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  1. Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Weina Cui

    Full Text Available Duchenne muscular dystrophy (DMD is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS approach to measure myocardial bioenergetics in the heart in vivo.Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05.Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.

  2. Targeting the Prodromal Stage of Alzheimer’s Disease: Bioenergetic and Mitochondrial Opportunities

    OpenAIRE

    Caldwell, Charles C.; Yao, Jia; Brinton, Roberta Diaz

    2014-01-01

    Alzheimer’s disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechan...

  3. Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic deficits and inflammatory changes in CCI-induced neuropathy.

    Science.gov (United States)

    Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

    2017-02-01

    Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in combination for 14 days to examine sciatic functional index, allodynia and hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate tests respectively. Malondialdehyde, nitrite and glutathione levels were estimated to detect oxidative/nitrosative stress; mitochondrial membrane potential and cytochrome c oxidase activity to assess mitochondrial function; NAD & ATP levels to examine the bioenergetic status and levels of inflammatory markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone improved the pain behaviour and biochemical alterations but the combination therapy demonstrated an appreciable reversal of CCI-induced changes. Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and nuclear factor erythroid 2-related factor (Nrf-2) levels were increased significantly in micro-sections of the sciatic nerve and dorsal root ganglion (DRG) of treatment group. These results suggest that simultaneous inhibition of oxidative stress-PARP activation cascade may potentially be useful strategies for management of trauma induced neuropathic pain.

  4. Targeting the prodromal stage of Alzheimer's disease: bioenergetic and mitochondrial opportunities.

    Science.gov (United States)

    Caldwell, Charles C; Yao, Jia; Brinton, Roberta Diaz

    2015-01-01

    Alzheimer's disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechanisms of action for current mitochondrial and bioenergetic therapeutics for AD broadly fall into the following categories: 1) glucose metabolism and substrate supply; 2) mitochondrial enhancers to potentiate energy production; 3) antioxidants to scavenge reactive oxygen species and reduce oxidative damage; 4) candidates that target apoptotic and mitophagy pathways to either remove damaged mitochondria or prevent neuronal death. Thus far, mitochondrial therapeutic strategies have shown promise at the preclinical stage but have had little-to-no success in clinical trials. Lessons learned from preclinical and clinical therapeutic studies are discussed. Understanding the bioenergetic adaptations that occur during aging and AD led us to focus on a systems biology approach that targets the bioenergetic system rather than a single component of this system. Bioenergetic system-level therapeutics personalized to bioenergetic phenotype would target bioenergetic deficits across the prodromal and clinical stages to prevent and delay progression of AD.

  5. Static and Dynamic Cognitive Deficits in Childhood Preceding Adult Schizophrenia: A 30-Year Study

    Science.gov (United States)

    Reichenberg, Abraham; Caspi, Avshalom; Harrington, HonaLee; Houts, Renate; Keefe, Richard S.E.; Murray, Robin M.; Poulton, Richie; Moffitt, Terrie E.

    2013-01-01

    Objective Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders? Methods Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects. Results Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression. Conclusions These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7–13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older. PMID:20048021

  6. Auditory efferent feedback system deficits precede age-related hearing loss: contralateral suppression of otoacoustic emissions in mice.

    Science.gov (United States)

    Zhu, Xiaoxia; Vasilyeva, Olga N; Kim, Sunghee; Jacobson, Michael; Romney, Joshua; Waterman, Marjorie S; Tuttle, David; Frisina, Robert D

    2007-08-10

    The C57BL/6J mouse has been a useful model of presbycusis, as it displays an accelerated age-related peripheral hearing loss. The medial olivocochlear efferent feedback (MOC) system plays a role in suppressing cochlear outer hair cell (OHC) responses, particularly for background noise. Neurons of the MOC system are located in the superior olivary complex, particularly in the dorsomedial periolivary nucleus (DMPO) and in the ventral nucleus of the trapezoid body (VNTB). We previously discovered that the function of the MOC system declines with age prior to OHC degeneration, as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAEs) in humans and CBA mice. The present study aimed to determine the time course of age changes in MOC function in C57s. DPOAE amplitudes and CS of DPOAEs were collected for C57s from 6 to 40 weeks of age. MOC responses were observed at 6 weeks but were gone at middle (15-30 kHz) and high (30-45 kHz) frequencies by 8 weeks. Quantitative stereological analyses of Nissl sections revealed smaller neurons in the DMPO and VNTB of young adult C57s compared with CBAs. These findings suggest that reduced neuron size may underlie part of the noteworthy rapid decline of the C57 efferent system. In conclusion, the C57 mouse has MOC function at 6 weeks, but it declines quickly, preceding the progression of peripheral age-related sensitivity deficits and hearing loss in this mouse strain.

  7. Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines

    OpenAIRE

    Silva, Diana F.; Selfridge, J. Eva; Lu, Jianghua; E, Lezi; Roy, Nairita; Hutfles, Lewis; Burns, Jeffrey M.; Michaelis, Elias K.; Yan, Shidu; Cardoso, Sandra M.; Swerdlow, Russell H.

    2013-01-01

    Bioenergetic dysfunction occurs in Alzheimer's disease (AD) and mild cognitive impairment (MCI), a clinical syndrome that frequently precedes symptomatic AD. In this study, we modeled AD and MCI bioenergetic dysfunction by transferring mitochondria from MCI, AD and control subject platelets to mtDNA-depleted SH-SY5Y cells. Bioenergetic fluxes and bioenergetics-related infrastructures were characterized in the resulting cytoplasmic hybrid (cybrid) cell lines. Relative to control cybrids, AD an...

  8. Bioenergetics in ecosystems

    Science.gov (United States)

    Madenjian, Charles P.; Farrell, Anthony P.

    2011-01-01

    A bioenergetics model for a fish can be defined as a quantitative description of the fish’s energy budget. Bioenergetics modeling can be applied to a fish population in a lake, river, or ocean to estimate the annual consumption of food by the fish population; such applications have proved to be useful in managing fisheries. In addition, bioenergetics models have been used to better understand fish growth and consumption in ecosystems, to determine the importance of the role of fish in cycling nutrients within ecosystems, and to identify the important factors regulating contaminant accumulation in fish from lakes, rivers, and oceans.

  9. Deficit

    CERN Multimedia

    2002-01-01

    UCL's former provost, Sir Derek Roberts, has been drafted in for a year to run the college. UCL is expected to have a 6 million pounds deficit this year and up to a 10 million pounds deficit next year. Sir Christopher Llewellyn-Smith took over at UCL nearly 4 years ago and decided then that the finanical situation was serious enough to warrant a reduction in the vast expansion policy undertaken by his predecessor (1 page).

  10. Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

    Science.gov (United States)

    Fong, Sheng; Teo, Emelyne; Ng, Li Fang; Chen, Ce-Belle; Lakshmanan, Lakshmi Narayanan; Tsoi, Sau Yee; Moore, Philip Keith; Inoue, Takao; Halliwell, Barry; Gruber, Jan

    2016-09-22

    Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1-42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1-42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.

  11. Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model

    Science.gov (United States)

    Fong, Sheng; Teo, Emelyne; Ng, Li Fang; Chen, Ce-Belle; Lakshmanan, Lakshmi Narayanan; Tsoi, Sau Yee; Moore, Philip Keith; Inoue, Takao; Halliwell, Barry; Gruber, Jan

    2016-01-01

    Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1–42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1–42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances. PMID:27653553

  12. Principles of Bioenergetics

    CERN Document Server

    Skulachev, Vladimir P; Kasparinsky, Felix O

    2013-01-01

    Principles of Bioenergetics summarizes one of the quickly growing branches of modern biochemistry. Bioenergetics concerns energy transductions occurring in living systems and this book pays special attention to molecular mechanisms of these processes. The main subject of the book is the "energy coupling membrane" which refers to inner membranes of intracellular organelles, for example, mitochondria and chloroplasts. Cellular cytoplasmic membranes where respiratory and photosynthetic energy transducers, as well as ion-transporting ATP-synthases (ATPases) are also part of this membrane. Significant attention is paid to the alternative function of mitochondria as generators of reactive oxygen species (ROS) that mediate programmed death of cells (apoptosis and necrosis) and organisms (phenoptosis). The latter process is considered as a key mechanism of aging which may be suppressed by mitochondria-targeted antioxidants.

  13. Overview of mitochondrial bioenergetics.

    Science.gov (United States)

    Madeira, Vitor M C

    2012-01-01

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

  14. Taurine, glutathione and bioenergetics

    DEFF Research Database (Denmark)

    Hansen, Svend Høime; Grunnet, Niels

    2013-01-01

    Biochemistry textbook presentations of bioenergetics and mitochondrial function normally focus on the chemiosmotic theory with introduction of the tricarboxylic acid cycle and the electron transport chain, the proton and electrical gradients and subsequent oxidative phosphorylation and ATP...... to be independent of the matrix pH. Finally a simplified model for mitochondrial oxidation is presented with introduction of GSH as redox buffer to stabilise the electrical gradient, and taurine as pH buffer stabilising the pH gradient, but simultaneously establishing the equilibrium between the NADH/NAD(+) redox...

  15. Modeling of Mitochondria Bioenergetics Using a Composable Chemiosmotic Energy Transduction Rate Law: Theory and Experimental Validation

    OpenAIRE

    Ivan Chang; Margit Heiske; Thierry Letellier; Douglas Wallace; Pierre Baldi

    2011-01-01

    Mitochondrial bioenergetic processes are central to the production of cellular energy, and a decrease in the expression or activity of enzyme complexes responsible for these processes can result in energetic deficit that correlates with many metabolic diseases and aging. Unfortunately, existing computational models of mitochondrial bioenergetics either lack relevant kinetic descriptions of the enzyme complexes, or incorporate mechanisms too specific to a particular mitochondrial system and ar...

  16. Heat shock protein 70 is necessary to improve mitochondrial bioenergetics and reverse diabetic sensory neuropathy following KU-32 therapy.

    Science.gov (United States)

    Ma, Jiacheng; Farmer, Kevin L; Pan, Pan; Urban, Michael J; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2014-02-01

    Impaired neuronal mitochondrial bioenergetics contributes to the pathophysiologic progression of diabetic peripheral neuropathy (DPN) and may be a focal point for disease management. We have demonstrated that modulating heat shock protein (Hsp) 90 and Hsp70 with the small-molecule drug KU-32 ameliorates psychosensory, electrophysiologic, morphologic, and bioenergetic deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of type 1 and type 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. The onset of DPN showed a tight temporal correlation with a decrease in mitochondrial bioenergetics in a genetic model of type 2 diabetes. In contrast, sensory hypoalgesia developed 10 weeks before the occurrence of significant declines in sensory neuron mitochondrial bioenergetics in the type 1 model. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70, since the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes, but not type 1 diabetes, and that modulating Hsp70 offers an effective approach toward correcting sensory neuron bioenergetic deficits and DPN in both type 1 and type 2 diabetes.

  17. Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines.

    Science.gov (United States)

    Silva, Diana F; Selfridge, J Eva; Lu, Jianghua; E, Lezi; Roy, Nairita; Hutfles, Lewis; Burns, Jeffrey M; Michaelis, Elias K; Yan, ShiDu; Cardoso, Sandra M; Swerdlow, Russell H

    2013-10-01

    Bioenergetic dysfunction occurs in Alzheimer's disease (AD) and mild cognitive impairment (MCI), a clinical syndrome that frequently precedes symptomatic AD. In this study, we modeled AD and MCI bioenergetic dysfunction by transferring mitochondria from MCI, AD and control subject platelets to mtDNA-depleted SH-SY5Y cells. Bioenergetic fluxes and bioenergetics-related infrastructures were characterized in the resulting cytoplasmic hybrid (cybrid) cell lines. Relative to control cybrids, AD and MCI cybrids showed changes in oxygen consumption, respiratory coupling and glucose utilization. AD and MCI cybrids had higher ADP/ATP and lower NAD+/NADH ratios. AD and MCI cybrids exhibited differences in proteins that monitor, respond to or regulate cell bioenergetic fluxes including HIF1α, PGC1α, SIRT1, AMPK, p38 MAPK and mTOR. Several endpoints suggested mitochondrial mass increased in the AD cybrid group and probably to a lesser extent in the MCI cybrid group, and that the mitochondrial fission-fusion balance shifted towards increased fission in the AD and MCI cybrids. As many of the changes we observed in AD and MCI cybrid models are also seen in AD subject brains, we conclude reduced bioenergetic function is present during very early AD, is not brain-limited and induces protean retrograde responses that likely have both adaptive and mal-adaptive consequences.

  18. No consistent bioenergetic defects in presynaptic nerve terminals isolated from mouse models of Alzheimer’s disease

    OpenAIRE

    Choi, Sung W.; Gerencser, Akos A.; Ng, Ryan; Flynn, James M.; Melov, Simon; Danielson, Steven R.; Gibson, Bradford W.; Nicholls, David G.; Bredesen, Dale E; Brand, Martin D.

    2012-01-01

    Depressed cortical energy supply and impaired synaptic function are predominant associations of Alzheimer’s disease (AD). To test the hypothesis that presynaptic bioenergetic deficits are associated with the progression of AD pathogenesis, we compared bioenergetic variables of cortical and hippocampal presynaptic nerve terminals (synaptosomes) from commonly used mouse models with AD-like phenotypes (J20 age 6 months, Tg2576 age 16 months and APP/PS age 9 and 14 months) to ag...

  19. Bioenergetics of Continental Serpentinites

    Science.gov (United States)

    Cardace, D.; Meyer-Dombard, D. R.

    2011-12-01

    methanogenesis. We find that there is strong energetic yield from most reactions considered, except for transformation of nitrite to nitrate, ammonia to nitrite, ferrous to ferric iron, and carbon dioxide to methane. Laying out foundational metabolic models for microbiological communities sustained by chemosynthesis in this setting (mining energy from ultramafic rocks and chemical systems, not tied to photosynthesis in any way) has enticing relevance to the search for extraterrestrial life, in that similar rocks have been detected on our sibling planet Mars, with transient atmospheric detection of hydrogen and methane (Schulte et al., 2006, Mumma et al., 2009). To a first order, this work explores the intersection of serpentinite groundwater chemistry and bioenergetics to determine what kinds of life can be sustained in these significant subsurface settings. References cited: Kelley et al. 2005. Science 307:1428-1434. McCollom and Bach. 2009. GCA 73:856-875. Mumma et al., 2009. Science 323:1041-1045. Schulte et al., 2006. Astrobiology 6:364-376.

  20. No consistent bioenergetic defects in presynaptic nerve terminals isolated from mouse models of Alzheimer's disease.

    Science.gov (United States)

    Choi, Sung W; Gerencser, Akos A; Ng, Ryan; Flynn, James M; Melov, Simon; Danielson, Steven R; Gibson, Bradford W; Nicholls, David G; Bredesen, Dale E; Brand, Martin D

    2012-11-21

    Depressed cortical energy supply and impaired synaptic function are predominant associations of Alzheimer's disease (AD). To test the hypothesis that presynaptic bioenergetic deficits are associated with the progression of AD pathogenesis, we compared bioenergetic variables of cortical and hippocampal presynaptic nerve terminals (synaptosomes) from commonly used mouse models with AD-like phenotypes (J20 age 6 months, Tg2576 age 16 months, and APP/PS age 9 and 14 months) to age-matched controls. No consistent bioenergetic deficiencies were detected in synaptosomes from the three models; only APP/PS cortical synaptosomes from 14-month-old mice showed an increase in respiration associated with proton leak. J20 mice were chosen for a highly stringent investigation of mitochondrial function and content. There were no significant differences in the quality of the synaptosomal preparations or the mitochondrial volume fraction. Furthermore, respiratory variables, calcium handling, and membrane potentials of synaptosomes from symptomatic J20 mice under calcium-imposed stress were not consistently impaired. The recovery of marker proteins during synaptosome preparation was the same, ruling out the possibility that the lack of functional bioenergetic defects in synaptosomes from J20 mice was due to the selective loss of damaged synaptosomes during sample preparation. Our results support the conclusion that the intrinsic bioenergetic capacities of presynaptic nerve terminals are maintained in these symptomatic AD mouse models.

  1. Novel model of neuronal bioenergetics

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Obel, Linea Lykke Frimodt; Walls, Anne B;

    2012-01-01

    -methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial...... is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based...... on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays...

  2. Bioenergetics of Mammalian Sperm Capacitation

    Directory of Open Access Journals (Sweden)

    Alessandra Ferramosca

    2014-01-01

    Full Text Available After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  3. Mitochondrial morphology-emerging role in bioenergetics.

    Science.gov (United States)

    Galloway, Chad A; Lee, Hakjoo; Yoon, Yisang

    2012-12-15

    Dynamic change in mitochondrial shape is a cellular process mediated mainly by fission and fusion of mitochondria. Studies have shown that mitochondrial fission and fusion are directly and indirectly associated with mitochondrial maintenance, bioenergetic demand, and cell death. Changes in mitochondrial morphology are frequently observed in response to changes in the surrounding cellular milieu, such as metabolic flux, that influence cellular bioenergetics. Connections between morphological regulation and the bioenergetic status of mitochondria are emerging as reciprocally responsive processes, though the nature of the signaling remains to be defined. Given the pivotal role mitochondria play in cellular fate, tight regulation of fission and fusion is therefore critical to preserving normal cellular physiology. Here we describe recent advancements in the understanding of the mechanisms governing mitochondrial morphology and their emerging role in mitochondrial bioenergetics.

  4. Bioenergetics modeling of percid fishes: Chapter 14

    Science.gov (United States)

    Madenjian, Charles P.; Kestemont, Patrick; Dabrowski, Konrad; Summerfelt, Robert C.

    2015-01-01

    A bioenergetics model for a percid fish represents a quantitative description of the fish’s energy budget. Bioenergetics modeling can be used to identify the important factors determining growth of percids in lakes, rivers, or seas. For example, bioenergetics modeling applied to yellow perch (Perca flavescens) in the western and central basins of Lake Erie revealed that the slower growth in the western basin was attributable to limitations in suitably sized prey in western Lake Erie, rather than differences in water temperature between the two basins. Bioenergetics modeling can also be applied to a percid population to estimate the amount of food being annually consumed by the percid population. For example, bioenergetics modeling applied to the walleye (Sander vitreus) population in Lake Erie has provided fishery managers valuable insights into changes in the population’s predatory demand over time. In addition, bioenergetics modeling has been used to quantify the effect of the difference in growth between the sexes on contaminant accumulation in walleye. Field and laboratory evaluations of percid bioenergetics model performance have documented a systematic bias, such that the models overestimate consumption at low feeding rates but underestimate consumption at high feeding rates. However, more recent studies have shown that this systematic bias was due, at least in part, to an error in the energy budget balancing algorithm used in the computer software. Future research work is needed to more thoroughly assess the field and laboratory performance of percid bioenergetics models and to quantify differences in activity and standard metabolic rate between the sexes of mature percids.

  5. Modeling mitochondrial bioenergetics with integrated volume dynamics.

    Directory of Open Access Journals (Sweden)

    Jason N Bazil

    2010-01-01

    Full Text Available Mathematical models of mitochondrial bioenergetics provide powerful analytical tools to help interpret experimental data and facilitate experimental design for elucidating the supporting biochemical and physical processes. As a next step towards constructing a complete physiologically faithful mitochondrial bioenergetics model, a mathematical model was developed targeting the cardiac mitochondrial bioenergetic based upon previous efforts, and corroborated using both transient and steady state data. The model consists of several modified rate functions of mitochondrial bioenergetics, integrated calcium dynamics and a detailed description of the K(+-cycle and its effect on mitochondrial bioenergetics and matrix volume regulation. Model simulations were used to fit 42 adjustable parameters to four independent experimental data sets consisting of 32 data curves. During the model development, a certain network topology had to be in place and some assumptions about uncertain or unobserved experimental factors and conditions were explicitly constrained in order to faithfully reproduce all the data sets. These realizations are discussed, and their necessity helps contribute to the collective understanding of the mitochondrial bioenergetics.

  6. Modeling mitochondrial bioenergetics with integrated volume dynamics.

    Science.gov (United States)

    Bazil, Jason N; Buzzard, Gregery T; Rundell, Ann E

    2010-01-01

    Mathematical models of mitochondrial bioenergetics provide powerful analytical tools to help interpret experimental data and facilitate experimental design for elucidating the supporting biochemical and physical processes. As a next step towards constructing a complete physiologically faithful mitochondrial bioenergetics model, a mathematical model was developed targeting the cardiac mitochondrial bioenergetic based upon previous efforts, and corroborated using both transient and steady state data. The model consists of several modified rate functions of mitochondrial bioenergetics, integrated calcium dynamics and a detailed description of the K(+)-cycle and its effect on mitochondrial bioenergetics and matrix volume regulation. Model simulations were used to fit 42 adjustable parameters to four independent experimental data sets consisting of 32 data curves. During the model development, a certain network topology had to be in place and some assumptions about uncertain or unobserved experimental factors and conditions were explicitly constrained in order to faithfully reproduce all the data sets. These realizations are discussed, and their necessity helps contribute to the collective understanding of the mitochondrial bioenergetics.

  7. Optical Flashes Preceding GRBs

    CERN Document Server

    Paczynski, B

    2001-01-01

    Only one optical flash associated with a gamma-ray burst has been detected so far by ROTSE. There are also upper limits obtained by several groups for several bursts. Recent model calculations indicate a possibility that optical flash may precede the GRB. Such flashes are undetectable in the currently popular observing mode, with optical instruments responding to GRB triggers. There is a need to develop all sky optical monitoring system capable of recognizing flashes in real time, and more powerful instruments that could respond robotically to optical triggers and carry out follow up observations.

  8. Estrogen regulation of mitochondrial bioenergetics: implications for prevention of Alzheimer's disease.

    Science.gov (United States)

    Yao, Jia; Brinton, Roberta Diaz

    2012-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised aerobic glycolysis pathway coupled with oxidative stress is first accompanied by a shift toward a ketogenic pathway that eventually progresses into fatty acid oxidation (FAO) pathways and leads to white matter degeneration and overproduction and mitochondrial accumulation of β-amyloid. Estrogen-induced signaling pathways converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis coupled with citric acid cycle-driven oxidative phosphorylation to potentiate ATP (Adenosine triphosphate) generation. In addition to potentiated mitochondrial bioenergetics, estrogen also enhances neural survival and health through maintenance of calcium homeostasis, promotion of antioxidant defense against free radicals, efficient cholesterol trafficking, and beta amyloid clearance. Significantly, the convergence of E2 mechanisms of action onto mitochondria is also a potential point of vulnerability when activated in diseased neurons that exacerbates degeneration through increased load on dysregulated calcium homeostasis. The "healthy cell bias of estrogen action" hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. As the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy.

  9. Evolutionary primacy of sodium bioenergetics

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2008-04-01

    Full Text Available Abstract Background The F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F-type (found in most bacteria and eukaryotic mitochondria and chloroplasts and V-type (found in archaea, some bacteria, and eukaryotic vacuoles ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments. Results We combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree. Conclusion Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton-permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton-tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions. Reviewers This article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section.

  10. Evaluation of a lake whitefish bioenergetics model

    Science.gov (United States)

    Madenjian, Charles P.; O'Connor, Daniel V.; Pothoven, Steven A.; Schneeberger, Philip J.; Rediske, Richard R.; O'Keefe, James P.; Bergstedt, Roger A.; Argyle, Ray L.; Brandt, Stephen B.

    2006-01-01

    We evaluated the Wisconsin bioenergetics model for lake whitefish Coregonus clupeaformis in the laboratory and in the field. For the laboratory evaluation, lake whitefish were fed rainbow smelt Osmerus mordax in four laboratory tanks during a 133-d experiment. Based on a comparison of bioenergetics model predictions of lake whitefish food consumption and growth with observed consumption and growth, we concluded that the bioenergetics model furnished significantly biased estimates of both food consumption and growth. On average, the model overestimated consumption by 61% and underestimated growth by 16%. The source of the bias was probably an overestimation of the respiration rate. We therefore adjusted the respiration component of the bioenergetics model to obtain a good fit of the model to the observed consumption and growth in our laboratory tanks. Based on the adjusted model, predictions of food consumption over the 133-d period fell within 5% of observed consumption in three of the four tanks and within 9% of observed consumption in the remaining tank. We used polychlorinated biphenyls (PCBs) as a tracer to evaluate model performance in the field. Based on our laboratory experiment, the efficiency with which lake whitefish retained PCBs from their food (I?) was estimated at 0.45. We applied the bioenergetics model to Lake Michigan lake whitefish and then used PCB determinations of both lake whitefish and their prey from Lake Michigan to estimate p in the field. Application of the original model to Lake Michigan lake whitefish yielded a field estimate of 0.28, implying that the original formulation of the model overestimated consumption in Lake Michigan by 61%. Application of the bioenergetics model with the adjusted respiration component resulted in a field I? estimate of 0.56, implying that this revised model underestimated consumption by 20%.

  11. Modulating Molecular Chaperones Improves Mitochondrial Bioenergetics and Decreases the Inflammatory Transcriptome in Diabetic Sensory Neurons.

    Science.gov (United States)

    Ma, Jiacheng; Pan, Pan; Anyika, Mercy; Blagg, Brian S J; Dobrowsky, Rick T

    2015-09-16

    We have previously demonstrated that modulating molecular chaperones with KU-32, a novobiocin derivative, ameliorates physiologic and bioenergetic deficits of diabetic peripheral neuropathy (DPN). Replacing the coumarin core of KU-32 with a meta-fluorinated biphenyl ring system created KU-596, a novobiocin analogue (novologue) that showed neuroprotective activity in a cell-based assay. The current study sought to determine whether KU-596 offers similar therapeutic potential for treating DPN. Administration of 2-20 mg/kg of KU-596 improved diabetes induced hypoalgesia and sensory neuron bioenergetic deficits in a dose-dependent manner. However, the drug could not improve these neuropathic deficits in diabetic heat shock protein 70 knockout (Hsp70 KO) mice. To gain further insight into the mechanisms by which KU-596 improved DPN, we performed transcriptomic analysis of sensory neuron RNA obtained from diabetic wild-type and Hsp70 KO mice using RNA sequencing. Bioinformatic analysis of the differentially expressed genes indicated that diabetes strongly increased inflammatory pathways and that KU-596 therapy effectively reversed these increases independent of Hsp70. In contrast, the effects of KU-596 on decreasing the expression of genes regulating the production of reactive oxygen species were more Hsp70-dependent. These data indicate that modulation of molecular chaperones by novologue therapy offers an effective approach toward correcting nerve dysfunction in DPN but that normalization of inflammatory pathways alone by novologue therapy seems to be insufficient to reverse sensory deficits associated with insensate DPN.

  12. Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease.

    Science.gov (United States)

    Martino Adami, Pamela V; Quijano, Celia; Magnani, Natalia; Galeano, Pablo; Evelson, Pablo; Cassina, Adriana; Do Carmo, Sonia; Leal, María C; Castaño, Eduardo M; Cuello, A Claudio; Morelli, Laura

    2017-01-01

    Synaptic bioenergetic deficiencies may be associated with early Alzheimer's disease (AD). To explore this concept, we assessed pre-synaptic mitochondrial function in hemizygous (+/-)TgMcGill-R-Thy1-APP rats. The low burden of Aβ and the wide array of behavioral and cognitive impairments described in 6-month-old hemizygous TgMcGill-R-Thy1-APP rats (Tg(+/-)) support their use to investigate synaptic bioenergetics deficiencies described in subjects with early Alzheimer's disease (AD). In this report, we show that pre-synaptic mitochondria from Tg(+/-) rats evidence a decreased respiratory control ratio and spare respiratory capacity associated with deficits in complex I enzymatic activity. Cognitive impairments were prevented and bioenergetic deficits partially reversed when Tg(+/-) rats were fed a nutritionally complete diet from weaning to 6-month-old supplemented with pyrroloquinoline quinone, a mitochondrial biogenesis stimulator with antioxidant and neuroprotective effects. These results provide evidence that, as described in AD brain and not proven in Tg mice models with AD-like phenotype, the mitochondrial bioenergetic capacity of synaptosomes is not conserved in the Tg(+/-) rats. This animal model may be suitable for understanding the basic biochemical mechanisms involved in early AD.

  13. Bioenergetics molecular biology, biochemistry, and pathology

    CERN Document Server

    Ozawa, Takayuki

    1990-01-01

    The emergence of the Biochemical Sciences is underlined by the FAOB symposium in Seoul and highlighted by this Satellite meeting on the "New Bioenergetics. " Classical mitochondrial electron transfer and energy coupling is now complemented by the emerging molecular biology of the respiratory chain which is studied hand in hand with the recognition of mitochondrial disease as a major and emerging study in the basic and clinical medical sciences. Thus, this symposium has achieved an important balance of the fundamental and applied aspects of bioenergetics in the modern setting of molecular biology and mitochondrial disease. At the same time, the symposium takes note not only of the emerging excellence of Biochemical Studies in the Orient and indeed in Korea itself, but also retrospectively enjoys the history of electron transport and energy conservation as represented by the triumvirate ofYagi, King and Slater. Many thanks are due Drs. Kim and Ozawa for their elegant organization of this meeting and its juxtapo...

  14. Evaluation of a Mysis bioenergetics model

    Science.gov (United States)

    Chipps, S.R.; Bennett, D.H.

    2002-01-01

    Direct approaches for estimating the feeding rate of the opossum shrimp Mysis relicta can be hampered by variable gut residence time (evacuation rate models) and non-linear functional responses (clearance rate models). Bioenergetics modeling provides an alternative method, but the reliability of this approach needs to be evaluated using independent measures of growth and food consumption. In this study, we measured growth and food consumption for M. relicta and compared experimental results with those predicted from a Mysis bioenergetics model. For Mysis reared at 10??C, model predictions were not significantly different from observed values. Moreover, decomposition of mean square error indicated that 70% of the variation between model predictions and observed values was attributable to random error. On average, model predictions were within 12% of observed values. A sensitivity analysis revealed that Mysis respiration and prey energy density were the most sensitive parameters affecting model output. By accounting for uncertainty (95% CLs) in Mysis respiration, we observed a significant improvement in the accuracy of model output (within 5% of observed values), illustrating the importance of sensitive input parameters for model performance. These findings help corroborate the Mysis bioenergetics model and demonstrate the usefulness of this approach for estimating Mysis feeding rate.

  15. Myocardial bioenergetic abnormalities in experimental uremia

    Directory of Open Access Journals (Sweden)

    Chesser AMS

    2016-05-01

    Full Text Available Alistair MS Chesser,1 Steven M Harwood,2 Martin J Raftery,1 Muhammad M Yaqoob1,2 1Department of Nephrology, Barts Health NHS Trust, Royal London Hospital, 2Translational Medicine and Therapeutics, William Harvey Research Institute, John Vane Science Centre, Queen Mary University of London, London, UK Purpose: Cardiac bioenergetics are known to be abnormal in experimental uremia as exemplified by a reduced phosphocreatine (PCr/adenosine triphosphate (ATP ratio. However, the progression of these bioenergetic changes during the development of uremia still requires further study and was therefore investigated at baseline, 4 weeks and 8 weeks after partial nephrectomy (PNx. Methods: A two-stage PNx uremia model in male Wistar rats was used to explore in vivo cardiac and skeletal muscles' bioenergetic changes over time. High-energy phosphate nucleotides were determined by phosphorus-31 nuclear magnetic resonance (31P-NMR and capillary zone electrophoresis. Results: 31P-NMR spectroscopy revealed lower PCr/ATP ratios in PNx hearts compared to sham (SH-operated animals 4 weeks after PNx (median values given ± SD, 0.64±0.16 PNx, 1.13±0.31 SH, P<0.02. However, 8 weeks after PNx, the same ratio was more comparable between the two groups (0.84±0.15 PNx, 1.04±0.44 SH, P= not significant, suggestive of an adaptive mechanism. When 8-week hearts were prestressed with dobutamine, the PCr/ATP ratio was again lower in the PNx group (1.08±0.36 PNx, 1.55±0.38 SH, P<0.02, indicating a reduced energy reserve during the progression of uremic heart disease. 31P-NMR data were confirmed by capillary zone electrophoresis, and the changes in myocardial bioenergetics were replicated in the skeletal muscle. Conclusion: This study provides evidence of the changes that occur in myocardial energetics in experimental uremia and highlights how skeletal muscle bioenergetics mirror those found in the cardiac tissue and so might potentially serve as a practical surrogate tissue

  16. Addenda to the Preceding Paper

    Science.gov (United States)

    Bhatnagar, Rajat; Finn, Robert

    2016-12-01

    This work contains largely afterthoughts, relating to the paper immediately preceding it. We correlate and interpret our contributions in that paper, relative to those of an earlier publication by Aspley, He and McCuan. We propose specific laboratory experiments, suggested by formal predictions of those two papers.

  17. Development of a bioenergetics model for age-0 American Shad

    Science.gov (United States)

    Sauter, Sally T.

    2011-01-01

    Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur. Bioenergetics modeling is particularly useful when research questions involve multiple species and trophic levels (e.g. plankton communities). Bioenergetics models are mass-balance equations where the energy acquired from food is partitioned between maintenance costs, waste products, and growth (Winberg 1956). Specifically, the Wisconsin bioenergetics model (Hanson et al. 1997) is widely used in fisheries science. Researchers have extensively tested, reviewed, and improved on this modeling approach for over 30 years (Petersen et al. 2008). Development of a bioenergetics model for any species requires three key components: 1) determine physiological parameters for the model through laboratory experiments or incorporate data from a closely related species, 2) corroboration of the model with growth and consumption estimates from independent research, and 3) error analysis of model parameters. Wisconsin bioenergetics models have been parameterized for many of the salmonids and

  18. Reevaluation of a walleye (Sander vitreus) bioenergetics model

    Science.gov (United States)

    Madenjian, Charles P.; Wang, Chunfang

    2013-01-01

    Walleye (Sander vitreus) is an important sport fish throughout much of North America, and walleye populations support valuable commercial fisheries in certain lakes as well. Using a corrected algorithm for balancing the energy budget, we reevaluated the performance of the Wisconsin bioenergetics model for walleye in the laboratory. Walleyes were fed rainbow smelt (Osmerus mordax) in four laboratory tanks each day during a 126-day experiment. Feeding rates ranged from 1.4 to 1.7 % of walleye body weight per day. Based on a statistical comparison of bioenergetics model predictions of monthly consumption with observed monthly consumption, we concluded that the bioenergetics model estimated food consumption by walleye without any significant bias. Similarly, based on a statistical comparison of bioenergetics model predictions of weight at the end of the monthly test period with observed weight, we concluded that the bioenergetics model predicted walleye growth without any detectable bias. In addition, the bioenergetics model predictions of cumulative consumption over the 126-day experiment differed fromobserved cumulative consumption by less than 10 %. Although additional laboratory and field testing will be needed to fully evaluate model performance, based on our laboratory results, the Wisconsin bioenergetics model for walleye appears to be providing unbiased predictions of food consumption.

