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Sample records for adaptations impaired oxidative

  1. Impaired visuomotor adaptation in adults with ADHD

    Kurdziel, Laura B. F.; Dempsey, Katherine; Zahara, Mackenzie; Valera, Eve; Rebecca M.C. Spencer

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children that often continues into adulthood. It has been suggested that motor impairments in ADHD are associated with underlying cerebellar pathology. If such is the case, individuals with ADHD should be impaired on motor tasks requiring healthy cerebellar function. To test this, we compared performance of individuals with ADHD and ADHD-like symptoms with non-ADHD controls on a visuomotor adaptation task k...

  2. Adaptive oxide electronics: A review

    Ha, Sieu D.; Ramanathan, Shriram

    2011-10-01

    Novel information processing techniques are being actively explored to overcome fundamental limitations associated with CMOS scaling. A new paradigm of adaptive electronic devices is emerging that may reshape the frontiers of electronics and enable new modalities. Creating systems that can learn and adapt to various inputs has generally been a complex algorithm problem in information science, albeit with wide-ranging and powerful applications from medical diagnosis to control systems. Recent work in oxide electronics suggests that it may be plausible to implement such systems at the device level, thereby drastically increasing computational density and power efficiency and expanding the potential for electronics beyond Boolean computation. Intriguing possibilities of adaptive electronics include fabrication of devices that mimic human brain functionality: the strengthening and weakening of synapses emulated by electrically, magnetically, thermally, or optically tunable properties of materials.In this review, we detail materials and device physics studies on functional metal oxides that may be utilized for adaptive electronics. It has been shown that properties, such as resistivity, polarization, and magnetization, of many oxides can be modified electrically in a non-volatile manner, suggesting that these materials respond to electrical stimulus similarly as a neural synapse. We discuss what device characteristics will likely be relevant for integration into adaptive platforms and then survey a variety of oxides with respect to these properties, such as, but not limited to, TaOx, SrTiO3, and Bi4-xLaxTi3O12. The physical mechanisms in each case are detailed and analyzed within the framework of adaptive electronics. We then review theoretically formulated and current experimentally realized adaptive devices with functional oxides, such as self-programmable logic and neuromorphic circuits. Finally, we speculate on what advances in materials physics and engineering may

  3. Effective Classroom Adaptations for Students with Visual Impairments.

    Cox, Penny R.; Dykes, Mary K.

    2001-01-01

    This article discusses strategies for including students with visual impairments in general education settings. It explains categories of visual impairments and how students with visual impairments learn. Auditory learning and visual learning accommodations are addressed, and checklists for orientation and mobility adaptations, and for classroom…

  4. Parkinson's disease associated with impaired oxidative phosphorylation

    Parkinson's disease may be due to primary or secondary oxidative phosphorylation (OXPHOS) defects. In a 76-year-old man with Parkinson's disease since 1992, slightly but recurrently elevated creatine phosphokinase, recurrently elevated blood glucose, thickening of the left ventricular myocardium, bifascicular block and hypacusis were found. Cerebral MRI showed atrophy, periventricular demyelination, multiple, disseminated, supra- and infratentorial lacunas, and haemosiderin deposits in both posterior horns. Muscle biopsy showed typical features of an OXPHOS defect. Whether the association of Parkinson's disease and impaired OXPHOS was causative or coincidental remains unknown. Possibly, the mitochondrial defect acted as an additional risk factor for Parkinson's disease or the OXPHOS defect worsened the preexisting neurological impairments by a cumulative or synergistic mechanism. In conclusion, this case shows that Parkinson's disease may be associated with a mitochondrially or nuclearly encoded OXPHOS defect, manifesting as hypacusis, myopathy, axonal polyneuropathy, cardiomyopathy and recurrent subclinical ischaemic strokes and haemorrhages. (orig.)

  5. Spatial compression impairs prism-adaptation in healthy individuals

    Roger Newport

    2013-01-01

    Neglect patients typically present with gross inattention to one side of space following damage to the contralateral hemisphere. While prism-adaptation is effective in ameliorating some neglect behaviours, the mechanisms involved and their relationship to neglect remain unclear. Recent studies have shown that conscious strategic control processes in prism-adaptation may be impaired in neglect patients, who are also reported to show extraordinarily long aftereffects compared to healthy partici...

  6. Familiar Sports and Activities Adapted for Multiply Impaired Persons.

    Schilling, Mary Lou, Ed.

    1984-01-01

    Means of adapting some familiar and popular physical activities for multiply impaired persons are described. Games reviewed are dice baseball, one base baseball, in-house bowling, wheelchair bowling, ramp bowling, swing-ball bowling, table tennis, shuffleboard, beanbag bingo and tic-tac-toe, balloon basketball, circle football, and wheelchair…

  7. Spatial compression impairs prism-adaptation in healthy individuals

    Roger Newport

    2013-05-01

    Full Text Available Neglect patients typically present with gross inattention to one side of space following damage to the contralateral hemisphere. While prism-adaptation is effective in ameliorating some neglect behaviours, the mechanisms involved and their relationship to neglect remain unclear. Recent studies have shown that conscious strategic control processes in prism-adaptation may be impaired in neglect patients, who are also reported to show extraordinarily long aftereffects compared to healthy participants. Determining the underlying cause of these effects may be the key to understanding therapeutic benefits. Alternative accounts suggest that reduced strategic control might result from a failure to detect prism-induced reaching errors properly either because a the size of the error is underestimated in compressed visual space or b pathologically increased error detection thresholds reduce the requirement for error correction. The purpose of this study was to model these two alternatives in healthy participants and to examine whether strategic control and subsequent aftereffects were abnormal compared to standard prism adaptation. Each participant completed three prism-adaptation procedures within a MIRAGE mediated reality environment with direction errors recorded before, during and after adaptation. During prism-adaptation, visual-feedback of the reach could be compressed, perturbed by noise or represented veridically. Compressed visual space significantly reduced strategic control and aftereffects compared to control and noise conditions. These results support recent observations in neglect patients, suggesting that a distortion of spatial representation may successfully model neglect and explain neglect performance while adapting to prisms.

  8. Is cognitive impairment in cirrhotic patients due to increased peroxynitrite and oxidative stress?

    Gimenez-Garzó, Carla; Urios, Amparo; Agustí, Ana; González-López, Olga; Escudero-García, Desamparados; Escudero-Sanchis, Amparo; Serra, Miguel Angel; Giner-Durán, Remedios; Montoliu, Carmina; Felipo, Vicente

    2015-04-01

    Cirrhotic patients may suffer minimal hepatic encephalopathy (MHE), with mild cognitive impairment. 3-Nitro-tyrosine levels are a good biomarker for diagnosis of the cognitive impairment and MHE in cirrhotic patients. This suggests that oxidative stress could be involved in the induction of cognitive and motor alterations in MHE. We have observed that patients with MHE show increased oxidative stress in blood compared with cirrhotic patients without MHE, with increased lipid peroxidation, DNA oxidation, protein carbonylation, 3-nitrotyrosine, oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, and GSH levels. The activities of antioxidant enzymes are enhanced in erythrocytes and mononuclear cells from patients with and without MHE compared with control subjects. Only glutathione peroxidase activity was increased in MHE patients compared with patients without MHE. Oxidative stress markers in blood, especially GSSG/GSH ratio, GSH, malondialdehyde, and 3-nitrotyrosine, correlate with deficits in attention and motor coordination. The increase in antioxidant activities in patients would be an adaptive mechanism to cope with enhanced oxidative stress, although it is not effective enough to normalize it. Our observations lead to the hypothesis that oxidative stress and increased peroxynitrite formation would mediate the synergistic effects of hyperammonemia and inflammation on cognitive and motor impairment in MHE. PMID:25557123

  9. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    Andrew S Levy

    2009-12-01

    Full Text Available Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: This review highlights a number of nitric oxide (NO-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been

  10. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    Pickering, Andrew. M.; Vojtovich, Lesya; Tower, John; Davies, Kelvin J. A.

    2012-01-01

    Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster,...

  11. Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle.

    Vandanmagsar, Bolormaa; Warfel, Jaycob D; Wicks, Shawna E; Ghosh, Sujoy; Salbaum, J Michael; Burk, David; Dubuisson, Olga S; Mendoza, Tamra M; Zhang, Jingying; Noland, Robert C; Mynatt, Randall L

    2016-05-24

    Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet-induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b-deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity. PMID:27184848

  12. Synaptic contacts impaired by styrene-7,8-oxide toxicity

    Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

  13. Increased oxidative stress and impaired antioxidant response in Lafora disease.

    Romá-Mateo, Carlos; Aguado, Carmen; García-Giménez, José Luis; Ibáñez-Cabellos, José Santiago; Seco-Cervera, Marta; Pallardó, Federico V; Knecht, Erwin; Sanz, Pascual

    2014-10-01

    Lafora Disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxirredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LD. PMID:26461389

  14. Linking Disability and Intercultural Studies: the adaptation journey of the visually impaired migrant in Ireland

    Murphy, Esther

    2011-01-01

    This study focuses on the lived experiences of the visually impaired migrant in Ireland and this is the first study to document the lives of these members of Irish society. It examines how visually impaired migrants are simultaneously adapting to their disability and a new cultural environment while living in Ireland. In so doing this study aims to link the two academic fields of Intercultural Studies and Disability Studies and theoretical underpinnings for this study are drawn and woven tog...

  15. High glucose-mediated oxidative stress impairs cell migration.

    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  16. [The role of preventing nitric oxide deficiency in the antihypertensive effect of adaptation to hypoxia].

    Mashina, S Iu; Smirin, B V; Pokidyshev, D A; Malyshev, I Iu; Liamina, N P; Senchikin, V N; Markov, Kh M; Manukhin, E B

    2001-01-01

    Shortage of endothelial nitric oxide (NO) manifested as decreased daily urinary excretion of nitrate and nitrite as well as attenuated endothelium-dependent relaxation of conduit and resistance vessels progresses with age-related increase of blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Simultaneous NO-dependent suppression of vascular contractions is, apparently, due to the inducible NO synthase activity in vascular smooth muscle specific for spontaneously hypertensive rat. Adaptation of rats to hypobaric hypoxia initiated at early hypertensive stage (at the age of 5-6 weeks) decelerates hypertension progress. The antihypertensive effect of the adaptation was accompanied by stimulation of endothelial NO synthesis and prevention of impaired NO-dependent response in isolated blood vessels. Nitric oxide stores were formed in the vascular wall of SHRSP and WKY rats at the same time. The obtained data indicate a significant role of correction of endothelial NO deficiency in the antihypertensive effect of adaptation to hypoxia. PMID:15926321

  17. Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

    Jan, J. E.; Groenveld, M.

    1993-01-01

    This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

  18. Cross-Cultural Adaptation of a Developmental Assessment for Arabic-Speaking Children with Visual Impairment

    Macrine, Sheila L.; Heji, Hayat; Sabri, Amel; Dalton, Sara

    2015-01-01

    Developmental screening has become an established component of child health programs in many developed countries. The research objective of this project was to translate and adapt a developmental assessment (Oregon Project Skills Inventory) for use with young children with visual impairments who speak Arabic. The study was prompted by the lack of…

  19. Guidelines for Assessing the Need for Adaptive Devices for Visually Impaired Pedestrians at Signalized Intersections.

    Gallagher, Brian R.; de Oca, Patricia Montes

    1998-01-01

    Presents guidelines for orientation and mobility instructors and traffic engineers to assess the need for adaptive devices to make crosswalks at signalized intersections accessible to pedestrians with visual impairments. The discussions of audible and tactile pedestrian devices, along with case examples, distinguish when each device should be…

  20. Humanin: a mitochondrial signaling peptide as a biomarker for impaired fasting glucose-related oxidative stress.

    Voigt, Annet; Jelinek, Herbert F

    2016-05-01

    Mitochondrial RNR-2 (mt-RNR2, humanin) has been shown to play a role in protecting several types of cells and tissues from the effects of oxidative stress. Humanin (HN) functions through extracellular and intracellular pathways adjusting mitochondrial oxidative phosphorylation and ATP production. Addition of HN improved insulin sensitivity in animal models of diabetes mellitus but no clinical studies have been carried out to measure HN levels in humans associated with hyperglycemia. The plasma levels of HN in participants attending a diabetes complications screening clinic were measured. Clinical history and anthropometric data were obtained from all participants. Plasma levels of HN were measured by a commercial ELISA kit. All data were analyzed applying nonparametric statistics and general linear modeling to correct for age and gender. A significant decrease (P = 0.0001) in HN was observed in the impaired fasting glucose (IFG) group (n = 23; 204.84 ± 92.87 pg mL(-1)) compared to control (n = 58; 124.3 ± 83.91 pg mL(-1)) consistent with an adaptive cellular response by HN to a slight increase in BGL. PMID:27173674

  1. Oxidative Injury and Neuropathy in Diabetes and Impaired Glucose Tolerance

    Russell, James W.; Berent-Spillson, Alison; Vincent, Andrea M.; Freimann, Catherine L.; Sullivan, Kelli A; Eva L Feldman

    2008-01-01

    Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor acti...

  2. Hereditary cerebellar ataxia progressively impairs force adaptation during goal-directed arm movements.

    Maschke, Matthias; Gomez, Christopher M; Ebner, Timothy J; Konczak, Jürgen

    2004-01-01

    We investigated how humans with hereditary cerebellar degeneration [spinocerebellar ataxia (SCA) type 6 and 8, n = 9] and age- and sex-matched healthy controls (n = 9) adapted goal-directed arm movements to an unknown external force field. We tested whether learning could be generalized to untrained regions in the workspace, an aspect central to the idea of an internal model, and if any learning could be retained. After removal of the force field, SCA patients showed little or no learning-related aftereffects indicating that repeated force-field exposure never led to successful force compensation. In contrast, healthy control subjects quickly adapted their movements to the new force field. The difference in force adaptation was significant for movements to targets that required both the shoulder and elbow joint (P < 0.001). Moreover, the generalization of learned movements to targets outside the learned workspace was prevented by the cerebellar degeneration (P < 0.01). Retention of force adaptation was significantly lower in SCA patients (P = 0.003). The severity of ataxia in SCA patients correlated negatively with the extent of learning (r = -0.84, P = 0.004). Our findings imply that progressive loss of cerebellar function gradually impairs force adaptation. The failure to generalize learning suggests that cerebellar degeneration prevents the formation of an internal representation of the limb dynamics. PMID:13679403

  3. A study of self-adaptive transmission control architectures in impairment-aware transparent WDM networks

    Liu, Yongjun; Gu, Wanyi; Zhang, Jie; Wang, Lei; Zhang, Hua; Ren, Jia

    2008-11-01

    This paper investigates the self-adaptive transmission control architectures (SATCA) in impairment-aware transparent WDM networks. Two approaches are proposed for the implementation of SATCA. Simulations are conducted to evaluate the benefits obtained by applying SATCA. In the transparent WDM networks, the control plane based on GMPLS protocols introduces connection intelligence into the optical networks. However, since dynamic setup/teardown of connection or fast re-route may introduce unpredictable physical impairments(i.e., fluctuation of optical power and residual dispersion) into the lightpath and in all-optical networks these physical impairments will accumulate along the lightpath, the optical signal quality and service survivablity can not be guaranteed. Therefore, the future optical networks should also have self-adaptive optical transmission ability to guarantee the physical quality of connections. Two proposed approaches to implement SATCA separately introduce extensions to routing protocols (routing-based approach) and signalling protocols (signaling-based approach) of GMPLS. For both approaches, the lightpath quality estimation (LQE) module, which is applied to evaluate the lightpath's QOT and make the compensation budgets, should be added to the optical control plane. The purpose of the simulations is to research the effect of SATCA approaches on the lightpath performance. We suppose that if OSNR or RD is out of the acceptable range, the lightpath is refused. So the blocking probability can be used for comparison among the signaling-based approach,routing-based approach and the traditional approach which is without considering physical impairments. Since the lightpath performance can be improved in the SATCA approach, the quality of lightpath is greatly guaranteed.

  4. The Muscle Oxidative Regulatory Response to Acute Exercise Is Not Impaired in Less Advanced COPD Despite a Decreased Oxidative Phenotype

    Slot, Ilse G. M.; Bram van den Borst; Hellwig, Valéry A. C. V.; Esther Barreiro; Schols, Annemie M. W. J.; Gosker, Harry R.

    2014-01-01

    Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in...

  5. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation

    Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

    2014-01-01

    Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citric acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  6. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  7. The role of nitrogen oxides in human adaptation to hypoxia

    Levett, Denny Z; Fernandez, Bernadette O.; Riley, Heather L.; Martin, Daniel S; Kay Mitchell; Leckstrom, Carl A.; Can Ince; Brian J. Whipp; Mythen, Monty G; Montgomery, Hugh E.; Grocott, Mike P.; Martin Feelisch

    2011-01-01

    Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxide...

  8. Impact of Adaptive Materials on Teachers and their Students with Visual Impairments in Secondary Science and Mathematics Classes

    Rule, Audrey C.; Stefanich, Greg P.; Boody, Robert M.; Peiffer, Belinda

    2011-04-01

    Science, technology, engineering, and mathematics (STEM) fields, important in today's world, are underrepresented by students with disabilities. Students with visual impairments, although cognitively similar to sighted peers, face challenges as STEM subjects are often taught using visuals. They need alternative forms of access such as enlarged or audio-converted text, tactile graphics, and involvement in hands-on science. This project focused on increasing teacher awareness of and providing funds for the purchase of supplemental adaptive resources, supplies, and equipment. We examined attitude and instructional changes across the year of the programme in 15 science and mathematics teachers educating students with visual impairments. Positive changes were noted from pretest to posttest in student and teacher perspectives, and in teacher attitudes towards students with disabilities in STEM classes. Teachers also provided insights into their challenges and successes through a reflective narrative. Several adolescent students resisted accommodations to avoid appearing conspicuous to peers. Teachers implemented three strategies to address this: providing the adaptations to all students in the class; convincing the student of the need for adaptation; and involving the class in understanding and accepting the student's impairment. A variety of teacher-created adaptations for various science and mathematics labs are reported. Another finding was many adaptations provided for the student with visual impairment benefitted the entire class. This study supports the claim that given knowledgeable, supportive teachers, and with appropriate accommodations such as tactile or auditory materials, students with visual impairments can be as successful and engaged as other students in science and mathematics.

  9. Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women

    Koyama, A; Stone, K.; Yaffe, K

    2012-01-01

    We investigated the association between serum level of oxidized low-density lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive impairment) among 572 nondemented community-dwelling women from a prospective cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed cognitive impairment; and this did not differ by tertile of baseline oxLDL level (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95% confidence interval, 0.63-1.43)...

  10. Impaired adaptation of gastrointestinal motility following chronic stress in maternally separated rats.

    Bülbül, Mehmet; Babygirija, Reji; Cerjak, Diana; Yoshimoto, Sazu; Ludwig, Kirk; Takahashi, Toku

    2012-04-01

    Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats. PMID:22241856

  11. Oxidative Stress Impairs Learning and Memory in apoE Knockout Mice

    Evola, Marianne; Hall, Allyson; Wall, Trevor; Young, Alice; Grammas, Paula

    2010-01-01

    Cardiovascular risk factors, such as oxidative stress and elevated lipids, are linked to the development of cognitive impairment. A mediator common to both stressors is the apolipoprotein E (apoE). The objectives of this study are to determine the effects of apoE deficiency and diet-induced systemic oxidative stress in mice on vascular expression of inflammatory proteins and on cognitive function. Mice are placed on a diet enriched in homocysteine for fifteen weeks and then assessed for spati...

  12. Maternal diabetes impairs oxidative and inflammatory response in murine placenta

    Mohamed I. Saad; Abdelkhalek, Taha M.; Moustafa M. Saleh; Haiba, Maha M.; Tawfik, Shady H.; Maher A. Kamel

    2016-01-01

    Placenta is the major exchange surface between mother and fetus and plays a pivotal role in fetal development. A better understanding of the mechanisms by which diabetes alters placental function may allow better management of diabetes pregnancies. In this study, we attempt to investigate the effect of diabetic milieu with and without malformation on placental function. In order to investigate the impact of diabetic pregnancy on oxidative stress, endothelial and vascular functions of placenta...

  13. Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?

    Leite, Natália Rodrigues Pereira; Siqueira de Medeiros, Mariana; Mury, Wanda Vianna; Matsuura, Cristiane; Perszel, Monique Bandeira Moss; Noronha Filho, Gerson; Brunini, Tatiana Mc; Mendes-Ribeiro, Antônio Claúdio

    2016-08-01

    Epidemiological evidence has shown that platelet activation markers are consistently elevated in obesity, contributing to its prothrombotic state. In order to improve the understanding of the regulation of platelet function in obesity, the aim of this study was to investigate the l-arginine-nitric oxide (NO) pathway in obese adults without other cardiovascular risk factor. Seventeen obese (body mass index [BMI] 35.9±1.0 kg/m(2) ) and eighteen age-matched normal weight subjects (BMI 22.0±0.6 kg/m(2) ) were included in this study. l-arginine influx was measured with incubation of l-[(3) H]-arginine. NO synthase (NOS) and arginase activities were determined by the citrulline assay and the conversion of l-[(14) C]-arginine to [(14) C]-urea, respectively. Cyclic guanosine monophosphate (cGMP) content was evaluated by enzyme-linked immunosorbent assay. In addition, the study analyzed: platelet aggregation; intraplatelet antioxidant enzymes, via superoxide dismutase (SOD) and catalase activities; and systemic levels of l-arginine, fibrinogen, and C-reactive protein (CRP). Obese patients presented a significant decrease of platelet l-arginine influx, NOS activity, and cGMP levels, along with platelet hyperaggregability. On the presence of NO donor, platelet aggregation was similar between the groups. The fibrinogen and CRP systemic levels were significantly higher and SOD activity was reduced in obesity. No significant differences were observed in plasma levels of l-arginine and intraplatelet arginase and catalase activities between groups. The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity. PMID:27145241

  14. The muscle oxidative regulatory response to acute exercise is not impaired in less advanced COPD despite a decreased oxidative phenotype.

    Slot, Ilse G M; van den Borst, Bram; Hellwig, Valéry A C V; Barreiro, Esther; Schols, Annemie M W J; Gosker, Harry R

    2014-01-01

    Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in COPD. For this, 28 patients with less advanced COPD (age 65 ± 7 yrs, FEV1 59 ± 16% predicted) and 15 age- and gender-matched healthy controls performed an incremental cycle ergometry test. The Oxphen response to exercise was determined by the measurement of gene expression levels of Oxphen markers in pre and 4h-post exercise quadriceps biopsies. Because exercise-induced hypoxia and oxidative stress may interfere with Oxphen response, oxygen saturation and oxidative stress markers were assessed as well. Regardless of oxygen desaturation and absolute exercise intensities, the Oxphen regulatory response to exercise was comparable between COPD patients and controls with no evidence of increased oxidative stress. In conclusion, the muscle Oxphen regulatory response to acute exercise is not blunted in less advanced COPD, regardless of exercise-induced hypoxia. Hence, this study provides further rationale for incorporation of exercise training as integrated part of disease management to prevent or slow down loss of muscle Oxphen and related functional impairment in COPD. PMID:24587251

  15. The muscle oxidative regulatory response to acute exercise is not impaired in less advanced COPD despite a decreased oxidative phenotype.

    Ilse G M Slot

    Full Text Available Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen. Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in COPD. For this, 28 patients with less advanced COPD (age 65 ± 7 yrs, FEV1 59 ± 16% predicted and 15 age- and gender-matched healthy controls performed an incremental cycle ergometry test. The Oxphen response to exercise was determined by the measurement of gene expression levels of Oxphen markers in pre and 4h-post exercise quadriceps biopsies. Because exercise-induced hypoxia and oxidative stress may interfere with Oxphen response, oxygen saturation and oxidative stress markers were assessed as well. Regardless of oxygen desaturation and absolute exercise intensities, the Oxphen regulatory response to exercise was comparable between COPD patients and controls with no evidence of increased oxidative stress. In conclusion, the muscle Oxphen regulatory response to acute exercise is not blunted in less advanced COPD, regardless of exercise-induced hypoxia. Hence, this study provides further rationale for incorporation of exercise training as integrated part of disease management to prevent or slow down loss of muscle Oxphen and related functional impairment in COPD.

  16. Does Vitamin C and E Supplementation Impair the Favorable Adaptations of Regular Exercise?

    Michalis G. Nikolaidis

    2012-01-01

    Full Text Available The detrimental outcomes associated with unregulated and excessive production of free radicals remains a physiological concern that has implications to health, medicine and performance. Available evidence suggests that physiological adaptations to exercise training can enhance the body’s ability to quench free radicals and circumstantial evidence exists to suggest that key vitamins and nutrients may provide additional support to mitigate the untoward effects associated with increased free radical production. However, controversy has risen regarding the potential outcomes associated with vitamins C and E, two popular antioxidant nutrients. Recent evidence has been put forth suggesting that exogenous administration of these antioxidants may be harmful to performance making interpretations regarding the efficacy of antioxidants challenging. The available studies that employed both animal and human models provided conflicting outcomes regarding the efficacy of vitamin C and E supplementation, at least partly due to methodological differences in assessing oxidative stress and training adaptations. Based on the contradictory evidence regarding the effects of higher intakes of vitamin C and/or E on exercise performance and redox homeostasis, a permanent intake of non-physiological dosages of vitamin C and/or E cannot be recommended to healthy, exercising individuals.

  17. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  18. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  19. Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

    Toda, Noboru; Okamura, Tomio

    2016-09-01

    Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures. PMID:27417104

  20. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-01-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (−40%) through reduced glucose tr...

  1. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine

    Omar M.E. Abdel-Salam; El-Mosallamy, Aliaa E.M.K.; El-Shamarka, Marwa El-Sayed; Salem, Neveen A.; Amany A. SLEEM

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg),...

  2. Behavioral impairments and changes of nitric oxide and inducible nitric oxide synthase in the brains of molarless KM mice.

    Pang, Qian; Hu, Xingxue; Li, Xinya; Zhang, Jianjun; Jiang, Qingsong

    2015-02-01

    More studies showed that as a common disorder in senior population, loss of teeth could adversely affect human cognitive function, and nitric oxide (NO) might play an important role in the cognitive function. However, the underlying mechanism has not yet been well-established. The objectives of this study are to evaluate behavior changes of KM mice after loss of molars, and levels of NO and inducible nitric oxide synthase (iNOS) in the brain in molarless condition. It is hypothesized that loss of molars of the mice tested results in the cognitive impairments and that the process is mediated by NO in the brain through the signaling pathways. Morris water maze is used to test the behavioral changes after 8 weeks of the surgery. The changes of NO and iNOS are evaluated by using Griess assay, western blot, and immunohistochemistry method. The results show that 8 weeks after loss of molars, the spatial learning and memory of KM mice impair and the levels of NO and iNOS in mice hippocampus increase. These findings suggest that molar extraction is associated with the behavioral impairment, and that the changes of NO and iNOS in the hippocampus may be involved in the behavioral changes in the molarless condition. PMID:25447296

  3. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  4. Rapid Evolution of Culture-Impaired Bacteria During Adaptation to Biofilm Growth

    Jon Penterman; Dao Nguyen; Erin Anderson; Benjamin J. Staudinger; Everett P. Greenberg; Joseph S. Lam; Pradeep K. Singh

    2014-01-01

    Biofilm growth increases the fitness of bacteria in harsh conditions. However, bacteria from clinical and environmental biofilms can exhibit impaired growth in culture, even when the species involved are readily culturable and permissive conditions are used. Here, we show that culture-impaired variants of Pseudomonas aeruginosa arise rapidly and become abundant in laboratory biofilms. The culture-impaired phenotype is caused by mutations that alter the outer-membrane lipopolysaccharide struct...

  5. Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection.

    Justin M Richner

    2015-07-01

    Full Text Available Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV, an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN. Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.

  6. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

    Cervellati, Carlo; Sticozzi, Claudia; Romani, Arianna; Belmonte, Giuseppe; De Rasmo, Domenico; Signorile, Anna; Cervellati, Franco; Milanese, Chiara; Mastroberardino, Pier Giorgio; Pecorelli, Alessandra; Savelli, Vinno; Forman, Henry J; Hayek, Joussef; Valacchi, Giuseppe

    2015-10-01

    A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment. PMID:26189585

  7. Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity.

    Jiang, Weijun; Xiong, Lei; Bin Yang; Li, Weiwei; Zhang, Jing; Zhou, Qing; Wu, Qiuyue; Li, Tianfu; Zhang, Cui; Zhang, Mingchao; Xia, Xinyi

    2016-01-01

    To investigate the effect of hyperhomocysteinaemia (HHCy) on penile erectile function in a rat model, a methionine-rich diet was used in which erectile function, the reproductive system, and nitric oxide synthase were characterized. The intracavernous pressure, apomorphine experiments, measurement of oxidative stress, hematoxylin and eosin staining, immunohistochemistry analysis, reverse transcription-polymerase chain reactions and measurement of endothelial nitric oxide synthase activity were utilized. Our results showed that erections in the middle-dose, high-dose, and interference (INF) groups were significantly lower than the control (P < 0.05). INF group, being fed with vitamins B and folic acid, demonstrated markedly improved penile erections compared with the middle-dose group (P < 0.05). HHCy-induced eNOS and phospho-eNOS protein expression was reduced and the antioxidant effect was markedly impaired. The data of the present data provide evidence that HHCy is a vascular risk factor for erectile dysfunction by impairing cavernosa endothelial nitric oxide synthase activity. Intake of vitamins B can alleviate this abnormality. PMID:27221552

  8. Mitochondrial impairment and oxidative stress compromise autophagosomal degradation of α-synuclein in oligodendroglial cells.

    Pukaß, Katharina; Goldbaum, Olaf; Richter-Landsberg, Christiane

    2015-10-01

    α-Synuclein (α-syn)-containing glial cytoplasmic inclusions originating in oligodendrocytes are characteristically observed in multiple system atrophy. The mechanisms of glial cytoplasmic inclusion formation remain rather elusive. α-Syn over-expression, uptake from the environment, oxidative stress or impairment of the proteolytic degradation systems have been discussed. Here, we investigated whether in oligodendrocytes autophagy plays a major role in the degradation and aggregation of endogenously expressed α-syn and of α-syn taken up from the extracellular environment. Furthermore, we studied whether in cells with impaired mitochondria the accumulation and aggregation of exogenously added α-syn is promoted. Using primary cultures of rat brain oligodendrocytes and an oligodendroglial cell line, genetically engineered to express green fluorescent protein-microtubule-associated light chain 3 with or without α-syn to monitor the autophagic flux, we demonstrate that both exogenously applied α-syn and α-syn stably expressed endogenously are effectively degraded by autophagy and do not affect the autophagic flux per se. Mitochondrial impairment with the protonophore carbonyl cyanide 3-chlorophenylhydrazone or 3-nitropropionic acid disturbs the autophagic pathway and leads to the accumulation of exogenously applied α-syn and enhances its propensity to form aggregates intracellularly. Thus, mitochondrial dysfunction and oxidative stress, which occur over time and are significant pathological features in synucleinopathies, have an impact on the autophagic pathway and participate in pathogenesis. Glial cytoplasmic inclusions are characteristically observed in multiple system atrophy, their occurrence might be related to failure in protein degradation systems. Here, we show that in oligodendrocytes autophagy is the major route of α-synuclein degradation which is either endogenously expressed or added exogenously (1, 2). Mitochondrial impairment (3) disturbs the

  9. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment

    Qian Guo

    2015-01-01

    Full Text Available The clinical application of doxorubicin (DOX is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH to oxidized glutathione (GSSG. Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α and nuclear respiratory factor 1 (NRF1, as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

  10. Impairment of extramitochondrial oxidative phosphorylation in mouse rod outer segments by blue light irradiation.

    Calzia, Daniela; Panfoli, Isabella; Heinig, Nora; Schumann, Ulrike; Ader, Marius; Traverso, Carlo Enrico; Funk, Richard H W; Roehlecke, Cora

    2016-06-01

    Exposure to short wavelength light causes increased reactive oxygen intermediates production in the outer retina, particularly in the rod Outer Segments (OS). Consistently, the OS were shown to conduct aerobic ATP production through the ectopic expression of the electron transfer chain complexes I-IV and F1Fo-ATP synthase. These facts prompted us to verify if the oxidative phosphorylation in the OS is implied in the oxidative damage of the blue-light (BL) treated OS, in an organotypic model of mouse retina. Whole mouse eyeball cultures were treated with short wavelength BL (peak at 405 nm, output power 1 mW/cm(2)) for 6 h. Immunogold transmission electron microscopy confirmed the expression of Complex I and F1Fo-ATP synthase in the OS. In situ histochemical assays on unfixed sections showed impairment of respiratory Complexes I and II after BL exposure, both in the OS and IS, utilized as a control. Basal O2 consumption and ATP synthesis were impaired in the OS purified from blue-light irradiated eyeball cultures. Electron transfer capacity between Complex I and II as well as activity of Complexes I and II was decreased in blue-light irradiated purified OS. The severe malfunctioning of the OS aerobic respiratory capacity after 6 h BL treatment may be the consequence of a self-induced damage. BL exposure would cause an initial over-functioning of both the phototransduction and respiratory chain, with reactive oxygen species production. In a self-renewal vicious cycle, membrane and protein oxidative damage, proton leakage and uncoupling, would impair redox chains, perpetuating the damage and causing hypo-metabolism with eventual apoptosis of the rod. Data may shed new light on the rod-driven retinopathies such as Age Related Macular Degeneration, of which blue-light irradiated retina represents a model. PMID:27059514

  11. KSR2 Mutations Are Associated with Obesity, Insulin Resistance, and Impaired Cellular Fuel Oxidation

    Pearce, Laura R.; Atanassova, Neli; Banton, Matthew C.; Bottomley, Bill; van der Klaauw, Agatha A.; Revelli, Jean-Pierre; Hendricks, Audrey; Keogh, Julia M.; Henning, Elana; Doree, Deon; Jeter-Jones, Sabrina; Garg, Sumedha; Bochukova, Elena G.; Bounds, Rebecca; Ashford, Sofie

    2013-01-01

    Summary Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEK-ERK pathway and impair cellular fatty acid oxidation and glucose oxida...

  12. Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress.

    Jaiswal, Manish; Haelterman, Nele A; Sandoval, Hector; Xiong, Bo; Donti, Taraka; Kalsotra, Auinash; Yamamoto, Shinya; Cooper, Thomas A; Graham, Brett H; Bellen, Hugo J

    2015-07-01

    Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration--defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise. PMID:26176594

  13. Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.

    Covarrubias-Pinto, Adriana; Moll, Pablo; Solís-Maldonado, Macarena; Acuña, Aníbal I; Riveros, Andrea; Miró, María Paz; Papic, Eduardo; Beltrán, Felipe A; Cepeda, Carlos; Concha, Ilona I; Brauchi, Sebastián; Castro, Maite A

    2015-12-01

    Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity. PMID:26456058

  14. Oxidative stress and APO E polymorphisms in Alzheimer's disease and in mild cognitive impairment.

    Chico, L; Simoncini, C; Lo Gerfo, A; Rocchi, A; Petrozzi, L; Carlesi, C; Volpi, L; Tognoni, G; Siciliano, G; Bonuccelli, U

    2013-08-01

    A number of evidences indicates oxidative stress as a relevant pathogenic factor in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Considering its recognized major genetic risk factors in AD, apolipoprotein (APO E) has been investigated in several experimental settings regarding its role in the process of reactive oxygen species (ROS) generation. The aim of this work has been to evaluate possible relationships between APO E genotype and plasma levels of selected oxidative stress markers in both AD and MCI patients. APO E genotypes were determined using restriction enzyme analysis. Plasma levels of oxidative markers, advanced oxidation protein products, iron-reducing ability of plasma and, in MCI, activity of superoxide dismutases were evaluated using spectrophotometric analysis. We found, compared to controls, increased levels of oxidized proteins and decreased values of plasma-reducing capacity in both AD patients (p < 0.0001) and MCI patients (p < 0.001); the difference between AD and MCI patients was significant only for plasma-reducing capacity (p < 0.0001), the former showing the lowest values. Superoxide dismutase activity was reduced, although not at statistical level, in MCI compared with that in controls. E4 allele was statistically associated (p < 0.05) with AD patients. When comparing different APO E genotype subgroups, no difference was present, as far as advanced oxidation protein products and iron-reducing ability of plasma levels were concerned, between E4 and non-E4 carriers, in both AD and MCI; on the contrary, E4 carriers MCI patients showed significantly decreased (p < 0.05) superoxide dismutase activity with respect to non-E4 carriers. This study, in confirming the occurrence of oxidative stress in AD and MCI patients, shows how it can be related, at least for superoxide dismutase activity in MCI, to APO E4 allele risk factor. PMID:23668794

  15. The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain".

    Gaman, Amelia Maria; Uzoni, Adriana; Popa-Wagner, Aurel; Andrei, Anghel; Petcu, Eugen-Bogdan

    2016-05-01

    Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis. PMID:27330845

  16. Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice.

    Al-Amin, Md Mamun; Reza, Hasan Mahmud; Saadi, Hasan Mahmud; Mahmud, Waich; Ibrahim, Abdirahman Adam; Alam, Musrura Mefta; Kabir, Nadia; Saifullah, A R M; Tropa, Sarjana Tarannum; Quddus, A H M Ruhul

    2016-04-15

    Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits. PMID:26927754

  17. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases.

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-05-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (-40%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (-70%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser(307)phosphorylation. This process was largely mediated by the activation of the inhibitor of kappaB-kinase beta (IKKbeta) and the c-Jun NH(2)-terminal kinase (JNK). Moreover, the activation of IKKbeta positively regulated the nuclear content of nuclear factor kappaB (NF-kappaB), by inactivating the inhibitor of NF-kappaB (IkappaBalpha). The activated NF-kappaB further impaired per se GLUT4 functionality. Specific inhibitors of IKKbeta, JNK, and NF-kappaB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance. PMID:19136667

  18. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning.

    Sarah J Borengasser

    Full Text Available In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001 and increases in RER values (p<0.001, which were further exacerbated by high fat diet (45% kcals from fat consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012 and mitochondrial protein content (p = 0.002, electron transport chain complexes (II, III, and ATPase, and fasting PGC-1α mRNA expression (p<0.001. Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p<0.001 but was also hyperacetylated in offspring of obese dams (p<0.005 suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD.

  19. Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

    Nyhan, Daniel; Kim, Soonyul; Dunbar, Stacey; Li, Dechun; Shoukas, Artin; Berkowitz, Dan E.

    2002-01-01

    Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

  20. Oxidative stress impairs the heat stress response and delays unfolded protein recovery.

    Masaaki Adachi

    Full Text Available BACKGROUND: Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability. PRINCIPAL FINDINGS: Pretreatment of hydrogen peroxide (H(2O(2 specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2O(2 exposure impaired the HSP40/HSP70 induction as heat shock response (HSR and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2O(2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2O(2-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2O(2-mediated enhanced heat sensitivity. CONCLUSIONS: H(2O(2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.

  1. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  2. Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension, and atherogenesis?

