphycus have a complicated taxonomic history particularly with regard to species identification. Many taxonomic challenges in this group have been currently addressed with the use of mtDNA sequences. The phylogenetic status and genetic diversity of one of the lesser known species, Kappaphycus cottonii, have repeatedly come into question. This study explored the genetic variation in Philippine K. cottonii using the mtDNA COI-5P gene and cox2-3 spacer sequences. The six phenotypic forms in K. cottonii did not correspond to the observed genetic variability; hinting at the greater involvement of environmental factors in determining changes to the morphology of this alga. Our results revealed that the Philippine K. cottonii has the richest number of haplotypes that have been detected, so far, for any Kappaphycus species. Our inferred phylogenetic trees suggested two lineages: a lineage, which exclusively includes K. cottonii and another lineage comprising the four known Kappaphycus species: K. alvarezii, K. inermis, K. malesianus, and K. striatus. The dichotomy supports the apparent synamorphy for each of these lineages (the strictly terete thalli, lack of protuberances, and the presence of a hyphal central core in the latter group, while the opposite of these morphologies in K. cottonii). These findings shed new light on understanding the evolutionary history of the genus. Assessing the breadth of the phenotypic and genetic variation in K. cottonii has implications for the conservation and management of the overall Kappaphycus genetic resources, especially in the Philippines.

  12. MtDNA barcode identification of fish larvae in the southern Great Barrier Reef – Australia

    Directory of Open Access Journals (Sweden)

    Graham G. Pegg

    2006-10-01

    Full Text Available Planktonic larvae were captured above a shallow coral reef study site on the Great Barrier Reef (GBR around spring-summer new moon periods (October-February using light trap or net capture devices. Larvae were identified to the genus or species level by comparison with a phylogenetic tree of tropical marine fish species using mtDNA HVR1 sequence data. Further analysis showed that within-species HVR1 sequence variation was typically 1-3%, whereas between-species variation for the same genus ranged up to 50%, supporting the suitability of HVR1 for species identification. Given the current worldwide interest in DNA barcoding and species identification using an alternative mtDNA gene marker (cox1, we also explored the efficacy of different primer sets for amplification of cox1 in reef fish, and its suitability for species identification. Of those tested, the Fish-F1 and -R1 primer set recently reported by Ward et al. (2005 gave the best results.

  13. A complete mtDNA genome of an early modern human from Kostenki, Russia.

    Science.gov (United States)

    Krause, Johannes; Briggs, Adrian W; Kircher, Martin; Maricic, Tomislav; Zwyns, Nicolas; Derevianko, Anatoli; Pääbo, Svante

    2010-02-09

    The recovery of DNA sequences from early modern humans (EMHs) could shed light on their interactions with archaic groups such as Neandertals and their relationships to current human populations. However, such experiments are highly problematic because present-day human DNA frequently contaminates bones [1, 2]. For example, in a recent study of mitochondrial (mt) DNA from Neolithic European skeletons, sequence variants were only taken as authentic if they were absent or rare in the present population, whereas others had to be discounted as possible contamination [3, 4]. This limits analysis to EMH individuals carrying rare sequences and thus yields a biased view of the ancient gene pool. Other approaches of identifying contaminating DNA, such as genotyping all individuals who have come into contact with a sample, restrict analyses to specimens where this is possible [5, 6] and do not exclude all possible sources of contamination. By studying mtDNA in Neandertal remains, where contamination and endogenous DNA can be distinguished by sequence, we show that fragmentation patterns and nucleotide misincorporations can be used to gauge authenticity of ancient DNA sequences. We use these features to determine a complete mtDNA sequence from a approximately 30,000-year-old EMH from the Kostenki 14 site in Russia.

  14. Do the Four Clades of the mtDNA Haplogroup L2 Evolve at Different Rates?

    Science.gov (United States)

    Torroni, Antonio; Rengo, Chiara; Guida, Valentina; Cruciani, Fulvio; Sellitto, Daniele; Coppa, Alfredo; Calderon, Fernando Luna; Simionati, Barbara; Valle, Giorgio; Richards, Martin; Macaulay, Vincent; Scozzari, Rosaria

    2001-01-01

    Forty-seven mtDNAs collected in the Dominican Republic and belonging to the African-specific haplogroup L2 were studied by high-resolution RFLP and control-region sequence analyses. Four sets of diagnostic markers that subdivide L2 into four clades (L2a–L2d) were identified, and a survey of published African data sets appears to indicate that these clades encompass all L2 mtDNAs and harbor very different geographic/ethnic distributions. One mtDNA from each of the four clades was completely sequenced by means of a new sequencing protocol that minimizes time and expense. The phylogeny of the L2 complete sequences showed that the two mtDNAs from L2b and L2d seem disproportionately derived, compared with those from L2a and L2c. This result is not consistent with a simple model of neutral evolution with a uniform molecular clock. The pattern of nonsynonymous versus synonymous substitutions hints at a role for selection in the evolution of human mtDNA. Regardless of whether selection is shaping the evolution of modern human mtDNAs, the population screening of L2 mtDNAs for the mutations identified by our complete sequence study should allow the identification of marker motifs of younger age with more restricted geographic distributions, thus providing new clues about African prehistory and the origin and relationships of African ethnic groups. PMID:11595973

  15. mtDNA Diversity and Phylogenetic State of Korean Cattle Breed, Chikso

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Kim

    2013-02-01

    Full Text Available In order to analyze the genetic diversity and phylogenetic status of the Korean Chikso breed, we determined sequences of mtDNA cytochrome b (cyt b gene and performed phylogenetic analysis using 239 individuals from 5 Chikso populations. Five non-synonymous mutations of a total of 15 polymorphic sites were identified among 239 cyt b coding sequences. Thirteen haplotypes were defined, and haplotype diversity was 0.4709 ranging from 0.2577 to 0.6114. Thirty-five haplotypes (C1–C35 were classified among 9 Asia and 3 European breeds. C2 was a major haplotype that contained 206 sequences (64.6% from all breeds used. C3–C13 haplotypes were Chikso-specific haplotypes. C1 and C2 haplotypes contained 80.5% of cyt b sequences of Hanwoo, Yanbian, Zaosheng and JB breeds. In phylogenetic analyses, the Chikso breed was contained into B. taurus lineage and was genetically more closely related to two Chinese breeds than to Korean brown cattle, Hanwoo. These results suggest that Chikso and Hanwoo have a genetic difference based on the mtDNA cyt b gene as well as their coat color, sufficient for classification as a separate breed.

  16. Effectiveness of cinnamon (Cinnamomum zeylanicum) bark oil in the prevention of carbon tetrachloride-induced damages on the male reproductive system.

    Science.gov (United States)

    Yüce, A; Türk, G; Çeribaşı, S; Güvenç, M; Çiftçi, M; Sönmez, M; Özer Kaya, Ş; Çay, M; Aksakal, M

    2014-04-01

    In this study, it was aimed to investigate the likelihood of detrimental effects of carbon tetrachloride (CCl4 ) on male reproductive system through oxidative stress mechanism and also protective effects of cinnamon bark oil (CBO). For this purpose, 28 healthy male Wistar rats were divided into four groups, seven rats in each. Group 1 received only olive oil daily; group 2 was treated with 100 mg kg(-1) CBO daily; group 3 was treated with only 0.25 ml kg(-1) CCl4 weekly; and group 4 received weekly CCl4 + daily CBO. All administrations were made by intragastric catheter and maintained for 10 weeks. Body and reproductive organ weights, sperm characteristics, testicular oxidative stress markers and testicular apoptosis were examined. CCl4 administration caused significant decreases in body and reproductive organ weights, testicular catalase (CAT) activity, sperm motility and concentration, and significant increases in lipid peroxidation (LPO) level, abnormal sperm rate and apoptotic index along with some histopathological damages compared with the control group. However, significant improvements were observed in absolute weights of testis and epididymis, all sperm quality parameters, LPO level, apoptotic index and testicular histopathological structure following the administration of CCl4 together with CBO when compared to group given CCl4 only. The findings of this study clearly suggest that CBO has protective effect against damages in male reproductive organs and cells induced by CCl4 . © 2013 Blackwell Verlag GmbH.

  17. Differences in mtDNA haplogroup distribution among 3 Jewish populations alter susceptibility to T2DM complications

    Directory of Open Access Journals (Sweden)

    Dadon Sarah

    2008-04-01

    Full Text Available Abstract Background Recent genome-wide association studies searching for candidate susceptibility loci for common complex diseases such as type 2 diabetes mellitus (T2DM and its common complications have uncovered novel disease-associated genes. Nevertheless these large-scale population screens often overlook the tremendous variation in the mitochondrial genome (mtDNA and its involvement in complex disorders. Results We have analyzed the mitochondrial DNA (mtDNA genetic variability in Ashkenazi (Ash, Sephardic (Seph and North African (NAF Jewish populations (total n = 1179. Our analysis showed significant differences (p Conclusion Our findings support the possibility that recent bottleneck events leading to over-representation of minor mtDNA alleles in specific genetic isolates, could result in population-specific susceptibility loci to complex disorders.

  18. Comparative mtDNA analyses of three sympatric macropodids from a conservation area on the Huon Peninsula, Papua New Guinea.

    Science.gov (United States)

    McGreevy, Thomas J; Dabek, Lisa; Husband, Thomas P

    2016-07-01

    Matschie's tree kangaroo (Dendrolagus matschiei), New Guinea pademelon (Thylogale browni), and small dorcopsis (Dorcopsulus vanheurni) are sympatric macropodid taxa, of conservation concern, that inhabit the Yopno-Urawa-Som (YUS) Conservation Area on the Huon Peninsula, Papua New Guinea. We sequenced three partial mitochondrial DNA (mtDNA) genes from the three taxa to (i) investigate network structure; and (ii) identify conservation units within the YUS Conservation Area. All three taxa displayed a similar pattern in the spatial distribution of their mtDNA haplotypes and the Urawa and Som rivers on the Huon may have acted as a barrier to maternal gene flow. Matschie's tree kangaroo and New Guinea pademelon within the YUS Conservation Area should be managed as single conservation units because mtDNA nucleotides were not fixed for a given geographic area. However, two distinct conservation units were identified for small dorcopsis from the two different mountain ranges within the YUS Conservation Area.

  19. Preventive measures against earthquake damage to museum collections: The recuperation of the exhibits at the Lorca archaeological museum; Medidas de prevencion ante seismos para las colecciones de museos: el caso del museo arqueologico de Lorca y la recuperacion de sus colecciones

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Alonso, E.; Hernandez, J. A.

    2012-11-01

    As a result of the earthquake on 11 May 2011 the Lorca municipal archaeological museum suffered serious damage to its structure and its exhibits. The lack of preventive measures and the inadequacy of steps taken before the earthquake aggravated the severity of damage. We have assessed the damage to the exhibits and analysed the causes that exacerbated the impact of the seismic movement. We also describe the work carried out by the Institute of Spain's Cultural Heritage (IPCE) to recuperate the collections and detail the measures and general criteria for the prevention and minimization of damage that the museum must implement to reduce the damage to its collections to a minimum during any subsequent earthquakes. (Author) 12 refs.

  20. mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

    Science.gov (United States)

    Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

    2008-02-01

    The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

  1. Programmed cell death triggered by nucleotide pool damage and its prevention by MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase.

    Science.gov (United States)

    Nakabeppu, Yusaku; Oka, Sugako; Sheng, Zijing; Tsuchimoto, Daisuke; Sakumi, Kunihiko

    2010-11-28

    Accumulation of oxidized bases such as 8-oxoguanine in either nuclear or mitochondrial DNA triggers various cellular dysfunctions including mutagenesis, and programmed cell death or senescence. Recent studies have revealed that oxidized nucleoside triphosphates such as 8-oxo-dGTP in the nucleotide pool are the main source of oxidized bases accumulating in the DNA of cells under oxidative stress. To counteract such deleterious effects of nucleotide pool damage, mammalian cells possess MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase and related enzymes, thus minimizing the accumulation of oxidized bases in cellular DNA. Depletion or increased expression of the MTH1 protein have revealed its significant roles in avoiding programmed cell death or senescence as well as mutagenesis, and accumulating evidences indicate that MTH1 is involved in suppression of degenerative disorders such as neurodegeneration. 2010 Elsevier B.V. All rights reserved.

  2. Post-bottleneck mtDNA diversity in a free-living population of European bison: implications for conservation

    DEFF Research Database (Denmark)

    Wojcik, J. M.; Kawalko, A.; Tokarska, M.

    2009-01-01

    genetic diversity. We studied a total of 195 individuals (127 males and 68 females). A 1429 bp fragment of mitochondrial DNA (mtDNA) including the D-loop region was analyzed in 87 individuals and revealed only three distinct haplotypes. Nucleotide (pi) and haplotype (H-d) diversity values were estimated...... for the European bison and were compared with pi and H-d estimated from three individuals of American bison Bison bison. Very low diversity values were found in the European bison in comparison with the diversity values found in the American bison. The low mtDNA variability in the European bison is in concordance...

  3. Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain.

    Science.gov (United States)

    Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Roy, Nairita; Ryan, Lauren N; Stanford, John A; Swerdlow, Russell H

    2016-12-01

    Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Aβ 1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers.

  4. Mitochondrial DNA Damage and Animal Longevity: Insights from Comparative Studies

    Directory of Open Access Journals (Sweden)

    Reinald Pamplona

    2011-01-01

    Full Text Available Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA. ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

  5. How few whales were there after whaling? Inference from contemporary mtDNA diversity.

    Science.gov (United States)

    Jackson, J A; Patenaude, N J; Carroll, E L; Baker, C Scott

    2008-01-01

    Reconstructing the history of exploited populations of whales requires fitting a trajectory through at least three points in time: (i) prior to exploitation, when abundance is assumed to be at the maximum allowed by environmental carrying capacity; (ii) the point of minimum abundance or 'bottleneck', usually near the time of protection or the abandonment of the hunt; and (iii) near the present, when protected populations are assumed to have undergone some recovery. As historical abundance is usually unknown, this trajectory must be extrapolated according to a population dynamic model using catch records, an assumed rate of increase and an estimate of current abundance, all of which have received considerable attention by the International Whaling Commission (IWC). Relatively little attention has been given to estimating minimum abundance (N(min)), although it is clear that genetic and demographic forces at this point are critical to the potential for recovery or extinction of a local population. We present a general analytical framework to improve estimates of N(min) using the number of mtDNA haplotypes (maternal lineages) surviving in a contemporary population of whales or other exploited species. We demonstrate the informative potential of this parameter as an a posteriori constraint on Bayesian logistic population dynamic models based on the IWC Comprehensive Assessment of the intensively exploited southern right whales (Eubalaena australis) and published surveys of mtDNA diversity for this species. Estimated historical trajectories from all demographic scenarios suggested a substantial loss of mtDNA haplotype richness as a result of 19th century commercial whaling and 20th century illegal whaling by the Soviet Union. However, the relatively high rates of population increase used by the IWC assessment predicted a bottleneck that was implausibly narrow (median, 67 mature females), given our corrected estimates of N(min). Further, high levels of remnant sequence

  6. Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin

    Directory of Open Access Journals (Sweden)

    Last Victoria

    2012-08-01

    Full Text Available Abstract Background Activation of phospholipase A2 (PLA2 and the subsequent metabolism of arachidonic acid (AA to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Results Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated proteins. Conversely, p-cPLA2 did significantly colocalise with the cytoskeletal protein beta III tubulin. Pre-treatment with the PLA2 inhibitor, palmitoyl trifluoromethyl ketone (PACOCF3 reduced cPLA2 activation, AA release and damage to the neuronal synapse. Furthermore, PACOCF3 reduced expression of p-cPLA2 in neurites and inhibited colocalisation with beta III tubulin, resulting in protection against PrP-induced cell death. Conclusions Collectively, these findings suggest that cPLA2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. Further work is needed to define exactly how PLA2 inhibitors protect neurons from peptide-induced toxicity and how this relates to intracellular structural changes occurring in neurodegeneration.

  7. Control of blood pressure and prevention of end-organ damage in patients with accelerated hypertension by combination with arotinolol and extended release nifedipine.

    Science.gov (United States)

    Suzuki, H; Nakamoto, H; Nemoto, H; Sugahara, S; Okada, H

    2000-03-01

    In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced. In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134 +/- 2 mmHg, the mean serum creatinine (mScr) was 4.5 +/- 0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150 +/- 9 g/m2. At 1 yr, the mDBP was reduced to 90 +/- 3 mmHg, the mScr to 2.9 +/- 0.9 mg/dl and the LVMi to 140 +/- 9 g/m2. At 3 yr, the mDBP was stabilized at 79 +/- 3 mmHg, the mScr maintained at 2.2 +/- 0.4 mg/dl, and the LVMi reduced to 128 +/- 9 g/m2. These results indicate that appropriate blood pressure control is important for

  8. Recent introgressive hybridization revealed by exclusive mtDNA transfer from Oreochromis leucostictus (Trewavas, 1933) to Oreochromis niloticus (Linnaeus, 1758) in Lake Baringo, Kenya

    OpenAIRE

    Nyingi, Dorothy W.; Agnèse, Jean-François

    2007-01-01

    Nuclear DNA and mtDNA polymorphisms were surveyed in various species of East African Oreochromis. In Lake Baringo, where only Oreochromis niloticus baringoensis is present, alien mtDNA haplotypes were observed, apparently the result of introgressive hybridization with Oreochromis leucostictus. This introgression is not accompanied by any substantial or recorded transfer of nuclear genes into O. n. baringoensis.

  9. A broad-spectrum sunscreen prevents cumulative damage from repeated exposure to sub-erythemal solar ultraviolet radiation representative of temperate latitudes.

    Science.gov (United States)

    Seité, S; Christiaens, F; Bredoux, C; Compan, D; Zucchi, H; Lombard, D; Fourtanier, A; Young, A R

    2010-02-01

    We have previously shown the detrimental effects of 19 sub-erythemal exposures to daily ultraviolet radiation (DUVR, which mimics non-extreme exposure conditions), delivered over 4 weeks to volunteers. This source had UVA (320-400 nm) to UVB (290-320 nm) irradiance ratio of 25, instead of that close to 10 that is typically the case with solar-simulated radiation (SSR) that represents summer global sunlight with a clear sky and quasi-zenith solar irradiance. Here, we report on an extension of this previous study, in which we evaluated the photoprotection afforded by a broad-spectrum daily-care product with a low-sun protection factor (SPF 8, UVA-PF 7 and 3* rated UVA protection). We assessed cellular and molecular markers of photodamage that are relevant to skin cancer and photoageing. This study shows that biological effects of repeated exposure to DUVR can be prevented by a broad-spectrum daily-care product and that the level of protection afforded varies with the studied endpoint. Efficient daily UVR protection, as provided by a broad-spectrum daily-care product, is necessary to prevent the 'silent' sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

  10. Tiliacora triandra (Colebr. Diels leaf extract enhances spatial learning and learning flexibility, and prevents dentate gyrus neuronal damage induced by cerebral ischemia/reperfusion injury in mice

    Directory of Open Access Journals (Sweden)

    Wachiryah Thong-asa

    2017-08-01

    Full Text Available Objective: The present study investigated the effects of a local Thai vegetable, Tiliacora triandra (Colebr. Diels, also known as Yanang, against cerebral ischemia/reperfusion injury in mice. Materials and Methods: Thirty male ICR mice were divided into three experimental groups of BLCCAO + 10% Tween 80, BLCCAO + T. triandra 300 mg/kg, and BLCCAO + T. triandra 600 mg/kg. Cerebral ischemia/reperfusion was induced by three minutes of bilateral common carotid artery occlusion (BLCCAO followed by 18 days of reperfusion. Leaf extract was administered orally 24 hours after arterial occlusion and continued for 18 consecutive days. Cognitive abilities were evaluated using the Morris water maze. Histological analysis was conducted in the dorsal hippocampus subregions CA1, CA3, and DG and white matter regions (the corpus callosum, internal capsule, and optic tract using 0.1 % cresyl violet and 0.1% Luxol fast blue staining. Results: Results showed that T. triandra leaf extract at the doses of 300 and 600 mg/kg significantly enhanced spatial learning, and learning flexibility, and prevented neuronal death in the DG of mice following ischemia/reperfusion. Conclusion: T. triandra leaf extract enhanced spatial learning, and learning flexibility, and prevented DG neuronal death in a mice model of cerebral ischemia/reperfusion.