  19. PRECEDENCE AS A PSYCHOLINGUISTIC CATEGORY

    Directory of Open Access Journals (Sweden)

    Panarina Nadezhda Sergeevna

    2015-06-01

    Full Text Available The use of particular linguistic units by representatives of a linguacultural community as the most preferable verbal actions is not necessary to be a case of verbal operations with some culturally specific knowledge. The analysis of a psychosocial mechanism used for generation and verbalization of such a knowledge allows to define the nature of precedence as a characteristic of meaning that is being effected in a speech act. The development of precedent meaning indispensably assumes not only generation of the definition component, but also entry into a structure of a culturological component meaning. The culturological component reflects a relationship between a subject-concept component of the meaning and the other elements of a speech situation – the relationship, which is notional for a person. Importance of the relationship consists in fact that definition of its content represents to a person their social identity. Until a person understands the content of relationship, which is represented by the culturological component, the use of corresponding linguistic units to nominate new objects of reality is a supraliminal appeal to the precedent knowledge, a speech act. But for new acts of usage the main thing is definitely quality of relationship as a characteristic of the cultural group stability, and the linguistic unit usage derives a new function. When the culturological component of the meaning is not included into generalization, since it is irrelevant one, and the core of meaning is composed of new and more relevant for the usage features, you can no more realize the inner form of the precedent meaning. The outer form is still relevant, since it is kept in mind by the representatives of linguaculture as the one which is preferable for usage. In this case the linguistic unit is just a tool not related to verbal representation of socially significant attitude, and its usage is a speech operation, a way to perform different speech acts

  20. Development of a bioenergetics model for age-0 American Shad

    Science.gov (United States)

    Sauter, Sally T.

    2011-01-01

    Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur.

  1. Real Time Measurement of Host Bioenergetics During Mycobacterium Tuberculosis Infection

    Science.gov (United States)

    2014-09-01

    metabolic flux analysis and demonstrated that MtbΔwhiB3, unlike wt Mtb and the complemented strain, was unable to re-establish bioenergetic...To determine the influence of WhiB3 on mycobacterial bioenergetics, metabolic flux of wt Mtb, MtbΔwhiB3 and the complemented strain was examined by...of glycolysis) using a XF96 Extracellular Flux Analyzer (Seahorse Biosciences, MA, USA) (Figure 10E, 10G). After basal metabolic flux was measured

  2. A full lifecycle bioenergetic model for bluefin tuna.

    OpenAIRE

    Marko Jusup; Tin Klanjscek; Hiroyuki Matsuda; Kooijman, S.A.L.M.

    2011-01-01

    We formulated a full lifecycle bioenergetic model for bluefin tuna relying on the principles of Dynamic Energy Budget theory. Traditional bioenergetic models in fish research deduce energy input and utilization from observed growth and reproduction. In contrast, our model predicts growth and reproduction from food availability and temperature in the environment. We calibrated the model to emulate physiological characteristics of Pacific bluefin tuna (Thunnus orientalis, hereafter PBT), a spec...

  3. Weak Precedence Story Parsing Grammar

    Institute of Scientific and Technical Information of China (English)

    张松懋

    1995-01-01

    Story understanding is one of the important branches of natural language understanding research in AI techniques.The story understanding approach based on Story Parsing Grammar (SPG) involves that SPG is used to represent different abstracting processes of stories with different levels in story understanding and that the story understanding process is converted to the recognition process of stories using the syntactic parser of SPG.This kind of story understanding is called story parsing.In this paper,firstly a subclass of SPG,called Weak Precedence SPG(WPSPG),is defined.Afterwards the syntactic parsing algorithm of WPSPG is studied.An example of story parsing is also given.

  4. Reevaluation of lake trout and lake whitefish bioenergetics models

    Science.gov (United States)

    Madenjian, Charles P.; Pothoven, Steve A.; Kao, Yu-Chun

    2013-01-01

    Using a corrected algorithm for balancing the energy budget, we reevaluated the Wisconsin bioenergetics model for lake trout (Salvelinus namaycush) in the laboratory and for lake whitefish (Coregonus clupeaformis) in the laboratory and in the field. For lake trout, results showed that the bioenergetics model slightly overestimated food consumption by the lake trout when they were fed low and intermediate rations, whereas the model predicted food consumption by lake trout fed ad libitum without any detectable bias. The slight bias in model predictions for lake trout on restricted rations may have been an artifact of the feeding schedule for these fish, and we would therefore recommend application of the Wisconsin lake trout bioenergetics model to lake trout populations in the field without any revisions to the model. Use of the Wisconsin bioenergetics model for coregonids resulted in overestimation of food consumption by lake whitefish both in the laboratory and in the field by between 20 and 30%, on average. This overestimation of food consumption was most likely due to overestimation of respiration rate. We therefore adjusted the respiration component of the bioenergetics model to obtain a good fit to the observed consumption in our laboratory tanks. The adjusted model predicted the consumption in the laboratory and the field without any detectable bias. Until a detailed lake whitefish respiration study can be conducted, we recommend application of our adjusted version of the Wisconsin generalized coregonid bioenergetics model to lake whitefish populations in the field.

  5. NMR methodologies for studying mitochondrial bioenergetics.

    Science.gov (United States)

    Alves, Tiago C; Jarak, Ivana; Carvalho, Rui A

    2012-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is a technique with an increasing importance in the study of metabolic diseases. Its initial important role in the determination of chemical structures (1, 2) has been considerably overcome by its potential for the in vivo study of metabolism (3-5). The main characteristic that makes this technique so attractive is its noninvasiveness. Only nuclei capable of transitioning between energy states, in the presence of an intense and constant magnetic field, are studied. This includes abundant nuclei such as proton ((1)H) and phosphorous ((31)P), as well as stable isotopes such as deuterium ((2)H) and carbon 13 ((13)C). This allows a wide range of applications that vary from the determination of water distribution in tissues (as obtained in a magnetic resonance imaging scan) to the calculation of metabolic fluxes under ex vivo and in vivo conditions without the need to use radioactive tracers or tissue biopsies (as in a magnetic resonance spectroscopy (MRS) scan). In this chapter, some technical aspects of the methodology of an NMR/MRS experiment as well as how it can be used to study mitochondrial bioenergetics are overviewed. Advantages and disadvantages of in vivo MRS versus high-resolution NMR using proton high rotation magic angle spinning (HRMAS) of tissue biopsies and tissue extracts are also discussed.

  6. Laboratory evaluation of a walleye (Sander vitreus) bioenergetics model

    Science.gov (United States)

    Madenjian, C.P.; Wang, C.; O'Brien, T. P.; Holuszko, M.J.; Ogilvie, L.M.; Stickel, R.G.

    2010-01-01

    Walleye (Sander vitreus) is an important game fish throughout much of North America. We evaluated the performance of the Wisconsin bioenergetics model for walleye in the laboratory. Walleyes were fed rainbow smelt (Osmerus mordax) in four laboratory tanks during a 126-day experiment. Based on a statistical comparison of bioenergetics model predictions of monthly consumption with the observed monthly consumption, we concluded that the bioenergetics model significantly underestimated food consumption by walleye in the laboratory. The degree of underestimation appeared to depend on the feeding rate. For the tank with the lowest feeding rate (1.4% of walleye body weight per day), the agreement between the bioenergetics model prediction of cumulative consumption over the entire 126-day experiment and the observed cumulative consumption was remarkably close, as the prediction was within 0.1% of the observed cumulative consumption. Feeding rates in the other three tanks ranged from 1.6% to 1.7% of walleye body weight per day, and bioenergetics model predictions of cumulative consumption over the 126-day experiment ranged between 11 and 15% less than the observed cumulative consumption. ?? 2008 Springer Science+Business Media B.V.

  7. Neurohormetic phytochemicals: An evolutionary-bioenergetic perspective.

    Science.gov (United States)

    Murugaiyah, Vikneswaran; Mattson, Mark P

    2015-10-01

    The impact of dietary factors on brain health and vulnerability to disease is increasingly appreciated. The results of epidemiological studies, and intervention trials in animal models suggest that diets rich in phytochemicals can enhance neuroplasticity and resistance to neurodegeneration. Here we describe how interactions of plants and animals during their co-evolution, and resulting reciprocal adaptations, have shaped the remarkable characteristics of phytochemicals and their effects on the physiology of animal cells in general, and neurons in particular. Survival advantages were conferred upon plants capable of producing noxious bitter-tasting chemicals, and on animals able to tolerate the phytochemicals and consume the plants as an energy source. The remarkably diverse array of phytochemicals present in modern fruits, vegetables spices, tea and coffee may have arisen, in part, from the acquisition of adaptive cellular stress responses and detoxification enzymes in animals that enabled them to consume plants containing potentially toxic chemicals. Interestingly, some of the same adaptive stress response mechanisms that protect neurons against noxious phytochemicals are also activated by dietary energy restriction and vigorous physical exertion, two environmental challenges that shaped brain evolution. In this perspective article, we describe some of the signaling pathways relevant to cellular energy metabolism that are modulated by 'neurohormetic phytochemicals' (potentially toxic chemicals produced by plants that have beneficial effects on animals when consumed in moderate amounts). We highlight the cellular bioenergetics-related sirtuin, adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 (IGF-1) pathways. The inclusion of dietary neurohormetic phytochemicals in an overall program for brain health that also includes exercise and energy restriction may find applications in the

  8. A bioenergetic model for zebrafish Danio rerio (Hamilton)

    Science.gov (United States)

    Chizinski, C.J.; Sharma, Bibek; Pope, K.L.; Patino, R.

    2008-01-01

    A bioenergetics model was developed from observed consumption, respiration and growth rates for zebrafish Danio rerio across a range (18-32?? C) of water temperatures, and evaluated with a 50 day laboratory trial at 28?? C. No significant bias in variable estimates was found during the validation trial; namely, predicted zebrafish mass generally agreed with observed mass. ?? 2008 The Authors.

  9. Modeling of mitochondria bioenergetics using a composable chemiosmotic energy transduction rate law: theory and experimental validation.

    Directory of Open Access Journals (Sweden)

    Ivan Chang

    Full Text Available Mitochondrial bioenergetic processes are central to the production of cellular energy, and a decrease in the expression or activity of enzyme complexes responsible for these processes can result in energetic deficit that correlates with many metabolic diseases and aging. Unfortunately, existing computational models of mitochondrial bioenergetics either lack relevant kinetic descriptions of the enzyme complexes, or incorporate mechanisms too specific to a particular mitochondrial system and are thus incapable of capturing the heterogeneity associated with these complexes across different systems and system states. Here we introduce a new composable rate equation, the chemiosmotic rate law, that expresses the flux of a prototypical energy transduction complex as a function of: the saturation kinetics of the electron donor and acceptor substrates; the redox transfer potential between the complex and the substrates; and the steady-state thermodynamic force-to-flux relationship of the overall electro-chemical reaction. Modeling of bioenergetics with this rate law has several advantages: (1 it minimizes the use of arbitrary free parameters while featuring biochemically relevant parameters that can be obtained through progress curves of common enzyme kinetics protocols; (2 it is modular and can adapt to various enzyme complex arrangements for both in vivo and in vitro systems via transformation of its rate and equilibrium constants; (3 it provides a clear association between the sensitivity of the parameters of the individual complexes and the sensitivity of the system's steady-state. To validate our approach, we conduct in vitro measurements of ETC complex I, III, and IV activities using rat heart homogenates, and construct an estimation procedure for the parameter values directly from these measurements. In addition, we show the theoretical connections of our approach to the existing models, and compare the predictive accuracy of the rate law with

  10. Modeling of mitochondria bioenergetics using a composable chemiosmotic energy transduction rate law: theory and experimental validation.

    Science.gov (United States)

    Chang, Ivan; Heiske, Margit; Letellier, Thierry; Wallace, Douglas; Baldi, Pierre

    2011-01-01

    Mitochondrial bioenergetic processes are central to the production of cellular energy, and a decrease in the expression or activity of enzyme complexes responsible for these processes can result in energetic deficit that correlates with many metabolic diseases and aging. Unfortunately, existing computational models of mitochondrial bioenergetics either lack relevant kinetic descriptions of the enzyme complexes, or incorporate mechanisms too specific to a particular mitochondrial system and are thus incapable of capturing the heterogeneity associated with these complexes across different systems and system states. Here we introduce a new composable rate equation, the chemiosmotic rate law, that expresses the flux of a prototypical energy transduction complex as a function of: the saturation kinetics of the electron donor and acceptor substrates; the redox transfer potential between the complex and the substrates; and the steady-state thermodynamic force-to-flux relationship of the overall electro-chemical reaction. Modeling of bioenergetics with this rate law has several advantages: (1) it minimizes the use of arbitrary free parameters while featuring biochemically relevant parameters that can be obtained through progress curves of common enzyme kinetics protocols; (2) it is modular and can adapt to various enzyme complex arrangements for both in vivo and in vitro systems via transformation of its rate and equilibrium constants; (3) it provides a clear association between the sensitivity of the parameters of the individual complexes and the sensitivity of the system's steady-state. To validate our approach, we conduct in vitro measurements of ETC complex I, III, and IV activities using rat heart homogenates, and construct an estimation procedure for the parameter values directly from these measurements. In addition, we show the theoretical connections of our approach to the existing models, and compare the predictive accuracy of the rate law with our experimentally

  11. Comparative bioenergetics modeling of two Lake Trout morphotypes

    Science.gov (United States)

    Kepler, Megan V.; Wagner, Tyler; Sweka, John A.

    2014-01-01

    Efforts to restore Lake Trout Salvelinus namaycush in the Laurentian Great Lakes have been hampered for decades by several factors, including overfishing and invasive species (e.g., parasitism by Sea Lampreys Petromyzon marinus and reproductive deficiencies associated with consumption of Alewives Alosa pseudoharengus). Restoration efforts are complicated by the presence of multiple body forms (i.e., morphotypes) of Lake Trout that differ in habitat utilization, prey consumption, lipid storage, and spawning preferences. Bioenergetics models constitute one tool that is used to help inform management and restoration decisions; however, bioenergetic differences among morphotypes have not been evaluated. The goal of this research was to investigate bioenergetic differences between two actively stocked morphotypes: lean and humper Lake Trout. We measured consumption and respiration rates across a wide range of temperatures (4–22°C) and size-classes (5–100 g) to develop bioenergetics models for juvenile Lake Trout. Bayesian estimation was used so that uncertainty could be propagated through final growth predictions. Differences between morphotypes were minimal, but when present, the differences were temperature and weight dependent. Basal respiration did not differ between morphotypes at any temperature or size-class. When growth and consumption differed between morphotypes, the differences were not consistent across the size ranges tested. Management scenarios utilizing the temperatures presently found in the Great Lakes (e.g., predicted growth at an average temperature of 11.7°C and 14.4°C during a 30-d period) demonstrated no difference in growth between the two morphotypes. Due to a lack of consistent differences between lean and humper Lake Trout, we developed a model that combined data from both morphotypes. The combined model yielded results similar to those of the morphotype-specific models, suggesting that accounting for morphotype differences may

  12. [Bioenergetics of the myocardiocytes in infectious-allergic myocarditis].

    Science.gov (United States)

    Odinokova, V A; Smirnov, V B; Gurevich, M A

    1989-01-01

    The role of myoglobin in myocardial bio-energetics was analyzed in cases of infectious-allergic myocarditis (38 endomyocardial biopsies and 18 autopsies). Myoglobin content is found to be directly related to the severity of the disease and the degree of circulatory compensation or decompensation. In conditions of progressive muscular cell dystrophy, an abrupt drop in myoglobin, detectable around the A discs, can be seen. In hypertrophic myocardiocytes of compensated circulation, myoglobin is detected as distinctly outlined large and small granules.

  13. Using bioenergetic models to estimate environmental conditions in anchialine caves

    OpenAIRE

    Klanjšček, Tin; Cukrov, Neven; Cukrov, Marijana; Geček, Sunčana; Legović, Tarzan

    2012-01-01

    Ways of deducing information on physicochemical characteristics of anchialine caves from measurements of sedentary biota are investigated. First, photographs of Ficopomatus enigmaticus from two different anchialine caves are used to draw qualitative conclusions on water circulation patterns and organic loads of the two caves. Next, the ability of bioenergetic models to quantify average conditions in anchialine caves from information on abundance, distribution, morphological characteristcs, an...

  14. Targeting Mitochondrial Bioenergetics for Alzheimer’s Prevention and Treatment

    OpenAIRE

    Yao, Jia; Brinton, Roberta Diaz

    2011-01-01

    Alzheimer’s is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. The progressive and multifaceted degenerative phenotype of Alzheimer’s suggests that successful treatment strategies necessarily will be equally multi-faceted and disease stage specific. Traditional therapeutic strategies based on the pathological aspect of the disease have achieved succ...

  15. Bioenergetics, Trophic Ecology, and Niche Separation of Tunas.

    Science.gov (United States)

    Olson, R J; Young, J W; Ménard, F; Potier, M; Allain, V; Goñi, N; Logan, J M; Galván-Magaña, F

    Tunas are highly specialized predators that have evolved numerous adaptations for a lifestyle that requires large amounts of energy consumption. Here we review our understanding of the bioenergetics and feeding dynamics of tunas on a global scale, with an emphasis on yellowfin, bigeye, skipjack, albacore, and Atlantic bluefin tunas. Food consumption balances bioenergetics expenditures for respiration, growth (including gonad production), specific dynamic action, egestion, and excretion. Tunas feed across the micronekton and some large zooplankton. Some tunas appear to time their life history to take advantage of ephemeral aggregations of crustacean, fish, and molluscan prey. Ontogenetic and spatial diet differences are substantial, and significant interdecadal changes in prey composition have been observed. Diet shifts from larger to smaller prey taxa highlight ecosystem-wide changes in prey availability and diversity and provide implications for changing bioenergetics requirements into the future. Where tunas overlap, we show evidence of niche separation between them; resources are divided largely by differences in diet percentages and size ranges of prey taxa. The lack of long-term data limits the ability to predict impacts of climate change on tuna feeding behaviour. We note the need for systematic collection of feeding data as part of routine monitoring of these species, and we highlight the advantages of using biochemical techniques for broad-scale analyses of trophic relations. We support the continued development of ecosystem models, which all too often lack the regional-specific trophic data needed to adequately investigate climate and fishing impacts.

  16. Premutation in the Fragile X Mental Retardation 1 (FMR1 Gene Affects Maternal Zn-milk and Perinatal Brain Bioenergetics and Scaffolding

    Directory of Open Access Journals (Sweden)

    Eleonora eNapoli

    2016-04-01

    Full Text Available Fragile X premutation alleles have 55-200 CGG repeats in the 5' UTR of the FMR1 gene. Altered zinc (Zn homeostasis has been reported in fibroblasts from > 60 y old premutation carriers, in which Zn supplementation significantly restored Zn-dependent mitochondrial protein import/processing and function. Given that mitochondria play a critical role in synaptic transmission, brain function, and cognition, we tested FMRP protein expression, brain bioenergetics and expression of the Zn-dependent synaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (Shank3 in a knock-in (KI premutation mouse model with 180 CGG repeats. Mitochondrial outcomes correlated with FMRP protein expression (but not FMR1 gene expression in KI mice and human fibroblasts from carriers of the pre- and full mutation. Significant deficits in brain bioenergetics, Zn levels, and Shank3 protein expression were observed in the Zn-rich regions KI hippocampus and cerebellum at PND21, with some of these effects lasting into adulthood (PND210. A strong genotype x age interaction was observed for most of the outcomes tested in hippocampus and cerebellum, whereas in cortex, age played a major role. Given that the most significant effects were observed at the end of the lactation period, we hypothesized that KI milk might have a role at compounding the deleterious effects on the FMR1 genetic background. A higher gene expression of ZnT4 and ZnT6, Zn transporters abundant in brain and lactating mammary glands, was observed in the latter tissue of KI dams. A cross-fostering experiment allowed improving cortex bioenergetics in KI pups nursing on WT milk. Conversely, WT pups nursing on KI milk showed deficits in hippocampus and cerebellum bioenergetics. A highly significant milk type x genotype interaction was observed for all three-brain regions, being cortex the most influenced. Finally, lower milk-Zn levels were recorded in milk from lactating women carrying the premutation as

  17. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

  18. Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents.

    Science.gov (United States)

    Chowdhury, Subir Roy; Saleh, Ali; Akude, Eli; Smith, Darrell R; Morrow, Dwane; Tessler, Lori; Calcutt, Nigel A; Fernyhough, Paul

    2014-07-01

    Mitochondrial dysfunction occurs in sensory neurons and contributes to diabetic neuropathy. Ciliary neurotrophic factor (CNTF) stimulates axon regeneration in type 1 diabetic rodents and prevents deficits in axonal caliber, nerve conduction, and thermal sensation. We tested the hypothesis that CNTF enhances sensory neuron function in diabetes through JAK/STAT (Janus kinase/signal transducers and activators of transcription) signaling to normalize impaired mitochondrial bioenergetics. The effect of CNTF on gene expression and neurite outgrowth of cultured adult dorsal root ganglia (DRG) sensory neurons derived from control and streptozotocin (STZ)-induced diabetic rodents was quantified. Polarization status and bioenergetics profile of mitochondria from cultured sensory neurons were determined. CNTF treatment prevented reduced STAT3 phosphorylation (Tyr 705) in DRG of STZ-diabetic mice and also enhanced STAT3 phosphorylation in rat DRG cultures. CNTF normalized polarization status of the mitochondrial inner membrane and corrected the aberrant oligomycin-induced mitochondrial hyperpolarization in axons of diabetic neurons. The mitochondrial bioenergetics profile demonstrated that spare respiratory capacity and respiratory control ratio were significantly depressed in sensory neurons cultured from STZ-diabetic rats and were corrected by acute CNTF treatment. The positive effects of CNTF on neuronal mitochondrial function were significantly inhibited by the specific JAK inhibitor, AG490. Neurite outgrowth of sensory neurons from age-matched control and STZ-induced diabetic rats was elevated by CNTF and blocked by AG490. We propose that CNTF's ability to enhance axon regeneration and protect from fiber degeneration in diabetes is associated with its targeting of mitochondrial function and improvement of cellular bioenergetics, in part, through JAK/STAT signaling.

  19. Optimal Solutions for the Temporal Precedence Problem

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Makris, Christos; Sioutas, Spyros;

    2002-01-01

    a in the structure, while the operation precedes (a,b) returns true iff element a was inserted before element b temporally. In [11] a solution was provided to the problem with worst-case time complexity O (log log n ) per operation and O(n log log n) space, where n is the number of elements inserted. It was also...... demonstrated that the precedes operation has a lower bound of Ω (log log n ) for the Pure Pointer Machine model of computation. In this paper we present two simple solutions with linear space and worst-case constant insertion time. In addition, we describe two algorithms that can handle the precedes (a...

  20. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

    Science.gov (United States)

    Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C; Morgan, Todd E; Finch, Caleb E; Pike, Christian J; Mack, Wendy J; Cadenas, Enrique; Brinton, Roberta D

    2015-07-01

    The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's.

  1. The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

    Directory of Open Access Journals (Sweden)

    Rüediger Hilker

    Full Text Available Mutations in the PINK1 gene cause autosomal recessive familial Parkinson's disease (PD. The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous ((31P and proton ((1H 3-T magnetic resonance spectroscopic imaging (MRSI in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6 compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA positron emission tomography (PET. The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K(i values correlated positively with MI (r = 0.879, p<0.001 and inversely with β-ATP (r = -0.784, p = 0.008 and GPC concentrations (r = -0.651, p = 0.030 in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.

  2. Pathways and Bioenergetics of Anaerobic Carbon Monoxide Fermentation.

    Science.gov (United States)

    Diender, Martijn; Stams, Alfons J M; Sousa, Diana Z

    2015-01-01

    Carbon monoxide can act as a substrate for different modes of fermentative anaerobic metabolism. The trait of utilizing CO is spread among a diverse group of microorganisms, including members of bacteria as well as archaea. Over the last decade this metabolism has gained interest due to the potential of converting CO-rich gas, such as synthesis gas, into bio-based products. Three main types of fermentative CO metabolism can be distinguished: hydrogenogenesis, methanogenesis, and acetogenesis, generating hydrogen, methane and acetate, respectively. Here, we review the current knowledge on these three variants of microbial CO metabolism with an emphasis on the potential enzymatic routes and bio-energetics involved.

  3. Pathways and bioenergetics of anaerobic carbon monoxide fermentation.

    Directory of Open Access Journals (Sweden)

    Martijn eDiender

    2015-11-01

    Full Text Available Carbon monoxide can act as a substrate for different modes of fermentative anaerobic metabolism. The trait of utilizing CO is spread among a diverse group of microorganisms, including members of bacteria as well as archaea. Over the last decade this metabolism has gained interest due to the potential of converting CO rich gas, such as synthesis gas, into bio-based products. Three main types of fermentative CO metabolism can be distinguished: hydrogenogenesis, methanogenesis and acetogenesis, generating hydrogen, methane and acetate, respectively. Here, we review the current knowledge on these three variants of microbial CO metabolism with an emphasis on the potential enzymatic routes and bio-energetics involved.

  4. Metabolomic change precedes apple superficial scald symptoms.

    Science.gov (United States)

    Rudell, David R; Mattheis, James P; Hertog, Maarten L A T M

    2009-09-23

    Untargeted metabolic profiling was employed to characterize metabolomic changes associated with 'Granny Smith' apple superficial scald development following 1-MCP or DPA treatment. Partial least-squares discriminant analyses were used to link metabolites with scald, postharvest treatments, and storage duration. Models revealed metabolomic differentiation between untreated controls and fruit treated with DPA or 1-MCP within 1 week following storage initiation. Metabolic divergence between controls and DPA-treated fruit after 4 weeks of storage preceded scald symptom development by 2 months. alpha-Farnesene oxidation products with known associations to scald, including conjugated trienols, 6-methyl-5-hepten-2-one, and 6-methyl-5-hepten-2-ol, were associated with presymptomatic as well as scalded control fruit. Likewise, a large group of putative triterpenoids with mass spectral features similar to those of ursolic acid and beta-sitosterol were associated with control fruit and scald. Results demonstrate that extensive metabolomic changes associated with scald precede actual symptom development.

  5. Learning New Principles from Precedents and Exercises.

    Science.gov (United States)

    1981-05-01

    number of corresponding things, for some Shakespeare comparisons are as follows: Patrick H. Winston - 34- Notes HA HA JU OT TA MAcbeth 199 HAmlet 110...constitute the competence to be understood. Let us begin, then, by specifying some tasks to be performed. Consider the following precis of Macbeth ...given by a teacher as a precedent: In MA there is Macbeth Lady- Macbeth Duncan and Macduff. Macbeth is an evil noble. Lady- Macbeth is a greedy ambitious

  6. Integrating dynamic energy budget (DEB) theory with traditional bioenergetic models.

    Science.gov (United States)

    Nisbet, Roger M; Jusup, Marko; Klanjscek, Tin; Pecquerie, Laure

    2012-03-15

    Dynamic energy budget (DEB) theory offers a systematic, though abstract, way to describe how an organism acquires and uses energy and essential elements for physiological processes, in addition to how physiological performance is influenced by environmental variables such as food density and temperature. A 'standard' DEB model describes the performance (growth, development, reproduction, respiration, etc.) of all life stages of an animal (embryo to adult), and predicts both intraspecific and interspecific variation in physiological rates. This approach contrasts with a long tradition of more phenomenological and parameter-rich bioenergetic models that are used to make predictions from species-specific rate measurements. These less abstract models are widely used in fisheries studies; they are more readily interpretable than DEB models, but lack the generality of DEB models. We review the interconnections between the two approaches and present formulae relating the state variables and fluxes in the standard DEB model to measured bioenergetic rate processes. We illustrate this synthesis for two large fishes: Pacific bluefin tuna (Thunnus orientalis) and Pacific salmon (Oncorhynchus spp.). For each, we have a parameter-sparse, full-life-cycle DEB model that requires adding only a few species-specific features to the standard model. Both models allow powerful integration of knowledge derived from data restricted to certain life stages, processes and environments.

  7. A full lifecycle bioenergetic model for bluefin tuna.

    Directory of Open Access Journals (Sweden)

    Marko Jusup

    Full Text Available We formulated a full lifecycle bioenergetic model for bluefin tuna relying on the principles of Dynamic Energy Budget theory. Traditional bioenergetic models in fish research deduce energy input and utilization from observed growth and reproduction. In contrast, our model predicts growth and reproduction from food availability and temperature in the environment. We calibrated the model to emulate physiological characteristics of Pacific bluefin tuna (Thunnus orientalis, hereafter PBT, a species which has received considerable scientific attention due to its high economic value. Computer simulations suggest that (i the main cause of different growth rates between cultivated and wild PBT is the difference in average body temperature of approximately 6.5°C, (ii a well-fed PBT individual can spawn an average number of 9 batches per spawning season, (iii food abundance experienced by wild PBT is rather constant and sufficiently high to provide energy for yearly reproductive cycle, (iv energy in reserve is exceptionally small, causing the weight-length relationship of cultivated and wild PBT to be practically indistinguishable and suggesting that these fish are poorly equipped to deal with starvation, (v accelerated growth rate of PBT larvae is connected to morphological changes prior to metamorphosis, while (vi deceleration of growth rate in the early juvenile stage is related to efficiency of internal heat production. Based on these results, we discuss a number of physiological and ecological traits of PBT, including the reasons for high Feed Conversion Ratio recorded in bluefin tuna aquaculture.

  8. Bioenergetic consequences of PINK1 mutations in Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Andrey Yurevich Abramov

    Full Text Available Mutations of the gene for PTEN-induced kinase 1 (PINK1 are a cause of familial Parkinson's disease (PD. PINK1 protein has been localised to mitochondria and PINK1 gene knockout models exhibit abnormal mitochondrial function. The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features.We investigated mitochondrial bioenergetics in live fibroblasts from PINK1 mutation patients using single cell techniques. We found that fibroblasts from PINK1 mutation patients had significant defects of bioenergetics including reduced mitochondrial membrane potential, altered redox state, a respiratory deficiency that was determined by substrate availability, and enhanced sensitivity to calcium stimulation and associated mitochondrial permeability pore opening. There was an increase in the basal rate of free radical production in the mutant cells. The pattern and severity of abnormality varied between different mutations, and the less severe defects in these cells were associated with later age of onset of PD.The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype--thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities.

  9. Kinetic and bioenergetic studies of Spirulina platensis in chemostat and turbidostat culture

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H.Y.; Erickson, L.E.; Scott, C.D. (ed.)

    1986-01-01

    The growth kinetics and bioenergetics of S. platensis were investigated as a function of pH, temperature, light intensity, and HCO/sub 3/ concentration. The effects of pH and temperature on growth rate and bioenergetic yield were examined using turbidostat operation. The Arrhenius activation energy for growth appears to be independent of light intensity for the range of values that were investigated. Under light-limited growth conditions, the values of pH and temperature which provide for the maximum growth rate also correspond to the maximum bioenergetic yield. Chemostat operation was used to investigate C-limited growth.

  10. [Psychosocial stress preceding drug-related deaths].

    Science.gov (United States)

    Kraus, L; Müller-Kalthoff, T

    2002-10-01

    This article analyses drug-related deaths in the German Federal States of Bavaria (Munich, Nuremberg and Augsburg counties) during 1999 and Baden-Wurttemberg (Stuttgart and Mannheim counties) during 1999 and in the first half of 2000. The persons who had been in contact with drug care services were studied for psychosocial stress preceding drug-related deaths. Epidemiological data from different sources (police, relatives, counselling centres, detoxification clinics, therapy and substitution treatment) were collated to estimate factors of psychosocial stress preceding drug deaths. The results in both Laender indicate high prevalence rates of a history of at least one non-fatal overdose (approx. 50%) or a suicide attempt (approx. 35%). More than 40% of the deceased had been suffering from at least one additional mental disorder, in most cases from depression. At least one critical life event (in most cases, a relapse) or a period of abstinence (i.e., due to imprisonment, therapy or detoxification) during the past three months before death was reported for more than half of the addicts. The results were discussed in the light of data on opiate users and the general population. Improved specialist training of therapeutic and medical workers as well as of any other co-operating professionals is considered a necessary prerequisite for an early detection of risk factors.

  11. Shedding light on fish otolith biomineralization using a bioenergetic approach.

    Directory of Open Access Journals (Sweden)

    Ronan Fablet

    Full Text Available Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm-following formation provides individual records of the age, the individual history and the natural environment of extinct and living fish species. Such data are critical for ecosystem and fisheries monitoring. They however often lack validation and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. Here we develop and validate a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves.

  12. Shedding light on fish otolith biomineralization using a bioenergetic approach.

    Science.gov (United States)

    Fablet, Ronan; Pecquerie, Laure; de Pontual, Hélène; Høie, Hans; Millner, Richard; Mosegaard, Henrik; Kooijman, Sebastiaan A L M

    2011-01-01

    Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm-following formation provides individual records of the age, the individual history and the natural environment of extinct and living fish species. Such data are critical for ecosystem and fisheries monitoring. They however often lack validation and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. Here we develop and validate a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves.

  13. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

    DEFF Research Database (Denmark)

    Feldman, Eva L; Nave, Klaus-Armin; Jensen, Troels Staehelin

    2017-01-01

    the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights......Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand...... gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our...

  14. Bioenergetic dysfunction and inflammation in alzheimer's disease: a possible connection

    Directory of Open Access Journals (Sweden)

    Heather M Wilkins

    2014-11-01

    Full Text Available Inflammation is observed in Alzheimer’s disease (AD subject brains. Inflammation-relevant genes are increasingly implicated in AD genetic studies, and inflammatory cytokines to some extent even function as peripheral biomarkers. What underlies AD inflammation is unclear, but no foreign agent has been implicated. This suggests that internally produced damage-associated molecular pattern molecules (DAMPs may drive inflammation in AD. A more complete characterization and understanding of AD-relevant DAMPs could advance our understanding of AD and suggest novel therapeutic strategies. In this review, we consider the possibility that mitochondria, intracellular organelles that resemble bacteria in many ways, trigger and maintain chronic inflammation in AD subjects. Data supporting the possible nexus between AD-associated bioenergetic dysfunction are discussed.