    Walsh, Thomas

    2012-01-31

    Endothelial-derived nitric oxide (NO) is responsible for maintaining continuous vasodilator tone and for regulating local perfusion and systemic blood pressure. It also has significant antiproliferative effects on vascular smooth muscle and platelet anti-aggregatory effects. Impaired endothelial-dependent (NO mediated) vasorelaxation is observed in most animal and human models of healthy aging. It also occurs in age-associated conditions such as atherosclerosis and hypertension. Such "endotheliopathy" increases vascular risk in older adults. Studies have indicated that pharmacotherapeutic intervention with angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase inhibitors may improve NO-mediated vasomotor function. This review, evaluates the association between impaired endothelial NO bioavailability, accelerated vascular aging, and the age-associated conditions hypertension and atherogenesis. This is important, because pharmacotherapy aimed at improving endothelial NO bioavailability could modify age-related vascular disease and transform age into a potentially modifiable vascular risk factor, at least in a subpopulation of older adults.

  3. Age-associated memory impairment. Assessing the role of nitric oxide.

    Meyer, R C; Spangler, E L; Kametani, H; Ingram, D K

    1998-11-20

    Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors. We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors. No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release. Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats. PMID:9928439

  4. Neutrophilic iron oxidizers adapted to highly oxic environments

    Gülay, Arda; Musovic, Sanin; Albrechtsen, Hans-Jørgen;

    carbon) while oxygen (O2) is the electron acceptor provided during the aeration process. Numerous previous studies have described neutrophilic iron oxidizers as a bacterial guild with a special niche preference, especially the transition zone between aerobic and anoxic regions, where abiotic chemical...... indicate that neutrophilic iron oxidizers in highly oxic environments like drinking water treatment systems can be abundant (5 E+04 to 7 E+05 cells per gram of wet sand material). It was furthermore observed that the diversity of the cultivated dominant iron oxidizers differs substantially from those...

  5. Effect of Lactobacillus pentosus-Fermented Artemisiae Argi Folium on Nitric Oxide Production of Macrophage impaired with Various Toxicants

    Wansu Park

    2009-01-01

    Objectives : The purpose of this study is to investigate the effect of Water Extract from Lactobacillus pentosus-fermented ARTEMISIAE ARGI FOLIUM (AFL) on nitric oxide production of mouse macrophage Raw 264.7 cells impaired by various toxicants such as gallic acid, EtOH, nicotine, acetaminophen, and acetaldehyde. Methods : ARTEMISIAE ARGI FOLIUM was fermented with Lactobacillus pentosus and extracted by water. Nitric oxide production of mouse macrophage Raw 264.7 cells was measured by Grie...

  6. Normal adaptations to exercise despite protection against oxidative stress

    Higashida, Kazuhiko; Kim, Sang Hyun; Higuchi, Mitsuru; Holloszy, John O.; Han, Dong-Ho

    2011-01-01

    It has been reported that supplementation with the antioxidant vitamins C and E prevents the adaptive increases in mitochondrial biogenesis and GLUT4 expression induced by endurance exercise. We reevaluated the effects of these antioxidants on the adaptive responses of rat skeletal muscle to swimming in a short-term study consisting of 9 days of vitamins C and E with exercise during the last 3 days and a longer-term study consisting of 8 wk of antioxidant vitamins with exercise during the las...

  7. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  8. 5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

    Adriana Secatto; Lilian Cataldi Rodrigues; Carlos Henrique Serezani; Simone Gusmão Ramos; Marcelo Dias-Baruffi; Lúcia Helena Faccioli; Medeiros, Alexandra I.

    2012-01-01

    5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/-) mice showed an intense in...

  9. Cross-cultural adaptation and validation of a Brazilian version of an instrument to assess impairments related to oral functioning of people with Down syndrome

    Bonanato Karina; Pordeus Isabela A; Compart Thiago; Oliveira Ana Cristina; Allison Paul J; Paiva Saul M

    2013-01-01

    Abstract Background An instrument was developed in Canada to assess impairments related to oral functioning of individuals with four years of age or older with Down syndrome (DS). The present study attempted to carry out the cross-cultural adaptation and validation of the instrument for the Brazilian Portuguese language and to test its reliability and validity. Findings After translation and cross-cultural adaptation, the instrument was tested on caregivers of people with DS. Clinical examina...

  10. Regional coherence evaluation in mild cognitive impairment and Alzheimer's disease based on adaptively extracted magnetoencephalogram rhythms

    This study assesses the connectivity alterations caused by Alzheimer's disease (AD) and mild cognitive impairment (MCI) in magnetoencephalogram (MEG) background activity. Moreover, a novel methodology to adaptively extract brain rhythms from the MEG is introduced. This methodology relies on the ability of empirical mode decomposition to isolate local signal oscillations and constrained blind source separation to extract the activity that jointly represents a subset of channels. Inter-regional MEG connectivity was analysed for 36 AD, 18 MCI and 26 control subjects in δ, θ, α and β bands over left and right central, anterior, lateral and posterior regions with magnitude squared coherence—c(f). For the sake of comparison, c(f) was calculated from the original MEG channels and from the adaptively extracted rhythms. The results indicated that AD and MCI cause slight alterations in the MEG connectivity. Computed from the extracted rhythms, c(f) distinguished AD and MCI subjects from controls with 69.4% and 77.3% accuracies, respectively, in a full leave-one-out cross-validation evaluation. These values were higher than those obtained without the proposed extraction methodology

  11. Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

    Jun Jiang

    2014-01-01

    Full Text Available Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA. Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF. We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP and phosphocreatine (PCr developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

  12. Ammonia-oxidizing archaea have better adaptability in oxygenated/hypoxic alternant conditions compared to ammonia-oxidizing bacteria.

    Liu, Shuai; Hu, Baolan; He, Zhanfei; Zhang, Bin; Tian, Guangming; Zheng, Ping; Fang, Fang

    2015-10-01

    Ammonia oxidation is performed by both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Few studies compared the adaptability of AOA and AOB for oxygenated/hypoxic alternant conditions in water-level-fluctuating zones. Here, using qPCR and 454 high-throughput sequencing of functional amoA genes of AOA and AOB, we examined the changes of abundances, diversities, and community structures of AOA and AOB in periodically flooded soils compared to the non-flooded soils in Three Gorges Reservoir. The increased AOA operational taxonomic unit (OTU) numbers and the higher ratios of abundance (AOA:AOB) in the periodically flooded soils suggested AOA have better adaptability for oxygenated/hypoxic alternant conditions in the water-level-fluctuating zones in the Three Gorges Reservoir and probably responsible for the ammonia oxidation there. Canonical correspondence analysis (CCA) showed that oxidation-reduction potential (ORP) had the most significant effect on the community distribution of AOA (p amoA gene abundances (AOA:AOB) (p < 0.05). ORP was also significantly positively correlated with AOB abundance (p < 0.05). PMID:26099334

  13. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  14. Isolation and characterization of Caulobacter mutants impaired in adaptation to stationary phase

    Italiani Valéria C. S.

    2003-01-01

    Full Text Available The entry into stationary phase causes a change in the pattern of gene expression of bacteria, when the cells must express a whole set of genes involved mainly with resistance to starvation and to environmental stresses. As an attempt to identify genes important for the survival of Caulobacter crescentus in stationary phase, we have screened a library of 5,000 clones generated by random transposon mutagenesis for mutants that showed reduced viability after prolonged growth. Four clones were selected, which displayed either lower viability or a longer time of recovery from stationary phase. The genes disrupted were identified, and the gene products were found to be mainly involved with amino acid metabolism (glutamate N-acetyltransferase, 4-hydroxyphenylpyruvate dioxygenase and L-aspartate oxidase or with recombination (exonuclease RecJ. Each mutant was tested for resistance to stresses, such as oxidative, saline, acidic, heat and UV exposure, showing different responses. Although the mutations obtained were not in genes involved specifically in stationary phase, our results suggest that amino acids metabolism may play an important role in keeping viability during this growth phase.

  15. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

    Malkus Kristen A

    2009-06-01

    Full Text Available Abstract While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.

  16. Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

    Aragonès Gemma; Saavedra Paula; Heras Mercedes; Cabré Anna; Girona Josefa; Masana Lluís

    2012-01-01

    Abstract Background Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation a...

  17. The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson's disease.

    Gerstenberger, Julia; Bauer, Anne; Helmschrodt, Christin; Richter, Angelika; Richter, Franziska

    2016-05-01

    Development of disease modifying therapeutics for Parkinson's disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models. PMID:26880341

  18. Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses

    Zhang, Weipeng

    2013-11-11

    Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses.

  19. Gamma radiation induces growth retardation, impaired egg production, and oxidative stress in the marine copepod Paracyclopina nana

    Won, Eun-Ji; Lee, Jae-Seong, E-mail: jslee2@skku.edu

    2014-05-01

    Highlights: • Mortality was increased with a dose dependent manner in ovigerous females of Paracyclopina nana. • Developmental impairments were observed in gamma irradiated nauplii. • Ovigerous females exposed to more than 50 Gy could not have normal two bilateral egg sacs. • Oxidative levels increased with antioxidant enzyme activities in the gamma irradiated P. nana. • The molecular indices (antioxidant enzymes and heat shock protein) were also increased. - Abstract: Accidental nuclear radioisotope release into the ocean from nuclear power plants is of concern due to ecological and health risks. In this study, we used the marine copepod Paracyclopina nana to examine the effects of radioisotopes on marine organisms upon gamma radiation, and to measure the effects on growth and fecundity, which affect population and community structure. Upon gamma radiation, mortality (LD50 – 96 h = 172 Gy) in P. nana was significantly increased in a dose-dependent manner in ovigerous P. nana females. For developmental impairment of gamma-irradiated nauplii, we observed growth retardation; in over 30 Gy-irradiated groups, offspring did not grow to adults. Particularly, over 50 Gy-irradiated ovigerous P. nana females did not have normal bilateral egg sacs, and their offspring did not develop normally to adulthood. Additionally, at over 30 Gy, we found dose-dependent increases in oxidative levels with elevated antioxidant enzyme activities and DNA repair activities. These findings indicate that gamma radiation can induce oxidative stress and DNA damage with growth retardation and impaired reproduction.

  20. Gamma radiation induces growth retardation, impaired egg production, and oxidative stress in the marine copepod Paracyclopina nana

    Highlights: • Mortality was increased with a dose dependent manner in ovigerous females of Paracyclopina nana. • Developmental impairments were observed in gamma irradiated nauplii. • Ovigerous females exposed to more than 50 Gy could not have normal two bilateral egg sacs. • Oxidative levels increased with antioxidant enzyme activities in the gamma irradiated P. nana. • The molecular indices (antioxidant enzymes and heat shock protein) were also increased. - Abstract: Accidental nuclear radioisotope release into the ocean from nuclear power plants is of concern due to ecological and health risks. In this study, we used the marine copepod Paracyclopina nana to examine the effects of radioisotopes on marine organisms upon gamma radiation, and to measure the effects on growth and fecundity, which affect population and community structure. Upon gamma radiation, mortality (LD50 – 96 h = 172 Gy) in P. nana was significantly increased in a dose-dependent manner in ovigerous P. nana females. For developmental impairment of gamma-irradiated nauplii, we observed growth retardation; in over 30 Gy-irradiated groups, offspring did not grow to adults. Particularly, over 50 Gy-irradiated ovigerous P. nana females did not have normal bilateral egg sacs, and their offspring did not develop normally to adulthood. Additionally, at over 30 Gy, we found dose-dependent increases in oxidative levels with elevated antioxidant enzyme activities and DNA repair activities. These findings indicate that gamma radiation can induce oxidative stress and DNA damage with growth retardation and impaired reproduction

  1. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  2. Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero.

    Cheng, Xinghua; Chapple, Sarah J; Patel, Bijal; Puszyk, William; Sugden, David; Yin, Xiaoke; Mayr, Manuel; Siow, Richard C M; Mann, Giovanni E

    2013-12-01

    In utero exposure to gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes and cardiovascular disease in later life, yet the underlying mechanisms remain to be elucidated. We examined the effects of GDM on the proteome, redox status, and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant gene expression in human fetal endothelial cells. Proteomic analysis revealed that proteins involved in redox homeostasis were significantly altered in GDM and associated with increased mitochondrial superoxide generation, protein oxidation, DNA damage, and diminished glutathione (GSH) synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreductase 1 (NQO1), Bach1, cystine/glutamate transporter, and glutamate cysteine ligase. Although methylation of CpG islands in Nrf2 or NQO1 promoters was unaltered by GDM, decreased DJ-1 and increased phosphorylated glycogen synthase kinase 3β levels may account for impaired Nrf2 signaling. HNE-induced increases in GSH and NQO1 levels were abrogated by Nrf2 small interfering RNA in normal cells, and overexpression of Nrf2 in GDM cells partially restored NQO1 induction. Dysregulation of Nrf2 in fetal endothelium may contribute to the increased risk of type 2 diabetes and cardiovascular disease in offspring. PMID:23974919

  3. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD. PMID:27038927

  4. Toxicity mechanisms of arsenic that are shared with neurodegenerative diseases and cognitive impairment: Role of oxidative stress and inflammatory responses.

    Escudero-Lourdes, Claudia

    2016-03-01

    Arsenic (As) is a worldwide naturally occurring metalloid. Human chronic exposure to inorganic As compounds (iAs), which are at the top of hazardous substances (ATSDR, 2013), is associated with different diseases including cancer and non- cancerous diseases. The neurotoxic effects of iAs and its methylated metabolites have been demonstrated in exposed populations and experimental models. Impaired cognitive abilities have been described in children and adults chronically exposed to iAs through drinking water. Even though different association studies failed to demonstrate that As causes neurodegenerative diseases, several toxicity mechanisms of iAs parallel those mechanisms associated with neurodegeneration, including oxidative stress and inflammation, impaired protein degradation, autophagy, and intracellular accumulation, endoplasmic reticulum stress, and mitochondrial dysfunction. Additionally, different reports have shown that specifically in brain tissue, iAs and its metabolites induce hyper-phosphorylation of the tau protein and over-regulation of the amyloid precursor protein, impaired neurotransmitters synthesis and synaptic transmission, increased glutamate receptors activation, and decreased glutamate transporters expression. Interestingly, increased and sustained pro-inflammatory responses mediated by cytokines and related factors, seems to be the triggering factor for all of such cellular pathological effects. Therefore, this review proposes that iAs-associated cognitive impairment could be the result of the activation of pro-inflammatory responses in the brain tissue, which also may favor neurodegeneration or increase the risk for neurodegenerative diseases in exposed human populations. PMID:26868456

  5. Estimation of Kinetic Parameters for Autocatalytic Oxidation of Cyclohexane Based on a Modified Adaptive Genetic Algorithm

    刘平乐; 邹丽珊; 罗和安; 王良芥; 郑金华

    2004-01-01

    A modified genetic algorithm of multiple selection strategies, crossover strategies and adaptive operator is constructed, and it is used to estimate the kinetic parameters in autocatalytic oxidation of cyclohexane. The influences of selection strategy, crossover strategy and mutation strategy on algorithm performance are discussed. This algorithm with a specially designed adaptive operator avoids the problem of local optimum usually associated with using standard genetic algorithm and simplex method. The kinetic parameters obtained from the modified genetic algorithm are credible and the calculation results using these parameters agree well with experimental data. Furthermore, a new kinetic model of cyclohexane autocatalytic oxidation is established and the kinetic parameters are estimated by using the modified genetic algorithm.

  6. Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

    Shetty, Ritu A.; Forster, Michael J.; Sumien, Nathalie

    2012-01-01

    Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. S...

  7. The Use of Complex Assessment of Morphofunctional State of Pancreatic Microvasculature to Study the Adaptation of the Body to Motor Activity in Impaired Glucose Tolerance

    Nikonova L.G.

    2012-03-01

    Full Text Available The aim of the investigation is to consider the possibility of using the assessment data of microvasculature to study morphofunctional state of terminal vessels of exocrine and endocrine parts of pancreas in dogs with impaired glucose tolerance after physical exertion. Materials and methods. 30 mature male dogs with impaired glucose tolerance were studied: the 1st group — with no physical exertion, the 2nd — with short-term physical exertion and the 3rd — with extreme physical exertion. Morphological changes of the microvasculature components of pancreatic exocrine and endocrine parts were studied after the single motor load actions on the organism using histological, histochemical, electron-microscopical and morphometric methods. Results. Complex assessment enabled to reveal various adaptive changes of pancreatic microvasculature in animals with impaired glucose tolerance when exposed to optimal and maximum physical exertion. The exposure to short-term load results in developing compensatory adaptive transformations in the terminal part of vasculature of the both parts of the pancreas. Extreme loads along with reactive changes caused by single physical exercise lead to destructive alterations of microvasculature elements of primarily exocrine part. The information can be taken into consideration when studying impairment mechanisms in physical exertion environment and when developing regimens of motor activity in prediabetic persons.

  8. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

    Arya A

    2016-03-01

    Full Text Available Aditya Arya,1 Anamika Gangwar,1 Sushil Kumar Singh,2 Manas Roy,3,4 Mainak Das,3 Niroj Kumar Sethy,1 Kalpana Bhargava1 1Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, 2Functional Materials Division, Solid State Physics Laboratory, Defense Research and Development Organization, Timarpur, Delhi, 3Biological Science and Bioengineering, Indian Institute of Technology, Kanpur, 4Department of Chemistry, Indian Institute of Engineering Science and Technology, Howrah, India Abstract: Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs, also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs, we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5'-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein

  9. Sex-dependent mitochondrial respiratory impairment and oxidative stress in a rat model of neonatal hypoxic-ischemic encephalopathy.

    Demarest, Tyler G; Schuh, Rosemary A; Waddell, Jaylyn; McKenna, Mary C; Fiskum, Gary

    2016-06-01

    Increased male susceptibility to long-term cognitive deficits is well described in clinical and experimental studies of neonatal hypoxic-ischemic encephalopathy. While cell death signaling pathways are known to be sexually dimorphic, a sex-dependent pathophysiological mechanism preceding the majority of secondary cell death has yet to be described. Mitochondrial dysfunction contributes to cell death following cerebral hypoxic-ischemia (HI). Several lines of evidence suggest that there are sex differences in the mitochondrial metabolism of adult mammals. Therefore, this study tested the hypothesis that brain mitochondrial respiratory impairment and associated oxidative stress is more severe in males than females following HI. Maximal brain mitochondrial respiration during oxidative phosphorylation was two-fold more impaired in males following HI. The endogenous antioxidant glutathione was 30% higher in the brain of sham females compared to males. Females also exhibited increased glutathione peroxidase (GPx) activity following HI injury. Conversely, males displayed a reduction in mitochondrial GPx4 protein levels and mitochondrial GPx activity. Moreover, a 3-4-fold increase in oxidative protein carbonylation was observed in the cortex, perirhinal cortex, and hippocampus of injured males, but not females. These data provide the first evidence for sex-dependent mitochondrial respiratory dysfunction and oxidative damage, which may contribute to the relative male susceptibility to adverse long-term outcomes following HI. Lower basal GSH levels, lower post-hypoxic mitochondrial glutathione peroxidase (mtGPx) activity, and mitochondrial glutathione peroxidase 4 (mtGPx4) protein levels may contribute to the susceptibility of the male brain to oxidative damage and mitochondrial dysfunction following neonatal hypoxic-ischemia (HI). Treatment of male pups with acetyl-L-carnitine (ALCAR) protects against the loss of mtGPx activity, mtGPx4 protein, and increases in protein

  10. Impaired learning in rats in a 14-unit T-maze by 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, is attenuated by the nitric oxide donor, molsidomine.

    Meyer, R C; Spangler, E L; Patel, N; London, E D; Ingram, D K

    1998-01-01

    In previous experiments, it was demonstrated that systemic or central administration of the nitric oxide synthase (NO synthase) inhibitor, NG-nitro-L-arginine (N-Arg), produced dose-dependent learning impairments in rats in a 14-unit T-maze; and that sodium nitroprusside, a NO donor, could attenuate the impairment. Since N-Arg is not specific for neuronal NO synthase and produces hypertension, it is possible that effects on the cardiovasculature may have contributed to the impaired maze performance. In the present experiment, we have investigated the maze performance of 3-4 months old male Fischer-344 rats following treatment with 7-nitroindazole, a NO synthase inhibitor that is selective for neuronal NO synthase and does not produce hypertension. In addition, we examined the effects of the NO donor, molsidomine, which is much longer acting than sodium nitroprusside. Rats were pretrained to avoid footshock in a straight runway and received training in a 14-unit T-maze 24 h later. In an initial dose-response study, rats received intraperitoneal (i.p.) injections of either 7-nitroindazole (25, 50, or 65 mg/kg) or peanut oil 30 min prior to maze training. 7-nitroindazole produced significant, dose-dependent maze acquisition deficits, with 65 mg/kg producing the greatest learning impairment. This dose of 7-nitroindazole had no significant effect on systolic blood pressure. Following the dose-response study, rats were given i.p. injections of either 7-nitroindazole (70 mg/kg) plus saline, 7-nitroindazole (70 mg/kg) plus the NO donor, molsidomine (2 or 4 mg/kg), or peanut oil plus saline as controls. Both doses of molsidomine significantly attenuated the learning deficit induced by 7-nitroindazole relative to controls. These findings represent the first evidence that impaired learning produced by inhibition of neuronal NO synthase can be overcome by systemic administration of a NO donor. PMID:9489851

  11. Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis

    Kazuya Shinmura; Masanori Goto; Hong Tao; Shun Matsuura; Tomonari Matsuda; Haruhiko Sugimura

    2012-01-01

    AIM:To investigate the suppressive activity of MUTYH variant proteins against mutations caused by oxidative lesion,8-hydroxyguanine (8OHG),in human cells.METHODS:p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants,which were previously found in patients with colorectal polyposis and cancer,were selected for use in this study.Human H1299 cancer cell lines inducibly expressing wild-type (WT) MUTYH (type 2) or one of the 4 above-mentioned MUTYH variants were established using the piggyBac transposon vector system,enabling the genomic integration of the transposon sequence for MUTYH expression.MUTYH expression was examined after cumate induction using Western blotting analysis and immunofiuorescence analysis.The intracellular localization of MUTYH variants tagged with FLAG was also immunofluorescently examined.Next,the mutation frequency in the supF of the shuttle plasmid pMY189 containing a single 8OHG residue at position 159 of the supFwas compared between empty vector cells and cells expressing WT MUTYH or one of the 4 MUTYH variants using a supF forward mutation assay.RESULTS:The successful establishment of human cell lines inducibly expressing WT MUTYH or one of the 4 MUTYH variants was concluded based on the detection of MUTYH expression in these cell lines after treatment with cumate.All of the MUTYH variants and WT MUTYH were localized in the nucleus,and nuclear localization was also observed for FLAG-tagged MUTYH.The mutation frequency ofsupFwas 2.2 x 102in the 8OHG-containing pMY189 plasmid and 2.5× 10-4 in WT pMY189 in empty vector cells,which was an 86-fold increase with the introduction of 8OHG.The mutation frequency (4.7 × 10-3) of supF in the 8OHG-containing pMY189 plasmid in cells overexpressing WT MUTYH was significantly lower than in the empty vector cells (P < 0.01).However,the mutation frequencies of the supF in the 8OHG-containing pMY189 plasmid in cells overexpressing the p.R154H,p.M255V,p.L360P,or p.P377L MUTYH variant were 1.84 × 10-2,1.55

  12. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Ole Lamp

    Full Text Available High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS and one pair-fed (PF at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1, cows were challenged for 6 days (P2 by heat stress (temperature humidity index (THI = 76 or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  13. Effect of protein oxidation on the impaired quality of dry-cured loins produced from frozen pork meat.

    Lorido, Laura; Ventanas, Sonia; Akcan, Tolga; Estévez, Mario

    2016-04-01

    Dry-cured loins elaborated from frozen (-20 °C/20 weeks)/thawed longissimus dorsi muscles (F) were compared with counterparts elaborated from fresh (unfrozen) muscles (UF) for the extent of protein oxidation (carbonylation and Schiff base formation) and their sensory profile (quantitative-descriptive analysis). All samples had similar moisture, fat and protein contents (p>0.05). In accordance with previous studies, freezing meat prior to processing affected the oxidative stability of meat proteins. This chemical change occurred concomitantly with modifications of the sensory profile of the loins as F-samples received significantly (p<0.05) higher scores for rancid and salty flavor, hardness and fibrousness than UF-counterparts. The formation of cross-links (assessed as Schiff bases) during freezing and the subsequent processing may have contributed to strengthening the meat structure and hence, impairing the texture properties of dry-cured loins. PMID:26593621

  14. Cultivation of a novel cold-adapted nitrite oxidizing betaproteobacterium from the Siberian Arctic.

    Alawi, Mashal; Lipski, André; Sanders, Tina; Pfeiffer, Eva Maria; Spieck, Eva

    2007-07-01

    Permafrost-affected soils of the Siberian Arctic were investigated with regard to identification of nitrite oxidizing bacteria active at low temperature. Analysis of the fatty acid profiles of enrichment cultures grown at 4 degrees C, 10 degrees C and 17 degrees C revealed a pattern that was different from that of known nitrite oxidizers but was similar to fatty acid profiles of Betaproteobacteria. Electron microscopy of two enrichment cultures grown at 10 degrees C showed prevalent cells with a conspicuous ultrastructure. Sequence analysis of the 16S rRNA genes allocated the organisms to a so far uncultivated cluster of the Betaproteobacteria, with Gallionella ferruginea as next related taxonomically described organism. The results demonstrate that a novel genus of chemolithoautotrophic nitrite oxidizing bacteria is present in polygonal tundra soils and can be enriched at low temperatures up to 17 degrees C. Cloned sequences with high sequence similarities were previously reported from mesophilic habitats like activated sludge and therefore an involvement of this taxon in nitrite oxidation in nonarctic habitats is suggested. The presented culture will provide an opportunity to correlate nitrification with nonidentified environmental clones in moderate habitats and give insights into mechanisms of cold adaptation. We propose provisional classification of the novel nitrite oxidizing bacterium as 'Candidatus Nitrotoga arctica'. PMID:18062041

  15. Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

    Aragonès Gemma

    2012-06-01

    Full Text Available Abstract Background Recent studies have shown that fatty acid-binding protein 4 (FABP4 plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D. In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO production by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells (HUVECs, we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1 and Akt. Results We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production. Conclusion These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.

  16. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  17. Performance Optimization of Metallic Iron and Iron Oxide Nanomaterials for Treatment of Impaired Water Supplies

    Xie, Yang

    2011-01-01

    Iron nanomaterials including nanoscale zero valent iron (NZVI), NZVI-based bimetallic reductants (e.g., Pd/NZVI) and naturally occurring nanoscale iron mineral phases represent promising treatment tools for impaired water supplies. However, questions pertaining to fundamental and practical aspects of their reactivity may limit their performance during applications.For NZVI treatment of pollutant source zones, a major hurdle is its limited reactive lifetime. In Chapter 2, we report the longevi...

  18. BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid

    Findlay, John A.; Hamilton, David L.; Ashford, Michael L J

    2015-01-01

    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity...

  19. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    Subbuswamy K. Prabu

    2011-05-01

    Full Text Available We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks. These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III and cytochrome c oxidase (Complex IV were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I and succinate:ubiquinone oxidoreductase (Complex II were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.

  20. Adapt

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  1. Ectomycorrhizal fungi decompose soil organic matter using oxidative mechanisms adapted from saprotrophic ancestors.

    Shah, Firoz; Nicolás, César; Bentzer, Johan; Ellström, Magnus; Smits, Mark; Rineau, Francois; Canbäck, Björn; Floudas, Dimitrios; Carleer, Robert; Lackner, Gerald; Braesel, Jana; Hoffmeister, Dirk; Henrissat, Bernard; Ahrén, Dag; Johansson, Tomas; Hibbett, David S; Martin, Francis; Persson, Per; Tunlid, Anders

    2016-03-01

    Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter (SOM). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocellulose-degrading enzymes that are present in their saprotrophic ancestors. Spectroscopic analyses and transcriptome profiling were used to examine the mechanisms by which five species of ectomycorrhizal fungi, representing at least four origins of symbiosis, decompose SOM extracted from forest soils. In the presence of glucose and when acquiring nitrogen, all species converted the organic matter in the SOM extract using oxidative mechanisms. The transcriptome expressed during oxidative decomposition has diverged over evolutionary time. Each species expressed a different set of transcripts encoding proteins associated with oxidation of lignocellulose by saprotrophic fungi. The decomposition 'toolbox' has diverged through differences in the regulation of orthologous genes, the formation of new genes by gene duplications, and the recruitment of genes from diverse but functionally similar enzyme families. The capacity to oxidize SOM appears to be common among ectomycorrhizal fungi. We propose that the ancestral decay mechanisms used primarily to obtain carbon have been adapted in symbiosis to scavenge nutrients instead. PMID:26527297

  2. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  3. The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis.

    Galarreta, Carolina I; Forbes, Michael S; Thornhill, Barbara A; Antignac, Corinne; Gubler, Marie-Claire; Nevo, Nathalie; Murphy, Michael P; Chevalier, Robert L

    2015-05-15

    Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, the so-called swan-neck lesion (SNL), and eventual renal failure. To determine the role of oxidative stress in cystinosis, histologic sections of kidneys from C57BL/6 Ctns(-/-) and wild-type mice were examined by immunohistochemistry and morphometry from 1 wk to 20 mo of age. Additional mice were treated from 1 to 6 mo with vehicle or mitoquinone (MitoQ), an antioxidant targeted to mitochondria. The leading edge of the SNL lost mitochondria and superoxide production, and became surrounded by a thickened tubular basement membrane. Progression of the SNL as determined by staining with lectin from Lotus tetragonolobus accelerated after 3 mo, but was delayed by treatment with MitoQ (38 ± 4% vs. 28 ± 1%, P injury molecule-1 (KIM-1) nor cell death was observed. After 9 mo, clusters of proximal tubules exhibited localized oxidative stress (4-hydroxynonenal binding), expressed KIM-1, and underwent apoptosis, leading to the formation of atubular glomeruli and accumulation of interstitial collagen. We conclude that nephron integrity is initially maintained in the Ctns(-/-) mouse by adaptive flattening of cells of the SNL through loss of mitochondria, upregulation of transgelin, and thickened basement membrane. This adaptation ultimately fails in adulthood, with proximal tubular disruption, formation of atubular glomeruli, and renal failure. Antioxidant treatment targeted to mitochondria delays initiation of the SNL, and may provide therapeutic benefit in children with cystinosis. PMID:25694483

  4. 听觉障碍学生学习适应性的调查研究%An Investigation on the Learning Adaptability of Students with Hearing Impairments

    杨福义; 谭和平; 陈进; 李方璐

    2012-01-01

    Abstract: With subjects of 242 students with hearing impairments from grade 7 to grade 12, this study investigated hearing im-paired students' learning adaptability. The results indicated that : ( 1 ) The global learning adaptability of hearing impaired students was universally medium or under medium level. Quite a few students with hearing impairments were diversely maladaptive in the domain of learning attitude, learning technology, learning environment and mental and physical health. ;(2)There existed significant grade differ- ence in hearing impaired students' learning adaptability. Their learning adaptability put up the trend to recede first and then rise with the increasing of grade. ; ( 3 ) There also existed significant gender difference in learning adaptability of students with hearing impair- ments. Females' global and four individual levels of learning adaptability were significantly higher than those of males ; (4) Hearing im- paired students' cognitive style model were mostly impulsive model. Their memory model were mostly visual model or in - between model; ( 5 ) More than half students with hearing impairments attributed their academic achievements to inner - directed reason. More than one third students with hearing impairments attributed their academic achievements to outer - directed reason; ( 6 ) Hearing im-paired students' learning time at home was less than that of normal students. Practitioners should take into account hearing impaired students' learning adaptability characteristics while giving instructions to this kind of students.%本研究采用《学习适应性测验》对242名初一——高三年级听觉障碍学生的学习适应性进行调查研究。结果表明:(1)听障学生的总体学习适应性普遍处于中等或中等以下水平,在学习态度、学习技术、学习环境和心身健康四个方面都有相当比例的学生表现出不同程

  5. Assessment of benzene induced oxidative impairment in rat isolated pancreatic islets and effect on insulin secretion.

    Bahadar, Haji; Maqbool, Faheem; Mostafalou, Sara; Baeeri, Maryam; Rahimifard, Mahban; Navaei-Nigjeh, Mona; Abdollahi, Mohammad

    2015-05-01

    Benzene (C6H6) is an organic compound used in petrochemicals and numerous other industries. It is abundantly released to our environment as a chemical pollutant causing widespread human exposure. This study mainly focused on benzene induced toxicity on rat pancreatic islets with respect to oxidative damage, insulin secretion and glucokinase (GK) activity. Benzene was dissolved in corn oil and administered orally at doses 200, 400 and 800mg/kg/day, for 4 weeks. In rats, benzene significantly raised the concentration of plasma insulin. Also the effect of benzene on the release of glucose-induced insulin was pronounced in isolated islets. Benzene caused oxidative DNA damage and lipid peroxidation, and also reduced the cell viability and total thiols groups, in the islets of exposed rats. In conclusion, the current study revealed that pancreatic glucose metabolism is susceptible to benzene toxicity and the resultant oxidative stress could lead to functional abnormalities in the pancreas. PMID:25935538

  6. Chelation of Free Zn(2+) Impairs Chemotaxis, Phagocytosis, Oxidative Burst, Degranulation, and Cytokine Production by Neutrophil Granulocytes.

    Hasan, Rafah; Rink, Lothar; Haase, Hajo

    2016-05-01

    Neutrophil granulocytes are the largest leukocyte population in the blood and major players in the innate immune response. Impaired neutrophil function has been reported in in vivo studies with zinc-deficient human subjects and experimental animals. Moreover, in vitro formation of neutrophil extracellular traps has been shown to depend on free intracellular Zn(2+). This study investigates the requirement of Zn(2+) for several other essential neutrophil functions, such as chemotaxis, phagocytosis, cytokine production, and degranulation. To exclude artifacts resulting from indirect effects of zinc deprivation, such as impaired hematopoietic development and influences of other immune cells, direct effects of zinc deprivation were tested in vitro using cells isolated from healthy human donors. Chelation of Zn(2+) by the membrane permeable chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) reduced granulocyte migration toward N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF) and IL-8, indicating a role of free intracellular Zn(2+) in chemotaxis. However, a direct action of Zn(2+) as a chemoattractant, as previously reported by others, was not observed. Similar to chemotaxis, phagocytosis, oxidative burst, and granule release were also impaired in TPEN-treated granulocytes. Moreover, Zn(2+) contributes to the regulatory role of neutrophil granulocytes in the inflammatory response by affecting the cytokine production by these cells. TPEN inhibited the lipopolysaccharide-induced secretion of chemotactic IL-8 and also anti-inflammatory IL-1ra. In conclusion, free intracellular Zn(2+) plays essential roles in multiple neutrophil functions, affecting extravasation to the site of the infection, uptake and killing of microorganisms, and inflammation. PMID:26400651

  7. Methodological Adaptations for Investigating the Perceptions of Language-Impaired Adolescents Regarding the Relative Importance of Selected Communication Skills

    Reed, Vicki A.; Brammall, Helen

    2006-01-01

    This article describes the systematic and detailed processes undertaken to modify a research methodology for use with language-impaired adolescents. The original methodology had been used previously with normally achieving adolescents and speech pathologists to obtain their opinions about the relative importance of selected communication skills…

  8. Impairment of mitochondrial β-oxidation in rats under cold-hypoxic environment

    Dutta, Arkadeb; Vats, Praveen; Singh, Vijay K.; Sharma, Yogendra K.; Singh, Som N.; Singh, Shashi B.

    2009-09-01

    Mitochondrial ß-oxidation of fatty acid provides a major source of energy in mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient temperatures, causes alteration in metabolic homeostasis. Several studies have depicted that hypoxic exposure in small mammals causes hypothermia due to hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia tolerance in animals. The present study investigated the rate of β-oxidation and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male Sprague Dawley rats (190-220 g) were randomly divided into eight groups ( n = 6 rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7 days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, 14C-palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in CH1 and CH7 as compared to respective controls. HAD activity was significantly reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed controls in muscle and liver, respectively. A concomitant decrease in 14C-palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia and cold-hypoxia suggested hypometabolic state. It can be concluded that ß-oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment due to the persisting hypometabolic state in cold-hypoxia exposure.

  9. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.

    Boeldt, D S; Yi, F X; Bird, I M

    2011-09-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](i) concentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca(2+)](i) signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension. PMID:21555345

  10. Protection from Palmitate-Induced Mitochondrial DNA Damage Prevents from Mitochondrial Oxidative Stress, Mitochondrial Dysfunction, Apoptosis, and Impaired Insulin Signaling in Rat L6 Skeletal Muscle Cells

    Yuzefovych, Larysa V.; Solodushko, Viktoriya A.; Wilson, Glenn L.; Rachek, Lyudmila I.

    2011-01-01

    Saturated free fatty acids have been implicated in the increase of oxidative stress, mitochondrial dysfunction, apoptosis, and insulin resistance seen in type 2 diabetes. The purpose of this study was to determine whether palmitate-induced mitochondrial DNA (mtDNA) damage contributed to increased oxidative stress, mitochondrial dysfunction, apoptosis, impaired insulin signaling, and reduced glucose uptake in skeletal muscle cells. Adenoviral vectors were used to deliver the DNA repair enzyme ...

  11. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2014-01-01

    using a targeted proteomics analysis we have found that proteins involved in protein quality control and glycolytic enzymes are the main targets of oxidation (carbonylation) and modification with advanced glycation/lipid peroxidation end products during replicative senescence of satellite cells...... leading to increased mobilization of non-carbohydrate substrates as branched chain amino acids or long chain fatty acids was observed in senescent cells. In addition, phospho-and glycerolipids metabolism was altered. Increased levels of acyl-carnitines indicated augmented turnover of storage and membrane...... lipids for energy production. Such changes reflect alterations in membrane composition and dysregulation of sphingolipids signaling during senescence. This study establishes a new concept connecting oxidative protein modifications with the altered cellular metabolism associated with the senescent...

  12. Mice Lacking Inducible Nitric Oxide Synthase Demonstrate Impaired Killing of Porphyromonas gingivalis

    Gyurko, Robert; Boustany, Gabriel; Huang, Paul L; Kantarci, Alpdogan; Van Dyke, Thomas E.; Genco, Caroline A.; Gibson III, Frank C.

    2003-01-01

    Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS−/−) mice with P. gingivalis by using a subcutaneous c...

  13. Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension.

    Campos, Lilian Brites; Gilglioni, Eduardo Hideo; Garcia, Rosângela Fernandes; Brito, Márcia do Nascimento; Natali, Maria Raquel Marçal; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

    2012-08-15

    The aim of this work was to evaluate the effects of therapeutic doses of Cimicifuga racemosa on cardiovascular parameters and on liver lipid metabolism and redox status in an animal model of estrogen deficiency associated with hypertension, a condition that could make the liver more vulnerable to drug-induced injuries. Female Wistar rats were subjected to the surgical procedures of bilateral ovariectomy (OVX) and induction of renovascular hypertension (two-kidneys, one-clip; 2K1C). These animals (OVX + 2K1C) were treated with daily doses of a C. racemosa extract, using a dose that is similar to that recommended to postmenopausal women (0.6 mg/kg), over a period of 15 days. The results were compared to those of untreated OVX + 2K1C, OVX, and control rats. The treatment with C. racemosa caused a significant reduction in blood pressure. In the liver, treatment did not prevent the development of steatosis, and it reduced the mitochondrial and peroxisomal capacity to oxidize octanoyl-CoA compared to the untreated animals. In addition, C. racemosa caused numerous undesirable effects on the liver redox status: it increased the mitochondrial reactive oxygen species generation, an event that was not accompanied by an increase in the activity of superoxide dismutase, and it induced a decrease in peroxisomal catalase activity. Although the reduced glutathione content had not been affected, a phenomenon that probably reflected the restoration of glucose-6-phosphate dehydrogenase activity by C. racemosa, oxidative damage was evidenced by the elevated level of thiobarbituric acid-reactive substances found in the liver of treated animals. PMID:22684021

  14. Speech communication strategies in older children: acoustic-phonetic and linguistic adaptations to a hearing-impaired peer

    Granlund, S. C.