  11. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  12. Moderate Dose of Trolox Preventing the Deleterious Effects of Wi-Fi Radiation on Spermatozoa In vitro through Reduction of Oxidative Stress Damage.

    Science.gov (United States)

    Ding, Shang-Shu; Sun, Ping; Zhang, Zhou; Liu, Xiang; Tian, Hong; Huo, Yong-Wei; Wang, Li-Rong; Han, Yan; Xing, Jun-Ping

    2018-02-20

    The worsening of semen quality, due to the application of Wi-Fi, can be ameliorated by Vitamin E. This study aimed to demonstrate whether a moderate dose of trolox, a new Vitamin E, inhibits oxidative damage on sperms in vitro after exposure to Wi-Fi radiation. Each of the twenty qualified semen, gathered from June to October 2014 in eugenics clinic, was separated into four aliquots, including sham, Wi-Fi-exposed, Wi-Fi plus 5 mmol/L trolox, and Wi-Fi plus 10 mmol/L trolox groups. At 0 min, all baseline parameters of the 20 samples were measured in sequence. Reactive oxygen species, glutathione, and superoxide dismutase were evaluated in the four aliquots at 45 and 90 min, as were sperm DNA fragments, sperm mitochondrial potential, relative amplification of sperm mitochondrial DNA, sperm vitality, and progressive and immotility sperm. The parameters were analyzed by one-way analysis of variance and Tukey's posttest. Among Wi-Fi plus 5 mmol/L trolox, Wi-Fi-exposed and Wi-Fi plus 10 mmol/L trolox groups, reactive oxygen species levels (45 min: 3.80 ± 0.41 RLU·10 -6 ·ml -1 vs. 7.50 ± 0.35 RLU·10 -6 ·ml -1 vs. 6.70 ± 0.47 RLU·10 -6 ·ml -1 , P electromagnetic radiation-induced oxidative stress.

  13. Identification of Polynesian mtDNA haplogroups in remains of Botocudo Amerindians from Brazil

    DEFF Research Database (Denmark)

    Gonçalves, Vanessa Faria; Stenderup, Jesper; Rodrigues-Carvalho, Cláudia

    2013-01-01

    There is a consensus that modern humans arrived in the Americas 15,000-20,000 y ago during the Late Pleistocene, most probably from northeast Asia through Beringia. However, there is still debate about the time of entry and number of migratory waves, including apparent inconsistencies between...... genetic and morphological data on Paleoa-mericans. Here we report the identification of mitochondrial sequences belonging to haplogroups characteristic of Polynesians in DNA extracted from ancient skulls of the now extinct Botocudo Indians from Brazil. The identification of these two Polynesian...... haplogroups was confirmed in independent replications in Brazil and Denmark, ensuring reliability of the data. Parallel analysis of 12 other Botocudo individuals yielded only the well-known Amerindian mtDNA hap-logroup C1. Potential scenarios to try to help understand these results are presented and discussed...

  14. Pearson syndrome and the role of deletion dimers and duplications in the mtDNA.

    Science.gov (United States)

    Jacobs, L J A M; Jongbloed, R J E; Wijburg, F A; de Klerk, J B C; Geraedts, J P M; Nijland, J G; Scholte, H R; de Coo, I F M; Smeets, H J M

    2004-01-01

    Pearson syndrome is an often fatal multisystem disease associated with mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with deletion dimers. The mutation percentage in different tissues (blood, muscle and liver) varied between 64% and 95%. After a remission period of about a year, the patient suddenly died at the age of 3 years owing to a severe lactic acidosis. A second patient with a previously reported deletion of 8 kb and a milder phenotype was found to have mitochondrial duplications and died at the age of 10 years. From these data and data from previous reports, we hypothesize that duplications might be beneficial in the clinical course of the disease and in life expectancy.

  15. mtDNA Deletion in an Iranian Infant with Pearson Marrow Syndrome.

    Science.gov (United States)

    Arzanian, Mohammad Taghi; Eghbali, Aziz; Karimzade, Parvaneh; Ahmadi, Mitra; Houshmand, Massoud; Rezaei, Nima

    2010-03-01

    Pearson syndrome (PS) is a rare multisystem mitochondrial disorder of hematopoietic system, characterized by refractory sideroblastic anemia, pancytopenia, exocrine pancreatic insufficiency, and variable neurologic, hepatic, renal, and endocrine failure. We describe a six-month-old female infant with Pearson marrow syndrome who presented with neurological manifestations. She had several episodes of seizures. Hematopoietic abnormalities were macrocytic anemia and neutropenia. Bone marrow aspiration revealed a cellular marrow with marked vacuolization of erythroid and myeloid precursors. Analysis of mtDNA in peripheral blood showed 8.5 kb deletion that was compatible with the diagnosis of PS. PS should be considered in infants with neurologic diseases, in patients with cytopenias, and also in patients with acidosis or refractory anemia.

  16. Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans.

    Science.gov (United States)

    Chatters, James C; Kennett, Douglas J; Asmerom, Yemane; Kemp, Brian M; Polyak, Victor; Blank, Alberto Nava; Beddows, Patricia A; Reinhardt, Eduard; Arroyo-Cabrales, Joaquin; Bolnick, Deborah A; Malhi, Ripan S; Culleton, Brendan J; Erreguerena, Pilar Luna; Rissolo, Dominique; Morell-Hart, Shanti; Stafford, Thomas W

    2014-05-16

    Because of differences in craniofacial morphology and dentition between the earliest American skeletons and modern Native Americans, separate origins have been postulated for them, despite genetic evidence to the contrary. We describe a near-complete human skeleton with an intact cranium and preserved DNA found with extinct fauna in a submerged cave on Mexico's Yucatan Peninsula. This skeleton dates to between 13,000 and 12,000 calendar years ago and has Paleoamerican craniofacial characteristics and a Beringian-derived mitochondrial DNA (mtDNA) haplogroup (D1). Thus, the differences between Paleoamericans and Native Americans probably resulted from in situ evolution rather than separate ancestry. Copyright © 2014, American Association for the Advancement of Science.

  17. Primary quantitative analysis of the mtDNA4977bp deletion induced by lonizing radiation in human peripheral blood u-sing real-time PCR

    International Nuclear Information System (INIS)

    Duan Zhikai; Liu Jiangong; Guo Wanlong; Zhang Shuxian

    2011-01-01

    Objective: To observe the influence of mtDNA4977bp deletion induced by different dose of γ ray in human peripheral blood in order to explore the feasibility of mtDNA4977bp deletion as biodosimeter. Methods: Human peripheral blood samples were collected from three healthy donors and irradiated by γ ray, MtDNA4977bp deletion was detected by real-time PCR. Results: It indicated that that from the range of 0 ∼ 8 Gy, the relationship between mtDNA4977bp deletion and irradiation dose represents certain curvilinear correlation (Y=1.2693+1.0660X+0.0198X 2 ). Conclusion: We find that γ ray has influence on the mtDNA4977bp deletion, so it may be an important biodosmeter in future. (authors)

  18. An economical mtDNA SNP assay detecting different mitochondrial haplogroups in identical HVR 1 samples of Caucasian ancestry.

    Science.gov (United States)

    Köhnemann, Stephan; Hohoff, Carsten; Pfeiffer, Heidi

    2009-09-01

    We had sequenced 329 Caucasian samples in Hypervariable Region 1 (HVR 1) and found that they belong to eleven different mitochondrial DNA (mtDNA) haplotypes. The sample set was further analysed by an mtDNA assay examining 32 single nucleotide polymorphisms (SNPs) for haplogroup discrimination. In a validation study on 160 samples of different origin it was shown that these SNPs were able to discriminate between the evolved superhaplogroups worldwide (L, M and N) and between the nine most common Caucasian haplogroups (H, I, J, K, T, U, V, W and X). The 32 mtDNA SNPs comprised 42 different SNP haplotypes instead of only eleven haplotypes after HVR 1 sequencing. The assay provided stable results in a range of 5ng genomic DNA down to virtually no genomic DNA per reaction. It was possible to detect samples of African, Asian and Eurasian ancestry, respectively. The 32 mtDNA SNP assay is a helpful adjunct to further distinguish between identical HVR 1 sequences of Caucasian origin. Our results suggest that haplogroup prediction using HVR 1 sequencing provides instable results. The use of coding region SNPs for haplogroup assignment is more suited than using HVR 1 haplotypes.

  19. Human aging and somatic point mutations in mtDNA: a comparative study of generational differences (grandparents and grandchildren

    Directory of Open Access Journals (Sweden)

    Anderson Nonato do Rosário Marinho

    2011-01-01

    Full Text Available The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years and their 62 grandchildren (mean age: 15 ± 4.1 years, the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old mutations (homoplasia and heteroplasmy. It is possible that both of these situations (homoplasia and heteroplasmy were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life.

  20. Rare mtDNA haplogroups and genetic differences in rich and poor Danish Iron-Age villages

    DEFF Research Database (Denmark)

    Melchior, L; Gilbert, M T P; Kivisild, T

    2008-01-01

    The Roman Iron-Age (0-400 AD) in Southern Scandinavia was a formative period, where the society changed from archaic chiefdoms to a true state formation, and the population composition has likely changed in this period due to immigrants from Middle Scandinavia. We have analyzed mtDNA from 22 indi...

  1. Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)

    Science.gov (United States)

    Sremba, Angela L.; Hancock-Hanser, Brittany; Branch, Trevor A.; LeDuc, Rick L.; Baker, C. Scott

    2012-01-01

    The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990–2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (FST = 0.032, pwhales. PMID:22412889

  2. Screen for abnormal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase deficiency and mtDNA depletion

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2014-02-01

    Full Text Available Mutations in subunits of succinyl-CoA synthetase/ligase (SCS, a component of the citric acid cycle, are associated with mitochondrial encephalomyopathy, elevation of methylmalonic acid (MMA, and mitochondrial DNA (mtDNA depletion. A FACS-based retroviral-mediated gene trap mutagenesis screen in mouse embryonic stem (ES cells for abnormal mitochondrial phenotypes identified a gene trap allele of Sucla2 (Sucla2SAβgeo, which was used to generate transgenic mice. Sucla2 encodes the ADP-specific β-subunit isoform of SCS. Sucla2SAβgeo homozygotes exhibited recessive lethality, with most mutants dying late in gestation (e18.5. Mutant placenta and embryonic (e17.5 brain, heart and muscle showed varying degrees of mtDNA depletion (20–60%. However, there was no mtDNA depletion in mutant liver, where the gene is not normally expressed. Elevated levels of MMA were observed in embryonic brain. SCS-deficient mouse embryonic fibroblasts (MEFs demonstrated a 50% reduction in mtDNA content compared with wild-type MEFs. The mtDNA depletion resulted in reduced steady state levels of mtDNA encoded proteins and multiple respiratory chain deficiencies. mtDNA content could be restored by reintroduction of Sucla2. This mouse model of SCS deficiency and mtDNA depletion promises to provide insights into the pathogenesis of mitochondrial diseases with mtDNA depletion and into the biology of mtDNA maintenance. In addition, this report demonstrates the power of a genetic screen that combines gene trap mutagenesis and FACS analysis in mouse ES cells to identify mitochondrial phenotypes and to develop animal models of mitochondrial dysfunction.

  3. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  4. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP.

    Science.gov (United States)

    Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S; Sutton, Robert

    2016-08-01

    Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site

    International Nuclear Information System (INIS)

    Jung, Dawoon; Cho, Youngeun; Collins, Leonard B.; Swenberg, James A.; Di Giulio, Richard T.

    2009-01-01

    Benzo[a]pyrene (BaP) is a known genotoxicant that affects both mitochondrial and nuclear DNA (mtDNA, nDNA). Here, we examined mtDNA and nDNA damage in the Atlantic killifish (Fundulus heteroclitus) from a highly contaminated Superfund site (Elizabeth River, VA, USA) and from a reference site (King's Creek, VA, USA) that were dosed with 10 mg/kg BaP. Using the long amplicon quantitative PCR technique, we observed similar increases in mitochondrial and nuclear DNA damage in King's Creek fish treated with BaP. Killifish from the Elizabeth River showed high levels of basal nDNA and mtDNA damage compared to fish from the reference site, but the level of damage induced due to BaP treatment was much lower in Elizabeth River killifish compared to King's Creek fish. Laboratory-reared offspring from both populations showed increased BaP-induced damage in mtDNA, relative to nDNA. Similar to the adult experiment, the Elizabeth River larvae had higher levels of basal DNA damage than those from the reference site, but were less impacted by BaP exposure. Measurements of oxidative DNA damage (8-oxo-deoxyguanine by LC-MS/MS) showed no differences among treatment groups, suggesting that the majority of DNA damage is from covalent binding of BaP metabolites to DNA. This study shows for the first time that mitochondria can be an important target of BaP toxicity in fish, indicating that BaP exposures could have important energetic consequences. Results also suggest that multi-generational exposures in the wild may lead to adaptations that dampen DNA damage arising from BaP exposure.

  6. Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site.

    Science.gov (United States)

    Jung, Dawoon; Cho, Youngeun; Collins, Leonard B; Swenberg, James A; Di Giulio, Richard T

    2009-10-19

    Benzo[a]pyrene (BaP) is a known genotoxicant that affects both mitochondrial and nuclear DNA (mtDNA, nDNA). Here, we examined mtDNA and nDNA damage in the Atlantic killifish (Fundulus heteroclitus) from a highly contaminated Superfund site (Elizabeth River, VA, USA) and from a reference site (King's Creek, VA, USA) that were dosed with 10 mg/kg BaP. Using the long amplicon quantitative PCR technique, we observed similar increases in mitochondrial and nuclear DNA damage in King's Creek fish treated with BaP. Killifish from the Elizabeth River showed high levels of basal nDNA and mtDNA damage compared to fish from the reference site, but the level of damage induced due to BaP treatment was much lower in Elizabeth River killifish compared to King's Creek fish. Laboratory-reared offspring from both populations showed increased BaP-induced damage in mtDNA, relative to nDNA. Similar to the adult experiment, the Elizabeth River larvae had higher levels of basal DNA damage than those from the reference site, but were less impacted by BaP exposure. Measurements of oxidative DNA damage (8-oxo-deoxyguanine by LC-MS/MS) showed no differences among treatment groups, suggesting that the majority of DNA damage is from covalent binding of BaP metabolites to DNA. This study shows for the first time that mitochondria can be an important target of BaP toxicity in fish, indicating that BaP exposures could have important energetic consequences. Results also suggest that multi-generational exposures in the wild may lead to adaptations that dampen DNA damage arising from BaP exposure.

  7. Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

    International Nuclear Information System (INIS)

    Jirkovský, Eduard; Lenčová-Popelová, Olga; Hroch, Miloš; Adamcová, Michaela; Mazurová, Yvona; Vávrová, Jaroslava

    2013-01-01

    Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300 mg/m 2 ), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3 mg/kg/week for 10 weeks); DEX (60 mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300 mg/m 2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug

  8. Population genetic structure of Santa Ynez rainbow trout – 2001 based on microsatellite and mtDNA analyses

    Science.gov (United States)

    Nielsen, Jennifer L.; Zimmerman, Christian E.; Olsen, Jeffrey B.; Wiacek, Talia; Kretschmer, E.J.; Greenwald, Glenn M.; Wenburg, John K.

    2003-01-01

    Microsatellite allelic and mitochondrial DNA (mtDNA) haplotype diversity are analyzed in eight rainbow trout (Oncorhynchus mykiss) collections: two from tributaries flowing into the upper Santa Ynez River watershed at Gibraltar Reservoir (Camuesa and Gidney creeks); three from tributaries between Gibraltar and Jameson reservoirs (Fox, Blue Canyon, and Alder creeks); one from a tributary above Jameson Reservoir (Juncal Creek); Jameson Reservoir; and one from the mainstem Santa Ynez River above the Jameson Reservoir. Both analyses reveal a high degree of population structure. Thirteen microsatellite loci are amplified from 376 fish. Population pairwise comparisons show significant differences in allelic frequency among all populations with the exception of Juncal Creek and Jameson Reservoir (p = 0.4). Pairwise Fst values range from 0.001 (Juncal Creek and Jameson Reservoir) to 0.17 (Camuesa and Juncal creeks) with an overall value of 0.021. Regression analyses (Slatkin 1993) supports an isolation-bydistance model in the five populations below Jameson Reservoir (intercept = 1.187, slope = -0.41, r2 = 0.67). A neighbor-joining bootstrap value of 100% (based on 2000 replicate trees) separates the populations sampled above and below Juncal Dam. Composite haplotypes from 321 fish generated using mtDNA sequence data (Dloop) reveal four previously described haplotypes (MYS1, MYS3, MYS5 and MYS8; Nielsen et al. 1994a), and one (MYS5) was found in all populations. Mean haplotype diversity is 0.48. Pairwise Fst values from mtDNA range from -0.019 to 0.530 (0.177 over all populations) and are larger than those for microsatellites in 26 of 28 pairwise comparisons. In addition, the mtDNA and microsatellites provide contrasting evidence of the relationship of Fox and Alder creeks to the other six populations. Discrepancies between the two markers are likely due to the unique properties of the two marker types and their value in revealing historic (mtDNA) versus contemporary

  9. Research into damage - avoiding damage

    International Nuclear Information System (INIS)

    1980-01-01

    The brochure reports on the work of five European materials testing institutions. Subjects covered are prevention of accidents and catastrophies, energy conservation, environmental pollution, and the safeguarding of values of national economy. (RW) [de

  10. Analysis of mtDNA sequence variants in colorectal adenomatous polyps

    Directory of Open Access Journals (Sweden)

    Grizzle William

    2010-10-01

    Full Text Available Abstract Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57% variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17 in tubular and 57% (13/23 in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was

  11. Machine learning classifier for identification of damaging missense mutations exclusive to human mitochondrial DNA-encoded polypeptides.

    Science.gov (United States)

    Martín-Navarro, Antonio; Gaudioso-Simón, Andrés; Álvarez-Jarreta, Jorge; Montoya, Julio; Mayordomo, Elvira; Ruiz-Pesini, Eduardo

    2017-03-07

    Several methods have been developed to predict the pathogenicity of missense mutations but none has been specifically designed for classification of variants in mtDNA-encoded polypeptides. Moreover, there is not available curated dataset of neutral and damaging mtDNA missense variants to test the accuracy of predictors. Because mtDNA sequencing of patients suffering mitochondrial diseases is revealing many missense mutations, it is needed to prioritize candidate substitutions for further confirmation. Predictors can be useful as screening tools but their performance must be improved. We have developed a SVM classifier (Mitoclass.1) specific for mtDNA missense variants. Training and validation of the model was executed with 2,835 mtDNA damaging and neutral amino acid substitutions, previously curated by a set of rigorous pathogenicity criteria with high specificity. Each instance is described by a set of three attributes based on evolutionary conservation in Eukaryota of wildtype and mutant amino acids as well as coevolution and a novel evolutionary analysis of specific substitutions belonging to the same domain of mitochondrial polypeptides. Our classifier has performed better than other web-available tested predictors. We checked performance of three broadly used predictors with the total mutations of our curated dataset. PolyPhen-2 showed the best results for a screening proposal with a good sensitivity. Nevertheless, the number of false positive predictions was too high. Our method has an improved sensitivity and better specificity in relation to PolyPhen-2. We also publish predictions for the complete set of 24,201 possible missense variants in the 13 human mtDNA-encoded polypeptides. Mitoclass.1 allows a better selection of candidate damaging missense variants from mtDNA. A careful search of discriminatory attributes and a training step based on a curated dataset of amino acid substitutions belonging exclusively to human mtDNA genes allows an improved

  12. MtDNA metagenomics reveals large-scale invasion of belowground arthropod communities by introduced species.

    Science.gov (United States)

    Cicconardi, Francesco; Borges, Paulo A V; Strasberg, Dominique; Oromí, Pedro; López, Heriberto; Pérez-Delgado, Antonio J; Casquet, Juliane; Caujapé-Castells, Juli; Fernández-Palacios, José María; Thébaud, Christophe; Emerson, Brent C

    2017-06-01

    Using a series of standardized sampling plots within forest ecosystems in remote oceanic islands, we reveal fundamental differences between the structuring of aboveground and belowground arthropod biodiversity that are likely due to large-scale species introductions by humans. Species of beetle and spider were sampled almost exclusively from single islands, while soil-dwelling Collembola exhibited more than tenfold higher species sharing among islands. Comparison of Collembola mitochondrial metagenomic data to a database of more than 80 000 Collembola barcode sequences revealed almost 30% of sampled island species are genetically identical, or near identical, to individuals sampled from often very distant geographic regions of the world. Patterns of mtDNA relatedness among Collembola implicate human-mediated species introductions, with minimum estimates for the proportion of introduced species on the sampled islands ranging from 45% to 88%. Our results call for more attention to soil mesofauna to understand the global extent and ecological consequences of species introductions. © 2017 John Wiley & Sons Ltd.