  15. Shedding Light on Fish Otolith Biomineralization Using a Bioenergetic Approach

    Science.gov (United States)

    Fablet, Ronan; Pecquerie, Laure; de Pontual, Hélène; Høie, Hans; Millner, Richard; Mosegaard, Henrik; Kooijman, Sebastiaan A. L. M.

    2011-01-01

    Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm-following formation provides individual records of the age, the individual history and the natural environment of extinct and living fish species. Such data are critical for ecosystem and fisheries monitoring. They however often lack validation and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. Here we develop and validate a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves. PMID:22110601

  16. The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

    Science.gov (United States)

    Chowdhury, Subir K Roy; Smith, Darrell R; Fernyhough, Paul

    2013-03-01

    Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). This article attempts to relate these findings to the development of critical neuropathological hallmarks of the disease. Recent work reveals that hyperglycemia in diabetes triggers nutrient excess in neurons that, in turn, mediates a phenotypic change in mitochondrial biology through alteration of the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling axis. This vital energy sensing metabolic pathway modulates mitochondrial function, biogenesis and regeneration. The bioenergetic phenotype of mitochondria in diabetic neurons is aberrant due to deleterious alterations in expression and activity of respiratory chain components as a direct consequence of abnormal AMPK/PGC-1α signaling. Utilization of innovative respirometry equipment to analyze mitochondrial function of cultured adult sensory neurons from diabetic rodents shows that the outcome for cellular bioenergetics is a reduced adaptability to fluctuations in ATP demand. The diabetes-induced maladaptive process is hypothesized to result in exhaustion of the ATP supply in the distal nerve compartment and induction of nerve fiber dissolution. The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich

  17. A bioenergetic basis for membrane divergence in archaea and bacteria.

    Science.gov (United States)

    Sojo, Víctor; Pomiankowski, Andrew; Lane, Nick

    2014-08-01

    Membrane bioenergetics are universal, yet the phospholipid membranes of archaea and bacteria-the deepest branches in the tree of life-are fundamentally different. This deep divergence in membrane chemistry is reflected in other stark differences between the two domains, including ion pumping and DNA replication. We resolve this paradox by considering the energy requirements of the last universal common ancestor (LUCA). We develop a mathematical model based on the premise that LUCA depended on natural proton gradients. Our analysis shows that such gradients can power carbon and energy metabolism, but only in leaky cells with a proton permeability equivalent to fatty acid vesicles. Membranes with lower permeability (equivalent to modern phospholipids) collapse free-energy availability, precluding exploitation of natural gradients. Pumping protons across leaky membranes offers no advantage, even when permeability is decreased 1,000-fold. We hypothesize that a sodium-proton antiporter (SPAP) provided the first step towards modern membranes. SPAP increases the free energy available from natural proton gradients by ∼60%, enabling survival in 50-fold lower gradients, thereby facilitating ecological spread and divergence. Critically, SPAP also provides a steadily amplifying advantage to proton pumping as membrane permeability falls, for the first time favoring the evolution of ion-tight phospholipid membranes. The phospholipids of archaea and bacteria incorporate different stereoisomers of glycerol phosphate. We conclude that the enzymes involved took these alternatives by chance in independent populations that had already evolved distinct ion pumps. Our model offers a quantitatively robust explanation for why membrane bioenergetics are universal, yet ion pumps and phospholipid membranes arose later and independently in separate populations. Our findings elucidate the paradox that archaea and bacteria share DNA transcription, ribosomal translation, and ATP synthase, yet

  18. Mitochondrial bioenergetics in young, adult, middle-age and senescent brown Norway rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and may play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identi...

  19. Life-stage and organ specific changes in mitochondrial bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identical ...

  20. Cochlear contributions to the precedence effect.

    Science.gov (United States)

    Verhulst, Sarah; Bianchi, Federica; Dau, Torsten

    2013-01-01

    Normal-hearing individuals have sharply tuned auditory filters, and consequently their basilar-membrane (BM) impulse responses (IRs) have durations of several ms at frequencies in the range from 0 to 5 kHz. When presenting clicks that are several ms apart, the BM IRs to the individual clicks will overlap in time, giving rise to complex interactions that have not been fully understood in the human cochlea. The perceptual consequences of these BM IR interactions are of interest as lead-lag click pairs are often used to study localization and the precedence effect. The present study aimed at characterizing perceptual consequences of BM IR interactions in individual listeners based on click-evoked otoacoustic emissions (CEOAEs) and auditory brainstem responses (ABRs). Lag suppression, denoting the level difference between the CEOAE or wave-V response amplitude evoked by the first and the second clicks, was observed for inter-click intervals (ICIs) between 1 and 4 ms. Behavioral correlates of lag suppression were obtained for the same individuals by investigating the percept of the lead-lag click pairs presented either monaurally or binaurally. The click pairs were shown to give rise to fusion (i.e., the inability to hear out the second click in a lead-lag click pair), regardless of monaural or binaural presentation. In both cases, the ICI range where the percept was a fused image correlated well with the ICI range for which monaural lag suppression occurred in the CEOAE and ABR (i.e., for ICIs below 4.3 ms). Furthermore, the lag suppression observed in the wave-V amplitudes to binaural stimulation did not show additional contributions to the lag suppression obtained monaurally, suggesting that peripheral lag suppression up to the level of the brainstem is dominant in the perception of the precedence effect.

  1. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy.

    Science.gov (United States)

    Obre, Emilie; Rossignol, Rodrigue

    2015-02-01

    The field of energy metabolism dramatically progressed in the last decade, owing to a large number of cancer studies, as well as fundamental investigations on related transcriptional networks and cellular interactions with the microenvironment. The concept of metabolic flexibility was clarified in studies showing the ability of cancer cells to remodel the biochemical pathways of energy transduction and linked anabolism in response to glucose, glutamine or oxygen deprivation. A clearer understanding of the large-scale bioenergetic impact of C-MYC, MYCN, KRAS and P53 was obtained, along with its modification during the course of tumor development. The metabolic dialog between different types of cancer cells, but also with the stroma, also complexified the understanding of bioenergetics and raised the concepts of metabolic symbiosis and reverse Warburg effect. Signaling studies revealed the role of respiratory chain-derived reactive oxygen species for metabolic remodeling and metastasis development. The discovery of oxidative tumors in human and mice models related to chemoresistance also changed the prevalent view of dysfunctional mitochondria in cancer cells. Likewise, the influence of energy metabolism-derived oncometabolites emerged as a new means of tumor genetic regulation. The knowledge obtained on the multi-site regulation of energy metabolism in tumors was translated to cancer preclinical studies, supported by genetic proof of concept studies targeting LDHA, HK2, PGAM1, or ACLY. Here, we review those different facets of metabolic remodeling in cancer, from its diversity in physiology and pathology, to the search of the genetic determinants, the microenvironmental regulators and pharmacological modulators.

  2. Extension of the preceding birth technique.

    Science.gov (United States)

    Aguirre, A

    1994-01-01

    The Brass-inspired Preceding Birth Technique (PBT), is an indirect estimation technique with low costs of administration. PBT involves asking women at a time close to delivery about the survival of the preceding births. The proportion dead is close to the probability of dying between the birth and the second birthday or an index of early childhood mortality (II or Q). Brass and Macrae have determined that II is an estimate of mortality between birth and an age lower than the birth interval or around 4/5 of the birth interval. Hospital and clinic data are likely to include a concentration of women with lower risks of disease because of higher educational levels and socioeconomic status. A simulation of PBT data from the World Fertility Survey for Mexico and Peru found that the proportions of previously dead children were 0.156 in Peru and 0.092 in Mexican home deliveries. Maternity clinic proportions were 0.088 in Peru and 0.066 in Mexico. Use of clinic and hospital data collection underestimated mortality by 32% in Peru and 15% in Mexico. Another alternative was proposed: interviewing women at some other time than delivery. If the interview was during a child/infant intervention after delivery, the subsample would still be subject to a bias, but this problem could be overcome by computing the weighted average of the actual probability of the older child being dead and the conditional probability of the younger child being dead or both younger and older children being dead. Correction factors could be applied using the general standard of the logit life table system of Brass. Calculation of a simple average of the ages of the younger children could provide enough information to help decide which tables to use. Five surveys were selected for testing the factors of dependence between probabilities of death of successive siblings: Bangladesh, Lesotho, Kenya, Ghana, and Guyana. Higher mortality was related to lower dependency factors between the probabilities of death

  3. Dengue Preceding Diabetic Ketoacidosis Dear Editor;

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2013-12-01

    Full Text Available Diabetic ketoacidosis (DKA is an important hyperglycemic complication of diabetes mellitus. Infection is confirmed as an important underlying etiology of DKA. Here, the author presents an interesting case of dengue preceding DKA. The case is a 61-year-old female presenting to the physician with the complaint of high fever without relief by self-prescription of acetaminophen. She had an underlying disease, diabetes mellitus (DM. Her body temperature was 39.4 degrees Celsius and her complete blood count showed an important finding: thrombocytopenia (platelet count = 85.000. The serological test was done and the diagnosis of dengue hemorrhagic fever was finally confirmed. This case was treated by standard fluid replacement therapy (normal saline regimen. On day 3, the patient developed new symptoms, frequent urination (more than 3 times in an hour, abdominal pain, nausea, vomiting and rapid breathing. Complete blood count was done but platelet count was within normal limit at this time. However, the urinalysis showed many positive findings, sugar 4+ and ketone 3+. Her additional blood chemistry results showed a blood glucose level of 454 mg/dL and positive serum ketone. The patient was finally diagnosed to have DKA and endocrinologists were consulted for the management. Of interest, this is a simple case of DKA but the interesting issue is the underlying condition leading to DKA in this patient. Although there are many reports confirming that infection can induce DKA, this is the first reported case of dengue preceding DKA. Indeed, there is a previous report from Thailand on a female patient presented to the physician with concurrent DKA and dengue infection (1. However, DM had not previously been diagnosed in the present case. The dengue infection is common in the tropical world and DM is also the important emerging health problem in this area. Some reports note that DM can be an aggravating factor in the development of dengue shock (2,3. There is

  4. Dysfunctional mitochondrial bioenergetics and the pathogenesis of hepatic disorders

    Directory of Open Access Journals (Sweden)

    Christopher eAuger

    2015-06-01

    Full Text Available The liver is involved in a variety of critical biological functions including the homeostasis of glucose, fatty acids, amino acids and the synthesis of proteins that are secreted in the blood. It is also at the forefront in the detoxification of noxious metabolites that would otherwise upset the functioning of the body. As such, this vital component of the mammalian system is exposed to a notable quantity of toxicants on a regular basis. It therefore comes as no surprise that there are over a hundred disparate hepatic disorders, encompassing such afflictions as fatty liver disease, hepatitis and liver cancer. Most if not all of liver functions are dependent on energy, an ingredient that is primarily generated by the mitochondrion, the power house of all cells. This organelle is indispensable in providing adenosine triphosphate (ATP, a key effector of most biological processes. Dysfunctional mitochondria lead to a shortage in ATP, the leakage of deleterious reactive oxygen species (ROS and the excessive storage of fats. Here we examine how incapacitated mitochondrial bioenergetics triggers the pathogenesis of various hepatic diseases. Exposure of liver cells to detrimental environmental hazards such as oxidative stress, metal toxicity and various xenobiotics results in the inactivation of crucial mitochondrial enzymes and decreased ATP levels. The contribution of the latter to hepatic disorders and potential therapeutic cues to remedy these conditions are elaborated.

  5. H2 cycling and microbial bioenergetics in anoxic sediments

    Science.gov (United States)

    Hoehler, Tori M.; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    The simple biochemistry of H2 is central to a large number of microbial processes, affecting the interaction of organisms with each other and with the environment. In anoxic sediments, the great majority of microbial redox processes involve H2 as a reactant, product, or potential by-product, and the thermodynamics of these processes are thus highly sensitive to fluctuations in environmental H2 concentrations. In turn, H2 concentrations are controlled by the activity of H2-consuming microorganisms, which efficiently utilize this substrate down to levels which correspond to their bioenergetic limitations. Consequently, any environmental change which impacts the thermodynamics of H2-consuming organisms is mirrored by a corresponding change in H2 concentrations. This phenomenon is illustrated in anoxic sediments from Cape Lookout Bight, NC, USA: H2 concentrations are controlled by a suite of environmental parameters (e.g., temperature, sulfate concentrations) in a fashion which can be quantitatively described by a simple thermodynamic model. These findings allow us to calculate the apparent minimum quantity of biologically useful energy in situ. We find that sulfate reducing bacteria are not active at energy yields below -18 kJ per mole sulfate, while methanogenic archaea exhibit a minimum close to -10 kJ per mole methane.

  6. Important roles for membrane lipids in haloarchaeal bioenergetics.

    Science.gov (United States)

    Kellermann, Matthias Y; Yoshinaga, Marcos Y; Valentine, Raymond C; Wörmer, Lars; Valentine, David L

    2016-11-01

    Recent advances in lipidomic analysis in combination with various physiological experiments set the stage for deciphering the structure-function of haloarchaeal membrane lipids. Here we focused primarily on changes in lipid composition of Haloferax volcanii, but also performed a comparative analysis with four other haloarchaeal species (Halobacterium salinarum, Halorubrum lacusprofundi, Halorubrum sodomense and Haloplanus natans) all representing distinctive cell morphologies and behaviors (i.e., rod shape vs. pleomorphic behavior). Common to all five haloarchaea, our data reveal an extraordinary high level of menaquinone, reaching up to 72% of the total lipids. This ubiquity suggests that menaquinones may function beyond their ordinary role as electron and proton transporter, acting simultaneously as ion permeability barriers and as powerful shield against oxidative stress. In addition, we aimed at understanding the role of cations interacting with the characteristic negatively charged surface of haloarchaeal membranes. We propose for instance that by bridging the negative charges of adjacent anionic phospholipids, Mg(2+) acts as surrogate for cardiolipin, a molecule that is known to control curvature stress of membranes. This study further provides a bioenergetic perspective as to how haloarchaea evolved following oxygenation of Earth's atmosphere. The success of the aerobic lifestyle of haloarchaea includes multiple membrane-based strategies that successfully balance the need for a robust bilayer structure with the need for high rates of electron transport - collectively representing the molecular basis to inhabit hypersaline water bodies around the planet.

  7. Respiratory infections precede adult-onset asthma.

    Directory of Open Access Journals (Sweden)

    Aino Rantala

    Full Text Available BACKGROUND: Respiratory infections in early life are associated with an increased risk of developing asthma but there is little evidence on the role of infections for onset of asthma in adults. The objective of this study was to assess the relation of the occurrence of respiratory infections in the past 12 months to adult-onset asthma in a population-based incident case-control study of adults 21-63 years of age. METHODS/PRINCIPAL FINDINGS: We recruited all new clinically diagnosed cases of asthma (n = 521 during a 2.5-year study period and randomly selected controls (n = 932 in a geographically defined area in South Finland. Information on respiratory infections was collected by a self-administered questionnaire. The diagnosis of asthma was based on symptoms and reversible airflow obstruction in lung function measurements. The risk of asthma onset was strongly increased in subjects who had experienced in the preceding 12 months lower respiratory tract infections (including acute bronchitis and pneumonia with an adjusted odds ratio (OR 7.18 (95% confidence interval [CI] 5.16-9.99, or upper respiratory tract infections (including common cold, sinusitis, tonsillitis, and otitis media with an adjusted OR 2.26 (95% CI 1.72-2.97. Individuals with personal atopy and/or parental atopy were more susceptible to the effects of respiratory infections on asthma onset than non-atopic persons. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that recently experienced respiratory infections are a strong determinant for adult-onset asthma. Reducing such infections might prevent onset of asthma in adulthood, especially in individuals with atopy or hereditary propensity to it.

  8. Amyloid-β–Induced Changes in Molecular Clock Properties and Cellular Bioenergetics

    Science.gov (United States)

    Schmitt, Karen; Grimm, Amandine; Eckert, Anne

    2017-01-01

    Ageing is an inevitable biological process that results in a progressive structural and functional decline, as well as biochemical alterations that altogether lead to reduced ability to adapt to environmental changes. As clock oscillations and clock-controlled rhythms are not resilient to the aging process, aging of the circadian system may also increase susceptibility to age-related pathologies such as Alzheimer's disease (AD). Besides the amyloid-beta protein (Aβ)-induced metabolic decline and neuronal toxicity in AD, numerous studies have demonstrated that the disruption of sleep and circadian rhythms is one of the common and earliest signs of the disease. In this study, we addressed the questions of whether Aβ contributes to an abnormal molecular circadian clock leading to a bioenergetic imbalance. For this purpose, we used different oscillator cellular models: human skin fibroblasts, human glioma cells, as well as mouse primary cortical and hippocampal neurons. We first evaluated the circadian period length, a molecular clock property, in the presence of different Aβ species. We report here that physiologically relevant Aβ1–42 concentrations ranging from 10 to 500 nM induced an increase of the period length in human skin fibroblasts, human A172 glioma cells as well as in mouse primary neurons whereas the reverse control peptide Aβ42-1, which is devoid of toxic action, did not influence the circadian period length within the same concentration range. To better understand the underlying mechanisms that are involved in the Aβ-related alterations of the circadian clock, we examined the cellular metabolic state in the human primary skin fibroblast model. Notably, under normal conditions, ATP levels displayed circadian oscillations, which correspond to the respective circadian pattern of mitochondrial respiration. In contrast, Aβ1–42 treatment provoked a strong dampening in the metabolic oscillations of ATP levels as well as mitochondrial respiration and

  9. Development and evaluation of a bioenergetics model for bull trout

    Science.gov (United States)

    Mesa, Matthew G.; Welland, Lisa K.; Christiansen, Helena E.; Sauter, Sally T.; Beauchamp, David A.

    2013-01-01

    We conducted laboratory experiments to parameterize a bioenergetics model for wild Bull Trout Salvelinus confluentus, estimating the effects of body mass (12–1,117 g) and temperature (3–20°C) on maximum consumption (C max) and standard metabolic rates. The temperature associated with the highest C max was 16°C, and C max showed the characteristic dome-shaped temperature-dependent response. Mass-dependent values of C max (N = 28) at 16°C ranged from 0.03 to 0.13 g·g−1·d−1. The standard metabolic rates of fish (N = 110) ranged from 0.0005 to 0.003 g·O2·g−1·d−1 and increased with increasing temperature but declined with increasing body mass. In two separate evaluation experiments, which were conducted at only one ration level (40% of estimated C max), the model predicted final weights that were, on average, within 1.2 ± 2.5% (mean ± SD) of observed values for fish ranging from 119 to 573 g and within 3.5 ± 4.9% of values for 31–65 g fish. Model-predicted consumption was within 5.5 ± 10.9% of observed values for larger fish and within 12.4 ± 16.0% for smaller fish. Our model should be useful to those dealing with issues currently faced by Bull Trout, such as climate change or alterations in prey availability.

  10. Impaired Myocardial Bioenergetics in HFpEF and the Role of Antioxidants.

    Science.gov (United States)

    Hiebert, John B; Shen, Qiuhua; Thimmesch, Amanda; Pierce, Janet

    2016-01-01

    Heart failure with preserved ejection fraction (HFpEF) is a significant cardiovascular condition for more than 50% of patients with heart failure. Currently, there is no effective treatment to decrease morbidity and mortality rates associated with HFpEF because of its pathophysiological heterogeneity. Recent evidence shows that deficiency in myocardial bioenergetics is one of the key pathophysiological factors contributing to diastolic dysfunction in HFpEF. Another known mechanism for HFpEF is an overproduction of free radicals, specifically reactive oxygen species. To reduce free radical formation, antioxidants are often used. This article is a summative review of the recent relevant literature that addresses cardiac bioenergetics, deficiency in myocardial bioenergetics, and increased reactive oxygen species associated with HFpEF and the promising potential use of antioxidants in managing this condition.

  11. Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Vikram Saini

    2016-01-01

    Full Text Available The mechanisms by which Mycobacterium tuberculosis (Mtb maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT and mycothiol (MSH are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping but distinct functions of EGT and MSH. Last, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity.

  12. Grammar Engineering Support for Precedence Rule Recovery and Compatibility Checking

    NARCIS (Netherlands)

    Bouwers, E.; Bravenboer, M.; Visser, E.

    2007-01-01

    A wide range of parser generators are used to generate parsers for programming languages. The grammar formalisms that come with parser generators provide different approaches for defining operator precedence. Some generators (e.g. YACC) support precedence declarations, others require the grammar to

  13. Application of a bioenergetics model for hatchery production: Largemouth bass fed commercial diets

    Science.gov (United States)

    Csargo, Isak J.; Michael L. Brown,; Chipps, Steven R.

    2012-01-01

    Fish bioenergetics models based on natural prey items have been widely used to address research and management questions. However, few attempts have been made to evaluate and apply bioenergetics models to hatchery-reared fish receiving commercial feeds that contain substantially higher energy densities than natural prey. In this study, we evaluated a bioenergetics model for age-0 largemouth bass Micropterus salmoidesreared on four commercial feeds. Largemouth bass (n ≈ 3,504) were reared for 70 d at 25°C in sixteen 833-L circular tanks connected in parallel to a recirculation system. Model performance was evaluated using error components (mean, slope, and random) derived from decomposition of the mean square error obtained from regression of observed on predicted values. Mean predicted consumption was only 8.9% lower than mean observed consumption and was similar to error rates observed for largemouth bass consuming natural prey. Model evaluation showed that the 97.5% joint confidence region included the intercept of 0 (−0.43 ± 3.65) and slope of 1 (1.08 ± 0.20), which indicates the model accurately predicted consumption. Moreover model error was similar among feeds (P = 0.98), and most error was probably attributable to sampling error (unconsumed feed), underestimated predator energy densities, or consumption-dependent error, which is common in bioenergetics models. This bioenergetics model could provide a valuable tool in hatchery production of largemouth bass. Furthermore, we believe that bioenergetics modeling could be useful in aquaculture production, particularly for species lacking historical hatchery constants or conventional growth models.

  14. Constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, J.R.

    1992-11-01

    The constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms were quantified. During this project we conducted studies: to determine the role of incubation temperature on the post-hatching growth rate of the snapping turtle, Chelydra serpentina; to establish the rate of energy expenditure of the slider turtle, Trachemys scripta, in the field; to determine the field metabolic rates, body temperatures and selected microclimates of the box turtle, Terrapene carolina, and to measure the effect of diet type on the consumption rate, digestion rate and digestive efficiency of adult T. scripta. We also completed our research on the three-dimensional bioenergetic climate space for freshwater turtles.

  15. An open circuit balance respirometer for bioenergetic studies of fish growth

    NARCIS (Netherlands)

    Hogendoorn, H.; Korlaar, van F.; Bosch, H.

    1981-01-01

    A description is given of an open circuit balance respirometer for bioenergetic studies of fish growth using indirect calorimetry. The installation was designed to enable the determination of gas and matter balances of fish, including air breathing species, during prolonged experimental periods. Des

  16. Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus

    OpenAIRE

    El-Bacha, Tatiana; Midlej, Victor; Silva, Ana Paula Pereira da; COSTA,LEANDRO SILVA DA; Benchimol, Marlene; Galina, Antonio; POIAN,ANDREA T. DA

    2007-01-01

    Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus correspondence: Corresponding author. Fax: +55 21 22708647. (El-Bacha, Tatiana) (El-Bacha, Tatiana) Laboratorio de Bioquimica de Virus, Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro - RJ-Brasil--> , Av. Bauhinia n? 400 ? CCS Bloco H 2? andar--> , sala 22. Ilha do Governador--> ...

  17. Role of thermal physiology and bioenergetics on adaptation in tree shrew (Tupaia belangeri): the experiment test

    Science.gov (United States)

    Zhang, Lin; Yang, Fang; Wang, Zheng-kun; Zhu, Wan-long

    2017-01-01

    Ambient conditions, as temperature and photoperiod, play a key role in animals’ physiology and behaviors. To test the hypothesis that the maximum thermal physiological and bioenergetics tolerances are induced by extreme environments in Tupaia belangeri. We integrated the acclimatized and acclimated data in several physiological, hormonal, and biochemical markers of thermogenic capacity and bioenergetics in T. belangeri. Results showed that T. belangeri increased body mass, thermogenesis capacity, protein contents and cytochrome c oxidase (COX) activity of liver and brown adipose tissue in winter-like environments, which indicated that temperature was the primary signal for T. belangeri to regulate several physiological capacities. The associated photoperiod signal also elevated the physiological capacities. The regulations of critical physiological traits play a primary role in meeting the survival challenges of winter-like condition in T. belangeri. Together, to cope with cold, leptin may play a potential role in thermogenesis and body mass regulation, as this hormonal signal is associated with other hormones. The strategies of thermal physiology and bioenergetics differs between typical Palearctic species and the local species. However, the maximum thermal physiology and bioenergetic tolerance maybe is an important strategy to cope with winter-like condition of T. belangeri. PMID:28145515

  18. Re-estimating temperature-dependent consumption parameters in bioenergetics models for juvenile Chinook salmon

    Science.gov (United States)

    Plumb, John M.; Moffitt, Christine M.

    2015-01-01

    Researchers have cautioned against the borrowing of consumption and growth parameters from other species and life stages in bioenergetics growth models. In particular, the function that dictates temperature dependence in maximum consumption (Cmax) within the Wisconsin bioenergetics model for Chinook Salmon Oncorhynchus tshawytscha produces estimates that are lower than those measured in published laboratory feeding trials. We used published and unpublished data from laboratory feeding trials with subyearling Chinook Salmon from three stocks (Snake, Nechako, and Big Qualicum rivers) to estimate and adjust the model parameters for temperature dependence in Cmax. The data included growth measures in fish ranging from 1.5 to 7.2 g that were held at temperatures from 14°C to 26°C. Parameters for temperature dependence in Cmax were estimated based on relative differences in food consumption, and bootstrapping techniques were then used to estimate the error about the parameters. We found that at temperatures between 17°C and 25°C, the current parameter values did not match the observed data, indicating that Cmax should be shifted by about 4°C relative to the current implementation under the bioenergetics model. We conclude that the adjusted parameters for Cmax should produce more accurate predictions from the bioenergetics model for subyearling Chinook Salmon.

  19. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    2014-04-15

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.

  20. Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome.

    Science.gov (United States)

    Kiebish, Michael A; Yang, Kui; Liu, Xinping; Mancuso, David J; Guan, Shaoping; Zhao, Zhongdan; Sims, Harold F; Cerqua, Rebekah; Cade, W Todd; Han, Xianlin; Gross, Richard W

    2013-05-01

    Barth syndrome is a complex metabolic disorder caused by mutations in the mitochondrial transacylase tafazzin. Recently, an inducible tafazzin shRNA knockdown mouse model was generated to deconvolute the complex bioenergetic phenotype of this disease. To investigate the underlying cause of hemodynamic dysfunction in Barth syndrome, we interrogated the cardiac structural and signaling lipidome of this mouse model as well as its myocardial bioenergetic phenotype. A decrease in the distribution of cardiolipin molecular species and robust increases in monolysocardiolipin and dilysocardiolipin were demonstrated. Additionally, the contents of choline and ethanolamine glycerophospholipid molecular species containing precursors for lipid signaling at the sn-2 position were altered. Lipidomic analyses revealed specific dysregulation of HETEs and prostanoids, as well as oxidized linoleic and docosahexaenoic metabolites. Bioenergetic interrogation uncovered differential substrate utilization as well as decreases in Complex III and V activities. Transgenic expression of cardiolipin synthase or iPLA2γ ablation in tafazzin-deficient mice did not rescue the observed phenotype. These results underscore the complex nature of alterations in cardiolipin metabolism mediated by tafazzin loss of function. Collectively, we identified specific lipidomic, bioenergetic, and signaling alterations in a murine model that parallel those of Barth syndrome thereby providing novel insights into the pathophysiology of this debilitating disease.

  1. Hybrid incompatibility arises in a sequence-based bioenergetic model of transcription factor binding.

    Science.gov (United States)

    Tulchinsky, Alexander Y; Johnson, Norman A; Watt, Ward B; Porter, Adam H

    2014-11-01

    Postzygotic isolation between incipient species results from the accumulation of incompatibilities that arise as a consequence of genetic divergence. When phenotypes are determined by regulatory interactions, hybrid incompatibility can evolve even as a consequence of parallel adaptation in parental populations because interacting genes can produce the same phenotype through incompatible allelic combinations. We explore the evolutionary conditions that promote and constrain hybrid incompatibility in regulatory networks using a bioenergetic model (combining thermodynamics and kinetics) of transcriptional regulation, considering the bioenergetic basis of molecular interactions between transcription factors (TFs) and their binding sites. The bioenergetic parameters consider the free energy of formation of the bond between the TF and its binding site and the availability of TFs in the intracellular environment. Together these determine fractional occupancy of the TF on the promoter site, the degree of subsequent gene expression and in diploids, and the degree of dominance among allelic interactions. This results in a sigmoid genotype-phenotype map and fitness landscape, with the details of the shape determining the degree of bioenergetic evolutionary constraint on hybrid incompatibility. Using individual-based simulations, we subjected two allopatric populations to parallel directional or stabilizing selection. Misregulation of hybrid gene expression occurred under either type of selection, although it evolved faster under directional selection. Under directional selection, the extent of hybrid incompatibility increased with the slope of the genotype-phenotype map near the derived parental expression level. Under stabilizing selection, hybrid incompatibility arose from compensatory mutations and was greater when the bioenergetic properties of the interaction caused the space of nearly neutral genotypes around the stable expression level to be wide. F2's showed higher

  2. Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents.

    Science.gov (United States)

    Saleh, Ali; Roy Chowdhury, Subir K; Smith, Darrell R; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E; Calcutt, Nigel A; Fernyhough, Paul

    2013-02-01

    Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-κB signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-κB, as assessed by Western blotting for the NF-κB p50 subunit and reporter assays for NF-κB promoter activity. Conversely, blockade of NF-κB signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-κB p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-κB-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-κB activation, and improvement of cellular bioenergetics.

  3. C-terminal heat shock protein 90 inhibitor decreases hyperglycemia-induced oxidative stress and improves mitochondrial bioenergetics in sensory neurons.

    Science.gov (United States)

    Zhang, Liang; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2012-04-06

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90). KU-32 ameliorates multiple sensory deficits associated with the progression of DPN and protects unmyelinated sensory neurons from glucose-induced toxicity. Mechanistically, KU-32 increased the expression of Hsp70, and this protein was critical for drug efficacy in reversing DPN. However, it remained unclear if KU-32 had a broader effect on chaperone induction and if its efficacy was linked to improving mitochondrial dysfunction. Using cultures of hyperglycemically stressed primary sensory neurons, the present study investigated whether KU-32 had an effect on the translational induction of other chaperones and improved mitochondrial oxidative stress and bioenergetics. A variation of stable isotope labeling with amino acids in cell culture called pulse SILAC (pSILAC) was used to unbiasedly assess changes in protein translation. Hyperglycemia decreased the translation of numerous mitochondrial proteins that affect superoxide levels and respiratory activity. Importantly, this correlated with a decrease in mitochondrial oxygen consumption and an increase in superoxide levels. KU-32 increased the translation of Mn superoxide dismutase and several cytosolic and mitochondrial chaperones. Consistent with these changes, KU-32 decreased mitochondrial superoxide levels and significantly enhanced respiratory activity. These data indicate that efficacy of modulating molecular chaperones in DPN may be due in part to improved neuronal mitochondrial bioenergetics and decreased oxidative stress.

  4. A C-Terminal Heat Shock Protein 90 Inhibitor Decreases Hyperglycemia-induced Oxidative Stress and Improves Mitochondrial Bioenergetics in Sensory Neurons

    Science.gov (United States)

    Zhang, Liang; Zhao, Huiping; Blagg, Brian S.J.; Dobrowsky, Rick T.

    2012-01-01

    Summary Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90). KU-32 ameliorates multiple sensory deficits associated with the progression of DPN and protects unmyelinated sensory neurons from glucose-induced toxicity. Mechanistically, KU-32 increased the expression of Hsp70 and this protein was critical for drug efficacy in reversing DPN. However, it remained unclear if KU-32 had a broader effect on chaperone induction and if its efficacy was linked to improving mitochondrial dysfunction. Using cultures of hyperglycemically stressed primary sensory neurons, the present study investigated whether KU-32 had an effect on the translational induction of other chaperones and improved mitochondrial oxidative stress and bioenergetics. A variation of stable isotope labeling with amino acids in cell culture called pulse SILAC (pSILAC) was used to unbiasedly assess changes in protein translation. Hyperglycemia decreased the translation of numerous mitochondrial proteins that affect superoxide levels and respiratory activity. Importantly, this correlated with a decrease in mitochondrial oxygen consumption and an increase in superoxide levels. KU-32 increased the translation of Mn superoxide dismutase and several cytosolic and mitochondrial chaperones. Consistent with these changes, KU-32 decreased mitochondrial superoxide levels and significantly enhanced respiratory activity. These data indicate that efficacy of modulating molecular chaperones in DPN may be due in part to improved neuronal mitochondrial bioenergetics and decreased oxidative stress. PMID:22413817

  5. Dealing With a Deficit

    Institute of Scientific and Technical Information of China (English)

    LAN XINZHEN

    2010-01-01

    @@ For the first time since April 2004,China experienced a monthly trade deficit as imports surpassed exports.Statistics released by the General Administration of Customs on April 10 showed China's export and import volume reached $112.11billion and $119.35 billion in March,respectively,leading to a trade deficit of $7.24 billion.

  6. Gestalt perception and the decline of global precedence in older subjects.

    Science.gov (United States)

    Staudinger, Markus R; Fink, Gereon R; Mackay, Clare E; Lux, Silke

    2011-01-01

    Our visual world is hierarchically organized. Hierarchical processing is frequently investigated using Navon figures (large letters made up of smaller ones). In young adults, many studies reported faster reaction times (RT) to target letters presented at the global level [i.e., global precedence (GP)]. Furthermore, an age-related decline of this GP has been reported. We tested whether deficits in perceptual grouping via Gestalt laws (Gestalt principles of Proximity and Continuity) might contribute to this decline. In a directed attention task with valid and invalid cues, 20 young (mean age 22) and 20 older (mean age 57) male subjects had to indicate whether a target letter appeared at the global or local level of a Navon figure. The number of local letters forming the global figure was modulated in 5 steps. As expected, during valid trials, young adults showed a GP that linearly increased with increasing numbers of local letters (i.e., GP enhancement). This suggests that GP is related to perceptual grouping via Gestalt laws. By contrast, the group of older subjects demonstrated no precedence effect in RT and a non-significant trend toward GP in error rates (ER). No GP enhancement with an increasing number of local elements was observed. Exploratory analysis revealed that individual insensitivity to the modulation of matrix density, as revealed by a lack of global RT acceleration, was restricted to subjects that showed an overall local precedence (LP). Because older subjects tended to more frequently display an insensitivity to matrix modulation and an LP, we conclude that deficient Gestalt detection as indicated by non-enhanced global RT might contribute to the RT-related decline of GP with age.