    2015-01-01

    This thesis examines the communication strategies used by both hearing (NH) and hearing-impaired (HI) children when interacting with a peer with hearing loss, focusing on the acoustic-phonetic and linguistic properties of their speech. To elicit frequent repetitions of segmental contrasts in HI children’s spontaneous speech in interaction, a new task was developed using minimal pair keywords in a communicative game context. In addition, another referential communication task, the ‘spot the di...

  15. Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress.

    Viviane Grazielle-Silva

    2015-06-01

    Full Text Available DNA repair mechanisms are crucial for maintenance of the genome in all organisms, including parasites where successful infection is dependent both on genomic stability and sequence variation. MSH2 is an early acting, central component of the Mismatch Repair (MMR pathway, which is responsible for the recognition and correction of base mismatches that occur during DNA replication and recombination. In addition, recent evidence suggests that MSH2 might also play an important, but poorly understood, role in responding to oxidative damage in both African and American trypanosomes.To investigate the involvement of MMR in the oxidative stress response, null mutants of MSH2 were generated in Trypanosoma brucei procyclic forms and in Trypanosoma cruzi epimastigote forms. Unexpectedly, the MSH2 null mutants showed increased resistance to H2O2 exposure when compared with wild type cells, a phenotype distinct from the previously observed increased sensitivity of T. brucei bloodstream forms MSH2 mutants. Complementation studies indicated that the increased oxidative resistance of procyclic T. brucei was due to adaptation to MSH2 loss. In both parasites, loss of MSH2 was shown to result in increased tolerance to alkylation by MNNG and increased accumulation of 8-oxo-guanine in the nuclear and mitochondrial genomes, indicating impaired MMR. In T. cruzi, loss of MSH2 also increases the parasite capacity to survive within host macrophages.Taken together, these results indicate MSH2 displays conserved, dual roles in MMR and in the response to oxidative stress. Loss of the latter function results in life cycle dependent differences in phenotypic outcomes in T. brucei MSH2 mutants, most likely because of the greater burden of oxidative stress in the insect stage of the parasite.

  16. Energy Efficient Glazing for Adaptive Solar Control Fabricated with Photothermotropic Hydrogels Containing Graphene Oxide

    Kim, Dowan; Lee, Eunsu; Lee, Heon Sang; Yoon, Jinhwan

    2015-01-01

    Glazing for adaptive solar control is the most promising for energy efficient development, because the use of this technology in buildings can be expected to significantly impact energy use and efficiency by screening sunlight that enters a building in summer. To achieve autonomous adjustable transparency, we have developed photothermotropic material system by combining photothermal materials with thermotropic hydrogels. We found that graphene oxide dispersed within a hydrogel matrix effectively converts the photo energy of sunlight into thermal energy, providing the efficient means to trigger transparency of thermotropic hydrogels. Therefore, we could develop switchable glazing of novel photothermotropic mechanism that screen strong sunlight and heat radiation in response to the sunlight intensity, as well as the temperature. Furthermore, in this study, a prototype device was manufactured with developed materials and successfully operated in outdoor testing.

  17. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

    Tatiana Barichello; Santos, Ana Lucia B.; Cintia Silvestre; Generoso, Jaqueline S.; Cipriano, Andreza L.; Fabricia Petronilho; Felipe Dal-Pizzol; Comim, Clarissa M.; João Quevedo

    2011-01-01

    Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10  μ L of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and corte...

  18. Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

    Sällström, Johan; Carlström, Mattias; Jensen, Boye L;

    2008-01-01

    wild-type (nNOS(+/+)) mice after 10 days of low (0.01% NaCl) and high (4% NaCl) sodium diets.ResultsThe resting heart rate was reduced in nNOS(-/-) mice, but the two genotypes had similar blood pressure during the low (nNOS(+/+) 104 +/- 2 mm Hg; nNOS(-/-) 103 +/- 2 mm Hg) and high (nNOS(+/+) 107 +/- 3......BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodium...... loads.MethodsBlood pressure and heart rate were measured telemetrically and assessed during periods of physical activity and inactivity. Urinary solute excretion was measured by metabolism cages and plasma renin concentration (PRC) was determined by radioimmunoassay; all in nNOS knockout (nNOS(-/-)) and...

  19. Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

    Ragoobirsingh Dalip

    2006-05-01

    Full Text Available Abstract Background Evidence demonstrates that exogenously administered nitric oxide (NO can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP and S-nitrosoglutathione (GSNO on the early events in insulin signaling in rat skeletal myocytes. Results Skeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml in the presence or absence of glucose (25 mM and insulin (100 nM. Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO. Conclusion These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

  20. Self-Adaptive Spike-Time-Dependent Plasticity of Metal-Oxide Memristors

    Prezioso, M.; Merrikh Bayat, F.; Hoskins, B.; Likharev, K.; Strukov, D.

    2016-02-01

    Metal-oxide memristors have emerged as promising candidates for hardware implementation of artificial synapses - the key components of high-performance, analog neuromorphic networks - due to their excellent scaling prospects. Since some advanced cognitive tasks require spiking neuromorphic networks, which explicitly model individual neural pulses (“spikes”) in biological neural systems, it is crucial for memristive synapses to support the spike-time-dependent plasticity (STDP). A major challenge for the STDP implementation is that, in contrast to some simplistic models of the plasticity, the elementary change of a synaptic weight in an artificial hardware synapse depends not only on the pre-synaptic and post-synaptic signals, but also on the initial weight (memristor’s conductance) value. Here we experimentally demonstrate, for the first time, an STDP behavior that ensures self-adaptation of the average memristor conductance, making the plasticity stable, i.e. insensitive to the initial state of the devices. The experiments have been carried out with 200-nm Al2O3/TiO2-x memristors integrated into 12 × 12 crossbars. The experimentally observed self-adaptive STDP behavior has been complemented with numerical modeling of weight dynamics in a simple system with a leaky-integrate-and-fire neuron with a random spike-train input, using a compact model of memristor plasticity, fitted for quantitatively correct description of our memristors.

  1. Glutamate-induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure.

    Rodrigo, Regina; Erceg, Slaven; Rodriguez-Diaz, Jesus; Saez-Valero, Javier; Piedrafita, Blanca; Suarez, Isabel; Felipo, Vicente

    2007-07-01

    It has been proposed that impairment of the glutamate-nitric oxide-cyclic guanosine monophosphate (cGMP) pathway in brain contributes to cognitive impairment in hepatic encephalopathy. The aims of this work were to assess whether the function of this pathway and of nitric oxide synthase (NOS) are altered in cerebral cortex in vivo in rats with chronic liver failure due to portacaval shunt (PCS) and whether these alterations are due to hyperammonemia. The glutamate-nitric oxide-cGMP pathway function and NOS activation by NMDA was analysed by in vivo microdialysis in cerebral cortex of PCS and control rats and in rats with hyperammonemia without liver failure. Similar studies were done in cortical slices from these rats and in cultured cortical neurons exposed to ammonia. Basal NOS activity, nitrites and cGMP are increased in cortex of rats with hyperammonemia or liver failure. These increases seem due to increased inducible nitric oxide synthase expression. NOS activation by NMDA is impaired in cerebral cortex in both animal models and in neurons exposed to ammonia. Chronic liver failure increases basal NOS activity, nitric oxide and cGMP but reduces activation of NOS induced by NMDA receptors activation. Hyperammonemia is responsible for both effects which will lead, independently, to alterations contributing to neurological alterations in hepatic encephalopathy. PMID:17286583

  2. Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Therapy

    Jehonathan H. Pinthus

    2007-01-01

    Full Text Available Radiation therapy is a standard treatment for prostate cancer (PC. The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS. Adjuvant androgen deprivation (AD therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR+ 22rv1 and AR− PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS levels, resulting in dose-dependent activation of phospho-p38 and pAKT, increased expression of clusterin, catalase, manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, glutathione reductase. Consequently, AD significantly facilitated the response of AR+ cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.

  3. Complete genome sequence of Nitrosomonas sp. Is79, an ammonia oxidizing bacterium adapted to low ammonium concentrations

    Bollmann, Annette [Miami University, Oxford, OH; Sedlacek, Christopher J [Miami University, Oxford, OH; Laanbroek, Hendrikus J [Netherlands Institute of Ecology (NIOO-KNAW); Suwa, Yuichi [Chuo University, Tokyo, Japan; Stein, Lisa Y [University of California, Riverside; Klotz, Martin G [University of Louisville, Louisville; Arp, D J [Oregon State University; Sayavedra-Soto, LA [Oregon State University; Lu, Megan [Los Alamos National Laboratory (LANL); Bruce, David [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Han, James [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Pennacchio, Len [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Huntemann, Marcel [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Szeto, Ernest [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Peters, Lin [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL)

    2013-01-01

    Nitrosomonas sp. Is79 is a chemolithoautotrophic ammonia-oxidizing bacterium that belongs to the family Nitrosomonadaceae within the phylum Proteobacteria. Ammonia oxidation is the first step of nitrification, an important process in the global nitrogen cycle ultimately resulting in the production of nitrate. Nitrosomonas sp. Is79 is an ammonia oxidizer of high interest because it is adapted to low ammonium and can be found in freshwater environments around the world. The 3,783,444-bp chromosome with a total of 3,553 protein coding genes and 44 RNA genes was sequenced by the DOE-Joint Genome Institute Program CSP 2006.

  4. L-Arginine reverses the impairment of nitric oxide-dependent collateral perfusion in dietary-induced hypercholesterolaemia in the rabbit

    1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial occlusion to investigate the effects of exogenous L-arginine on the severe impairment of collateral perfusion associated with dietary-induced hypercholesterolaemia. The effects of L-arginine on hypercholesterolaemia-related impairment of endothelium-dependent relaxations to acetylcholine were also investigated in unligated, isolated rabbit ears perfused with buffer. 2. Cholesterol feeding for 8 weeks (blood cholesterol level 66.5 +/- 5.3 versus 1.4 +/- 0.2 mmol/l, P < 0.001) was associated with almost complete impairment of collateral perfusion, an effect previously observed after inhibition of nitric oxide synthesis. The impairment of collateral perfusion found in hypercholesterolaemia was completely reversed by the addition of 10 mmol/l L-arginine to the perfusion fluid. In control preparations from rabbits fed a normal diet, the addition of 10 mmol/l L-arginine did not influence collateral perfusion. 3. Endothelium-dependent relaxation to acetylcholine was impaired in preparations from the rabbits fed the high cholesterol diet for 8 weeks: the maximum relaxation of tone was 24.6 +/- 0.8% and was significantly (P < 0.01) less than that in the controls (70.3 +/- 2.4%). Addition of L-arginine to the perfusion fluid caused a modest improvement in the endothelium-dependent relaxations to acetylcholine, with a maximum response of 43.2 +/- 1.3%. 4. We conclude that nitric oxide-dependent collateral perfusion is severely impaired in hypercholesterolaemia and that the addition of exogenous L-arginine fully reverses these changes. Endothelium-dependent relaxations to acetylcholine are similarly impaired by hypercholesterolaemia; however, this deficit was only partially reversed by L-arginine

  5. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

    Ferroni, Patrizia; Riondino, Silvia; Buonomo, Oreste; Palmirotta, Raffaele; Guadagni, Fiorella; Roselli, Mario

    2015-01-01

    Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols. PMID:26171112

  6. Polychlorinated biphenyls PCB 153 and PCB 126 impair the glutamate-nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms.

    Llansola, Marta; Piedrafita, Blanca; Rodrigo, Regina; Montoliu, Carmina; Felipo, Vicente

    2009-08-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in human blood and milk. Exposure to PCBs during pregnancy and lactation leads to cognitive impairment in children. Perinatal exposure to PCB 153 or PCB 126 impairs the glutamate-nitric oxide-cGMP pathway in cerebellum in vivo and learning ability in adult rats. The aims of this work were: (1) to assess whether long-term exposure of primary cultures of cerebellar neurons to PCB 153 or PCB 126 reproduces the impairment in the function of the glutamate-nitric oxide-cGMP pathway found in rat cerebellum in vivo; (2) to provide some insight on the steps of the pathway affected by these PCBs; (3) to assess whether the mechanisms of interference of the pathway are different for PCB 126 and PCB 153. Both PCB 153 and PCB 126 increase basal levels of cGMP by different mechanisms. PCB 126 increases the amount of soluble guanylate cyclase while PCB 153 does not. PCB 153 reduces the amount of calmodulin while PCB 126 does not. Also both PCBs impair the function of the glutamate-nitric oxide-cGMP pathway by different mechanisms, PCB 153 impairs nitric oxide-induced activation of soluble guanylate cyclase and increase in cGMP while PCB 126 does not. PCB 126 reduces NMDA-induced increase in calcium while PCB 153 does not. When PCB 153 and PCB 126 exhibit the same effect, PCB 126 was more potent than PCB 153, as occurs in vivo. PMID:19526286

  7. Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

    Brouwers, O; Niessen, P M; Haenen, G;

    2010-01-01

    of high glucose and methylglyoxal on NO-dependent vasorelaxation in isolated rat mesenteric arteries from wild-type and transgenic glyoxalase (GLO)-I (also known as GLO1) rats, i.e. the enzyme detoxifying methylglyoxal, were recorded in a wire myograph. AGE formation of the major methylglyoxal-adduct 5...... for AGE ligand S100b did (p stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....

  8. Mice Lacking Inducible Nitric Oxide Synthase Demonstrate Impaired Killing of Porphyromonas gingivalis

    Gyurko, Robert; Boustany, Gabriel; Huang, Paul L.; Kantarci, Alpdogan; Van Dyke, Thomas E.; Genco, Caroline A.; Gibson III, Frank C.

    2003-01-01

    Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS−/−) mice with P. gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P. gingivalis infection. iNOS−/− mice inoculated with P. gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS−/− mice possessed significantly more P. gingivalis than that of WT mice. The immunoglobulin G responses to P. gingivalis in serum was similar in WT and iNOS−/− mice, and the inductions of tumor necrosis factor alpha, interleukin-1β and interleukin-6, and prostaglandin E2 were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS−/− and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS−/− mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS−/− mice released more superoxide than did WT PMNs when stimulated with P. gingivalis. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P. gingivalis. PMID:12933833

  9. Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

    Zhang, Yaping; Zhang, Wei; Edvinsson, Lars; Xu, Cang-Bao

    2014-01-01

    Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentra......Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different...... concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI2) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with......-dependently attenuated the endothelium-dependent vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was weaker in the presence of LDL, indicating that LDL induced damage to the endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced impairing vasodilation was mainly due...

  10. PEGylated Carbon Nanotubes Impair Retrieval of Contextual Fear Memory and Alter Oxidative Stress Parameters in the Rat Hippocampus

    Lidiane Dal Bosco

    2015-01-01

    Full Text Available Carbon nanotubes (CNT are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions.

  11. Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring.

    Michelle Lane

    Full Text Available Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2, which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity.

  12. Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

    Marcella Mauro

    2015-07-01

    Full Text Available Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1 and needle-abraded human skin (experiment 2. Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2, while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2 and those with intact skin (1.08 ± 0.20 ng·cm−2. To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI uptake assays. The results indicate that a long exposure time (i.e., seven days was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay. This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure.

  13. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  14. Oleic Acid Increases Synthesis and Secretion of VEGF in Rat Vascular Smooth Muscle Cells: Role of Oxidative Stress and Impairment in Obesity

    Mariella Trovati

    2013-09-01

    Full Text Available Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF action on vascular smooth muscle cells (VSMC. Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic acid (OA enhances VEGF synthesis/secretion in VSMC, and whether this effect is impaired in obesity. In cultured aortic VSMC from lean and obese Zucker rats (LZR and OZR, respectively we measured the influence of OA on VEGF-A synthesis/secretion, signaling molecules and reactive oxygen species (ROS. In VSMC from LZR we found the following: (a OA increases VEGF-A synthesis/secretion by a mechanism blunted by inhibitors of Akt, mTOR, ERK-1/2, PKC-beta, NADPH-oxidase and mitochondrial electron transport chain complex; (b OA activates the above mentioned signaling pathways and increases ROS; (c OA-induced activation of PKC-beta enhances oxidative stress, which activates signaling pathways responsible for the increased VEGF synthesis/secretion. In VSMC from OZR, which present enhanced baseline oxidative stress, the above mentioned actions of OA on VEGF-A, signaling pathways and ROS are impaired: this impairment is reproduced in VSMC from LZR by incubation with hydrogen peroxide. Thus, in OZR chronically elevated oxidative stress causes a resistance to the action on VEGF that OA exerts in LZR by increasing ROS.

  15. Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

    Engelen, Mariëlle P K J; Safar, Ahmed M; Bartter, Thaddeus; Koeman, Fari; Deutz, Nicolaas E P

    2016-07-01

    Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear. PMID:27129191

  16. Genome-Guided Analysis of Physiological Capacities of Tepidanaerobacter acetatoxydans Provides Insights into Environmental Adaptations and Syntrophic Acetate Oxidation

    Müller, Bettina; Manzoor, Shahid; Niazi, Adnan; Bongcam-Rudloff, Erik; Schnürer, Anna

    2015-01-01

    This paper describes the genome-based analysis of Tepidanaerobacter acetatoxydans strain Re1, a syntrophic acetate-oxidising bacterium (SAOB). Principal issues such as environmental adaptations, metabolic capacities, and energy conserving systems have been investigated and the potential consequences for syntrophic acetate oxidation discussed. Briefly, in pure culture, T. acetatoxydans grows with different organic compounds and produces acetate as the main product. In a syntrophic consortium w...

  17. Cross-cultural adaptation and validation of a Brazilian version of an instrument to assess impairments related to oral functioning of people with Down syndrome

    Bonanato Karina

    2013-01-01

    Full Text Available Abstract Background An instrument was developed in Canada to assess impairments related to oral functioning of individuals with four years of age or older with Down syndrome (DS. The present study attempted to carry out the cross-cultural adaptation and validation of the instrument for the Brazilian Portuguese language and to test its reliability and validity. Findings After translation and cross-cultural adaptation, the instrument was tested on caregivers of people with DS. Clinical examination for malocclusion was carried out in people with DS by two calibrated examiners. Inter and Intra examiner agreement was assessed by Intraclass Correlation Coefficient (ICC and ranged from 0.92 to 0.97 respectively. Total of 157 people with DS and their caregivers were able to compose the sample. They were selected from eight institutions for people with DS in five cities of southeastern Brazil. The mean age of people with DS was 20.7 [±13.1] and for caregivers was 53.1 [±13.7]. The mean instrument score was 18.6 [±9.0]. Internal reliability ranged from 0.49 to 0.80 and external reliability ranged from 0.78 to 0.88. Construct validity was verified by significant correlations identified between malocclusion and the total instrument; and caregivers’ educational level and the instrument (p Conclusions Initial validity tests indicated that the instrument related to the oral health for people with DS may be a valid instrument to this segment of the population in Brazil.

  18. The ‘Goldilocks Zone’ from a redox perspective - Adaptive versus deleterious responses to oxidative stress in striated muscle

    Rick J Alleman

    2014-09-01

    Full Text Available Consequences of oxidative stress may be beneficial or detrimental in physiological systems. An organ system’s position on the ‘hormetic curve’ is governed by the source and temporality of reactive oxygen species (ROS production, proximity of ROS to moieties most susceptible to damage, and the capacity of the endogenous cellular ROS scavenging mechanisms. Most importantly, the resilience of the tissue (the capacity to recover from damage is a decisive factor, and this is reflected in the disparate response to ROS in cardiac and skeletal muscle. In myocytes, a high oxidative capacity invariably results in a significant ROS burden which in homeostasis, is rapidly neutralized by the robust antioxidant network. The up-regulation of key pathways in the antioxidant network is a central component of the hormetic response to ROS. Despite such adaptations, persistent oxidative stress over an extended time-frame (e.g. months to years inevitably leads to cumulative damages, maladaptation and ultimately the pathogenesis of chronic diseases. Indeed, persistent oxidative stress in heart and skeletal muscle has been repeatedly demonstrated to have causal roles in the etiology of heart disease and insulin resistance, respectively. Deciphering the mechanisms that underlie the divergence between adaptive and maladaptive responses to oxidative stress remains an active area of research for basic scientists and clinicians alike, as this would undoubtedly lead to novel therapeutic approaches. Here, we provide an overview of major types of ROS in striated muscle and the divergent adaptations that occur in response to them. Emphasis is placed on highlighting newly uncovered areas of research on this topic, with particular focus on the mitochondria, and the diverging roles that ROS play in muscle health (e.g., exercise or preconditioning and disease (e.g., cardiomyopathy, ischemia, metabolic syndrome.

  19. Impairment of nitric oxide synthase but not heme oxygenase accounts for baroreflex dysfunction caused by chronic nicotine in female rats.

    Mohamed A Fouda

    Full Text Available We recently reported that chronic nicotine impairs reflex chronotropic activity in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS and/or heme oxygenase (HO in the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate to increases (phenylephrine or decreases (sodium nitroprusside in blood pressure were generated in conscious female rats treated with nicotine or saline in absence and presence of pharmacological modulators of NOS or HO activity. Compared with saline-treated rats, nicotine (2 mg/kg/day i.p., for 14 days significantly reduced the slopes of baroreflex curves, a measure of baroreflex sensitivity (BRS. Findings that favor the involvement of NOS inhibition in the nicotine effect were (i NOS inhibition (Nω-Nitro-L-arginine methyl ester, L-NAME reduced BRS in control rats but failed to do so in nicotine-treated rats, (ii L-arginine, NO donor, reversed the BRS inhibitory effect of nicotine. Alternatively, HO inhibition (zinc protoporphyrin IX, ZnPP had no effect on BRS in nicotine- or control rats and failed to reverse the beneficial effect of L-arginine on nicotine-BRS interaction. Similar to female rats, BRS was reduced by L-NAME, but not ZnPP, in male rats and the L-NAME effect was not accentuated after concomitant administration of nicotine. Baroreflex dysfunction caused by nicotine in female rats was blunted after supplementation with hemin (HO inducer but not tricarbonyldichlororuthenium(II dimer (CORM-2, a carbon monoxide (CO releasing molecule, or bilirubin, the breakdown product of heme catabolism. The facilitatory effect of hemin was abolished upon simultaneous treatment with L-NAME or 1H-[1], [2], [4] oxadiazolo[4,3-a] quinoxalin-1-one (inhibitor of soluble guanylate cyclase, sGC. The activities of HO and NOS in brainstem tissues were also significantly increased by hemin. Thus, the inhibition of NOS, but not HO, accounts for the baroreflex depressant of chronic nicotine

  20. Visual Impairment, Including Blindness

    ... top Adapting the Environment Making adaptations to the environment where a child with a visual impairment lives, works, or plays ... can consult, depending on your role in the child’s life, are: Family Connect ... to the Physical Environment: Setting up a Classroom for Students with Visual ...

  1. Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts.

    Frederico D Lima

    Full Text Available BACKGROUND AND AIMS: Although acute exhaustive exercise is known to increase liver reactive oxygen species (ROS production and aerobic training has shown to improve the antioxidant status in the liver, little is known about mitochondria adaptations to aerobic training. The main objective of this study was to investigate the effects of the aerobic training on oxidative stress markers and antioxidant defense in liver mitochondria both after training and in response to three repeated exhaustive swimming bouts. METHODS: Wistar rats were divided into training (n = 14 and control (n = 14 groups. Training group performed a 6-week swimming training protocol. Subsets of training (n = 7 and control (n = 7 rats performed 3 repeated exhaustive swimming bouts with 72 h rest in between. Oxidative stress biomarkers, antioxidant activity, and mitochondria functionality were assessed. RESULTS: Trained group showed increased reduced glutathione (GSH content and reduced/oxidized (GSH/GSSG ratio, higher superoxide dismutase (MnSOD activity, and decreased lipid peroxidation in liver mitochondria. Aerobic training protected against exhaustive swimming ROS production herein characterized by decreased oxidative stress markers, higher antioxidant defenses, and increases in methyl-tetrazolium reduction and membrane potential. Trained group also presented higher time to exhaustion compared to control group. CONCLUSIONS: Swimming training induced positive adaptations in liver mitochondria of rats. Increased antioxidant defense after training coped well with exercise-produced ROS and liver mitochondria were less affected by exhaustive exercise. Therefore, liver mitochondria also adapt to exercise-induced ROS and may play an important role in exercise performance.

  2. Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson's disease.

    Gokul, Krishna; Muralidhara

    2014-07-01

    Although tomato seeds (an industrial by-product) are known to contain several bioactive compounds, studies describing their health effects are limited. Previously, we evidenced that aqueous extract of tomato seeds (TSE) markedly attenuated rotenone (ROT)-induced oxidative stress and neurotoxicity in Drosophila system. This study investigated the neuroprotective effect of TSE in a chronic ROT model of neurotoxicity in mice. Initially, we assessed the potential of oral supplements of TSE to modulate the levels of endogenous markers of oxidative stress in brain regions of mice. Subsequently, employing a co-exposure paradigm, the propensity of TSE (100 mg/kg bw, 3 weeks) to attenuate ROT-induced behavioral phenotype (gait abnormalities, anxiety-like state), oxidative dysfunctions and neurotoxicity was examined. We found that mice provided with TSE supplements exhibited progressive improvement in gait pattern and exploratory behavior. TSE markedly offset ROT-induced oxidative impairments, restored reduced glutathione levels, antioxidant defenses (superoxide dismutase, glutathione peroxidase) and protein carbonyls content in brain regions. Specifically, TSE effectively diminished ROT induced elevation in the activity levels of acetylcholinesterase and restored the dopamine levels in striatum. Interestingly, in mitochondria, TSE was able to restore the activity of mitochondrial complexes and redox state. Collectively, our findings in the chronic ROT model demonstrate the ability of TSE to alleviate behavioral phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity. Further studies in dopaminergic cell models are necessary to understand the precise molecular mechanism/s by which tomato seed bioactives offer significant neuroprotection. PMID:24831121

  3. Polychlorinated biphenyls PCB 52, PCB 180, and PCB 138 impair the glutamate-nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms.

    Llansola, Marta; Montoliu, Carmina; Boix, Jordi; Felipo, Vicente

    2010-04-19

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in the food chain and are present in human blood and milk. Children born to mothers exposed to PCBs show cognitive deficits, which are reproduced in rats perinatally exposed to PCBs. It has been proposed that PCB-induced cognitive impairment is due to impairment of the glutamate-nitric oxide (NO)-cGMP pathway. The aim of the present work was to assess whether chronic exposure to the nondioxin-like PCB52, PCB138, or PCB180 alters the function of this pathway in primary cultures of rat cerebellar neurons and to assess whether different PCBs have similar or different mechanisms of action. PCB180 and PCB138 impair the function of the glutamate-NO-cGMP pathway at nanomolar concentrations, and PCB52 impairs the function of the glutamate-NO-cGMP pathway at micromolar concentrations. The mechanisms by which different PCBs impair the function of the glutamate-NO-cGMP pathway are different. Each PCB affects the pathway at more than one step but with different potency and, for some steps, in opposite ways. Exposure to the PCBs alters the basal concentrations of intracellular calcium, NO, and cGMP. The three PCBs increase NO; however, PCB52 and PCB138 increase basal cGMP, while PCB180 decreases it. PCB52 and PCB138 decrease the activation of soluble guanylate cyclase by NO, and PCB180 increases it. Long-term exposure to PCB52, PCB180, or PCB138 reduces the activation of NO synthase and the whole glutamate-NO-cGMP pathway in response to activation of N-methyl-d-aspartate receptors. The EC(50) was 300 nM for PCB52 and 2 nM for PCB138 or PCB180. These results show that chronic exposure to nondioxin like PCBs impairs the function of the glutamate-NO-cGMP pathway in cerebellar neurons by different mechanisms and with different potencies. Impaired function of this pathway would contribute to the cognitive alterations induced by perinatal exposure to PCBs in humans. PMID:20297801

  4. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  5. Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

    Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

    2013-01-01

    Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

  6. Oxidative stress adaptation in aggressive prostate cancer may be counteracted by the reduction of glutathione reductase

    Freitas, Mariana; Baldeiras, Inês; Proença, Teresa; Alves, Vera; Mota-Pinto, Anabela; Sarmento-Ribeiro, Ana Bela

    2012-01-01

    Oxidative stress has been associated with prostate cancer development and progression due to an increase of reactive oxygen species (ROS). However, the mechanisms whereby ROS and the antioxidant system participate in cancer progression remain unclear. In order to clarify the influence of oxidative stress in prostate cancer progression, we performed this study in two human prostate cancer cell lines, PC3 and HPV10 (from metastasis and from localized cancer, respectively) and RWPE1 cells derive...

  7. Involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of Reaumuria soongorica to salt stress

    YuBing Liu; Bo Cao; MeiLing Liu

    2013-01-01

    Reaumuria soongorica is a short woody shrub widely found in semi-arid areas of China. It can survive severe environ-mental stress including high salinity in its natural habitat. Thus, we investigated the involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of R. soongorica to saline environments. R. soon-gorica was treated with 0, 100, 200 and 400 mM NaCl solutions for 14 days. Soil salt content increased significantly by watering with high content of NaCl solution, and no variation between 8 and 14 days during treatment. The levels of pe-roxidation of lipid membranes (measured by malondialdehyde content) and the activities of three antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX)) increased under salt stress. Chlorophyll and carotenoid content decreased with increasing salt content. The ratio of Chl a/Chl b and carotenoid/Chl exhibited sig-nificant increase under 400 mM NaCl. However, total flavonoid and anthocyanin contents and key enzyme activities in the flavonoid pathway including phenylalanine ammonialyase (PAL) and Chalcone isomerase (CHI) decreased under salt stress. These findings possibly suggest that R. soongorica has an adaptation protection mechanism against salt-induced oxidative damage by inducing the activity of antioxidant enzymes and maintaining a steady level of carotenoid/Chl.

  8. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

    Muhsain, Siti Nur Fadzilah, E-mail: sitinurfadzilah077@ppinang.uitm.edu.my [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Faculty of Pharmacy, University Teknologi Mara (Malaysia); Lang, Matti A., E-mail: m.lang@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia)

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200 mg pyrazole/kg/day for 3 days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. - Highlights: • Pyrazole induces oxidative stress in the mouse liver. • Pyrazole-induced oxidative stress induces mitochondrial targeting of key bilirubin regulatory enzymes, HMOX1

  9. Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury.

    Singh, Prabhat; Sharma, Bhupesh

    2016-01-01

    Hypertension has been reported to induce cognitive decline and dementia of vascular origin. Serotonin- norepinephrine reuptake transporters take part in the control of inflammation, cognitive functions, motivational acts and deterioration of neurons. This study was carried out to examine the effect of venlafaxine; a specific serotonin-norepinephrine reuptake inhibitor (SNRI), in two-kidney-one-clip-2K1C (renovascular hypertension) provoked vascular dementia (VaD) in albino rats. 2K1C technique was performed to provoke renovascular-hypertension in adult male albino Wistar rats. Learning and memory were assessed by using the elevated plus maze and Morris water maze. Mean arterial blood pressure- MABP, as well as endothelial function, were assessed by means of BIOPAC system. Serum nitrosative stress (nitrite/ nitrate), aortic superoxide anion, brain oxidative stress, inflammation, cholinergic dysfunction and brain damage (2,3,5-triphenylterazolium chloride staining) were also assessed. 2K1C has increased MABP, endothelial dysfunction as well as learning and memory impairments. 2K1C method has increased serum nitrosative stress (reduced nitrite/nitrate level), oxidative stress (increased brain thiobarbituric acid reactive species and aortic superoxide anion content along with decreased levels of brain superoxide dismutase, glutathione, and catalase), brain inflammation (increased myeloperoxidase), cholinergic dysfunction (increased acetylcholinesterase activity) and brain damage. Treatment with venlafaxine considerably attenuated renovascular-hypertension induced cognition impairment, endothelial dysfunction, serum nitrosative stress, brain and aortic oxidative stress, cholinergic function, inflammation as well as cerebral damage. The finding of this study indicates that specific modulation of the serotonin-norepinephrine transporter perhaps regarded as potential interventions for the management of renovascular hypertension provoked VaD. PMID:26915517

  10. Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery.

    Subramani, Jaganathan; Leo, Marie Dennis Marcus; Kathirvel, Kandaswamy; Arunadevi, Rathinam; Singh, Thakur Uttam; Prakash, Vellanki Ravi; Mishra, Santosh Kumar

    2010-03-25

    Both endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are important vasodilators in pulmonary circulation. Sepsis is known to impair endothelium-dependent dilation in the pulmonary vasculature, but the mechanisms are incompletely understood. We have examined the relative contribution of EDHF/NO to the attenuated endothelium-dependent relaxation of pulmonary artery in sepsis, and the role of inducible nitric oxide synthase (iNOS)-derived NO in this mechanism. Sepsis was induced in male adult Wistar rats by caecal ligation and puncture. At 18h after surgery, left and right branches of pulmonary arteries were isolated for tension recording, NO/cyclic guanosine monophosphate (cGMP) measurements, mRNA and protein expressions. Despite a marked decrease in the arterial endothelial nitric oxide synthase (eNOS) mRNA and phosphorylated-eNOS (p-eNOS) protein expressions in sepsis, endothelium-dependent relaxation to acetylcholine (ACh) mediated by NO, acetylcholine-stimulated NO release and tissue cGMP levels were moderately inhibited. Sepsis however abolished the N(G)-Nitro-l-arginine methyl ester (L-NAME)/indomethacin-resistant arterial relaxation (EDHF response) to acetylcholine in this vessel. In vitro treatment of the arterial rings from septic rats with 1400W, a selective inhibitor of iNOS restored the EDHF response, but had no effect on the acetylcholine-induced relaxation mediated by endothelial NO. The functional role of iNOS-derived NO in impairing EDHF-mediated relaxation was coincident with an increased basal NO production, iNOS mRNA and protein expressions in the rat pulmonary artery. In conclusion, the loss of the EDHF response may be primarily responsible for the endothelial dysfunction in sepsis, and its restoration by a selective iNOS inhibitor may improve pulmonary vasodilation. PMID:20035746

  11. Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer’s disease and mild cognitive impairment

    Poulsen, Keld; Bahl, Justyna Mc; Simonsen, Anja H;

    2014-01-01

    BACKGROUND: Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such...... (MCI, n = 17)), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated...... with diagnostic information and with levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid β1-42 peptide. RESULTS: Preliminary data highlighted the high risk of artifactual TTR modification due to ex vivo oxidation and thus the samples for this study were all collected using strict and...

  12. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

    Malkus Kristen A; Tsika Elpida; Ischiropoulos Harry

    2009-01-01

    Abstract While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with o...

  13. Cultivation of a novel cold-adapted nitrite oxidizing betaproteobacterium from the Siberian Arctic

    Alawi, Mashal; Lipski, André; Sanders, Tina; Pfeiffer, Eva-Maria; Spieck, Eva

    2007-01-01

    Permafrost-affected soils of the Siberian Arctic were investigated with regard to identification of nitrite oxidizing bacteria active at low temperature. Analysis of the fatty acid profiles of enrichment cultures grown at 4°C, 10°C and 17°C revealed a pattern that was different from that of known nitrite oxidizers but was similar to fatty acid profiles of Betaproteobacteria. Electron microscopy of two enrichment cultures grown at 10°C showed prevalent cells with a conspicuous ultrastructure. ...

  14. Adaptation of the phosphotungstate method to determine reduced and oxidized vitamin C in blood plasma.

    Rutkowski, Maciej; Grzegorczyk, Krzysztof; Greger, Janusz

    2004-01-01

    The phosphotungstate reagent (PTR) was used for quantitative spectrophotometric determination of physiological forms of vitamin C in blood plasma. An immediate action of PTR on the first half of the tested samples allowed to determine reduced vitamin C concentrations (I) at 700 nm. 10 mM dithiothreitol added to the second half of the samples reduced oxidized vitamin C in it--hence the total amount of this vitamin was reduced with a concentration (II) determined as above (remains of dithiothreitol were removed with N-ethylmaleimide). The difference of results (II) and (I) gave the concentration of oxidized vitamin C. The method is characterised by fault-less analytical parameters: correlation coefficients of analytical curves > 0.99, recovery factor 100.5%, variation coefficients intra- and inter-serial < 3% and < 5%, respectively, detection limit 0.05 microM. The simplicity of the method enables an easy control of the ratio of oxidized and reduced vitamin C concentrations in blood plasma--the biomarker of the level of oxidative damage to cells. PMID:15540612

  15. Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes

    Anna Lados-Krupa

    2015-01-01

    Full Text Available Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks and clot lysis time induced by recombinant tissue plasminogen activator (CLT in 163 consecutive type 2 diabetic patients (92 men and 71 women aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE, 8-iso-prostaglandin F2α (8-iso-PGF2α, oxidized low-density lipoprotein (oxLDL, and advanced glycation end products (AGE. Results. There were inverse correlations between Ks and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for Ks after adjustment for fibrinogen, disease duration, and HbA1c (all P<0.05, while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.

  16. Impaired inflammatory response and increased oxidative stress and neurodegeneration after brain injury in interleukin-6-deficient mice

    Penkowa, M; Giralt, M; Carrasco, J;

    2000-01-01

    In order to determine the role of the neuropoietic cytokine interleukin-6 (IL-6) during the first 3 weeks after a focal brain injury, we examined the inflammatory response, oxidative stress and neuronal survival in normal and interleukin-6-deficient (knockout, IL-6KO) mice subjected to a cortical...... of the antioxidants Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, and catalase remained unaffected by the IL-6 deficiency. The lesioned mice showed increased oxidative stress, as judged by malondialdehyde (MDA) and nitrotyrosine (NITT) levels and by formation of inducible nitric oxide synthase (i...... freeze lesion. In normal mice, the brain injury was followed by reactive astrogliosis and recruitment of macrophages from 1 day postlesion (dpl), peaking at 3-10 dpl, and by 20 dpl the transient immunoreactions were decreased, and a glial scar was present. In IL-6KO mice, the reactive astrogliosis and...

  17. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo. PMID:26766427

  18. Near infrared spectroscopy (NIRS as a new non-invasive tool to detect oxidative skeletal muscle impairment in children survived to acute lymphoblastic leukaemia.