  13. MtDNA diversity and genetic lineages of four cattle breeds in Malaysia

    Directory of Open Access Journals (Sweden)

    Somarny, W.W.M.Z.

    2015-06-01

    Full Text Available There is lack of comprehensive studies on the genetic diversity or phylogenetic analysis of beef cattle breeds in Malaysia. In this study, the partial sequence of mitochondrial DNA cytochrome b gene (cyt b was analysed from blood samples obtained from 25 Chinese Yellow Cattle (CY, 33 Kedah-Kelantan (KK, 32 Brakmas (BM and 30 Bali cattle (BC. Based on these 120 individuals, 19 mtDNA haplotypes (GenBank Accession No. GU67340 - GU67358 were identified by polymorphisms at 31 sites. Hap19 was predominant in BM (78%, KK (82% and CY (100% indicating similar origin or gene flow between breeds whilst Hap11 was exclusively for BC. However, there were only two nucleotide differences between these two major haplotypes. These results can be interpreted that these representative cattle in these haplotypes are admixtures of B. indicus or B. javanicus through maternal ancestry. Conversely, the CY cattle investigated are highly inbred where no variation could be observed in the short segment investigated.

  14. VARIASI GENETIK IKAN TUNA SIRIP KUNING, Thunnus albacares DENGAN ANALISIS ELEKTROFORESIS ALLOZYME DAN Mt-DNA

    Directory of Open Access Journals (Sweden)

    Gusti Ngurah Permana

    2007-04-01

    Full Text Available Sampel ikan tuna sirip kuning, T. albacares diambil dari tiga lokasi (perairan Bali, Sulawesi Utara, dan Maluku Utara dan dilakukan analisis variasi genetik dengan metode elektroforesis allozyme menggunakan 15 enzim dan mt-DNA dengan 4 enzim restriksi. Hasil penelitian ini diperoleh 4 lokus enzim polimorfik yaitu: Idh-*2 (isocitrate dehydrogenase, Gpi-2* (glucose phoshate dehydrogenase , Mdh-1* (malat e dehydrogenase, dan Est-1* (esterase. Frekuensi alel allozyme terlihat adanya perbedaan yang nyata (Fst = 0,12; P<0,05 antar lokasi yaitu Bali (A, B, C, D, Sulawesi Utara dan Maluku Utara (A, B, C. 15 komposit haplotipe ditemukan pada populasi Bali, Sulawesi Utara, dan Maluku Utara. Haplotype diversity pada populasi Bali 0,886; Sulawesi Utara 0,790; dan Maluku Utara 0,785; dengan rata-rata dari haplotype diversity adalah 0,857. Jarak genetik dari ketiga populasi berkisar antara 0,003--0,023 (rata-rata 0,016. Populasi Maluku Utara dan Sulawesi Utara mempunyai jarak genetik terdekat yaitu 0,003. Hal ini merupakan indikator bahwa Sulawesi Utara dan Maluku Utara sering digunakan sebagai jalur migrasi dengan adanya kesamaan alel yang ditemukan pada kedua populasi tesebut, jika dibandingkan dengan populasi Bali (0,023.

  15. Rampant nuclear insertion of mtDNA across diverse lineages within Orthoptera (Insecta.

    Directory of Open Access Journals (Sweden)

    Hojun Song

    Full Text Available Nuclear mitochondrial pseudogenes (numts are non-functional fragments of mtDNA inserted into the nuclear genome. Numts are prevalent across eukaryotes and a positive correlation is known to exist between the number of numts and the genome size. Most numt surveys have relied on model organisms with fully sequenced nuclear genomes, but such analyses have limited utilities for making a generalization about the patterns of numt accumulation for any given clade. Among insects, the order Orthoptera is known to have the largest nuclear genome and it is also reported to include several species with a large number of numts. In this study, we use Orthoptera as a case study to document the diversity and abundance of numts by generating numts of three mitochondrial loci across 28 orthopteran families, representing the phylogenetic diversity of the order. We discover that numts are rampant in all lineages, but there is no discernable and consistent pattern of numt accumulation among different lineages. Likewise, we do not find any evidence that a certain mitochondrial gene is more prone to nuclear insertion than others. We also find that numt insertion must have occurred continuously and frequently throughout the diversification of Orthoptera. Although most numts are the result of recent nuclear insertion, we find evidence of very ancient numt insertion shared by highly divergent families dating back to the Jurassic period. Finally, we discuss several factors contributing to the extreme prevalence of numts in Orthoptera and highlight the importance of exploring the utility of numts in evolutionary studies.

  16. Rampant nuclear insertion of mtDNA across diverse lineages within Orthoptera (Insecta).

    Science.gov (United States)

    Song, Hojun; Moulton, Matthew J; Whiting, Michael F

    2014-01-01

    Nuclear mitochondrial pseudogenes (numts) are non-functional fragments of mtDNA inserted into the nuclear genome. Numts are prevalent across eukaryotes and a positive correlation is known to exist between the number of numts and the genome size. Most numt surveys have relied on model organisms with fully sequenced nuclear genomes, but such analyses have limited utilities for making a generalization about the patterns of numt accumulation for any given clade. Among insects, the order Orthoptera is known to have the largest nuclear genome and it is also reported to include several species with a large number of numts. In this study, we use Orthoptera as a case study to document the diversity and abundance of numts by generating numts of three mitochondrial loci across 28 orthopteran families, representing the phylogenetic diversity of the order. We discover that numts are rampant in all lineages, but there is no discernable and consistent pattern of numt accumulation among different lineages. Likewise, we do not find any evidence that a certain mitochondrial gene is more prone to nuclear insertion than others. We also find that numt insertion must have occurred continuously and frequently throughout the diversification of Orthoptera. Although most numts are the result of recent nuclear insertion, we find evidence of very ancient numt insertion shared by highly divergent families dating back to the Jurassic period. Finally, we discuss several factors contributing to the extreme prevalence of numts in Orthoptera and highlight the importance of exploring the utility of numts in evolutionary studies.

  17. Haplogroup Classification of Korean Cattle Breeds Based on Sequence Variations of mtDNA Control Region

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Kim

    2016-05-01

    Full Text Available Many studies have reported the frequency and distribution of haplogroups among various cattle breeds for verification of their origins and genetic diversity. In this study, 318 complete sequences of the mtDNA control region from four Korean cattle breeds were used for haplogroup classification. 71 polymorphic sites and 66 haplotypes were found in these sequences. Consistent with the genetic patterns in previous reports, four haplogroups (T1, T2, T3, and T4 were identified in Korean cattle breeds. In addition, T1a, T3a, and T3b sub-haplogroups were classified. In the phylogenetic tree, each haplogroup formed an independent cluster. The frequencies of T3, T4, T1 (containing T1a, and T2 were 66%, 16%, 10%, and 8%, respectively. Especially, the T1 haplogroup contained only one haplotype and a sample. All four haplogroups were found in Chikso, Jeju black and Hanwoo. However, only the T3 and T4 haplogroups appeared in Heugu, and most Chikso populations showed a partial of four haplogroups. These results will be useful for stable conservation and efficient management of Korean cattle breeds.

  18. Regional Variation in mtDNA of the Lesser Prairie-Chicken

    Science.gov (United States)

    Hagen, Christian A.; Pitman, James C.; Sandercock, Brett K.; Wolfe, Don H.; Robel, Robel J.; Applegate, Roger D.; Oyler-McCance, Sara J.

    2010-01-01

    Cumulative loss of habitat and long-term decline in the populations of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) have led to concerns for the species' viability throughout its range in the southern Great Plains. For more efficient conservation past and present distributions of genetic variation need to be understood. We examined the distribution of mitochondrial DNA (mtDNA) variation in the Lesser Prairie-Chicken across Kansas, Colorado, Oklahoma, and New Mexico. Throughout the range we found little genetic differentiation except for the population in New Mexico, which was significantly different from most other publications. We did, however, find significant isolation by distance at the rangewide scale (r=0.698). We found no relationship between haplotype phylogeny and geography, and our analyses provide evidence for a post-glacial population expansion within the species that is consistent with the idea that speciation within Tympanuchus is recent. Conservation actions that increase the likelihood of genetically viable populations in the future should be evaluated for implementation.

  19. Evolution of sex-dependent mtDNA transmission in freshwater mussels (Bivalvia: Unionida).

    Science.gov (United States)

    Guerra, Davide; Plazzi, Federico; Stewart, Donald T; Bogan, Arthur E; Hoeh, Walter R; Breton, Sophie

    2017-05-08

    Doubly uniparental inheritance (DUI) describes a mode of mtDNA transmission widespread in gonochoric freshwater mussels (Bivalvia: Palaeoheterodonta: Unionida). In this system, both female- and male-transmitted mtDNAs, named F and M respectively, coexist in the same species. In unionids, DUI is strictly correlated to gonochorism and to the presence of the atypical open reading frames (ORFans) F-orf and M-orf, respectively inside F and M mtDNAs, which are hypothesized to participate in sex determination. However, DUI is not found in all three Unionida superfamilies (confirmed in Hyrioidea and Unionoidea but not in Etherioidea), raising the question of its origin in these bivalves. To reconstruct the co-evolution of DUI and of ORFans, we sequenced the mtDNAs of four unionids (two gonochoric with DUI, one gonochoric and one hermaphroditic without DUI) and of the related gonochoric species Neotrigonia margaritacea (Palaeoheterodonta: Trigoniida). Our analyses suggest that rearranged mtDNAs appeared early during unionid radiation, and that a duplicated and diverged atp8 gene evolved into the M-orf associated with the paternal transmission route in Hyrioidea and Unionoidea, but not in Etherioidea. We propose that novel mtDNA-encoded genes can deeply influence bivalve sex determining systems and the evolution of the mitogenomes in which they occur.

  20. Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion.

    Science.gov (United States)

    Santorelli, F M; Barmada, M A; Pons, R; Zhang, L L; DiMauro, S

    1996-11-01

    Pearson syndrome is a systemic disorder of oxidative phosphorylation in infants, predominantly affecting the bone marrow and exocrine pancreas and associated with single deletions in mitochondrial DNA (mtDNA). CNS involvement may occur in patients who survive the infantile hematopoietic disorder. We describe a Pearson syndrome patient who developed neurologic manifestations associated with the pathologic features of Leigh syndrome. Biochemical studies in muscle and skin fibroblasts showed partial deficiencies of complexes I and IV of the respiratory chain. Adenosine triphosphate production in mitochondria isolated from skin fibroblasts was reduced to 25% of controls. We detected a novel 3.6 Kb mtDNA deletion in skin fibroblasts from the proband but not in his mother's white blood cells. Leigh syndrome seems to be the common neuropathologic expression of any disorder causing severe impairment of oxidative energy production in the CNS.

  1. Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury.

    Science.gov (United States)

    Lee, Yann-Leei; King, Madelyn B; Gonzalez, Richard P; Brevard, Sidney B; Frotan, M Amin; Gillespie, Mark N; Simmons, Jon D

    2014-10-01

    Transfusion-related acute lung injury (TRALI) is the most frequent and severe complication in patients receiving multiple blood transfusions. Current pathogenic concepts hold that proinflammatory mediators present in transfused blood products are responsible for the initiation of TRALI, but the identity of the critical effector molecules is yet to be determined. We hypothesize that mtDNA damage-associated molecular patterns (DAMPs) are present in blood transfusion products, which may be important in the initiation of TRALI. DNA was extracted from consecutive samples of packed red blood cells, fresh frozen plasma (FFP), and platelets procured from the local blood bank. Quantitative real-time polymerase chain reaction was used to quantify ≈200 bp sequences from the COX1, ND1, ND6, and D-loop regions of the mitochondrial genome. A range of mtDNA DAMPs were detected in all blood components measured, with FFP displaying the largest variation. We conclude that mtDNA DAMPs are present in packed red blood cells, FFP, and platelets. These observations provide proof of the concept that mtDNA DAMPs may be mediators of TRALI. Further studies are needed to test this hypothesis and to determine the origin of mtDNA DAMPs in transfused blood. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Extreme mitochondrial evolution in the ctenophore Mnemiopsis leidyi: Insight from mtDNA and the nuclear genome.

    Science.gov (United States)

    Pett, Walker; Ryan, Joseph F; Pang, Kevin; Mullikin, James C; Martindale, Mark Q; Baxevanis, Andreas D; Lavrov, Dennis V

    2011-08-01

    Recent advances in sequencing technology have led to a rapid accumulation of mitochondrial DNA (mtDNA) sequences, which now represent the wide spectrum of animal diversity. However, one animal phylum--Ctenophora--has, to date, remained completely unsampled. Ctenophores, a small group of marine animals, are of interest due to their unusual biology, controversial phylogenetic position, and devastating impact as invasive species. Using data from the Mnemiopsis leidyi genome sequencing project, we Polymerase Chain Reaction (PCR) amplified and analyzed its complete mitochondrial (mt-) genome. At just over 10 kb, the mt-genome of M. leidyi is the smallest animal mtDNA ever reported and is among the most derived. It has lost at least 25 genes, including atp6 and all tRNA genes. We show that atp6 has been relocated to the nuclear genome and has acquired introns and a mitochondrial targeting presequence, while tRNA genes have been genuinely lost, along with nuclear-encoded mt-aminoacyl tRNA synthetases. The mt-genome of M. leidyi also displays extremely high rates of sequence evolution, which likely led to the degeneration of both protein and rRNA genes. In particular, encoded rRNA molecules possess little similarity with their homologs in other organisms and have highly reduced secondary structures. At the same time, nuclear encoded mt-ribosomal proteins have undergone expansions, likely to compensate for the reductions in mt-rRNA. The unusual features identified in M. leidyi mtDNA make this organism an interesting system for the study of various aspects of mitochondrial biology, particularly protein and tRNA import and mt-ribosome structures, and add to its value as an emerging model species. Furthermore, the fast-evolving M. leidyi mtDNA should be a convenient molecular marker for species- and population-level studies.

  3. Extreme Mitochondrial Evolution in the Ctenophore Mnemiopsis leidyi: Insights from mtDNA and the Nuclear Genome

    Science.gov (United States)

    Pett, Walker; Ryan, Joseph F.; Pang, Kevin; Mullikin, James C.; Martindale, Mark Q.; Baxevanis, Andreas D.; Lavrov, Dennis V.

    2012-01-01

    Recent advances in sequencing technology have led to a rapid accumulation of mitochondrial DNA (mtDNA) sequences, which now represent the wide spectrum of animal diversity. However, one animal phylum – Ctenophora – has, to date, remained completely unsampled. Ctenophores, a small group of marine animals, are of interest due to their unusual biology, controversial phylogenetic position, and devastating impact as an invasive species. Using data from the Mnemiopsis leidyi genome sequencing project, we PCR amplified and analyzed its complete mitochondrial (mt-) genome. At just over 10kb, the mt-genome of M. leidyi is the smallest animal mtDNA ever reported and is among the most derived. It has lost at least 25 genes, including atp6 and all tRNA genes. We show that atp6 has been relocated to the nuclear genome and has acquired introns and a mitochondrial targeting presequence, while tRNA genes have been genuinely lost, along with nuclear-encoded mt-aminoacyl tRNA synthetases. The mt-genome of M. leidyi also displays extremely high rates of sequence evolution, which likely led to the degeneration of both protein and rRNA genes. In particular, encoded rRNA molecules possess little similarity with their homologues in other organisms and have highly reduced secondary structures. At the same time, nuclear encoded mt-ribosomal proteins have undergone expansions, probably to compensate for the reductions in mt-rRNA. The unusual features identified in M. leidyi mtDNA make this organism an interesting system for the study of various aspects of mitochondrial biology, particularly protein and tRNA import and mt-ribosome structures, and add to its value as an emerging model species. Furthermore, the fast-evolving M. leidyi mtDNA should be a convenient molecular marker for species- and population-level studies. PMID:21985407

  4. Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia.

    Directory of Open Access Journals (Sweden)

    Angela L Sremba

    Full Text Available The Antarctic blue whale (Balaenoptera musculus intermedia was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86 have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004, perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST = 0.032, p<0.005 and microsatellite alleles (F(ST = 0.005, p<0.05 among the six Antarctic Areas historically used by the IWC for management of blue whales.

  5. [Sequence polymorphism of mtDNA HVR Iand HVR II of Oroqen ethnic group in Inner Mongolia].

    Science.gov (United States)

    Yan, Chun-Xia; Chen, Feng; Dang, Yong-Hui; Li, Tao; Zheng, Hai-Bo; Chen, Teng; Li, Sheng-Bin

    2008-04-01

    Venous blood samples from 50 unrelated Oroqen individuals living in Inner Mongolia were collected and their mtDNA HVR I and HVR II sequences were detected by using ABI PRISM377 sequencers. The number of polymorphic loci, haplotype, haplotype frequence, average nucleotide variability and other polymorphic parameters were calculated. Based on Oroqen mtDNA sequence data obtained in our experiments and published data, genetic distance between Oroqen ethnic group and other populations were computered by Nei's measure. Phylogenetic tree was constructed by Neighbor Joining method. Comparing with Anderson sequence, 52 polymorphic loci in HVR I and 24 loci in HVR II were found in Oroqen mtDNA sequence, 38 and 27 haplotypes were defined herewith. Haplotype diversity and average nucleotide variability were 0.964+/-0.018 and 7.379 in HVR I, 0.929+/-0.019 and 2.408 in HVR II respectively. Fst and dA genetic distance between 12 populations were calculated based on HVR I sequence, and their relative coefficients were 0.993(P HVR I and HVR II in Oroqen ethnic group has some specificities compared with that of other populations. These data provide a useful tool in forensic identification, population genetic study and other research fields.

  6. Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA mutator mouse.

    Directory of Open Access Journals (Sweden)

    Lloye M Dillon

    Full Text Available Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs and PPAR γ coactivator-1α (PGC-1α pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of premature aging including hair loss, anemia, osteoporosis, sarcopenia and decreased lifespan. They also have increased mtDNA mutations and marked mitochondrial dysfunction. We found that mutator mice treated with bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging-like phenotypes. Although we observed an increase in markers of fatty acid oxidation in these tissues, we did not detect a generalized increase in mitochondrial markers. On the other hand, there were no improvements in muscle function or lifespan of the mutator mouse, which we attributed to the rodent-specific hepatomegaly associated with fibrate treatment. These results showed that despite its secondary effects in rodent's liver, bezafibrate was able to improve some of the aging phenotypes in the mutator mouse. Because the associated hepatomegaly is not observed in primates, long-term bezafibrate treatment in humans could have beneficial effects on tissues undergoing chronic bioenergetic-related degeneration.

  7. Detection of polymorphisms of the mtDNA control region of Caretta caretta (Testudines: Cheloniidae) by PCR-SSCP.

    Science.gov (United States)

    Reis, E C; Albano, R M; Bondioli, A C V; Soares, L S; Lôbo-Hajdu, G

    2009-02-25

    Marine turtles are increasingly being threatened worldwide by anthropogenic activities. Better understanding of their life cycle, behavior and population structure is imperative for the design of adequate conservation strategies. The mtDNA control region is a fast-evolving matrilineal marker that has been employed in the study of marine turtle populations. We developed and tested a simple molecular tracing system for Caretta caretta mtDNA haplotypes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Using this technique, we were able to distinguish the SSCP patterns of 18 individuals of the haplotypes CC-A4, CC-A24 and CCxLO, which are commonly found in turtles sampled on the Brazilian coast. When we analyzed 15 turtles with previously unknown sequences, we detected two other haplotypes, in addition to the other four. Based on DNA sequencing, they were identified as the CC-A17 and CC-A1 haplotypes. Further analyses were made with the sea turtles, Chelonia mydas (N = 8), Lepidochelys olivacea (N = 3) and Eretmochelys imbricata (N = 1), demonstrating that the PCR-SSCP technique is able to distinguish intra- and interspecific variation in the family Cheloniidae. We found that this technique can be useful for identifying sea turtle mtDNA haplotypes, reducing the need for sequencing.