  7. Distinct effects of rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine on cellular bioenergetics and cell death.

    Directory of Open Access Journals (Sweden)

    Samantha Giordano

    Full Text Available Parkinson's disease is characterized by dopaminergic neurodegeneration and is associated with mitochondrial dysfunction. The bioenergetic susceptibility of dopaminergic neurons to toxins which induce Parkinson's like syndromes in animal models is then of particular interest. For example, rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and its active metabolite 1-methyl-4-phenylpyridinium (MPP(+, and 6-hydroxydopamine (6-OHDA, have been shown to induce dopaminergic cell death in vivo and in vitro. Exposure of animals to these compounds induce a range of responses characteristics of Parkinson's disease, including dopaminergic cell death, and Reactive Oxygen Species (ROS production. Here we test the hypothesis that cellular bioenergetic dysfunction caused by these compounds correlates with induction of cell death in differentiated dopaminergic neuroblastoma SH-SY5Y cells. At increasing doses, rotenone induced significant cell death accompanied with caspase 3 activation. At these concentrations, rotenone had an immediate inhibition of mitochondrial basal oxygen consumption rate (OCR concomitant with a decrease of ATP-linked OCR and reserve capacity, as well as a stimulation of glycolysis. MPP(+ exhibited a different behavior with less pronounced cell death at doses that nearly eliminated basal and ATP-linked OCR. Interestingly, MPP(+, unlike rotenone, stimulated bioenergetic reserve capacity. The effects of 6-OHDA on bioenergetic function was markedly less than the effects of rotenone or MPP(+ at cytotoxic doses, suggesting a mechanism largely independent of bioenergetic dysfunction. These studies suggest that these dopaminergic neurotoxins induce cell death through distinct mechanisms and differential effects on cellular bioenergetics.

  8. Understanding Attention Deficit Disorders.

    Science.gov (United States)

    Villegas, Orlando; And Others

    This booklet provides basic information regarding attention deficit hyperactivity disorders (ADHD), in their separate modalities, with hyperactivity, impulsivity, and inattention. Explanations are offered concerning short attention span, impulsive behavior, hyperactivity, and beginning new activities before completing the previous one. Theories…

  9. Disentangling deficits in adults with attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Bekker, E.M.; Overtoom, C.C.; Kooij, J.J.; Buitelaar, J.K.; Verbaten, M.N.; Kenemans, J.L.

    2005-01-01

    CONTEXT: A lack of inhibitory control has been suggested to be the core deficit in attention-deficit/hyperactivity disorder (ADHD), especially in adults. This means that a primary deficit in inhibition mediates a cascade of secondary deficits in other executive functions, such as attention. Impaired

  10. Preceding trauma in childhood hematogenous bone and joint infections.

    Science.gov (United States)

    Pääkkönen, Markus; Kallio, Markku J T; Lankinen, Petteri; Peltola, Heikki; Kallio, Pentti E

    2014-03-01

    Preceding trauma may play a role in the etiology and pathogenesis of hematogenous bone and joint infections. Among 345 children with an acute hematogenous bone and/or joint infection, 20% reported trauma during a 2-week period leading to infection. Blunt impact, bruises, or excoriations were commonly reported. The rate was similar to that in the general pediatric population obtained from the literature. In the study group, patients with and without trauma were similar in age, serum C-reactive protein and erythrocyte sedimentation rate, length of hospitalization, and late sequelae. Preceding minor trauma did not prove to be significant as an etiological or as a prognostic factor.

  11. An ex-vivo model for evaluating bioenergetics in aortic rings

    Directory of Open Access Journals (Sweden)

    Kyle P. Feeley

    2014-01-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide and it exhibits a greatly increasing incidence proportional to aging. Atherosclerosis is a chronic condition of arterial hardening resulting in restriction of oxygen delivery and blood flow to the heart. Relationships between mitochondrial DNA damage, oxidant production, and early atherogenesis have been recently established and it is likely that aspects of atherosclerotic risk are metabolic in nature. Here we present a novel method through which mitochondrial bioenergetics can be assessed from whole aorta tissue. This method does not require mitochondrial isolation or cell culture and it allows for multiple technical replicates and expedient measurement. This procedure facilitates quantitative bioenergetic analysis and can provide great utility in better understanding the link between mitochondria, metabolism, and atherogenesis.

  12. Parameter uncertainty, sensitivity, and sediment coupling in bioenergetics-based food web models

    Energy Technology Data Exchange (ETDEWEB)

    Barron, M.G.; Cacela, D.; Beltman, D. [Hagler Bailly, Boulder, CO (United States)

    1995-12-31

    A bioenergetics-based food web model was developed and calibrated using measured PCB water and sediment concentrations in two Great Lakes food webs: Green Bay, Michigan and Lake Ontario. The model incorporated functional based trophic levels and sediment, water, and food chain exposures of PCBs to aquatic biota. Sensitivity analysis indicated the parameters with the greatest influence on PCBs in top predators were lipid content of plankton and benthos, planktivore assimilation efficiency, Kow, prey selection, and ambient temperature. Sediment-associated PCBs were estimated to contribute over 90% of PCBs in benthivores and less than 50% in piscivores. Ranges of PCB concentrations in top predators estimated by Monte Carlo simulation incorporating parameter uncertainty were within one order of magnitude of modal values. Model applications include estimation of exceedences of human and ecological thresholds. The results indicate that point estimates from bioenergetics-based food web models have substantial uncertainty that should be considered in regulatory and scientific applications.

  13. Mitochondria: 3-bromopyruvate vs. mitochondria? A small molecule that attacks tumors by targeting their bioenergetic diversity.

    Science.gov (United States)

    Galina, Antonio

    2014-09-01

    Enhanced glycolysis, the classic bioenergetic phenotype of cancer cells was described by Otto Warburg approximately 90 years ago. However, the Warburg hypothesis does not necessarily imply mitochondrial dysfunction. The alkyl-halogen, 3-bromopyruvate (3BP), would not be expected to have selective targets for cancer therapy due to its high potential reactivity toward many SH side groups. Contrary to predictions, 3BP interferes with glycolysis and oxidative phosphorylation in cancer cells without side effects in normal tissues. The mitochondrial hexokinase II has been claimed as the main target. This "Organelle in focus" article presents a historical view of the use of 3BP in biochemistry and its effects on ATP-producing pathways of cancer cells. I will discuss how the alkylated enzymes contribute to the cooperative collapse of mitochondria and apoptosis. Perspectives for targeting 3BP to bioenergetics enzymes for cancer treatment will be considered.

  14. Real-Time Measurement of Host Bioenergetics During Mycobacterium Tuberculosis Infection

    Science.gov (United States)

    2015-05-01

    control. We adapted a novel technology termed metabolic flux analysis and demonstrated that MtbΔwhiB3, unlike wt Mtb and the complemented strain...successfully adapted metabolic flux analysis using a Seahorse XF96 metabolic flux analyzer to study Mycobacterium tuberculosis energy metabolism in an...carbon sources and CCCP were added. 10 To determine the influence of WhiB3 on mycobacterial bioenergetics, metabolic flux of wt Mtb

  15. Acute bioenergetic intervention or pharmacological preconditioning protects neuron against ischemic injury

    OpenAIRE

    2013-01-01

    Although acute ischemic stroke has high mortality and morbidity rate but yet still has very limited treatment. In this study we have tested the concept of neuron protection by acute bioenergetic intervention or by pharmacological preconditioning with natural antioxidants. Adenosine triphosphate (ATP), pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used as bioenergy stabilizer. We induced ATP depletion model by incubating cells with media added with ATP-depleting ag...

  16. Development of a bioenergetics model for the threespine stickleback Gasterosteus aculeatus

    Science.gov (United States)

    Hovel, Rachel A.; Beauchamp, David A.; Hansen, Adam G.; Sorel, Mark H.

    2016-01-01

    The Threespine Stickleback Gasterosteus aculeatus is widely distributed across northern hemisphere ecosystems, has ecological influence as an abundant planktivore, and is commonly used as a model organism, but the species lacks a comprehensive model to describe bioenergetic performance in response to varying environmental or ecological conditions. This study parameterized a bioenergetics model for the Threespine Stickleback using laboratory measurements to determine mass- and temperature-dependent functions for maximum consumption and routine respiration costs. Maximum consumption experiments were conducted across a range of temperatures from 7.5°C to 23.0°C and a range of fish weights from 0.5 to 4.5 g. Respiration experiments were conducted across a range of temperatures from 8°C to 28°C. Model sensitivity was consistent with other comparable models in that the mass-dependent parameters for maximum consumption were the most sensitive. Growth estimates based on the Threespine Stickleback bioenergetics model suggested that 22°C is the optimal temperature for growth when food is not limiting. The bioenergetics model performed well when used to predict independent, paired measures of consumption and growth observed from a separate wild population of Threespine Sticklebacks. Predicted values for consumption and growth (expressed as percent body weight per day) only deviated from observed values by 2.0%. Our model should provide insight into the physiological performance of this species across a range of environmental conditions and be useful for quantifying the trophic impact of this species in food webs containing other ecologically or economically important species.

  17. Impaired Myocardial Bioenergetics in HFpEF and the Role of Antioxidants

    OpenAIRE

    Hiebert, John B.; Shen, Qiuhua; Thimmesch, Amanda; Pierce, Janet

    2016-01-01

    Heart failure with preserved ejection fraction (HFpEF) is a significant cardiovascular condition for more than 50% of patients with heart failure. Currently, there is no effective treatment to decrease morbidity and mortality rates associated with HFpEF because of its pathophysiological heterogeneity. Recent evidence shows that deficiency in myocardial bioenergetics is one of the key pathophysiological factors contributing to diastolic dysfunction in HFpEF. Another known mechanism for HFpEF i...

  18. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2011-03-01

    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  19. A comparison of maximal bioenergetic enzyme activities obtained with commonly used homogenization techniques.

    Science.gov (United States)

    Grace, M; Fletcher, L; Powers, S K; Hughes, M; Coombes, J

    1996-12-01

    Homogenization of tissue for analysis of bioenergetic enzyme activities is a common practice in studies examining metabolic properties of skeletal muscle adaptation to disease, aging, inactivity or exercise. While numerous homogenization techniques are in use today, limited information exists concerning the efficacy of specific homogenization protocols. Therefore, the purpose of this study was to compare the efficacy of four commonly used approaches to homogenizing skeletal muscle for analysis of bioenergetic enzyme activity. The maximal enzyme activity (Vmax) of citrate synthase (CS) and lactate dehydrogenase (LDH) were measured from homogenous muscle samples (N = 48 per homogenization technique) and used as indicators to determine which protocol had the highest efficacy. The homogenization techniques were: (1) glass-on-glass pestle; (2) a combination of a mechanical blender and a teflon pestle (Potter-Elvehjem); (3) a combination of the mechanical blender and a biological detergent; and (4) the combined use of a mechanical blender and a sonicator. The glass-on-glass pestle homogenization protocol produced significantly higher (P < 0.05) enzyme activities compared to all other protocols for both enzymes. Of the four protocols examined, the data demonstrate that the glass-on-glass pestle homogenization protocol is the technique of choice for studying bioenergetic enzyme activity in skeletal muscle.

  20. Design and fine-tuning redox potentials of metalloproteins involved in electron transfer in bioenergetics.

    Science.gov (United States)

    Hosseinzadeh, Parisa; Lu, Yi

    2016-05-01

    Redox potentials are a major contributor in controlling the electron transfer (ET) rates and thus regulating the ET processes in the bioenergetics. To maximize the efficiency of the ET process, one needs to master the art of tuning the redox potential, especially in metalloproteins, as they represent major classes of ET proteins. In this review, we first describe the importance of tuning the redox potential of ET centers and its role in regulating the ET in bioenergetic processes including photosynthesis and respiration. The main focus of this review is to summarize recent work in designing the ET centers, namely cupredoxins, cytochromes, and iron-sulfur proteins, and examples in design of protein networks involved these ET centers. We then discuss the factors that affect redox potentials of these ET centers including metal ion, the ligands to metal center and interactions beyond the primary ligand, especially non-covalent secondary coordination sphere interactions. We provide examples of strategies to fine-tune the redox potential using both natural and unnatural amino acids and native and nonnative cofactors. Several case studies are used to illustrate recent successes in this area. Outlooks for future endeavors are also provided. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

  1. Effects of high fat diets on rodent liver bioenergetics and oxidative imbalance

    Directory of Open Access Journals (Sweden)

    Pâmela A. Kakimoto

    2016-08-01

    Full Text Available Human metabolic diseases can be mimicked in rodents by using dietary interventions such as high fat diets (HFD. Nonalcoholic fatty liver disease (NAFLD develops as a result of HFD and the disease may progress in a manner involving increased production of oxidants. The main intracellular source of these oxidants are mitochondria, which are also responsible for lipid metabolism and thus widely recognized as important players in the pathology and progression of steatosis. Here, we review publications that study redox and bioenergetic effects of HFD in the liver. We find that dietary composition and protocol implementations vary widely, as do the results of these dietary interventions. Overall, all HFD promote steatosis, changes in β-oxidation, generation and consequences of oxidants, while effects on body weight, insulin signaling and other bioenergetic parameters are more variable with the experimental models adopted. Our review provides a broad analysis of the bioenergetic and redox changes promoted by HFD as well as suggestions for changes and specifications in methodologies that may help explain apparent disparities in the current literature.

  2. Deactivation of the Parahippocampal Gyrus Preceding Auditory Hallucinations in Schizophrenia

    NARCIS (Netherlands)

    Diederen, Kelly M. J.; Neggers, Sebastiaan F. W.; Daalman, Kirstin; Blom, Jan Dirk; Goekoop, Rutger; Kahn, Rene S.; Sommer, Iris E. C.

    2010-01-01

    Objective: Activation in a network of language-related regions has been reported during auditory verbal hallucinations. It remains unclear, however, how this activation is triggered. Identifying brain regions that show significant signal changes preceding auditory hallucinations might reveal the ori

  3. Impact of preceding crop on alfalfa competitiveness with weeds

    Science.gov (United States)

    Organic producers would like to include no-till practices in their farming systems. We are seeking to develop a continuous no-till system for organic farming, based on a complex rotation that includes a 3-year sequence of alfalfa. In this study, we evaluated impact of preceding crop on weed infest...

  4. Metrical expectations from preceding prosody influence perception of lexical stress.

    Science.gov (United States)

    Brown, Meredith; Salverda, Anne Pier; Dilley, Laura C; Tanenhaus, Michael K

    2015-04-01

    Two visual-world experiments tested the hypothesis that expectations based on preceding prosody influence the perception of suprasegmental cues to lexical stress. The results demonstrate that listeners' consideration of competing alternatives with different stress patterns (e.g., 'jury/gi'raffe) can be influenced by the fundamental frequency and syllable timing patterns across material preceding a target word. When preceding stressed syllables distal to the target word shared pitch and timing characteristics with the first syllable of the target word, pictures of alternatives with primary lexical stress on the first syllable (e.g., jury) initially attracted more looks than alternatives with unstressed initial syllables (e.g., giraffe). This effect was modulated when preceding unstressed syllables had pitch and timing characteristics similar to the initial syllable of the target word, with more looks to alternatives with unstressed initial syllables (e.g., giraffe) than to those with stressed initial syllables (e.g., jury). These findings suggest that expectations about the acoustic realization of upcoming speech include information about metrical organization and lexical stress and that these expectations constrain the initial interpretation of suprasegmental stress cues. These distal prosody effects implicate online probabilistic inferences about the sources of acoustic-phonetic variation during spoken-word recognition.

  5. Cross-frequency interactions in the precedence effect.

    Science.gov (United States)

    Shinn-Cunningham, B G; Zurek, P M; Durlach, N I; Clifton, R K

    1995-07-01

    This paper concerns the extent to which the precedence effect is observed when leading and lagging sounds occupy different spectral regions. Subjects, listening under headphones, were asked to match the intracranial lateral position of an acoustic pointer to that of a test stimulus composed of two binaural noise bursts with asynchronous onsets, parametrically varied frequency content, and different interaural delays. The precedence effect was measured by the degree to which the interaural delay of the matching pointer was independent of the interaural delay of the lagging noise burst in the test stimulus. The results, like those of Blauert and Divenyi [Acustica 66, 267-274 (1988)], show an asymmetric frequency effect in which the lateralization influence of a lagging high-frequency burst is almost completely suppressed by a leading low-frequency burst, whereas a lagging low-frequency burst is weighted equally with a leading high-frequency burst. This asymmetry is shown to be the result of an inherent low-frequency dominance that is seen even with simultaneous bursts. When this dominance is removed (by attenuating the low-frequency burst) the precedence effect operates with roughly equal strength both upward and downward in frequency. Within the scope of the current study (with lateralization achieved through the use of interaural time differences alone, stimuli from only two frequency bands, and only three subjects performing in all experiments), these results suggest that the precedence effect arises from a fairly central processing stage in which information is combined across frequency.

  6. Does Operational Diagnosis of Schizophrenia Significantly Impact Intellectual Deficits in Psychotic Disorders?

    Science.gov (United States)

    Kitamura, H.; Shioiri, T.; Itoh, M.; Sato, Y.; Shichiri, K.; Someya, T.

    2007-01-01

    Background: Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Methods: Using Wechsler Adult…

  7. Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients.

    Science.gov (United States)

    Kramer, Philip A; Chacko, Balu K; George, David J; Zhi, Degui; Wei, Chih-Cheng; Dell'Italia, Louis J; Melby, Spencer J; George, James F; Darley-Usmar, Victor M

    2015-07-01

    Monitoring the bioenergetics of leucocytes is now emerging as an important approach in translational research to detect mitochondrial dysfunction in blood or other patient samples. Using the mitochondrial stress test, which involves the sequential addition of mitochondrial inhibitors to adherent leucocytes, we have calculated a single value, the Bioenergetic Health Index (BHI), which represents the mitochondrial function in cells isolated from patients. In the present report, we assess the BHI of monocytes isolated from the post-operative blood and post-operative pericardial fluid (PO-PCF) from patients undergoing cardiac surgery. Analysis of the bioenergetics of monocytes isolated from patients' PO-PCF revealed a profound decrease in mitochondrial function compared with monocytes isolated from their blood or from healthy controls. Further, patient blood monocytes showed no significant difference in the individual energetic parameters from the mitochondrial stress test but, when integrated into the BHI evaluation, there was a significant decrease in BHI compared with healthy control monocytes. These data support the utility of BHI measurements in integrating the individual parameters from the mitochondrial stress test into a single value. Supporting our previous finding that the PO-PCF is pro-oxidant, we found that exposure of rat cardiomyocytes to PO-PCF caused a significant loss of mitochondrial membrane potential and increased reactive oxygen species (ROS). These findings support the hypothesis that integrated measures of bioenergetic health could have prognostic and diagnostic value in translational bioenergetics.

  8. ARMA-GARCH Model and temporal precedence between stock indices

    Directory of Open Access Journals (Sweden)

    Diego Garcia Angelico

    2016-03-01

    Full Text Available Faced with the need for risk valuation of financial assets, investors demand sophisticated methods of modeling that can judge the variability of their investments. At the same time, financial globalization has been characterized by common movements and trends between different international markets. In this context, the main objective of this paper was to model the statistical volatility of the Bovespa Index (Ibovespa and the Dow Jones Industrial Average Index, using ARMA-GARCH adjustments, in addition to checking the existence of a long- -term balance and temporal precedence between these variables, using the Johansen co-integration and Granger causality tests, respectively. The results established a higher heterogeneous variance for Ibovespa and the existence of temporal precedence for the Dow Jones Index, despite the absence of any long-term balance between the series. It is understood that the latter behavior may have been caused by the existing difference between the conditional heteroscedasticity of each index.

  9. Human electrophysiological examination of buildup of the precedence effect.

    Science.gov (United States)

    Dimitrijevic, Andrew; Stapells, David R

    2006-07-31

    Event-related potential correlates of the buildup of precedence effect were examined. Buildup is a type of precedence effect illusion in which perception changes (from hearing two clicks to hearing one click) during a click train. Buildup occurs faster for right-leading than left-leading clicks. Continuous click trains that changed leading sides every 15 clicks were presented. Event-related potential N1 amplitudes became smaller with click train for right-leading only. N1 latency decreased with click trains. Mismatch negativity was seen after lead-lag sides were changed. When the perceived change differed in location (left-to-right), mismatch negativity peaked earlier than when the perceived change differed in location and number of clicks (right-to-left). Results suggest that buildup relates to: N1 refractoriness, event-related potential 'lead domination' and mismatch negativity differences.

  10. A Visual lexicon to Handle Semantic Similarity in Design precedents

    DEFF Research Database (Denmark)

    Restrepo-Giraldo, John Dairo

    2007-01-01

    . The shaping and establishing of this image is supported by creating sketches, collages, models and other types of external representations. This process is largely supported by the use of design precedents. In design, precedents provide the frame of reference for the development of new solution principles...... for visual information. The reason is that the algorithms available cannot recognize what the image contains (in semantic terms) but humans can, and with great facility. This ability was reflected in the searching process of the designers in our studies. It is very natural for them to expect living room......The adequate use of existing knowledge, and not only the creation of completely new solutions, is also an important part of creative thinking. When conceiving a solution, designers oftentimes report having a vague image of the form that will embody the final solution to the design task at hand...

  11. Cardiac tamponade preceding skin involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    L. Bozzola

    2011-09-01

    Full Text Available The frequency of pericardial involvement in Systemic Sclerosis (SSc is high on autoptic or echocardiographic studies, but the clinical recognition of pericarditis with or without effusion is rare. We describe a case of a 71-year-old female with no previous history of heart disease, who presented with a large pericardial effusion and tamponade that required pericardial drain. She had suffered from Raynaud’s phenomenon since 25 years. Six weeks after hospital discharge she complained of skin hardening on left leg. Pericardial tamponade is a very rare manifestation of SSc and occurs both early or late in the course of the disease, but in our case it preceded the recognition of scleroderma. We have only identified two other cases of pericardial effusion preceding cutaneous involvement in scleroderma.

  12. Motility precedes egress of malaria parasites from oocysts

    Science.gov (United States)

    Klug, Dennis; Frischknecht, Friedrich

    2017-01-01

    Malaria is transmitted when an infected Anopheles mosquito deposits Plasmodium sporozoites in the skin during a bite. Sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. We found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (TRP1) is important for oocyst egress and salivary gland invasion, and hence for the transmission of malaria. We imaged the release of sporozoites from oocysts in situ, which was preceded by active motility. Parasites lacking TRP1 failed to migrate within oocysts and did not egress, suggesting that TRP1 is a vital component of the events that precede intra-oocyst motility and subsequently sporozoite egress and salivary gland invasion. DOI: http://dx.doi.org/10.7554/eLife.19157.001 PMID:28115054

  13. Explicit Precedence Constraints in Safety-Critical Java

    DEFF Research Database (Denmark)

    Puffitsch, Wolfgang; Noulard, Eric; Pagetti, Claire

    2013-01-01

    Safety-critical Java (SCJ) aims at making the amenities of Java available for the development of safety-critical applications. The multi-rate synchronous language Prelude facilitates the specification of the communication and timing requirements of complex real-time systems. This paper combines...... to provide explicit support for precedence constraints. We present the considerations behind the design of this extension and discuss our experiences with a first prototype implementation based on the SCJ implementation of the Java Optimized Processor....

  14. Diversity and Physiology of Siderophilic Cyanobacteria: Implication for the Bioenergetics

    Science.gov (United States)

    Brown, Igor; Sarkisova, Svetlana; Thomas-Kerprta, Kathie; McKay, David S.

    2008-01-01

    . Phylogenetic analysis of 16S rRNA genes indicated that 6 of 12 new isolates examined could not be placed within established CB genera. Some of the isolates exhibited pronounced requirements for elevated iron concentrations, with maximum growth rates observed when 0.4-1 mM Fe(3+) was present in the media. However, the pronounced effect of iron limitation on the proliferation of siderophilic CB can be observed only after several passages through iron "free" media. TEM studies of several species of siderophilic CB revealed that the cultures JSC-3 and -11 are probably capable of some sort of pinocytosis of precipitated iron. This phenomenon may explain high tolerance of siderophilic CB to iron deficit. We also found that the stimulation of the growth of siderophilic CB by oxidized iron is accompanied by the decrease of O2 evolution by some species after addition Fe(2+) in iron "free" medium.

  15. Attention deficit hyperactivity disorder (ADHD)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001551.htm Attention deficit hyperactivity disorder To use the sharing features on this page, please enable JavaScript. Attention deficit hyperactivity disorder (ADHD) is a problem caused by the presence ...

  16. Bioenergetics model for estimating food requirements of female Pacific walruses (Odobenus rosmarus divergens)

    Science.gov (United States)

    Noren, S.R.; Udevitz, M.S.; Jay, C.V.

    2012-01-01

    Pacific walruses Odobenus rosmarus divergens use sea ice as a platform for resting, nursing, and accessing extensive benthic foraging grounds. The extent of summer sea ice in the Chukchi Sea has decreased substantially in recent decades, causing walruses to alter habitat use and activity patterns which could affect their energy requirements. We developed a bioenergetics model to estimate caloric demand of female walruses, accounting for maintenance, growth, activity (active in-water and hauled-out resting), molt, and reproductive costs. Estimates for non-reproductive females 0–12 yr old (65−810 kg) ranged from 16359 to 68960 kcal d−1 (74−257 kcal d−1 kg−1) for years with readily available sea ice for which we assumed animals spent 83% of their time in water. This translated into the energy content of 3200–5960 clams per day, equivalent to 7–8% and 14–9% of body mass per day for 5–12 and 2–4 yr olds, respectively. Estimated consumption rates of 12 yr old females were minimally affected by pregnancy, but lactation had a large impact, increasing consumption rates to 15% of body mass per day. Increasing the proportion of time in water to 93%, as might happen if walruses were required to spend more time foraging during ice-free periods, increased daily caloric demand by 6–7% for non-lactating females. We provide the first bioenergetics-based estimates of energy requirements for walruses and a first step towards establishing bioenergetic linkages between demography and prey requirements that can ultimately be used in predicting this population’s response to environmental change.

  17. Systems analysis of bioenergetics and growth of the extreme halophile Halobacterium salinarum.

    Directory of Open Access Journals (Sweden)

    Orland Gonzalez

    2009-04-01

    Full Text Available Halobacterium salinarum is a bioenergetically flexible, halophilic microorganism that can generate energy by respiration, photosynthesis, and the fermentation of arginine. In a previous study, using a genome-scale metabolic model, we have shown that the archaeon unexpectedly degrades essential amino acids under aerobic conditions, a behavior that can lead to the termination of growth earlier than necessary. Here, we further integratively investigate energy generation, nutrient utilization, and biomass production using an extended methodology that accounts for dynamically changing transport patterns, including those that arise from interactions among the supplied metabolites. Moreover, we widen the scope of our analysis to include phototrophic conditions to explore the interplay between different bioenergetic modes. Surprisingly, we found that cells also degrade essential amino acids even during phototropy, when energy should already be abundant. We also found that under both conditions considerable amounts of nutrients that were taken up were neither incorporated into the biomass nor used as respiratory substrates, implying the considerable production and accumulation of several metabolites in the medium. Some of these are likely the products of forms of overflow metabolism. In addition, our results also show that arginine fermentation, contrary to what is typically assumed, occurs simultaneously with respiration and photosynthesis and can contribute energy in levels that are comparable to the primary bioenergetic modes, if not more. These findings portray a picture that the organism takes an approach toward growth that favors the here and now, even at the cost of longer-term concerns. We believe that the seemingly "greedy" behavior exhibited actually consists of adaptations by the organism to its natural environments, where nutrients are not only irregularly available but may altogether be absent for extended periods that may span several years

  18. The evolving role of the NAD+/nicotinamide metabolome in skin homeostasis, cellular bioenergetics, and aging.

    Science.gov (United States)

    Oblong, John E

    2014-11-01

    Human skin is exposed to daily environmental insults, particularly solar radiation, that triggers a range of molecular responses. These perturbations to the normal homeostatic state can lead to cellular dysfunction and, ultimately, impacts tissue integrity and accelerates skin aging (photoaging). One of the responses is increased oxidative stress which has been shown to disrupt cellular bioenergetics. This can be detected by depletion of the nucleotide energy metabolites NAD+ and ATP as both an acute transient decrease and, over time, a more permanent chronic reduction due in part to cumulative damage of mitochondria. NAD+ and its primary precursor nicotinamide have been known for some time to impact skin homeostasis based on linkages to dietary requirements, treatment of various inflammatory conditions, photoaging, and prevention of cancer. Cellular NAD+ pools are known to be lower in aged skin and treatment with nicotinamide is hypothesized to restore these levels, thereby mitigating cellular bioenergetics dysfunction. In dermal fibroblasts, nicotinamide is able to protect against oxidative stress to glycolysis, oxidative phosphorylation as well as increase mitochondrial efficiency via sirtuin-dependent selective mitophagy. Recent research has found that NAD+ cellular pools are more dynamic than previously thought, oscillating in tandem with free nicotinamide, and serves as a regulatory point and feedback loop in cellular metabolism regulation, maintenance of mitochondrial efficiency, and circadian rhythmicity. Since UV-induced oxidative stress in skin can disrupt these processes, continued molecular understanding of the role of NAD+ and nicotinamide in skin biology is important to identify interventions that would help maintain its normal homeostatic functions and efficient cellular bioenergetics.

  19. Bioenergetics of Stromal Cells As a Predictor of Aggressive Prostate Cancer

    Science.gov (United States)

    2015-09-01

    easily measured by detailed bioenergetic profiling using XF-Analyzer. These differences obtained by metabolic phenotyping of cancer and CAFs may have...malignant characteristics (RWPE-1<WPE-NA22<WPE-NB14<WPE-NB11<WPE-NB26) using high-throughput respirometry. Extracellular flux (XF) analyzer (Seahorse...glycolytic stress test (MiST and GlyST). Cells were plated at an optimal cell density which was determined for each cell line before the analysis and

  20. Some Aspects of the Origin and Early Evolution of Bioenergetic Processes

    Science.gov (United States)

    Masinovský, Z.

    1984-12-01

    Model experiments demonstrating some possibilities of the primitive bioenergetics were performed. Comparing the catalytic properties of heme and hemoproteinoid in electron transfer reactions, it was shown that hemin acts as an active dark catalyst, whereas hemoproteinoid is a photosensitizer of these processes. The heme-containing enzyme, peroxidase/or even the hemoproteinoid/is also able to provide the phosphorylation of different substrates. It is proposed, that the phosphorylation is initiated by a hydroxyl radical occuring in the peroxidase reaction. We believe that those reactions could play a role in prebiotic energetics by coupling the electron transfer with the phosphorylation of suitable substrates.

  1. Constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms. Final report, 1 September 1988--30 June 1990

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, J.R.

    1992-11-01

    The constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms were quantified. During this project we conducted studies: to determine the role of incubation temperature on the post-hatching growth rate of the snapping turtle, Chelydra serpentina; to establish the rate of energy expenditure of the slider turtle, Trachemys scripta, in the field; to determine the field metabolic rates, body temperatures and selected microclimates of the box turtle, Terrapene carolina, and to measure the effect of diet type on the consumption rate, digestion rate and digestive efficiency of adult T. scripta. We also completed our research on the three-dimensional bioenergetic climate space for freshwater turtles.

  2. APOE polymorphisms influence longitudinal lipid trends preceding intracerebral hemorrhage

    Science.gov (United States)

    Phuah, Chia-Ling; Raffeld, Miriam R.; Ayres, Alison M.; Gurol, M. Edip; Viswanathan, Anand; Greenberg, Steven M.; Biffi, Alessandro; Rosand, Jonathan

    2016-01-01

    Objective: We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk. Methods: We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele–specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects. Results: A total of 124 ICH cases were analyzed. APOE ε4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: −7.30 mg/dL/mo, p = 0.0035; LDL: −8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ε2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends. Conclusions: APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype–specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk. PMID:27433544

  3. Vitiligo disease triggers: psychological stressors preceding the onset of disease.

    Science.gov (United States)

    Silverberg, Jonathan I; Silverberg, Nanette B

    2015-05-01

    Vitiligo is the loss of skin pigmentation caused by autoimmune destruction of melanocytes. Little is known about the impact of psychological stressors preceding vitiligo onset on symptoms associated with vitiligo and the extent of disease. We performed a questionnaire-based study of 1541 adults with vitiligo to evaluate the impact of psychological stressors in this patient population. Psychological stressors should be considered as potential disease triggers in vitiligo patients, and screening of vitiligo patients for psychological stressors and associated symptoms should be included in routine assessment.

  4. USING PRECEDENTS FOR REDUCTION OF DECISION TREE BY GRAPH SEARCH

    Directory of Open Access Journals (Sweden)

    I. A. Bessmertny

    2015-01-01

    Full Text Available The paper considers the problem of mutual payment organization between business entities by means of clearing that is solved by search of graph paths. To reduce the decision tree complexity a method of precedents is proposed that consists in saving the intermediate solution during the moving along decision tree. An algorithm and example are presented demonstrating solution complexity coming close to a linear one. The tests carried out in civil aviation settlement system demonstrate approximately 30 percent shortage of real money transfer. The proposed algorithm is planned to be implemented also in other clearing organizations of the Russian Federation.

  5. Design of a Secure RFID Authentication Scheme Preceding Market Transactions

    Directory of Open Access Journals (Sweden)

    Chin-Ling Chen

    2011-01-01

    Full Text Available In recent years, as RFID reader equipment is ever more widely deployed in handled devices, the importance of security problems among RFID reader, tags and server have obviously gained increased attention. However, there are still many security issues preceding transactions; these issues are well worth discussing. In this paper, we propose a novel authentication scheme, conforming EPC C1G2 standards, at a low implementation cost for market application. In order to achieve mutual authentication, the proposed scheme integrates fingerprint biometrics, related cryptology and a hash function mechanism to ensure the security of the transmitted messages. The proposed scheme also can resist known attacks.