    Francesca Lanfranconi

    Full Text Available BACKGROUND: Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL. The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively. METHODS AND FINDINGS: Participants underwent an incremental exercise test on a treadmill until exhaustion. Oxygen uptake ([Formula: see text], heart rate (HR, and tissue oxygenation status (Δ[HHb] of the vastus lateralis muscle evaluated by NIRS, were measured. The results showed that, in children with ALL, a significant linear regression was found by plotting [Formula: see text] vs Δ[HHb] both measured at peak of exercise. In children with ALL, the slope of the HR vs [Formula: see text] linear response (during sub-maximal and peak work rates was negatively correlated with the peak value of Δ[HHb]. CONCLUSIONS: The present study proves that the NIRS technique allows us to identify large inter-individual differences in levels of impairment in muscle O2 extraction in children with ALL. The outcome of these findings is variable and may reflect either muscle atrophy due to lack of use or, in the most severe cases, an undiagnosed myopathy.

  19. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene;

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these...... processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA......), whereas release of beta-oxidation products was unchanged at baseline, but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO(2)) and beta-oxidation of PA, whereas EPA increased only beta-oxidation significantly...

  20. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

    Tanda Koichi

    2009-06-01

    Full Text Available Abstract Background Neuronal nitric oxide synthase (nNOS is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.

  1. Modified Self-adaptive Immune Genetic Algorithm for Optimization of Combustion Side Reaction of p-Xylene Oxidation

    陶莉莉; 孔祥东; 钟伟民; 钱锋

    2012-01-01

    In recent years, immune genetic algorithm (IGA) is gaining popularity for finding the optimal solution for non-linear optimization problems in many engineering applications. However, IGA with deterministic mutation factor suffers from the problem of premature convergence. In this study, a modified self-adaptive immune genetic algorithm (MSIGA) with two memory bases, in which immune concepts are applied to determine the mutation parameters, is proposed to improve the searching ability of the algorithm and maintain population diversity. Performance comparisons with other well-known population-based iterative algorithms show that the proposed method converges quickly to the global optimum and overcomes premature problem. This algorithm is applied to optimize a feed forward neural network to measure the content of products in the combustion side reaction of p-xylene oxidation, and satisfactory results are obtained.

  2. Whole-genome analysis of the ammonia-oxidizing bacterium, Nitrosomonas eutropha C91: implications for niche adaptation

    Stein, Lisa Y [University of California, Riverside; Arp, D J [Oregon State University; Berube, PM [University of Washington, Seattle; Chain, Patrick S. G. [Lawrence Livermore National Laboratory (LLNL); Hauser, Loren John [ORNL; Jetten, MSM [Radboud University Nijmegen; Klotz, Martin G [University of Louisville, Louisville; Larimer, Frank W [ORNL; Norton, Jeanette M. [Utah State University (USU); Op den Camp, HJM [Radboud University Nijmegen; Shin, M [U.S. Department of Energy, Joint Genome Institute; Wei, Xueming [Oregon State University

    2007-12-01

    Analysis of the structure and inventory of the genome of Nitrosomonas eutropha C91 revealed distinctive features that may explain the adaptation of N. eutropha-like bacteria to N-saturated ecosystems. Multiple gene-shuffling events are apparent, including mobilized and replicated transposition, as well as plasmid or phage integration events into the 2.66 Mbp chromosome and two plasmids (65 and 56 kbp) of N. eutropha C91. A 117 kbp genomic island encodes multiple genes for heavy metal resistance, including clusters for copper and mercury transport, which are absent from the genomes of other ammonia-oxidizing bacteria (AOB). Whereas the sequences of the two ammonia monooxygenase and three hydroxylamine oxidoreductase gene clusters in N. eutropha C91 are highly similar to those of Nitrosomonas europaea ATCC 19718, a break of synteny in the regions flanking these clusters in each genome is evident. Nitrosomonas eutropha C91 encodes four gene clusters for distinct classes of haem-copper oxidases, two of which are not found in other aerobic AOB. This diversity of terminal oxidases may explain the adaptation of N. eutropha to environments with variable O2 concentrations and/or high concentrations of nitrogen oxides. As with N. europaea, the N. eutropha genome lacks genes for urease metabolism, likely disadvantaging nitrosomonads in low-nitrogen or acidic ecosystems. Taken together, this analysis revealed significant genomic variation between N. eutropha C91 and other AOB, even the closely related N. europaea, and several distinctive properties of the N. eutropha genome that are supportive of niche specialization.

  3. Electroacupuncture pretreatment prevents cognitive impairment induced by limb ischemia-reperfusion via inhibition of microglial activation and attenuation of oxidative stress in rats.

    Chen, Ye; Zhou, Jun; Li, Jun; Yang, Shi-Bin; Mo, Li-Qun; Hu, Jie-Hui; Yuan, Wan-Li

    2012-01-13

    Limb ischemia-reperfusion (LI/R) is associated with high morbidity and mortality. Furthermore, critical trauma survivors can present cognitive impairment. Cognitive function, survival rate, oxidative stress and neuronal health were examined to elucidate (1) the magnitude of cognitive effects of prolonged reperfusion, (2) potential players in the mechanistic pathway mediating such effects, and (3) possible benefits of electroacupuncture (EA) pretreatment at Baihui (GV20), Yanglingquan (GB34), Taichong (LR3), Zusanli (ST36) and Xuehai (SP10) acupoints. LI/R was induced in rats by placing a rubber tourniquet on each hind limb for 3h, and the animals were evaluated periodically for 7d after LI/R. Rats subjected to LI/R had significantly lower survival rates, and displayed evidence of brain injury and cognitive dysfunction (as determined by the Morris water maze test) 1d and 3d after reperfusion compared to sham-operated controls. LI/R also resulted in higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA), microglial activation, and decreased superoxide dismutase (SOD) activity within Cornu Ammonis area 1 (CA1) of the hippocampus. Depressed survival rates, microglial activation, oxidative damage, and histological changes, as well as cognitive dysfunction were partially or fully attenuated in rats that received 14d of EA prior to LI/R. These findings indicate that LI/R can result in cognitive dysfunction related to activated microglia and elevated oxidative stress, and that EA has neuroprotective potential mediated, at least in part, by inhibition of microglial activation and attenuation of oxidative stress. PMID:22129788

  4. A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat.

    Krishna, Gokul; Divyashri, Gangaraju; Prapulla, S G; Muralidhara

    2015-09-01

    Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200 ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota. PMID:26248513

  5. A low-voltage complementary metal-oxide semiconductor adapter circuit suitable for input rail-to-rail operation

    Tadić, Nikša; Zogović, Milena; Banjević, Mirjana; Zimmermann, Horst

    2010-11-01

    In this article, a low-voltage complementary metal-oxide semiconductor (CMOS) input signal adapter (ISA) suitable for input rail-to-rail operation of various types of analogue basic building blocks is presented. The adapter acts as a pre-stage with infinite input resistance and linear transfer characteristics. Its input signal is translated into the region fitting the operating range of the following stage. The generality of the proposed method is proven through the application of the ISA in different types of analogue basic building blocks designed in 0.5 μm CMOS technology. They are the following: below-negative-rail-to-above-positive-rail voltage-controlled transconductor, quasi rail-to-rail voltage-controlled resistor (VCR), rail-to-rail operational amplifier (OA) and quasi rail-to-rail second generation current conveyor. The proposed negative resistance quasi rail-to-rail VCR and rail-to-rail OA have been used in a Sallen and Key band-pass filter. All of these analogue basic building blocks and their applications in the form of the Sallen and Key band-pass filter operate from a single supply of 1.5 V. Simulation results confirm the predictions of the analysis performed.

  6. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  7. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Sobinoff, A.P.; Pye, V. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); Nixon, B.; Roman, S.D. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia)

    2012-04-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  8. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

    Gao F

    2014-11-01

    hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden. Keywords: status epilepticus, pilocarpine, memory impairment, oxidative stress, neuroprotection

  9. Chlorogenic acid protection of neuronal nitric oxide synthase-positive neurons in the hippocampus of mice with impaired learning and memory

    Qiuyun Tu; Xiangqi Tang; Zhiping Hu

    2008-01-01

    BACKGROUND: Clinical practice and modern pharmacology have confirmed that ehlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE: To observe the effects of chlorogenic acid on neuronal nitric oxide synthase (nNOS)-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING: The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005.MATERIALS: Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 μL kainic acid (0.4 mg/mL) into the hippocampus.METHODS: The mice were randomized into three groups (n = 16): model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5 μ L physiological saline into the hippocampus, and 2 days later, they received an intragastric administration of physiological saline. Each mouse received two intragastric administrations (1 mL solution once) per day, for a total of 35 days. MAIN OUTCOME MEASURES: Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device.RESULTS: At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups (P > 0.05). Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group (P 0.05). At day 7 following intervention, the number

  10. Gain of Cellular Adaptation Due to Prolonged p53 Impairment Leads to Functional Switchover from p53 to p73 during DNA Damage in Acute Myeloid Leukemia Cells*

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar

    2010-01-01

    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expressi...

  11. Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

    Bruno Pereira Carreira; Maria Inês Morte; Ana Isabel Santos; Ana Sofia Lourenço; António Francisco Ambrósio; Carvalho, Caetana M.; Araújo, Inês M.

    2014-01-01

    Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an...

  12. Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats.

    Kyathanahalli, Chandrashekara Nagaraj; Manjunath, Mallayya Jayawanth; Muralidhara

    2014-09-01

    Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ+WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats. PMID:24488064

  13. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

    Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.

    2012-10-24

    High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

  14. The architecture of iron microbial mats reflects the adaptation of chemolithotrophic iron oxidation in freshwater and marine environments

    Clara S Chan

    2016-06-01

    Full Text Available Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to

  15. The Architecture of Iron Microbial Mats Reflects the Adaptation of Chemolithotrophic Iron Oxidation in Freshwater and Marine Environments

    Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Glazer, Brian T.; Krepski, Sean T.; Emerson, David

    2016-01-01

    Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to chemolithotrophic Fe

  16. Pretreatment with Rhodiola Rosea Extract Reduces Cognitive Impairment Induced by Intracerebroventricular Streptozotocin in Rats: Implication of Anti-oxidative and Neuroprotective Effects

    ZE-QIANG QU; YAN ZHOU; YUAN-SHAN ZENGt; YAN LI; PETER CHUNG

    2009-01-01

    Objectives To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

  17. Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster.

    Manjunath, M J; Muralidhara

    2015-04-01

    Withania somnifera (Ashwagandha, WS) or Indian ginseng possesses multiple pharmacological properties which are mainly attributed to the active constituents, withanolides. Despite its extensive usage as a memory enhancer and a nerve tonic, few attempts have been made to ascertain its usage in the management of Parkinson's disease. In the present study, we investigated the neuroameliorative effects of WS in a rotenone (ROT) model of Drosophila melanogaster (Oregon-K). Initially, we ascertained the ability of WS-enriched diet (0-0.05 %) to protect against ROT induced lethality and locomotor phenotype in adult male flies. Further, employing a co-exposure paradigm, we investigated the propensity of WS to offset ROT-induced oxidative stress, mitochondrial dysfunctions and neurotoxicity. WS conferred significant protection against ROT-induced lethality, while the survivor flies exhibited improved locomotor phenotype. Biochemical investigations revealed that ROT-induced oxidative stress was significantly diminished by WS enrichment. WS caused significant elevation in the levels of reduced GSH/non-protein thiols. Furthermore, the altered activity levels of succinate dehydrogenase, MTT, membrane bound enzymes viz., NADH-cytochrome-c reductase and succinate-cytochrome-c reductase were markedly restored to normalcy. Interestingly, ROT-induced perturbations in cholinergic function and depletion in dopamine levels were normalized by WS. Taken together these data suggests that the neuromodulatory effect of WS against ROT- induced neurotoxicity is probably mediated via suppression of oxidative stress and its potential to attenuate mitochondrial dysfunctions. Our further studies aim to understand the underlying neuroprotective mechanisms of WS and withanolides employing neuronal cell models. PMID:25829577

  18. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

  19. Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

    Ortiz-Avila, Omar; Gallegos-Corona, Marco Alonso; Sánchez-Briones, Luis Alberto; Calderón-Cortés, Elizabeth; Montoya-Pérez, Rocío; Rodriguez-Orozco, Alain R; Campos-García, Jesús; Saavedra-Molina, Alfredo; Mejía-Zepeda, Ricardo; Cortés-Rojo, Christian

    2015-08-01

    Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis. PMID:26060181

  20. Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production.

    Suman, Shubhankar; Rodriguez, Olga C; Winters, Thomas A; Fornace, Albert J; Albanese, Chris; Datta, Kamal

    2013-08-01

    Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion 56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation. PMID:23928451

  1. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated carbon ion beams (290 MeV/u, 31 keV/μm or 135 MeV/u, 31 keV/μm). Then, the cells were allowed forming colonies. ICR male mice (Jcl: ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm or 135 MeV/u, 25 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The small intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TUNEL- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant elevated surviving fractions of cells was observed when the cells were challengingly irradiated after the priming irradiation with accelerate carbon ion beams. This enhancement was partially suppressed by Nitric oxide (NO) radical scavenger, carboxy-PTIO (c-PTIO). The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in the unirradiated small intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. In addition, a significant reduction of apoptotic cells in the intestine and testis, when mice were challengingly irradiated after the priming irradiation with accelerate carbon or argon ion beams. These observations were partially suppressed by c-PTIO into the peritoneal cavity. Furthermore, it is suggested that the apoptosis may be induced in the tissue stem cells of small intestine and testis. (author)

  2. Adaptive cytoprotection through modulation of nitric oxide in ethanol-evoked gastritis

    Joshua Ka-Shun Ko; Chi-Hin Cho; Shiu-Kum Lam

    2004-01-01

    AIM: To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats.METHODS: Either 200 ml/L ethanol, 50 g/L NaCl or 0.3 mol/LHCl was pretreated to normal or 800 mL/L ethanol-induced acute gastritis Sprague-Dawley rats before a subsequent challenge with 500 mL/L ethanol. Both macroscopic lesion areas and histological damage scores were determined in the gastric mucosa of each group of animals. Besides,gastric mucosal activities of NO synthase isoforms and of superoxide dismutase, along with mucosal level of leukotriene (LT)C4 were measured.RESULTS: Macroscopic mucosal damages were protected by 200 mL/L ethanol and 50 g/L NaCl in gastritis rats.However, although 200 mL/L ethanol could protect the surface layers of mucosal cells in normal animals (protection attenuated by NG-nitro-L-arginine methyl ester), no cytoprotection against deeper histological damages was found in gastritis rats. Besides, inducible NO synthase activity was increased in the mucosa of gastritis animals and unaltered by mild irritants. Nevertheless, the elevation in mucosal LTC4 level following 500 mL/L ethanol administration and under gastritis condition was significantly reduced by pretreatment of all three mild irritants in both normal and gastritis animals.CONCLUSION: These findings suggest that the aggravated 500 mL/L ethanol-evoked mucosal damages under gastritis condition could be due to increased inducible NO and LTC4 production in the gastric mucosa. Only 200 mL/L ethanol is truly "cytoprotective" at the surface glandular level of nongastritis mucosa. Furthermore, the macroscopic protection of the three mild irritants involves reduction of LTC4 level in both normal and gastritis mucosa, implicating preservation of the vasculature.

  3. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated neon (400 MeV/u, 31 keV/μm) or iron (500 MeV/u, 200 keV/μm) ion beams. Then, the cells were allowed forming colonies, were cultured for 48 h to obtained samples for Western blot analysis, or were cultured for several weeks to fix mutations in the locus of hprt gene. ICR male mice (Jcl:ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TdT-mediated dUTP-biotin nick end-labeling (TUNEL)- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant reduction of mutation rate of the hprt gene was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. This reduction was partially suppressed by NO radical scavenger, carboxy-PTIO. The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in unirradiated intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. These observations were partially suppressed by carboxy-PTIO into the peritoneal cavity. (author)

  4. Accumulation of small heat shock proteins, including mitochondrial HSP22, induced by oxidative stress and adaptive response in tomato cells

    Changes in gene expression, by application of H2O2, O2.- generating agents (methyl viologen, digitonin) and gamma irradiation to tomato suspension cultures, were investigated and compared to the well-described heat shock response. Two-dimensional gel protein mapping analyses gave the first indication that at least small heat shock proteins (smHSP) accumulated in response to application of H2O2 and gamma irradiation, but not to O2.- generating agents. While some proteins seemed to be induced specifically by each treatment, only part of the heat shock response was observed. On the basis of Northern hybridization experiments performed with four heterologous cDNA, corresponding to classes I-IV of pea smHSP, it could be concluded that significant amounts of class I and II smHSP mRNA are induced by H2O2 and by irradiation. Taken together, these results demonstrate that in plants some HSP genes are inducible by oxidative stresses, as in micro-organisms and other eukaryotic cells. HSP22, the main stress protein that accumulates following H2O2 action or gamma irradiation, was also purified. Sequence homology of amino terminal and internal sequences, and immunoreactivity with Chenopodium rubrum mitochondrial smHSP antibody, indicated that the protein belongs to the recently discovered class of plant mitochondrial smHSP. Heat shock or a mild H2O2 pretreatment was also shown to lead to plant cell protection against oxidative injury. Therefore, the synthesis of these stress proteins can be considered as an adaptive mechanism in which mitochondrial protection could be essential

  5. The Relationship between Visual Impairment and Gestures.

    Frame, Melissa J.

    2000-01-01

    A study found the gestural activity of 15 adolescents with visual impairments differed from that of 15 adolescents with sight. Subjects with visual impairments used more adapters (especially finger-to-hand gestures) and fewer conversational gestures. Differences in gestural activity by degree of visual impairment and grade in school were also…

  6. Subtle reproductive impairment through nitric oxide-mediated mechanisms in sea urchins from an area affected by harmful algal blooms

    Migliaccio, Oriana; Castellano, Immacolata; di Cioccio, Davide; Tedeschi, Gabriella; Negri, Armando; Cirino, Paola; Romano, Giovanna; Zingone, Adriana; Palumbo, Anna

    2016-05-01

    The health of the sea urchin Paracentrotus lividus, a key species in the Mediterranean Sea, is menaced by several pressures in coastal environments. Here, we aimed at assessing the reproductive ability of apparently healthy P. lividus population in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata. Wide-ranging analyses were performed in animals collected prior to and during the bloom, as well as at several times thereafter, during the reproductive season. Adults showed a low fertilization rate, along with high nitric oxide (NO) levels in the gonads and the nitration of the major yolk protein toposome, which is an important player in sea urchin development. Serious developmental anomalies were observed in the progeny, which persist several months after the bloom. NO levels were high in the different developmental stages, which also showed variations in the transcription of several genes that were found to be directly or indirectly modulated by NO. These results highlight subtle but important reproductive flaws transmitted from the female gonads to the offspring with the NO involvement. Despite a recovery along time after the bloom, insidious damages can be envisaged in the local sea urchin population, with possible reverberation on the whole benthic system.

  7. Impaired Nitric Oxide Mediated Vasodilation In The Peripheral Circulation In The R6/2 Mouse Model Of Huntington's Disease.

    Kane, Andrew D; Niu, Youguo; Herrera, Emilio A; Morton, A Jennifer; Giussani, Dino A

    2016-01-01

    Recent evidence shows that the Huntington's disease (HD) extends beyond the nervous system to other sites, including the cardiovascular system. Further, the cardiovascular pathology pre-dates neurological decline, however the mechanisms involved remain unclear. We investigated in the R6/2 mouse model of HD nitric oxide (NO) dependent and independent endothelial mechanisms. Femoral artery reactivity was determined by wire myography in wild type (WT) and R6/2 mice at 12 and 16 weeks of adulthood. WT mice showed increased endothelial relaxation between 12 and 16 weeks (Rmax: 72 ± 7% vs. 97 ± 13%, P R6/2 mice showed enhanced endothelial relaxation already by 12 weeks (Rmax at 12w: 72 ± 7% vs. 94 ± 5%, WT vs. R6/2, P R6/2, P R6/2 mouse developed overt endothelial dysfunction due to an inability to increase NO dependent vasodilation. The data add to the growing literature of non-neural manifestations of HD and implicate NO depletion as a key mechanism underlying the HD pathophysiology in the peripheral vasculature. PMID:27181166

  8. Endogenous nitric oxide mediates He-Ne laser-induced adaptive responses in salt stressed-tall fescue leaves.

    Li, Yongfeng; Gao, Limei; Han, Rong

    2016-10-01

    The aim of this study was to investigate the role of endogenous nitric oxide in protective effects of He-Ne laser on salt stressed-tall fescue leaves. Salt stress resulted in significant increases of membrane injury, reactive oxygen species (ROS) production, polyamine accumulation, and activities of SOD, POD, and APX, while pronounced decreases of antioxidant contents, CAT activity and intracellular Ca(2+) concentration in seedlings leaves. He-Ne laser illumination caused a distinct alleviation of cellular injury that was reflected by the lower MDA amounts, polyamine accumulation and ROS levels at the stress period. In contrast, the laser treatment displayed a higher Ca(2+) concentration, antioxidant amounts, NO release, antioxidant enzyme, and NOS activities. These responses could be blocked due to the inhibition of NO biosynthesis by PTIO (NO scavenger) or LNNA (NOS inhibitor). The presented results demonstrated that endogenous NO might be involved in the progress of He-Ne laser-induced plant antioxidant system activation and ROS degradation in order to enhance adaptive responses of tall fescue to prolonged saline conditions. PMID:27309569

  9. Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation

    Zhiqian Yi

    2015-09-01

    Full Text Available Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress.

  10. Mitigation of peroxynitrite-mediated nitric oxide (NO) toxicity as a mechanism of induced adaptive NO resistance in the CNS.

    Bishop, Amy; Gooch, Renea; Eguchi, Asuka; Jeffrey, Stephanie; Smallwood, Lorraine; Anderson, James; Estevez, Alvaro G

    2009-04-01

    During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY), leading to cell death. Previously, we have found that motor neurons exposed to low levels of NO become resistant to subsequent cytotoxic NO challenge; an effect dubbed induced adaptive resistance (IAR). Here, we report IAR mitigates, not only cell death, but 3NY formation in response to cytotoxic NO. Addition of an NO scavenger before NO challenge duplicates IAR, implicating reactive nitrogenous species in cell death. Addition of uric acid (a peroxynitrite scavenger) before cytotoxic NO challenge, duplicates IAR, implicating peroxynitrite, with subsequent 3NY formation, in cell death, and abrogation of this pathway as a mechanism of IAR. IAR is dependent on the heme-metabolizing enzyme, heme oxygenase-1 (HO1), as indicated by the elimination of IAR by a specific HO1 inhibitor, and by the finding that neurons isolated from HO1 null mice have increased NO sensitivity with concomitant increased 3NY formation. This data indicate that IAR is an HO1-dependent mechanism that prevents peroxynitrite-mediated NO toxicity in motor neurons, thereby elucidating therapeutic targets for the mitigation of CNS disease and injury. PMID:19183270

  11. Genome-guided analysis of physiological capacities of Tepidanaerobacter acetatoxydans provides insights into environmental adaptations and syntrophic acetate oxidation.

    Müller, Bettina; Manzoor, Shahid; Niazi, Adnan; Bongcam-Rudloff, Erik; Schnürer, Anna

    2015-01-01

    This paper describes the genome-based analysis of Tepidanaerobacter acetatoxydans strain Re1, a syntrophic acetate-oxidising bacterium (SAOB). Principal issues such as environmental adaptations, metabolic capacities, and energy conserving systems have been investigated and the potential consequences for syntrophic acetate oxidation discussed. Briefly, in pure culture, T. acetatoxydans grows with different organic compounds and produces acetate as the main product. In a syntrophic consortium with a hydrogenotrophic methanogen, it can also reverse its metabolism and instead convert acetate to formate/H2 and CO2. It can only proceed if the product formed is continuously removed. This process generates a very small amount of energy that is scarcely enough for growth, which makes this particular syntrophy of special interest. As a crucial member of the biogas-producing community in ammonium-rich engineered AD processes, genomic features conferring ammonium resistance, bacterial defense, oxygen and temperature tolerance were found, as well as attributes related to biofilm formation and flocculation. It is likely that T. acetatoxydans can form an electrochemical gradient by putative electron-bifurcating Rnf complex and [Fe-Fe] hydrogenases, as observed in other acetogens. However, genomic deficiencies related to acetogenic metabolism and anaerobic respiration were discovered, such as the lack of formate dehydrogenase and F1F0 ATP synthase. This has potential consequences for the metabolic pathways used under SAO and non-SAO conditions. The two complete sets of bacteriophage genomes, which were found to be encoded in the genome, are also worthy of mention. PMID:25811859

  12. Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation.

    Yi, Zhiqian; Xu, Maonian; Magnusdottir, Manuela; Zhang, Yuetuan; Brynjolfsson, Sigurdur; Fu, Weiqi

    2015-10-01

    Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress. PMID:26426027

  13. Calycosin ameliorates diabetes-induced cognitive impairments in rats by reducing oxidative stress via the PI3K/Akt/GSK-3β signaling pathway.

    Wang, Xiang; Zhao, Linhui

    2016-04-29

    Diabetic encephalopathy is one of the most prevalent chronic complications of diabetes mellitus (DM), but there is currently no effective method of prevention nor proven therapeutic regimen for it. In this study, we investigated the effects of calycosin on cognitive behavior and the potential mechanism involved in streptozocin-induced diabetic rats. The effects of diabetes and calycosin treatment on spatial learning and memory were evaluated using the Morris Water Maze, passive avoidance and motor coordination tests. Histological analysis of the hippocampus cornu ammonis 1 (CA1) region was conducted in rats. The decreased expression of the synapsin (SYN) and postsynatptic density protein (PSD-95), as well as brain-derived neurotrophic factor (BDNF) in diabetic rats was measured by quantitative real-time PCR and western blot. Treatment with calycosin promoted a reduction in the expression of SYN, PSD-95 and BDNF. In addition, diabetic rats showed increased MDA levels, and decreased SOD levels and GSH-Px activities in the hippocampus, as well as increased AChE activity in the cerebral cortex; these changes were reversed by calycosin supplementation. Thus, the impairment of learning and memory in STZ-induced diabetic rats was alleviated by calycosin, and that the degree of alleviation was associated with oxidative stress. We also found that calycosin treatment significantly stimulated Akt phosphorylation and decreased GSK-3β and tau phosphorylation, and that these changes could be restored by the PI3K/Akt inhibitor LY294002. In conclusion, calycosin had a beneficial effect on the amelioration, prevention and treatment of diabetes-associated cognitive deficits, through its involvement in oxidative stress, synaptic function and the PI3K/Akt/GSK-3β pathway. PMID:26970304

  14. Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide.

    Rajeshwary Ghosh

    Full Text Available INTRODUCTION: Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI. Nitric oxide (NO has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median compared to 4.0 µM (median in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. METHODS AND RESULTS: The restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm containing 0.28 mmol sodium nitroprusside (SNP in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283 were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 µM the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. CONCLUSION: Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. TRIAL REGISTRATION: www.ctri.nic.in CTRI/2013/12/004236.

  15. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice

    Rhein, Virginie; Song, Xiaomin; Wiesner, Andreas; Ittner, Lars M.; Baysang, Ginette; Meier, Fides; Ozmen, Laurence; Bluethmann, Horst; Dröse, Stefan; Brandt, Ulrich; Savaskan, Egemen; Czech, Christian; Götz, Jürgen; Eckert, Anne

    2009-01-01

    Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ)-containing plaques, neurofibrillary tangles, and neuron and synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APPswPS2N141I double-transgenic APP152 mice develop Aβ plaques. Cross-breeding generates triple transgenic (tripleAD) mice that combine both pathologies in one model. To determine functional consequences of the combined Aβ and tau pathologies, we performed a proteomic analysis followed by functional validation. Specifically, we obtained vesicular preparations from tripleAD mice, the parental strains, and nontransgenic mice, followed by the quantitative mass-tag labeling proteomic technique iTRAQ and mass spectrometry. Within 1,275 quantified proteins, we found a massive deregulation of 24 proteins, of which one-third were mitochondrial proteins mainly related to complexes I and IV of the oxidative phosphorylation system (OXPHOS). Notably, deregulation of complex I was tau dependent, whereas deregulation of complex IV was Aβ dependent, both at the protein and activity levels. Synergistic effects of Aβ and tau were evident in 8-month-old tripleAD mice as only they showed a reduction of the mitochondrial membrane potential at this early age. At the age of 12 months, the strongest defects on OXPHOS, synthesis of ATP, and reactive oxygen species were exhibited in the tripleAD mice, again emphasizing synergistic, age-associated effects of Aβ and tau in perishing mitochondria. Our study establishes a molecular link between Aβ and tau protein in AD pathology in vivo, illustrating the potential of quantitative proteomics. PMID:19897719

  16. Cardiomyocyte-Restricted Deletion of PPARβ/δ in PPARα-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation

    Jian Liu

    2011-01-01

    Full Text Available It is well documented that PPARα and PPARβ/δ share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPARβ/δ deficiency in mice leads to severe cardiac pathological development, whereas global PPARα knockout shows a benign cardiac phenotype. It is unknown whether a PPARα-null background would alter the pathological development in mice with cardiomyocyte-restricted PPARβ/δ deficiency. In the present study, a mouse model with long-term PPARβ/δ deficiency in PPARα-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPARα-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPARβ/δ deficiency. Moreover, PPARα-null did not alter the phenotypic development in adult mice with the short-term deletion of PPARβ/δ in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPARβ/δ in PPARα-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPARβ/δ is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPARα.

  17. Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus

    Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Hwang, Un-Ki [Marine Ecological Risk Assessment Center, West Sea Fisheries Research Institute, National Fisheries Research and Development Institute, Incheon 400-420 (Korea, Republic of); Kim, Il-Chan; Yim, Joung Han [Division of Life Sciences, Korea Polar Research Institute, Incheon 406-840 (Korea, Republic of); Leung, Kenneth Mei Yee [School of Biological Sciences and the Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Lee, Yong Sung [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2014-07-01

    irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50–200 Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus.

  18. Impaired Driving

    ... help prevent injuries and deaths from alcohol-impaired driving. The Problem Risk Factors BAC Effects Prevention Additional Resources How big is the problem? In 2014, 9,967 people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of ...

  19. Visual Impairment

    ... poorly lit spaces, and colors that seem faded. Diabetic retinopathy (pronounced: reh-ton-AH-pa-thee) occurs when ... that is likely to cause visual impairment, many treatments are available. Options may include eyeglasses, contact lenses, ...

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

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

    2016-09-01

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

  1. Effect of Modified Wuzi Yanzong Granule(加味五子衍宗颗粒)on Patients with Mild Cognitive Impairment from Oxidative Damage Aspect

    2007-01-01

    Objective:To observe the effects of modified Wuzi Yanzong Granule(加味五子洐宗颗粒,WYG)on memory function and the activity of serum superoxide dismutase(SOD),malondialdehyde(MDA)levels,leukocyte mitochondrial DNA(mtDNA)deletion rate and β-amyloid protein1-28(Aβ1-28 )in patients with mild cognitive impairment(MCI).Methods:Thirty-six patients with MCI were selected based on the internationally recognized Petersen's criteria,and equally and randomly assigned to two groups.The treated group was treated with WYG and the control group was treated with placebo for 3 months.In addition,20 healthy subjects were included in the study as the normal control group.Changes of memory function,SOD activity,MDA content,leukocyte mtDNA deletion rate and Aβ1-28 content were observed before and after treatment.Results:Compared with the normal control group,the memory quotient and SOD activity in patients with MCI decreased significantly(P<0.01),while MDA,Aβ1-28 levels and the leukocyte mtDNA deletion rate increased significantly(P<0.01).After treatment,levels of memory quotient and serum SOD activity increased while the serum MDA level,leukocyte mtDNA deletion rate and Aβ1-28 level decreased in the treated group compared with those before treatment(P<0.01,P<0.05).Meanwhile,leukocyte mtDNA deletion rate and Aβ1-28 content in the treated group were all lower than those in the control group(P<0.05).Conclusion:WYG could improve memory function in patients with MCI and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase,the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage.WYG shows clinical significance in delaying the progression of MCI.

  2. Impaired Phagocytosis of Apoptotic Cells by Macrophages in Chronic Granulomatous Disease Is Reversed by IFN-γ in a Nitric Oxide-Dependent Manner

    Fernandez-Boyanapalli, Ruby; McPhillips, Kathleen A.; Frasch, S. Courtney; Janssen, William J.; Dinauer, Mary C.; Riches, David W.H.; Henson, Peter M.; Byrne, Aideen; Bratton, Donna L.

    2010-01-01

    Immunodeficiency in chronic granulomatous disease (CGD) is well characterized. Less understood are exaggerated sterile inflammation and autoimmunity associated with CGD. Impaired recognition and clearance of apoptotic cells resulting in their disintegration may contribute to CGD inflammation. We hypothesized that priming of macrophages (Mϕs) with IFN-γ would enhance impaired engulfment of apoptotic cells in CGD. Diverse Mϕ populations from CGD (gp91phox−/−) and wild-type mice, as well as huma...

  3. Adaptation of a thermo assay balance to the study of oxidation by water vapor and / or oxygen at high temperatures

    The construction of an apparatus which allows the continuous follow-up of oxidation in the presence of steam, with different addition of O2 is described. This apparatus permits to abserve the initial kinetics of oxidation of the stainless steel type 18-10 in mixtures steam/oxygen. (A.R.)

  4. Hearing Impairment

    ... hearing loss is present at birth. Acquired hearing loss happens later in life — during childhood, the teen years, or in adulthood — ... for your ears to avoid a permanent hearing loss. See your doctor right away ... basis. What's Life Like for People Who Are Hearing Impaired? For ...

  5. Developmental exposure to polychlorinated biphenyls or methylmercury, but not to its combination, impairs the glutamate-nitric oxide-cyclic GMP pathway and learning in 3-month-old rats.

    Piedrafita, B; Erceg, S; Cauli, O; Felipo, V

    2008-07-17

    Prenatal exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) contaminated food may affect brain development, leading to long-term alterations in cognitive function. Both types of contaminants, PCBs and MeHg, are often found together contaminating food, especially fish in some polluted areas. Exposure to combinations of neurotoxicants may exert different effects on the developing nervous system than exposure to individual contaminants. Developmental exposure (during pregnancy and lactation) to PCB126 or PCB153 impairs learning ability when the rats are 3 months old. Impairment of learning seems to be a consequence of impairment of the function of the glutamate-nitric oxide (NO)-cGMP pathway in brain in vivo. The aims of the present work were 1) to assess whether perinatal exposure to MeHg also affects the function of the glutamate-NO-cGMP pathway in brain in vivo analyzed by in vivo brain microdialysis and/or the ability to learn the Y maze task when the rats are 3 months old, and 2) to assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 potentiates, decreases or does not modify the effects of the individual neurotoxicants. Perinatal exposure to PCB126, PCB153 or MeHg impaired the function of the glutamate-NO-cGMP pathway in cerebellum and learning ability. However, co-exposure to PCB126+MeHg or PCB153+MeHg inhibits the impairment of the pathway or learning ability. These results support that the function of this pathway modulates learning of the Y maze task. Moreover, they show that co-exposure to these PCBs and MeHg does not exacerbate, but reduces the effects on the ability to learn this task. PMID:18556134

  6. Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines

    Vesper, B; Onul, A; Haines III, G; Tarjan, G; Xue, J; Elseth, K; Aydogan, B.; Altman, M.; Roeske, J; Paradise, W; De Vitto, H; Radosevich, J

    2013-01-01

    There is a lack of understanding of the casual mechanisms behind the observation that some breast adenocarcinomas have identical morphology and comparatively different cellular growth behavior. This is exemplified by a differential response to radiation, chemotherapy, and other biological intervention therapies. Elevated concentrations of the free radical nitric oxide (NO), coupled with the up-regulated enzyme nitric oxide synthase (NOS) which produces NO, are activities which impact tumor gr...

  7. AMPK-mediated increase of glycolysis as an adaptive response to oxidative stress in human cells: implication of the cell survival in mitochondrial diseases.

    Wu, Shi-Bei; Wei, Yau-Huei

    2012-02-01

    We report that the energy metabolism shifts to anaerobic glycolysis as an adaptive response to oxidative stress in the primary cultures of skin fibroblasts from patients with MERRF syndrome. In order to unravel the molecular mechanism involved in the alteration of energy metabolism under oxidative stress, we treated normal human skin fibroblasts (CCD-966SK cells) with sub-lethal doses of H(2)O(2). The results showed that several glycolytic enzymes including hexokinase type II (HK II), lactate dehydrogenase (LDH) and glucose transporter 1 (GLUT1) were up-regulated in H(2)O(2)-treated normal skin fibroblasts. In addition, the glycolytic flux of skin fibroblasts was increased by H(2)O(2) in a dose-dependent manner through the activation of AMP-activated protein kinase (AMPK) and phosphorylation of its downstream target, phosphofructokinase 2 (PFK2). Moreover, we found that the AMPK-mediated increase of glycolytic flux by H(2)O(2) was accompanied by an increase of intracellular NADPH content. By treatment of the cells with glycolysis inhibitors, an AMPK inhibitor or genetic knockdown of AMPK, respectively, the H(2)O(2)-induced increase of NADPH was abrogated leading to the overproduction of intracellular ROS and cell death. Significantly, we showed that phosphorylation levels of AMPK and glycolysis were up-regulated to confer an advantage of survival for MERRF skin fibroblasts. Taken together, our findings suggest that the increased production of NADPH by AMPK-mediated increase of the glycolytic flux contributes to the adaptation of MERRF skin fibroblasts and H(2)O(2)-treated normal skin fibroblasts to oxidative stress. PMID:22001850

  8. The 2013 SFRBM discovery award: selected discoveries from the butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment.

    Butterfield, D Allan

    2014-09-01

    This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy-induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called "chemobrain" by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a proinflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent with

  9. Integrating nitric oxide, nitrite and hydrogen sulfide signaling in the physiological adaptations to hypoxia: A comparative approach

    Fago, Angela; Jensen, Frank Bo; Tota, Bruno;

    2012-01-01

    Hydrogen sulfide (H2S), nitric oxide (NO) and nitrite (NO2-) are formed in vivo and are of crucial importance in the tissue response to hypoxia, particularly in the cardiovascular system, where these signaling molecules are involved in a multitude of processes including the regulation of vascular...

  10. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

    Gao, Fei; Gao, Ying; Liu, Yang-Feng; Wang, Li; Li, Ya-Jun

    2014-01-01

    Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 day...

  11. The Architecture of Iron Microbial Mats Reflects the Adaptation of Chemolithotrophic Iron Oxidation in Freshwater and Marine Environments

    Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Brian T. Glazer; Krepski, Sean T.; Emerson, David

    2016-01-01

    Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respecti...

  12. Application of adaptive neuro-fuzzy inference system techniques and artificial neural networks to predict solid oxide fuel cell performance in residential microgeneration installation

    Entchev, Evgueniy; Yang, Libing [Integrated Energy Systems Laboratory, CANMET Energy Technology Centre, 1 Haanel Dr., Ottawa, Ontario (Canada)

    2007-06-30

    This study applies adaptive neuro-fuzzy inference system (ANFIS) techniques and artificial neural network (ANN) to predict solid oxide fuel cell (SOFC) performance while supplying both heat and power to a residence. A microgeneration 5 kW{sub el} SOFC system was installed at the Canadian Centre for Housing Technology (CCHT), integrated with existing mechanical systems and connected in parallel to the grid. SOFC performance data were collected during the winter heating season and used for training of both ANN and ANFIS models. The ANN model was built on back propagation algorithm as for ANFIS model a combination of least squares method and back propagation gradient decent method were developed and applied. Both models were trained with experimental data and used to predict selective SOFC performance parameters such as fuel cell stack current, stack voltage, etc. The study revealed that both ANN and ANFIS models' predictions agreed well with variety of experimental data sets representing steady-state, start-up and shut-down operations of the SOFC system. The initial data set was subjected to detailed sensitivity analysis and statistically insignificant parameters were excluded from the training set. As a result, significant reduction of computational time was achieved without affecting models' accuracy. The study showed that adaptive models can be applied with confidence during the design process and for performance optimization of existing and newly developed solid oxide fuel cell systems. It demonstrated that by using ANN and ANFIS techniques SOFC microgeneration system's performance could be modelled with minimum time demand and with a high degree of accuracy. (author)

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

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

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. ...