  8. Dysphagia is prevalent in patients with CPEO and single, large-scale deletions in mtDNA

    DEFF Research Database (Denmark)

    Pedersen, Gitte Hedermann; Løkken, Nicoline; Dahlqvist, Julia R.

    2017-01-01

    Background  The aim of this study was to assess the frequency of subjective and objective dysphagia in patients with chronic progressive external ophthalmoplegia (CPEO) due to single, large-scale deletions (LSDs) of mitochondrial DNA (mtDNA). Methods  Sixteen patients with CPEO and single LSDs...... and single LSDs of mtDNA had a prolonged cold-water test, including one with a PEG-tube, who was unable to perform the test, and nine patients reported subjective swallowing problems (56.3%). All mitochondrial myopathy patients in the control group had a normal duration of the cold-water test.  Conclusions......  The study shows that dysphagia is a common problem in patients with CPEO and LSDs of mtDNA. Dysphagia seems to be progressive with age as abnormal swallowing occurred preferentially in persons ≥ 45 years. The study shows that increased awareness of this symptom should be given to address appropriate...

  9. The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific

    DEFF Research Database (Denmark)

    Raule, Nicola; Sevini, Federica; Li, Shengting

    2014-01-01

    , while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se...... analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.......To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification...

  10. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes.

    Science.gov (United States)

    Sibley, Cailin H; Plass, Nikki; Snow, Joseph; Wiggs, Edythe A; Brewer, Carmen C; King, Kelly A; Zalewski, Christopher; Kim, H Jeffrey; Bishop, Rachel; Hill, Suvimol; Paul, Scott M; Kicker, Patrick; Phillips, Zachary; Dolan, Joseph G; Widemann, Brigitte; Jayaprakash, Nalini; Pucino, Frank; Stone, Deborah L; Chapelle, Dawn; Snyder, Christopher; Butman, John A; Wesley, Robert; Goldbach-Mansky, Raphaela

    2012-07-01

    Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long-term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID. We conducted a cohort study of 26 NOMID patients ages 0.80-42.17 years who were followed up at the NIH and treated with anakinra 1-5 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated. Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all Phearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication. These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall. Copyright © 2012 by the American College of Rheumatology.

  11. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2017-10-01

    difference We therefore conclude that it is more likely that female hormones are protecting against susceptibility as opposed to male hormones...of synapse counts among all experimental conditions, those in A as well as saline/vehicle and systemic 4 mg/Kg IEM-1460 (IEMs4mg). There is no... animals at the approximate level of the animals ’ ears. The variation of the noise level across the animals ’ ears and across time is ə dB

  12. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2016-10-01

    neurotrophic factor CNTF in promoting synapse regeneration. KEYWORDS Anandamide Auditory Brainstem Response Calcium Ion Calcium-Permeable AMPA Receptors...excitotoxic trauma (kainic acid) in vitro? f) Does CNTF promote synapse regeneration in vitro as does NT-3? W81XWH-14-1-0494 Annual Progress Report 29... CNTF ) is expressed in the organ of Corti at high levels, comparable to NT-3. We have also found that CNTF is approximately as effective as NT-3 in

  13. Sulfur Mustard Damage to Cornea: Preventive Studies

    National Research Council Canada - National Science Library

    Varma, Shambhu

    2004-01-01

    Studies are in progress to determine the efficacy and mechanism of a formulation containing anti-alkylating, antioxidants and metabolic accelerators present in VM against mustard induced skin toxicity...

  14. Vitamin C for DNA damage prevention

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim; Binková, B.; Rössner ml., Pavel

    2012-01-01

    Roč. 733, 1-2 (2012), s. 39-49 ISSN 0027-5107 R&D Projects: GA MŠk 2B08005; GA MŽP(CZ) SP/1B3/50/07 Institutional research plan: CEZ:AV0Z50390703 Keywords : Chromosomal aberrations * DNA adducts * DNA repair Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.902, year: 2012

  15. Phylogeography of mtDNA haplogroup R7 in the Indian peninsula

    Directory of Open Access Journals (Sweden)

    Shukla Parul

    2008-08-01

    Full Text Available Abstract Background Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic speaking populations originated in India or derive from a relatively recent migration from further East. Results Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1, is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between

  16. Nuclear transfer to prevent mitochondrial DNA disorders: revisiting the debate on reproductive cloning.

    Science.gov (United States)

    Bredenoord, A L; Dondorp, W; Pennings, G; De Wert, G

    2011-02-01

    Preclinical experiments are currently performed to examine the feasibility of several types of nuclear transfer to prevent mitochondrial DNA (mtDNA) disorders. Whereas the two most promising types of nuclear transfer to prevent mtDNA disorders, spindle transfer and pronuclear transfer, do not amount to reproductive cloning, one theoretical variant, blastomere transfer does. This seems the most challenging both technically and ethically. It is prohibited by many jurisdictions and also the scientific community seems to avoid it. Nevertheless, this paper examines the moral acceptability of blastomere transfer as a method to prevent mtDNA disorders. The reason for doing so is that most objections against reproductive cloning refer to reproductive adult cloning, while blastomere transfer would amount to reproductive embryo cloning. After clarifying this conceptual difference, this paper examines whether the main non-safety objections brought forward against reproductive cloning also apply in the context of blastomere transfer. The conclusion is that if this variant were to become safe and effective, dismissing it because it would involve reproductive cloning is unjustified. Nevertheless, as it may lead to more complex ethical appraisals than the other variants, researchers should initially focus on the development of the other types of nuclear transfer to prevent mtDNA disorders. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

    Science.gov (United States)

    Bertola, Laura D; Tensen, Laura; van Hooft, Pim; White, Paula A; Driscoll, Carlos A; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A; Tumenta, Pricelia N; Jirmo, Tuqa H; de Snoo, Geert R; de Iongh, Hans H; Vrieling, Klaas

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

  18. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

    Directory of Open Access Journals (Sweden)

    Laura D Bertola

    Full Text Available The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1 West/Central Africa, 2 East Africa, 3 Southern Africa and 4 India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

  19. Association of mtDNA mutation with Autism in Iranian patients

    Directory of Open Access Journals (Sweden)

    Massoud Houshmand

    2013-12-01

    Full Text Available The autism spectrum disorders (ASD are amongst the most heritable complex disorders. Although there have been many efforts to locate the genes associated with ASD risk, many has been remained to be disclosed about the genetics of ASD. Scrutiny's have only disclosed a small number of de novo and inherited variants significantly associated with susceptibility to ASD. These only comprise a small number of total genetic risk factors. Some studies confirm the contribution of mitochondrial genome mutations to the pathophysiology of the autism, but some other studies rejected such a contribution. In the current study we tried to scrutinize the association between mitochondrial tRNA genes mutations and the risk of Autism. DNA was extracted from the blood of 24 patients with ASD and 40 age-matched healthy controls from Special Medical Center in Tehran. 22 tRNA genes of mitochondrial genome were PCR amplified using 12 primer pairs and sequenced. Sequencing results were searched for mutations using clustalW Progran and then the association of mutations with the autism risk was assessed by statistical analysis using SPSS version 15. Many of the observed mutations were sporadic mutations without any significant relationship with the risk of autism, and the other mutations including those of high frequency showed no significant relationship with the risk of disease as well (p-value > 0.05 except mutations 16126T>C (p-value=0.01 , 14569G>A(pvalue=0.02 and 1811A>G(p-value=0.04. These three mutations were in the noncoding regions of the mitochondrial genome near tRNA genes. The mutation 16126T>C was in the mtDNA control region.

  20. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

    Science.gov (United States)

    Bertola, Laura D.; Tensen, Laura; van Hooft, Pim; White, Paula A.; Driscoll, Carlos A.; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A.; Tumenta, Pricelia N.; Jirmo, Tuqa H.; de Snoo, Geert R.

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. PMID:26466139

  1. The structure of selective dinucleotide interactions and periodicities in D melanogaster mtDNA

    Directory of Open Access Journals (Sweden)

    Carlos Y Valenzuela

    2014-01-01

    Full Text Available BACKGROUND: We found a strong selective 3-sites periodicity of deviations from randomness of the dinucleotide (DN distribution, where both bases of DN were separated by 1, 2, K sites in prokaryotes and mtDNA. Three main aspects are studied. I the specific 3 K-sites periodic structure of the 16 DN. II to discard the possibility that the periodicity was produced by the highly nonrandom interactive association of contiguous bases, by studying the interaction of non-contiguous bases, the first one chosen each I sites and the second chosen J sites downstream. III the difference between this selective periodicity of association (distance to randomness of the four bases with the described fixed periodicities of base sequences. RESULTS: I The 16 pairs presented a consistent periodicity in the strength of association of both bases of the pairs; the most deviated pairs are those where G and C are involved and the least deviated ones are those where A and T are involved. II we found significant non-random interactions when the first nucleotide is chosen every I sites and the second J sites downstream until I = J = 76. III we showed conclusive differences between these internucleotide association periodicities and sequence periodicities. CONCLUSIONS: This relational selective periodicity is different from sequence periodicities and indicates that any base strongly interacts with the bases of the residual genome; this interaction and periodicity is highly structured and systematic for every pair of bases. This interaction should be destroyed in few generations by recurrent mutation; it is only compatible with the Synthetic Theory of Evolution and agrees with the Wright's adaptive landscape conception and evolution by shifting balanced adaptive peaks.

  2. Structural damage

    International Nuclear Information System (INIS)

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  3. Damaged Skylab

    Science.gov (United States)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  4. SG-ADVISER mtDNA: a web server for mitochondrial DNA annotation with data from 200 samples of a healthy aging cohort.

    Science.gov (United States)

    Rueda, Manuel; Torkamani, Ali

    2017-08-18

    Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians. We have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115-3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002-1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes. SG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdna .

  5. Optimizing service failure and damage control

    OpenAIRE

    Halbheer, D; Gartner, D; Gerstner, E; Koenigsberg, O

    2018-01-01

    Should a provider deliver a reliable service or should it allow for occasional service failures? This paper derives conditions under which randomizing service quality can\\ud benefit the provider and society. In addition to cost considerations, heterogeneity in customer damages from service failures allows the provider to generate profit\\ud from selling damage prevention services or offering compensation to high-damage customers. This strategy is viable even when reputation counts and markets ...

  6. Nerve damage from diabetes - self-care

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000326.htm Nerve damage from diabetes - self-care To use the sharing features on ... or at other unusual times. Treating and Preventing Nerve Damage from Diabetes Treating diabetic neuropathy can make some symptoms of ...

  7. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2010-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  8. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    Science.gov (United States)

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  9. Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses.

    Science.gov (United States)

    Lin, Xiang; Zheng, Hong-Xiang; Davie, Allan; Zhou, Shi; Wen, Li; Meng, Jun; Zhang, Yong; Aladaer, Qimude; Liu, Bin; Liu, Wu-Jun; Yao, Xin-Kui

    2018-03-01

    Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (p = .0003) and its sub-haplogroup L3b1a (p = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (p > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.

  10. Species phylogeny and diversification process of Northeast Asian Pungitius revealed by AFLP and mtDNA markers

    DEFF Research Database (Denmark)

    Takahashi, Hiroshi; Møller, Peter Rask; Shedko, Sergei V.

    2016-01-01

    clade with conspecific allopatric populations. The phylogeny showed that two lineages arose early; one gave rise to two species (circumpolar species P. pungitius and Paratethys species P. platygaster) and the other to five species endemic to Northeast Asia (P. sinensis, P. tymensis, P. polyakovi, P....... kaibarae, and P. bussei). The brackish-water, freshwater, and Omono types previously discovered in Japan were reidentified as P. pungitius, P. sinensis, and P. kaibarae, respectively. A marked incongruence was noted between the phylogenies of AFLP and mtDNA markers, suggesting the occasional occurrence...

  11. Screening of respiration deficiency mutants of yeasts (Saccharomyces cerevisiae) induced by ion irradiation and the mtDNA restriction analysis

    International Nuclear Information System (INIS)

    Mao Shuhong; Chinese Academy of Sciences, Beijing; Jin Genming; Wei Zengquan; Xie Hongmei; Ma Qiufeng; Gu Ying

    2005-01-01

    Screening of the respiration deficiency mutants of Saccharomyces cerevisiae induced by 5.19 MeV/u 22 Ne 5+ ion irradiation is reported in this paper. Some respiration deficiency mutants of white colony phenotype, in a condition of selective culture of TTC medium, were obtained. A new and simplified method based on mtDNA restriction analysis is described. The authors found that there are many obvious differences in mtDNAs between wild yeasts and the respiration deficiency mutants. The mechanism of obtaining the respiration deficiency mutants induced by heavy ion irradiation is briefly discussed. (authors)

  12. On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola

    Directory of Open Access Journals (Sweden)

    Beleza Sandra

    2009-04-01

    Full Text Available Abstract Background Current information about the expansion of Bantu-speaking peoples is hampered by the scarcity of genetic data from well identified populations from southern Africa. Here, we fill an important gap in the analysis of the western edge of the Bantu migrations by studying for the first time the patterns of Y-chromosome, mtDNA and lactase persistence genetic variation in four representative groups living around the Namib Desert in southwestern Angola (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale. We assessed the differentiation between these populations and their levels of admixture with Khoe-San groups, and examined their relationship with other sub-Saharan populations. We further combined our dataset with previously published data on Y-chromosome and mtDNA variation to explore a general isolation with migration model and infer the demographic parameters underlying current genetic diversity in Bantu populations. Results Correspondence analysis, lineage sharing patterns and admixture estimates indicate that the gene pool from southwestern Angola is predominantly derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people were additionally characterized by relatively high frequencies of Y-chromosome (12% and mtDNA (22% Khoe-San lineages, as well as by the presence of the -14010C lactase persistence mutation (6%, which likely originated in non-Bantu pastoralists from East Africa. Inferred demographic parameters show that both male and female populations underwent significant size growth after the split between the western and eastern branches of Bantu expansions occurring 4000 years ago. However, males had lower population sizes and migration rates than females throughout the Bantu dispersals. Conclusion Genetic variation in southwestern Angola essentially results from the encounter of an offshoot of West-Central Africa with autochthonous Khoisan-speaking peoples from the south. Interactions between the Bantus

  13. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  14. Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

    Science.gov (United States)

    Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

    2011-01-01

    Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

  15. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Markus Böhm

    2016-05-01

    Full Text Available Alpha-melanocyte-stimulating hormone (alpha-MSH increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

  16. Japanese Wolves are Genetically Divided into Two Groups Based on an 8-Nucleotide Insertion/Deletion within the mtDNA Control Region.

    Science.gov (United States)

    Ishiguro, Naotaka; Inoshima, Yasuo; Yanai, Tokuma; Sasaki, Motoki; Matsui, Akira; Kikuchi, Hiroki; Maruyama, Masashi; Hongo, Hitomi; Vostretsov, Yuri E; Gasilin, Viatcheslav; Kosintsev, Pavel A; Quanjia, Chen; Chunxue, Wang

    2016-02-01

    The mitochondrial DNA (mtDNA) control region (198- to 598-bp) of four ancient Canis specimens (two Canis mandibles, a cranium, and a first phalanx) was examined, and each specimen was genetically identified as Japanese wolf. Two unique nucleotide substitutions, the 78-C insertion and the 482-G deletion, both of which are specific for Japanese wolf, were observed in each sample. Based on the mtDNA sequences analyzed, these four specimens and 10 additional Japanese wolf samples could be classified into two groups- Group A (10 samples) and Group B (4 samples)-which contain or lack an 8-bp insertion/deletion (indel), respectively. Interestingly, three dogs (Akita-b, Kishu 25, and S-husky 102) that each contained Japanese wolf-specific features were also classified into Group A or B based on the 8-bp indel. To determine the origin or ancestor of the Japanese wolf, mtDNA control regions of ancient continental Canis specimens were examined; 84 specimens were from Russia, and 29 were from China. However, none of these 113 specimens contained Japanese wolf-specific sequences. Moreover, none of 426 Japanese modern hunting dogs examined contained these Japanese wolf-specific mtDNA sequences. The mtDNA control region sequences of Groups A and B appeared to be unique to grey wolf and dog populations.

  17. Experimental study of oxidative DNA damage

    DEFF Research Database (Denmark)

    Loft, S; Deng, Xiaohong; Tuo, J

    1998-01-01

    of the use of 2-nitropropane as a model for oxidative DNA damage relate particularly to formation of 8-aminoguanine derivatives that may interfere with HPLC-EC assays and have unknown consequences. Other model compounds for induction of oxidative DNA damage, such as ferric nitriloacetate, iron dextran...... studies provide powerful tools to investigate agents inducing and preventing oxidative damage to DNA and its role in carcinogenesis. So far, most animal experiments have concerned 8-oxodG and determination of additional damaged bases should be employed. An ideal animal model for prevention of oxidative......Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of dose-response relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical...

  18. Damage Atlas for Photographic materials

    Directory of Open Access Journals (Sweden)

    Kristel Van Camp

    2010-11-01

    Full Text Available La conservation des documents photographiques peut nécessiter des interventions préventives ou curatives. Ce choix est guidé par leur état de conservation. Une meilleure connaissance des détériorations est donc cruciale. Le répertoire présenté ici essaie de les classifier selon des caractéristiques spécifiques et leur niveau de gravité. Les différents types de dégradation sont illustrés et décrits avec une terminologie précise. L’auteur propose en regard de ceux-ci l’intervention qui semble la plus appropriée. Ce répertoire s’adresse à toutes les personnes concernées par la photographie, qu’ils soient dans le milieu de la conservation ou dans le domaine artistique, dans les musées ou dans les archives. In order to rescue a damaged photographic object, preventive or conservative actions are needed. Knowing the specific characteristics of different types of damage is crucial. A damage atlas can provide these characteristics. With this atlas the damage can be recognised and appropriate actions can be taken. This damage atlas offers a first attempt to such a characterisation in the field of photography. The damage atlas contains images and the necessary information about damage on photographic material. The atlas with special annotations about the terminology and the grade of the damage is meant for everybody who works with photographic material, as well in museums as in archives.

  19. Killer whale nuclear genome and mtDNA reveal widespread population bottleneck during the last glacial maximum.

    Science.gov (United States)

    Moura, Andre E; Janse van Rensburg, Charlene; Pilot, Malgorzata; Tehrani, Arman; Best, Peter B; Thornton, Meredith; Plön, Stephanie; de Bruyn, P J Nico; Worley, Kim C; Gibbs, Richard A; Dahlheim, Marilyn E; Hoelzel, Alan Rus

    2014-05-01

    Ecosystem function and resilience is determined by the interactions and independent contributions of individual species. Apex predators play a disproportionately determinant role through their influence and dependence on the dynamics of prey species. Their demographic fluctuations are thus likely to reflect changes in their respective ecological communities and habitat. Here, we investigate the historical population dynamics of the killer whale based on draft nuclear genome data for the Northern Hemisphere and mtDNA data worldwide. We infer a relatively stable population size throughout most of the Pleistocene, followed by an order of magnitude decline and bottleneck during the Weichselian glacial period. Global mtDNA data indicate that while most populations declined, at least one population retained diversity in a stable, productive ecosystem off southern Africa. We conclude that environmental changes during the last glacial period promoted the decline of a top ocean predator, that these events contributed to the pattern of diversity among extant populations, and that the relatively high diversity of a population currently in productive, stable habitat off South Africa suggests a role for ocean productivity in the widespread decline.