  6. Cancer preceding Wegener's granulomatosis: a case-control study

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Sørensen, Inge Juul;

    2009-01-01

    OBJECTIVE: To investigate whether patients with WG have an increased risk of malignancies prior to and/or around the time of the vasculitis diagnosis, as suggested by previous studies. METHODS: A total of 293 WG patients were included in the study. Ten gender- and age-matched controls were selected...... interval (OR 4.0; 95% CI 1.4, 12). CONCLUSIONS: We did not find clear evidence of an increased prevalence of preceding cancer in our WG cohort, indicating that shared risk factors are of minor importance for the excess of malignancies that occur in WG patients after the vasculitis diagnosis. Furthermore...

  7. Cognitive Impairments Preceding and Outlasting Autoimmune Limbic Encephalitis

    Directory of Open Access Journals (Sweden)

    Robert Gross

    2016-01-01

    Full Text Available Mild cognitive impairment (MCI can be the initial manifestation of autoimmune limbic encephalitis (ALE, a disorder that at times presents a diagnostic challenge. In addition to memory impairment, clinical features that might suggest this disorder include personality changes, agitation, insomnia, alterations of consciousness, and seizures. Once recognized, ALE typically responds to treatment with immune therapies, but long-term cognitive deficits may remain. We report two cases of patients with MCI who were ultimately diagnosed with ALE with antibodies against the voltage gated potassium channel complex. Months after apparent resolution of their encephalitides, both underwent neuropsychological testing, which demonstrated persistent cognitive deficits, primarily in the domains of memory and executive function, for cases 1 and 2, respectively. A brief review of the literature is included.

  8. Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy

    Science.gov (United States)

    Long, Jianyin; Badal, Shawn S.; Ye, Zengchun; Wang, Yin; Ayanga, Bernard A.; Galvan, Daniel L.; Green, Nathanael H.; Chang, Benny H.; Overbeek, Paul A.

    2016-01-01

    The regulatory roles of long noncoding RNAs (lncRNAs) in transcriptional coactivators are still largely unknown. Here, we have shown that the peroxisome proliferator–activated receptor γ (PPARγ) coactivator α (PGC-1α, encoded by Ppargc1a) is functionally regulated by the lncRNA taurine-upregulated gene 1 (Tug1). Further, we have described a role for Tug1 in the regulation of mitochondrial function in podocytes. Using a murine model of diabetic nephropathy (DN), we performed an unbiased RNA-sequencing (RNA-seq) analysis of kidney glomeruli and identified Tug1 as a differentially expressed lncRNA in the diabetic milieu. Podocyte-specific overexpression (OE) of Tug1 in diabetic mice improved the biochemical and histological features associated with DN. Unexpectedly, we found that Tug1 OE rescued the expression of PGC-1α and its transcriptional targets. Tug1 OE was also associated with improvements in mitochondrial bioenergetics in the podocytes of diabetic mice. Mechanistically, we found that the interaction between Tug1 and PGC-1α promotes the binding of PGC-1α to its own promoter. We identified a Tug1-binding element (TBE) upstream of the Ppargc1a gene and showed that Tug1 binds with the TBE to enhance Ppargc1a promoter activity. These findings indicate that a direct interaction between PGC-1α and Tug1 modulates mitochondrial bioenergetics in podocytes in the diabetic milieu. PMID:27760051

  9. Homeostatic bioenergetic network regulation – a novel concept to avoid pharmacoresistance in epilepsy

    Science.gov (United States)

    Boison, Detlev; Masino, Susan A.; Geiger, Jonathan D.

    2011-01-01

    Introduction Despite epilepsy being one of the most prevalent neurological disorders, one third of all patients with epilepsy cannot adequately be treated with available antiepileptic drugs. One of the significant causes for the failure of conventional pharmacotherapeutic treatment is the development of pharmacoresistance in many forms of epilepsy. The problem of pharmacoresistance has called for the development of new conceptual strategies that improve future drug development efforts. Areas covered A thorough review of the recent literature on pharmacoresistance in epilepsy was completed and select examples were chosen to highlight the mechanisms of pharmacoresistance in epilepsy and to demonstrate how those mechanistic findings might lead to improved treatment of pharmacoresistant epilepsy. The reader will gain a thorough understanding of pharmacoresistance in epilepsy and an appreciation of the limitations of conventional drug development strategies. Expert opinion Conventional drug development efforts aim to achieve specificity of symptom control by enhancing the selectivity of drugs acting on specific downstream targets; this conceptual strategy bears the undue risk of development of pharmacoresistance. Modulation of homeostatic bioenergetic network regulation is a novel conceptual strategy to affect whole neuronal networks synergistically by mobilizing multiple endogenous biochemical and receptor-dependent molecular pathways. In our expert opinion we conclude that homeostatic bioenergetic network regulation might thus be used as an innovative strategy for the control of pharmacoresistant seizures. Recent focal adenosine augmentation strategies support the feasibility of this strategy. PMID:21731576

  10. Bioenergetic evaluation of diel vertical migration by bull trout (Salvelinus confluentus) in a thermally stratified reservoir

    Science.gov (United States)

    Eckmann, Madeleine; Dunham, Jason; Connor, Edward J.; Welch, Carmen A.

    2016-01-01

    Many species living in deeper lentic ecosystems exhibit daily movements that cycle through the water column, generally referred to as diel vertical migration (DVM). In this study, we applied bioenergetics modelling to evaluate growth as a hypothesis to explain DVM by bull trout (Salvelinus confluentus) in a thermally stratified reservoir (Ross Lake, WA, USA) during the peak of thermal stratification in July and August. Bioenergetics model parameters were derived from observed vertical distributions of temperature, prey and bull trout. Field sampling confirmed that bull trout prey almost exclusively on recently introduced redside shiner (Richardsonius balteatus). Model predictions revealed that deeper (>25 m) DVMs commonly exhibited by bull trout during peak thermal stratification cannot be explained by maximising growth. Survival, another common explanation for DVM, may have influenced bull trout depth use, but observations suggest there may be additional drivers of DVM. We propose these deeper summertime excursions may be partly explained by an alternative hypothesis: the importance of colder water for gametogenesis. In Ross Lake, reliance of bull trout on warm water prey (redside shiner) for consumption and growth poses a potential trade-off with the need for colder water for gametogenesis.

  11. A method for assessing mitochondrial bioenergetics in whole white adipose tissues.

    Science.gov (United States)

    Dunham-Snary, Kimberly J; Sandel, Michael W; Westbrook, David G; Ballinger, Scott W

    2014-01-01

    Obesity is a primary risk factor for numerous metabolic diseases including metabolic syndrome, type II diabetes (T2DM), cardiovascular disease and cancer. Although classically viewed as a storage organ, the field of white adipose tissue biology is expanding to include the consideration of the tissue as an endocrine organ and major contributor to overall metabolism. Given its role in energy production, the mitochondrion has long been a focus of study in metabolic dysfunction and a link between the organelle and white adipose tissue function is likely. Herein, we present a novel method for assessing mitochondrial bioenergetics from whole white adipose tissue. This method requires minimal manipulation of tissue, and eliminates the need for cell isolation and culture. Additionally, this method overcomes some of the limitations to working with transformed and/or isolated primary cells and allows for results to be obtained more expediently. In addition to the novel method, we present a comprehensive statistical analysis of bioenergetic data as well as guidelines for outlier analysis.

  12. Impact of oxidative stress on Acanthamoeba castellanii mitochondrial bioenergetics depends on cell growth stage.

    Science.gov (United States)

    Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Antos-Krzeminska, Nina; Jarmuszkiewicz, Wieslawa

    2011-06-01

    Addition of a moderate (1.4 mM) concentration of H(2)O(2) to protozoon Acanthamoeba castellanii cell cultures at different growth phases caused a different response to oxidative stress. H(2)O(2) treatment of exponentially growing cells significantly delayed their growth; however, in mitochondria isolated from these cells, no damage to their bioenergetic function was observed. In contrast, addition of H(2)O(2) to A. castellanii cells approaching the stationary phase did not influence their growth and viability while seriously affecting mitochondrial bioenergetic function. Although mitochondrial integrity was maintained, oxidative damage was revealed in the reduction of cytochrome pathway activity, uncoupling protein activity, and the efficiency of oxidative phosphorylation as well as the membrane potential and the endogenous ubiquinone reduction level of the resting state. An increase in the alternative oxidase protein level and activity as well as an increase in the membranous ubiquinone content were observed in mitochondria isolated from late H(2)O(2)-treated cells. For the first time, the regulation of ubiquinone content in the inner mitochondrial membrane is shown to play a role in the response to oxidative stress. A physiological role for the higher activity of the alternative oxidase in response to oxidative stress in unicellular organisms, such as amoeba A. castellanii, is discussed.

  13. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Directory of Open Access Journals (Sweden)

    Bruno Chausse

    Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  14. Effect of Feeding-Fasting Cycles on Oxygen Consumption and Bioenergetics of Yellow Perch

    Science.gov (United States)

    Chipps, Steven R.; Travis W. Schaeffer,; Daniel E. Spengler,; Casey W. Schoenebeck,; Michael L. Brown,

    2012-01-01

    We measured growth and oxygen consumption of age-1 yellow perch Perca flavescenssubjected to ad libitum (control) or variable feeding cycles of 2 (i.e., 2 d of feed, 2 d of deprivation), 6, or 12 d for a 72-d period. Individual, female yellow perch (initial weight = 51.9 ± 0.9 g [mean ± SE]) were stocked in 110-L aquaria to provide six replicates per treatment and fed measured rations of live fathead minnow Pimephales promelas. Consumption, absolute growth rate, growth efficiency, and oxygen consumption were similar among feeding regimens. However, growth trajectories for fish on the 2-d cycle were significantly lower than other feed–fast cycles. Hyperphagia occurred in all treatments. Bioenergetics model simulations indicated that consumption was significantly underestimated (t = 5.4, df = 4, P = 0.006), while growth was overestimated (t = −5.5, df = 4, P = 0.005) for fish on the 12-d cycle. However, model errors detected between observed and predicted values were low, ranging from −10.1% to +7.8%. We found that juvenile yellow perch exhibited compensatory growth (CG), but none of the feed–fast treatments resulted in growth overcompensation. Likewise, we found no evidence that respiration rates varied with CG, implying that yellow perch bioenergetics models could be used to predict the effects of feeding history and CG response on food consumption and fish growth.

  15. Effects of activity and energy budget balancing algorithm on laboratory performance of a fish bioenergetics model

    Science.gov (United States)

    Madenjian, Charles P.; David, Solomon R.; Pothoven, Steven A.

    2012-01-01

    We evaluated the performance of the Wisconsin bioenergetics model for lake trout Salvelinus namaycush that were fed ad libitum in laboratory tanks under regimes of low activity and high activity. In addition, we compared model performance under two different model algorithms: (1) balancing the lake trout energy budget on day t based on lake trout energy density on day t and (2) balancing the lake trout energy budget on day t based on lake trout energy density on day t + 1. Results indicated that the model significantly underestimated consumption for both inactive and active lake trout when algorithm 1 was used and that the degree of underestimation was similar for the two activity levels. In contrast, model performance substantially improved when using algorithm 2, as no detectable bias was found in model predictions of consumption for inactive fish and only a slight degree of overestimation was detected for active fish. The energy budget was accurately balanced by using algorithm 2 but not by using algorithm 1. Based on the results of this study, we recommend the use of algorithm 2 to estimate food consumption by fish in the field. Our study results highlight the importance of accurately accounting for changes in fish energy density when balancing the energy budget; furthermore, these results have implications for the science of evaluating fish bioenergetics model performance and for more accurate estimation of food consumption by fish in the field when fish energy density undergoes relatively rapid changes.

  16. Bioenergetic relevance of hydrogen sulfide and the interplay between gasotransmitters at human cystathionine β-synthase.

    Science.gov (United States)

    Vicente, João B; Malagrinò, Francesca; Arese, Marzia; Forte, Elena; Sarti, Paolo; Giuffrè, Alessandro

    2016-08-01

    Merely considered as a toxic gas in the past, hydrogen sulfide (H2S) is currently viewed as the third 'gasotransmitter' in addition to nitric oxide (NO) and carbon monoxide (CO), playing a key signalling role in human (patho)physiology. H2S can either act as a substrate or, similarly to CO and NO, an inhibitor of mitochondrial respiration, in the latter case by targeting cytochrome c oxidase (CcOX). The impact of H(2)S on mitochondrial energy metabolism crucially depends on the bioavailability of this gaseous molecule and its interplay with the other two gasotransmitters. The H(2)S-producing human enzyme cystathionine β-synthase (CBS), sustaining cellular bioenergetics in colorectal cancer cells, plays a role in the interplay between gasotransmitters. The enzyme was indeed recently shown to be negatively modulated by physiological concentrations of CO and NO, particularly in the presence of its allosteric activator S-adenosyl-l-methionine (AdoMet). These newly discovered regulatory mechanisms are herein reviewed. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

  17. Changes in autonomic activity preceding onset of nonsustained ventricular tachycardia

    Science.gov (United States)

    Osaka, M.; Saitoh, H.; Sasabe, N.; Atarashi, H.; Katoh, T.; Hayakawa, H.; Cohen, R. J.

    1996-01-01

    Background: The triggering role of the autonomic nervous system in the initiation of ventricular tachycardia has not been established. To investigate the relationship between changes in autonomic activity and the occurrence of nonsustained ventricular tachycardia (NSVT) we examined heart rate variability (HRV) during the 2-hour period preceding spontaneous episodes of NSVT. Twenty-four subjects were identified retrospectively as having had one episode of NSVT during 24-hour Holter ECC recording. Methods: We measured the mean interval between normal heats (meanRR), the standard deviation of the intervals between beats (SD), the percentage of counts of sequential intervals between normal beats with a change of >50 ms (%RR50), the logarithms of low- and high-frequency spectral components (lnLF, lnHF) of HRV for sequential 10-minute segments preceding NSVT. The correlation dimension (CDim) of HRV was calculated similarly for sequential 20-minute segments. We assessed the significance of the time-course change of each marker over the 120-minute period prior to NSVT onset. Results: MeanRR (P parasympathetic activity, perhaps in conjunction with an increase in sympathetic activity, may trigger NSVT.

  18. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    Science.gov (United States)

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  19. Hydroclimatic conditions preceding the March 2014 Oso landslide

    Science.gov (United States)

    Henn, Brian; Cao, Qian; Lettenmaier, Dennis P.; Magirl, Christopher S.; Mass, Clifford; Bower, J. Brent; St. Laurent, Michael; Mao, Yixin; Perica, Sanja

    2015-01-01

    The 22 March 2014 Oso landslide was one of the deadliest in U.S. history, resulting in 43 fatalities and the destruction of more than 40 structures. We examine synoptic conditions, precipitation records and soil moisture reconstructions in the days, months, and years preceding the landslide. Atmospheric reanalysis shows a period of enhanced moisture transport to the Pacific Northwest beginning on 11 February 2014. The 21- to 42-day periods prior to the landslide had anomalously high precipitation; we estimate that 300-400 mm of precipitation fell at Oso in the 21 days prior to the landslide. Relative only to historical periods ending on 22 March, the return periods of these precipitation accumulations are large (25-88 years). However, relative to the largest accumulations from any time of the year (annual maxima), return periods are more modest (2-6 years). In addition to the 21-42 days prior to the landslide, there is a secondary maximum in the precipitation return periods for the 4 years preceding the landslide. Reconstructed soil moisture was anomalously high prior to the landslide, with a return period that exceeded 40 years about a week before the event.

  20. Expectations from preceding prosody influence segmentation in online sentence processing.

    Science.gov (United States)

    Brown, Meredith; Salverda, Anne Pier; Dilley, Laura C; Tanenhaus, Michael K

    2011-12-01

    Previous work examining prosodic cues in online spoken-word recognition has focused primarily on local cues to word identity. However, recent studies have suggested that utterance-level prosodic patterns can also influence the interpretation of subsequent sequences of lexically ambiguous syllables (Dilley, Mattys, & Vinke, Journal of Memory and Language, 63:274-294, 2010; Dilley & McAuley, Journal of Memory and Language, 59:294-311, 2008). To test the hypothesis that these distal prosody effects are based on expectations about the organization of upcoming material, we conducted a visual-world experiment. We examined fixations to competing alternatives such as pan and panda upon hearing the target word panda in utterances in which the acoustic properties of the preceding sentence material had been manipulated. The proportions of fixations to the monosyllabic competitor were higher beginning 200 ms after target word onset when the preceding prosody supported a prosodic constituent boundary following pan-, rather than following panda. These findings support the hypothesis that expectations based on perceived prosodic patterns in the distal context influence lexical segmentation and word recognition.

  1. Cellular contraction precedes membrane depolarization in Vorticella convallaria

    Science.gov (United States)

    Shiono; Naitoh

    1997-01-01

    Application of a mechanical stimulus to the cell body of the peritrich ciliate Vorticella convallaria evoked an all-or-nothing membrane depolarization, the large pulse. This was always accompanied by an all-or-nothing cellular contraction, and simultaneous recordings of the two events revealed that the large pulse was always preceded by the cellular contraction. A smaller graded membrane depolarization (the medium pulse) was sometimes produced in response to a weaker mechanical stimulus. The medium pulse was accompanied by a small, graded, localized contraction of the cell body and was occasionally followed by a large pulse. When a large pulse occurred during a medium pulse, it reached the same peak level as that of a large pulse evoked without a preceding medium pulse. When a medium pulse occurred during a medium pulse, summation of the two pulses was observed. Sustained contraction causes V. convallaria to become rounded, and in this state a mechanical stimulus stronger than that used to evoke the large pulse evoked a graded depolarizing mechanoreceptor potential in the cell. We conclude that both the large and medium pulses are caused by an inward receptor current that is activated mechanically following contraction of the cell body. A localized contraction evokes a small mechanoreceptor current, causing a medium pulse. An all-or-nothing contraction evokes a saturated, all-or-nothing mechanoreceptor current, causing a large pulse.

  2. Hot days induced by precipitation deficits at the global scale.

    Science.gov (United States)

    Mueller, Brigitte; Seneviratne, Sonia I

    2012-07-31

    Global warming increases the occurrence probability of hot extremes, and improving the predictability of such events is thus becoming of critical importance. Hot extremes have been shown to be induced by surface moisture deficits in some regions. In this study, we assess whether such a relationship holds at the global scale. We find that wide areas of the world display a strong relationship between the number of hot days in the regions' hottest month and preceding precipitation deficits. The occurrence probability of an above-average number of hot days is over 70% after precipitation deficits in most parts of South America as well as the Iberian Peninsula and Eastern Australia, and over 60% in most of North America and Eastern Europe, while it is below 30-40% after wet conditions in these regions. Using quantile regression analyses, we show that the impact of precipitation deficits on the number of hot days is asymmetric, i.e. extreme high numbers of hot days are most strongly influenced. This relationship also applies to the 2011 extreme event in Texas. These findings suggest that effects of soil moisture-temperature coupling are geographically more widespread than commonly assumed.

  3. Accumulation of 3-hydroxytetradecenoic acid: Cause or corollary of glucolipotoxic impairment of pancreatic β-cell bioenergetics?

    Directory of Open Access Journals (Sweden)

    Nicolai M. Doliba

    2015-12-01

    Conclusions: As long chain 3-hydroxylated FA metabolites are known to uncouple heart and brain mitochondria [53–55], we propose that under glucolipotoxic condition, unsaturated hydroxylated long-chain FAs accumulate, uncouple and ultimately inhibit β-cell respiration. This leads to the slow deterioration of mitochondrial function progressing to bioenergetics β-cell failure.

  4. Growth, condition factor, and bioenergetics modeling link warmer stream temperatures below a small dam to reduced performance of juvenile steelhead

    Science.gov (United States)

    Sauter, S.T.; Connolly, P.J.

    2010-01-01

    We investigated the growth and feeding performance of juvenile steelhead Oncorhynchus mykiss using field measures and bioenergetics modeling. Juvenile steelhead populations were sampled from mid-June through August 2004 at study sites upstream and downstream of Hemlock Dam. The growth and diet of juvenile steelhead were determined for a warm (summer) and subsequent (late summer) transitional period at each study site. Empirical data on the growth and diet of juvenile steelhead and mean daily temperatures were used in a bioenergetics model to estimate the proportion of maximum consumption achieved by juvenile steelhead by site and period. Modeled estimates of feeding performance were better for juvenile steelhead at the upstream compared to the downstream site during both periods. The median condition factor of juvenile steelhead did not change over the summer at the upstream site, but showed a significant decline over time at the downstream site. A negative trend in median condition factor at the downstream site supported bioenergetics modeling results that suggested the warmer stream temperatures had a negative impact on juvenile steelhead. Bioenergetics modeling predicted a lower feeding performance for juvenile steelhead rearing downstream compared to upstream of Hemlock Dam although food availability appeared to be limited at both study sites during the warm period. Warmer water temperatures, greater diel variation, and change in diel pattern likely led to the reduced feeding performance and reduced growth, which could have affected the overall survival of juvenile steelhead downstream of Hemlock Dam. ?? 2010 by the Northwest Scientific Association.

  5. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer

    NARCIS (Netherlands)

    Isidoro, Antonio; Martínez, Marta; Fernández, Pedro L; Ortega, Alvaro Dario; Santamaría, Gema; Chamorro, Margarita; Reed, John C; Cuezva, José M

    2004-01-01

    Recent findings indicate that the expression of the beta-catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is depressed in liver, kidney and colon carcinomas, providing further a bioenergetic signature of cancer that is associated with patient survival. In the present study, we

  6. Neurofibromatozis and Attention Deficit

    Directory of Open Access Journals (Sweden)

    Mehmet ERYILMAZ et al.

    2010-05-01

    Full Text Available Neurofibromatosis type VI, a disease characterized by the presence of café-au-lait spots withoutthe presence of neurofibromas typically present in neurofibromatosis, as well as cognitivefunction and speech problems, often shows neurological involvement. We describe a case of a14-year-old child who has speech problems and isolated cafè-au-lait macules. We performedan IQ test on him and he scored 70 points. His problems started when he was approximately 5years old (school age. He was diagnosed with attention deficit disorder syndrome withouthyperactivity after neuropsychiatric investigation. We reported this case to improve recognitionof NF VI in children who have cognitive function problems.

  7. Beyond the knowledge deficit

    DEFF Research Database (Denmark)

    Hansen, Janus Staffan; Holm, Lotte; Frewer, Lynn

    2003-01-01

    The paper reviews psychological and social scientific research on lay attitudes to food risks. Many experts (scientists, food producers and public health advisors) regard public unease about food risks as excessive. This expert-lay discrepancy is often attributed to a 'knowledge deficit' among lay...... people. However, much research in psychology and sociology suggests that lay risk assessments are complex, situationally sensitive expressions of personal value systems. The paper is organised around four themes: risk perception, the communication of risk, lay handling of risk, and public trust...... in institutions and experts. It suggests that an interdisciplinary, contextualised and psychologically sound approach to the study of risk is needed....

  8. Revisiting Precede-Proceed: A Leading Model for Ecological and Ethical Health Promotion

    Science.gov (United States)

    Porter, Christine M.

    2016-01-01

    Background: The Precede-Proceed model has provided moral and practical guidance for the fields of health education and health promotion since Lawrence Green first developed Precede in 1974 and Green and Kreuter added Proceed in 1991. Precede-Proceed today remains the most comprehensive and one of the most used approaches to promoting health.…

  9. Growth and food consumption by tiger muskellunge: Effects of temperature and ration level on bioenergetic model predictions

    Science.gov (United States)

    Chipps, S.R.; Einfalt, L.M.; Wahl, David H.

    2000-01-01

    We measured growth of age-0 tiger muskellunge as a function of ration size (25, 50, 75, and 100% C(max))and water temperature (7.5-25??C) and compared experimental results with those predicted from a bioenergetic model. Discrepancies between actual and predicted values varied appreciably with water temperature and growth rate. On average, model output overestimated winter consumption rates at 10 and 7.5??C by 113 to 328%, respectively, whereas model predictions in summer and autumn (20-25??C) were in better agreement with actual values (4 to 58%). We postulate that variation in model performance was related to seasonal changes in esocid metabolic rate, which were not accounted for in the bioenergetic model. Moreover, accuracy of model output varied with feeding and growth rate of tiger muskellunge. The model performed poorly for fish fed low rations compared with estimates based on fish fed ad libitum rations and was attributed, in part, to the influence of growth rate on the accuracy of bioenergetic predictions. Based on modeling simulations, we found that errors associated with bioenergetic parameters had more influence on model output when growth rate was low, which is consistent with our observations. In addition, reduced conversion efficiency at high ration levels may contribute to variable model performance, thereby implying that waste losses should be modeled as a function of ration size for esocids. Our findings support earlier field tests of the esocid bioenergetic model and indicate that food consumption is generally overestimated by the model, particularly in winter months and for fish exhibiting low feeding and growth rates.

  10. Enhanced Precedence Scheduling Algorithm with Dynamic Time Quantum (EPSADTQ

    Directory of Open Access Journals (Sweden)

    G. Siva Nageswara Rao

    2015-07-01

    Full Text Available This study proposes a new algorithm which is a logical extension of the popular Round Robin CPU scheduling algorithm. The Round Robin algorithm can be effective only if the time quantum is chosen accurately. Even by taking mean average of burst times as time quantum, the performance of the RR cannot be improved beyond a certain point. However, the novel method proposed here, suggests that a priority be assigned to each process based on balanced precedence factor. The novel method also uses mean average as a time quantum. Experiments are conducted in order to measure the effectiveness of this novel method. The results clearly showed that EPSADTQ is superior to RR and PSMTQ and its variants. EPSADTQ resulted in a significant reduction of the no. of context switches, average waiting time and average turnaround time.

  11. Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway

    Energy Technology Data Exchange (ETDEWEB)

    Módis, Katalin [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Asimakopoulou, Antonia [Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Coletta, Ciro [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Papapetropoulos, Andreas [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Szabo, Csaba, E-mail: szabocsaba@aol.com [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States)

    2013-04-19

    Highlights: •Oxidative stress impairs 3-MST-derived H{sub 2}S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H{sub 2}S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H{sub 2}S), as well as endogenous, intramitochondrial production of H{sub 2}S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H{sub 2}S pathway in vitro. Hydrogen peroxide (H{sub 2}O{sub 2}, 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H{sub 2}O{sub 2} (50–500 μM) caused a concentration-dependent decrease in production of H{sub 2}S from 3-MP. In cultured murine hepatoma cells H{sub 2}O{sub 2}, (3–100 μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100–300 nM) was completely abolished by pre-treatment of the cells with H{sub 2}O{sub 2} (50 μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H{sub 2}S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging.

  12. The bioenergetic consequences of invasive-induced food web disruption to Lake Ontario alewives

    Science.gov (United States)

    Stewart, Thomas J.; O'Gorman, Robert; Sprules, W. Gary; Lantry, B.F.

    2010-01-01

    Alewives Alosa pseudoharengus are the dominant prey fish in Lake Ontario, and their response to ecological change can alter the structure and function of the Lake Ontario food web. Using stochastic population-based bioenergetic models of Lake Ontario alewives for 1987–1991 and 2001–2005, we evaluated changes to alewife production, consumption, and associated bioenergetic ratios after invasive-induced food web disruption. After the disruption, mean biomass of alewives declined from 28.0 to 14.6 g/m2, production declined from 40.8 to 13.6 g·m−2·year−1, and consumption declined from 342.1 to 137.2 g·m−2·year−1, but bootstrapping of error sources suggested that the changes were not statistically significant. Population-based bioenergetic ratios of production to biomass (P/B ratio), total consumption to biomass (Q/B ratio), and production efficiency did not change. Pathways of energy flow measured as prey-group-specific Q/B ratios changed significantly between the two time periods for invasive predatory cladocerans (from 0.6 to 1.3), Mysis diluviana (from 0.4 to 2.5), and other prey (from 0.8 to 0.1), but the observed decline in the zooplankton Q/B ratio (from 10.6 to 5.5) was not significant. Gross production efficiency did not change; values ranged from 8% to 15%. Age-group mean gross conversion efficiency (GCE) declined with age; GCE ranged from 7.5% to 11.0% for yearlings, was approximately 5% for age-2 alewives, and was less than 2% for age-3 and older alewives. The GCE increased significantly between the time periods for yearling alewives. Our analyses support the hypothesis that after 2003, alewives could not sustain their growth while feeding on zooplankton closer to shore. Modeling of observed spatial variation in diet and alternative occupied temperatures demonstrates the potential for reducing consumption by alewives. Our results suggest that Lake Ontario alewives can exploit spatial heterogeneity in resource patches and thermal habitat to

  13. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-10-01

    The 'healthy cell bias of estrogen action' hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance aerobic glycolysis coupled to the citric acid cycle, mitochondrial respiration and ATP generation. Convergence of estrogen-induced signaling onto mitochondria is also a point of vulnerability when activated in diseased neurons which exacerbates degeneration through increased load on dysregulated calcium homeostasis. As the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess disparities in outcomes across basic and clinical science and on which to predict outcomes of estrogen interventions for sustaining neurological health and preventing age-associated neurodegenerative diseases such as Alzheimer's.

  14. The Quantum Biology of Reactive Oxygen Species Partitioning Impacts Cellular Bioenergetics

    Science.gov (United States)

    Usselman, Robert J.; Chavarriaga, Cristina; Castello, Pablo R.; Procopio, Maria; Ritz, Thorsten; Dratz, Edward A.; Singel, David J.; Martino, Carlos F.

    2016-12-01

    Quantum biology is the study of quantum effects on biochemical mechanisms and biological function. We show that the biological production of reactive oxygen species (ROS) in live cells can be influenced by coherent electron spin dynamics, providing a new example of quantum biology in cellular regulation. ROS partitioning appears to be mediated during the activation of molecular oxygen (O2) by reduced flavoenzymes, forming spin-correlated radical pairs (RPs). We find that oscillating magnetic fields at Zeeman resonance alter relative yields of cellular superoxide (O2•-) and hydrogen peroxide (H2O2) ROS products, indicating coherent singlet-triplet mixing at the point of ROS formation. Furthermore, the orientation-dependence of magnetic stimulation, which leads to specific changes in ROS levels, increases either mitochondrial respiration and glycolysis rates. Our results reveal quantum effects in live cell cultures that bridge atomic and cellular levels by connecting ROS partitioning to cellular bioenergetics.

  15. Aging synaptic mitochondria exhibit dynamic proteomic changes while maintaining bioenergetic function.

    Science.gov (United States)

    Stauch, Kelly L; Purnell, Phillip R; Fox, Howard S

    2014-04-01

    Aging correlates with a progressive impairment of mitochondrial homeostasis and is an influential factor for several forms of neurodegeneration. However, the mechanisms underlying age-related alterations in synaptosomal mitochondria, a neuronal mitochondria population highly susceptible to insults and critical for brain function, remain incompletely understood. Therefore this study investigates the synaptic mitochondrial proteomic and bioenergetic alterations that occur with age. The utilization of a state of the art quantitative proteomics approach allowed for the comparison of protein expression levels in synaptic mitochondria isolated from 5 (mature), 12 (old), and 24 (aged) month old mice. During the process of aging we find that dynamic proteomic alterations occur in synaptic mitochondria. Despite direct (mitochondrial DNA deletions) and indirect (increased antioxidant protein levels) signs of mitochondrial damage in the aged mice, there was an overall maintenance of mitochondrial function. Therefore the synaptic mitochondrial proteomic changes that occur with aging correlate with preservation of synaptic mitochondrial function.

  16. Acid-base and bio-energetics during balanced versus unbalanced normovolaemic haemodilution.

    Science.gov (United States)

    Morgan, T J; Venkatesh, B; Beindorf, A; Andrew, I; Hall, J

    2007-04-01

    Fluids balanced to avoid acid-base disturbances may be preferable to saline, which causes metabolic acidosis in high volume. We evaluated acid-base and bio-energetic effects of haemodilution with a crystalloid balanced on physical chemical principles, versus crystalloids causing metabolic acidosis or metabolic alkalosis. Anaesthetised, mechanically ventilated Sprague-Dawley rats (n=32, allocated to four groups) underwent six exchanges of 9 ml crystalloid for 3 ml blood. Exchange was with one of three crystalloids with strong ion difference (SID) values of 0, 24 (balanced) and 40 mEq/l. Controls did not undergo haemodilution. Mean haemoglobin concentration fell to approximately 50 g/l after haemodilution. With SID 24 mEq/l fluid, metabolic acid-base remained unchanged. Dilution with SID 0 mEq/l and 40 mEq/l fluids caused a progressive metabolic acidosis and alkalosis respectively. Standard base excess (SBE) and haemoglobin concentration were directly correlated in the SID 0 mEq/l group (R2 = 0.61), indirectly correlated in the SBE 40 mEq/l group (R2 = 0.48) and showed no correlation in the SID 24 mEq/l group (R2 = 0.003). There were no significant differences between final ileal values of CO2 gap, nucleotides concentration, energy charge, or luminal lactate concentration. SID 40 mEq/l crystalloid dilution caused a significant rise in subcutaneous lactate. In this group mean kidney ATP concentration was significantly less than controls and renal energy charge significantly lower than SID 0 mEq/l and control groups. We conclude that a crystalloid SID of 24 mEq/l provides balanced haemodilution. Bio-energetic perturbations with higher SID haemodilution may be more severe and need further investigation.

  17. Suitability of Lake Erie for bigheaded carps based on bioenergetic models and remote sensing

    Science.gov (United States)

    Anderson, Karl R.; Chapman, Duane C.; Wynne, Timothy; Masagounder, Karthik; Paukert, Craig

    2015-01-01

    Algal blooms in the Great Lakes are a potential food source for silver carp (Hypophthalmichthys molitrix) and bighead carp (H. nobilis; together bigheaded carps). Understanding these blooms thus plays an important role in understanding the invasion potential of bigheaded carps. We used remote sensing imagery, temperatures, and improved species specific bioenergetics models to determine algal concentrations sufficient for adult bigheaded carps. Depending on water temperature we found that bigheaded carp require between 2 and 7 μg/L chlorophyll or between 0.3 and 1.26 × 105cells/mL Microcystis to maintain body weight. Algal concentrations in the western basin and shoreline were found to be commonly several times greater than the concentrations required for weight maintenance. The remote sensing images show that area of sufficient algal foods commonly encompassed several hundred square kilometers to several thousands of square kilometers when blooms form. From 2002 to 2011, mean algal concentrations increased 273%–411%. This indicates Lake Erie provides increasingly adequate planktonic algal food for bigheaded carps. The water temperatures and algal concentrations detected in Lake Erie from 2008 to 2012 support positive growth rates such that a 4 kg silver carp could gain between 19 and 57% of its body weight in a year. A 5 kg bighead carp modeled at the same water temperatures could gain 20–81% of their body weight in the same period. The remote sensing imagery and bioenergetic models suggest that bigheaded carps would not be food limited if they invaded Lake Erie.