  14. ECONOMIC EFFICIENT PRODUCTION OF BIOMASS ADAPTED TO THE SUBSTRATE OF OIL OXIDIZING ACTINOBACILLOSIS USED IN BIOREMEDIATION PROCESSES

    Khudokormov A. A.

    2013-10-01

    Full Text Available In the article we have studied the technology of obtaining a biomass of oil oxidizing microorganisms in a nutrient medium containing vegetable oil as the sole source of carbon and energy. In vitro and in soil experiment we have confirmed the effectiveness of the resulting biomass at work on bioremediation of oil contaminated sites. It is shown that the use of vegetable oil during culturing allows obtaining the same amount of biomass and carbohydrate raw materials, but the efficiency of its use is 20% higher, in average

  15. Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes.

    Park, Sun-Ji; Choe, Young-Geun; Kim, Jung-Hak; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

    2016-07-01

    Isoliquritigenin (ISL) is an abundant dietary flavonoid with a chalcone structure, which is an important constituent in Glycyrrhizae Radix (GR). ISL exhibits anti-oxidant activity, and this activity has been shown to play a beneficial role in various health conditions. However, it is unclear whether the anti-oxidant activity of ISL affects insulin signaling pathway and lipid accumulation of adipocytes. We sought to investigate the effects and molecular mechanisms of ISL on insulin-stimulated adipogenesis in 3T3-L1 cells. We investigated whether ISL attenuates insulin-induced Reactive Oxygen Species (ROS) generation, and whether ISL inhibits the lipid accumulation and the expression of adipogenic-genes during the differentiation of 3T3-L1 cells. ISL blocked the ROS generation, suppressed the lipid accumulation and the expression of adipocyte-specific proteins, which are increased in response to insulin stimulation during adipocyte differentiation of 3T3-L1 cells. We also investigated whether the anti-oxidant capacity of ISL is involved in regulating the molecular events of insulin-signaling cascade in 3T3-L1 adipocytes. ISL restores PTP1B activity by inhibiting PTP1B oxidation and IR/PI3K/AKT phosphorylation during the early stages of insulin-induced adipogenesis. Our findings show that the anti-oxidant capacity of ISL attenuated insulin IR/PI3K/AKT signaling through inhibition of PTP1B oxidation, and ultimately attenuated insulin-induced adipocyte differentiation of 3T3-L1 cells. PMID:27117918

  16. Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages

    1991-01-01

    The ability of macrophages (Mos) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Mos metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mo pHi regulation in thioglycolate-elicited murine peritoneal Mos. H+ ATPase- mediated pHi recov...

  17. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Petra Maria Hermann

    2014-12-01

    Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  18. Acompanhamento da adaptação de próteses auditivas em crianças surdas Evaluating the adaptation of hearing aids for hearing impaired children

    Bianca Pinheiro Lanzetta

    2010-06-01

    Full Text Available OBJETIVOS: descrever as características audiológicas e sociais de crianças surdas e avaliar a incidência de retornos para acompanhamento no Programa de Saúde Auditiva. MÉTODOS: foram analisados os prontuários de crianças que receberam as próteses auditivas pelo Programa de Saúde Auditiva, em Vila Velha - Espírito Santo. A população estudada foi constituída por 50 crianças, na faixa etária de zero a oito anos, de ambos os sexos, com diagnóstico de perda auditiva sensorioneural de grau leve a profundo. O protocolo de pesquisa foi preenchido a partir dos dados de prontuários para a obtenção das informações desejadas. RESULTADOS: a solicitação de retorno pelo Serviço Social propiciou o comparecimento de quase da metade da população (44%; os demais achados foram indicativos da associação entre o retorno para acompanhamento e a rotina escolar. CONCLUSÕES: o referido programa atinge predominantemente famílias com rendimento mensal entre um e dois salários mínimos; o diagnóstico da surdez ocorre entre dois e três anos de idade cronológica neste estudo; a época da primeira adaptação de próteses auditivas, aos seis anos de idade, é bastante tardia; o contato com os pais, por meio do Serviço Social, viabiliza o acompanhamento proposto, influenciado positivamente também pela rotina escolar.PURPOSE: to describe the compliance and attitudes of hearing-impaired children towards the treatment and support offered by the Hearing Health Program, a public health endeavor, and assessing patients’ returns for follow-ups. METHODS: participants consisted of fifty children aged from 0 to 8 years, with a diagnosis of mild to severe sensorineural hearing loss. The children received the hearing aids from the Hearing Health Program, in Vila Velha, in the state of Espírito Santo, Brazil. The research protocol was completed using both medical records and a socio-economical profile survey of the affected children, including the

  19. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells.

    Rebollo, Alba; Roglans, Núria; Baena, Miguel; Sánchez, Rosa M; Merlos, Manel; Alegret, Marta; Laguna, Juan C

    2014-04-01

    Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation. PMID:24434080

  20. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    Yun-Ching Huang

    Full Text Available Cigarette use is an independent risk factor for the development of erectile dysfunction (ED. While the association between chronic smoking and ED is well established, the fundamental mechanism(s of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS for 4 weeks (n = 10, 12 weeks (n = 10, and 24 weeks (n = 10. At the 24-week time point all rats were assessed with intracavernous pressure (ICP during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS. Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  1. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    Huang, Yun-Ching; Chin, Chih-Chien; Chen, Chih-Shou; Shindel, Alan W; Ho, Dong-Ru; Lin, Ching-Shwun; Shi, Chung-Sheng

    2015-01-01

    Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED. PMID:26491965

  2. Gestural Interfaces for Hearing-Impaired Communication

    Aran, Oya; Burger, Thomas; Akarun, Lale; Caplier, Alice

    2008-01-01

    International audience Gestural interfaces, besides providing natural means of human computer interaction for everyone, enable the hearing impaired to use sign language or better understand speech through vision. This chapter overviews (1) the various modalities involved in gestured languages (2) the mean to automatically apprehend them individually and (3) to fuse them in order to provide a communication medium adapted to hearing-impaired. We present two example applications, a sign langu...

  3. Creating workshops for blind and visually impaired

    Rot, Peter

    2013-01-01

    The thesis Načrtovanje projektnih delavnic za osebe s slepoto in slabovidnostjo discusses the planning stage and the performance of projects for blind and visually impaired adults. It points out the positive effects of those projects on the life of an individual. Adults and senior citizens who are not blind from birth often lack professional help which would enable their adaptation to the life of blind and visually impaired. The thesis concentrates on one of the ways of integrating blind and ...

  4. Toxicity of cobalt ferrite (CoFe2O4) nanobeads in Chlorella vulgaris: interaction, adaptation and oxidative stress.

    Ahmad, Farooq; Yao, Hongzhou; Zhou, Ying; Liu, Xiaoyi

    2015-11-01

    The potential toxicity of CoFe2O4 nanobeads (NBs) in Chlorella vulgaris was observed up to 72h. Algal cell morphology, membrane integrity and viability were severely compromised due to adsorption and aggregation of NBs on algal surfaces, release of Fe(3+) and Co(2+) ions and possible mechanical damage by NBs. Interactions with NBs and effective decrease in ions released by aggregation and exudation of algal cells as a self defense mechanism were observed by Fourier transform infrared attenuated total reflectance (FTIR-ATR) and inductively coupled plasma mass spectrometry (ICP-MS). The results corroborated CoFe2O4 NBs induced ROS triggered oxidative stress, leading to a reduction in catalase activity, activation of the mutagenic glutathione s-transferase (mu-GST) and acid phosphatase (AP) antioxidant enzymes, and an increase in genetic aberrations, metabolic and cellular signal transduction dysfunction. Circular dichroism (CD) spectra indicated the weak interactions of NBs with BSA, with slight changes in the α-helix structure of BSA confirming conformational changes in structure, hence the potential for functional interactions with biomolecules. Possible interferences of CoFe2O4 NBs with assay techniques and components indicated CoFe2O4 NBs at lower concentration do not show any significant interference with ROS, catalase, mu-GST and no interference with CD measurements. This study showed ROS production is one of the pathways of toxicity initiated by CoFe2O4 NBs and illustrates the complex processes that may occur between organisms and NBs in natural complex ecosystem. PMID:26291677

  5. Adaptive Inverse Control Based on Least Square Support Vector Machines for Solid Oxide Fuel Cell%基于LS-SVM的SOFC系统自适应逆控制

    刘宗辉; 王阳华; 杨慧君

    2013-01-01

    The operating temperature and voltage are the key parameters affecting the performance of Solid Oxide Fuel Cell( SOFC) . Aiming at the strong nonlinear of SOFC and conventional mature linear theory does not apply, the paper adopted an adaptive inverse control strategy based on least square support vector machine. First, the principle dynamic model of SOFC was constructed. Then, the LS-SVM method was used to establish the inverse dynamics model of SOFC. Based on the inverse dynamic model acquired, a control algorithm based on recursive least squares support vector machine(RLS-SVM) of inverse dynamics was designed. In this adaptive inverse control mechanism, the inverse dynamic model was updated by RLS algorithm. The parameters of controller were adjusted on—line with e—filtering. The simulations of SOFC system identification and control show that the method is credibility, the inverse dynamic model identified has high precision and the designed controller has good control performance. The simulation results can provide certain theoretical basis for the practical and industrialization of SOFC.%关于固体氧化物燃料电池(Solid Oxide Fuel Cell,SOFC)性能的优化问题,其中工作温度和电压是关键参数.针对固体氧化物燃料具有较强的非线性且常规成熟线性理论不适用的特点,提出了一种最小二乘支持向量机(LS-SVM)的自适应逆控制策略.首先建立了SOFC的机理模型,然后采用LS-SVM方法建立了SOFC系统的逆动力学模型.在获得逆动力学模型的基础上,设计了一种逆动力学递推最小二乘支持向量机的控制方法.在自适应逆控制下,逆模型通过RLS算法更新,控制器依据ε-滤波进行在线调整.SOFC系统辨识和仿真结果表明,改进方法的可信性,辨识出的逆动力模型具有较高的精度,所设计的控制器能获得较好的控制性能.仿真结果可以为SOFC的实用化和产业化提供一定的理论依据.

  6. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    Keeney Paula M

    2009-09-01

    Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age

  7. Antioxidant enzymes and oxidative stress adaptation to exercise training: Comparison of endurance, resistance, and concurrent training in untrained males

    Kamal Azizbeigi

    2014-06-01

    Full Text Available The aim of this study was to compare the effect of endurance training (ET, resistance training (RT, and concurrent training (CT on circulating antioxidant capacity and oxidative stress. For this purpose, 30 men aged 21.7 ± 2.4 years were assigned to the following three training groups: ET, which included continuous running with incremental intensity that was increased up to 80% of maximal heart rate (n = 10; RT, which included a beginning load of 50% of one repetition maximum (1RM that was increased up to 80% of 1RM (n = 10; and CT, which included ET and RT programs every other day during the week (n = 10. Activities of superoxide dismutase (SOD and glutathione peroxidase (GPx in erythrocytes and total antioxidant capacity (TAC and malondialdehyde (MDA level in plasma were measured. The results showed that SOD significantly increased by 21.85% (p = 0.020, 9.54% (p = 0.032, and 14.55% (p = 0.038 in the ET, RT, and CT groups, respectively. Furthermore, the activity of erythrocyte GPx significantly increased in the ET (p = 0.018 and CT (p = 0.042 groups. The TAC increased significantly in the ET (p = 0.040 and CT (p = 0.049 groups compared with the pretest values. The MDA level significantly decreased in the ET group by 32.7% (p = 0.028, by 32% in the RT group (p = 0.025, and by 29.1% (p = 0.047 in the CT group. However, there was no significant difference in the interaction of time and group between variables of SOD and GPx enzymes and TAC of plasma and MDA in the ET, RT, and CT groups (p < 0.05. It can be concluded that all three training types induced the same changes in redox state (increased SOD activity and reduction in MDA levels, but at different rates.

  8. Saponin-rich fraction from Clematis chinensis Osbeck roots protects rabbit chondrocytes against nitric oxide-induced apoptosis via preventing mitochondria impairment and caspase-3 activation.

    Wu, Wenjun; Gao, Xinghua; Xu, Xianxiang; Luo, Yubin; Liu, Mei; Xia, Yufeng; Dai, Yue

    2013-03-01

    Our previous study reported that the saponin-rich fraction from Clematis chinensis Osbeck roots (SFC) could effectively alleviate experimental osteoarthritis induced by monosodium iodoacetate in rats through protecting articular cartilage and inhibiting local inflammation. The present study was performed to investigate the preventive effects of SFC on articular chondrocyte, and explore the underlying mechanisms. Primary rabbit chondrocytes were cultured and exposed to sodium nitroprusside (SNP), a NO donor. After treatment with different concentrations of SFC (30, 100, 300, 1,000 μg/ml) for 24 h, nucleic morphology, apoptotic rate, mitochondrial function and caspase-3 activity of chondrocytes were examined. The results showed that SNP induced remarkable apoptosis of rabbit chondrocytes evidenced by Hoechst 33258 staining and flow cytometry analysis, and SFC prevented the apoptosis in a concentration-dependent manner. Further studies indicated that SFC could prevent the depolarization of mitochondrial membrane potential (∆ψm) in SNP-treated chondrocytes and suppress the activation of caspase-3. It can be concluded that the protection of SFC on articular chondrocytes is associated with the anti-apoptosis effects via inhibiting the mitochondrion impairment and caspase-3 activation. PMID:22821055

  9. Antagonism of lycopene on pulmonary oxidative impairment induced by O3 in rats%番茄红素对臭氧致大鼠肺氧化损伤的拮抗作用

    潘洪志; 万丽葵; 常东

    2004-01-01

    ,差异有显著性意义(P<0 05).结论:吸入臭氧能够造成机体氧化损伤,番茄红素可以拮抗臭氧造成的氧化损伤.%BACKGROUND: O3 is a kind of strong oxidant, which induces lipid peroxidation, impairs organic anti-oxidase and results in oxidative impairment. Lung is the main organ in charge of air exchange between the human body and outer environment. Since it connects with the outer environment directly, the lung is the first organ to be attacked earliest by O3 and results in oxidative impairment. Lycopene is a kind of important carotenoid with various biological functions, such as antioxidation, anti-carcinoma, inducing message connection among inter-cells, etc.OBJECTIVE: To probe into the oxidative impairment of O3 in rats and protection of lycopene.DESIGN: A randomized controlled experimental study.SETTINGS: Sanitary Test Center, College of Public Health, Harbin Medical University; Heilongjiang Center for Disease Control and Prevention; Department of Laboratory, the First Affiliated Hospital of Harbin Medical University.PARTICIPANTS: The experiment was performed in the Animal Room of College of Public Health, Harbin Medical University. Forty pure male SD rats were emplored, provided by the Experimental Animal Center of the Second Affiliated Hospital of Haerbin Medical University.INTERVENTIONS: To divide normal control, O3 impaired model group,low dosage of lycopene group( 10 mg/kg) and high dosage of lycopene group (20 mg/kg). Except in the control, the rats in the rest groups were poisoned by O3. Lycopene was applied for lycopene groups except model and control groups. The rats were sacrificed 3 weeks later and the serum and pulmonary tissues were collected to prepare homogenate.MAIN OUTCOME MEASURES: Activity of superoxide dismutase(SOD), activity of glutathione peroxides(GSH-Px) and content of malondi aldehyde(MDA) in serum and pulmonary homogenate.RESULTS: O3 could remarkably affect the activity of anti-oxidase, reduce SOD activity[(4 645.60±891.85) μkat/L in

  10. Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors.

    De Vitto, H; Mendonça, B S; Elseth, K M; Vesper, B J; Portari, E A; Gallo, C V M; Paradise, W A; Rumjanek, F D; Radosevich, J A

    2013-02-01

    Mitochondria combine hydrogen and oxygen to produce heat and adenosine triphosphate (ATP). As a toxic by-product of oxidative phosphorylation (OXPHOS), mitochondria generate reactive oxygen species (ROS). These free radicals may cause damage to mitochondrial DNA (mtDNA) and other molecules in the cell. Nitric oxide (NO) plays an important role in the biology of human cancers, including breast cancer; however, it is still unclear how NO might affect the mitochondrial genome. The aim of the current study is to determine the role of mtDNA in the breast oncogenic process. Using DNA sequencing, we studied one breast cancer cell line as a model system to investigate the effects of oxidative stress. The BT-20 cell line was fully adapted to increasing concentrations of the NO donor DETA-NONOate and is referred to as BT-20-HNO, a high NO (HNO) cell line. The HNO cell line is biologically different from the "parent" cell line from which it originated. Moreover, we investigated 71 breast cancer biopsies and the corresponding noncancerous breast tissues. The free radical NO was able to generate somatic mtDNA mutations in the BT-20-HNO cell line that were missing in the BT-20 parent cell line. We identified two somatic mutations, A4767G and G13481A, which changed the amino acid residues. Another two point mutations were identified in the mtDNA initiation replication site at nucleotide 57 and at the 'hot spot' cytidine-rich D300-310 segment. Furthermore, the NO regulated the mtDNA copy number and selected different mtDNA populations by clonal expansion. Interestingly, we identified eight somatic mutations in the coding regions of mtDNAs of eight breast cancer patients (8/71, 11.2 %). All of these somatic mutations changed amino acid residues in the highly conserved regions of mtDNA which potentially leads to mitochondrial dysfunctions. The other two somatic mtDNA mutations in the displacement loop (D-loop) region [303:315 C(7-8)TC(6) and nucleotide 57] were distributed among 14

  11. Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study.

    Hattingen, Elke; Jurcoane, Alina; Bähr, Oliver; Rieger, Johannes; Magerkurth, Jörg; Anti, Sandra; Steinbach, Joachim P; Pilatus, Ulrich

    2011-12-01

    Bevacizumab shows unprecedented rates of response in recurrent glioblastomas (GBM), but the detailed mechanisms are still unclear. We employed in vivo magnetic resonance spectroscopic imaging (MRSI) and quantitative magnetic resonance imaging to investigate whether bevacizumab alters oxygen and energy metabolism and whether this effect has antitumoral activity in recurrent GBM. (31)P and (1)H MRSI, apparent diffusion coefficient (ADC), and high-resolution T2 and T2' mapping (indirect marker of oxygen extraction) were investigated in 16 patients with recurrent GBM at 3 Tesla before and 1.5-2 months after initiation of therapy with bevacizumab. Changes of metabolite concentrations and of the quantitative values in the tumor and normal appearing brain tissue were calculated. The Wilcoxon signed-ranks test was used to evaluate differences for tumor/edema versus control as well as changes before versus after commencement of therapy. Survival analyses were performed for significant parameters. Tumor T2', pH, ADC, and T2 decreased significantly in patients responding to bevacizumab therapy (n = 10). Patients with at least 25% T2' decrease during treatment showed longer progression-free and overall survival durations. Levels of high-energy metabolites were lower at baseline; these persisted under therapy. Glycerophosphoethanolamine as catabolic phospholipid metabolite increased in responders. The MRSI data support the hypothesis that bevacizumab induces relative tumor hypoxia (T2' decrease) and affects energy homeostasis in recurrent GBM, suggesting that bevacizumab impairs vascular function. The antiangiogenic effect of bevacizumab is predictive of better outcome and seems to induce antitumoral activity in the responding GBMs. PMID:21890539

  12. Triclosan (TCS) and Triclocarban (TCC) cause lifespan reduction and reproductive impairment through oxidative stress-mediated expression of the defensome in the monogonont rotifer (Brachionus koreanus).

    Han, Jeonghoon; Won, Eun-Ji; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Lee, Jae-Seong

    2016-01-01

    Triclosan (TCS) and Triclocarban (TCC) are used as antimicrobial agents and have been widely dispersed and detected in the marine environment. However, the toxicities of TCS and TCC have been poorly investigated in marine invertebrates. In this study, the effects of TCS and TCC on mortality, population growth, lifespan, and fecundity were examined in the monogonont rotifer (Brachionus koreanus) using cellular ROS levels, GST enzymatic activity, and gene expression of defensomes. The median lethal concentration (LC50) of TCS (393.1μg/L) and TCC (388.1μg/L) was also determined in the same species. In TCS- and TCC-exposed B. koreanus, growth retardation and reduced fecundity were observed and were shown to have a potentially deleterious effect on the life cycle of B. koreanus. In addition, time-dependent increases in ROS content (%) and GST enzymatic activity were shown in response to TCS and TCC exposure. Additionally, transcript levels of detoxification proteins (e.g., CYPs), antioxidant proteins (e.g., GST-sigma, Cu/ZnSOD, CAT), and heat shock proteins (Hsps) were modulated in response to TCS and TCC exposure over a 24h period. Our results indicate that TCS and TCC induce oxidative stress and transcriptional regulation of detoxification, antioxidant, and heat shock proteins, resulting in changes in lifespan and fecundity. PMID:27067728

  13. Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.

    Sudip Bhattacharyya

    Full Text Available Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP levels, reactive oxygen species (ROS generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin.

  14. Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by rHuEPO in the rat.

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-04-15

    Our aim was to study the effect of a broad range of recombinant human erythropoietin (rHuEPO) doses on hematological and biochemical parameters, blood pressure (BP), renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600IU/kg body weight (BW)/week) and saline solution (control), during 3weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. BP was measured by the tail-cuff method. Kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHuEPO600 groups presented increased kidney protein levels of HIF2α, a reduction in kidney protein levels of eNOS, and the highest grade of vascular and tubular renal lesions. Our study showed that rHuEPO-induced hypertension is present before significant hematological changes occur and, therefore, might involve direct (renal) and indirect (hematological) effects, which varies according to the dose used. The presence of renal hypoxia reduces eNOS activity. Excessive erythrocytosis increases blood hyperviscosity, which can be modulated by an increase in reticulocytes. Hypertension leads to early renal damage without alterations in traditional markers of renal function, thus underestimating the serious adverse effects and risks. PMID:26924494

  15. Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response.

    Painter, Kimberley L; Strange, Elizabeth; Parkhill, Julian; Bamford, Kathleen B; Armstrong-James, Darius; Edwards, Andrew M

    2015-05-01

    The development of chronic and recurrent Staphylococcus aureus infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of S. aureus to sublethal concentrations of H2O2 leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H2O2 exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the S. aureus population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H2O2 also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H2O2 than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H2O2. Taken together, these data reveal a mechanism by which S. aureus adapts to oxidative stress via the production of a subpopulation of H2O2-resistant SCVs with enhanced catalase production. PMID:25690100

  16. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  17. Neutralization by Acetyl Salicylic Acid of the Testosterone induced Impaired Maspin Synthesis Stimulated by Estriol in Neutrophils through Nitric Oxide Synthesis

    Manna, Emili; Bank, Sarbashri; Maiti, Smarajit; Jana, Pradipta; Sinha, Asru K.

    2015-01-01

    Purpose: Maspin, an anti breast cancer protein in the mammary cell and normal neutrophil has been reported to be synthesised by the stimulation of NO production induced by estriol. The role of testosterone was investigated in the synthesis of maspin in relation to that of estriol. Methods: Fifty normal female between the ages of 25-65 years old participated in the study. Maspin synthesis was demonstrated by in vitro translation of maspin mRNA, followed by the quantification of maspin by enzyme linked immune absorbent assay. NO was determined by methomoglobin method. Results: Incubation of the neutrophils in HBSS both with 30 nM estriol resulted in the synthesis of 1.8 ngm maspin with simultaneous increase of NO synthesis. In contrast incubating neutrophils with 20 nM testosterone in the presence of estriol inhibited maspin synthesis to 0.33 nM with simultaneous inhibition of NO synthesis from 1.89 nM to 0 nM at the same time. Addition of 0.2 μM flutamide, a testosterone receptor blocker to the incubation mixture restored the synthesis of maspin by 60.64 %. Incubation of 25 μM aspirin that stimulated NO synthesis restored the inhibition of maspin synthesis by testosterone by 79.1%. I-NAME, an inhibitor of nitric oxide synthase, abolished both maspin and NO synthesis. Scatchard plot of estriol binding in the presence of testosterone demonstrated that the male sex hormone inhibited the female sex hormone binding to its receptor by “cross talk” between the receptors. It was found that while 1.02 × 103 molecules of estriol bind each neutrophil at equilibrium, in the presence of testosterone (20 nM) in the binding mixture decreases the binding of estriol to 0.5 × 103 with little change in the dissociation constant compared to controls. Conclution: Estriol was found to stimulate maspin synthesis through the stimulation of NO, testosterone inhibited maspin synthesis through the inhibition of NO synthesis. PMID:26759534

  18. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

    This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H2O2, act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

  19. All Vision Impairment

    ... Cases of Vision Impairment (in thousands) by Age, Gender, and Race/Ethnicity Table for 2010 U.S. Prevalent ... Cases of Vision Impairment (in thousands) by Age, Gender, and Race/Ethnicity Table for 2000 U.S. Prevalent ...

  20. Speech impairment (adult)

    ... impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... in others the condition does not get better. DYSARTHRIA With dysarthria, the person has ongoing difficulty expressing ...

  1. Mild Cognitive Impairment

    ... Research Portfolio (IADRP) AMP-AD Detecting Cognitive Impairment Database ... Mild cognitive impairment (MCI) is a condition in which people have more memory or other thinking problems than normal for their ...

  2. Space Activities for the Visually Impaired

    Ries, J. G.; Baguio, M.

    2005-12-01

    To a visually impaired person celestial objects or concepts of space exploration are likely to be more abstract than to other people, but they encounter news about the universe through their daily life. A partnership between Texas Space Grant Consortium, The University of Texas at Austin, and the Texas School for the Blind and Visually Impaired provided the opportunity to assist visually impaired students increase their understanding of astronomy and space science. The activities helped visually impaired students activity engage in inquiry-based, hands-on astronomy activities. The experiences provided during the educator workshops, adapted instructional classroom activities, and tactile learning aids will be shared in the hopes that others may be able to incorporate these lessons into their regular teaching activities.

  3. Evaluation of packet loss impairment on streaming video

    RUI Hua-xia; LI Chong-rong; QIU Sheng-ke

    2006-01-01

    Video compression technologies are essential in video streaming application because they could save a great amount of network resources. However compressed videos are also extremely sensitive to packet loss which is inevitable in today's best effort IP network. Therefore we think accurate evaluation of packet loss impairment on compressed video is very important. In this work, we develop an analytic model to describe these impairments without the reference of the original video (NR) and propose an impairment metric based on the model, which takes into account both impairment length and impairment strength. To evaluate an impaired frame or video, we design a detection and evaluation algorithm (DE algorithm) to compute the above metric value. The DE algorithm has low computational complexity and is currently being implemented in the real-time monitoring module of our HDTV over IP system. The impairment metric and DE algorithm could also be used in adaptive system or be used to compare diffeient error concealment strategies.

  4. Visual impairment in the hearing impaired students

    Gogate Parikshit

    2009-01-01

    Full Text Available Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen′s E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis : Excel software was used for data entry and SSPS for analysis. Results : The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24% had ocular problems. Refractive errors were the most common morbidity 167(18.5%, but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3% children, and retinal pigmentary dystrophy in five (0.6% children. Conclusion : Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  5. Adaptive Lighting

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive LightingAdaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled i...

  6. Oxidative stress and anxiety

    Bouayed, Jaouad; Rammal, Hassan; Soulimani, Rachid

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  7. Hypertension and cognitive impairment

    Su-hang SHANG

    2015-08-01

    Full Text Available As a leading risk factor for stroke, hypertension is also an important risk factor for cognitive impairment. Midlife hypertension doubles the risk of dementia later in life and accelerates the progression of dementia, but the correlation between late-life blood pressure and cognitive impairment is still unclear. Beside blood pressure, the effect of pulse pressure, blood pressure variability and circadian rhythm of blood pressure on cognition is currently attracting more and more attention. Hypertension induces alterations in cerebrovascular structure and functions, which lead to brain lesions including cerebral atrophy, stroke, lacunar infarcts, diffuse white matter damage, microinfarct and microhemorrhage, resuling in cognitive impairment. Hypertension also impairs the metabolism and transfer of amyloid-β protein (Aβ, thus accelerates cognitive impairment. Individualized therapy, focusing on characteristics of hypertensive patients, may be a good choice for prevention and treatment of cognitive impairment. DOI: 10.3969/j.issn.1672-6731.2015.08.004

  8. Impaired oxidative phosphorylation in overtrained rat myocardium

    Kadaja, Lumme; Eimre, Margus; Paju, Kalju; Roosimaa, Mart; Põdramägi, Taavi; Kaasik, Priit; Pehme, Ando; Orlova, Ehte; Mudist, Margareeta; Peet, Nadezhda; Piirsoo, Andres; Seene, Teet; Gellerich, Frank N; Seppet, Enn K

    2010-01-01

    The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearan...

  9. The Influence of green tea on oxidative stress r esponse of patients with vascular cognitive impairment%绿茶对血管性认知功能障碍患者氧化应激反应的影响

    徐艳; 肖云月; 杨英; 鞠洁阳; 张磊; 訚亚涛

    2015-01-01

    目的:探讨饮用绿茶对血管性认知功能障碍( VCI)患者体内氧化应激反应的影响。方法将入选的VCI患者依据饮用绿茶的习惯分为两组,即饮茶者组和非饮茶者组,采用简易精神状态检查表(MMSE)和蒙特利尔认识评估量表(MoCA)检测认知功能,取肘静脉血测定丙二醛(MDA)、4-羟基壬烯醛(4-HNE)及8-羟化脱氧鸟苷(8-OHdG )的含量。结果所入选的 VCI 患者中,饮茶者组的 MMSE 评分(26.62±0.41)稍高于非饮茶者组(26.17±0.38),统计学分析显示两组差异无统计学意义(P>0.05)。但饮茶者组的MoCA评分(23.29±0.61)高于非饮用绿茶者组(21.12±0.50),差异具有统计学意义(P<0.05)。饮茶者外周血的 MDA 含量(2.345±0.3697)低于非饮茶者(4.437±0.3710),以及饮茶者外周血4-HNE 含量(4.919±0.9378)低于非饮茶者(8.660±0.7883),差异均具有统计学意义(P<0.01),而饮茶者8-OHdG浓度(1845±121.5)虽低于非饮茶者(2322±203.4),但差异无统计学意义(P>0.05)。结论常饮绿茶可能具有抑制VCI患者的氧化应激反应,改善认知功能的作用,但绿茶对抑制氧化性DNA损伤的作用较弱。%Objective To explore the influence of drinking green tea on oxidative stress response of patients with vascular cognitive impairment( VCI) .Methods The involved patients with vascular cognitive impairment were divided into two groups according to the habit of drinking green tea:drinking green tea group and non-drinking green tea group.The cognitive function was measured by Mini Mental State Examination ( MMSE)and Montreal Cognitive Assessment ( MoCA ) .The oxidative stress response was evaluated by the level of malondialdehyde ( MDA ) , 4-hydroxynonenal(4-HNE) and 8-hydroxy-2ˊ-deoxyguanosine (8 -OHdG) in elbow venous blood.Results Of all participants with VCI, the

  10. Adaptive skills

    Staša Stropnik; Jana Kodrič

    2013-01-01

    Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with g...

  11. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID:25141153

  12. Adaptive Lighting

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... distributed differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial...

  13. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments.

    Fujisawa, Haruki; Sugimura, Yoshihisa; Takagi, Hiroshi; Mizoguchi, Hiroyuki; Takeuchi, Hideyuki; Izumida, Hisakazu; Nakashima, Kohtaro; Ochiai, Hiroshi; Takeuchi, Seiji; Kiyota, Atsushi; Fukumoto, Kazuya; Iwama, Shintaro; Takagishi, Yoshiko; Hayashi, Yoshitaka; Arima, Hiroshi; Komatsu, Yukio; Murata, Yoshiharu; Oiso, Yutaka

    2016-03-01

    Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality. PMID:26376860

  14. Adaptive Lighting

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and...

  15. Adaptive skills

    Staša Stropnik

    2013-02-01

    Full Text Available Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with greater need for control and help with everyday tasks. Assessment of adaptive skills is often connected to assessment of intellectual disability, due to the reason that the diagnosis of intellectual disability includes lower levels of achievements on standardized tests of intellectual abilities as well as important deficits in adaptive skills. Assessment of adaptive behavior is a part of standard assessment battery with children and adults with different problems, disorders or disabilities that affect their everyday functioning. This contribution also presents psychometric tools most regularly used for assessment of adaptive skills and characteristics of adaptive skills with individual clinical groups.

  16. ADAPT Dataset

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  17. Impairments to Vision

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  18. Aids for visual impairment.

    Dudley, N. J.

    1990-01-01

    This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue.

  19. Kids' Quest: Vision Impairment

    ... and neighborhood . Step 8: Now see if your attitudes have changed. Take the Fact Checkup again. ... impairment also have at least one other developmental disability, such as intellectual disabilities, cerebral palsy, hearing loss, ...

  20. Speech impairment (adult)

    ... ALS or Lou Gehrig disease), cerebral palsy, myasthenia gravis, or multiple sclerosis (MS) Facial trauma Facial weakness, ... provider will likely ask about the speech impairment. Questions may include when the problem developed, whether there ...

  1. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mark P Mattson; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-01-01

    Background Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Methods Rats on ...

  2. Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

    Richard Gorlick; Levy, Adam S.; John H. Healey; Paul A. Meyers; Wenzel, Bethanne D.; Condon Richardson; Rebecca Sowers

    2010-01-01

    Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine pe...

  3. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    Hove, Michael J.; Peter E Keller

    2015-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize...

  4. Fluorescence changes accompanying short-term light adaptations in photosystem I and photosystem II of the cyanobacterium Synechocystis sp. PCC 6803 and phycobiliprotein-impaired mutants: State 1/State 2 transitions and carotenoid-induced quenching of phycobilisomes.

    Stadnichuk, Igor N; Lukashev, Evgeny P; Elanskaya, Irina V

    2009-03-01

    The features of the two types of short-term light-adaptations of photosynthetic apparatus, State 1/State 2 transitions, and non-photochemical fluorescence quenching of phycobilisomes (PBS) by orange carotene-protein (OCP) were compared in the cyanobacterium Synechocystis sp. PCC 6803 wild type, CK pigment mutant lacking phycocyanin, and PAL mutant totally devoid of phycobiliproteins. The permanent presence of PBS-specific peaks in the in situ action spectra of photosystem I (PSI) and photosystem II (PSII), as well as in the 77 K fluorescence excitation spectra for chlorophyll emission at 690 nm (PSII) and 725 nm (PSI) showed that PBS are constitutive antenna complexes of both photosystems. The mutant strains compensated the lack of phycobiliproteins by higher PSII content and by intensification of photosynthetic linear electron transfer. The detectable changes of energy migration from PBS to the PSI and PSII in the Synechocystis wild type and the CK mutant in State 1 and State 2 according to the fluorescence excitation spectra measurements were not registered. The constant level of fluorescence emission of PSI during State 1/State 2 transitions and simultaneous increase of chlorophyll fluorescence emission of PSII in State 1 in Synechocystis PAL mutant allowed to propose that spillover is an unlikely mechanism of state transitions. Blue-green light absorbed by OCP diminished the rout of energy from PBS to PSI while energy migration from PBS to PSII was less influenced. Therefore, the main role of OCP-induced quenching of PBS is the limitation of PSI activity and cyclic electron transport under relatively high light conditions. PMID:19169839

  5. What determines goodwill impairment?

    Verriest, Arnt; Gaeremynck, Ann

    2009-01-01

    This study investigates determinants of goodwill impairment decisions and their disclosure quality. Under IAS36 goodwill is subject to an annual impairment test in which the carrying amount of goodwill is not allowed to exceed the recoverable amount. However, valuing this recoverable amount is subject to substantial managerial discretion. Therefore, we predict that ownership concentration, corporate governance quality and firm performance provide incentives for managers to engage in goodwill ...

  6. Characteristics and adaptability of iron- and sulfur-oxidizing microorganisms used for the recovery of metals from minerals and their concentrates.

    Rawlings, Douglas E

    2005-05-01

    Microorganisms are used in large-scale heap or tank aeration processes for the commercial extraction of a variety of metals from their ores or concentrates. These include copper, cobalt, gold and, in the past, uranium. The metal solubilization processes are considered to be largely chemical with the microorganisms providing the chemicals and the space (exopolysaccharide layer) where the mineral dissolution reactions occur. Temperatures at which these processes are carried out can vary from ambient to 80 degrees C and the types of organisms present depends to a large extent on the process temperature used. Irrespective of the operation temperature, biomining microbes have several characteristics in common. One shared characteristic is their ability to produce the ferric iron and sulfuric acid required to degrade the mineral and facilitate metal recovery. Other characteristics are their ability to grow autotrophically, their acid-tolerance and their inherent metal resistance or ability to acquire metal resistance. Although the microorganisms that drive the process have the above properties in common, biomining microbes usually occur in consortia in which cross-feeding may occur such that a combination of microbes including some with heterotrophic tendencies may contribute to the efficiency of the process. The remarkable adaptability of these organisms is assisted by several of the processes being continuous-flow systems that enable the continual selection of microorganisms that are more efficient at mineral degradation. Adaptability is also assisted by the processes being open and non-sterile thereby permitting new organisms to enter. This openness allows for the possibility of new genes that improve cell fitness to be selected from the horizontal gene pool. Characteristics that biomining microorganisms have in common and examples of their remarkable adaptability are described. PMID:15877814

  7. Characteristics and adaptability of iron- and sulfur-oxidizing microorganisms used for the recovery of metals from minerals and their concentrates

    Rawlings Douglas E

    2005-05-01

    Full Text Available Abstract Microorganisms are used in large-scale heap or tank aeration processes for the commercial extraction of a variety of metals from their ores or concentrates. These include copper, cobalt, gold and, in the past, uranium. The metal solubilization processes are considered to be largely chemical with the microorganisms providing the chemicals and the space (exopolysaccharide layer where the mineral dissolution reactions occur. Temperatures at which these processes are carried out can vary from ambient to 80°C and the types of organisms present depends to a large extent on the process temperature used. Irrespective of the operation temperature, biomining microbes have several characteristics in common. One shared characteristic is their ability to produce the ferric iron and sulfuric acid required to degrade the mineral and facilitate metal recovery. Other characteristics are their ability to grow autotrophically, their acid-tolerance and their inherent metal resistance or ability to acquire metal resistance. Although the microorganisms that drive the process have the above properties in common, biomining microbes usually occur in consortia in which cross-feeding may occur such that a combination of microbes including some with heterotrophic tendencies may contribute to the efficiency of the process. The remarkable adaptability of these organisms is assisted by several of the processes being continuous-flow systems that enable the continual selection of microorganisms that are more efficient at mineral degradation. Adaptability is also assisted by the processes being open and non-sterile thereby permitting new organisms to enter. This openness allows for the possibility of new genes that improve cell fitness to be selected from the horizontal gene pool. Characteristics that biomining microorganisms have in common and examples of their remarkable adaptability are described.