  20. Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

    Directory of Open Access Journals (Sweden)

    AMIEN RAMADHAN ISHAK

    2014-12-01

    Full Text Available Mitochondrial gene mutation plays a role in the development of type two diabetes mellitus (T2DM. A point mutation in the mitochondrial gene Nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND1 gene mainly reported as the most common mutation related to T2DM. However, several studies have identified another SNP (single-nucleotide polymorphisms in the RNA region of mtDNA from patients from specific ethnic populations in Indonesia. Building on those findings, this study aimed to use PCR and DNA sequencing technology to identify nucleotides in RNA and ND1 fragment from 20 Gorontalonese and 20 Javanese T2DM patients, that may trigger T2DM expression. The results showed successful amplification of RNA along 294 bp for all samples. From these samples, we found two types of point mutation in Javanese patients in the G3316A and T3200C points of the rRNA and ND1 gene. In samples taken from Gorontalonese patients, no mutation were found in the RNA or ND1 region. We conclude that T2DM was triggered differently in our two populations. While genetic mutation is implicated for the 20 Javanese patients, T2DM pathogenesis in the Gorontalonese patients must be traced to other genetic, environmental, or behavioral factors.

  1. Forensic analysis of mtDNA haplotypes from two rural communities in Haiti reflects their population history.

    Science.gov (United States)

    Wilson, Jamie L; Saint-Louis, Vertus; Auguste, Jensen O; Jackson, Bruce A

    2012-11-01

    Very little genetic data exist on Haitians, an estimated 1.2 million of whom, not including illegal immigrants, reside in the United States. The absence of genetic data on a population of this size reduces the discriminatory power of criminal and missing-person DNA databases in the United States and Caribbean. We present a forensic population study that provides the first genetic data set for Haiti. This study uses hypervariable segment one (HVS-1) mitochondrial DNA (mtDNA) nucleotide sequences from 291 subjects primarily from rural areas of northern and southern Haiti, where admixture would be minimal. Our results showed that the African maternal genetic component of Haitians had slightly higher West-Central African admixture than African-Americans and Dominicans, but considerably less than Afro-Brazilians. These results lay the foundation for further forensic genetics studies in the Haitian population and serve as a model for forensic mtDNA identification of individuals in other isolated or rural communities. © 2012 American Academy of Forensic Sciences.

  2. Phylogeographical analysis of mtDNA data indicates postglacial expansion from multiple glacial refugia in woodland caribou (Rangifer tarandus caribou.

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    Cornelya F C Klütsch

    Full Text Available Glacial refugia considerably shaped the phylogeographical structure of species and may influence intra-specific morphological, genetic, and adaptive differentiation. However, the impact of the Quaternary ice ages on the phylogeographical structure of North American temperate mammalian species is not well-studied. Here, we surveyed ~1600 individuals of the widely distributed woodland caribou (Rangifer tarandus caribou using mtDNA control region sequences to investigate if glacial refugia contributed to the phylogeographical structure in this subspecies. Phylogenetic tree reconstruction, a median-joining network, and mismatch distributions supported postglacial expansions of woodland caribou from three glacial refugia dating back to 13544-22005 years. These three lineages consisted almost exclusively of woodland caribou mtDNA haplotypes, indicating that phylogeographical structure was mainly shaped by postglacial expansions. The putative centres of these lineages are geographically separated; indicating disconnected glacial refugia in the Rocky Mountains, east of the Mississippi, and the Appalachian Mountains. This is in congruence with the fossil record that caribou were distributed in these areas during the Pleistocene. Our results suggest that the last glacial maximum substantially shaped the phylogeographical structure of this large mammalian North American species that will be affected by climatic change. Therefore, the presented results will be essential for future conservation planning in woodland caribou.

  3. A 28,000 years old Cro-Magnon mtDNA sequence differs from all potentially contaminating modern sequences.

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    David Caramelli

    Full Text Available BACKGROUND: DNA sequences from ancient specimens may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal and early modern (Cro-Magnoid Europeans. METHODOLOGY/PRINCIPAL FINDINGS: We typed the mitochondrial DNA (mtDNA hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23 and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences. CONCLUSIONS/SIGNIFICANCE: The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans.

  4. Killer Whale Nuclear Genome and mtDNA Reveal Widespread Population Bottleneck during the Last Glacial Maximum

    Science.gov (United States)

    Moura, Andre E.; Janse van Rensburg, Charlene; Pilot, Malgorzata; Tehrani, Arman; Best, Peter B.; Thornton, Meredith; Plön, Stephanie; de Bruyn, P.J. Nico; Worley, Kim C.; Gibbs, Richard A.; Dahlheim, Marilyn E.; Hoelzel, Alan Rus

    2014-01-01

    Ecosystem function and resilience is determined by the interactions and independent contributions of individual species. Apex predators play a disproportionately determinant role through their influence and dependence on the dynamics of prey species. Their demographic fluctuations are thus likely to reflect changes in their respective ecological communities and habitat. Here, we investigate the historical population dynamics of the killer whale based on draft nuclear genome data for the Northern Hemisphere and mtDNA data worldwide. We infer a relatively stable population size throughout most of the Pleistocene, followed by an order of magnitude decline and bottleneck during the Weichselian glacial period. Global mtDNA data indicate that while most populations declined, at least one population retained diversity in a stable, productive ecosystem off southern Africa. We conclude that environmental changes during the last glacial period promoted the decline of a top ocean predator, that these events contributed to the pattern of diversity among extant populations, and that the relatively high diversity of a population currently in productive, stable habitat off South Africa suggests a role for ocean productivity in the widespread decline. PMID:24497033

  5. Tracing the phylogeography of human populations in Britain based on 4th-11th century mtDNA genotypes.

    Science.gov (United States)

    Töpf, A L; Gilbert, M T P; Dumbacher, J P; Hoelzel, A R

    2006-01-01

    Some of the transitional periods of Britain during the first millennium A.D. are traditionally associated with the movement of people from continental Europe, composed largely of invading armies (e.g., the Roman, Saxon, and Viking invasions). However, the extent to which these were migrations (as opposed to cultural exchange) remains controversial. We investigated the history of migration by women by amplifying mitochondrial DNA (mtDNA) from ancient Britons who lived between approximately A.D. 300-1,000 and compared these with 3,549 modern mtDNA database genotypes from England, Europe, and the Middle East. The objective was to assess the dynamics of the historical population composition by comparing genotypes in a temporal context. Towards this objective we test and calibrate the use of rho statistics to identify relationships between founder and source populations. We find evidence for shared ancestry between the earliest sites (predating Viking invasions) with modern populations across the north of Europe from Norway to Estonia, possibly reflecting common ancestors dating back to the last glacial epoch. This is in contrast with a late Saxon site in Norwich, where the genetic signature is consistent with more recent immigrations from the south, possibly as part of the Saxon invasions.

  6. Damage analysis: damage function development and application

    International Nuclear Information System (INIS)

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  7. Material Induced Anisotropic Damage

    NARCIS (Netherlands)

    Niazi, Muhammad Sohail; Wisselink, H.H.; Meinders, Vincent T.; van den Boogaard, Antonius H.; Hora, P.

    2012-01-01

    The anisotropy in damage can be driven by two different phenomena; anisotropic defor-mation state named Load Induced Anisotropic Damage (LIAD) and anisotropic (shape and/or distribution) second phase particles named Material Induced Anisotropic Damage (MIAD). Most anisotropic damage models are based

  8. Autophagy in DNA Damage Response

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    Piotr Czarny

    2015-01-01

    Full Text Available DNA damage response (DDR involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1. mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADPribose polymerase 1 (PARP-1, Mre11–Rad50–Nbs1 (MRN complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy.

  9. Plasma Nuclear and Mitochondrial DNA Levels, and Markers of Inflammation, Shock, and Organ Damage in Patients with Septic Shock.

    Science.gov (United States)

    Timmermans, Kim; Kox, Matthijs; Scheffer, Gert Jan; Pickkers, Peter

    2016-06-01

    Plasma levels of the danger-associated molecular patterns (DAMPs) nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been shown to be related to sepsis mortality. However, the intermediate factors and/or mechanisms contributing to this relation are largely unknown. Our aim was to determine whether plasma levels of nDNA and mtDNA are related to the markers of inflammation, severity of shock, and organ damage in septic shock patients. Moreover, we investigated the relationship between plasma levels of nDNA/mtDNA and inflammatory cytokines during experimental human endotoxemia, a model of systemic inflammation in humans in vivo mimicking some of the hallmarks of early sepsis. Blood was sampled from the onset of septic shock until day 28 in 121 septic shock patients and from 1 h before endotoxin administration until 8 h afterward in 12 healthy volunteers. Plasma concentrations of five cytokines and circulating levels of nDNA and mtDNA were measured, and correlations with shock-related parameters and markers of organ damage were investigated. In septic shock patients plasma cytokine concentrations, as well as nDNA and mtDNA levels, were increased at the onset of septic shock and remained elevated. During the first 5 days of septic shock, nDNA levels consistently correlated with plasma cytokine concentrations as well as with the shock-related parameter norepinephrine infusion rate and markers of organ damage (total bilirubin and creatinine). Experimental human endotoxemia also resulted in increased levels of plasma nDNA and mtDNA, but to a lesser extent than in septic shock patients. Furthermore, nDNA levels correlated with pro-inflammatory cytokines during endotoxemia. Our findings indicate a relationship between plasma nDNA levels and the inflammatory response. Furthermore, nDNA levels are associated with markers of shock and organ damage in septic shock patients. Nevertheless, the correlations found are relatively weak and it remains to be determined whether n

  10. PROFIL PEMIJAHAN IKAN TUNA SIRIP KUNING, Thunnus albacares DALAM BAK TERKONTROL DENGAN ANALISIS MITOKONDRIA DNA (mt-DNA

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    Gusti Ngurah Permana

    2016-11-01

    Full Text Available Variasi mitokondria DNA pada ikan tuna sirip kuning, Thunnus albacares menggunakan analisis RFLP (restriction fragment length polymorphism dapat menyediakan data yang akurat dan memberikan bukti tentang profil pemijahan ikan tuna dalam bak terkontrol. Genotipe mt-DNA yang berasal dari induk dibandingkan dengan genotipe yang ada pada telur untuk memonitor dan mengetahui profil dari pemijahan ikan tuna dalam bak terkontrol. Telur dikumpulkan setiap pemijahan dari tahun 2004-2006. Profil pemijahan dari induk betina diamati dari jumlah genotipe yang ditemukan pada telur. Hasil dari penelitian ini adalah 49 induk yang dianalisis ditemukan 42 genotipe, 6 genotipe yang teramati ditemukan pada telur dan 4 diantaranya memiliki genotipe tunggal sedangkan satu genotipe (DABEA dimiliki oleh dua induk. Prakiraan panjang cagak dan bobot induk pada saat memijah adalah 82,2-164 cm and 9,183-28,142 kg. Genotipe yang sama ditemukan hampir setiap hari pada saat sampling selama setahun. Hasil ini mengindikasikan bahwa ikan tuna sirip kuning dapat bertelur sepanjang tahun tergantung kepada suhu air dan kondisi pakan. Study of mitochondrial (mt-DNA variations of yellowfin tuna, Thunnus albacares using (RFLP restriction fragment length polymorphisms can provide evidence of spawning profile of the species in captivity. Mt-DNA genotypes of broodstock were compared with their eggs in order to monitor spawning profile. Spawned eggs were collected on every spawning from 2004 to 2006. The spawning profiles of these females were determined from the genotypes of the eggs. The result showed that from 49  broodstock individuals, 42 genotypes were observed, in which 6 genotypes were observed in their eggs and 4 of them established a single female’s identity and one type (DABEA was shared by two females. Fork length and weight of broodstock female when spawning were ranging from 82.2–164 cm and 9.183-28.142 kg. The same genotypes were observed in almost every sampling

  11. Circular Mitochondrial DNA: A Geant4-DNA User Application for Evaluating Radiation-induced Damage in Circular Mitochondrial DNA.

    Science.gov (United States)

    Tavakoli, Mohammad Bagher; Moradi, Habiballah; Khanahmad, Hossein; Hosseini, Mohsen

    2017-01-01

    The aim of this study was to develop a nucleotide geometrical model of the circular mitochondrial DNA (mt-DNA) structure using Geant4-DNA toolkit to predict the radiation-induced damages such as single-strand breaks (SSB), double-strand breaks (DSB), and some other physical parameters. Our model covers the organization of a circular human mt genetic system. The current model includes all 16,659 base pairs of human mt-DNA. This new mt-DNA model has been preliminarily tested in this work by determining SSB and DSB DNA damage yields and site-hit probabilities due to the impact of proton particles. The accuracy of the geometry was determined by three-dimensional visualization in various ring element numbers. The hit locations were determined with respect to a reference coordinate system, and the corresponding base pairs were stored in the ROOT output file. The coordinate determination according to the algorithm was consistent with the expected results. The output results contain the information about the energy transfers in the backbone region of the DNA double helix. The output file was analyzed by root analyzing tools. Estimation of SSBs and DSBs yielded similar results with the increment of incident particle linear energy transfer. In addition, these values seem to be consistent with the corresponding experimental determinations. This model can be used in numerical simulations of mt-DNA radiation interactions to perform realistic evaluations of DNA-free radical reactions. This work will be extended to supercoiled conformation in the near future.

  12. Phylogeography of the rice frog, Fejervarya multistriata (Anura: Ranidae), from China based on mtDNA D-loop sequences.

    Science.gov (United States)

    Zhong, Jing; Liu, Zhong-Quan; Wang, Yi-Quan

    2008-08-01

    The rice frog, Fejervarya multistriata, is an amphibian widely distributed in China. In this study, we sampled the species across its distributional area in China and sequenced the mtDNA D-loop to investigate the genetic diversity and geographical pattern of the frog population. The results revealed 38 haplotypes in the population, with K2P values varying from 0.19% to 4.22%. Both a phylogenetic analysis and a nested clade analysis (NCA) detected two geographically isolated lineages respectively distributed around the Yangtze drainage (Yangtze lineage) and the south of China (southern lineage). NCA inferred a contiguous range expansion within the Yangtze lineage and allopatric fragmentation within the southern lineage, which might be partly due to the limited samples from this lineage. Accordingly, Fu's Fs test also indicated a population expansion after glacial movement. Therefore, we assumed that the species history responding to glacial events shaped the present population pattern of F. multistriata on the Chinese mainland.

  13. A molecular phylogeny of the Cephinae (Hymenoptera, Cephidae based on mtDNA COI gene: a test of traditional classification

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    Mahir Budak

    2011-09-01

    Full Text Available Cephinae is traditionally divided into three tribes and about 24 genera based on morphology and host utilization. There has been no study testing the monophyly of taxa under a strict phylogenetic criterion. A molecular phylogeny of Cephinae based on a total of 68 sequences of mtDNA COI gene, representing seven genera of Cephinae, is reconstructed to test the traditional limits and relationships of taxa. Monophyly of the traditional tribes is not supported. Monophyly of the genera are largely supported except for Pachycephus. A few host shift events are suggested based on phylogenetic relationships among taxa. These results indicate that a more robust phylogeny is required for a more plausible conclusion. We also report two species of Cephus for the first time from Turkey.

  14. Integration of mtDNA pseudogenes into the nuclear genome coincides with speciation of the human genus. A hypothesis.

    Science.gov (United States)

    Gunbin, Konstantin; Peshkin, Leonid; Popadin, Konstantin; Annis, Sofia; Ackermann, Rebecca R; Khrapko, Konstantin

    2017-05-01

    Fragments of mitochondrial DNA are known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear pseudogenes of the mtDNA. The insertion of a NUMT is a rare event. Hundreds of pseudogenes have been cataloged in the human genome. NUMTs are, in essence, a special type of mutation with their own internal timer, which is synchronized with an established molecular clock, the mtDNA. Thus insertion of NUMTs can be timed with respect to evolution milestones such as the emergence of new species. We asked whether NUMTs were inserted uniformly over time or preferentially during certain periods of evolution, as implied by the "punctuated evolution" model. To our surprise, the NUMT insertion times do appear nonrandom with at least one cluster positioned at around 2.8 million years ago (Ma). Interestingly, 2.8Ma closely corresponds to the time of emergence of the genus Homo, and to a well-documented period of major climate change ca. 2.9-2.5Ma. It is tempting to hypothesize that the insertion of NUMTs is related to the speciation process. NUMTs could be either "riders", i.e., their insertion could be facilitated by the overall higher genome rearrangement activity during speciation, or "drivers", i.e. they may more readily get fixed in the population due to positive selection associated with speciation. If correct, the hypothesis would support the idea that evolution of our genus may have happened in a rapid, punctuated manner. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  15. Migration and interaction in a contact zone: mtDNA variation among Bantu-speakers in Southern Africa.

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    Chiara Barbieri

    Full Text Available Bantu speech communities expanded over large parts of sub-Saharan Africa within the last 4000-5000 years, reaching different parts of southern Africa 1200-2000 years ago. The Bantu languages subdivide in several major branches, with languages belonging to the Eastern and Western Bantu branches spreading over large parts of Central, Eastern, and Southern Africa. There is still debate whether this linguistic divide is correlated with a genetic distinction between Eastern and Western Bantu speakers. During their expansion, Bantu speakers would have come into contact with diverse local populations, such as the Khoisan hunter-gatherers and pastoralists of southern Africa, with whom they may have intermarried. In this study, we analyze complete mtDNA genome sequences from over 900 Bantu-speaking individuals from Angola, Zambia, Namibia, and Botswana to investigate the demographic processes at play during the last stages of the Bantu expansion. Our results show that most of these Bantu-speaking populations are genetically very homogenous, with no genetic division between speakers of Eastern and Western Bantu languages. Most of the mtDNA diversity in our dataset is due to different degrees of admixture with autochthonous populations. Only the pastoralist Himba and Herero stand out due to high frequencies of particular L3f and L3d lineages; the latter are also found in the neighboring Damara, who speak a Khoisan language and were foragers and small-stock herders. In contrast, the close cultural and linguistic relatives of the Herero and Himba, the Kuvale, are genetically similar to other Bantu-speakers. Nevertheless, as demonstrated by resampling tests, the genetic divergence of Herero, Himba, and Kuvale is compatible with a common shared ancestry with high levels of drift, while the similarity of the Herero, Himba, and Damara probably reflects admixture, as also suggested by linguistic analyses.

  16. Evaluation of GeneMarker® HTS for improved alignment of mtDNA MPS data, haplotype determination, and heteroplasmy assessment.

    Science.gov (United States)

    Holland, Mitchell M; Pack, Erica D; McElhoe, Jennifer A

    2017-05-01

    Existing software has not allowed for effective alignment of mitochondrial (mt) DNA sequence data generated using a massively parallel sequencing (MPS) approach, combined with the ability to perform a detailed assessment of the data. The regions of sequence that are typically difficult to align are homopolymeric stretches, isolated patterns of SNPs (single nucleotide polymorphisms), and INDELs (insertions/deletions). A custom software solution, GeneMarker ® HTS, was developed and evaluated to address these limitations, and to provide a user-friendly interface for forensic practitioners and others interested in mtDNA analysis of MPS data. GeneMarker ® HTS generates an exportable consensus mtDNA sequence that produces phylogenetically correct SNP and INDEL calls using a customizable motif-based alignment algorithm. Sequence data from 500 individuals, with various alignment asymmetries and levels of heteroplasmy, were used to assess the software. Accuracy in producing mtDNA haplotypes, the ability to correctly identify low-level heteroplasmic sequence variants, and the user-based features of the software were evaluated. Analyzed sequences yielded correct mtDNA haplotypes, and heteroplasmic variants were properly identified with minimal manual interpretation. The software offers numerous user-defined parameters for filtering the data that address the interests of researchers and practitioners, and provides multiple options for viewing and navigating through the data. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: Duplication and non-random loss

    Energy Technology Data Exchange (ETDEWEB)

    Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.