  18. Quantifying the role of woody debris in providing bioenergetically favorable habitat for juvenile salmon

    Science.gov (United States)

    Harrison, L.; Hafs, A. W.; Utz, R.; Dunne, T.

    2013-12-01

    The habitat complexity of a riverine ecosystem substantially influences aquatic communities, and especially the bioenergetics of drift feeding fish. We coupled hydrodynamic and bioenergetic models to assess the influence of habitat complexity, generated via large woody debris (LWD) additions, on juvenile Chinook salmon (Oncorhynchus tshawytscha) growth potential in a river that lacked large wood. Model simulations indicated that LWD diversified the flow field, creating pronounced velocity gradients, which enhanced fish feeding and resting activities at the micro-habitat (sub-meter) scale. Fluid drag created by individual wood structures was increased under higher wood loading rates, leading to a 5-19% reduction in the reach-averaged velocity. We found that wood loading was asymptotically related to the reach-scale growth potential, suggesting that the river became saturated with LWD and additional loading would produce minimal benefit. In our study reach, LWD additions could potentially quadruple the potential growth area available before that limit was reached. Wood depletion in the world's rivers has been widely documented, leading to widespread attempts by river managers to reverse this trend by adding wood to simplified aquatic habitats, though systematic prediction of the effects of wood on fish growth has not been previously accomplished. We offer a quantitative, theory-based approach for assessing the role of wood on habitat potential as it affects fish growth at the micro-habitat and reach-scales. Fig. 1. Predicted flow field and salmon growth potential maps produced from model simulations with no woody debris (Graphs A and D), a low density (Graphs B and E), and a high density (Graphs C and E) of woody debris.

  19. Behavioural thermoregulation and bioenergetics of riverine smallmouth bass associated with ambient cold-period thermal refuge

    Science.gov (United States)

    Westhoff, Jacob T.; Paukert, Craig P.; Ettinger-Dietzel, Sarah; Dodd, H.R.; Siepker, Michael

    2016-01-01

    Smallmouth bass in thermally heterogeneous streams may behaviourally thermoregulate during the cold period (i.e., groundwater temperature greater than river water temperature) by inhabiting warm areas in the stream that result from high groundwater influence or springs. Our objectives were to determine movement of smallmouth bass (Micropterus dolomieu) that use thermal refuge and project differences in growth and consumption among smallmouth bass exhibiting different thermal-use patterns. We implanted radio transmitters in 29 smallmouth bass captured in Alley Spring on the Jacks Fork River, Missouri, USA, during the winter of 2012. Additionally, temperature archival tags were implanted in a subset of nine fish. Fish were tracked using radio telemetry monthly from January 2012 through January of 2013. The greatest upstream movement was 42.5 km, and the greatest downstream movement was 22.2 km. Most radio tagged fish (69%) departed Alley Spring when daily maximum river water temperature first exceeded that of the spring (14 °C) and during increased river discharge. Bioenergetic modelling predicted that a 350 g migrating smallmouth bass that used cold-period thermal refuge would grow 16% slower at the same consumption level as a fish that did not seek thermal refuge. Contrary to the bioenergetics models, extrapolation of growth scope results suggested migrating fish grow 29% more than fish using areas of stream with little groundwater influence. Our results contradict previous findings that smallmouth bass are relatively sedentary, provide information about potential cues for migratory behaviour, and give insight to managers regarding use and growth of smallmouth bass in thermally heterogeneous river systems.

  20. Hybrid incompatibility despite pleiotropic constraint in a sequence-based bioenergetic model of transcription factor binding.

    Science.gov (United States)

    Tulchinsky, Alexander Y; Johnson, Norman A; Porter, Adam H

    2014-12-01

    Hybrid incompatibility can result from gene misregulation produced by divergence in trans-acting regulatory factors and their cis-regulatory targets. However, change in trans-acting factors may be constrained by pleiotropy, which would in turn limit the evolution of incompatibility. We employed a mechanistically explicit bioenergetic model of gene expression wherein parameter combinations (number of transcription factor molecules, energetic properties of binding to the regulatory site, and genomic background size) determine the shape of the genotype-phenotype (G-P) map, and interacting allelic variants of mutable cis and trans sites determine the phenotype along that map. Misregulation occurs when the phenotype differs from its optimal value. We simulated a pleiotropic regulatory pathway involving a positively selected and a conserved trait regulated by a shared transcription factor (TF), with two populations evolving in parallel. Pleiotropic constraints shifted evolution in the positively selected trait to its cis-regulatory locus. We nevertheless found that the TF genotypes often evolved, accompanied by compensatory evolution in the conserved trait, and both traits contributed to hybrid misregulation. Compensatory evolution resulted in "developmental system drift," whereby the regulatory basis of the conserved phenotype changed although the phenotype itself did not. Pleiotropic constraints became stronger and in some cases prohibitive when the bioenergetic properties of the molecular interaction produced a G-P map that was too steep. Likewise, compensatory evolution slowed and hybrid misregulation was not evident when the G-P map was too shallow. A broad pleiotropic "sweet spot" nevertheless existed where evolutionary constraints were moderate to weak, permitting substantial hybrid misregulation in both traits. None of these pleiotropic constraints manifested when the TF contained nonrecombining domains independently regulating the respective traits.

  1. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance.

    Science.gov (United States)

    Raefsky, Sophia M; Mattson, Mark P

    2017-01-01

    An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans. The metabolic 'switch' in fuel source from liver glycogen store-derived glucose to adipose cell-derived fatty acids and their ketone metabolites during fasting and sustained exercise, appears to be a pivotal trigger of both brain-intrinsic and peripheral organ-derived signals that enhance learning and memory and underlying synaptic plasticity and neurogenesis. Brain-intrinsic extracellular signals include the excitatory neurotransmitter glutamate and the neurotrophic factor BDNF, and peripheral signals may include the liver-derived ketone 3-hydroxybutyrate and the muscle cell-derived protein irisin. Emerging findings suggest that fasting, exercise and an intellectually challenging lifestyle can protect neurons against the dysfunction and degeneration that they would otherwise suffer in acute brain injuries (stroke and head trauma) and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease. Among the prominent intracellular responses of neurons to these bioenergetic challenges are up-regulation of antioxidant defenses, autophagy/mitophagy and DNA repair. A better understanding of such fundamental hormesis-based adaptive neuronal response mechanisms is expected to result in the development and implementation of novel interventions to promote optimal brain function and healthy brain aging.

  2. Docosahexaenoic acid attenuates breast cancer cell metabolism and the Warburg phenotype by targeting bioenergetic function.

    Science.gov (United States)

    Mouradian, Michael; Kikawa, Keith D; Dranka, Brian P; Komas, Steven M; Kalyanaraman, Balaraman; Pardini, Ronald S

    2015-09-01

    Docosahexaenoic acid (DHA; C22:6n-3) depresses mammary carcinoma proliferation and growth in cell culture and in animal models. The current study explored the role of interrupting bioenergetic pathways in BT-474 and MDA-MB-231 breast cancer cell lines representing respiratory and glycolytic phenotypes, respectively and comparing the impacts of DHA with a non-transformed cell line, MCF-10A. Metabolic investigation revealed that DHA supplementation significantly diminished the bioenergetic profile of the malignant cell lines in a dose-dependent manner. DHA enrichment also resulted in decreases in hypoxia-inducible factor (HIF-1α) total protein level and transcriptional activity in the malignant cell lines but not in the non-transformed cell line. Downstream targets of HIF-1α, including glucose transporter 1 (GLUT 1) and lactate dehydrogenase (LDH), were decreased by DHA treatment in the BT-474 cell line, as well as decreases in LDH protein level in the MDA-MB-231 cell line. Glucose uptake, total glucose oxidation, glycolytic metabolism, and lactate production were significantly decreased in response to DHA supplementation; thereby enhancing metabolic injury and decreasing oxidative metabolism. The DHA-induced metabolic changes led to a marked decrease of intracellular ATP levels by 50% in both cancer cell lines, which mediated phosphorylation of metabolic stress marker, AMPK, at Thr172. These findings show that DHA contributes to impaired cancer cell growth and survival by altering cancer cell metabolism, increasing metabolic stress and altering HIF-1α-associated metabolism, while not affecting non-transformed MCF-10A cells. This study provides rationale for enhancement of current cancer prevention models and current therapies by combining them with dietary sources, like DHA.

  3. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

    Directory of Open Access Journals (Sweden)

    William Dott

    2014-01-01

    Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

  4. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

    Directory of Open Access Journals (Sweden)

    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  5. Dyscalculia and Attention Deficit Subtypes

    OpenAIRE

    1999-01-01

    The association of specific academic deficits with attention deficit disorder (ADD) subtypes was determined in 20 students (ages 8-12) with ADD with hyperactivity (ADD/H) compared to 20 with ADD without hyperactivity (ADD/noH), at the Department of Educational Psychology, University of Texas at Austin, TX.

  6. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease

    Directory of Open Access Journals (Sweden)

    Adrienne L. King

    2016-10-01

    Conclusion: Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the attenuation of hypoxic stress.

  7. Cerebral potentials preceding unilateral and simultaneous bilateral finger movements.

    Science.gov (United States)

    Kristeva, R; Keller, E; Deecke, L; Kornhuber, H H

    1979-08-01

    Cerebral potentials preceding voluntary bilateral simultaneous finger movements were investigated in 19 right-handed young adult subjects, and were compared with unilateral right-sided finger m n the same experiment. With bilateral movements, the Bereitschaftspotential (BP) was not symmetrical or larger over the dominant hemisphere, but surprisingly, it was larger over the minor hemisphere. The BP averaged -3.66 microV (S.D. 1.96) over the left precentral region and -4.82 microV (S.D. 3.73) over the right precentral region in this condition. The difference was significant at 2P less than 0.01. This difference was pronounced in precentral leads but very small and almost missing in parietal leads. The pre-motion positivity (PMP) was well developed and even larger with bilateral than with unilateral (right-sides) movements. At the vertex it averaged +1.33 microV (S.D.4.16) with bilateral movements and only +0.15 microV (S.D. 1.42) with right-sided unilateral movements (2P less than 0.05). With bilateral movements the PMP could be observed in any record, but with unilateral movements it was missing at the left precentral lead, in accordance with previous publications (Deecke et al. 1969, 1976). The motor potential (MP), measured in a bipolar record from left and right precentral leads, was larger with unilateral (-1.25 microV, S.D. 1.33) than with bilateral movements (-0.36 microV, S.D. 0.92). Onset time differences of the BP preceding unilateral and bilateral movements were very small. However, there was a tendency towards earlier onset with unilateral than with bilateral movements (1031 msec, S.D. 358, as compared with 951 msec, S.D. 305). The averaged EMG revealed differences in movement onset. Muscular contraction tended to be earlier in the right than in the left m. flexor indicis in our right-handed subjects, on the average by 16 msec (S.D. 15). With unilateral right-sided movements, the left m. flexor indicis was not silent but showed an abortive mirror activity

  8. Lithospheric Convergence Preceded Extension in the Pannonian-Carpathian System

    Science.gov (United States)

    Houseman, Gregory; Stuart, Graham; Dando, Ben; Hetenyi, Gyorgy; Lorinczi, Piroska; Hegedus, Endre; Brueckl, Ewald

    2010-05-01

    The continuing collision of the Adriatic block with European continental lithosphere has its clearest expression now in the Alpine collision zone. Recent tomographic images of the upper mantle beneath the eastern Alps and western Pannonian Basin support the interpretation that in the Early Miocene the collision zone extended further east: a steeply dipping seismically fast structure stretches downward beneath the Eastern Alps reaching to the base of the transition zone, consistent with the long history of convergence in this region. This high velocity structure also extends eastward beneath the extensional Pannonian Basin. The high velocity anomaly beneath the Basin is strongly developed in transition zone depths (410 to 660 km) but the anomaly weakens upward. High velocities beneath the center of the extensional basin are unexpected because there is substantive evidence that the onset of extension in the Pannonian domain at around 17 Ma produced rapid extension of the lithosphere and replacement of the lower part of the lithosphere by hot asthenosphere. These deeper structures, however, must be explained by the long history of convergence that preceded the extension of the basin. Further evidence of a history of sustained convergence in the present Pannonian region is found in the depression of the 660 km seismic discontinuity beneath the Alps (Lombardi et al., EPSL, 2009) and also beneath the Pannonian Basin (Hetenyi et al., GRL, 2009). The 660 km discontinuity in both places is depressed by as much as 40 km, whereas the 410 km discontinuity is at approximately nominal depths. Evidently in both regions relatively dense material derived from the mid-Miocene collision sits stagnant on top of the 660 km discontinuity, where further descent is obstructed by the negative Clapeyron slope of the spinel-to-perovskite phase transition and/or the high viscosity of the lower mantle. The rapid extension of the Intra-Carpathian Basins in the Mid-Miocene (between about 17 and

  9. Severe hyponatremia as the initial sign preceding Guillain-Barré syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Abhishek Wankar

    2014-01-01

    Full Text Available Diagnosis of Guillain-Barrι syndrome (GBS is established clinically and is supported by nerve conduction studies and cerebrospinal fluid examination. Renal function is usually not affected, but recent case reports have established a link between GBS and hyponatremia. A 60-year-old woman presenting with lower back ache since 3 days, became drowsy the next day and developed paraparesis and bulbar symptoms. Her sensorium and power deteriorated progressively over the next 2 days and she was brought to hospital in a drowsy state. She was found to have severe hyponatremia (Na + at 113 and nerve conduction study (NCS was son of AMAN. The patient was started on intravenous immunoglobulin and her sodium levels were corrected, and the patient recovered completely. The occurrence of hyponatremia in patients diagnosed with GBS is well described. However, there have been only two prior case reports in which hyponatremia had been observed before the manifestation of neuromuscular deficits. Our patient case is unique in that severe hyponatremia occurred simultaneously with neurologic symptoms and the diagnosis of GBS. In most cases reported in the literature, hyponatremia was noted after a diagnosis of GBS was established. The mean period of onset of syndrome of inappropriate antidiuretic hormone (SIADH was 8.8 days after the onset of symptoms of GBS. In Conclusion , this presentation raises the possibility that early changes in the autonomic nervous system triggered by GBS might lead to alterations in water and sodium balance that can precede symptomatic changes in the peripheral nervous system. Although rarely, but both GBS and its treatment, intravenous immunoglobulin, should be considered in the differential diagnosis of hyponatremia.

  10. Critical Data Analysis Precedes Soft Computing Of Medical Data

    DEFF Research Database (Denmark)

    Keyserlingk, Diedrich Graf von; Jantzen, Jan; Berks, G.

    2000-01-01

    extracted. The factors had different relationships (loadings) to the symptoms. Although the factors were gained only by computations, they seemed to express some modular features of the language disturbances. This phenomenon, that factors represent superior aspects of data, is well known in factor analysis....... Factor I mediates the overall severity of the disturbance, factor II points to expressive versus comprehensive character of the language disorder, factor III represents the granularity of the phonetic mistakes, factor IV accentuates the patients' awareness of his disease, and factor V exposes...... the deficits in communication. Sets of symptoms corresponding to the traditional symptoms in Broca and Wernicke aphasia may be represented in the factors, but the factor itself does not represent a syndrome. It is assumed that this kind of data analysis shows a new approach to the understanding of language...

  11. Faking attention deficit hyperactivity disorder.

    Science.gov (United States)

    Sansone, Randy A; Sansone, Lori A

    2011-08-01

    Attention-deficit hyperactivity disorder is a common malady in the general population, with up to 8.1 percent of adults meeting criteria for this syndrome. In the college setting, the diagnosis of attention deficit hyperactivity disorder may offer specific academic advantages. Once the diagnosis is assigned, the prescription of stimulant medication may provide additional secondary gains through misuse and/or diversion. For example, these drugs may be used by college consumers to increase alertness, energy, academic performance, and athletic performance. Stimulants may also decrease psychological distress, alleviate restlessness and weight concerns, and be used for recreational purposes. According to the findings of five studies, the symptoms of attention deficit hyperactivity disorder can be believably faked, particularly when assessed with attention deficit hyperactivity disorder symptom checklists. Thus, the faking of attention deficit hyperactivity disorder is a realistic concern in both psychiatric and primary care settings.

  12. Altered Bioenergetics in Primary Dermal Fibroblasts from Adult Carriers of the FMR1 Premutation Before the Onset of the Neurodegenerative Disease Fragile X-Associated Tremor/Ataxia Syndrome.

    Science.gov (United States)

    Napoli, Eleonora; Song, Gyu; Wong, Sarah; Hagerman, Randi; Giulivi, Cecilia

    2016-10-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder, characterized by tremors, ataxia, impaired coordination, and cognitive decline. While all FXTAS individuals are carriers of a 55-200 CGG expansion at the 5'-UTR of the fragile X mental retardation gene (FMR1), also known as premutation, not all carriers develop FXTAS symptoms and some display other types of psychological/emotional disorders (e.g., autism, anxiety). The goal of this study was to investigate whether the mitochondrial dysfunction previously observed in fibroblasts from older premutation individuals (>60 years) was already present in younger (17-48 years), non-FXTAS-affected carriers and to identify the type and severity of the bioenergetic deficit. Since FXTAS affects mostly males, while females account for a small part of the FXTAS-affected population displaying less severe symptoms, only fibroblasts from males were evaluated in this study. Based on polarographic and enzymatic measurements, a generalized OXPHOS deficit was noted accompanied by increases in the matrix biomarker citrate synthase, oxidative stress (as increased mtDNA copy number and deletions), and mitochondrial network disruption/disorganization. Some of the outcomes (ATP-linked oxygen uptake, coupling, citrate synthase activity, and mitochondrial network organization) strongly correlated with the extent of the CGG expansion, with more severe deficits observed in cell lines carrying higher CGG number. Furthermore, mitochondrial outcomes can identify endophenotypes among carriers and are robust predictors of the premutation diagnosis before the onset of FXTAS, with the potential to be used as markers of prognosis and/or as readouts of pharmacological interventions.

  13. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Yuta Iwai

    Full Text Available Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS, suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP amplitude (index of motor neuronal loss and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44, ALS patients (n = 140 had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p 5mV. Regression analyses showed that SDTC (R = -0.22 and depolarizing threshold electrotonus (R = -0.22 increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.

  14. PRECEDENTS FOR AUTHORIZATION OF CONTENTS USING DOSE RATE MEASUREMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Abramczyk, G.; Bellamy, S.; Nathan, S.; Loftin, B.

    2012-06-05

    For the transportation of Radioactive Material (RAM) packages, the requirements for the maximum allowed dose rate at the package surface and in its vicinity are given in Title 10 of the Code of Federal Regulations, Section 71.47. The regulations are based on the acceptable dose rates to which the public, workers, and the environment may be exposed. As such, the regulations specify dose rates, rather than quantity of radioactive isotopes and require monitoring to confirm the requirements are met. 10CFR71.47 requires that each package of radioactive materials offered for transportation must be designed and prepared for shipment so that under conditions normally incident to transportation the radiation level does not exceed 2 mSv/h (200 mrem/h) at any point on the external Surface of the package, and the transport index does not exceed 10. Before shipment, the dose rate of the package is determined by measurement, ensuring that it conforms to the regulatory limits, regardless of any analyses. This is the requirement for all certified packagings. This paper discusses the requirements for establishing the dose rates when shipping RAM packages and the precedents for meeting these requirements by measurement.

  15. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2006-01-01

    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  16. Casual sequences preceding coal dust explosions; Ursachenkette einer Kohlenstaubexplosion

    Energy Technology Data Exchange (ETDEWEB)

    Cichowski, E. [Schlesische Technische Univ., Gleiwitz (Poland); Faber, M. [Bergbau-Versuchsstrecke, DMT Gas and Fire Division, Bochum (Germany)

    2002-12-01

    The paper examines the causal sequence which precedes a possible coaldust explosion in the Polish coal industry. Each occurrence is prefaced by a sequence of necessary causes. Here it is assumed that the component parts of the required causal sequence are always present when the undesired final occurrence takes place. An identification of the causality of the coal-dust explosion often complicates this process, such that both the initiation and the consequences of the explosion can be linked to various changes in the parameters associated with the working environment. The essential aspect of the accident hazard and of the ensuing risk to the winning operation results from the causality factor, which is dependent on various safety deficiencies. The safety deficiencies presented can be due to parameters associated with the working environment or to human actions. (orig.) [German] Im vorliegenden Beitrag wird die Ursachenkette betrachtet, die einer moeglichen Kohlenstaubexplosion im polnischen Steinkohlenbergbau vorausgeht. Jeder Folge geht eine Kette notwendiger Ursachen voraus. Dabei wird angenommen, dass Bestandteile der notwendigen Ursachenkette immer auftreten, wenn die unerwuenschte Endfolge geschieht. Die Identifizierung der Kausalitaet der Kohlenstaubexplosion kompliziert oft diesen Vorgang, so dass sowohl das Initiieren als auch die Folgen der Kohlenstaubexplosion mit verschiedenen Aenderungen der Arbeitsumweltparameter verknuepft sein koennen. Das Wesentliche der Unfallgefaehrdung und des auftretenden Risikos der Gewinnung resultiert aus der Kausalitaet, die unterschiedliche Sicherheitsdefizite bedingen. Die angefuehrten Sicherheitsdefizite koennen seitens der Arbeitsumweltparameter sowie seitens menschlicher Einfluesse auftreten. (orig.)

  17. Faststats: Attention Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Attention Deficit Hyperactivity Disorder (ADHD)* Recommend on Facebook Tweet Share Compartir Data ... attention deficit disorder (ADD)" is used rather than "attention deficit hyperactivity disorder (ADHD)" in some data sources. More data Association ...

  18. [Attention deficit hyperactivity disorder].

    Science.gov (United States)

    Cunill, Ruth; Castells, Xavier

    2015-04-20

    Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and can persist into the adulthood. ADHD has important social, academic and occupational consequences. ADHD diagnosis is based on the fulfillment of several clinical criteria, which can vary depending on the diagnostic system used. The clinical presentation can show great between-patient variability and it has been related to a dysfunction in the fronto-striatal and meso-limbic circuits. Recent investigations support a model in which multiple genetic and environmental factors interact to create a neurobiological susceptibility to develop the disorder. However, no clear causal association has yet been identified. Although multimodal treatment including both pharmacological and psychosocial interventions is usually recommended, no convincing evidence exists to support this recommendation. Pharmacological treatment has fundamentally shown to improve ADHD symptoms in the short term, while efficacy data for psychosocial interventions are scarce and inconsistent. Yet, drug treatment is increasingly popular and the last 2 decades have witnessed a sharp increase in the prescription of anti-ADHD medications coinciding with the marketing of new drugs to treat ADHD.

  19. Pregnancy and employment leave: legal precedents and future policy.

    Science.gov (United States)

    Gardin, S K; Richwald, G A

    1986-01-01

    An estimated 85% of female workers in the US become pregnant during their working lives; 62% of married US women were employed for some period during the 12 months preceding childbirth. Historically, US legislation has assumed a protectionist policy with regard to restricting prenatal and postpartum employment, yet this stance has not been backed up by protection of income, benefits, reinstatement, or seniority. The passage in 1964 of Title VII of the Federal Civil Rights Act banning discrimination on the basis of sex triggered a long string of legal battles fought on the premise that pregnancy is a disability. As a result of Congressional efforts, an amendment to Title VII--the Pregnancy Discrimination Act--was passed in 1978. This law requires that women disabled due to pregnancy or childbirth be provided with the same benefits as those provided other disabled employees. However, the law does not require an employer who does not provide disability benefits, paid sick leave, or medical benefits to other employees to provide them to pregnant women. A weakness of existing legislation is its failure to address the difficulties inherent in accommodating childbearing women in the labor force. Accommodation under the current employment system results in productivity disruption and financial losses for both employer and employee. In all other major industrial countries, maternity benefits such as paid leave before and after childbirth, reinstatement rights, and nursing breaks on the job are guaranteed through national legislation. Such benefits emanate from acknowledgment of women's essential participation in the labor force as well as their unique ability to give birth. Under a more flexible employment system, equal protection would not result in the denial of maternity leave to female employees, but rather the provision parental leave to male and female employees.

  20. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

    Science.gov (United States)

    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  1. Distinct Effects of Rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine on Cellular Bioenergetics and Cell Death

    OpenAIRE

    Samantha Giordano; Jisun Lee; Victor M. Darley-Usmar; Jianhua Zhang

    2012-01-01

    Parkinson's disease is characterized by dopaminergic neurodegeneration and is associated with mitochondrial dysfunction. The bioenergetic susceptibility of dopaminergic neurons to toxins which induce Parkinson's like syndromes in animal models is then of particular interest. For example, rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP(+)), and 6-hydroxydopamine (6-OHDA), have been shown to induce dopaminergic cell death ...

  2. Effect of high-intensity interval training on body composition and bioenergetic indices in boys - futsal players

    OpenAIRE

    Fatemeh Balbasi; Ramin Shabani; Marzieh Nazari

    2016-01-01

    Background: High-intensity interval trainings (HIIT) can result in the best improvement of body fitness among athletes in the shortest possible time. The impact of HIIT on bioenergetic factors of futsal players has not been studied extensively. The objective of the present study was to investigate the effect of 3-week HIIT on body composition indices, maximum aerobic power, and maximum anaerobic power, anaerobic power among boys - futsal players. Material: 30 boys - futsal players (mean± SD a...

  3. Bioenergetics and diving activity of internesting leatherback turtles Dermochelys coriacea at Parque Nacional Marino Las Baulas, Costa Rica.

    Science.gov (United States)

    Wallace, Bryan P; Williams, Cassondra L; Paladino, Frank V; Morreale, Stephen J; Lindstrom, R Todd; Spotila, James R

    2005-10-01

    Physiology, environment and life history demands interact to influence marine turtle bioenergetics and activity. However, metabolism and diving behavior of free-swimming marine turtles have not been measured simultaneously. Using doubly labeled water, we obtained the first field metabolic rates (FMRs; 0.20-0.74 W kg(-1)) and water fluxes (16-30% TBW day(-1), where TBW=total body water) for free-ranging marine turtles and combined these data with dive information from electronic archival tags to investigate the bioenergetics and diving activity of reproductive adult female leatherback turtles Dermochelys coriacea. Mean dive durations (7.8+/-2.4 min (+/-1 s.d.), bottom times (2.7+/-0.8 min), and percentage of time spent in water temperatures (Tw) or =0.99). This suggests that low FMRs and activity levels, combined with shuttling between different water temperatures, could allow leatherbacks to avoid overheating while in warm tropical waters. Additionally, internesting leatherback dive durations were consistently shorter than aerobic dive limits calculated from our FMRs (11.7-44.3 min). Our results indicate that internesting female leatherbacks maintained low FMRs and activity levels, thereby spending relatively little energy while active at sea. Future studies should incorporate data on metabolic rate, dive patterns, water temperatures, and body temperatures to develop further the relationship between physiological and life history demands and marine turtle bioenergetics and activity.

  4. Testing a bioenergetics-based habitat choice model: bluegill (Lepomis macrochirus) responses to food availability and temperature

    Science.gov (United States)

    2011-01-01

    Using an automated shuttlebox system, we conducted patch choice experiments with 32, 8–12 g bluegill sunfish (Lepomis macrochirus) to test a behavioral energetics hypothesis of habitat choice. When patch temperature and food levels were held constant within patches but different between patches, we expected bluegill to choose patches that maximized growth based on the bioenergetic integration of food and temperature as predicted by a bioenergetics model. Alternative hypotheses were that bluegill may choose patches based only on food (optimal foraging) or temperature (behavioral thermoregulation). The behavioral energetics hypothesis was not a good predictor of short-term (from minutes to weeks) patch choice by bluegill; the behavioral thermoregulation hypothesis was the best predictor. In the short-term, food and temperature appeared to affect patch choice hierarchically; temperature was more important, although food can alter temperature preference during feeding periods. Over a 19-d experiment, mean temperatures occupied by fish offered low rations did decline as predicted by the behavioral energetics hypothesis, but the decline was less than 1.0 °C as opposed to a possible 5 °C decline. A short-term, bioenergetic response to food and temperature may be precluded by physiological costs of acclimation not considered explicitly in the behavioral energetics hypothesis.

  5. Accumulation of 3-hydroxytetradecenoic acid: Cause or corollary of glucolipotoxic impairment of pancreatic β-cell bioenergetics?

    Science.gov (United States)

    Doliba, Nicolai M.; Liu, Qing; Li, Changhong; Chen, Jie; Chen, Pan; Liu, Chengyang; Frederick, David W.; Baur, Joseph A.; Bennett, Michael J.; Naji, Ali; Matschinsky, Franz M.

    2015-01-01

    Objectives Hyperglycemia and elevated blood lipids are the presumed precipitating causes of β-cell damage in T2DM as the result of a process termed “glucolipotoxicity”. Here, we tested whether glucolipotoxic pathophysiology is caused by defective bioenergetics using islets in culture. Methods Insulin secretion, respiration, ATP generation, fatty acid (FA) metabolite profiles and gene expression were determined in isolated islets treated under glucolipotoxic culture conditions. Results Over time, chronic exposure of mouse islets to FAs with glucose leads to bioenergetic failure and reduced insulin secretion upon stimulation with glucose or amino acids. Islets exposed to glucolipotoxic conditions displayed biphasic changes of the oxygen consumption rate (OCR): an initial increase in baseline and Vmax of OCR after 3 days, followed by decreased baseline and glucose stimulated OCR after 5 days. These changes were associated with lower islet ATP levels, impaired glucose-induced ATP generation, a trend for reduced mitochondrial DNA content and reduced expression of mitochondrial transcription factor A (Tfam). We discovered the accumulation of carnitine esters of hydroxylated long chain FAs, in particular 3-hydroxytetradecenoyl-carnitine. Conclusions As long chain 3-hydroxylated FA metabolites are known to uncouple heart and brain mitochondria [53], [54], [55], we propose that under glucolipotoxic condition, unsaturated hydroxylated long-chain FAs accumulate, uncouple and ultimately inhibit β-cell respiration. This leads to the slow deterioration of mitochondrial function progressing to bioenergetics β-cell failure. PMID:26909309

  6. Exploring geomorphic controls on fish bioenergetics in mountain streams: linkages between channel morphology and rearing habitat for cutthroat trout

    Science.gov (United States)

    Cienciala, P.; Hassan, M. A.

    2013-12-01

    Landscape heterogeneity constitutes an important control on spatial distribution of habitat for living organisms, at a range of spatial scales. For example, spatial variation in geomorphic processes can spatially structure populations as well as entire communities, and affect various ecosystem processes. We have coupled a 2D hydrodynamic model with a bioenergetic model to study the effects of various channel morphologies and bed textures on rearing habitat for coastal cutthroat trout (Oncorhynchus clarki clarki) in four reaches of a mountain stream. The bioenergetic model uses energy conservation principle to calculate energy budget for fish at any point of the study domain, given a set of relevant local conditions. Specifically, the energy intake is a function of food availability (invertebrate drift) while the energy expenditure occurs through, for example, basal metabolism and swimming to hold position against the flow. Channel morphology and bed texture, through their influence on channel hydraulics, can exert strong control on the spatial pattern of both food flux and swimming cost for drift-feeding fish. Therefore, the coupled hydrodynamic and bioenergetic models, parameterized using an extensive field data set, enabled us to explore mechanistic linkages between geomorphic properties of the study reaches, food resource availability, and the energetic profitability of rearing habitat for different age-classes at both between- and within-reach spatial scales.

  7. Arabidopsis Seed Mitochondria Are Bioenergetically Active Immediately upon Imbibition and Specialize via Biogenesis in Preparation for Autotrophic Growth.

    Science.gov (United States)

    Paszkiewicz, Gaël; Gualberto, José M; Benamar, Abdelilah; Macherel, David; Logan, David C

    2017-01-01

    Seed germination is a vital developmental transition for production of progeny by sexual reproduction in spermatophytes. Quiescent cells in nondormant dry embryos are reawakened first by imbibition and then by perception of germination triggers. Reanimated tissues enter into a germination program requiring energy for expansion growth. However, germination requires that embryonic tissues develop to support the more energy-demanding processes of cell division and organogenesis of the new seedling. Reactivation of mitochondria to supply the required energy is thus a key process underpinning germination and seedling survival. Using live imaging, we investigated reactivation of mitochondrial bioenergetics and dynamics using Arabidopsis thaliana as a model. Bioenergetic reactivation, visualized by presence of a membrane potential, is immediate upon rehydration. However, reactivation of mitochondrial dynamics only occurs after transfer to germination conditions. Reactivation of mitochondrial bioenergetics is followed by dramatic reorganization of the chondriome (all mitochondrial in a cell, collectively) involving massive fusion and membrane biogenesis to form a perinuclear tubuloreticular structure enabling mixing of previously discrete mitochondrial DNA nucleoids. The end of germination coincides with fragmentation of the chondriome, doubling of mitochondrial number, and heterogeneous redistribution of nucleoids among the mitochondria, generating a population of mitochondria tailored to seedling growth.

  8. Effects of Neospora caninum infection on brain microvascular endothelial cells bioenergetics

    Directory of Open Access Journals (Sweden)

    Elsheikha Hany M

    2013-01-01

    Full Text Available Abstract Background The brain is the most commonly affected organ during Neospora caninum infection but the mechanisms utilized by this protozoan parasite for traversal of the blood–brain barrier (BBB are not yet understood. Herein, we investigate the cellular pathogenicity of N. caninum infection on bioenergetics of human brain microvascular endothelial cells (HBMECs, a fundamental component of the BBB. Methods We tracked the growth kinetics of N. caninum in HBMECs. Focusing on cell bioenergetics, oxygen consumption rate (OCR was determined using Clark electrode system and mitochondrial membrane potential (ΔΨm was evaluated using DePsipher staining by fluorescence microscopy in the presence and absence of infection. Results HBMECs provided a receptive environment for parasite proliferation. N. caninum tachyzoites were able to invade and replicate within HBMECs without significantly altering cell proliferation rate, as measured with the MTT assay, up to 24 hr post infection (pi. The oxygen consumption rate (OCR was significantly inhibited (p 6 cell min-1 and from −0.29±0.09 to −0.16±0.1 nmol 106 cell min-1 for uninfected HBMECs and free N. Caninum tachyzoites, respectively]. After normalization for DNA content the basal OCR did not differ between two host cell types: HBMECs and K562. The OCR of HBMECs was significantly elevated 24 hr pi in the absence of substrate, in 10 mM glucose and in the presence of a tetramethyl-p-phenylenediamine (TMPD/ascorbate redox shuttle. Although quantitatively similar results were observed for uninfected K562 cells, there was no effect on their OCR 24 hr pi with N. caninum under any of the above substrate conditions. 6mM azide abolished OCR in all situations. Mitochondrial staining with DePsipher indicated no change in their membrane potential (Δψm up to 24 hr pi. Conclusions N. caninum is able to grow in HBMECs without markedly disrupting their normal proliferation or mitochondrial integrity. However

  9. Faking Attention Deficit Hyperactivity Disorder

    OpenAIRE

    2011-01-01

    Attention-deficit hyperactivity disorder is a common malady in the general population, with up to 8.1 percent of adults meeting criteria for this syndrome. In the college setting, the diagnosis of attention deficit hyperactivity disorder may offer specific academic advantages. Once the diagnosis is assigned, the prescription of stimulant medication may provide additional secondary gains through misuse and/or diversion. For example, these drugs may be used by college consumers to increase aler...