  8. Severity-based adaptation with limited data for ASR to aid dysarthric speakers.

    Mustafa, Mumtaz Begum; Salim, Siti Salwah; Mohamed, Noraini; Al-Qatab, Bassam; Siong, Chng Eng

    2014-01-01

    Automatic speech recognition (ASR) is currently used in many assistive technologies, such as helping individuals with speech impairment in their communication ability. One challenge in ASR for speech-impaired individuals is the difficulty in obtaining a good speech database of impaired speakers for building an effective speech acoustic model. Because there are very few existing databases of impaired speech, which are also limited in size, the obvious solution to build a speech acoustic model of impaired speech is by employing adaptation techniques. However, issues that have not been addressed in existing studies in the area of adaptation for speech impairment are as follows: (1) identifying the most effective adaptation technique for impaired speech; and (2) the use of suitable source models to build an effective impaired-speech acoustic model. This research investigates the above-mentioned two issues on dysarthria, a type of speech impairment affecting millions of people. We applied both unimpaired and impaired speech as the source model with well-known adaptation techniques like the maximum likelihood linear regression (MLLR) and the constrained-MLLR(C-MLLR). The recognition accuracy of each impaired speech acoustic model is measured in terms of word error rate (WER), with further assessments, including phoneme insertion, substitution and deletion rates. Unimpaired speech when combined with limited high-quality speech-impaired data improves performance of ASR systems in recognising severely impaired dysarthric speech. The C-MLLR adaptation technique was also found to be better than MLLR in recognising mildly and moderately impaired speech based on the statistical analysis of the WER. It was found that phoneme substitution was the biggest contributing factor in WER in dysarthric speech for all levels of severity. The results show that the speech acoustic models derived from suitable adaptation techniques improve the performance of ASR systems in recognising

  9. Vascular cognitive impairment

    N.V. Vakhnina

    2014-05-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  10. Time-dependent effects of trimethylamine-N-oxide/urea on lactate dehydrogenase activity: an unexplored dimension of the adaptation paradigm.

    Baskakov, I; Bolen, D. W.

    1998-01-01

    Given that enzymes in urea-rich cells are believed to be just as sensitive to urea effects as enzymes in non-urea-rich cells, it is argued that time-dependent inactivation of enzymes by urea could become a factor of overriding importance in the biology of urea-rich cells. Time-independent parameters (e.g. Tm, k(cat), and Km) involving protein stability and enzyme function have generally been the focus of inquiries into the efficacy of naturally occurring osmolytes like trimethylamine-N-oxide ...

  11. Ambiguous Adaptation

    Møller Larsen, Marcus; Lyngsie, Jacob

    We investigate why some exchange relationships terminate prematurely. We argue that investments in informal governance structures induce premature termination in relationships already governed by formal contracts. The formalized adaptive behavior of formal governance structures and the flexible and...... reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  12. Strategic Adaptation

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation...

  13. Work at high altitude and oxidative stress: antioxidant nutrients.

    Askew, E W

    2002-11-15

    A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. Some investigators have linked the development of these symptoms with the condition of altered blood-brain barrier permeability, possibly related to hypoxia induced free radical formation. The burden of oxidative stress increases during the time spent at altitude and may even persist for some time upon return to sea level. The physiological and medical consequences of increased oxidative stress engendered by altitude is unclear; indeed, hypoxia is believed to be the trigger for the cascade of signaling events that ultimately leads to adaptation to altitude. These signaling events include the generation of reactive oxygen species (ROS) that may elicit important adaptive responses. If produced in excess, however, these ROS may contribute to impaired muscle function and reduced capillary perfusion at altitude or may even play a role in precipitating more serious neurological and pulmonary crisis. Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is

  14. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  15. Specific Language Impairment

    ... to distinguish between children who are struggling to learn a new language and children with true language impairments. After studying a large group of Hispanic children who speak English as a second language, NIDCD-funded researchers have developed a dual ...

  16. Resilience in Parents of Young Adults with Visual Impairments

    de Klerk, Heidi; Greeff, Abraham P.

    2011-01-01

    This article reports on a study of the adaptation of parents with children with visual impairment in South Africa. The results showed that familial values (such as attitude toward the disability, religious faith, and familial closeness) permit a process of inclusion (through the use of resources and acceptance of help) and the development of a…

  17. Perturbed Energy Metabolism and Neuronal Circuit Dysfunction in Cognitive Impairment

    Kapogiannis, Dimitrios; Mattson, Mark P.

    2010-01-01

    Epidemiological, neuropathological and functional neuroimaging evidence implicates global and regional derangements in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified adaptively by excitatory and inhibitory synaptic activity and neurotrophic factors. Aging and Alzheimer’s disease (AD) cause perturbations in cellular energy metabolism, level of excitation/inhibition and neurotrophic factor release that overwhelm compensatory me...

  18. The New DSM-5 Impairment Criterion: A Challenge to Early Autism Spectrum Disorder Diagnosis?

    Zander, Eric; Bölte, Sven

    2015-01-01

    The possible effect of the DSM-5 impairment criterion on diagnosing autism spectrum disorder (ASD) in young children was examined in 127 children aged 20-47 months with a DSM-IV-TR clinical consensus diagnosis of ASD. The composite score of the Vineland Adaptive Behavior Scales (VABS) served as a proxy for the DSM-5 impairment criterion. When…

  19. Free Recall Behaviour in Children with and without Spelling Impairment: The Impact of Working Memory Subcapacities

    Malstadt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

    2012-01-01

    This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with…

  20. Adaptive test

    Kjeldsen, Lars Peter; Eriksen, Mette Rose

    2010-01-01

    Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale.......Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale....

  1. Moving towards adaptive management of cyanotoxin-impaired water bodies.

    Paerl, Hans W; Otten, Timothy G; Joyner, Alan R

    2016-09-01

    The cyanobacteria are a phylum of bacteria that have played a key role in shaping the Earth's biosphere due to their pioneering ability to perform oxygenic photosynthesis. Throughout their history, cyanobacteria have experienced major biogeochemical changes accompanying Earth's geochemical evolution over the past 2.5+ billion years, including periods of extreme climatic change, hydrologic, nutrient and radiation stress. Today, they remain remarkably successful, exploiting human nutrient over-enrichment as nuisance "blooms." Cyanobacteria produce an array of unique metabolites, the functions and biotic ramifications of which are the subject of diverse ecophysiological studies. These metabolites are relevant from organismal and ecosystem function perspectives because some can be toxic and fatal to diverse biota, including zooplankton and fish consumers of algal biomass, and high-level consumers of aquatic food sources and drinking water, including humans. Given the long history of environmental extremes and selection pressures that cyanobacteria have experienced, it is likely that that these toxins serve ecophysiological functions aimed at optimizing growth and fitness during periods of environmental stress. Here, we explore the molecular and ecophysiological mechanisms underlying cyanotoxin production, with emphasis on key environmental conditions potentially controlling toxin production. Based on this information, we offer potential management strategies for reducing cyanotoxin potentials in natural waters; for cyanotoxins with no clear drivers yet elucidated, we highlight the data gaps and research questions that are still lacking. We focus on the four major classes of toxins (anatoxins, cylindrospermopsins, microcystins and saxitoxins) that have thus far been identified as relevant from environmental health perspectives, but caution there may be other harmful metabolites waiting to be elucidated. PMID:27418325

  2. Adaptive Memory: Animacy Enhances Free Recall but Impairs Cued Recall

    Popp, Earl Y.; Serra, Michael J.

    2016-01-01

    Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of…

  3. The functional interactome of GSTP: A regulatory biomolecular network at the interface with the Nrf2 adaption response to oxidative stress.

    Bartolini, Desirée; Galli, Francesco

    2016-04-15

    Glutathione S-transferase P (GSTP), and possibly other members of the subfamily of cytosolic GSTs, are increasingly proposed to have roles far beyond the classical GSH-dependent enzymatic detoxification of electrophilic metabolites and xenobiotics. Emerging evidence suggests that these are essential components of the redox sensing and signaling platform of cells. GSTP monomers physically interact with cellular proteins, such as other cytosolic GSTs, signaling kinases and the membrane peroxidase peroxiredoxin 6. Other interactions reported in literature include that with regulatory proteins such as Fanconi anemia complementation group C protein, transglutaminase 2 and several members of the keratin family of genes. Transcription factors downstream of inflammatory and oxidative stress pathways, namely STAT3 and Nrf2, were recently identified to be further components of this interactome. Together these pieces of evidence suggest the existence of a regulatory biomolecular network in which GSTP represents a node of functional convergence and coordination of signaling and transcription proteins, namely the "GSTP interactome", associated with key cellular processes such as cell cycle regulation and the stress response. These aspects and the methodological approach to explore the cellular interactome(s) are discussed in this review paper. PMID:26922696

  4. Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

    Rebecca Sowers

    2011-01-01

    Full Text Available Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored.

  5. Neurological Impairment: Nomenclature and Consequences.

    Spears, Catherine E.; Weber, Robert E.

    Neurological impairment as discussed includes a range of disabilities referred to as neurological impairment: minimal brain dysfunction/damage, developmental disability, perceptual handicap, learning disability, hyperkinetic behavioral syndrome, and others. Defined are causes of neurological impairment and methods of diagnosis. Symptoms…

  6. Impaired Consciousness in Epilepsy

    Blumenfeld, Hal

    2012-01-01

    Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—mai...

  7. Cryotherapy impairs proprioception function?

    Cordeiro, Nuno; Henriques, Sara

    2014-01-01

    INTRODUCTION: Cryotherapy application over a joint causes a nerve conduction velocity decrease and proprioceptive changes. OBJECTIVE: This study aims to determine if cryotherapy impairs proprioception acuity. METHODS: Proprioception was assessed by joint position sense (JPS), measured with an isokinetic dynamometer Biodex System 3, in twenty one females on experimental group, before 15 minutes cryotherapy (T0) and immediately after (T1). A control group (n=20) performed also the JPS...

  8. Test Anxiety, Computer-Adaptive Testing and the Common Core

    Colwell, Nicole Makas

    2013-01-01

    This paper highlights the current findings and issues regarding the role of computer-adaptive testing in test anxiety. The computer-adaptive test (CAT) proposed by one of the Common Core consortia brings these issues to the forefront. Research has long indicated that test anxiety impairs student performance. More recent research indicates that…

  9. Adaptation Laboratory

    Huq, Saleemul

    2011-11-15

    Efforts to help the world's poor will face crises in coming decades as climate change radically alters conditions. Action Research for Community Adapation in Bangladesh (ARCAB) is an action-research programme on responding to climate change impacts through community-based adaptation. Set in Bangladesh at 20 sites that are vulnerable to floods, droughts, cyclones and sea level rise, ARCAB will follow impacts and adaptation as they evolve over half a century or more. National and international 'research partners', collaborating with ten NGO 'action partners' with global reach, seek knowledge and solutions applicable worldwide. After a year setting up ARCAB, we share lessons on the programme's design and move into our first research cycle.

  10. Hedonic "adaptation"

    Paul Rozin

    2008-02-01

    Full Text Available People live in a world in which they are surrounded by potential disgust elicitors such as ``used'' chairs, air, silverware, and money as well as excretory activities. People function in this world by ignoring most of these, by active avoidance, reframing, or adaptation. The issue is particularly striking for professions, such as morticians, surgeons, or sanitation workers, in which there is frequent contact with major disgust elicitors. In this study, we study the ``adaptation'' process to dead bodies as disgust elicitors, by measuring specific types of disgust sensitivity in medical students before and after they have spent a few months dissecting a cadaver. Using the Disgust Scale, we find a significant reduction in disgust responses to death and body envelope violation elicitors, but no significant change in any other specific type of disgust. There is a clear reduction in discomfort at touching a cold dead body, but not in touching a human body which is still warm after death.

  11. Adaptive ethnography

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin to...... design and develop educational materials for mobile media platforms we must first understand everyday use and behaviour with a medium such as a mobile phone. The paper outlines the research design for a PhD project on mobile learning which focuses on mobile phones as a way to bridge the gap between...... formal and informal learning contexts. The paper also proposes several adaptive methodological techniques for studying young people's interaction with mobiles....

  12. Adaptable positioner

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 22 fig. 6 ref

  13. Adaptive positioner

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 6 refs

  14. Adaptive noise

    Viney, Mark; Reece, Sarah E.

    2013-01-01

    In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise ...

  15. The visually impaired child.

    Thompson, Lisa; Kaufman, Lawrence M

    2003-02-01

    This article discusses the causes of childhood blindness and how the primary care provider may begin the appropriate steps toward diagnosing and managing the visually impaired child. Community resources (see Box 3) and low-vision programs in schools should be used so that parents do not need to reinvent strategies to raise a blind child. Worldwide, childhood blindness, which places is a tremendous burden on families and communities of the third world, is mostly preventable with improved hygiene, diet, and immunization. PMID:12713115

  16. Validity and suitability of the Bayley-III Low Motor/Vision version : A comparative study among young children with and without motor and/or visual impairments

    Visser, Linda; Ruiter, Selma; van der Meulen, Bieuwe; Ruijssenaars, Wied; Timmerman, Marieke

    2013-01-01

    The aim of the present study was to examine the validity of the Bayley-III Low Motor/Vision version, and its suitability for children with motor and/or visual impairment(s). This version contains accommodated items, that is, adaptations to minimize impairment bias, without altering what the test mea

  17. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Highlights: → In 3T3-L1 adipocytes iAs3+ decreases insulin-stimulated glucose uptake. → iAs3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs3+ activates the cellular adaptive oxidative stress response. → iAs3+ impairs insulin-stimulated ROS signaling. → iAs3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes

  18. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  19. Mild cognitive impairment

    Pavlović Dragan M.

    2009-01-01

    Full Text Available Mild cognitive impairment (MCI is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer's disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

  20. Specific language impairment.

    Kamhi, Alan G; Clark, Mary Kristen

    2013-01-01

    The acquisition of language is one of the most important achievements in young children, in part because most children appear to acquire language with little effort. Some children are not so fortunate, however. There is a large group of children who also have difficulty learning language, but do not have obvious neurological, cognitive, sensory, emotional, or environmental deficits. Clinicians often refer to these children as language disordered or language impaired. Researchers tend to refer to these children as specific language impaired (SLI). Children with SLI have intrigued researchers for many years because there is no obvious reason for their language learning difficulties. SLI has been found to be an enduring condition that begins in early childhood and often persists into adolescence and adulthood. The language problems of children with SLI are not limited to spoken language; they also affect reading and writing and thus much of academic learning. Knowledge of the characteristics of SLI should aid physicians, pediatricians, and early childhood specialists to identify these children during the preschool years and ensure that they receive appropriate services. With high-quality language intervention and literacy instruction, most children with SLI should be able to perform and function adequately in school and beyond. PMID:23622167

  1. Dimethylfumarate Impairs Neutrophil Functions.

    Müller, Susen; Behnen, Martina; Bieber, Katja; Möller, Sonja; Hellberg, Lars; Witte, Mareike; Hänsel, Martin; Zillikens, Detlef; Solbach, Werner; Laskay, Tamás; Ludwig, Ralf J

    2016-01-01

    Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates-in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases. PMID:26763431

  2. Niche specialization of terrestrial archaeal ammonia oxidizers

    Gubry-Rangin, Cécile; Hai, Brigitte; Quince, Christopher; Engel, Marion; Thomson, Bruce C.; James, Phillip; Schloter, Michael; Robert I. Griffiths; Prosser, James I.; Nicol, Graeme W.

    2011-01-01

    Soil pH is a major determinant of microbial ecosystem processes and potentially a major driver of evolution, adaptation, and diversity of ammonia oxidizers, which control soil nitrification. Archaea are major components of soil microbial communities and contribute significantly to ammonia oxidation in some soils. To determine whether pH drives evolutionary adaptation and community structure of soil archaeal ammonia oxidizers, sequences of amoA, a key functional gene of ammonia oxidation, were...

  3. Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

    Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

    2005-01-01

    We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

  4. 基于免疫系统的自适应差分进化算法及在水银氧化动力学参数估计中的应用%An immune self-adaptive differential evolution algorithm with application to estimate kinetic parameters for homogeneous mercury oxidation

    胡春平; 颜学峰

    2009-01-01

    A new version of differential evolution(DE)algorithm,in which immurle concepts and methods are applied to determine the parameter setting.named immune self-adaptive difierential evolution(ISDE),iS proposed to improve the performance of the DE algorithm.During the actual operation.ISDE seeks the optimal parameters arising from the evolutionary process.which enable ISDE to alter the algorithm for different optimization problems and improve the performance Of ISDE bv the control parameters'self-adaptation.The performance of the proposed method is studied with the use of nine benchmark problems and compared with original DE algorithm and other well-known self-adaptive DE algorithms.The experiments conducted show that the ISDE clearly outperforms the othcr DE algorithms in all benchmark functions.Furthermore.ISDE iS applied to develop the kinetic model for homogeneous mercury (Hg) oxidation in tlue gas,and satistactory results are obtained.

  5. Adaptive management

    Rist, Lucy; Campbell, Bruce Morgan; Frost, Peter

    2013-01-01

    in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how......Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used...... the concept might be further assessed. AM is currently being used to describe many different management contexts, scales and locations. Few authors define the term explicitly or describe how it offers a means to improve management outcomes in their specific management context. Many do not adhere to the idea...

  6. Astrocytes Underlie Neuroinflammatory Memory Impairment

    Osso, LA; Chan, JR

    2015-01-01

    © 2015 Elsevier Inc. All rights reserved. Neuroinflammation is being increasingly recognized as a potential mediator of cognitive impairments in various neurological conditions. Habbas et al. demonstrate that the pro-inflammatory cytokine tumor necrosis factor alpha signals through astrocytes to alter synaptic transmission and impair cognition in a mouse model of multiple sclerosis.

  7. Locomotion and Grasping impairment in preschoolers with autism spectrum disorder

    Francesca Fulceri

    2015-08-01

    Full Text Available Objective: To investigate expressiveness of motor impairment in autism spectrum disorder (ASD and its correlation with developmental and clinical features of ASD. Method: Thirty-five male preschoolers with ASD completed the Peabody Developmental Motor Scales-2 (PDMS-2; Folio and Fewell, 2000 and underwent a multidisciplinary assessment including medical examination, standardized assessment of cognitive abilities, administration of Autism_Diagnostic_Observation_Schedule (ADOS and a parent interview about adaptive skills. Results: Results revealed a substantial impairment in locomotion and grasping skills. Both fine and gross motor skills were significantly correlated with non verbal IQ and adaptive behaviours (p<0.01 but not with chronological age or ADOS scores. Children with weaker motor skills have greater cognitive and adaptive behaviours deficits. Conclusions: Motor development in ASD can be detected at preschool age and locomotion and grasping skills are substantially the most impaired area. These findings support the need to assess motor skills in preschoolers with ASD in addition to other developmental skill areas. Along with the increasingly acknowledged importance of motor skills for subsequent social, cognitive, and communicative development our findings support the need to consider motor intervention as a key area in therapeutic program to improve outcome in preschoolers with ASD.

  8. A hypoxia-inducible factor (HIF)-3α splicing variant, HIF-3α4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3α4

    Highlights: ► HIF-3α4 is silenced by DNA methylation in meningiomas. ► Induction of HIF-3α4 impaired angiogenesis in meningiomas. ► Induction of HIF-3α4 impaired proliferation and oxygen-dependent metabolism. -- Abstract: Hypoxia inducible factor is a dominant regulator of adaptive cellular responses to hypoxia and controls the expression of a large number of genes regulating angiogenesis as well as metabolism, cell survival, apoptosis, and other cellular functions in an oxygen level-dependent manner. When a neoplasm is able to induce angiogenesis, tumor progression occurs more rapidly because of the nutrients provided by the neovasculature. Meningioma is one of the most hypervascular brain tumors, making anti-angiogenic therapy an attractive novel therapy for these tumors. HIF-3α has been conventionally regarded as a dominant-negative regulator of HIF-1α, and although alternative HIF-3α splicing variants are extensively reported, their specific functions have not yet been determined. In this study, we found that the transcription of HIF-3α4 was silenced by the promoter DNA methylation in meningiomas, and inducible HIF-3α4 impaired angiogenesis, proliferation, and metabolism/oxidation in hypervascular meningiomas. Thus, HIF-3α4 could be a potential molecular target in meningiomas

  9. Oficinas de estimulação cognitiva adaptadas para idosos analfabetos com transtorno cognitivo leve Talleres de estimulación cognitiva adaptadas para ancianos analfabetos con deterioro cognitivo leve Workshops for cognitive stimulation adapted for elderly illiterate individuals with mild cognitive impairment

    Izabel Borges dos Santos

    2012-12-01

    los talleres y conferencias produjeron mejora en la memoria de los ancianos en la funcionalidad y en la socialización/integración.The aim of this study was to assess the self-perception of memory in elderly illiterate with mild cognitive impairment, before and after workshops of cognitive stimulation adapted for illiterate individuals. The research was qualitative, held at the Health Unit of Taguatinga-DF, involving 63 elderly illiterate: 22 in the experimental group (EG, with 10 workshops; 21 in control group 1 (CG1, with 10 lectures; and 20 in the control group 2 (GC2, without intervention. Semi-structured interviews were carried on before and after the interventions, asking about memory status. The activities offered weekly to EG and CG1 have had two hours of duration. The mean age of the participants was 72.8 years, and 92% were female. In pre-intervention, 82% reported worsening memory during the last year. In post-intervention, CG1 and CG2 kept memory changes, while EG improved cognition. One concludes that the provided workshops and lectures improved functionality and socialization / integration.

  10. Management of impaired fracture healing: Historical aspects

    Gajdobranski Đorđe; Micić Ivan; Mitković Milorad B.; Mladenović Desimir; Milankov Miroslav

    2005-01-01

    Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthr...

  11. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content...... expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review will...... discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  12. Mitochondrial oxidative function and type 2 diabetes

    Rabøl, Rasmus; Boushel, Robert; Dela, Flemming

    2006-01-01

    discussed. Several studies show reduced activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The reductions are independent of muscle fiber type, and are accompanied by visual evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme activity is explained by decreases...... in mitochondrial content; thus, evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing. These impairments in oxidative function and mitochondrial morphology could reflect the sedentary lifestyle of the diabetic subjects, and the influence of physical activity on...... insulin stimulation. The decreased basal ATP production does not affect overall lipid or glucose oxidation, and no studies linking changes in oxidative activity and insulin sensitivity in type 2 diabetes have been published. It is concluded that evidence of a functional impairment in mitochondria in type...

  13. The aging of the adaptive immune system

    Grubeck-Loebenstein, B.; Weinberger, B.; Herndler-Brandstetter, D.; Weiskopf, D.; Pfister, G.

    2011-01-01

    Adaptive immune responses are severely affected by the aging process as reflected by an increased morbidity and mortality from infectious diseases and a low efficacy of vaccination in elderly persons. Age-related changes within the bone marrow and thymus lead to an impaired generation of new T and B cells severely compromising the maintenance of a diverse and balanced T and B cell repertoire in old age. The maintenance of a balanced T cell repertoire is further challenged by latent persistent...

  14. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  15. [Cognitive Impairment in Multiple Sclerosis].

    Niino, Masaaki; Miyazaki, Yusei

    2016-04-01

    While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855

  16. [Drug-induced Cognitive Impairment].

    Shinohara, Moeko; Yamada, Masahito

    2016-04-01

    Elderly people are more likely than young people to develop cognitive impairments associated with medication use. One of the reasons for this is that renal and liver functions are often impaired in elderly people. Dementia and delirium (an acute confused state) are known to be associated with drug toxicity. Anticholinergic medications are common causes of both acute and chronic cognitive impairment. Psychoactive drugs, antidepressants and anticonvulsants can cause dementia and delirium. In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, corticosteroids, NSAIDs (nonsteroidal anti-inflammatory agent), and cardiac medications, may cause acute or chronic cognitive impairment. Early diagnosis and withdrawal of the offending agent are essential for the prevention of drug-induced dementia and delirium. PMID:27056860

  17. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Ignacio Negrón-Oyarzo; Francisco Aboitiz; Pablo Fuentealba

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral response...

  18. Low Motor Assessment: A Comparative Pilot Study with Young Children With and Without Motor Impairment

    Ruiter, Selma Anne José; Nakken, Han; van der Meulen, Bieuwe F.; Lunenborg, Carolien B.

    2009-01-01

    Most of the developmental instruments that measure cognitive development in children rely heavily on fine motor skills, especially for young children whose language skills are not yet well developed. This is problematic when evaluating the cognitive development of young children with motor impairment. The purpose of this study is to assess the need for a Low Motor adapation of a standardized instrument when testing children with motor impairment. To accomplish this, we have adapted the proced...

  19. Use Case Design for AdaptIVe

    Wolter, Stefan; Kelsch, Johann

    2014-01-01

    AdaptIVe is a large scale European project on vehicle automation and the pertaining human-machine interaction. The use case design process is a crucial part of the system design process and a part of the human-vehicle integration subproject. This paper explains the methodology for describing use cases in AdaptIVe. They are primarily based on sequence diagrams with main and alternative flows.

  20. Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

    Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.

  1. ENVIRONMENTAL INJUSTICE AND MOBILITY IMPAIRMENT

    Michael Cahill

    2013-06-01

    Full Text Available The study of mobility is a growth area in the social sciences.  The car system (automobility has had as one of its consequences reduced opportunities for mobility impaired people to walk in their local environment. Immobility has resulted for many people with disabilities. Despite the promotion of physical activity by public health guidance local environments are often hazardous for mobility impaired people.  In particular, there is a problem with cars parking on pavements and pavement cycling.

  2. Emotional impairment in Parkinson's disease

    CHEN Hai-bo

    2013-08-01

    Full Text Available Emotional impairment is the common complication of Parkinson's disease (PD. Depression, anxiety and apathy affect the quality of life and the prognosis of PD patients. Neuropsychological and neuroimaging studies of emotional impairment in PD patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways, but the specific mechanism needs further study. In this review we discuss the clinical manifestation, possible pathological mechanism, diagnosis and treatment in PD patients.

  3. 美满霉素改善血管性痴呆大鼠认知功能损伤并抑制氧化应激%Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

    蔡志友; 晏勇; 孙善全; 张骏; 黄良国; 晏宁; 吴芳; 李洁颖

    2008-01-01

    Objective Nitric oxide(NO)was speculated to play an important role in the pathophysiology of cerebral ischemia.Minocycline,a tetracycline derivative,reduced inflammation and protected against cerebral ischemia.To study the neuroprotection mechanism of minocycline for vascular dementia,the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats.Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO).Wistar rats were divideded into 3 groups randomly: sham-operation group (S group),vascular dementia model group (M group),and minocycline treatment group (MT group).The behaviour was tested with Morris water maze and open-field task.Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR).The optical density value was measured by imaging analysis.Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope.Results Minocycline attenuated cognitive impairment.Inducible NOS was significantly down-regulated in MT group,compared with that in M group (P<0.01),while eNOS was significantly up-regulated,compared with that in M group (P<0.01).The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P<0.01).Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia,which restrains apoptosis and oxidative stress to protect neural function.%目的 观察美满霉素(minocycline)对血管性痴呆大鼠学习记忆功能和脑组织内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响,探讨美满霉素对血管性痴呆的脑保护作用的机制.方法 Wistar大鼠随机分为假手术组(S组)、痴呆模

  4. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Manuel A. Fernández-Rojo

    2013-07-01

    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  5. Adaptively robust filtering with classified adaptive factors

    CUI Xianqiang; YANG Yuanxi

    2006-01-01

    The key problems in applying the adaptively robust filtering to navigation are to establish an equivalent weight matrix for the measurements and a suitable adaptive factor for balancing the contributions of the measurements and the predicted state information to the state parameter estimates. In this paper, an adaptively robust filtering with classified adaptive factors was proposed, based on the principles of the adaptively robust filtering and bi-factor robust estimation for correlated observations. According to the constant velocity model of Kalman filtering, the state parameter vector was divided into two groups, namely position and velocity. The estimator of the adaptively robust filtering with classified adaptive factors was derived, and the calculation expressions of the classified adaptive factors were presented. Test results show that the adaptively robust filtering with classified adaptive factors is not only robust in controlling the measurement outliers and the kinematic state disturbing but also reasonable in balancing the contributions of the predicted position and velocity, respectively, and its filtering accuracy is superior to the adaptively robust filter with single adaptive factor based on the discrepancy of the predicted position or the predicted velocity.

  6. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  7. Computer interfaces for the visually impaired

    Higgins, Gerry

    1991-01-01

    Information access via computer terminals extends to blind and low vision persons employed in many technical and nontechnical disciplines. Two aspects are detailed of providing computer technology for persons with a vision related handicap. First, research into the most effective means of integrating existing adaptive technologies into information systems was made. This was conducted to integrate off the shelf products with adaptive equipment for cohesive integrated information processing systems. Details are included that describe the type of functionality required in software to facilitate its incorporation into a speech and/or braille system. The second aspect is research into providing audible and tactile interfaces to graphics based interfaces. Parameters are included for the design and development of the Mercator Project. The project will develop a prototype system for audible access to graphics based interfaces. The system is being built within the public domain architecture of X windows to show that it is possible to provide access to text based applications within a graphical environment. This information will be valuable to suppliers to ADP equipment since new legislation requires manufacturers to provide electronic access to the visually impaired.

  8. Experimental Adaptive Digital Performance Monitoring for Optical DP-QPSK Coherent Receiver

    Borkowski, Robert; Zhang, Xu; Zibar, Darko;

    2011-01-01

    We report on a successful experimental demonstration of a digital optical performance monitoring (OPM) yielding satisfactory estimation accuracy along with adaptive impairment equalization. No observable penalty is measured when equalizer is driven by monitoring module....

  9. Assessing functional impairment in individuals with mild cognitive impairment

    Patrícia Belchior

    2016-04-01

    Full Text Available To date, there is no consensus on how to assess functional impairment in individuals with mild cognitive impairment (MCI, and this lack of consensus is reflected in the clinical practice. Since the criterion used in the literature is very vague, clinicians are still left without much guidance in this area. Thus, the main goal of this study was to examine how functional impairment in individuals with MCI has been assessed in the literature. An electronic database search strategy was developed in consultation with an experienced librarian. Four databases (CINAHL, PsycINFO, PubMed, and MEDLINE were searched from 2000 to May 2014 to provide a comprehensive coverage of the literature. The literature search yielded 14 tools that assessed functional impairment in MCI. Among those, nine tools were performance-based measures in which participants were observed while executing a task in a simulated environment using real life material. In terms of questionnaires (either informant- or self-reports, five tools were found. Different functional domains have been assessed in each tool. According to this review, the characteristics of the instruments used in the literature to assess functional impairment in individuals with MCI vary greatly. Nonetheless, results of this study allow clinicians to make better-informed decisions when choosing a functional assessment for this population.

  10. Adaptive Image Denoising by Mixture Adaptation.

    Luo, Enming; Chan, Stanley H; Nguyen, Truong Q

    2016-10-01

    We propose an adaptive learning procedure to learn patch-based image priors for image denoising. The new algorithm, called the expectation-maximization (EM) adaptation, takes a generic prior learned from a generic external database and adapts it to the noisy image to generate a specific prior. Different from existing methods that combine internal and external statistics in ad hoc ways, the proposed algorithm is rigorously derived from a Bayesian hyper-prior perspective. There are two contributions of this paper. First, we provide full derivation of the EM adaptation algorithm and demonstrate methods to improve the computational complexity. Second, in the absence of the latent clean image, we show how EM adaptation can be modified based on pre-filtering. The experimental results show that the proposed adaptation algorithm yields consistently better denoising results than the one without adaptation and is superior to several state-of-the-art algorithms. PMID:27416593

  11. Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis

    Neitemeier, S; Dolga, A M; Honrath, B; Karuppagounder, S S; Alim, I; Ratan, R R; Culmsee, C

    2016-01-01

    Mitochondrial impairment induced by oxidative stress is a main characteristic of intrinsic cell death pathways in neurons underlying the pathology of neurodegenerative diseases. Therefore, protection of mitochondrial integrity and function is emerging as a promising strategy to prevent neuronal dama

  12. Adaptive Technology that Provides Access to Computers. DO-IT Program.

    Washington Univ., Seattle.

    This brochure describes the different types of barriers individuals with mobility impairments, blindness, low vision, hearing impairments, and specific learning disabilities face in providing computer input, interpreting output, and reading documentation. The adaptive hardware and software that has been developed to provide functional alternatives…

  13. Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation

    Celi, Pietro; Gabai, Gianfranco

    2015-01-01

    This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functi...

  14. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

    Sven Joubert

    2008-01-01

    Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

  15. Unimpaired Neuro-Adaptive Plasticity in an Elderly Astronaut

    Paloski, William H.; Black, F. Owen; Metter, E. Jeffrey; Dawson, David L. (Technical Monitor)

    1999-01-01

    Quantitative analyses of a 77 year old astronaut's balance control performances on a standardized test battery revealed few differences between his neuro-adaptive responses to space flight and those of a group of younger astronauts tested following missions of similar duration. This finding suggests that the physiological changes associated with age do not necessarily impair adaptive plasticity in the human following removal and subsequent reintroduction of gravity.

  16. Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.

    Alzoubi, Karem H; Mayyas, Fadia A; Khabour, Omar F; Bani Salama, Fatima M; Alhashimi, Farah H; Mhaidat, Nizar M

    2016-07-01

    Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P sleep-deprived rats (P  0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD. PMID:26084441

  17. Staged membrane oxidation reactor system

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2012-09-11

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  18. Adaptive Modular Playware

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user’s...

  19. Language Impairment and Generative Analysis

    Andrej Stopar

    2004-12-01

    Full Text Available This article deals with different types of language impairment from the perspective of generative grammar. The paper focuses on syntactic deficiencies observed in aphasic and SLI (specific language impairment patients. We show that the observed ungrammatical structures do not appear in a random fashion but can be predicted by that theory of universal sentence structure which posits a strict hierarchy of its constituent parts. The article shows that while the hierarchically lower elements remain unaffected, the higher positions in the hierarchy show various degrees of syntactic impairment. The paper supports the implementation of recent developments in the field of generative grammar with the intention of encouraging further theoretical, experimental and therapeutic research in the field.

  20. Local intensity adaptive image coding

    Huck, Friedrich O.

    1989-01-01

    The objective of preprocessing for machine vision is to extract intrinsic target properties. The most important properties ordinarily are structure and reflectance. Illumination in space, however, is a significant problem as the extreme range of light intensity, stretching from deep shadow to highly reflective surfaces in direct sunlight, impairs the effectiveness of standard approaches to machine vision. To overcome this critical constraint, an image coding scheme is being investigated which combines local intensity adaptivity, image enhancement, and data compression. It is very effective under the highly variant illumination that can exist within a single frame or field of view, and it is very robust to noise at low illuminations. Some of the theory and salient features of the coding scheme are reviewed. Its performance is characterized in a simulated space application, the research and development activities are described.

  1. Dopamine Oxidation and Autophagy

    Patricia Muñoz

    2012-01-01

    Full Text Available The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxic α-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i the formation of α-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii the formation of adducts with α- and β-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.

  2. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

    Sopi Ramadan B; Zaidi Syed IA; Mladenov Mitko; Sahiti Hazbije; Istrefi Zahide; Gjorgoski Icko; Lajçi Azem; Jakupaj Muharrem

    2012-01-01

    Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS) and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM). Methods Electrical field stimulation (EFS, 2–20 V)-induced relaxation was measured under in vitro c...

  3. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

    Chadderdon, Scott M.; Belcik, J. Todd; Smith, Elise; Pranger, Lindsay; Kievit, Paul; Grove, Kevin L.; Lindner, Jonathan R

    2012-01-01

    Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) ...

  4. Adaptive Sticky Generalized Metropolis

    Fabrizio Leisen; Roberto Casarin; David Luengo; Luca Martino

    2013-01-01

    We introduce a new class of adaptive Metropolis algorithms called adaptive sticky algorithms for efficient general-purpose simulation from a target probability distribution. The transition of the Metropolis chain is based on a multiple-try scheme and the different proposals are generated by adaptive nonparametric distributions. Our adaptation strategy uses the interpolation of support points from the past history of the chain as in the adaptive rejection Metropolis. The algorithm efficiency i...

  5. Driver Compensation: Impairment or Improvement?

    Young, Richard A

    2015-12-01

    Strayer et al.'s conclusion that their "cognitive distraction scale" for auditory-vocal tasks indicates "significant impairments to driving" is not supported by their data. Additional analysis demonstrates that slower brake reaction times during auditory-vocal tasks were fully compensated for by longer following distances to the lead car. Naturalistic driving data demonstrate that cellular conversation decreases crash risk, the opposite of the article's assumption. Hence, the scale's internal and external validities for indicating driving impairment are highly questionable. PMID:26534851

  6. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  7. Interest of 50% nitrous oxide and oxygen premix sedation in gerodontology

    Emmanuel Nicolas

    2008-12-01

    Full Text Available Emmanuel Nicolas1,2, Claire Lassauzay1,21CHU de Clermont-Ferrand, 63000 Clermont-Ferrand, France; 2Université Clermont 1, EA 3847, Faculty of Dentistry, 63000 Clermont-Ferrand, FranceAbstract: Elderly patients presenting cardiovascular, respiratory, or neurological disorders require a specific dental care approach, especially patients presenting Alzheimer’s disease. Sedative procedures can prevent dental care-induced stress, even when there is effective pain control, but they have to be adapted to accommodate age-induced physiological modifications, age-related pathologies, and the concomitant treatments. In many situations, routine sedative prescriptions for dental care, such as benzodiazepine or antihistaminics, are not recommended for these patients. Nitrous oxide inhalation together with a specific behavioral threshold is currently the only sedative procedure adapted to cognitively-impaired elderly patients. Nitrous oxide is able to curb stress and its cardiovascular consequences, improve oxygenation, and optimize cooperation during dental care, making not only rehabilitation treatments but also routine dental care a viable option.Keywords: nitrous oxide, oxygen, premix, sedation, gerodontology, dental care

  8. OXIDATIVE STRESS, INSULIN SIGNALING AND DIABETES

    Rains, Justin L.; Jain, Sushil K.

    2010-01-01

    Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can ...

  9. Adapting Web Information to Disabled and Elderly Users.

    Kobsa, Alfred

    This paper describes work aimed at catering the content of World Wide Web (WWW) pages to the needs of different users, including elderly people and users with vision and motor impairments. An overview is provided of the AVANTI system, a European WWW-based tourist information system that adapts Web pages to each user's individual needs before…

  10. Oceanography for the Visually Impaired

    Fraser, Kate

    2008-01-01

    Amy Bower is a physical oceanographer and senior scientist at the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Massachusetts--she has also been legally blind for 14 years. Through her partnership with the Perkins School for the Blind in Watertown, Massachusetts, the oldest K-12 school for the visually impaired in the United States,…

  11. Language Impairment in Autistic Children.

    Deaton, Ann Virginia

    Discussed is the language impairment of children with infantile autism. The speech patterns of autistic children, including echolalia, pronomial reversal, silent language, and voice imitation, are described. The clinical picture of the autistic child is compared to that of children with such other disorders as deafness, retardation, and…

  12. Language Impairment in Cerebellar Ataxia

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    2014-01-01

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  13. Cognitive Impairment in Multiple Sclerosis

    Farnaz Etesam

    2014-01-01

    Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

  14. Expressing Adaptation Strategies Using Adaptation Patterns

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  15. Cognitive impairments may mimic delusions.