    2001-11-08

    We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

  18. Data on haplotype diversity in the hypervariable region I, II and III of mtDNA amongst the Brahmin population of Haryana

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    Kapil Verma

    2018-04-01

    Full Text Available Human mitochondrial DNA (mtDNA is routinely analysed for pathogenic mutations, evolutionary studies, estimation of time of divergence within or between species, phylogenetic studies and identification of degraded remains. The data on various regions of human mtDNA has added enormously to the knowledge pool of population genetics as well as forensic genetics. The displacement-loop (D-loop in the control region of mtDNA is rated as the most rapidly evolving part, due to the presence of variations in this region. The control region consists of three hypervariable regions. These hypervariable regions (HVI, HVII and HVIII tend to mutate 5–10 times faster than nuclear DNA. The high mutation rate of these hypervariable regions is used in population genetic studies and human identity testing. In the present data, potentially informative hypervariable regions of mitochondrial DNA (mtDNA i.e. HVI (np 16024–16365, HVII (np 73–340 and HVIII (np 438–576 were estimated to understand the genetic diversity amongst Brahmin population of Haryana. Blood samples had been collected from maternally unrelated individuals from the different districts of Haryana. An array of parameters comprising of polymorphic sites, transitions, transversions, deletions, gene diversity, nucleotide diversity, pairwise differences, Tajima's D test, Fu's Fs test, mismatch observed variance and expected heterozygosity were estimated. The observed polymorphisms with their respective haplogroups in comparison to rCRS were assigned. Keywords: Mitochondrial DNA, D-loop, Hypervariable regions, Forensic genetics

  19. Damage control surgery in the era of damage control resuscitation.

    Science.gov (United States)

    Lamb, C M; MacGoey, P; Navarro, A P; Brooks, A J

    2014-08-01

    Damage control surgery (DCS) is a concept of abbreviated laparotomy, designed to prioritize short-term physiological recovery over anatomical reconstruction in the seriously injured and compromised patient. Over the last 10 yr, a new addition to the damage control paradigm has emerged, referred to as damage control resuscitation (DCR). This focuses on initial hypotensive resuscitation and early use of blood products to prevent the lethal triad of acidosis, coagulopathy, and hypothermia. This review aims to present the evidence behind DCR and its current application, and also to present a strategy of overall damage control to include DCR and DCS in conjunction. The use of DCR and DCS have been associated with improved outcomes for the severely injured and wider adoption of these principles where appropriate may allow this trend of improved survival to continue. In particular, DCR may allow borderline patients, who would previously have required DCS, to undergo early definitive surgery as their physiological derangement is corrected earlier. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  1. A reevaluation of the Native American mtDNA genome diversity and its bearing on the models of early colonization of Beringia.

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    Nelson J R Fagundes

    Full Text Available The Americas were the last continents to be populated by humans, and their colonization represents a very interesting chapter in our species' evolution in which important issues are still contentious or largely unknown. One difficult topic concerns the details of the early peopling of Beringia, such as for how long it was colonized before people moved into the Americas and the demography of this occupation. A recent work using mitochondrial genome (mtDNA data presented evidence for a so called "three-stage model" consisting of a very early expansion into Beringia followed by approximately 20,000 years of population stability before the final entry into the Americas. However, these results are in disagreement with other recent studies using similar data and methods. Here, we reanalyze their data to check the robustness of this model and test the ability of Native American mtDNA to discriminate details of the early colonization of Beringia. We apply the Bayesian Skyline Plot approach to recover the past demographic dynamic underpinning these events using different mtDNA data sets. Our results refute the specific details of the "three-stage model", since the early stage of expansion into Beringia followed by a long period of stasis could not be reproduced in any mtDNA data set cleaned from non-Native American haplotypes. Nevertheless, they are consistent with a moderate population bottleneck in Beringia associated with the Last Glacial Maximum followed by a strong population growth around 18,000 years ago as suggested by other recent studies. We suggest that this bottleneck erased the signals of ancient demographic history from recent Native American mtDNA pool, and conclude that the proposed early expansion and occupation of Beringia is an artifact caused by the misincorporation of non-Native American haplotypes.

  2. Unexpected population genetic structure of European roe deer in Poland: an invasion of the mtDNA genome from Siberian roe deer.

    Science.gov (United States)

    Matosiuk, Maciej; Borkowska, Anetta; Świsłocka, Magdalena; Mirski, Paweł; Borowski, Zbigniew; Krysiuk, Kamil; Danilkin, Aleksey A; Zvychaynaya, Elena Y; Saveljev, Alexander P; Ratkiewicz, Mirosław

    2014-05-01

    Introgressive hybridization is a widespread evolutionary phenomenon which may lead to increased allelic variation at selective neutral loci and to transfer of fitness-related traits to introgressed lineages. We inferred the population genetic structure of the European roe deer (Capreolus capreolus) in Poland from mitochondrial (CR and cyt b) and sex-linked markers (ZFX, SRY, DBY4 and DBY8). Analyses of CR mtDNA sequences from 452 individuals indicated widespread introgression of Siberian roe deer (C. pygargus) mtDNA in the European roe deer genome, 2000 km from the current distribution range of C. pygargus. Introgressed individuals constituted 16.6% of the deer studied. Nearly 75% of them possessed haplotypes belonging to the group which arose 23 kyr ago and have not been detected within the natural range of Siberian roe deer, indicating that majority of present introgression has ancient origin. Unlike the mtDNA results, sex-specific markers did not show signs of introgression. Species distribution modelling analyses suggested that C. pygargus could have extended its range as far west as Central Europe after last glacial maximum. The main hybridization event was probably associated with range expansion of the most abundant European roe deer lineage from western refugia and took place in Central Europe after the Younger Dryas (10.8-10.0 ka BP). Initially, introgressed mtDNA variants could have spread out on the wave of expansion through the mechanism of gene surfing, reaching high frequencies in European roe deer populations and leading to observed asymmetrical gene flow. Human-mediated introductions of C. pygargus had minimal effect on the extent of mtDNA introgression. © 2014 John Wiley & Sons Ltd.

  3. Regionalized pathology correlates with augmentation of mtDNA copy numbers in a patient with myoclonic epilepsy with ragged-red fibers (MERRF-syndrome.

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    Anja Brinckmann

    Full Text Available Human patients with myoclonic epilepsy with ragged-red fibers (MERRF suffer from regionalized pathology caused by a mutation in the mitochondrial DNA (m.8344A→G. In MERRF-syndrome brain and skeletal muscles are predominantly affected, despite mtDNA being present in any tissue. In the past such tissue-specificity could not be explained by varying mtDNA mutation loads. In search for a region-specific pathology in human individuals we determined the mtDNA/nDNA ratios along with the mutation loads in 43 different post mortem tissue samples of a 16-year-old female MERRF patient and in four previously healthy victims of motor vehicle accidents. In brain and muscle we further determined the quantity of mitochondrial proteins (COX subunits II and IV, transcription factors (NRF1 and TFAM, and VDAC1 (Porin as a marker for the mitochondrial mass. In the patient the mutation loads varied merely between 89-100%. However, mtDNA copy numbers were increased 3-7 fold in predominantly affected brain areas (e.g. hippocampus, cortex and putamen and in skeletal muscle. Similar increases were absent in unaffected tissues (e.g. heart, lung, kidney, liver, and gastrointestinal organs. Such mtDNA copy number increase was not paralleled by an augmentation of mitochondrial mass in some investigated tissues, predominantly in the most affected tissue regions of the brain. We thus conclude that "futile" stimulation of mtDNA replication per se or a secondary failure to increase the mitochondrial mass may contribute to the regionalized pathology seen in MERRF-syndrome.

  4. Evolutionary history of the European whitefish Coregonus lavaretus (L.) species complex as inferred from mtDNA phylogeography and gill-raker numbers.

    Science.gov (United States)

    Østbye, K; Bernatchez, L; Naesje, T F; Himberg, K-J M; Hindar, K

    2005-12-01

    We compared mitochondrial DNA and gill-raker number variation in populations of the European whitefish Coregonus lavaretus (L.) species complex to illuminate their evolutionary history, and discuss mechanisms behind diversification. Using single-strand conformation polymorphism (SSCP) and sequencing 528 bp of combined parts of the cytochrome oxidase b (cyt b) and NADH dehydrogenase subunit 3 (ND3) mithochondrial DNA (mtDNA) regions, we documented phylogeographic relationships among populations and phylogeny of mtDNA haplotypes. Demographic events behind geographical distribution of haplotypes were inferred using nested clade analysis (NCA) and mismatch distribution. Concordance between operational taxonomical groups, based on gill-raker numbers, and mtDNA patterns was tested. Three major mtDNA clades were resolved in Europe: a North European clade from northwest Russia to Denmark, a Siberian clade from the Arctic Sea to southwest Norway, and a South European clade from Denmark to the European Alps, reflecting occupation in different glacial refugia. Demographic events inferred from NCA were isolation by distance, range expansion, and fragmentation. Mismatch analysis suggested that clades which colonized Fennoscandia and the Alps expanded in population size 24 500-5800 years before present, with minute female effective population sizes, implying small founder populations during colonization. Gill-raker counts did not commensurate with hierarchical mtDNA clades, and poorly with haplotypes, suggesting recent origin of gill-raker variation. Whitefish designations based on gill-raker numbers were not associated with ancient clades. Lack of congruence in morphology and evolutionary lineages implies that the taxonomy of this species complex should be reconsidered.

  5. A trans-Amazonian screening of mtDNA reveals deep intraspecific divergence in forest birds and suggests a vast underestimation of species diversity.

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    Borja Milá

    Full Text Available The Amazonian avifauna remains severely understudied relative to that of the temperate zone, and its species richness is thought to be underestimated by current taxonomy. Recent molecular systematic studies using mtDNA sequence reveal that traditionally accepted species-level taxa often conceal genetically divergent subspecific lineages found to represent new species upon close taxonomic scrutiny, suggesting that intraspecific mtDNA variation could be useful in species discovery. Surveys of mtDNA variation in Holarctic species have revealed patterns of variation that are largely congruent with species boundaries. However, little information exists on intraspecific divergence in most Amazonian species. Here we screen intraspecific mtDNA genetic variation in 41 Amazonian forest understory species belonging to 36 genera and 17 families in 6 orders, using 758 individual samples from Ecuador and French Guiana. For 13 of these species, we also analyzed trans-Andean populations from the Ecuadorian Chocó. A consistent pattern of deep intraspecific divergence among trans-Amazonian haplogroups was found for 33 of the 41 taxa, and genetic differentiation and genetic diversity among them was highly variable, suggesting a complex range of evolutionary histories. Mean sequence divergence within families was the same as that found in North American birds (13%, yet mean intraspecific divergence in Neotropical species was an order of magnitude larger (2.13% vs. 0.23%, with mean distance between intraspecific lineages reaching 3.56%. We found no clear relationship between genetic distances and differentiation in plumage color. Our results identify numerous genetically and phenotypically divergent lineages which may result in new species-level designations upon closer taxonomic scrutiny and thorough sampling, although lineages in the tropical region could be older than those in the temperate zone without necessarily representing separate species. In

  6. War damages and reconstruction of Peruca dam

    International Nuclear Information System (INIS)

    Nonveiller, E.; Sever, Z.

    1999-01-01

    The paper describes the heavy damages caused by blasting in the Peruca rockfill dam in Croatia in January 1993. Complete collapse of the dam by overtopping was prevented through quick action of the dam owner by dumping clayey gravel on the lowest sections of the dam crest and opening the bottom outlet of the reservoir, thus efficiently lowering the water level. After the damages were sufficiently established and alternatives for restoration of the dam were evaluated, it was decided to construct a diaphragm wall through the damaged core in the central dam part as the impermeable dam element and to rebuild the central clay core at the dam abutments. Reconstruction works are described

  7. Dealing with uncertainties: ethics of prenatal diagnosis and preimplantation genetic diagnosis to prevent mitochondrial disorders.

    Science.gov (United States)

    Bredenoord, A L; Pennings, G; Smeets, H J; de Wert, G

    2008-01-01

    This paper aims to address the ethical issues regarding prenatal diagnosis and preimplantation genetic diagnosis (PGD) of mitochondrial disorders. Owing to the absence of effective treatment, the prevention of the transmission of mitochondrial disorders is considered to be of key importance. The characteristics of mtDNA, such as heteroplasmy and the genetic bottleneck, make it difficult to estimate recurrence risks correctly and to provide an accurate prognosis for many mtDNA mutations. A limited number of mtDNA mutations allow reliable predictions, though results in the 'grey zone' are problematic. Both prenatal diagnosis and PGD for mtDNA disorders are complicated by the interpretation of the test results. As a consequence, these applications confront both clinical practice and society at large with several ethical questions and issues for further debate, among which the acceptability of suboptimal genetic testing, the value and research use of embryos, the evaluation of late abortion, the ethics of PGD for disorders with an incomplete penetrance and variable expression, the possible transfer of embryos with residual health risks, the acceptability of risks and drawbacks of genetic reproductive technology in general, and the scope and limits of reproductive autonomy and professional responsibility.

  8. RILEM recommendations for the prevention of damage by alkali-aggregate reactions in new concrete structures state-of-the-art report of the RILEM technical committee 219-ACS

    CERN Document Server

    Sims, Ian

    2016-01-01

    This book contains the full set of RILEM Recommendations which have been produced to enable engineers, specifiers and testing houses to design and produce concrete which will not suffer damage arising from alkali reactions in the concrete. There are five recommended test methods for aggregates (designated AAR-1 to AAR-5), and an overall recommendation which describes how these should be used to enable a comprehensive aggregate assessment (AAR-0). Additionally, there are two Recommended International Specifications for concrete (AAR-7.1 & 7.2) and a Preliminary International Specification for dams and other hydro structures (AAR-7.3), which describe how the aggregate assessment can be combined with other measures in the design of the concrete to produce a concrete with a minimised risk of developing damage from alkali-aggregate reactions.

  9. Radiation damage of structural materials

    CERN Document Server

    Koutsky, Jaroslav

    1994-01-01

    Maintaining the integrity of nuclear power plants is critical in the prevention or control of severe accidents. This monograph deals with both basic groups of structural materials used in the design of light-water nuclear reactors, making the primary safety barriers of NPPs. Emphasis is placed on materials used in VVER-type nuclear reactors: Cr-Mo-V and Cr-Ni-Mo-V steel for RPV and Zr-Nb alloys for fuel element cladding. The book is divided into 7 main chapters, with the exception of the opening one and the chapter providing a phenomenological background for the subject of radiation damage. Ch

  10. Nuclear and mtDNA phylogenetic analyses clarify the evolutionary history of two species of native Hawaiian bats and the taxonomy of Lasiurini (Mammalia: Chiroptera).

    Science.gov (United States)

    Baird, Amy B; Braun, Janet K; Engstrom, Mark D; Holbert, Ashlyn C; Huerta, Maritza G; Lim, Burton K; Mares, Michael A; Patton, John C; Bickham, John W

    2017-01-01

    Previous studies on genetics of hoary bats produced differing conclusions on the timing of their colonization of the Hawaiian Islands and whether or not North American (Aeorestes cinereus) and Hawaiian (A. semotus) hoary bats are distinct species. One study, using mtDNA COI and nuclear Rag2 and CMA1, concluded that hoary bats colonized the Hawaiian Islands no more than 10,000 years ago based on indications of population expansion at that time using Extended Bayesian Skyline Plots. The other study, using 3 mtDNA and 1 Y-chromosome locus, concluded that the Hawaiian Islands were colonized about 1 million years ago. To address the marked inconsistencies between those studies, we examined DNA sequences from 4 mitochondrial and 2 nuclear loci in lasiurine bats to investigate the timing of colonization of the Hawaiian Islands by hoary bats, test the hypothesis that Hawaiian and North American hoary bats belong to different species, and further investigate the generic level taxonomy within the tribe. Phylogenetic analysis and dating of the nodes of mtDNA haplotypes and of nuclear CMA1 alleles show that A. semotus invaded the Hawaiian Islands approximately 1.35 Ma and that multiple arrivals of A. cinereus occurred much more recently. Extended Bayesian Skyline plots show population expansion at about 20,000 years ago in the Hawaiian Islands, which we conclude does not represent the timing of colonization of the Hawaiian Islands given the high degree of genetic differentiation among A. cinereus and A. semotus (4.2% divergence at mtDNA Cytb) and the high degree of genetic diversity within A. semotus. Rather, population expansion 20,000 years ago could have resulted from colonization of additional islands, expansion after a bottleneck, or other factors. New genetic data also support the recognition of A. semotus and A. cinereus as distinct species, a finding consistent with previous morphological and behavioral studies. The phylogenetic analysis of CMA1 alleles shows the

  11. Integrating phylogeographic patterns of microsatellite and mtDNA divergence to infer the evolutionary history of chamois (genus Rupicapra).

    Science.gov (United States)

    Rodríguez, Fernando; Pérez, Trinidad; Hammer, Sabine E; Albornoz, Jesús; Domínguez, Ana

    2010-07-22

    ornata as an extremely low diversity. The phylogeographic patterns for mtDNA and microsatellites suggest an evolutionary history with limited range contractions and expansions during the Quaternary period and reflect a major effect of the Alpine barrier on west-east differentiation. The contrasting phylogenies for mtDNA and microsatellites indicate events of hybridization among highly divergent lineages in the central area of distribution. Our study points to the importance of reticulate evolution, with periods of isolation and reduction of population size followed by expansions and hybridizations, in the diversification at the level of close species or subspecies.

  12. Integrating phylogeographic patterns of microsatellite and mtDNA divergence to infer the evolutionary history of chamois (genus Rupicapra

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    Albornoz Jesús

    2010-07-01

    Full Text Available Abstract Background The chamois, distributed over most of the medium to high altitude mountain ranges of southern Eurasia, provides an excellent model for exploring the effects of historical and evolutionary events on diversification. Populations have been grouped into two species, Rupicapra pyrenaica from southwestern Europe and R. rupicapra from eastern Europe. However, a previous study of cytochrome b revealed that the two proposed species were non-monophyletic. The reconstruction of phylogenetic relationships between animal species often depends on the markers studied. To further elucidate the evolutionary history of chamois, we extended earlier studies by analysing DNA sequences of four mitochondrial regions (ND1, 12S, tRNApro and Control Region and microsatellites (20 loci to include all subspecies and cover its entire distribution range. Results We found discordant microsatellite (μsat and mitochondrial (mt DNA phylogenies. Mitochondrial phylogenies form three clades, West, Central and East (mtW, mtC and mtE, at variance with taxonomic classification. Our divergence age estimates indicate an initial separation into branches mtW-mtC and mtE 1.7 million years ago (mya, in the late Pliocene-early Pleistocene, quickly followed by the split of clades mtW and mtC. Clade mtW contains haplotypes from the Iberian peninsula and the western Alps, Clade mtC includes haplotypes from the Apennines and the Massif of Chartreuse and Clade mtE comprises populations to the east of the Alps. Divergence among populations within these three major clades is recent (ornata as an extremely low diversity. Conclusions The phylogeographic patterns for mtDNA and microsatellites suggest an evolutionary history with limited range contractions and expansions during the Quaternary period and reflect a major effect of the Alpine barrier on west-east differentiation. The contrasting phylogenies for mtDNA and microsatellites indicate events of hybridization among highly

  13. Multiple differences in calling songs and other traits between solitary and gregarious Mormon crickets from allopatric mtDNA clades

    Science.gov (United States)

    Bailey, Nathan W; Gwynne, Darryl T; Bailey, William V; Ritchie, Michael G

    2007-01-01

    Background In acoustic species, traits such as male calling song are likely to diverge quickly between allopatric populations due to sexual selection, and divergence in parameters such as carrier frequency, chirp structure, and other important song characters can influence sexual isolation. Here we make use of two forms of Mormon crickets to examine differences in a broad suite of traits that have the potential to influence speciation via sexual isolation. Mormon crickets in "gregarious" populations aggregate into dense migratory bands, and females are the sexually competitive sex (sex-role reversal). There is also a non-outbreak "solitary" form. These two forms are largely but not perfectly correlated with a significant mtDNA subdivision within the species that is thought to have arisen in allopatry. Combined information about multiple, independently evolving traits, such as morphology and structural and behavioural differences in calling song, provides greater resolution of the overall differences between these allopatric populations, and allows us to assess their stage of divergence. We test two predictions, first that the forms differ in song and second that gregarious males are more reluctant to sing than solitary males due to sex role reversal. We also tested for a difference in the relationship between the size of the forewing resonator, the mirror, and carrier frequency, as most models of sound production in crickets indicate that mirror size should predict carrier frequency. Results Multivariate analyses showed that solitary and gregarious individuals from different populations representing the two mtDNA clades had almost non-overlapping distributions based on multiple song and morphological measurements. Carrier frequency differed between the two, and gregarious males were more reluctant to sing overall. Mirror size predicted carrier frequency; however, the relationship between mirror size and surface area varied between solitary and gregarious forms