  10. Visuospatial deficits of dyslexic children

    OpenAIRE

    Lipowska, Małgorzata; Czaplewska, Ewa; Wysocka, Anna

    2011-01-01

    Summary Background The visuospatial deficit is recognized as typical for dyslexia only in some definitions. However problems with visuospatial orientation may manifest themselves as difficulties with letter identification or the memorizing and recalling of sign sequences, something frequently experienced by dyslexics. Material/Methods The experimental group consisted of 62 children with developmental dyslexia. The control group consisted of 67 pupils with no diagnosed deficits, matched to the...

  11. A Precedent-setting Case of Dynamic Triggering

    Science.gov (United States)

    Gomberg, J. S.

    2013-12-01

    On October 28, 2012 the M7.7 Haida Gwaii, British Columbia earthquake broke the southern end of the Queen Charlotte plate-boundary fault system. Less than 3 months later on January 5, 2013 the M7.5 Craig, Alaska earthquake broke the same fault system ~385 km to the northwest. In its public statements about the Craig earthquake, the US Geological Survey noted its likely causal connection with the Haida Gwaii earthquake three months earlier. This inference was based on the improbability of two large earthquakes with recurrence intervals of hundreds of years or more on the same fault system occurring within the same 3-month interval by chance (the Poisson probability is ~.0004% assuming a 100 yr recurrence interval). What physical processes plausibly connect these two events? Although of the correct sign to encourage failure, static stress changes were more than an order of magnitude smaller than triggering thresholds documented elsewhere, and the duration between the events was too small for accrual of significant visco-elastic stress changes. The M7.7 Haida Gwaii earthquake was noteworthy in many aspects, but most remarkable was that the seismic waves it radiated probably dynamically triggered the M7.5 Craig earthquake thereby setting two new important precedents. First, the magnitude of the triggered earthquake exceeds all previously documented cases of dynamic triggering of frictional, shear failure earthquakes. Second, the extraordinarily large amplitude (peak velocities in excess of 1 cm/s) and long duration (several 100 sec) triggering waves likely resulted from trapping of energy within a sedimentary trough, rather than from focusing due to source effects as in most previous examples of clear dynamic triggering. Unlike source characteristics that vary unpredictably from event to event, the permanence of structural features that act as wave-guides suggests enhanced triggering probabilities in this and likely the numerous other settings. In these settings

  12. Bioenergetics Race: Teaching Cellular Metabolism to High School Students Through an Educational Game

    Directory of Open Access Journals (Sweden)

    I.E.P. Silva

    2011-04-01

    Full Text Available Biochemistry is a science that deals with complex and abstract topics, which are often not understood by high school students, thus interfering in theteaching/learning process. The educational teaching game isa methodology advocated by several educators. The aim of this study was to develop a pedagogical practice to assist in the teaching/learning of high school students. Inthis context we designed a game about Metabolism, which was named "Bioenergetics Race". The game issimple, uses low cost materials and have easy access. The game consists of a board, chips, and a list with 100 multiple questions. Operation of the game: Selected questions lead the students to draw a card and move the corresponding number of squares on the board. The one who reachesthe finish line first is the winner. To consolidate the proposal information, every answer was discussed. At the end of the game the students answered a questionnaire. According to 77.5% of players the level of difficulty was large and 83% rated the game as good for educational proposal. It was found that 100% of students had neverparticipated in such activity in the classroom. It is notable the interest of students andthe abstract and complex topics are better assimilated.

  13. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  14. Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial Bioenergetics Associated to the Ageing Process.

    Science.gov (United States)

    Colom, Bartomeu; Oliver, Jordi; Garcia-Palmer, Francisco J

    2015-11-01

    The incidence of cardiac disease is age and sex dependent, but the mechanisms governing these associations remain poorly understood. Mitochondria are the organelles in charge of producing energy for the cells, and their malfunction has been linked to cardiovascular disease and heart failure. Interestingly, heart mitochondrial content and functionality are also age and sex dependent. Here we investigated the combinatory effects of age and sex in mitochondrial bioenergetics that could help to understand their role on cardiac disease. Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were isolated, and the enzymatic activities of the oxidative-phosphorylative complexes I, III, and IV and ATPase, as well as the protein levels of complex IV, β-ATPase, and mitochondrial transcription factor A (TFAM), were measured. Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein content, oxygen consumption, and H2O2 generation were also determined. Results showed a reduction in heart mitochondrial mass and functionality with age that correlated with increased H2O2 generation. Moreover, sex-dependent differences were found in several of these parameters. In particular, old females exhibited a significant loss of mitochondrial function and increased relative H2O2 production compared with their male counterparts. The results demonstrate a sex dimorphism in the age-associated defects on cardiac mitochondrial function.

  15. Genome Analysis of Structure-Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme.

    Science.gov (United States)

    Degli Esposti, Mauro

    2015-11-27

    Respiratory complex I (NADH:ubiquinone oxidoreductase) is a ubiquitous bioenergetic enzyme formed by over 40 subunits in eukaryotes and a minimum of 11 subunits in bacteria. Recently, crystal structures have greatly advanced our knowledge of complex I but have not clarified the details of its reaction with ubiquinone (Q). This reaction is essential for bioenergy production and takes place in a large cavity embedded within a conserved module that is homologous to the catalytic core of Ni-Fe hydrogenases. However, how a hydrogenase core has evolved into the protonmotive Q reductase module of complex I has remained unclear. This work has exploited the abundant genomic information that is currently available to deduce structure-function relationships in complex I that indicate the evolutionary steps of Q reactivity and its adaptation to natural Q substrates. The results provide answers to fundamental questions regarding various aspects of complex I reaction with Q and help re-defining the old concept that this reaction may involve two Q or inhibitor sites. The re-definition leads to a simplified classification of the plethora of complex I inhibitors while throwing a new light on the evolution of the enzyme function.

  16. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration

    Directory of Open Access Journals (Sweden)

    Kira M. Holmström

    2013-06-01

    Transcription factor Nrf2 and its repressor Keap1 regulate a network of cytoprotective genes involving more than 1% of the genome, their best known targets being drug-metabolizing and antioxidant genes. Here we demonstrate a novel role for this pathway in directly regulating mitochondrial bioenergetics in murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial depolarisation, decreased ATP levels and impaired respiration, whereas genetic activation of Nrf2 increases the mitochondrial membrane potential and ATP levels, the rate of respiration and the efficiency of oxidative phosphorylation. We further show that Nrf2-deficient cells have increased production of ATP in glycolysis, which is then used by the F1Fo-ATPase for maintenance of the mitochondrial membrane potential. While the levels and in vitro activities of the respiratory complexes are unaffected by Nrf2 deletion, their activities in isolated mitochondria and intact live cells are substantially impaired. In addition, the rate of regeneration of NADH after inhibition of respiration is much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken together, these results show that Nrf2 directly regulates cellular energy metabolism through modulating the availability of substrates for mitochondrial respiration. Our findings highlight the importance of efficient energy metabolism in Nrf2-mediated cytoprotection.

  17. A bioenergetic approach to model and reconstruct individual life traits from fish otoliths

    DEFF Research Database (Denmark)

    Fablet, Ronan; Pecquerie, Laure; Høie, Hans;

    2012-01-01

    Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm‐following formation provides individual records of the age, the individual history, and the natural environment of extinct and living fish species. Such data are critical for ecosy...... observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves...... for ecosystem and fisheries monitoring. They often lack validation, however, and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. From the characterization of the physico......‐chemical characteristics of fish otoliths, we present a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood...

  18. Bio-energetic changes in human gastrocnemius muscle 1-2 days after strenuous exercise.

    Science.gov (United States)

    Kemp, G J; Taylor, D J; Radda, G K; Rajagopalan, B

    1992-09-01

    [31P]magnetic resonance spectroscopy was used to study the metabolic sequelae of intense muscular activity in gastrocnemius of seven subjects 1-2 days after a 67-mile bicycle ride. The muscle was examined at rest, during a test exercise and during recovery from test exercise. Post-ride and pre-ride results were compared. At rest, the ratio of phosphocreatine to ATP (PCr/ATP) was increased post-ride; during test exercise PCr/(PCr+Pi) was lower post-ride; and the recoveries of PCr, Pi and PCr/(PCr+Pi) after test exercise were delayed, with decreased 'overshoot' of PCr/(PCr+Pi) (which is due to recovery of Pi to below its resting value). Mild mitochondrial damage (perhaps due to exposure to high cytosolic [Pi] during the bicycle ride) may explain some of these results. In contrast to reports of largely eccentric exercise there was no increase in resting Pi/ATP. We have thus demonstrated perturbations of muscle bio-energetics 1-2 days after strenuous exercise, in the absence of convincing enzymological evidence of muscle damage.

  19. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    George H. Trksak

    2013-01-01

    Full Text Available In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate, α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

  20. Study of bioenergetics of mouse pregnant uterine muscle by magnetic resonance spectroscopy (MRS)

    Energy Technology Data Exchange (ETDEWEB)

    Negami, Akira; Tominaga, Toshiro

    1989-06-01

    To investigate the bioenergetics of uterine muscles in vivo, we examined the energy state of mouse preterm uterus by means of magnetic resonance spectroscopy. Full-term mouse uterus contained ATP, PCr, phospho-di and mono ester (PDE and PME) and inorganic phosphate (Pi). The oxytocin-induced uterine muscle contraction peaks level and positions changed. Multiple peak analysis indicated a muscle contraction induced increase in the Pi concentration and decrease in the PCr concentration. The peak position of Pi was shifted in the contractive state also, indicating that the intracellular pH was lower than in the non-contractive state and this low pH level was recovered within several minutes. There was no change in the AMP peak neight in the contractive and non-contractive states. These data indicated that the energetics of mouse uterine muscle was maintained by the ATP-PCr system and acidosis of muscle was recovered within several minutes at rest. The constant AMP peak levels may indicate that phosphorylase is not regulated by AMP, but the phosphorylated phosphorylase kinase and pH levels in the contractive and non-contractive states also may indicate that phosphorylase kinase is not regulated by proteolysis or by the intracellular pH level but by the elevated intracellular calcium ion and calmodulin system. (author).

  1. Effect of a levee setback on aquatic resources using two-dimensional flow and bioenergetics models

    Science.gov (United States)

    Black, Robert W.; Czuba, Christiana R.; Magirl, Christopher S.; McCarthy, Sarah; Berge, Hans; Comanor, Kyle

    2016-04-05

    Watershed restoration is the focus of many resource managers and can include a multitude of restoration actions each with specific restoration objectives. For the White River flowing through the cities of Pacific and Sumner, Washington, a levee setback has been proposed to reconnect the river with its historical floodplain to help reduce flood risks, as well as provide increased habitat for federally listed species of salmonids. The study presented here documents the use of a modeling framework that integrates two-dimensional hydraulic modeling with process-based bioenergetics modeling for predicting how changes in flow from reconnecting the river with its floodplain affects invertebrate drift density and the net rate of energy intake of juvenile salmonids. Modeling results were calculated for flows of 25.9 and 49.3 cubic meters per second during the spring, summer, and fall. Predicted hypothetical future mean velocities and depths were significantly lower and more variable when compared to current conditions. The abundance of low energetic cost and positive growth locations for salmonids were predicted to increase significantly in the study reach following floodplain reconnection, particularly during the summer. This modeling framework presents a viable approach for evaluating the potential fisheries benefits of reconnecting a river to its historical floodplain that integrates our understanding of hydraulic, geomorphology, and organismal biology.

  2. A novel method for pulmonary research: assessment of bioenergetic function at the air-liquid interface.

    Science.gov (United States)

    Xu, Weiling; Janocha, Allison J; Leahy, Rachel A; Klatte, Ryan; Dudzinski, Dave; Mavrakis, Lori A; Comhair, Suzy A A; Lauer, Mark E; Cotton, Calvin U; Erzurum, Serpil C

    2014-01-01

    Air-liquid interface cell culture is an organotypic model for study of differentiated functional airway epithelium in vitro. Dysregulation of cellular energy metabolism and mitochondrial function have been suggested to contribute to airway diseases. However, there is currently no established method to determine oxygen consumption and glycolysis in airway epithelium in air-liquid interface. In order to study metabolism in differentiated airway epithelial cells, we engineered an insert for the Seahorse XF24 Analyzer that enabled the measure of respiration by oxygen consumption rate (OCR) and glycolysis by extracellular acidification rate (ECAR). Oxidative metabolism and glycolysis in airway epithelial cells cultured on the inserts were successfully measured. The inserts did not affect the measures of OCR or ECAR. Cells under media with apical and basolateral feeding had less oxidative metabolism as compared to cells on the inserts at air-interface with basolateral feeding. The design of inserts that can be used in the measure of bioenergetics in small numbers of cells in an organotypic state may be useful for evaluation of new drugs and metabolic mechanisms that underlie airway diseases.

  3. A novel method for pulmonary research: Assessment of bioenergetic function at the air–liquid interface

    Directory of Open Access Journals (Sweden)

    Weiling Xu

    2014-01-01

    Full Text Available Air–liquid interface cell culture is an organotypic model for study of differentiated functional airway epithelium in vitro. Dysregulation of cellular energy metabolism and mitochondrial function have been suggested to contribute to airway diseases. However, there is currently no established method to determine oxygen consumption and glycolysis in airway epithelium in air–liquid interface. In order to study metabolism in differentiated airway epithelial cells, we engineered an insert for the Seahorse XF24 Analyzer that enabled the measure of respiration by oxygen consumption rate (OCR and glycolysis by extracellular acidification rate (ECAR. Oxidative metabolism and glycolysis in airway epithelial cells cultured on the inserts were successfully measured. The inserts did not affect the measures of OCR or ECAR. Cells under media with apical and basolateral feeding had less oxidative metabolism as compared to cells on the inserts at air-interface with basolateral feeding. The design of inserts that can be used in the measure of bioenergetics in small numbers of cells in an organotypic state may be useful for evaluation of new drugs and metabolic mechanisms that underlie airway diseases.

  4. The Bioenergetics of Isolated Mitochondria from Different Animal Models for Diabetes.

    Science.gov (United States)

    Rendon, Dairo A

    2016-01-01

    Diabetes is a metabolic alteration characterized by a higher than normal blood glucose level. For the experimental study of the metabolic changes that occur during this illness, various animal models have been introduced: alloxan- and streptozotocin-injected animals, as well as depancreatized animals, as models for type 1 diabetes, and high-fat fed diabetic animals and laboratory animals with genetic diabetes as models for type 2 diabetes. All these models have been used to investigate specific events on the cellular and organ levels that occur as a consequence of diabetes. In particular, mitochondrial energy metabolism has been extensively studied using these experimental models for diabetes. The experimental results for the bioenergetics of isolated mitochondria harvested from different animal models for diabetes, with the exception of those obtained with high-fat fed diabetic animals, are conflicting; nevertheless, many researchers now consider mitochondrial energy dysfunction as one of the direct causes of the serious complications, in various organs and tissues, that are exhibited as a result of this illness. For this reason, it is important that future research clarify the true energy functional state of these organelles isolated from diabetic animals. In the present paper, the published data on this controversial but important issue of the energetic functioning of the mitochondria isolated from diabetic animals is reviewed. This paper also includes commentary on the status of current research and makes useful suggestions for the future direction of research on this topic.

  5. Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.

    Science.gov (United States)

    Skinner, F P; Levitzky, M G; Scott, R F; Fricks, J

    1975-05-01

    Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.

  6. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics.

    Science.gov (United States)

    Tomar, Dhanendra; Dong, Zhiwei; Shanmughapriya, Santhanam; Koch, Diana A; Thomas, Toby; Hoffman, Nicholas E; Timbalia, Shrishiv A; Goldman, Samuel J; Breves, Sarah L; Corbally, Daniel P; Nemani, Neeharika; Fairweather, Joseph P; Cutri, Allison R; Zhang, Xueqian; Song, Jianliang; Jaña, Fabián; Huang, Jianhe; Barrero, Carlos; Rabinowitz, Joseph E; Luongo, Timothy S; Schumacher, Sarah M; Rockman, Michael E; Dietrich, Alexander; Merali, Salim; Caplan, Jeffrey; Stathopulos, Peter; Ahima, Rexford S; Cheung, Joseph Y; Houser, Steven R; Koch, Walter J; Patel, Vickas; Gohil, Vishal M; Elrod, John W; Rajan, Sudarsan; Madesh, Muniswamy

    2016-05-24

    Mitochondrial Ca(2+) Uniporter (MCU)-dependent mitochondrial Ca(2+) uptake is the primary mechanism for increasing matrix Ca(2+) in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired [Ca(2+)]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca(2+)-dependent mitochondrial metabolism.

  7. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Dhanendra Tomar

    2016-05-01

    Full Text Available Mitochondrial Ca2+ Uniporter (MCU-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1 have severely impaired [Ca2+]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca2+-dependent mitochondrial metabolism.

  8. Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics.

    Science.gov (United States)

    Pancrazi, Laura; Di Benedetto, Giulietta; Colombaioni, Laura; Della Sala, Grazia; Testa, Giovanna; Olimpico, Francesco; Reyes, Aurelio; Zeviani, Massimo; Pozzan, Tullio; Costa, Mario

    2015-11-10

    Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show that a fraction of Foxg1 is localized within the mitochondria in cell lines, primary neuronal or glial cell cultures, and in the mouse cortex. Import of Foxg1 in isolated mitochondria appears to be membrane potential-dependent. Amino acids (aa) 277-302 were identified as critical for mitochondrial localization. Overexpression of full-length Foxg1 enhanced mitochondrial membrane potential (ΔΨm) and promoted mitochondrial fission and mitosis. Conversely, overexpression of the C-term Foxg1 (aa 272-481), which is selectively localized in the mitochondrial matrix, enhanced organelle fusion and promoted the early phase of neuronal differentiation. These findings suggest that the different subcellular localizations of Foxg1 control the machinery that brings about cell differentiation, replication, and bioenergetics, possibly linking mitochondrial functions to embryonic development and pathological conditions.

  9. Coupling calcium dynamics and mitochondrial bioenergetic: an in silico study to simulate cardiomyocyte dysfunction.

    Science.gov (United States)

    Das, Phonindra Nath; Pedruzzi, Gabriele; Bairagi, Nandadulal; Chatterjee, Samrat

    2016-03-01

    The coupling of intracellular Ca(2+) dynamics with mitochondrial bioenergetic is crucial for the functioning of cardiomyocytes both in healthy and disease conditions. The pathophysiological signature of the Cardiomyocyte Dysfunction (CD) is commonly related to decreased ATP production due to mitochondrial functional impairment and to an increased mitochondrial calcium content ([Ca(2+)]m). These features advanced the therapeutic approaches which aim to reduce [Ca(2+)]m. But whether [Ca(2+)]m overload is the pathological trigger for CD or a physiological consequence, remained controversial. We addressed this issue in silico and showed that [Ca(2+)]m might not directly cause CD. Through model parameter recalibration, we demonstrated how mitochondria cope up with functionally impaired processes and consequently accumulate calcium. A strong coupling of the [Ca(2+)]m oscillations with the ATP synthesis rate ensures robust calcium cycling and avoids CD. We suggested a cardioprotective role of the mitochondrial calcium uniporter and predicted that a mitochondrial sodium calcium exchanger could be a potential therapeutic target to restore the normal functioning of the cardiomyocyte.

  10. Bioenergetic and pharmacokinetic model for exposure of common loon (Gavia immer) chicks to methylmercury

    Science.gov (United States)

    Karasov, W.H.; Kenow, K.P.; Meyer, M.W.; Fournier, F.

    2007-01-01

    A bioenergetics model was used to predict food intake of common loon (Gavia immer) chicks as a function of body mass during development, and a pharmacokinetics model, based on first-order kinetics in a single compartment, was used to predict blood Hg level as a function of food intake rate, food Hg content, body mass, and Hg absorption and elimination. Predictions were tested in captive growing chicks fed trout (Salmo gairdneri) with average MeHg concentrations of 0.02 (control), 0.4, and 1.2 ??g/g wet mass (delivered as CH3HgCl). Predicted food intake matched observed intake through 50 d of age but then exceeded observed intake by an amount that grew progressively larger with age, reaching a significant overestimate of 28% by the end of the trial. Respiration in older, nongrowing birds probably was overestimated by using rates measured in younger, growing birds. Close agreement was found between simulations and measured blood Hg, which varied significantly with dietary Hg and age. Although chicks may hatch with different blood Hg levels, their blood level is determined mainly by dietary Hg level beyond approximately two weeks of age. The model also may be useful for predicting Hg levels in adults and in the eggs that they lay, but its accuracy in both chicks and adults needs to be tested in free-living birds. ?? 2007 SETAC.

  11. Improving mitochondrial bioenergetics under ischemic conditions increases warm ischemia tolerance in the kidney.

    Science.gov (United States)

    Szeto, Hazel H; Liu, Shaoyi; Soong, Yi; Birk, Alexander V

    2015-01-01

    Ischemia time during partial nephrectomy is strongly associated with acute and chronic renal injury. ATP depletion during warm ischemia inhibits ATP-dependent processes, resulting in cell swelling, cytoskeletal breakdown, and cell death. The duration of ischemia tolerated by the kidney depends on the amount of ATP that can be produced with residual substrates and oxygen in the tissue to sustain cell function. We previously reported that the rat can tolerate 30-min ischemia quite well but 45-min ischemia results in acute kidney injury and progressive interstitial fibrosis. Here, we report that pretreatment with SS-20 30 min before warm ischemia in the rat increased ischemia tolerance from 30 to 45 min. Histological examination of kidney tissues revealed that SS-20 reduced cytoskeletal breakdown and cell swelling after 45-min ischemia. Electron microscopy showed that SS-20 reduced mitochondrial matrix swelling and preserved cristae membranes, suggesting that SS-20 enhanced mitochondrial ATP synthesis under ischemic conditions. Studies with isolated kidney mitochondria showed dramatic reduction in state 3 respiration and respiratory control ratio after 45-min ischemia, and this was significantly improved by SS-20 treatment. These results suggest that SS-20 increases efficiency of the electron transport chain and improves coupling of oxidative phosphorylation. SS-20 treatment after ischemia also significantly reduced interstitial fibrosis. These new findings reveal that enhancing mitochondrial bioenergetics may be an important target for improving ischemia tolerance, and SS-20 may serve well for minimizing acute kidney injury and chronic kidney disease following surgical procedures such as partial nephrectomy and transplantation.

  12. Wavy membranes and the growth rate of a planar chemical garden: Enhanced diffusion and bioenergetics.

    Science.gov (United States)

    Ding, Yang; Batista, Bruno; Steinbock, Oliver; Cartwright, Julyan H E; Cardoso, Silvana S S

    2016-08-16

    To model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is approximately linear and quadratic, respectively. We show that such a difference in ionic transport dynamics arises from the enhanced transport of metal ions across a thin gel layer present at the surface of the precipitate. The fluctuations in transverse velocity in this wavy porous gel layer allow an enhanced transport of the cation, so that the effective diffusivity is about one order of magnitude higher than that expected from molecular diffusion alone. Our theoretical predictions are in excellent agreement with our laboratory measurements of the growth of a manganese hydroxide membrane in a microfluidic channel, and this enhanced transport is thought to have been needed to account for the bioenergetics of the first single-celled organisms.

  13. In vivo and in vitro assessment of brain bioenergetics in aging rats.

    Science.gov (United States)

    Vančová, Ol'ga; Bačiak, Ladislav; Kašparová, Svatava; Kucharská, Jarmila; Palacios, Hector H; Horecký, Jaromír; Aliev, Gjumrakch

    2010-11-01

    Brain energy disorders can be present in aged men and animals. To this respect, the mitochondrial and free radical theory of aging postulates that age-associated brain energy disorders are caused by an imbalance between pro- and anti-oxidants that can result in oxidative stress. Our study was designed to investigate brain energy metabolism and the activity of endogenous antioxidants during their lifespan in male Wistar rats. In vivo brain bioenergetics were measured using ³¹P nuclear magnetic resonance (NMR) spectroscopy and in vitro by polarographic analysis of mitochondrial oxidative phosphorylation. When compared to the young controls, a significant decrease of age-dependent mitochondrial respiration and adenosine-3-phosphate (ATP) production measured in vitro correlated with significant reduction of forward creatine kinase reaction (kfor) and with an increase in phosphocreatine (PCr)/ATP, PCr/Pi and PME/ATP ratio measured in vivo. The levels of enzymatic antioxidants catalase, GPx and GST significantly decreased in the brain tissue as well as in the peripheral blood of aged rats. We suppose that mitochondrial dysfunction and oxidative inactivation of endogenous enzymes may participate in age-related disorders of brain energy metabolism.

  14. Cardiac system bioenergetics: metabolic basis of the Frank-Starling law.

    Science.gov (United States)

    Saks, Valdur; Dzeja, Petras; Schlattner, Uwe; Vendelin, Marko; Terzic, Andre; Wallimann, Theo

    2006-03-01

    The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation-contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for 'metabolic pacing', synchronizing the cellular electrical and mechanical activities with energy supply processes.

  15. 22 CFR 42.68 - Informal evaluation of family members if principal applicant precedes them.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Informal evaluation of family members if principal applicant precedes them. 42.68 Section 42.68 Foreign Relations DEPARTMENT OF STATE VISAS VISAS... Visas § 42.68 Informal evaluation of family members if principal applicant precedes them....

  16. Perspective-Free Pragmatics: Broken Precedents and the Recovery-from-Preemption Hypothesis

    Science.gov (United States)

    Kronmuller, Edmundo; Barr, Dale J.

    2007-01-01

    When speakers refer to the same referent multiple times in a conversation, they tend to follow established patterns of usage, known as "conversational precedents." Research has found that listeners expect speakers to follow precedents, and that this expectation guides their search for referents (Barr, D. J., & Keysar, B. (2002). "Anchoring…

  17. PRAGMATIC DEFICITS OF ASPERGER SYNDROME

    Directory of Open Access Journals (Sweden)

    Silmy Arizatul Humaira’

    2015-08-01

    Full Text Available Human being is social creature who needs other people to interact with. One of the ways to interact with others is communication with language. However, communication could be a complicated problem for those who were born with developmental disorder called Asperger Syndrome (AS. The communication challenge of Asperger’s is the difficulty using language appropriately for social purposes or known as pragmatic deficits. Many excellent books about autism are published whereas knowledge on pragmatic deficits are still very limited. Thus, it is expected to be a beneficial reference to understand the pragmatic deficits and to create strategies for them to communicate effectively. Therefore, this study aimed at exploring the kinds of pragmatic deficits of an individual with AS. The verbal language profiles of autism purposed by MacDonald (2004 is used to analyzed the data in depth. The descriptive qualitative method is applied to develop a comprehensive understanding about the AS case in Temple Grandin movie.The finding shows that all of the five types of communication deficits are appearing and the dominant of which is unresponsive.

  18. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice

    Directory of Open Access Journals (Sweden)

    Karen S. Coughlan

    2016-09-01

    Full Text Available Transgenic transactivation response DNA-binding protein 43 (TDP-43 mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS; however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK activation at postnatal day (P80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS.

  19. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice

    Science.gov (United States)

    Coughlan, Karen S.; Halang, Luise; Woods, Ina

    2016-01-01

    ABSTRACT Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK) activation at postnatal day (P)80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS. PMID:27491077

  20. Visual Search Deficits Are Independent of Magnocellular Deficits in Dyslexia

    Science.gov (United States)

    Wright, Craig M.; Conlon, Elizabeth G.; Dyck, Murray

    2012-01-01

    The aim of this study was to investigate the theory that visual magnocellular deficits seen in groups with dyslexia are linked to reading via the mechanisms of visual attention. Visual attention was measured with a serial search task and magnocellular function with a coherent motion task. A large group of children with dyslexia (n = 70) had slower…

  1. Attention Deficits, Attention-Deficit Hyperactivity Disorder, and Intellectual Disabilities

    Science.gov (United States)

    Deutsch, Curtis K.; Dube, William V.; McIlvane, William J.

    2008-01-01

    Attention-Deficit Hyperactivity Disorder (ADHD) and its earlier nosologic classifications have been extensively investigated since the 1960s, with PubMed listings alone exceeding 13,000 entries. Strides have been made in the diagnosis and treatment of ADHD in individuals with intellectual function in the normal range, as described in companion…

  2. S-Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics.

    Science.gov (United States)

    Módis, Katalin; Ju, YoungJun; Ahmad, Akbar; Untereiner, Ashley A; Altaany, Zaid; Wu, Lingyun; Szabo, Csaba; Wang, Rui

    2016-11-01

    Mammalian cells can utilize hydrogen sulfide (H2S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S-sulfhydration (a H2S-induced posttranslational modification, also known as S-persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the α subunit (ATP5A1) of ATP synthase in response to exposure to H2S in vitro. The H2S generator compound NaHS induced S-sulfhydration of ATP5A1 in HepG2 and HEK293 cell lysates in a concentration-dependent manner (50-300μM). The activity of immunocaptured mitochondrial ATP synthase enzyme isolated from HepG2 and HEK293 cells was stimulated by NaHS at low concentrations (10-100nM). Site-directed mutagenesis of ATP5A1 in HEK293 cells demonstrated that cysteine residues at positions 244 and 294 are subject to S-sulfhydration. The double mutant ATP synthase protein (C244S/C294S) showed a significantly reduced enzyme activity compared to control and the single-cysteine-mutated recombinant proteins (C244S or C294S). To determine whether endogenous H2S plays a role in the basal S-sulfhydration of ATP synthase in vivo, we compared liver tissues harvested from wild-type mice and mice deficient in cystathionine-gamma-lyase (CSE, one of the three principal mammalian H2S-producing enzymes). Significantly reduced S-sulfhydration of ATP5A1 was observed in liver homogenates of CSE(-/-) mice, compared to wild-type mice, suggesting a physiological role for CSE-derived endogenous H2S production in the S-sulfhydration of ATP synthase. Various forms of critical illness (including burn injury) upregulate H2S-producing enzymes and stimulate H2S biosynthesis. In liver tissues collected from mice subjected to burn injury, we detected an increased S-sulfhydration of ATP5A1 at the early time points post-burn. At later time points (when systemic H2S

  3. Effect of oxygen tension on bioenergetics and proteostasis in young and old myoblast precursor cells

    Directory of Open Access Journals (Sweden)

    M. Konigsberg

    2013-01-01

    Full Text Available In the majority of studies using primary cultures of myoblasts, the cells are maintained at ambient oxygen tension (21% O2, despite the fact that physiological O2 at the tissue level in vivo is much lower (~1–5% O2. We hypothesized that the cellular response in presence of high oxygen concentration might be particularly important in studies comparing energetic function or oxidative stress in cells isolated from young versus old animals. To test this, we asked whether oxygen tension plays a role in mitochondrial bioenergetics (oxygen consumption, glycolysis and fatty acid oxidation or oxidative damage to proteins (protein disulfides, carbonyls and aggregates in myoblast precursor cells (MPCs isolated from young (3–4 m and old (29–30 m C57BL/6 mice. MPCs were grown under physiological (3% or ambient (21% O2 for two weeks prior to exposure to an acute oxidative insult (H2O2. Our results show significantly higher basal mitochondrial respiration in young versus old MPCs, an increase in basal respiration in young MPCs maintained at 3% O2 compared to cells maintained at 21% O2, and a shift toward glycolytic metabolism in old MPCs grown at 21% O2. H2O2 treatment significantly reduced respiration in old MPCs grown at 3% O2 but did not further repress respiration at 21% O2 in old MPCs. Oxidative damage to protein was higher in cells maintained at 21% O2 and increased in response to H2O2 in old MPCs. These data underscore the importance of understanding the effect of ambient oxygen tension in cell culture studies, in particular studies measuring oxidative damage and mitochondrial function.

  4. Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

    Science.gov (United States)

    Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

    2011-10-01

    Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

  5. Formulation, General Features and Global Calibration of a Bioenergetically-Constrained Fishery Model

    Science.gov (United States)

    Bianchi, Daniele; Galbraith, Eric D.

    2017-01-01

    Human exploitation of marine resources is profoundly altering marine ecosystems, while climate change is expected to further impact commercially-harvested fish and other species. Although the global fishery is a highly complex system with many unpredictable aspects, the bioenergetic limits on fish production and the response of fishing effort to profit are both relatively tractable, and are sure to play important roles. Here we describe a generalized, coupled biological-economic model of the global marine fishery that represents both of these aspects in a unified framework, the BiOeconomic mArine Trophic Size-spectrum (BOATS) model. BOATS predicts fish production according to size spectra as a function of net primary production and temperature, and dynamically determines harvest spectra from the biomass density and interactive, prognostic fishing effort. Within this framework, the equilibrium fish biomass is determined by the economic forcings of catchability, ex-vessel price and cost per unit effort, while the peak harvest depends on the ecosystem parameters. Comparison of a large ensemble of idealized simulations with observational databases, focusing on historical biomass and peak harvests, allows us to narrow the range of several uncertain ecosystem parameters, rule out most parameter combinations, and select an optimal ensemble of model variants. Compared to the prior distributions, model variants with lower values of the mortality rate, trophic efficiency, and allometric constant agree better with observations. For most acceptable parameter combinations, natural mortality rates are more strongly affected by temperature than growth rates, suggesting different sensitivities of these processes to climate change. These results highlight the utility of adopting large-scale, aggregated data constraints to reduce model parameter uncertainties and to better predict the response of fisheries to human behaviour and climate change. PMID:28103280

  6. A bioenergetics-kinetics coupled modeling study on subsurface microbial metabolism in a field biostimulation experiment

    Science.gov (United States)

    Jin, Q.; Zheng, Z.; Zhu, C.