    Eterović, Marija; Kozarić-Kovačić, Dragica

    2015-12-01

    Delusions are often recognized as key to the concept of psychosis. What is delusion is one of the basic questions of psychopathology. The common denominator of definitions of delusions is the divergence between the strong conviction in the delusional belief and superior evidences to the contrary which are continually ignored. An implicit, sustainably unspoken assumption is that the person with delusional belief has cognitive capacities to process the (counter-)arguments relevant to their delusion. However, individual's cognitive capacities are not being emphasized when delusions are evaluated. Moreover, the impact of cognitive decline on formation of delusions is neglected, both in theory and practice. We elaborate that cognitive deficits may facilitate, oppose, or mimic delusions. We focus on the last, which can lead to diagnosing as delusion what could be explained by cognitive decline and better called pseudo-delusion. The risk is significant when cognition is impaired, as in demented people; an issue which has not yet been debated. True delusions are incompatible with person's cognitive capacities, i.e., if we take into account person's cognitive status, we still cannot understand how the person holds the strange belief with an extraordinary conviction. Pseudo-delusions would be beliefs, thoughts or judgments that at first seem delusional (they are false, subculturally atypical beliefs that are strongly maintained in the face of counterargument), but lose the essence of delusions after we take cognitive impairment into account. Pseudo-delusions could actually be explained or understood by person's cognitive impairments, they "fit into" them. The reported reality-based contents of delusions in the elderly, poor response to antipsychotics and lack of association with early or family history of psychiatric disorders could in part be accounted for by the bias of misdiagnosing the cognitive impairment as the delusion. Not recognizing that the cognitive impairment

  16. Cognitive impairments in cerebrovascular disease

    A. Yu. Emelin

    2014-12-01

    Full Text Available Cerebrovascular diseases belong to a group of the major causes of cognitive impairments, in the elderly in particular. The paper presents current ideas on the etiology and pathogenesis of vascular cognitive impairments (VCI. The etiological factors of VCI may be divided into genetic, sociodemographic, and common risk factors for vascular and other diseases. The pathogenesis of VCI is multifactorial; cognitive function decrement results from brain damage due to cerebral circulatory disorders. Damage to the deep white matter portions and basal ganglions plays a leading role in the development of cognitive deficit in cerebral circulatory insufficiency, disrupting the connections between the frontal lobes and subcortical structures (a dissociation phenomenon. Regulatory functions are impaired; instability of volitional attention develops; the speed of thinking processes and the performance of professional and everyday skills are suffered, mnestic functions being impaired to a lesser extent. Impairments in other higher cortical functions, such as speech, gnosis, praxis, thinking, generally occur in the later stages of cognitive deficit. The comprehensive approach to examining patients with cognitive dysfunctions, which encompasses physical examination with a mandatory evaluation of neurological symptoms, neuropsychological testing, laboratory studies, instrumental diagnostic methods, and structural and functional neuroimaging techniques, are most justified now. VCI therapy is a challenging task requiring the specific features of different types of cognitive deficit to be analyzed, by providing a rationale for the choice of medications. Therapeutic effectiveness may be enhanced by rational combined multimodal therapy, by keeping in mind a variety of factors for the pathogenesis of VCI.

  17. Stress Constellations and Coping Styles of Older Adults with Age-Related Visual Impairment

    Lee, Kyoung Othelia; Brennan, Mark

    2006-01-01

    Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…

  18. Inventory of Electronic Mobility Aids for Persons with Visual Impairments: A Literature Review

    Roentgen, Uta R.; Gelderblom, Gert Jan; Soede, Mathijs; de Witte, Luc P.

    2008-01-01

    This literature review of existing electronic mobility aids for persons who are visually impaired and recent developments in this field identified and classified 146 products, systems, and devices. The 21 that are currently available that can be used without environmental adaptation are described in functional terms. (Contains 2 tables.)

  19. Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach

    Mazzetti, Marta Blanca; Taira, Maria Cristina; Lelli, Sandra Marcela; Viale, Leonor Carmen San Martin de [Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA, Ciudad Autonoma Buenos Aires (Argentina); Dascal, Eduardo; Basabe, Juan Carlos [Centro de Investigaciones Endocrinologicas (CEDIE). Hospital de Ninos, Dr. Ricardo Gutierrez, C1425EDF, Ciudad Autonoma Buenos Aires (Argentina)

    2004-01-01

    Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative

  20. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

    Wang, Dan; Strandgaard, Svend; Iversen, Jens; Wilcox, Christopher S

    2009-01-01

    We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n = 9) compared with normal controls (n = 10). We now test the hypothesis...

  1. Verbal learning impairment in euthymic bipolar disorder: BDI v BDII

    Bourne, Corin; Bilderbeck, Amy; Drennan, Rebecca; Atkinson, Lauren; Price, Jonathan; Geddes, John R.; Goodwin, Guy M.

    2015-01-01

    Objectives Cognitive impairment is known to occur in bipolar disorder (BD), even in euthymic patients, with largest effect sizes often seen in Verbal Learning and Memory Tasks (VLT). However, comparisons between BD Type-I and Type-II have produced inconsistent results partly due to low sample sizes. Methods This study compared the performance of 183 BDI with 96 BDII out-patients on an adapted version of the Rey Verbal Learning Task. Gender, age, years of education, mood scores and age at onse...

  2. Impaired glycemia increases disease progression in mild cognitive impairment

    Morris, Jill K.; Vidoni, Eric D.; Honea, Robyn A.; Burns, Jeffrey M.

    2013-01-01

    Insulin resistance and Type 2 Diabetes are associated with cognitive decline and increased risk for Alzheimer’s disease (AD). Relatively few studies have assessed the impact of metabolic dysfunction on conversion to AD in mild cognitive impairment (MCI), and it is unclear whether glycemic status is associated with clinically-relevant measures of cognitive decline and brain structure in MCI. This study used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the relation...

  3. Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND)

    Stephan, Blossom CM; Matthews, Fiona E; Khaw, Kay-Tee; Dufouil, Carole; Brayne, Carol

    2009-01-01

    Identifying the causes of dementia is important in the search for effective preventative and treatment strategies. The concept of mild cognitive impairment (MCI), as prodromal dementia, has been useful but remains controversial since in population-based studies it appears to be a limited predictor of progression to dementia. Recognising the relative contribution of neurodegenerative and vascular causes, as well as their interrelationship, may enhance predictive accuracy. The concept of vascul...

  4. Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles.

    Matin, Nusrat; Fisher, Courtney; Jackson, William F; Dorrance, Anne M

    2016-05-15

    Chronic cerebral hypoperfusion is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral carotid artery stenosis (BCAS) is a physiologically relevant model of chronic cerebral hypoperfusion. We hypothesized that BCAS in 20-wk-old Wistar-Kyoto (WKY) rats would impair cognitive function and lead to reduced endothelium-dependent dilation and outward remodeling in the parenchymal arterioles (PAs). After 8 wk of BCAS, both short-term memory and spatial discrimination abilities were impaired. In vivo assessment of cerebrovascular reserve capacity showed a severe impairment after BCAS. PA endothelial function and structure were assessed by pressure myography. BCAS impaired endothelial function in PAs, as evidenced by reduced dilation to carbachol. Addition of nitric oxide synthase and cyclooxygenase inhibitors did not change carbachol-mediated dilation in either group. Inhibiting CYP epoxygenase, the enzyme that produces epoxyeicosatrienoic acid (EETs), a key determinant of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation, abolished dilation in PAs from Sham rats, but had no effect in PAs from BCAS rats. Expression of TRPV4 channels, a target for EETs, was decreased and maximal dilation to a TRPV4 agonist was attenuated after BCAS. Together these data suggest that EET-mediated dilation is impaired in PAs after BCAS. Thus impaired endothelium-dependent dilation in the PAs may be one of the contributing factors to the cognitive impairment observed after BCAS. PMID:26968546

  5. Uncertainty in adaptive capacity

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  6. Adaptive Rationality, Adaptive Behavior and Institutions

    Volchik Vyacheslav, V.

    2015-12-01

    Full Text Available The economic literature focused on understanding decision-making and choice processes reveals a vast collection of approaches to human rationality. Theorists’ attention has moved from absolutely rational, utility-maximizing individuals to boundedly rational and adaptive ones. A number of economists have criticized the concepts of adaptive rationality and adaptive behavior. One of the recent trends in the economic literature is to consider humans irrational. This paper offers an approach which examines adaptive behavior in the context of existing institutions and constantly changing institutional environment. It is assumed that adaptive behavior is a process of evolutionary adjustment to fundamental uncertainty. We emphasize the importance of actors’ engagement in trial and error learning, since if they are involved in this process, they obtain experience and are able to adapt to existing and new institutions. The paper aims at identifying relevant institutions, adaptive mechanisms, informal working rules and practices that influence actors’ behavior in the field of Higher Education in Russia (Rostov Region education services market has been taken as an example. The paper emphasizes the application of qualitative interpretative methods (interviews and discourse analysis in examining actors’ behavior.

  7. Markers of neurodevelopmental impairments in early-onset psychosis

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  8. Adaptive Coordinate Descent

    Loshchilov, Ilya; Schoenauer, Marc; Sebag, Michèle

    2011-01-01

    Independence from the coordinate system is one source of efficiency and robustness for the Covariance Matrix Adaptation Evolution Strategy (CMA-ES). The recently proposed Adaptive Encoding (AE) procedure generalizes CMA-ES adaptive mechanism, and can be used together with any optimization algorithm. Adaptive Encoding gradually builds a transformation of the coordinate system such that the new coordinates are as decorrelated as possible with respect to the objective function. But any optimizat...

  9. Adaptation to climate change

    J. Carmin; K. Tierney; E. Chu; L.M. Hunter; J.T. Roberts; L. Shi

    2015-01-01

    Climate change adaptation involves major global and societal challenges such as finding adequate and equitable adaptation funding and integrating adaptation and development programs. Current funding is insufficient. Debates between the Global North and South center on how best to allocate the financ

  10. Diagnosis advances in vascular cognitive impairment

    Hua Zhou; Zhong Zhao

    2009-01-01

    Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.

  11. Endocrine Risk Factors for Cognitive Impairment

    Moon, Jae Hoon

    2016-01-01

    Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment h...

  12. Saccade adaptation in autism and Asperger's disorder.

    Johnson, B P; Rinehart, N J; White, O; Millist, L; Fielding, J

    2013-07-23

    Autism and Asperger's disorder (AD) are neurodevelopmental disorders primarily characterized by deficits in social interaction and communication, however motor coordination deficits are increasingly recognized as a prevalent feature of these conditions. Although it has been proposed that children with autism and AD may have difficulty utilizing visual feedback during motor learning tasks, this has not been directly examined. Significantly, changes within the cerebellum, which is implicated in motor learning, are known to be more pronounced in autism compared to AD. We used the classic double-step saccade adaptation paradigm, known to depend on cerebellar integrity, to investigate differences in motor learning and the use of visual feedback in children aged 9-14 years with high-functioning autism (HFA; IQ>80; n=10) and AD (n=13). Performance was compared to age and IQ matched typically developing children (n=12). Both HFA and AD groups successfully adapted the gain of their saccades in response to perceived visual error, however the time course for adaptation was prolonged in the HFA group. While a shift in saccade dynamics typically occurs during adaptation, we revealed aberrant changes in both HFA and AD groups. This study contributes to a growing body of evidence centrally implicating the cerebellum in ocular motor dysfunction in autism. Specifically, these findings collectively imply functional impairment of the cerebellar network and its inflow and outflow tracts that underpin saccade adaptation, with greater disturbance in HFA compared to AD. PMID:23562581

  13. Impaired sleep and allostatic load

    Clark, Alice Jessie; Dich, Nadya; Lange, Theis;

    2014-01-01

    Objective: Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load...... Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions. Results: Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated...... with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL, the...

  14. Alcohol and the Physically Impaired: Special Focus.

    Boros, Alexander, Ed.

    1989-01-01

    The articles in this special issue explore the connections between the dual disabilities of alcohol abuse and physical impairment, and reflect progress made in exploring the causes and treatments of alcohol abuse among the physically impaired. Selected articles include: "Results of a Model Intervention Program for Physically Impaired Persons"…

  15. Specific Language Impairment Across Languages

    Leonard, Laurence B.

    2013-01-01

    Children with specific language impairment (SLI) have a significant and longstanding deficit in spoken language ability that adversely affects their social and academic well-being. Studies of children with SLI in a wide variety of languages reveal diverse symptoms, most of which seem to reflect weaknesses in grammatical computation and phonological short-term memory. The symptoms of the disorder are sensitive to the type of language being acquired, with extraordinary weaknesses seen in those ...

  16. Nutrition in neurologically impaired children

    2009-01-01

    Malnutrition, either under- or overnutrition, is a common condition among neurologically impaired children. Energy needs are difficult to define in this heterogeneous population, and there is a lack of information on what normal growth should be in these children. Non-nutritional factors may influence growth, but nutritional factors such as insufficient caloric intake, excessive nutrient losses and abnormal energy metabolism also contribute to growth failure. Malnutrition is associated with s...

  17. Epigenetic Treatments for Cognitive Impairments

    Day, Jeremy J.; Sweatt, J. David

    2011-01-01

    Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In t...

  18. Multilingualism and Specific Language Impairment

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  19. Electrophysiology in visually impaired children

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates its value in establishing diagnoses and predicting the course of a disease, with consequences for the rehabilitation process. The electrophysiological results also contribute to the understanding of...

  20. Cognitive impairment in Parkinson's disease.

    Cosgrove, Jeremy; Alty, Jane Elizabeth; Jamieson, Stuart

    2015-04-01

    Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential. PMID:25814509

  1. Impairments of astrocytes are involved in the D-galactose-induced brain aging

    Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of D-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of D-galactose injection. D-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of D-galactose

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

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

    2016-01-01

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

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

    Amy C. Keller

    2016-01-01

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

  4. ANALYSIS OF BIOLOGICAL SCIENCES FOR TEACHING STUDENTS WITH VISUAL IMPAIRMENT IN DISTRITO FEDERAL’S SCHOOLS

    Júlia Carvalho Mota de Souza

    2014-05-01

    Full Text Available Visual impairment is a limitation that occurs in the sensory part of the vision, and can be classified as blindness, low vision or subnormal vision. The people with visually impaired have guaranteed rights to study in regular schools or special education schools. Therefore, a differentiated teaching is necessary for the learning of visually impaired students to happen effectively and ensure educational inclusion within the school. The aim of this study was to qualitatively analyze the teaching of Biological Sciences for the visually impaired in schools of the Distrito Federal, noting the institution, teachers and visually impaired students. The study was conducted using semi-structured interviews analyzed epistemologically. The results showed that: the institutions do not have adequate physical infrastructure; Biology teachers have no qualifications required; teachers of resource rooms are able to meet visually impaired students, even if resources are not sufficient, and the students do not understand all the benefits they could have. Therefore, it is necessary to adapt the teaching and learning materials to allow for a better education for visually impaired students and thus ensure appropriate learning for all students within the same educational institution.

  5. Protective Effects of Punica Granatum Seeds Extract Against Aging and Scopolamine Induced Cognitive Impairments in Mice

    Kumar, Sokindra; Maheshwari, Kamal Kishore; Singh, Vijender

    2008-01-01

    Dementia is one of the age related mental problems and characteristic symptom of various neurodegenerative diseases including Alzheimer's disease. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Many studies have shown that certain phenolic antioxidants attenuate neuronal cell death induced by oxidative stress. The present work was undertaken to assess the effect of ethanolic extract of Punica granatum seeds on cognit...

  6. Hyperglycaemia and diabetes impair gap junctional communication among astrocytes

    Gautam K Gandhi

    2010-03-01

    Full Text Available Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15–25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin-treated rats at 20–24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

  7. Oxidative Stress and Anxiety: Relationship and Cellular Pathways

    Jaouad Bouayed; Hassan Rammal; Rachid Soulimani

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  8. Cryopreservation of human skeletal muscle impairs mitochondrial function

    Larsen, Steen; Wright-Paradis, C; Gnaiger, E;

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...... of oxidative phosphorylation was significantly (P skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P

  9. Communication Partners’ Journey through Their Partner’s Hearing Impairment

    Vinaya K. C. Manchaiah

    2013-01-01

    Full Text Available The objective of this study was to further develop the Ida Institute model on communication partners’ (CPs journey through experiences of person with hearing impairment (PHI, based on the perspectives of CPs. Nine CPs of hearing aid users participated in this study, recruited through the Swansea hearing impaired support group. Semi-structured interviews were conducted, the data were analysed using qualitative thematic analysis and presented with the use of process mapping approach. Seven main phases were identified in the CP journey which includes: (1 contemplation, (2 awareness, (3 persuasion, (4 validation, (5 rehabilitation, (6 adaptation, and (7 resolution. The Ida Institute model (based on professionals’ perspective was compared with the new template developed (based on CPs’ perspectives. The results suggest some commonalities and differences between the views of professionals and CPs. A new phase, adaptation, was identified from CPs reported experiences, which was not identified by professionals in the Ida Institute model. The CP’s journey model could be a useful tool during audiological enablement/rehabilitation sessions to promote discussion between the PHI and the CP. In addition, it can be used in the training of hearing healthcare professionals.

  10. Clinical features, comorbidity, and cognitive impairment in elderly bipolar patients

    Rise, Ida Vikan; Haro, Josep Maria; Gjervan, Bjørn

    2016-01-01

    Introduction Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. Objectives We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. Methods Eligible studies were identified in MedLine by the Medical Subject Headings terms “bipolar disorder” and “aged”. We only included original research reports published in English between 2012 and 2015. Results From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. Conclusion There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established.

  11. The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2).

    Rigalli, Juan Pablo; Perdomo, Virginia Gabriela; Ciriaci, Nadia; Francés, Daniel Eleazar Antonio; Ronco, María Teresa; Bataille, Amy Michele; Ghanem, Carolina Inés; Ruiz, María Laura; Manautou, José Enrique; Catania, Viviana Alicia

    2016-08-01

    Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3h of exposure, returning to normality at 24h. Additionally, BZL increased glutathione peroxidase activity at 12h and the oxidized glutathione/total glutathione (GSSG/GSSG+GSH) ratio that reached a peak at 24h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG+GSH returned to control values at 48h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48h, explaining normalization of GSSG/GSSG+GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. PMID:27180241

  12. Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

    Grevengoed, Trisha J; Martin, Sarah A; Katunga, Lalage; Cooper, Daniel E; Anderson, Ethan J; Murphy, Robert C; Coleman, Rosalind A

    2015-01-01

    Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 (Acsl1(T-/-)) have impaired cardiac fatty acid oxidation and rely on glucose for ATP producti...

  13. Origins of adaptive immunity.

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity. PMID:21395512

  14. Technology transfer for adaptation

    Biagini, Bonizella; Kuhl, Laura; Gallagher, Kelly Sims; Ortiz, Claudia

    2014-09-01

    Technology alone will not be able to solve adaptation challenges, but it is likely to play an important role. As a result of the role of technology in adaptation and the importance of international collaboration for climate change, technology transfer for adaptation is a critical but understudied issue. Through an analysis of Global Environment Facility-managed adaptation projects, we find there is significantly more technology transfer occurring in adaptation projects than might be expected given the pessimistic rhetoric surrounding technology transfer for adaptation. Most projects focused on demonstration and early deployment/niche formation for existing technologies rather than earlier stages of innovation, which is understandable considering the pilot nature of the projects. Key challenges for the transfer process, including technology selection and appropriateness under climate change, markets and access to technology, and diffusion strategies are discussed in more detail.

  15. Diffusion Adaptation over Networks

    Sayed, Ali H

    2012-01-01

    Adaptive networks are well-suited to perform decentralized information processing and optimization tasks and to model various types of self organized and complex behavior encountered in nature. Adaptive networks consist of a collection of agents with processing and learning abilities. The agents are linked together through a connection topology, and they cooperate with each other through local interactions to solve distributed inference problems in real-time. The continuous diffusion of information across the network enables agents to adapt their performance in relation to changing data and network conditions; it also results in improved adaptation and learning performance relative to non-cooperative networks. This article provides an overview of diffusion strategies for adaptation and learning over networks. The article is divided into several sections: 1. Motivation; 2. Mean-Square-Error Estimation; 3. Distributed Optimization via Diffusion Strategies; 4. Adaptive Diffusion Strategies; 5. Performance of Ste...

  16. Consciousness And Adaptive Behavior

    Sieb, Richard/A.

    2005-01-01

    Consciousness has resisted scientific explanation for centuries. The main problem in explaining consciousness is its subjectivity. Subjective systems may be adaptive. Humans can produce voluntary new or novel intentional (adaptive) action and such action is always accompanied by consciousness. Action normally arises from perception. Perception must be rerepresented in order to produce new or novel adaptive action. The internal explicit states produced by a widespread nonlinear emergen...

  17. Human Adaptations: Free divers

    Tournat, Troy Z.

    2014-01-01

    Freediving has been around for thousands of years and was only way to dive until the inventionof oxygen tanks in the 19th century. Around the world, people dove for goods such as pearls, andtoday people freedive for sport. Divers stretch the limit of their body and mind’s capabilitiesthrough psychological adaptations from thermal, respiratory, and cardiovascular responses.Findings conclude that thermal adaptations are a similar process to cold adaptive response. Withthe implementation of wets...

  18. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity

    Lantier, Louise; Fentz, Joachim; Mounier, Rémi;

    2014-01-01

    AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a central role in skeletal muscle metabolism. We used skeletal muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence of the physiological importance of AMPK in regulating muscle...... as an elevated expression of interleukin 6 (IL-6) mRNA, possibly consistent with mild skeletal muscle injury. Notably, we found that AMPKα1 and AMPKα2 isoforms are dispensable for contraction-induced skeletal muscle glucose transport, except for male soleus muscle. However, the lack of skeletal...... muscle AMPK diminished maximal ADP-stimulated mitochondrial respiration, showing an impairment at complex I. This effect was not accompanied by changes in mitochondrial number, indicating that AMPK regulates muscle metabolic adaptation through the regulation of muscle mitochondrial oxidative capacity and...

  19. Adaptive Multimedia Retrieval: Semantics, Context, and Adaptation

    This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous submissi......This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous...

  20. Decentralized adaptive control

    Oh, B. J.; Jamshidi, M.; Seraji, H.

    1988-01-01

    A decentralized adaptive control is proposed to stabilize and track the nonlinear, interconnected subsystems with unknown parameters. The adaptation of the controller gain is derived by using model reference adaptive control theory based on Lyapunov's direct method. The adaptive gains consist of sigma, proportional, and integral combination of the measured and reference values of the corresponding subsystem. The proposed control is applied to the joint control of a two-link robot manipulator, and the performance in computer simulation corresponds with what is expected in theoretical development.

  1. Adaptive Wireless Transceiver Project

    National Aeronautics and Space Administration — Wireless technologies are an increasingly attractive means for spatial data, input, manipulation, and distribution. Mobitrum is proposing an innovative Adaptive...

  2. Sleep, Torpor and Memory Impairment

    Palchykova, S.; Tobler, I.

    It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.

  3. Empathy in schizophrenia: impaired resonance.

    Haker, Helene; Rössler, Wulf

    2009-09-01

    Resonance is the phenomenon of one person unconsciously mirroring the motor actions as basis of emotional expressions of another person. This shared representation serves as a basis for sharing physiological and emotional states of others and is an important component of empathy. Contagious laughing and contagious yawning are examples of resonance. In the interpersonal contact with individuals with schizophrenia we can often experience impaired empathic resonance. The aim of this study is to determine differences in empathic resonance-in terms of contagion by yawning and laughing-in individuals with schizophrenia and healthy controls in the context of psychopathology and social functioning. We presented video sequences of yawning, laughing or neutral faces to 43 schizophrenia outpatients and 45 sex- and age-matched healthy controls. Participants were video-taped during the stimulation and rated regarding contagion by yawning and laughing. In addition, we assessed self-rated empathic abilities (Interpersonal Reactivity Index), psychopathology (Positive and Negative Syndrome Scale in the schizophrenia group resp. Schizotypal Personality Questionnaire in the control group), social dysfunction (Social Dysfunction Index) and executive functions (Stroop, Fluency). Individuals with schizophrenia showed lower contagion rates for yawning and laughing. Self-rated empathic concern showed no group difference and did not correlate with contagion. Low rate of contagion by laughing correlated with the schizophrenia negative syndrome and with social dysfunction. We conclude that impaired resonance is a handicap for individuals with schizophrenia in social life. Blunted observable resonance does not necessarily reflect reduced subjective empathic concern. PMID:19377866

  4. Validation of the Dutch version of the quick mild cognitive impairment screen (Qmci-D).

    Bunt, Steven

    2015-10-01

    Differentiating mild cognitive impairment (MCI) from dementia is important, as treatment options differ. There are few short (<5 min) but accurate screening tools that discriminate between MCI, normal cognition (NC) and dementia, in the Dutch language. The Quick Mild Cognitive Impairment (Qmci) screen is sensitive and specific in differentiating MCI from NC and mild dementia. Given this, we adapted the Qmci for use in Dutch-language countries and validated the Dutch version, the Qmci-D, against the Dutch translation of the Standardised Mini-Mental State Examination (SMMSE-D).

  5. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  6. Endothelial dysfunction impairs vascular neurotransmission in tail arteries.

    Sousa, Joana B; Fresco, Paula; Diniz, Carmen

    2015-01-01

    The present study intends to clarify if endothelium dysfunction impairs vascular sympathetic neurotransmission. Electrically-evoked tritium overflow (100 pulses/5 Hz) was evaluated in arteries (intact and denuded) or exhibiting some degree of endothelium dysfunction (spontaneously hypertensive arteries), pre-incubated with [(3)H]-noradrenaline in the presence of enzymes (nitric oxide synthase (NOS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; xanthine oxidase; cyclooxygenase; adenosine kinase) inhibitors and a nucleoside transporter inhibitor. Inhibition of endothelial nitric oxide synthase with L-NIO dihydrochloride reduced tritium overflow in intact arteries whereas inhibition of neuronal nitric oxide synthase with Nω-Propyl-L-arginine hydrochloride was devoid of effect showing that only endothelial nitric oxide synthase is involved in vascular sympathetic neuromodulation. Inhibition of enzymes involved in reactive oxygen species or prostaglandins production with apocynin and allopurinol or indomethacin, respectively, failed to alter tritium overflow. A facilitation or reduction of tritium overflow was observed in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or of 5-iodotubericidin, respectively, but only in intact arteries. These effects can be ascribed to a tonic inhibitory effect mediated by A1 receptors. In denuded and hypertensive arteries, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH 58261) reduced tritium overflow, suggesting the occurrence of a tonic activation of A2A receptors. When endogenous adenosine bioavailability was increased by the nucleoside transporter inhibitor, S-(4-Nitrobenzyl)-6-thioinosine, tritium overflow increased in intact, denuded and hypertensive arteries. Among the endothelium-derived substances studied that could alter vascular sympathetic transmission only adenosine/adenosine receptor mediated mechanisms were clearly impaired by endothelium injury

  7. When sustained attention impairs perception

    Ling, Sam; Carrasco, Marisa

    2006-01-01

    Virtually all behavioral and neurophysiological studies have shown that sustained (endogenous, conceptually driven) attention enhances perception. But can this enhancement be held indefinitely? We assessed the time course of attention’s effects on contrast sensitivity, reasoning that if attention does indeed boost stimulus strength, the strengthened representation could result in stronger adaptation over time. We found that attention initially enhances contrast sensitivity, but that over time...

  8. Vision impairment in Liverpool: prevalence and morbidity.

    Rogers, M.

    1996-01-01

    A database related to the activities of the Liverpool vision assessment team was used to identify all children with vision impairment aged 0-16 years, resident in Liverpool, UK, on 1 April 1995. Prevalence rates were calculated for all children with vision impairment, and separately for two groups: those with uncomplicated vision impairment, and those with additional pathology. Visual tract pathologies were tabulated and compared. Associated handicapping conditions were defined and the extent...

  9. Visual Impairments in Children with Cerebral Palsy

    Alimović, Sonja

    2012-01-01

    Cerebral palsy (CP) is the neurological developmental disorder mainly affecting motor abilities. Considering the high rate of associated impairments even the definition of CP is revised and changed. Visual impairment is one of the most common associated impairment. Unfortunately, it is often unrecognized and considered to be a normal consequence of motor problems. Sense of sight is most important for early child development, motivation, learning through imitation. It is, therefore, indispensa...

  10. Behavioral Adaptation and Acceptance

    Martens, M.H.; Jenssen, G.D.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  11. Behavioural adaptation and acceptance

    Martens, M.H.; Jenssen, G.D.; Eskandarian, A.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  12. Adaptive Capacity and Traps

    William A. Brock

    2008-12-01

    Full Text Available Adaptive capacity is the ability of a living system, such as a social–ecological system, to adjust responses to changing internal demands and external drivers. Although adaptive capacity is a frequent topic of study in the resilience literature, there are few formal models. This paper introduces such a model and uses it to explore adaptive capacity by contrast with the opposite condition, or traps. In a social–ecological rigidity trap, strong self-reinforcing controls prevent the flexibility needed for adaptation. In the model, too much control erodes adaptive capacity and thereby increases the risk of catastrophic breakdown. In a social–ecological poverty trap, loose connections prevent the mobilization of ideas and resources to solve problems. In the model, too little control impedes the focus needed for adaptation. Fluctuations of internal demand or external shocks generate pulses of adaptive capacity, which may gain traction and pull the system out of the poverty trap. The model suggests some general properties of traps in social–ecological systems. It is general and flexible, so it can be used as a building block in more specific and detailed models of adaptive capacity for a particular region.

  13. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

    Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

    2009-01-01

    Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (...

  14. Cognitive impairment related changes in the elemental concentration in the brain of old rat

    In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied

  15. Cognitive impairment related changes in the elemental concentration in the brain of old rat

    Serpa, R.F.B. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil)]. E-mail: renata@lin.ufrj.br; Jesus, E.F.O. de [University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Anjos, M.J. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Lopes, R.T. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); Carmo, M.G.T. do [Federal University of Rio de Janeiro, Nutrition Institute, RJ (Brazil); Rocha, M.S. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Rodrigues, L.C. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Moreira, S. [University of Campinas State, Civil Engineering Department, SP (Brazil); Martinez, A.M.B. [Federal University of Rio de Janeiro, Department of Histology and Embryology, RJ (Brazil)

    2006-11-15

    In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.

  16. Ammonia-oxidizing archaea have more important role than ammonia-oxidizing bacteria in ammonia oxidation of strongly acidic soils

    Zhang, Li-Mei; Hu, Hang-Wei; Shen, Ju-Pei; He, Ji-Zheng

    2011-01-01

    Increasing evidence demonstrated the involvement of ammonia-oxidizing archaea (AOA) in the global nitrogen cycle, but the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to ammonia oxidation are still in debate. Previous studies suggest that AOA would be more adapted to ammonia-limited oligotrophic conditions, which seems to be favored by protonation of ammonia, turning into ammonium in low-pH environments. Here, we investigated the autotrophic nitrification activity of AOA...

  17. Family Members Responding to a Visual Impairment.

    Tuttle, Dean W.

    1986-01-01

    A literature review regarding family adjustment to a visually impaired family member considered the stages of denial, withdrawal, acceptance, depression, reaffirmation, coping, mobilization, and self-acceptance. (CB)

  18. The Differences Between Revaluation and Assets Impairment

    BOBIȚAN Nicolae

    2013-05-01

    Full Text Available Impairment and revaluation are terms closely related to one another, with subtle differences. Revaluation and impairment both require the company to evaluate the assets for their fair value, and then take appropriate action in updating the accounting books. The major difference between the two is that a revaluation can be made upwards (to increase the value of the asset to market value or downwards (to ecrease the value. An impairment, on the other hand, only refers to one of the two, a fall in the market value which is then written down. The purpose of the paper is to establish what are the differences between revaluation and impairment of assets.

  19. Evacuation characteristics of visually impaired people

    Sørensen, Janne Gress; Dederichs, Anne

    2015-01-01

    Evacuation characteristics for blind and visually impaired people are presented in the current study. The study was carried out in 2011 and engaged 40 participants in the age from 10 to 69 years. The participants had impairments for all of the four Danish categories for visual impairments (A......-bodied adults. It was found that people with visual impairments were able to uphold a higher walking speed descending stairs than able-bodied adults for increasing person density. The initial walking speed on horizontal planes is lower than the value suggested by the N&M-model. The horizontal mean free walking...

  20. Adapt or Become Extinct!

    Goumas, Georgios; McKee, Sally A.; Själander, Magnus;

    2011-01-01

    boundaries (walls) for applications which limit software development (parallel programming wall), performance (memory wall, communication wall) and viability (power wall). The only way to survive in such a demanding environment is by adaptation. In this paper we discuss how dynamic information collected...... during the execution of an application can be utilized to adapt the execution context and may lead to performance gains beyond those provided by static information and compile-time adaptation. We consider specialization based on dynamic information like user input, architectural characteristics such as...... from static analysis (either during ahead-of-time or just-in-time) compilation. We extend the notion of information-driven adaptation and outline the architecture of an infrastructure designed to enable information ow and adaptation throughout the life-cycle of an application....

  1. Appraising Adaptive Management

    Kai N. Lee

    1999-12-01

    Full Text Available Adaptive management is appraised as a policy implementation approach by examining its conceptual, technical, equity, and practical strengths and limitations. Three conclusions are drawn: (1 Adaptive management has been more influential, so far, as an idea than as a practical means of gaining insight into the behavior of ecosystems utilized and inhabited by humans. (2 Adaptive management should be used only after disputing parties have agreed to an agenda of questions to be answered using the adaptive approach; this is not how the approach has been used. (3 Efficient, effective social learning, of the kind facilitated by adaptive management, is likely to be of strategic importance in governing ecosystems as humanity searches for a sustainable economy.

  2. Adaptive noise cancellation

    In this report we describe the concept of adaptive noise canceling, an alternative method of estimating signals corrupted by additive noise of interference. The method uses 'primary' input containing the corrupted signal and a 'reference' input containing noise correlated in some unknown way with the primary noise, the reference input is adaptively filtered and subtracted from the primary input to obtain the signal estimate. Adaptive filtering before subtraction allows the treatment of inputs that are deterministic or stochastic, stationary or time variable. When the reference input is free of signal and certain other conditions are met then noise in the primary input can be essentially eliminated without signal distortion. It is further shown that the adaptive filter also acts as notch filter. Simulated results illustrate the usefulness of the adaptive noise canceling technique. (author)

  3. Adaptive signal processor

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  4. Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy

    Gabriele Pizzino

    2014-01-01

    Conclusions: Continuous exposure at relatively low concentrations of heavy metals is associated with increased oxidative DNA damage and impaired expression of DNA repair and detoxification genes in adolescents.

  5. Cognitive impairment in Parkinson's disease.

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  6. Verbal memory impairments in dyslexia.

    Kramer, J H; Knee, K; Delis, D C

    2000-01-01

    Although verbal memory deficits are frequently reported in reading disabled children, the specific mechanisms underlying these impairments have yet to be clearly defined. The present study used the California Verbal Learning Test-Children's Version (CVLT-C) to assess verbal learning in 57 dyslexic children and 114 controls matched for gender, age, and WISC-R Vocabulary score. Three areas of verbal memory were investigated: Recall and recognition, use of learning strategies, and interference effects. The dyslexic group learned the list items more slowly, recalled fewer words on the last learning trial and the delayed trials, and performed less well on the recognition condition. Dyslexics and controls displayed similar vulnerability to interference, but group differences were evident in serial position effects. Taken together, our data suggest that dyslexics have less efficient rehearsal and encoding mechanisms, resulting in deficient encoding of new information, but normal retention and retrieval. PMID:14590570

  7. Clean Water Act 303(d) Listed Impaired Waters and their Causes of Impairment from All Years

    U.S. Environmental Protection Agency — Waters identified as impaired as well as their associated causes of impairment from all approved Clean Water Act 303(d) lists submitted by the states. Includes all...

  8. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  9. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

    Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

    2013-08-01

    This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action. PMID:23838966

  10. Magnesium Oxide

    Magnesium is an element your body needs to function normally. Magnesium oxide may be used for different reasons. Some ... to relieve heartburn, sour stomach, or acid indigestion. Magnesium oxide also may be used as a laxative ...

  11. The Walking Trail-Making Test is an early detection tool for mild cognitive impairment

    Perrochon A

    2014-01-01

    Full Text Available Anaick Perrochon, Gilles Kemoun Laboratoire Mobilité, Vieillissement, Exercice (MOVE, EA 6314, Faculté des Sciences du Sport, Université de Poitiers, 8 Allée Jean Monnet, 86000 Poitiers, France; ISIS, Research Institute on Handicap and Aging, Paris, France Background: Executive function impairment (in particular, mental flexibility in the elderly, and in patients with mild cognitive impairment (MCI, is strongly correlated with difficulties in performing complex walking tasks. The aim of this study was to determine if the adaptation of a neuropsychological test (the Trail-Making Test, to evaluate executive functions during walking, can be an early detection tool for cognitive impairment. Methods: Fifty subjects (15 young, 20 older, presumably healthy, and 15 MCI were first evaluated for cognitive functions (Mini-Mental State Examination, Frontal Assessment Battery, and Trail-Making Test and motor functions (10-meter walking test. All subjects then performed a spatial navigation, or a complex walking test (the Walking Trail-Making Test: [WTMT], and their spatiotemporal walking variables were analyzed using cluster analysis. Results: Following evaluation of WTMT locomotor performance, cluster analysis revealed three groups that were distinctly different in age and cognitive abilities: a group of young subjects, a group of healthy older subjects, MCI subjects with amnestic impairment, and a group of MCI subjects with executive function impairment. The WTMT enabled early detection, (ie, borderline MCI of dysexecutive impairment, with 78% sensitivity and 90% specificity. Conclusion: The WTMT is of interest in that it can help provide early detection of dysexecutive cognitive impairment. Keywords: spatial navigation, walking, trail making test, detection, mild cognitive impairment

  12. Cognitive functions in drivers with brain injury : Anticipation and adaption

    Lundqvist, Anna

    2001-01-01

    The purpose of this thesis was to improve the understanding of what cognitive functions are important for driving performance, investigate the impact of impaired cognitive functions on drivers with brain injury, and study adaptation strategies relevant for driving performance after brain injury. Finally, the predictive value of a neuropsychological test battery was evaluated for driving performance. Main results can be summarized in the following conclusions: (a) Cognitive functions in terms ...

  13. The process of organisational adaptation through innovations, and organisational adaptability

    Tikka, Tommi

    2010-01-01

    This study is about the process of organisational adaptation and organisational adaptability. The study generates a theoretical framework about organisational adaptation behaviour and conditions that have influence on success of organisational adaptation. The research questions of the study are: How does an organisation adapt through innovations, and which conditions enhance or impede organisational adaptation through innovations? The data were gathered from five case organisations withi...

  14. Adaptive network countermeasures.

    McClelland-Bane, Randy; Van Randwyk, Jamie A.; Carathimas, Anthony G.; Thomas, Eric D.