  14. Multiple differences in calling songs and other traits between solitary and gregarious Mormon crickets from allopatric mtDNA clades

    Directory of Open Access Journals (Sweden)

    Bailey William V

    2007-01-01

    Full Text Available Abstract Background In acoustic species, traits such as male calling song are likely to diverge quickly between allopatric populations due to sexual selection, and divergence in parameters such as carrier frequency, chirp structure, and other important song characters can influence sexual isolation. Here we make use of two forms of Mormon crickets to examine differences in a broad suite of traits that have the potential to influence speciation via sexual isolation. Mormon crickets in "gregarious" populations aggregate into dense migratory bands, and females are the sexually competitive sex (sex-role reversal. There is also a non-outbreak "solitary" form. These two forms are largely but not perfectly correlated with a significant mtDNA subdivision within the species that is thought to have arisen in allopatry. Combined information about multiple, independently evolving traits, such as morphology and structural and behavioural differences in calling song, provides greater resolution of the overall differences between these allopatric populations, and allows us to assess their stage of divergence. We test two predictions, first that the forms differ in song and second that gregarious males are more reluctant to sing than solitary males due to sex role reversal. We also tested for a difference in the relationship between the size of the forewing resonator, the mirror, and carrier frequency, as most models of sound production in crickets indicate that mirror size should predict carrier frequency. Results Multivariate analyses showed that solitary and gregarious individuals from different populations representing the two mtDNA clades had almost non-overlapping distributions based on multiple song and morphological measurements. Carrier frequency differed between the two, and gregarious males were more reluctant to sing overall. Mirror size predicted carrier frequency; however, the relationship between mirror size and surface area varied between

  15. Xanthohumol, a prenylated flavonoid contained in beer, prevents the induction of preneoplastic lesions and DNA damage in liver and colon induced by the heterocyclic aromatic amine amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    International Nuclear Information System (INIS)

    Ferk, Franziska; Huber, Wolfgang W.; Filipic, Metka; Bichler, Julia; Haslinger, Elisabeth; Misik, Miroslav; Nersesyan, Armen; Grasl-Kraupp, Bettina; Zegura, Bojana; Knasmueller, Siegfried

    2010-01-01

    Xanthohumol (XN) is a hop derived prenylated flavonoid contained in beer. Earlier findings indicated that it has promising chemopreventive properties and protects cells against DNA damage by carcinogens via inhibition of their activation. Furthermore, it was found that XN inhibits DNA synthesis and proliferation of cancer cells in vitro, inactivates oxygen radicals and induces apoptosis. Since evidence for its chemoprotective properties is restricted to results from in vitro experiments, we monitored the impact of XN on the formation of amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced preneoplastic foci in livers and colons of rats (9/group). Additionally, we studied its effects on IQ-induced DNA damage in colonocytes and hepatocytes in single cell gel electrophoresis assays and on the activities of a panel of drug metabolising enzymes. Consumption of the drinking water supplemented with XN (71 μg/kg b.w.) before and during carcinogen treatment led to a significant reduction of the number of GST-p + foci in the liver by 50% and also to a decrease of the foci area by 44%. DNA migration was decreased significantly in both, colon mucosa and liver cells, but no alterations of the activities of different phases I and II enzymes were found in hepatic tissue. Our findings indicate that XN protects against DNA damage and cancer induced by the cooked food mutagen. Since the effects were observed with low doses of XN which are reached after consumption of brews with high XN levels, our findings may be relevant for humans.

  16. Choking Prevention

    Science.gov (United States)

    ... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations At Home ...

  17. Iberian red deer: paraphyletic nature at mtDNA but nuclear markers support its genetic identity.

    Science.gov (United States)

    Carranza, Juan; Salinas, María; de Andrés, Damián; Pérez-González, Javier

    2016-02-01

    Red deer populations in the Iberian glacial refugium were the main source for postglacial recolonization and subspecific radiation in north-western Europe. However, the phylogenetic history of Iberian red deer (Cervus elaphus hispanicus) and its relationships with northern European populations remain uncertain. Here, we study DNA sequences at the mitochondrial control region along with STR markers for over 680 specimens from all the main red deer populations in Spain and other west European areas. Our results from mitochondrial and genomic DNA show contrasting patterns, likely related to the nature of these types of DNA markers and their specific processes of change over time. The results, taken together, bring support to two distinct, cryptic maternal lineages for Iberian red deer that predated the last glacial maximum and that have maintained geographically well differentiated until present. Haplotype relationships show that only one of them contributed to the northern postglacial recolonization. However, allele frequencies of nuclear markers evidenced one main differentiation between Iberian and northern European subspecies although also supported the structure of both matrilines within Iberia. Thus, our findings reveal a paraphyletic nature for Iberian red deer but also its genetic identity and differentiation with respect to northern subspecies. Finally, we suggest that maintaining the singularity of Iberian red deer requires preventing not only restocking practices with red deer specimens belonging to other European populations but also translocations between both Iberian lineages.

  18. HUBUNGAN KEKERABATAN BEBERAPA POPULASI KERANG HIJAU (Perna viridis DI INDONESIA BERDASARKAN SEKUEN CYTROCROME B mtDNA

    Directory of Open Access Journals (Sweden)

    Achmad Sudradjat

    2016-11-01

    Full Text Available Penelitian ini dilakukan untuk mengetahui hubungan kekerabatan stok kerang hijau (Perna viridis di beberapa perairan Indonesia sebagai informasi dasar bagi program pemuliaan. Sampel kerang hijau yang berasal dari populasi alam perairan Tanjung Kait, Kamal, Panimbang, Cirebon, Pasuruan, Kenjeran, dan Pangkep diambil secara acak. Amplifikasi PCR dan sekuensing mitokondria daerah cytochrome B adalah HCO (F: 5’-TAA ACT TCA GGG TGA CCA AAA AAT CA-3’ (26 bp dan LCO (R: 5’-GGT CAA CAA ATC ATA AAG ATA TTG G-3’ (25 bp. Sekuen DNA yang diperoleh digunakan untuk analisis homologi, analisis genetic distance dan analisis kekerabatan. Hasil analisis homologi susunan nukleotida berdasarkan BLAST-N terhadap sekuen mtDNA Perna viridis yang tersimpan di Genebank menunjukkan similaritas 97%. Hasil analisis didapatkan jarak genetik yang terdekat adalah populasi Tanjung Kait dengan Kenjeran sedangkan jarak genetik terjauh adalah populasi Cirebon dengan Kamal. Hubungan kekerabatan yang ditunjukkan dengan dendrogram diperoleh 2 kelompok yaitu 6 populasi membentuk satu kelompok dan populasi Cirebon membentuk kluster tersendiri. Sekuens tersebut mungkin dapat digunakan sebagai penanda dalam program breeding kerang hijau di Indonesia

  19. Length heteroplasmy of the polyC-polyT-polyC stretch in the dog mtDNA control region.

    Science.gov (United States)

    Verscheure, Sophie; Backeljau, Thierry; Desmyter, Stijn

    2015-09-01

    Previously, the mitochondrial control region of 214 Belgian dogs was sequenced. Analysis of this data indicated length heteroplasmy of the polyT stretch in the polyC-polyT-polyC stretch from positions 16661 to 16674. Nine polyC-polyT-polyC haplotype combinations were observed, consisting of seven major haplotypes (highest signal intensity) combined with minor haplotypes (lower signal intensity) one T shorter than the major haplotype in all but three dogs. The longer the polyT stretch, the smaller was the difference in signal intensity between the major and minor haplotype peaks. Additional sequencing, cloning, and PCR trap experiments were performed to further study the intra-individual variation of this mitochondrial DNA (mtDNA) region. Cloning experiments demonstrated that the proportion of clones displaying the minor haplotypes also increased with the length of the polyT stretch. Clone amplification showed that in vitro polymerase errors might contribute to the length heteroplasmy of polyT stretches with at least 10 Ts. Although major and minor polyC-polyT-polyC haplotypes did not differ intra-individually within and between tissues in this study, interpretation of polyT stretch variation should be handled with care in forensic casework.

  20. A new mtDNA COI gene lineage near An. janconnae of the Albitarsis Complex from Caribbean Colombia

    Science.gov (United States)

    Gutiérrez, Lina A; Orrego, Lina M; Gómez, Giovan F; López, Andrés; Luckhart, Shirley; Conn, Jan E; Correa, Margarita M

    2011-01-01

    An understanding of the taxonomic status and vector distribution of anophelines is crucial to malaria control efforts. Previous phylogenetic analyses have supported the description of six species of the Neotropical malaria vector Anopheles (Nyssorhynchus) albitarsis s.l. (Diptera: Culicidae): Anopheles albitarsis, An. deaneorum, An. marajoara, An. oryzalimnetes, An. janconnae and An. albitarsis F. To evaluate the taxonomic status of An. albitarsis s.l. mosquitoes collected in various localities of the Colombian Caribbean region, specimens were analyzed using the complete mtDNA Cytochrome Oxidase I (COI) gene, the ribosomal DNA internal transcribed spacer 2 (ITS2) region and partial nuclear DNA White gene sequences. Phylogenetic analyses of the COI sequences detected a new lineage near An. janconnae in the Caribbean region of Colombia and determined its position relative to the other members of the complex. However, the ITS2 and White gene sequences lacked resolution to support a new lineage near An. janconnae or the An. janconnae clade. Nothing is known about the possible involvement in malaria transmission in Colombia of this new lineage, but its phylogenetic closeness to Anopheles janconnae, which has been incriminated in local malaria transmission in Brazil, is provocative. PMID:21225199

  1. A new view on the European feline population from mtDNA analysis in Polish domestic cats.

    Science.gov (United States)

    Głażewska, Iwona; Kijewski, Tomasz

    2017-03-01

    Domestic cats from Eastern Europe have been poorly represented in studies on mitochondrial DNA diversity for forensic purposes until now. The aim of the present study was to contribute to closing this gap. The genetic structure and the origin of a cat population in Poland were examined against the background of human migrations over the centuries. One hundred and eighty-one cats from animal shelters in seven cities were genotyped. Twenty-one mtDNA haplotypes were found, with only one haplotype present in each of the populations, at an average frequency of 63.54%, and 13 haplotypes being found only in single populations. The analysis revealed the unexpectedly high frequency of haplotype PL02, in previous studies observed only in single cats. Differences in the number of the haplotypes, from four to eight, were observed among the shelters. The findings are discussed with regard to a world-wide database of feline sequences and to the complicated history of Poland. The study underscores the necessity of creating local databases of haplotypes that are of high evidentiary value to the forensic investigations conducted in a given country. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Comparison between Mt-DNA D-Loop and Cyt B primers for porcine DNA detection in meat products

    Science.gov (United States)

    Hamzah, Azhana; Mutalib, Sahilah Abd.; Babji, Abdul Salam

    2013-11-01

    This study was conducted to detect the presence of porcine DNA in meat products in the market using conventional polymerase chain reaction (PCR) and commercial PCR-southern hybridization analysis. Porcine DNA detection in meat products was tested due to some issues associated with the adulteration of food products in Malaysia. This is an important issue especially for Halal authentication which is required for some religious practices such as in Islam and Hinduisms. Many techniques have been developed for determining the Halal status of food products. In this paper, mt-DNA D-loop primer and cytochrome (cyt) b were used to detect the presence of porcine DNA in meat products. Positive and negative controls were always present for each batch of extraction. DNA of raw pork meat was used as a positive control while nucleus free water is used as negative control. A pair of oligonucleotide primer was used namely Pork1 and Pork2 which produced amplicon of 531 base pair (bp) in size. While, PCR-southern hybridization was conducted using primers readily supplied by commercial PCR-Southern hybridization and produced amplicon with 276 bp in size. In the present study, demonstrated that none of the samples were contaminated with porcine residuals but selected samples with pork meat were positive. The species-specific PCR amplification yielded excellent results for identification of pork derivatives in food products and it is a potentially reliable and suitable technique in routine food analysis for Halal certification.

  3. Reconstructing the origin of the Lapita Cultural Complex: mtDNA analyses of East Sepik Province, PNG.

    Science.gov (United States)

    Vilar, Miguel G; Kaneko, Akira; Hombhanje, Francis W; Tsukahara, Takahiro; Hwaihwanje, Ilomo; Lum, J Koji

    2008-01-01

    The colonization of Oceania occurred in two waves. By 32,000 BP, humans had reached New Guinea and settled all intervisible islands east to the Solomon Islands. Around 3,500 BP, a distinct intrusive group from Southeast Asia reached coastal New Guinea, integrated their components with indigenous resources, and gave rise to the Lapita Cultural Complex. Within 2,500 years, Lapita and its descendant cultures colonized the Pacific. To uncover the origin of the Lapita Cultural Complex, we analyzed the hypervariable region I of the mitochondrial deoxyribonucleic acid (mtDNA) in 219 individuals from eight East Sepik Province villages: two villages in each of four environmental zones. Same-zone villages spoke different languages: one Austronesian and three Papuan (Arapesh, Abelam, and Boiken). Our analysis examined whether language or geography better predicted gene flow. In general, language better predicted genetic affinities. Boiken villages across all four zones showed no significant genetic difference (F(ST) P value > 0.05). In contrast, the Austronesian village was significantly different to most other villages (P 0.05). We interpret the data to reflect limited gene flow inland by Austronesians overshadowed by a regional displacement by inland Boiken speakers migrating seaward. These results are consistent with oral histories and ethnographic accounts.

  4. Worldwide structure of mtDNA diversity among Cuvier's beaked whales (Ziphius cavirostris): implications for threatened populations.

    Science.gov (United States)

    Dalebout, Merel L; Robertson, Kelly M; Frantzis, Alexandros; Engelhaupt, Dan; Mignucci-Giannoni, Antonio A; Rosario-Delestre, Raul J; Baker, C Scott

    2005-10-01

    We present the first description of phylogeographic structure among Cuvier's beaked whales (Ziphius cavirostris) worldwide using mitochondrial DNA (mtDNA) control region sequences obtained from strandings (n = 70), incidental fisheries takes (n = 11), biopsy (n = 1), and whale-meat markets (n = 5). Over a 290-base pair fragment, 23 variable sites defined 33 unique haplotypes among the total of 87 samples. Nucleotide diversity at the control region was relatively low (pi = 1.27%+/- 0.723%) compared to wide-ranging baleen whales, but higher than strongly matrifocal sperm, pilot and killer whales. Phylogenetic reconstruction using maximum likelihood revealed four distinct haplotype groups, each of which displayed strong frequency differences among ocean basins, but no reciprocal monophyly or fixed character differences. Consistent with this phylogeographic pattern, an analysis of molecular variance showed high levels of differentiation among ocean basins (F(ST) = 0.14, Phi ST = 0.42; P fisheries by-catch, direct hunting, and disturbance or mortality from anthropogenic sound.

  5. Geographic structure and demographic history of Iranian brown bear (Ursus arctos based on mtDNA control region sequences

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Ashrafzadeh

    2015-12-01

    Full Text Available In recent years, the brown bear's range has declined and its populations in some areas have faced extinction. Therefore, to have a comprehensive picture of genetic diversity and geographic structure of populations is essential for effective conservation strategies. In this research, we sequenced a 271bp segment of mtDNA control region of seven Iranian brown bears, where a total dataset of 467 sequences (brown and polar bears were used in analyses. Overall, 113 different haplotypes and 77 polymorphic sites were identified within the segment. Based on phylogenetic analyses, Iranian brown bears were not nested in any other clades. The low values of Nm (range=0.014-0.187 and high values of Fst (range=0.728-0.972 among Iranian bears and others revealed a genetically significant differentiation. We aren't found any significant signal of demographic reduction in Iranian bears. The time to the most recent common ancestor of Iranian brown bears (Northern Iran was found to be around 19000 BP.

  6. Personal identification of cold case remains through combined contribution from anthropological, mtDNA, and bomb-pulse dating analyses.

    Science.gov (United States)

    Speller, Camilla F; Spalding, Kirsty L; Buchholz, Bruce A; Hildebrand, Dean; Moore, Jason; Mathewes, Rolf; Skinner, Mark F; Yang, Dongya Y

    2012-09-01

    In 1968, a child's cranium was recovered from the banks of a northern Canadian river and held in a trust until the "cold case" was reopened in 2005. The cranium underwent reanalysis at the Centre for Forensic Research, Simon Fraser University, using recently developed anthropological analysis, "bomb-pulse" radiocarbon analysis, and forensic DNA techniques. Craniometrics, skeletal ossification, and dental formation indicated an age-at-death of 4.4 ± 1 year. Radiocarbon analysis of enamel from two teeth indicated a year of birth between 1958 and 1962. Forensic DNA analysis indicated the child was a male, and the obtained mitochondrial profile matched a living maternal relative to the presumed missing child. These multidisciplinary analyses resulted in a legal identification 41 years after the discovery of the remains, highlighting the enormous potential of combining radiocarbon analysis with anthropological and mtDNA analyses in producing confident personal identifications for forensic cold cases dating to within the last 60 years. © 2012 American Academy of Forensic Sciences.

  7. Novel 12S mtDNA findings in sloths (Pilosa, Folivora and anteaters (Pilosa, Vermilingua suggest a true case of long branch attraction

    Directory of Open Access Journals (Sweden)

    Maria Claudene Barros

    2008-01-01

    Full Text Available We sequenced 12S RNA mtDNA for the majority of the extant species of sloths and anteaters and compared our results with previous data obtained by our group using 16S RNA mtDNA in the same specimens and to GenBank sequences of the extinct giant sloth Mylodon. Our results suggest that pigmy-anteaters may be a case of the long-branch attraction phenomenon and also show the large genetic difference between the Amazonian and Atlantic forest three-toed sloths, contrasting with the small differences observed between the two non-Atlantic forest forms of sloths. These results have important implications for the taxonomy of sloths and anteaters and strongly suggest the placement of pigmy anteaters in their own family (Cyclopidae and raising the taxonomic status of Bradypus torquatus to a genus.

  8. A novel mtDNA large-scale mutation clinically exclusively presenting with refractory anemia: is there a chance to predict disease progression?

    Science.gov (United States)

    Binder, Vera; Steenpass, Laura; Laws, Hans-Juergen; Ruebo, Jochen; Borkhardt, Arndt

    2012-05-01

    Because of the diversity of clinical symptoms, the diagnosis of mitochondrial DNA (mtDNA) deletion disorders can be difficult. Here, we describe an 8-month-old boy presenting clinically exclusively with refractory anemia. Mutation analysis in our patient revealed a large, novel deletion in his mtDNA encompassing ATPase 6, cytochrome oxidase subunit III, NADH dehydrogenase genes ND3 to ND6, and cytochrome b. Comparison with other cases from the literature showed that there is no genotype-phenotype correlation regarding hematologic features. It is not possible to predict whether our patient will develop additional features from Pearson syndrome or Kearns-Sayre syndrome, both syndromic mitochondrial disorders with hematological manifestations.

  9. The investigation of genetic diversity and evolution of Daweishan Mini chicken based on the complete mitochondrial (mt)DNA D-loop region sequence.

    Science.gov (United States)

    Jia, Xiao-Xu; Tang, Xiu-Jun; Lu, Jun-Xian; Fan, Yan-Feng; Chen, Da-Wei; Tang, Meng-Jun; Gu, Rong; Gao, Yu-Shi

    2016-07-01

    This study evaluated the genetic diversity and origin of Daweishan Mini chickens using mtDNA sequence polymorphism. Blood samples from 30 Daweishan Mini chickens were collected. The complete D-loop was PCR amplified, sequenced and compared with the DNA data of five Red Junglefowl (Gallus gallus) subspecies. Eighteen variable sites that defined six haplotypes were observed. The six haplotypes were clustered into four clades (A, B, D and E), of which clade A and B were dominant. Clades Aand B were clustered with G.g. spadiceus, indicating these two clades may have originated from this subspecies. These results show there is diversity in the middle of the mtDNA D-loop, and indicate there are multiple maternal origins for Daweishan Mini chickens. It appears that G.g. spadiceus contributed more to the evolution of the Daweishan Mini chickens breed than the other four subspecies tested here.