    2003-10-01

    This report describes the results of a two-year LDRD funded by the Differentiating Technologies investment area. The project investigated the use of countermeasures in protecting computer networks as well as how current countermeasures could be changed in order to adapt with both evolving networks and evolving attackers. The work involved collaboration between Sandia employees and students in the Sandia - California Center for Cyber Defenders (CCD) program. We include an explanation of the need for adaptive countermeasures, a description of the architecture we designed to provide adaptive countermeasures, and evaluations of the system.

  15. Introduction to adaptive arrays

    Monzingo, Bob; Haupt, Randy

    2011-01-01

    This second edition is an extensive modernization of the bestselling introduction to the subject of adaptive array sensor systems. With the number of applications of adaptive array sensor systems growing each year, this look at the principles and fundamental techniques that are critical to these systems is more important than ever before. Introduction to Adaptive Arrays, 2nd Edition is organized as a tutorial, taking the reader by the hand and leading them through the maze of jargon that often surrounds this highly technical subject. It is easy to read and easy to follow as fundamental concept

  16. [Adaptive optics for ophthalmology].

    Saleh, M

    2016-04-01

    Adaptive optics is a technology enhancing the visual performance of an optical system by correcting its optical aberrations. Adaptive optics have already enabled several breakthroughs in the field of visual sciences, such as improvement of visual acuity in normal and diseased eyes beyond physiologic limits, and the correction of presbyopia. Adaptive optics technology also provides high-resolution, in vivo imaging of the retina that may eventually help to detect the onset of retinal conditions at an early stage and provide better assessment of treatment efficacy. PMID:27019970

  17. Theory of adaptive adjustment

    Weihong Huang

    2000-01-01

    Full Text Available Conventional adaptive expectation as a mechanism of stabilizing an unstable economic process is reexamined through a generalization to an adaptive adjustment framework. The generic structures of equilibria that can be stabilized through an adaptive adjustment mechanism are identified. The generalization can be applied to a broad class of discrete economic processes where the variables interested can be adjusted or controlled directly by economic agents such as in cobweb dynamics, Cournot games, Oligopoly markets, tatonnement price adjustment, tariff games, population control through immigration etc.

  18. Symmetry Adapted Basis Sets

    Avery, John Scales; Rettrup, Sten; Avery, James Emil

    In theoretical physics, theoretical chemistry and engineering, one often wishes to solve partial differential equations subject to a set of boundary conditions. This gives rise to eigenvalue problems of which some solutions may be very difficult to find. For example, the problem of finding...... such problems can be much reduced by making use of symmetry-adapted basis functions. The conventional method for generating symmetry-adapted basis sets is through the application of group theory, but this can be difficult. This book describes an easier method for generating symmetry-adapted basis sets...

  19. Impairment of pancreatic islet β cell function induced by intermittent high glucose through oxidative and endoplasmic reticulum stress:experiment with rat pancreatic islet β cells%高糖波动诱导氧化应激及内质网应激损伤胰岛β细胞功能

    侯志强; 李宏亮; 赵家军; 李光伟

    2008-01-01

    .04 respectively,both significantly lower than that of the control group(1.67±0.23,both P<0.05).The intracellularinsulin contents of the IHG and SHG groupswere(10.91±0.14)and(11.08±O.03)μU/μg respectively,both significantly lower than that of the control group[(12.37±0.37)μU/μg,both Pimpairment in pancreatic islet β cell functions,especially IHG,which is closely associated with the aggravation of oxidative stress and endoplasmic reticulum stress triggered by intermittent high glucose.

  20. Library Automation Design for Visually Impaired People

    Yurtay, Nilufer; Bicil, Yucel; Celebi, Sait; Cit, Guluzar; Dural, Deniz

    2011-01-01

    Speech synthesis is a technology used in many different areas in computer science. This technology can bring a solution to reading activity of visually impaired people due to its text to speech conversion. Based on this problem, in this study, a system is designed needed for a visually impaired person to make use of all the library facilities in…

  1. Resources for Visually Impaired or Blind Students.

    Hart, Elizabeth

    2000-01-01

    Suggests resources for school librarians who need materials for visually impaired or blind students. Highlights include the National Library Service for the Blind and Physically Handicapped; Louis Database of Accessible Materials for People Who Are Blind or Visually Impaired; Braille books; large print books, audio books; assistive technology; and…

  2. Pegasus Project for the Hearing-Impaired.

    Krahe, Jane M.

    The Pegasus Project offered nine gifted hearing impaired students (11-15 years old) a summer enrichment experience with hearing peers. Courses included computer programming, literature, fine arts, physical and biological sciences, math enrichment, and sign language. All hearing impaired students also attended a special class on issues for the…

  3. Behaviour Problems in Children with Language Impairment

    van Daal, John; Verhoeven, Ludo; van Balkom, Hans

    2007-01-01

    Background: Language impairment is often associated with behaviour problems. However, detailed relations between different types of language impairment and specific behaviour problems in children have yet to be demonstrated. The present study attempted to do just this with an eye to the implications to identify foci for early intervention.…

  4. Signs and Symptoms of the Impaired Counselor.

    Emerson, Shirley; Markos, Patricia A.

    1996-01-01

    Although the problem of impaired professionals has been with us for as long as professionals have been so designated, this article considers potential harm to clients and the profession's obligation to monitor its members and provide appropriate rehabilitation. Definitions of distress and professional impairment are discussed, as are the…

  5. Cognitive impairment in COPD: a systematic review

    Irene Torres-Sánchez

    2015-04-01

    Full Text Available The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.

  6. Endocrine Risk Factors for Cognitive Impairment.

    Moon, Jae Hoon

    2016-06-01

    Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment has expanded from epidemiology to molecular pathogenesis and therapeutic management. This review focuses on the epidemiological evidence for the association between cognitive impairment and several endocrine risk factors, including insulin resistance, dyslipidemia, thyroid dysfunction, vitamin D deficiency, and subclinical atherosclerosis. Researches suggesting possible mechanisms for this association are reviewed. The research investigating modifiable endocrine risk factors for cognitive impairment provides clues for understanding the pathogenesis of cognitive impairment and developing novel treatment modalities. However, so far, interventional studies investigating the beneficial effect of the "modification" of these "modifiable risk factors" on cognitive impairment have reported variable results. Therefore, well-designed, randomized prospective interventional studies are needed. PMID:27118278

  7. Depressive Symptoms and Impaired Respiration in Sleep.

    Bliwise, Donald L.; And Others

    1986-01-01

    Associations between depression and impaired respiration in sleep are frequently noted clinically. This relationship was documented psychometrically with the Geriatric Depression Scale, a self-report measure of nonsomatic depressive symptoms. Mean values and effect size suggest that impaired respiration in sleep was associated with only relatively…

  8. Impaired gap detection in juvenile microgyric rats.

    Peiffer, Ann M; Friedman, Jennifer T; Rosen, Glenn D; Fitch, R Holly

    2004-09-17

    Previous research with adult animal models links the presence of cortical neuromigrational anomalies (i.e., microgyria similar to that found in brains of dyslexics) with rapid auditory processing (RAP) impairments. RAP impairments are in turn found in children with specific language impairment (SLI) and also in individuals with dyslexia. Gap detection, a simple measure of auditory temporal acuity, appears to be impaired in children with SLI but not in dyslexic adults, even though both groups exhibit impaired processing on more complex, rapid auditory tasks. In the current study, juvenile rats with bilateral microgyria, but not their adult counterparts, exhibited impaired detection of short duration silent gaps in white noise when compared to age-matched sham littermates. Results lend further support to: (1) an association between neuromigrational anomalies and RAP impairments; and (2) the validity of an animal model of RAP impairments associated with language disturbances in humans. Current results also support the view that auditory processing disturbances associated with cortical malformations may be evident early in development at a relatively "low" level (e.g., simple gap detection), but may require "higher-order" auditory discrimination tasks (e.g., tone sequences, phonemic discriminations) to be elicited later in life. PMID:15351496

  9. Mild Cognitive Impairment Status and Mobility Performance

    Pedersen, Mette; Holt, Nicole E; Grande, Laura;

    2014-01-01

    : An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (a...

  10. Survivable Impairment-Aware Traffic Grooming

    Beshir, A.; Nuijts, R.; Malhotra, R.; Kuipers, F.

    2011-01-01

    Traffic grooming allows efficient utilization of network capacity by aggregating several independent traffic streams into a wavelength. In addition, survivability and impairment-awareness (i.e., taking into account the effect of physical impairments) are two important issues that have gained a lot o

  11. Feasibility of the adaptive and automatic presentation of tasks (ADAPT system for rehabilitation of upper extremity function post-stroke

    Choi Younggeun

    2011-08-01

    Full Text Available Abstract Background Current guidelines for rehabilitation of arm and hand function after stroke recommend that motor training focus on realistic tasks that require reaching and manipulation and engage the patient intensively, actively, and adaptively. Here, we investigated the feasibility of a novel robotic task-practice system, ADAPT, designed in accordance with such guidelines. At each trial, ADAPT selects a functional task according to a training schedule and with difficulty based on previous performance. Once the task is selected, the robot picks up and presents the corresponding tool, simulates the dynamics of the tasks, and the patient interacts with the tool to perform the task. Methods Five participants with chronic stroke with mild to moderate impairments (> 9 months post-stroke; Fugl-Meyer arm score 49.2 ± 5.6 practiced four functional tasks (selected out of six in a pre-test with ADAPT for about one and half hour and 144 trials in a pseudo-random schedule of 3-trial blocks per task. Results No adverse events occurred and ADAPT successfully presented the six functional tasks without human intervention for a total of 900 trials. Qualitative analysis of trajectories showed that ADAPT simulated the desired task dynamics adequately, and participants reported good, although not excellent, task fidelity. During training, the adaptive difficulty algorithm progressively increased task difficulty leading towards an optimal challenge point based on performance; difficulty was then continuously adjusted to keep performance around the challenge point. Furthermore, the time to complete all trained tasks decreased significantly from pretest to one-hour post-test. Finally, post-training questionnaires demonstrated positive patient acceptance of ADAPT. Conclusions ADAPT successfully provided adaptive progressive training for multiple functional tasks based on participant's performance. Our encouraging results establish the feasibility of ADAPT; its

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

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

  13. Cognitive impairment and mortality among nonagenarians

    Andersen, Kjeld; Nybo, Hanne; Gaist, David;

    2002-01-01

    regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence......Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined the...... impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox...

  14. Impaired Leydig cell function in infertile men

    Andersson, A-M; Jørgensen, N; Frydelund-Larsen, L; Rajpert-De Meyts, E; Skakkebaek, N E

    2004-01-01

    To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio, and...... fertile levels.Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous...... epithelium and the Leydig cells, triggered by distorted function of the seminiferous epithelium. On the other hand, the parallel impairment of spermatogenesis and Leydig cells may reflect a congenital dysfunction of both compartments caused by a testicular dysgenesis during fetal/infant development....

  15. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

  16. Asimovian Adaptive Agents

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  17. Limits to adaptation

    Dow, Kirstin; Berkhout, Frans; Preston, Benjamin L.; Klein, Richard J. T.; Midgley, Guy; Shaw, M. Rebecca

    2013-04-01

    An actor-centered, risk-based approach to defining limits to social adaptation provides a useful analytic framing for identifying and anticipating these limits and informing debates over society's responses to climate change.

  18. The genomics of adaptation.

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation. PMID:23097510

  19. Adaptive shared control system

    Sanders, David

    2009-01-01

    A control system to aid mobility is presented that is intended to assist living independently and that provides physical guidance. The system has two levels: a human machine interface and an adaptive shared controller.

  20. Adaptations, exaptations, and spandrels.

    Buss, D M; Haselton, M G; Shackelford, T K; Bleske, A L; Wakefield, J C

    1998-05-01

    Adaptation and natural selection are central concepts in the emerging science of evolutionary psychology. Natural selection is the only known causal process capable of producing complex functional organic mechanisms. These adaptations, along with their incidental by-products and a residue of noise, comprise all forms of life. Recently, S. J. Gould (1991) proposed that exaptations and spandrels may be more important than adaptations for evolutionary psychology. These refer to features that did not originally arise for their current use but rather were co-opted for new purposes. He suggested that many important phenomena--such as art, language, commerce, and war--although evolutionary in origin, are incidental spandrels of the large human brain. The authors outline the conceptual and evidentiary standards that apply to adaptations, exaptations, and spandrels and discuss the relative utility of these concepts for psychological science. PMID:9612136

  1. Adapt or Die

    Brody, Joshua Eric; Larsen, Kasper Green

    2015-01-01

    In this paper, we study the role non-adaptivity plays in maintaining dynamic data structures. Roughly speaking, a data structure is non-adaptive if the memory locations it reads and/or writes when processing a query or update depend only on the query or update and not on the contents of previously...... read cells. We study such non-adaptive data structures in the cell probe model. This model is one of the least restrictive lower bound models and in particular, cell probe lower bounds apply to data structures developed in the popular word-RAM model. Unfortunately, this generality comes at a high cost......: the highest lower bound proved for any data structure problem is only polylogarithmic. Our main result is to demonstrate that one can in fact obtain polynomial cell probe lower bounds for non-adaptive data structures. To shed more light on the seemingly inherent polylogarithmic lower bound barrier, we...

  2. Adaptive Space Structures

    Wada, B.

    1993-01-01

    The term adaptive structures refers to a structural control approach in which sensors, actuators, electronics, materials, structures, structural concepts, and system-performance-validation strategies are integrated to achieve specific objectives.

  3. Adaptive Spectral Doppler Estimation

    Gran, Fredrik; Jakobsson, Andreas; Jensen, Jørgen Arendt

    2009-01-01

    In this paper, 2 adaptive spectral estimation techniques are analyzed for spectral Doppler ultrasound. The purpose is to minimize the observation window needed to estimate the spectrogram to provide a better temporal resolution and gain more flexibility when designing the data acquisition sequence....... The methods can also provide better quality of the estimated power spectral density (PSD) of the blood signal. Adaptive spectral estimation techniques are known to pro- vide good spectral resolution and contrast even when the ob- servation window is very short. The 2 adaptive techniques are tested and...... compared with the averaged periodogram (Welch’s method). The blood power spectral capon (BPC) method is based on a standard minimum variance technique adapted to account for both averaging over slow-time and depth. The blood amplitude and phase estimation technique (BAPES) is based on finding a set of...

  4. Adaptive multiresolution methods

    Schneider Kai

    2011-12-01

    Full Text Available These lecture notes present adaptive multiresolution schemes for evolutionary PDEs in Cartesian geometries. The discretization schemes are based either on finite volume or finite difference schemes. The concept of multiresolution analyses, including Harten’s approach for point and cell averages, is described in some detail. Then the sparse point representation method is discussed. Different strategies for adaptive time-stepping, like local scale dependent time stepping and time step control, are presented. Numerous numerical examples in one, two and three space dimensions validate the adaptive schemes and illustrate the accuracy and the gain in computational efficiency in terms of CPU time and memory requirements. Another aspect, modeling of turbulent flows using multiresolution decompositions, the so-called Coherent Vortex Simulation approach is also described and examples are given for computations of three-dimensional weakly compressible mixing layers. Most of the material concerning applications to PDEs is assembled and adapted from previous publications [27, 31, 32, 34, 67, 69].

  5. Adaptive Heat Engine

    Allahverdyan, A. E.; Babajanyan, S. G.; Martirosyan, N. H.; Melkikh, A. V.

    2016-07-01

    A major limitation of many heat engines is that their functioning demands on-line control and/or an external fitting between the environmental parameters (e.g., temperatures of thermal baths) and internal parameters of the engine. We study a model for an adaptive heat engine, where—due to feedback from the functional part—the engine's structure adapts to given thermal baths. Hence, no on-line control and no external fitting are needed. The engine can employ unknown resources; it can also adapt to results of its own functioning that make the bath temperatures closer. We determine resources of adaptation and relate them to the prior information available about the environment.

  6. Adaptive Architectural Envelope

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or...... two different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up...

  7. Statistical Physics of Adaptation

    Perunov, Nikolai; England, Jeremy

    2014-01-01

    All living things exhibit adaptations that enable them to survive and reproduce in the natural environment that they inhabit. From a biological standpoint, it has long been understood that adaptation comes from natural selection, whereby maladapted individuals do not pass their traits effectively to future generations. However, we may also consider the phenomenon of adaptation from the standpoint of physics, and ask whether it is possible to delineate what the difference is in terms of physical properties between something that is well-adapted to its surrounding environment, and something that is not. In this work, we undertake to address this question from a theoretical standpoint. Building on past fundamental results in far-from-equilibrium statistical mechanics, we demonstrate a generalization of the Helmholtz free energy for the finite-time stochastic evolution of driven Newtonian matter. By analyzing this expression term by term, we are able to argue for a general tendency in driven many-particle systems...

  8. Adaptive trial designs.

    Lai, Tze Leung; Lavori, Philip William; Shih, Mei-Chiung

    2012-01-01

    We review adaptive designs for clinical trials, giving special attention to the control of the Type I error in late-phase confirmatory trials, when the trial planner wishes to adjust the final sample size of the study in response to an unblinded analysis of interim estimates of treatment effects. We point out that there is considerable inefficiency in using the adaptive designs that employ conditional power calculations to reestimate the sample size and that maintain the Type I error by using certain weighted test statistics. Although these adaptive designs have little advantage over familiar group-sequential designs, our review also describes recent developments in adaptive designs that are both flexible and efficient. We also discuss the use of Bayesian designs, when the context of use demands control over operating characteristics (Type I and II errors) and correction of the bias of estimated treatment effects. PMID:21838549

  9. Minocycline attenuates interferon-α-induced impairments in rat fear extinction

    Bi, Qiang; Shi, Lijuan; Yang, Pingting; Wang, Jianing; Qin, Ling

    2016-01-01

    Background Extinction of conditioned fear is an important brain function for animals to adapt to a new environment. Accumulating evidence suggests that innate immune cytokines are involved in the pathology of psychotic disorders. However, the involvement of cytokines in fear dysregulation remains less investigated. In the present study, we investigated how interferon (IFN)-α disrupts the extinction of conditioned fear and propose an approach to rescue IFN-α-induced neurologic impairment. Meth...

  10. EMPLOYABILITY SKILLS OF TECHNICAL AND VOCATIONAL STUDENTS WITH HEARING IMPAIREMENTS: EMPLOYERS’ PERSPECTIVES

    Fazlinda Ab Halim; Ab. Rahim Bakar; Ramlah Hamzah; Abdullah Mat Rashid

    2013-01-01

    This study aims to explore the employers’ requirement for employability skills of the technical and vocational students who are hearing impaired. The research instrument used was adapted from the Secretary's Commission on Achieving Necessary Skills (SCANS) which consists of thirty nine items. The employability skills surveyed include basic skills, thinking skills, personal qualities, sourcing skills, information skills, interpersonal skills, system skills and technology skills. The instrument...

  11. Exercise training reverses aging-induced impairment of myogenic constriction in skeletal muscle arterioles

    Ghosh, Payal; Mora Solis, Fredy R.; Dominguez, James M.; Spier, Scott A.; Donato, Anthony J.; Delp, Michael D.; Muller-Delp, Judy M.

    2015-01-01

    To investigate whether exercise training can reverse age-related impairment of myogenic vasoconstriction in skeletal muscle arterioles, young (4 mo) and old (22 mo) male Fischer 344 rats were randomly assigned to either sedentary or exercise-trained groups. The roles of the endothelium and Kv1 channels in age- and exercise training-induced adaptations of myogenic responses were assessed through evaluation of pressure-induced constriction in endothelium-intact and denuded soleus muscle arterio...

  12. Reward learning impairments in patients with first-episode schizophrenia-spectrum disorder

    Chan, Chi-wan, Tracey; 陳緻韻

    2015-01-01

    Reward learning refers to outcome-based learning that involves selecting optimal response choices from feedback which facilitate adaptive behavior. It is believed that reward learning paradigm represents a promising translational target in schizophrenia research. Previous studies generated relatively consistent evidence of rapid learning deficits but mixed findings on gradual learning deficits. Reward learning impairments were also associated with symptoms as well as antipsychotics treatment....

  13. Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

    Szczawinska-Poplonyk, Aleksandra; Breborowicz, Anna; Samara, Husam; Ossowska, Lidia; Dworacki, Grzegorz

    2015-01-01

    The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a def...

  14. Leak test adapter for containers

    Hallett, Brian H.; Hartley, Michael S.

    1996-01-01

    An adapter is provided for facilitating the charging of containers and leak testing penetration areas. The adapter comprises an adapter body and stem which are secured to the container's penetration areas. The container is then pressurized with a tracer gas. Manipulating the adapter stem installs a penetration plug allowing the adapter to be removed and the penetration to be leak tested with a mass spectrometer. Additionally, a method is provided for using the adapter.

  15. Frustratingly Easy Domain Adaptation

    Daumé, Hal

    2009-01-01

    We describe an approach to domain adaptation that is appropriate exactly in the case when one has enough ``target'' data to do slightly better than just using only ``source'' data. Our approach is incredibly simple, easy to implement as a preprocessing step (10 lines of Perl!) and outperforms state-of-the-art approaches on a range of datasets. Moreover, it is trivially extended to a multi-domain adaptation problem, where one has data from a variety of different domains.

  16. Adaptive quantum teleportation

    Modlawska, Joanna; Grudka, Andrzej

    2008-01-01

    We consider multiple teleportation in the Knill-Laflamme-Milburn (KLM) scheme. We introduce adaptive teleportation, i.e., such that the choice of entangled state used in the next teleportation depends on the results of the measurements performed during the previous teleportations. We show that adaptive teleportation enables an increase in the probability of faithful multiple teleportation in the KLM scheme. In particular if a qubit is to be teleported more than once then it is better to use n...

  17. The Adaptive Automation Design

    Calefato, Caterina; Montanari, Roberto; TESAURI, Francesco

    2008-01-01

    After considering the positive effects of adaptive automation implementation, this chapter focuses on two partly overlapping phenomena: on the one hand, the role of trust in automation is considered, particularly as to the effects of overtrust and mistrust in automation's reliability; on the other hand, long-term lack of exercise on specific operation may lead users to skill deterioration. As a future work, it will be interesting and challenging to explore the conjunction of adaptive automati...

  18. The genomics of adaptation

    Radwan, Jacek; Babik, Wiesław

    2012-01-01

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far ...

  19. Facilitation of CRISPR adaptation

    Abedon, Stephen T.

    2011-01-01

    CRISPR systems, as bacterial defenses against phages, logically must display in their functioning a sequence of at least three major steps. These, in order of occurrence, are “facilitation,” adaptation and interference, where the facilitation step is the main issue considered in this commentary. Interference is the blocking of phage infections as mediated in part by CRISPR spacer sequences. Adaptation, at least as narrowly defined, is the acquisition of these spacer sequences by CRISPR loci. ...

  20. Robust Adaptive Control

    Narendra, K. S.; Annaswamy, A. M.

    1985-01-01

    Several concepts and results in robust adaptive control are are discussed and is organized in three parts. The first part surveys existing algorithms. Different formulations of the problem and theoretical solutions that have been suggested are reviewed here. The second part contains new results related to the role of persistent excitation in robust adaptive systems and the use of hybrid control to improve robustness. In the third part promising new areas for future research are suggested which combine different approaches currently known.

  1. Climate Adaptation in Europe

    At the Conference of Parties in Copenhagen, Denmark, December 7-18, 2009 Change Magazine will present a special issue on 'Climate Adaptation in Europe'. The magazine contains articles on climate policy strategies in European countries and cross-border studies on climate change, articles on climate adaptation in the Alps, on water quality as a bottleneck for the agricultural sector, and drought in the mediterranean countries. How will member countries in the European Union tackle the climate crisis?.

  2. Network and adaptive sampling

    Chaudhuri, Arijit

    2014-01-01

    Combining the two statistical techniques of network sampling and adaptive sampling, this book illustrates the advantages of using them in tandem to effectively capture sparsely located elements in unknown pockets. It shows how network sampling is a reliable guide in capturing inaccessible entities through linked auxiliaries. The text also explores how adaptive sampling is strengthened in information content through subsidiary sampling with devices to mitigate unmanageable expanding sample sizes. Empirical data illustrates the applicability of both methods.

  3. Opportunistic Adaptation Knowledge Discovery

    Badra, Fadi; Cordier, Amélie; Lieber, Jean

    2009-01-01

    The original publication is available at www.springerlink.com International audience Adaptation has long been considered as the Achilles' heel of case-based reasoning since it requires some domain-specific knowledge that is difficult to acquire. In this paper, two strategies are combined in order to reduce the knowledge engineering cost induced by the adaptation knowledge (CA) acquisition task: CA is learned from the case base by the means of knowledge discovery techniques, and the CA a...

  4. Adapting the SLIM diabetes prevention intervention to a Dutch real-life setting: joint decision making by science and practice

    2013-01-01

    Background Although many evidence-based diabetes prevention interventions exist, they are not easily applicable in real-life settings. Moreover, there is a lack of examples which describe the adaptation process of these interventions to practice. In this paper we present an example of such an adaptation. We adapted the SLIM (Study on Lifestyle intervention and Impaired glucose tolerance Maastricht) diabetes prevention intervention to a Dutch real-life setting, in a joint decision making proce...

  5. Adapting the SLIM diabetes prevention intervention to a Dutch real-life setting: joint decision making by science and practice

    Jansen, S.C.; Haveman-Nies, A.; Duijzer, G.; Beek, ter, J.; Hiddink, G.; Feskens, E.J.M.

    2013-01-01

    Background - Although many evidence-based diabetes prevention interventions exist, they are not easily applicable in real-life settings. Moreover, there is a lack of examples which describe the adaptation process of these interventions to practice. In this paper we present an example of such an adaptation. We adapted the SLIM (Study on Lifestyle intervention and Impaired glucose tolerance Maastricht) diabetes prevention intervention to a Dutch real-life setting, in a joint decision making pro...

  6. Learning to Adapt. Organisational Adaptation to Climate Change Impacts

    Analysis of human adaptation to climate change should be based on realistic models of adaptive behaviour at the level of organisations and individuals. The paper sets out a framework for analysing adaptation to the direct and indirect impacts of climate change in business organisations with new evidence presented from empirical research into adaptation in nine case-study companies. It argues that adaptation to climate change has many similarities with processes of organisational learning. The paper suggests that business organisations face a number of obstacles in learning how to adapt to climate change impacts, especially in relation to the weakness and ambiguity of signals about climate change and the uncertainty about benefits flowing from adaptation measures. Organisations rarely adapt 'autonomously', since their adaptive behaviour is influenced by policy and market conditions, and draws on resources external to the organisation. The paper identifies four adaptation strategies that pattern organisational adaptive behaviour

  7. Peculiarities psychological and educational work on the adaptation of children the senior preschool age with serious speech defects to the conditions groups the compensating preschool of combined type

    Buchilova Irina

    2013-06-01

    Full Text Available This article discusses the features of adaptation senior preschool age children severe speech impairment to the conditions of the compensation groups preschool of combined type. The directions, methods, form of psychological and pedagogical work on its optimization

  8. Adaptation and perceptual norms

    Webster, Michael A.; Yasuda, Maiko; Haber, Sara; Leonard, Deanne; Ballardini, Nicole

    2007-02-01

    We used adaptation to examine the relationship between perceptual norms--the stimuli observers describe as psychologically neutral, and response norms--the stimulus levels that leave visual sensitivity in a neutral or balanced state. Adapting to stimuli on opposite sides of a neutral point (e.g. redder or greener than white) biases appearance in opposite ways. Thus the adapting stimulus can be titrated to find the unique adapting level that does not bias appearance. We compared these response norms to subjectively defined neutral points both within the same observer (at different retinal eccentricities) and between observers. These comparisons were made for visual judgments of color, image focus, and human faces, stimuli that are very different and may depend on very different levels of processing, yet which share the property that for each there is a well defined and perceptually salient norm. In each case the adaptation aftereffects were consistent with an underlying sensitivity basis for the perceptual norm. Specifically, response norms were similar to and thus covaried with the perceptual norm, and under common adaptation differences between subjectively defined norms were reduced. These results are consistent with models of norm-based codes and suggest that these codes underlie an important link between visual coding and visual experience.

  9. Social, occupational and cultural adaptation in Antarctica

    Nicolas, Michel; Bishop, Sheryl; Weiss, Karine; Gaudino, Marvin

    2016-07-01

    Life in isolated and confined environments (ICEs, e.g., polar stations, submarine or space missions), is subject to important constraints which can generate psychosociological impaired outcomes. This study investigated psychological, social, occupational and cultural variables which are among the most important determinants in adaptation to a one-year wintering in Antarctica with 13 international participants. Our findings confirm and give further insight into the role of social (Cohesiveness, Social Support) and occupational (Implementation / Preparedness, Counterproductive Activity, Decision Latitude and Psychological Job Demands) dimensions of adaptation to ICE environments. Relationships between various social and occupational dimensions studies reflected detrimental effects ranging from decrements in cohesiveness, social support and work performance which differed across professional status and multicultural factors. These psychosocial issues have important implications for pre-mission selection and training, monitoring and support of crews during the mission and post-mission readaptation. Operational recommendations are suggested to improve adaptation, success and well-being for long-term ICE missions, e.g., to Mars and beyond.

  10. A methoxydiphenidine-impaired driver.

    Stachel, Nicole; Jacobsen-Bauer, Andrea; Skopp, Gisela

    2016-03-01

    Methoxydiphenidine (MXP) was first reported in 1989 as a dissociative anesthetic but did not enter the market for pharmaceuticals. The substance re-appeared in 2013 as a new psychoactive substance. A case of driving under the influence of MXP is reported. The concentration of MXP has been determined from a serum sample (57 ng/mL) by liquid chromatography tandem mass spectrometry following liquid-liquid extraction. In addition, amphetamine, methylenedioxymethamphetamine, and its major metabolite were present in concentrations of 111, 28, and 3 ng/mL, respectively. The subject presented with amnesia, out-of-body experiences, bizarre behavior, and decreased motor abilities. At present, information on human toxicity of MXP is not available. MXP is comparable in structure as well as in action at the N-methyl-D-aspartate (NMDA) receptor to phencyclidine or ketamine. Therefore, it is likely that MXP exerts similar severe psychotropic action in man. However, there is no information on the duration and intensity of MXP's impairing effects, the interpretation of a particular concentration in the blood or serum, and its detectability in routine drug screenings. Confirmation analysis may be confined to cases where the police has specific intelligence that points to MXP use. PMID:26482953

  11. Coping with cognitive impairment and dementia: Rural caregivers' perspectives.

    Branger, Camille; Burton, Rachel; O'Connell, Megan E; Stewart, Norma; Morgan, Debra

    2016-07-01

    Caregiving in a rural context is unique, but the experience of rural caregivers is understudied. This paper describes how rural caregivers cope with caring for a loved one diagnosed with mild cognitive impairment or dementia using qualitative description to generate a low-inference summary of a response to an open-ended question. This approach allowed these rural caregivers to describe their positive experiences in addition to the more commonly explored caregiver experiences related to stress. Analyses of coping revealed use of social support, engaging in relaxing and physical activity, and cognitive reframing. In addition, caregivers reported strong faith and religiosity, and to a lesser frequency behavioral changes, checking in with the person with dementia via telephone, and joint activity. Predominantly, these methods reflect approach-based strategies. The current data suggest that these caregivers manage well and adopt adaptive coping strategies to meet the demands of the caregiving role. PMID:24951255

  12. On Adaptive vs. Non-adaptive Security of Multiparty Protocols

    Canetti, Ran; Damgård, Ivan Bjerre; Dziembowski, Stefan; Ishai, Yuval; Malkin, Tal

    course of the computation. We study the relations between adaptive security (i.e., security in the adaptive setting) and non-adaptive security, according to two definitions and in several models of computation. While affirming some prevailing beliefs, we also obtain some unexpected results. Some...... definition of Canetti, for honest-but-curious adversaries, adaptive security is equivalent to non-adaptive security when the number of parties is logarithmic, and is strictly stronger than non-adaptive security when the number of parties is super-logarithmic. For Byzantine adversaries, adaptive security is...

  13. Is Hearing Impairment Associated with Rheumatoid Arthritis?

    Emamifar, Amir; Bjoerndal, Kristine; Jensen Hansen, Inger Marie

    2016-01-01

    BACKGROUND: Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects 1% of the population. The auditory system may be involved during the course of disease; however the association of RA and hearing impairment has not been clearly defined. OBJECTIVE: The objective of this review......, hearing test, audiometry, auditory dysfunction and rheumatoid arthritis. CONCLUSION: Based on our review it can be postulated that patients with RA are at higher risk of hearing impairment compared to healthy subjects in their course of the disease. The hearing impairment in RA seems to be a...

  14. Goα regulates olfactory adaptation by antagonizing Gqα-DAG signaling in Caenorhabditis elegans

    Matsuki, Masahiro; Kunitomo, Hirofumi; Iino, Yuichi

    2006-01-01

    The heterotrimeric G protein Go is abundantly expressed in the mammalian nervous system and modulates neural activities in response to various ligands. However, Go's functions in living animals are less well understood. Here, we demonstrate that GOA-1 Goα has a fundamental role in olfactory adaptation in Caenorhabditis elegans. Impairment of GOA-1 Goα function and excessive activation of EGL-30 Gqα cause a defect in adaptation to AWC-sensed odorants. These pathways antagonistically modulate o...

  15. Reduced short term adaptation to robot generated dynamic environment in children affected by Cerebral Palsy

    Di Rosa Giuseppe; Morasso Pietro; Frascarelli Flaminia; Masia Lorenzo; Petrarca Maurizio; Castelli Enrico; Cappa Paolo

    2011-01-01

    Abstract Background It is known that healthy adults can quickly adapt to a novel dynamic environment, generated by a robotic manipulandum as a structured disturbing force field. We suggest that it may be of clinical interest to evaluate to which extent this kind of motor learning capability is impaired in children affected by cerebal palsy. Methods We adapted the protocol already used with adults, which employs a velocity dependant viscous field, and compared the performance of a group of sub...

  16. Measurement of the functional impact of adaptive seating technology in children with cerebral palsy

    Ryan, S.E.

    2009-01-01

    Many young children with cerebral palsy have motor impairments that affect their ability to sit and do activities unsupported. They often rely on special adaptive seating devices for postural control and stability. Healthcare practitioners generally accept that these products improve functioning in children with cerebral palsy. However, little empirical proof exists. The objective of this thesis is to propose a theoretical foundation to ground adaptive seating outcomes research and provide ev...

  17. Solar Adaptive Optics

    Thomas R. Rimmele

    2011-06-01

    Full Text Available Adaptive optics (AO has become an indispensable tool at ground-based solar telescopes. AO enables the ground-based observer to overcome the adverse effects of atmospheric seeing and obtain diffraction limited observations. Over the last decade adaptive optics systems have been deployed at major ground-based solar telescopes and revitalized ground-based solar astronomy. The relatively small aperture of solar telescopes and the bright source make solar AO possible for visible wavelengths where the majority of solar observations are still performed. Solar AO systems enable diffraction limited observations of the Sun for a significant fraction of the available observing time at ground-based solar telescopes, which often have a larger aperture than equivalent space based observatories, such as HINODE. New ground breaking scientific results have been achieved with solar adaptive optics and this trend continues. New large aperture telescopes are currently being deployed or are under construction. With the aid of solar AO these telescopes will obtain observations of the highly structured and dynamic solar atmosphere with unprecedented resolution. This paper reviews solar adaptive optics techniques and summarizes the recent progress in the field of solar adaptive optics. An outlook to future solar AO developments, including a discussion of Multi-Conjugate AO (MCAO and Ground-Layer AO (GLAO will be given.

  18. Adaptation and risk management

    Preston, Benjamin L [ORNL

    2011-01-01

    Adaptation assessment methods are compatible with the international risk management standard ISO:31000. Risk management approaches are increasingly being recommended for adaptation assessments at both national and local levels. Two orientations to assessments can commonly be identified: top-down and bottom-up, and prescriptive and diagnostic. Combinations of these orientations favor different types of assessments. The choice of orientation can be related to uncertainties in prediction and taking action, in the type of adaptation and in the degree of system stress. Adopting multiple viewpoints is to be encouraged, especially in complex situations. The bulk of current guidance material is consistent with top-down and predictive approaches, thus is most suitable for risk scoping and identification. Abroad range ofmaterial fromwithin and beyond the climate change literature can be used to select methods to be used in assessing and implementing adaptation. The framing of risk, correct formulation of the questions being investigated and assessment methodology are critical aspects of the scoping phase. Only when these issues have been addressed should be issue of specific methods and tools be addressed. The reorientation of adaptation from an assessment focused solely on anthropogenic climate change to broader issues of vulnerability/resilience, sustainable development and disaster risk, especially through a risk management framework, can draw from existing policy and management understanding in communities, professions and agencies, incorporating existing agendas, knowledge, risks, and issues they already face.

  19. Decoupled Adapt-then-Combine diffusion networks with adaptive combiners

    Fernandez-Bes, Jesus; Arenas-García, Jerónimo; Silva, Magno T. M.; Azpicueta-Ruiz, Luis A.

    2015-01-01

    In this paper we analyze a novel diffusion strategy for adaptive networks called Decoupled Adapt-then-Combine, which keeps a fully local estimate of the solution for the adaptation step. Our strategy, which is specially convenient for heterogeneous networks, is compared with the standard Adapt-then-Combine scheme and theoretically analyzed using energy conservation arguments. Such comparison shows the need of implementing adaptive combiners for both schemes to obtain a good performance in cas...

  20. Evaluation of non-verbal cognitive function in infants with severe hearing impairment

    Shuyu Wang; Xiaoming Li; Li Zhao; Jianhong Li; Yuxia Pan

    2008-01-01

    BACKGROUND: The relationship between hearing impairment and verbal developmental deficits in infants has become a hotspot in research, focusing on improving hearing and promoting verbal development. However, language is only one element of cognition. There are other elements of non-verbal cognitive deficits in infants with hearing impairment.OBJECTIVE: This study was designed to compare the differences in gross motor, fine motor, adaptability, and behavioral development between infants with severe hearing impairment and ordinary children of the same age. DESIGN: Case-control observation.SETTING: Department of Otolaryngology-Head Surgery, Bethune International Peace Hospital.PARTICIPANTS: Fifty-two infants with hearing impairment, who received treatment in the Department of Otolaryngology-Head Surgery, Bethune International Peace Hospital from February to December 2007, were confirmed to suffer from severe (or extremely severe) sensorineural deafness by auditory brain-stem response (ABR) and were recruited for this study. The infants comprised 30 males and 22 females. Among them, 18 were aged 0-1 year, 18 were aged 1-2 years, and 16 were aged 2-3 years. An additional 60 individuals, aged 0-3 years, who received developmental monitoring simultaneously, and were confirmed to have normal hearing and verbal ability, were included as controls. Among the control subjects, there were 31 males and 29 females: 20 were 0.05). The behavioral developmental quotient was significantly less in hearing-impaired infants compared to control infants, who were between 1 and 2 years of age (P < 0.05). The development quotients of fine motor and behavioral development were significantly less in hearing-impaired infants than in control infants, who were 2-3 years of age (P < 0.05).CONCLUSION: Compared to control infants, severe hearing-impaired infants have a lower behavioral developmental quotient after 1 year and a lower fine motor developmental quotient after 2 years of age.