  10. Disaster: Prevention, Preparedness and Action.

    Science.gov (United States)

    Buchanan, Sally

    1981-01-01

    Discission of threat of disaster to library archival materials focuses on prevention (building maintenance, materials storage, fire prevention), preparedness (preplanning, procedures for handling emergencies, finances of recovery operation), and action (instructions for handling damaged materials). Current library activities in disaster planning…

  11. Impact damage of composites

    Science.gov (United States)

    Wu, Hsi-Young T.; Springer, George S.

    1986-01-01

    A model is described for estimating the impact damage of fiber reinforced composite plates. The displacements and stresses are calculated by a three dimensional transient, finite element method of solution of the governing equations applicable to a linearly elastic body. The region in which damage occurs is estimated using the Tsai-Wu failure criterion. A computer code was developed which can be used to calculate the impact force, displacements and velocities of the plate and the impact body, stresses and strains in the plate, and the damage area. Sample numerical results are presented illustrating the type of information provided by the code. Comparisons between measured and calculated damage areas are also given.

  12. mtDNA as a Mediator for Expression of Hypoxia-Inducible Factor 1α and ROS in Hypoxic Neuroblastoma Cells.

    Science.gov (United States)

    Kuo, Chung-Wen; Tsai, Meng-Han; Lin, Tsu-Kung; Tiao, Mao-Meng; Wang, Pei-Wen; Chuang, Jiin-Haur; Chen, Shang-Der; Liou, Chia-Wei

    2017-06-07

    Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol. Moreover, elevation of HIF-1α also resulted in increases of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase kinase 1 (PDK1) in both hypoxic cells. The expression of mitochondrial biogenesis related proteins and metabolic components were noted to increase significantly in hypoxic SK-N-AS cells, indicating that mtDNA was involved in mitochondrial retrograde signaling and metabolic pathways. An analysis of dynamic proteins found elevated levels of HIF-1α causing an increased expression of dynamin-related protein 1 (DRP1) during hypoxia; further, the existence of mtDNA also resulted in higher expression of DRP1 during hypoxia. By using siRNA of HIF-1α or DRP1, expression of DRP1 decreased after suppression of HIF-1α; moreover, the expression of HIF-1α was also affected by the suppression of DRP1. In this study, we demonstrated that mtDNA is a mediator of HIF-1α in eliciting metabolic reprogramming, and mitochondrial biogenesis. Identification of a mutual relationship between HIF-1α and DRP1 may be a critical tool in the future development of clinical applications.

  13. mtDNA and Y-chromosome diversity in Aymaras and Quechuas from Bolivia: different stories and special genetic traits of the Andean Altiplano populations.

    Science.gov (United States)

    Gayà-Vidal, Magdalena; Moral, Pedro; Saenz-Ruales, Nancy; Gerbault, Pascale; Tonasso, Laure; Villena, Mercedes; Vasquez, René; Bravi, Claudio M; Dugoujon, Jean-Michel

    2011-06-01

    Two Bolivian samples belonging to the two main Andean linguistic groups (Aymaras and Quechuas) were studied for mtDNA and Y-chromosome uniparental markers to evaluate sex-specific differences and give new insights into the demographic processes of the Andean region. mtDNA-coding polymorphisms, HVI-HVII control regions, 17 Y-STRs, and three SNPs were typed in two well-defined populations with adequate size samples. The two Bolivian samples showed more genetic differences for the mtDNA than for the Y-chromosome. For the mtDNA, 81% of Aymaras and 61% of Quechuas presented haplogroup B2. Native American Y-chromosomes were found in 97% of Aymaras (89% hg Q1a3a and 11% hg Q1a3*) and 78% of Quechuas (100% hg Q1a3a). Our data revealed high diversity values in the two populations, in agreement with other Andean studies. The comparisons with the available literature for both sets of markers indicated that the central Andean area is relatively homogeneous. For mtDNA, the Aymaras seemed to have been more isolated throughout time, maintaining their genetic characteristics, while the Quechuas have been more permeable to the incorporation of female foreigners and Peruvian influences. On the other hand, male mobility would have been widespread across the Andean region according to the homogeneity found in the area. Particular genetic characteristics presented by both samples support a past common origin of the Altiplano populations in the ancient Aymara territory, with independent, although related histories, with Peruvian (Quechuas) populations. Copyright © 2011 Wiley-Liss, Inc.

  14. Rozmanitost projevů heteroplazmické mtDNA mutace 8993 T>G ve dvou rodinách

    Czech Academy of Sciences Publication Activity Database

    Tesařová, M.; Hansíková, H.; Hlavatá, A.; Klement, P.; Houšťková, H.; Houštěk, Josef; Zeman, J.

    2002-01-01

    Roč. 141, č. 17 (2002), s. 551-554 ISSN 0008-7335 R&D Projects: GA MZd(CZ) NE6533; GA MZd(CZ) NE6555; GA MŠk(CZ) LN00A079 Institutional research plan: CEZ:AV0Z5011922 Keywords : NARP syndrome * mtDNA mutation 8993 T>G Subject RIV: EB - Genetics ; Molecular Biology

  15. CANCERIZATION OF CUTANEOUS FLAP RECONSTRUCTION FOR ORAL SQUAMOUS CELL CARCINOMA: REPORT OF THREE CASES STUDIED WITH THE mtDNA D-LOOP SEQUENCE ANALYSIS

    OpenAIRE

    Foschini , Maria Pia; Morandi , Luca; Marchetti , Claudio; Cocchi , Roberto; Eusebi , Leonardo Henry; Farnedi , Anna; Badiali , Giovanni; Gissi , Davide Bartolomeo; Pennesi , Maria Gabriella; Montebugnoli , Lucio

    2011-01-01

    Abstract Aims: tissue defects, resulting from surgical resection of oral squamous cell carcinoma (OSCC), are routinely reconstructed with skin graft. OSCC arising from the grafted skin have been described, however, it is still unclear whether primary and second tumours have a common clonal origin. By screening mitochondrial DNA D-loop region (mtDNA), we evaluated the clonal relationship between the primary OSCC and the second neoplastic features appearing in the skin graft in three...

  16. Comparison of two Neolithic mtDNA haplotypes from a Czech excavation site with the results of mitochondrial DNA studies on European Neolithic and Mesolithic individuals

    Czech Academy of Sciences Publication Activity Database

    Votrubová, J.; Emmerová, B.; Brzobohatá, Hana; Šumberová, Radka; Vaněk, D.

    2017-01-01

    Roč. 6, December (2017), „e125”-„e128” ISSN 1875-1768 R&D Projects: GA ČR GB14-36938G Institutional support: RVO:67985912 Keywords : ancient DNA * mtDNA * sequencing * haplotype * haplogroup Subject RIV: AC - Archeology, Anthropology, Ethnology OBOR OECD: Archaeology http://www.fsigeneticssup.com/article/S1875-1768(17)30162-2/pdf

  17. Regional Differences in the Distribution of the Sub-Saharan, West Eurasian, and South Asian mtDNA Lineages in Yemen

    Czech Academy of Sciences Publication Activity Database

    Černý, Viktor; Mulligan, C. J.; Rídl, J.; Žaloudková, M.; Edens, C. M.; Hájek, Martin; Pereira, L.

    2008-01-01

    Roč. 136, č. 2 (2008), s. 128-137 ISSN 0002-9483 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA diversity * regional sampling * population distances * phylogeography Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.353, year: 2008 http://www3.interscience.wiley.com/journal/117899911/abstract

  18. Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

    Science.gov (United States)

    Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

    2005-01-01

    We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

  19. MtDNA COI-COII marker and drone congregation area: an efficient method to establish and monitor honeybee (Apis mellifera L.) conservation centres.

    Science.gov (United States)

    Bertrand, Bénédicte; Alburaki, Mohamed; Legout, Hélène; Moulin, Sibyle; Mougel, Florence; Garnery, Lionel

    2015-05-01

    Honeybee subspecies have been affected by human activities in Europe over the past few decades. One such example is the importation of nonlocal subspecies of bees which has had an adverse impact on the geographical repartition and subsequently on the genetic diversity of the black honeybee Apis mellifera mellifera. To restore the original diversity of this local honeybee subspecies, different conservation centres were set up in Europe. In this study, we established a black honeybee conservation centre Conservatoire de l'Abeille Noire d'Ile de France (CANIF) in the region of Ile-de-France, France. CANIF's honeybee colonies were intensively studied over a 3-year period. This study included a drone congregation area (DCA) located in the conservation centre. MtDNA COI-COII marker was used to evaluate the genetic diversity of CANIF's honeybee populations and the drones found and collected from the DCA. The same marker (mtDNA) was used to estimate the interactions and the haplotype frequency between CANIF's honeybee populations and 10 surrounding honeybee apiaries located outside of the CANIF. Our results indicate that the colonies of the conservation centre and the drones of the DCA show similar stable profiles compared to the surrounding populations with lower level of introgression. The mtDNA marker used on both DCA and colonies of the conservation centre seems to be an efficient approach to monitor and maintain the genetic diversity of the protected honeybee populations. © 2014 John Wiley & Sons Ltd.

  20. Quantitative analysis of gene-specific DNA damage in human spermatozoa

    International Nuclear Information System (INIS)

    Sawyer, Dennis E.; Mercer, Belinda G.; Wiklendt, Agnieszka M.; Aitken, R. John

    2003-01-01

    Recent studies have suggested that human spermatozoa are highly susceptible to DNA damage induced by oxidative stress. However, a detailed analysis of the precise nature of this damage and the extent to which it affects the mitochondrial and nuclear genomes has not been reported. To induce DNA damage, human spermatozoa were treated in vitro with hydrogen peroxide (H 2 O 2 ; 0-5 mM) or iron (as Fe(II)SO 4 , 0-500 μM). Quantitative PCR (QPCR) was used to measure DNA damage in individual nuclear genes (hprt, β-pol and β-globin) and mitochondrial DNA. Single strand breaks were also assessed by alkaline gel electrophoresis. H 2 O 2 was found to be genotoxic toward spermatozoa at concentrations as high as 1.25 mM, but DNA damage was not detected in these cells with lower concentrations of H 2 O 2 . The mitochondrial genome of human spermatozoa was significantly (P 2 O 2 -induced DNA damage than the nuclear genome. However, both nDNA and mtDNA in human spermatozoa were significantly (P<0.001) more resistant to damage than DNA from a variety of cell lines of germ cell and myoblastoid origin. Interestingly, significant DNA damage was also not detected in human spermatozoa treated with iron. These studies report, for the first time, quantitative measurements of DNA damage in specific genes of male germ cells, and challenge the commonly held belief that human spermatozoa are particularly vulnerable to DNA damage

  1. Bilding (Kay) Ki Damaje PSA (:60) (Damaged Buildings)

    Centers for Disease Control (CDC) Podcasts

    2010-02-18

    An important public health announcement about your safety when entering damaged buildings. Language: Haitian Creole.  Created: 2/18/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 2/18/2010.

  2. Damage Theory Validation

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1998-01-01

    This report contains a series of validation examples for the theoretical model implemented in the computer program DAMAGE. note that the validation examples are for assembled structures.......This report contains a series of validation examples for the theoretical model implemented in the computer program DAMAGE. note that the validation examples are for assembled structures....

  3. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  4. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  5. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  6. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  7. Fluorescent duplex allele-specific PCR and amplicon melting for rapid homogeneous mtDNA haplogroup H screening and sensitive mixture detection.

    Directory of Open Access Journals (Sweden)

    Harald Niederstätter

    Full Text Available BACKGROUND: For large scale studies aiming at a better understanding of mitochondrial DNA (mtDNA, sequence variation in particular mt haplogroups (hgs and population structure, reliable low-cost high-throughput genotyping assays are needed. Furthermore, methods facilitating sensitive mixture detection and relative quantification of allele proportions are indispensable for the study of heteroplasmy, mitochondrial sequence evolution, and mitochondrial disorders. Here the properties of a homogeneous competitive duplex allele specific PCR (ARMS assay were scrutinized in the light of these requirements. METHODOLOGY/PRINCIPAL FINDINGS: A duplex ARMS assay amplifying either the ancestral mtDNA 2706G allele (non-hg H samples or the derived 7028C allele (hg H samples in the presence of SYBR Green fluorescent reporter dye was developed and characterized. Product detection, allele calling, and hg inference were based on the amplicon-characteristic melting-point temperatures obtained with on-line post-PCR fluorescent dissociation curve analysis (DCA. The analytical window of the assay covered at least 5 orders of magnitude of template DNA input with a detection limit in the low picogram range of genomic DNA. A set of forensically relevant test specimens was analyzed successfully. The presence of mtDNA mixtures was detected over a broad range of input DNA amounts and mixture ratios, and the estimation of allele proportions in samples with known total mtDNA content was feasible with limitations. A qualified DNA analyst successfully analyzed approximately 2,200 DNA extracts within three regular working days, without using robotic lab-equipment. By performing the amplification on-line, the assay also facilitated absolute mtDNA quantification. CONCLUSIONS: Although this assay was developed just for a particular purpose, the approach is general in that it is potentially suitable in a broad variety of assay-layouts for many other applications, including the

  8. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  9. The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

    Directory of Open Access Journals (Sweden)

    Kotal M

    2008-08-01

    Full Text Available Abstract Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP. However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is

  10. Y-chromosome and mtDNA variation confirms independent domestications and directional hybridization in South American camelids.

    Science.gov (United States)

    Marín, J C; Romero, K; Rivera, R; Johnson, W E; González, B A

    2017-10-01

    Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally-inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex-specific markers (male specific Y-chromosome and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns. Three male-specific Y-chromosome markers and control region sequences of mitochondrial DNA are studied here. Although no sequence variation was found in SRY and ZFY, there were seven variable sites in DBY generating five haplotypes on the Y-chromosome. The haplotype network showed clear separation between haplogroups of guanaco-llama and vicuña-alpaca, indicating two genetically distinct patrilineages with near absence of shared haplotypes between guanacos and vicuñas. Although we document some examples of directional hybridization, the patterns strongly support the hypothesis that llama (Lama glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos) from vicuña (Vicugna vicugna). Within male guanacos we identified a haplogroup formed by three haplotypes with different geographical distributions, the northernmost of which (Peru and northern Chile) was also observed in llamas, supporting the commonly held hypothesis that llamas were domesticated from the northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared the other two haplotypes. A second haplogroup, consisting of two haplotypes, was mostly present in vicuñas and alpacas. However, Y-chromosome variation did not distinguish the two subspecies of vicuñas. © 2017 Stichting International Foundation for Animal Genetics.

  11. 1,25-(OH)2-vitamin D3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4−/− model

    International Nuclear Information System (INIS)

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-01-01

    Background/Purpose of the study: Vitamin D 3 -deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D 3 -administration has thus been proposed as a therapeutic approach. Vitamin D 3 has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH) 2 -vitamin D 3 inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen ® -assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4 −/− (Abcb4 −/− )-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4 −/− -mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4 −/− -mice, administration of calcitriol ameliorates inflammatory liver-damage but has no effect on biliary fibrosis after 4 weeks

  12. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    Energy Technology Data Exchange (ETDEWEB)

    Reiter, Florian P., E-mail: florian.reiter@med.uni-muenchen.de [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany); Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany); Makeschin, Marie-Christine; Mayr, Doris [Institute of Pathology, University of Munich, Thalkirchner Str. 36, D-80337 Munich (Germany); Rust, Christian [Department of Medicine I, Krankenhaus Barmherzige Brüder, Romanstr. 93, D-80639 Munich (Germany); Trauner, Michael [Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna (Austria); Denk, Gerald U. [Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich (Germany)

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  13. Clinical research of teeth damage from radiotherapy

    International Nuclear Information System (INIS)

    Li Erzhou; Yan Maosheng; Chen Wei; Li Qing

    2003-01-01

    Objective: To analyze various factors inducing teeth damage from radiotherapy and the preventive and treatment methods. Methods: One hundred cases of patients treated by radiotherapy were divided into two groups. In group one there were 60 cases whose teeth were irradiated during treatment; in group two there were 40 cases whose teeth were not irradiated during treatment. Results: The caries incidence was 60% for group one and 15% for group two (P<0.01). By auto-control in 15 patients, the caries incidence on the sick side was obviously higher than that of the healthy side. Hundred percent caries incidence was found in 6 cases who received a dosage of 70 Gy. Conclusion: The authors believe that radiation damage to the teeth is associated with the following factors: 1. The dosage and location of irradiation are closely related to caries incidence; 2. The active dentinoblasts are very sensitive to radiation; 3. Damage to the salivary glands from radiotherapy can result in reduction of salvia and pH value, leading to a high growth rate of Streptococcus mutans. Following preventive measures could be considered in future cases: to apply a caries prevention coating or protective dental crown and TPS, to adjust the dose and time of irradiation, to select conformal radiotherapy technique. The key points for protecting the teeth and salivary gland from caries and damage are protection of the proliferation ability of pulp cells, anti-inflammation, promotion of microcirculation, and strengthening body resistance

  14. Prevenção de agravos à saúde do trabalhador: replanejando o trabalho através das negociações cotidianas Preventing damage to workers' health: redesigning jobs through day-to-day negotiation

    Directory of Open Access Journals (Sweden)

    Leny Sato

    2002-10-01

    Full Text Available Este artigo tem por objetivo apresentar algumas reflexões sobre a prevenção de agravos à saúde do trabalhador através do replanejamento do trabalho. Compreendendo o replanejamento como processo de negociação de escolhas organizacionais, apresenta as características das negociações cotidianas processadas no chão de fábrica e relata, a título de exemplo, um caso de negociação cotidiana que toma por objeto a organização do processo de trabalho da produção fabril de uma indústria de alimentos. Por fim, discute os alcances e os limites de tais negociações à luz da prevenção de agravos à saúde do trabalhador.This paper reflects on prevention of harm to workers' health by redesigning jobs. Assuming redesign as the process of negotiating organizational choices, the author discusses the characteristics of routine negotiation at the workplace, illustrated by daily negotiations in work process organization at a Brazilian food-processing factory. Finally, the author discusses both the range and limits of such negotiations in the prevention of harm to workers' health.

  15. Prevention of cisplatin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Hayati Fatemeh

    2016-01-01

    Full Text Available Cisplatin has a well-established role in the treatment of broad spectrum of malignancies; however its use is limited because of cisplatin-induced nephrotoxicity (CIN which can be progressive in more than 50% of cases. The most important risk factors for CIN include higher doses of cisplatin, previous cisplatin chemotherapy, underlying kidney damage and concurrent treatment with other potential nephrotoxin agents, such as aminoglycosides, nonsteroidal anti-inflammatory agents, or iodinated contrast media. Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. The standard approach for prevention of CIN is the administration of lower doses of cisplatin in combination with full intravenous hydration prior and after cisplatin administration. Cisplatin-induced oxidative stress in the kidney may be prevented by natural antioxidant compounds. The results of this review show that many strategies for prevention of CIN exist, however, attention to the administration of these agent for CIN is necessary.

  16. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  17. Continuous damage mechanics

    International Nuclear Information System (INIS)

    Chaboche, J.L.

    1981-01-01

    The classical structural life predictions are based on stabilized stress-strain analysis and some parametric relations with the number of cycles to failure. During the last ten years a different approach, initiated by the works of Kachanov and Rabotnov for creep rupture, has been developed by different laboratories. This continuous Damage Mechanics, treating the damaged material as a macroscopically homogeneous one, leads to the possibility of globally modelling the nucleation and the propagation of microdefects including their effect on the stress-strain behaviour. This paper presents the general theory and several applications to a turbine blade refractory alloy. It includes the description of sequence effects and creep-fatigue interaction. The generalization for three-dimensional conditions, where anisotropic damage effects are possible, is discussed and some new proposals are given for the determination of simple anisotropic damage equations. (orig.)

  18. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  19. Rape prevention

    Science.gov (United States)

    Date rape - prevention; Sexual assault - prevention ... Centers for Disease Control and Prevention website. Sexual assault and abuse and STDs. In: 2015 sexually transmitted diseases treatment guidelines 2015. www.cdc.gov/std/tg2015/sexual- ...

  20. Dengue Prevention

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Prevention Recommend on Facebook Tweet Share Compartir This photograph ... medications to treat a dengue infection. This makes prevention the most important step, and prevention means avoiding ...