    2006-12-01

    Microorganisms in nature conserve energy by catalyzing various geochemical reactions. To build a quantitative relationship between geochemical conditions and metabolic rates, we propose a bioenergetics-kinetics coupled modeling approach. This approach describes microbial community as a metabolic network, i.e., fermenting microbes degrade organic substrates while aerobic respirer, nitrate reducer, metal reducer, sulfate reducer, and methanogen consume the fermentation products. It quantifies the control of substrate availability and biological energy conservation on the metabolic rates using thermodynamically consistent rate laws. We applied this simulation approach to study the progress of microbial metabolism during a field biostimulation experiment conducted in Oak Ridge, Tennessee. In the experiment, ethanol was injected into a monitoring well and groundwater was sampled to monitor changes in the chemistry. With time, concentrations of ethanol and SO42- decreased while those of NH4+, Fe2+, and Mn2+ increased. The simulation results fitted well to the observation, indicating simultaneous ethanol degradation and terminal electron accepting processes. The rates of aerobic respiration and denitrification were mainly controlled by substrate concentrations while those of ethanol degradation, sulfate reduction, and methanogenesis were controlled dominantly by the energy availability. The simulation results suggested two different microbial growth statuses in the subsurface. For the functional groups with significant growth, variations with time in substrate concentrations demonstrated a typical S curve. For the groups without significant growth, initial decreases in substrate concentrations were linear with time. Injecting substrates followed by monitoring environmental chemistry therefore provides a convenient approach to characterize microbial growth in the subsurface where methods for direct observation are currently unavailable. This research was funded by the

  7. An overview of methods for developing bioenergetic and life history models for rare and endangered species

    Science.gov (United States)

    Petersen, J.H.; DeAngelis, D.L.; Paukert, C.P.

    2008-01-01

    Many fish species are at risk to some degree, and conservation efforts are planned or underway to preserve sensitive populations. For many imperiled species, models could serve as useful tools for researchers and managers as they seek to understand individual growth, quantify predator-prey dynamics, and identify critical sources of mortality. Development and application of models for rare species however, has been constrained by small population sizes, difficulty in obtaining sampling permits, limited opportunities for funding, and regulations on how endangered species can be used in laboratory studies. Bioenergetic and life history models should help with endangered species-recovery planning since these types of models have been used successfully in the last 25 years to address management problems for many commercially and recreationally important fish species. In this paper we discuss five approaches to developing models and parameters for rare species. Borrowing model functions and parameters from related species is simple, but uncorroborated results can be misleading. Directly estimating parameters with laboratory studies may be possible for rare species that have locally abundant populations. Monte Carlo filtering can be used to estimate several parameters by means of performing simple laboratory growth experiments to first determine test criteria. Pattern-oriented modeling (POM) is a new and developing field of research that uses field-observed patterns to build, test, and parameterize models. Models developed using the POM approach are closely linked to field data, produce testable hypotheses, and require a close working relationship between modelers and empiricists. Artificial evolution in individual-based models can be used to gain insight into adaptive behaviors for poorly understood species and thus can fill in knowledge gaps. ?? Copyright by the American Fisheries Society 2008.

  8. Comparison of selenium bioaccumulation in the clams Corbicula fluminea and Potamocorbula amurensis: A bioenergetic modeling approach

    Science.gov (United States)

    Lee, B.-G.; Lee, J.-S.; Luoma, S.N.

    2006-01-01

    Selenium uptake from food (assimilation efficiency) and dissolved phase (influx rate) as well as loss kinetics (efflux rate) were compared between two bivalves, Corbicula fluminea and Potamocorbula amurensis. The effects of salinity and temperature on these kinetic parameters for both clam species also were evaluated. The Asiatic clam, C. fluminea, more efficiently assimilated Se associated with algae (66-87%) than Se associated with oxic sediments (20-37%). However, no consistent difference was found between Se assimilation efficiencies from both food types (19-60%) for P. amurensis. The temperature and salinity had a minor influence on the Se assimilation from ingested food. However, the effects of temperature and salinity were more evident in the uptake from dissolved sources. The influx rate of Se(IV) increased by threefold with the increase of temperature from 5 to 21??C for C. fluminea. The increase of salinity from 4 to 20 psu decreased the uptake rate constant (ku) of Se in P. amurensis from 0.011 to 0.005 L/g/h, whereas salinity change (0-8 psu) had a negligible effect on the Se influx rate of C. fluminea. The Se influx rate of P. amurensis decreased by half with the 3.5-fold increase in tissue dry weight. The rate constant of loss was greater for P. amurensis (0.029/d at 8 psu) than for C. fluminea (0.014/d at 0 psu and 0.01/d at 8 psu). A bioenergetic model suggests that dietary uptake is the dominant pathway for Se bioaccumulation in the two clams in San Francisco Bay and that interspecies differences in Se bioaccumulation can be explained by differences in food ingestion rates. ?? 2006 SETAC.

  9. The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria.

    Science.gov (United States)

    Macchioni, Lara; Davidescu, Magdalena; Roberti, Rita; Corazzi, Lanfranco

    2014-10-01

    Tumor cells favor abnormal energy production via aerobic glycolysis and show resistance to apoptosis, suggesting the involvement of mitochondrial dysfunction. The differences between normal and cancer cells in their energy metabolism provide a biochemical basis for developing new therapeutic strategies. The energy blocker 3-bromopyruvate (3BP) can eradicate liver cancer in animals without associated toxicity, and is a potent anticancer towards glioblastoma cells. Since mitochondria are 3BP targets, in this work the effects of 3BP on the bioenergetics of normal rat brain mitochondria were investigated in vitro, in comparison with the anticancer agent lonidamine (LND). Whereas LND impaired oxygen consumption dependent on any complex of the respiratory chain, 3BP was inhibitory to malate/pyruvate and succinate (Complexes I and II), but preserved respiration from glycerol-3-phosphate and ascorbate (Complex IV). Accordingly, although electron flow along the respiratory chain and ATP levels were decreased by 3BP in malate/pyruvate- and succinate-fed mitochondria, they were not significantly influenced from glycerol-3-phosphate- or ascorbate-fed mitochondria. LND produced a decrease in electron flow from all substrates tested. No ROS were produced from any substrate, with the exception of 3BP-induced H(2)O(2) release from succinate, which suggests an antimycin-like action of 3BP as an inhibitor of Complex III. We can conclude that 3BP does not abolish completely respiration and ATP synthesis in brain mitochondria, and has a limited effect on ROS production, confirming that this drug may have limited harmful effects on normal cells.

  10. Acute starvation in C57BL/6J mice increases myocardial UCP2 and UCP3 protein expression levels and decreases mitochondrial bio-energetic function.

    Science.gov (United States)

    Wang, Chun-Ming; Almsherqi, Zakaria A; McLachlan, Craig S; Matthews, Slade; Ramachandran, Malarmathy; Tay, Stacey Kh; Deng, Yuru

    2011-01-01

    Associations between uncoupling protein (UCP) expression and functional changes in myocardial mitochondrial bio-energetics have not been well studied during periods of starvation stress. Our aim was to study the effects of acute starvation, for 24 or 48 h, on combined cardiac mitochondrial function and UCP expression in mice. Isolated heart mitochondria from female mice starved for 48 h compared to that from mice fed revealed a significantly (p bio-energetic functional changes were associated with increases in mitochondrial UCP2 and UCP3 protein expression. In conclusion, our findings suggest that increased UCP2 and UCP3 levels may contribute to decreased myocardial mitochondrial bio-energetic function due to starvation.

  11. Constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms: Progress report for period 1 January 1987 to 31 December 1987

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, J.R.; Standora, E.A.

    1987-09-01

    We quantified the constraints of bioenergetics on the ecology and distribution of vertebrate ectotherms. We completed studies on the thermoregulation of largemouth bass, on the bioenergetics of the slider turtle, Trachemys scripta, and on the role of temperature dependent sex determination in the extinction of dinosaurs. We also began research to develop the three dimensional bioenergetic climate space for freshwater turtles, to determine the role of incubation temperature on the post hatching growth rate of the snapping turtle, Chelydra serpentina, to establish the rate of energy expenditure of the slider turtle, Trachemys scripta, in the field, to determine the field metabolic rates, body temperatures and water flux rates of the box turtle, Terrapene carolina, and to measure the effect of diet type on the consumption rate, digestion rate and digestive efficiency of adult T. scripta. 60 refs., 9 figs.

  12. Influence of a preceding auditory stimulus on evoked potential of the succeeding stimulus

    Institute of Scientific and Technical Information of China (English)

    WANG Mingshi; LIU Zhongguo; ZHU Qiang; LIU Jin; WANG Liqun; LIU Haiying

    2004-01-01

    In the present study, we investigated the influence of the preceding auditory stimulus on the auditory-evoked potential (AEP) of the succeeding stimuli, when the human subjects were presented with a pair of auditory stimuli. We found that the evoked potential of the succeeding stimulus was inhibited completely by the preceding stimulus, as the inter-stimulus interval (ISI) was shorter than 150 ms. This influence was dependent on the ISI of two stimuli, the shorter the ISI the stronger the influence would be. The inhibitory influence of the preceding stimulus might be caused by the neural refractory effect.

  13. Lazy males? Bioenergetic differences in energy acquisition and metabolism help to explain sexual size dimorphism in percids.

    Science.gov (United States)

    Rennie, Michael D; Purchase, Craig F; Lester, Nigel; Collins, Nicholas C; Shuter, Brian J; Abrams, Peter A

    2008-09-01

    1. Differences in energy use between genders is a probable mechanism underlying sexual size dimorphism (SSD), but testing this hypothesis in the field has proven difficult. We evaluated this mechanism as an explanation for SSD in two North American percid species--walleye Sander vitreus and yellow perch Perca flavescens. 2. Data from 47 walleye and 67 yellow perch populations indicated that SSD is associated with the onset of maturation: typically, males of both species matured smaller and earlier and attained a smaller asymptotic size than females. Males also demonstrated equal (perch) or longer (walleye) reproductive life spans compared with females. 3. To examine whether reduced post-maturation growth in males was due to lower energy acquisition or higher reproductive costs we applied a contaminant mass-balance model combined with a bioenergetics model to estimate metabolic costs and food consumption of each sex. Mature males exhibited lower food consumption, metabolic costs and food conversion efficiencies compared with females. 4. We propose that slower growth in males at the onset of maturity is a result of decreased feeding activity to reduce predation risk. Our finding that SSD in percids is associated with the onset of maturity is supported by laboratory-based observations reported elsewhere, showing that changes in growth rate, consumption and food conversion efficiency were elicited by oestrogen (positive effects) or androgen (negative effects) exposure in P. flavescens and P. fluviatilis. 5. Researchers applying bioenergetic models for comparative studies across populations should use caution in applying bioenergetic models in the absence of information on population sex ratio and potential differences between the sexes in energetic parameters.

  14. Methane efflux from marine sediments in passive and active margins: Estimations from bioenergetic reaction-transport simulations

    Science.gov (United States)

    Dale, A. W.; Van Cappellen, P.; Aguilera, D. R.; Regnier, P.

    2008-01-01

    A simplified version of a kinetic-bioenergetic reaction model for anaerobic oxidation of methane (AOM) in marine sediments [Dale, A.W., Regnier, P., Van Cappellen, P., 2006. Bioenergetic controls on anaerobic oxidation of methane (AOM) in coastal marine sediments: a theoretical analysis. Am. J. Sci. 306, 246-294.] is used to assess the impact of transport processes on biomass distributions, AOM rates and methane release fluxes from the sea floor. The model explicitly represents the functional microbial groups and the kinetic and bioenergetic limitations of the microbial metabolic pathways involved in AOM. Model simulations illustrate the dominant control exerted by the transport regime on the activity and abundance of AOM communities. Upward fluid flow at active seep systems restricts AOM to a narrow subsurface reaction zone and sustains high rates of methane oxidation. In contrast, pore-water transport dominated by molecular diffusion leads to deeper and broader zones of AOM, characterized by much lower rates and biomasses. Under steady-state conditions, less than 1% of the upward dissolved methane flux reaches the water column, irrespective of the transport regime. However, a sudden increase in the advective flux of dissolved methane, for example as a result of the destabilization of methane hydrates, causes a transient efflux of methane from the sediment. The benthic efflux of dissolved methane is due to the slow growth kinetics of the AOM community and lasts on the order of 60 years. This time window is likely too short to allow for a significant escape of pore-water methane following a large scale gas hydrate dissolution event such as the one that may have accompanied the Paleocene/Eocene Thermal Maximum (PETM).

  15. Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

    Science.gov (United States)

    Savourey, G; Clerc, L; Vallerand, A L; Leftheriotis, G; Mehier, H; Bittel, J H

    1992-01-01

    To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.

  16. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders.

    Science.gov (United States)

    Romero-Munguía, Miguel Ángel

    2013-01-01

    Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.

  17. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Romero-Munguía

    2013-01-01

    Full Text Available Individuals with autism spectrum disorders (ASD have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad. Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.

  18. Attention Deficit Hyperactivity Disorder (ADHD)

    Centers for Disease Control (CDC) Podcasts

    2014-04-10

    This podcast discusses Attention Deficit Hyperactivity Disorder, or ADHD, the most common behavioral disorder in children. Learn about symptoms, risk factors, and treatment.  Created: 4/10/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  19. The influence of behavior preceding a reinforced response on behavior change in the classroom.

    Science.gov (United States)

    Kazdin, A E

    1977-01-01

    The influence of behavior that immediately precedes a reinforced target response on the effectiveness of a reinforcement contingency was examined in two experiments with mentally retarded children in a special-education classroom. Two reinforcement schedules were examined in each experiment. For each schedule, a prespecified period of attentive behavior served as the target response. The schedules differed in whether inattentive or attentive behavior was required immediately to precede the target response. These schedules were examined with one child in a simultaneous treatment design using praise as the reinforcer (Experiment I), and with two children in separate reversal designs using tokens as the reinforcer (Experiment II). While attentive behavior increased under each schedule, the increase was greater when attentive rather than inattentive behavior preceded the reinforced response. The results indicated that the effect of a contingency may be determined not only by the specific response reinforced but also by the behavior that immediately precedes that response.

  20. Exact and Heuristic Algorithms for Routing AGV on Path with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2016-01-01

    Full Text Available A new problem arises when an automated guided vehicle (AGV is dispatched to visit a set of customers, which are usually located along a fixed wire transmitting signal to navigate the AGV. An optimal visiting sequence is desired with the objective of minimizing the total travelling distance (or time. When precedence constraints are restricted on customers, the problem is referred to as traveling salesman problem on path with precedence constraints (TSPP-PC. Whether or not it is NP-complete has no answer in the literature. In this paper, we design dynamic programming for the TSPP-PC, which is the first polynomial-time exact algorithm when the number of precedence constraints is a constant. For the problem with number of precedence constraints, part of the input can be arbitrarily large, so we provide an efficient heuristic based on the exact algorithm.

  1. Historical Uses of Meteoritic Metals as Precedent for Modern In-Situ Asteroid Mining

    Science.gov (United States)

    Krispin, D.; Mardon, A. A.; Fawcett, B. G.

    2016-08-01

    The strain on earth's resources of metal and the metallic density of meteorites mean that in situ asteroid mining is advisable. This has precedent: Use of meteoritic metal dates back to ancient times.

  2. Jogando com os precedentes: regras, analogias, princípios Playing with precedents: rules, analogies, principles

    Directory of Open Access Journals (Sweden)

    Antonio Moreira Maués

    2012-12-01

    Full Text Available Este artigo analisa decisões recentes do STF envolvendo a aplicação de súmulas vinculantes à luz de três concepções de precedentes, desenvolvidas por F. Schauer (precedentes como regras, C. Sunstein (precedentes como analogias e R. Dworkin (precedentes como princípios. Após a exposição dos principais aspectos de cada uma dessas teorias baseadas, respectivamente, nos conceitos de generalizações enraizadas, acordos teóricos incompletos e romance em cadeia, e discute os fundamentos que elas podem oferecer para o uso de precedentes no direito brasileiro.This article analyses the use of binding precedents by the Brazilian Supreme Court in the light of three conceptions of precedents, which are developed by F. Schauer (precedents as rules, C. Sunstein (precedents as analogies and R. Dworkin (precedents as principles. After the exposition of the main aspects of each theory, based respectively on the concepts of entrenched generalizations, incompletely theorized agreements and chain novel, the article debates the arguments that they can provide for the use of precedents in Brazilian law.

  3. An improved car-following model with two preceding cars' average speed

    Science.gov (United States)

    Yu, Shao-Wei; Shi, Zhong-Ke

    2015-01-01

    To better describe cooperative car-following behaviors under intelligent transportation circumstances and increase roadway traffic mobility, the data of three successive following cars at a signalized intersection of Jinan in China were obtained and employed to explore the linkage between two preceding cars' average speed and car-following behaviors. The results indicate that two preceding cars' average velocity has significant effects on the following car's motion. Then an improved car-following model considering two preceding cars' average velocity was proposed and calibrated based on full velocity difference model and some numerical simulations were carried out to study how two preceding cars' average speed affected the starting process and the traffic flow evolution process with an initial small disturbance, the results indicate that the improved car-following model can qualitatively describe the impacts of two preceding cars' average velocity on traffic flow and that taking two preceding cars' average velocity into account in designing the control strategy for the cooperative adaptive cruise control system can improve the stability of traffic flow, suppress the appearance of traffic jams and increase the capacity of signalized intersections.

  4. Effects of Different Preceding Crops on Soil Micro-ecological Environment and Yield of Cucumber

    Institute of Scientific and Technical Information of China (English)

    LIU Shouwei; LIU Shuqin; PAN Kai; WANG Lili; WU Fengzhi

    2011-01-01

    Pepper, celery, eggplant and tomato were used as preceding crops to study their effects on the yield, soil microorganism quantity and soil enzyme activities of cucumber. Results showed that four preceding crops all increased soil microorganism quantity in cucumber, but decreased population of Fusarium oxysporum. The effect of pepper was more significant than that of the others Populations of soil bacteria, fungi and actinomyces of pepper treatment were significantly higher than those of the other treatments, except that the populations of fungi had no significant difference with celery and eggplant treatments on 50 days after transplanting, while that of Fusarium oxysporum was fewer than that of the other treatments. The soil microorganism quantity in celery and eggplant treatment was more significant than tomato, but lower population of Fusarium oxysporum. Four preceding crops all increased sol enzyme activities, lnvertase and urease activities of pepper treatment were significantly higher than those of the other treatments, catalase activities of pepper, celery and eggplant treatments were significantly higher than those of tomato and the control treatments All preceding crops remarkably increased cucumber yield, with pepper as the highest. Comparing with the control, cucumber yields of pepper, celery and eggplant treatments increased by 24.9%, 13.6% and 11.9%, respectively. Results suggested that four preceding crops all improved soil microbial ecology and increased cucumber yield. The pepper was the most suitable preceding crop, then followed by celery and eggplant. Tomato had the similar effect as the control.

  5. Pramipexole reverses Parkinson's disease-related motivational deficits in rats.

    Science.gov (United States)

    Favier, Mathieu; Duran, Theo; Carcenac, Carole; Drui, Guillaume; Savasta, Marc; Carnicella, Sebastien

    2014-06-01

    Recent evidence suggests that Parkinson's disease affects not only movement, but also cognitive and psychiatric functions. Among these nonmotor complications, apathy, which is defined as a lack of motivation and operationalized as a quantitative reduction in goal-directed behavior, may even precede motor impairments, disappearing with the introduction of dopaminergic (DA) therapies and possibly reappearing with its discontinuation, suggesting a causal role of DA. We recently developed a lesion-based model, with stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into precise areas of the rat SNc or ventral tegmental area and showed, in several operant tasks, that a partial denervation of the nigrostriatal, but not of the mesocorticolimbic, DA system induced profound motivational deficits during instrumental action. We investigated the time course of the effects of nigrostriatal DA denervation on motivation in rats, by assessing the negative effect of SNc bilateral 6-OHDA infusion on preacquired operant behavior, and determining whether the induced deficits were sensitive to the introduction and withdrawal of a clinically relevant PD treatment, the DA D2/D3 receptor agonist, pramipexole (PRA). Partial nigrostriatal DA denervation was accompanied by a significant reduction in operant behavior. This deficit, indicative of a decrease in motivation, was fully reversed by PRA and reappeared after treatment withdrawal. This longitudinal preclinical study provides evidence for the implication of the DA nigrostriatal system in PD-associated apathy. Moreover, by showing a good isomorphy and predictive value, our model highlights the relevance of D2/D3 receptors as potential targets for alleviating apathy in PD.

  6. Neuropsychological basic deficits in preschoolers at risk for ADHD: a meta-analysis.

    Science.gov (United States)

    Pauli-Pott, Ursula; Becker, Katja

    2011-06-01

    Widely accepted neuropsychological theories on attention deficit hyperactivity disorder (ADHD) assume that the complex symptoms of the disease arise from developmentally preceding neuropsychological basic deficits. These deficits in executive functions and delay aversion are presumed to emerge in the preschool period. The corresponding normative developmental processes include phases of relative stability and rapid change. These non-linear developmental processes might have implications for concurrent and predictive associations between basic deficits and ADHD symptoms. To derive a description of the nature and strength of these associations, a meta-analysis was conducted. It is assumed that weighted mean effect sizes differ between basic deficits and depend on age. The meta-analysis included 25 articles (n=3005 children) in which associations between assessments of basic deficits (i.e. response inhibition, interference control, delay aversion, working memory, flexibility, and vigilance/arousal) in the preschool period and concurrent or subsequent ADHD symptoms or diagnosis of ADHD had been analyzed. For response inhibition and delay aversion, mean effect sizes were of medium to large magnitude while the mean effect size for working memory was small. Meta-regression analyses revealed that effect sizes of delay aversion tasks significantly decreased with increasing age while effect sizes of interference control tasks and Continuous Performance Tests (CPTs) significantly increased. Depending on the normative maturational course of each skill, time windows might exist that allow for a more or less valid assessment of a specific deficit. In future research these time windows might help to describe early developing forms of ADHD and to identify children at risk.

  7. Pragmatic Communication Deficits in Children with Epilepsy

    Science.gov (United States)

    Broeders, Mark; Geurts, Hilde; Jennekens-Schinkel, Aag

    2010-01-01

    Background: Various psychiatric and neurological disorders including epilepsy have been associated with language deficits. Pragmatic language deficits, however, have seldom been the focus of earlier studies in children with epilepsy. Moreover, it is unknown whether these pragmatic deficits are related to general intellectual functioning. Both…

  8. Bioenergetic studies of coal sulfur oxidation by extremely thermophilic bacteria. Final report, September 15, 1992--August 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, R.M.; Han, C.J.

    1997-12-31

    Thermoacidophilic microorganisms have been considered for inorganic sulfur removal from coal because of expected improvements in rates of both biotic and abiotic sulfur oxidation reactions with increasing temperature. In this study, the bioenergetic response of the extremely thermoacidophilic archaeon, Metallosphaera sedula, to environmental changes have been examined in relation to its capacity to catalyze pyrite oxidation in coal. Given an appropriate bioenergetic challenge, the metabolic response was to utilize additional amounts of energy sources (i.e., pyrite) to survive. Of particular interest were the consequences of exposing the organism to various forms of stress (chemical, nutritional, thermal, pH) in the presence of coal pyrite. Several approaches to take advantage of stress response to accelerate pyrite oxidation by this organism were examined, including attempts to promote acquired thermal tolerance to extend its functional range, exposure to chemical uncouplers and decouplers, and manipulation of heterotrophic and chemolithotrophic tendencies to optimize biomass concentration and biocatalytic activity. Promising strategies were investigated in a continuous culture system. This study identified environmental conditions that promote better coupling of biotic and abiotic oxidation reactions to improve biosulfurization rates of thermoacidophilic microorganisms.

  9. The impact of mitochondrial and thermal stress on the bioenergetics and reserve respiratory capacity of fish cell lines.

    Science.gov (United States)

    Beck, Benjamin H; Fuller, S Adam

    2012-12-01

    Various stressors affect the health of wild and cultured fish and can cause metabolic disturbances that first manifest at the cellular level. Here, we sought to further our understanding of cellular metabolism in fish by examining the metabolic responses of cell lines derived from channel catfish Ictalurus puntatus (CCO), white bass Morone chrysops (WBE), and fathead minnow Pimephales promelas (EPC) to both mitochondrial and thermal stressors. Using extracellular flux (EF) technology, we simultaneously measured the oxygen consumption rate (OCR; a measure of mitochondrial function) and extracellular acidification rate (ECAR; a surrogate of glycolysis) in each cell type. We performed a mitochondrial function protocol whereby compounds modulating different components of mitochondrial respiration were sequentially exposed to cells. This provided us with basal and maximal OCR, OCR linked to ATP production, OCR from ion movement across the mitochondrial inner membrane, the reserve capacity, and OCR independent of the electron transport chain. After heat shock, EPC and CCO significantly decreased OCR and all three cell lines modestly increased ECAR. After heat shock, the reserve capacity, the mitochondrial energetic reserve used to cope with stress and increased bioenergetic demand, was unaffected in EPC and CCO and completely abrogated in WBE. These findings provide proof-of-concept experimental data that further highlight the utility of fish cell lines as tools for modeling bioenergetics.

  10. Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice.

    Science.gov (United States)

    Giulivi, Cecilia; Ross-Inta, Catherine; Omanska-Klusek, Alicja; Napoli, Eleonora; Sakaguchi, Danielle; Barrientos, Genaro; Allen, Paul D; Pessah, Isaac N

    2011-01-07

    Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca(2+) concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca(2+), increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca(2+)-responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca(2+) in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.

  11. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function.

    Science.gov (United States)

    Esteras, Noemí; Dinkova-Kostova, Albena T; Abramov, Andrey Y

    2016-05-01

    The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor well-known for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.

  12. Relating suborganismal processes to ecotoxicological and population level endpoints using a bioenergetic model.

    Science.gov (United States)

    Ananthasubramaniam, Bharath; McCauley, Edward; Gust, Kurt A; Kennedy, Alan J; Muller, Erik B; Perkins, Edward J; Nisbet, Roger M

    2015-09-01

    Ecological effects of environmental stressors are commonly evaluated using organismal or suborganismal data, such as standardized toxicity tests that characterize responses of individuals (e.g., mortality and reproduction) and a rapidly growing body of "omics" data. A key challenge for environmental risk assessment is relating such information to population dynamics. One approach uses dynamic energy budget (DEB) models that relate growth and reproduction of individuals to underlying flows of energy and elemental matter. We hypothesize that suborganismal information identifies DEB parameters that are most likely impacted by a particular stressor and that the DEB model can then project suborganismal effects on life history and population endpoints. We formulate and parameterize a model of growth and reproduction for the water flea Daphnia magna. Our model resembles previous generic bioenergetic models, but has explicit representation of discrete molts, an important feature of Daphnia life history. We test its ability to predict six endpoints commonly used in chronic toxicity studies in specified food environments. With just one adjustable parameter, the model successfully predicts growth and reproduction of individuals from a wide array of experiments performed in multiple laboratories using different clones of D. magna raised on different food sources. Fecundity is the most sensitive endpoint, and there is broad correlation between the sensitivities of fecundity and long-run growth rate, as is desirable for the default metric used in chronic toxicity tests. Under some assumptions, we can combine our DEB model with the Euler-Lotka equation to estimate longrun population growth rates at different food levels. A review of Daphnia gene-expression experiments on the effects of contaminant exposure reveals several connections to model parameters, in particular a general trend of increased transcript expression of genes involved in energy assimilation and utilization at

  13. Interactions of copper and thermal stress on mitochondrial bioenergetics in rainbow trout, Oncorhynchus mykiss

    Energy Technology Data Exchange (ETDEWEB)

    Sappal, Ravinder [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); MacDonald, Nicole [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Fast, Mark [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada); Siah, Ahmed [British Columbia Centre for Aquatic Health Sciences, 871A Island Highway, Campbell River, BC V9W 2C2 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3 (Canada)

    2014-12-15

    Highlights: • Interacting effects of Cu and temperature were investigated in rainbow trout liver mitochondria. • Mitochondrial functional indices are highly sensitive to temperature change. • High and low temperatures sensitize mitochondria to adverse effects of Cu. • Cu induces a highly temperature-sensitive mitochondrial permeability transition pore. • Cu-imposed mitochondrial membrane potential dissipation is mediated by reactive oxygen species. - Abstract: Thermal stress may influence how organisms respond to concurrent or subsequent chemical, physical and biotic stressors. To unveil the potential mechanisms via which thermal stress modulates metals-induced bioenergetic disturbances, the interacting effects of temperature and copper (Cu) were investigated in vitro. Mitochondria isolated from rainbow trout livers were exposed to a range of Cu concentrations at three temperatures (5, 15 and 25 °C) with measurement of mitochondrial complex I (mtCI)-driven respiratory flux indices and uncoupler-stimulated respiration. Additional studies assessed effects of temperature and Cu on mtCI enzyme activity, induction of mitochondrial permeability transition pore (MPTP), swelling kinetics and mitochondrial membrane potential (MMP). Maximal and basal respiration rates, as well as the proton leak, increased with temperature with the Q{sub 10} effects being higher at lower temperatures. The effect of Cu depended on the mitochondrial functional state in that the maximal respiration was monotonically inhibited by Cu exposure while low and high Cu concentrations stimulated and inhibited the basal respiration/proton leak, respectively. Importantly, temperature exacerbated the effects of Cu by lowering the concentration of the metal required for toxicity and causing loss of thermal dependence of mitochondrial respiration. Mitochondrial complex I activity was inhibited by Cu but was not affected by incubation temperature. Compared with the calcium (Ca) positive control

  14. Quantifying the effect of predators on endangered species using a bioenergetics approach : Caspian terns and juvenile salmonids in the Columbia River estuary

    NARCIS (Netherlands)

    Roby, DD; Lyons, DE; Craig, DP; Collis, K; Visser, GH

    2003-01-01

    We estimated the consumption of juvenile salmonids (Oncorhynchus spp.) and other forage fishes by Caspian terns (Sterna caspia) nesting on Rice Island in the Columbia River estuary in 1997 and 1998 using a bioenergetics modeling approach. The study was prompted by concern that Caspian tern predation

  15. The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Cuezva José M

    2011-02-01

    Full Text Available Abstract Background Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H+-ATPase (β-F1-ATPase. The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH, which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP and iodoacetate (IA, and the anti-metabolite, 5-fluorouracil (5-FU. Methods The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. Results We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the bioenergetic signature directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the in vitro cell-death responses associated with 3BrP, IA and 5-FU, the in vivo tumor regression activities of these agents were comparable. Conclusions Overall, we suggest that the

  16. Error-preceding brain activity reflects (mal-)adaptive adjustments of cognitive control: a modeling study.

    Science.gov (United States)

    Steinhauser, Marco; Eichele, Heike; Juvodden, Hilde T; Huster, Rene J; Ullsperger, Markus; Eichele, Tom

    2012-01-01

    Errors in choice tasks are preceded by gradual changes in brain activity presumably related to fluctuations in cognitive control that promote the occurrence of errors. In the present paper, we use connectionist modeling to explore the hypothesis that these fluctuations reflect (mal-)adaptive adjustments of cognitive control. We considered ERP data from a study in which the probability of conflict in an Eriksen-flanker task was manipulated in sub-blocks of trials. Errors in these data were preceded by a gradual decline of N2 amplitude. After fitting a connectionist model of conflict adaptation to the data, we analyzed simulated N2 amplitude, simulated response times (RTs), and stimulus history preceding errors in the model, and found that the model produced the same pattern as obtained in the empirical data. Moreover, this pattern is not found in alternative models in which cognitive control varies randomly or in an oscillating manner. Our simulations suggest that the decline of N2 amplitude preceding errors reflects an increasing adaptation of cognitive control to specific task demands, which leads to an error when these task demands change. Taken together, these results provide evidence that error-preceding brain activity can reflect adaptive adjustments rather than unsystematic fluctuations of cognitive control, and therefore, that these errors are actually a consequence of the adaptiveness of human cognition.

  17. An improved car-following model with multiple preceding cars' velocity fluctuation feedback

    Science.gov (United States)

    Guo, Lantian; Zhao, Xiangmo; Yu, Shaowei; Li, Xiuhai; Shi, Zhongke

    2017-04-01

    In order to explore and evaluate the effects of velocity variation trend of multiple preceding cars used in the Cooperative Adaptive Cruise Control (CACC) strategy on the dynamic characteristic, fuel economy and emission of the corresponding traffic flow, we conduct a study as follows: firstly, with the real-time car-following (CF) data, the close relationship between multiple preceding cars' velocity fluctuation feedback and the host car's behaviors is explored, the evaluation results clearly show that multiple preceding cars' velocity fluctuation with different time window-width are highly correlated to the host car's acceleration/deceleration. Then, a microscopic traffic flow model is proposed to evaluate the effects of multiple preceding cars' velocity fluctuation feedback in the CACC strategy on the traffic flow evolution process. Finally, numerical simulations on fuel economy and exhaust emission of the traffic flow are also implemented by utilizing VT-micro model. Simulation results prove that considering multiple preceding cars' velocity fluctuation feedback in the control strategy of the CACC system can improve roadway traffic mobility, fuel economy and exhaust emission performance.

  18. [The mechanism of phenoptosis: I. Age-dependent decrease of the overall rate of protein synthesis is caused by the programmed attenuation of bio-energetics].

    Science.gov (United States)

    Trubitsyn, A G

    2009-01-01

    The age-dependent degradation of all vital processes of an organism can be result of influences of destructive factors (the stochastic mechanism of aging), or effect of realizations of the genetic program (phenoptosis). The stochastic free-radical theory of aging dominating now contradicts the set of empirical data, and the semicentenial attempts to create the means to slow down aging did not give any practical results. It makes obvious that the stochastic mechanism of aging is incorrect. At the same time, the alternative mechanism of the programmed aging is not developed yet but preconditions for it development have already been created. It is shown that the genes controlling process of aging exist (contrary to the customary opinion) and the increase in the level of damaged macromolecules (basic postulate of the free-radical theory) can be explained by programmed attenuation of bio-energetics. As the bio-energetics is a driving force of all vital processes, decrease of its level is capable to cause degradation of all functions of an organism. However to transform this postulate into a basis of the theory of phenoptosis it is necessary to show, that attenuation of bio-energetics predetermines such fundamental processes accompanying aging as decrease of the overall rate of protein biosynthesis, restriction of cellular proliferations (Hayflick limit), loss of telomeres etc. This article is the first step in this direction: the natural mechanism of interaction of overall rate of protein synthesis with a level of cellular bio-energetics is shown. This is built-in into the translation machine and based on dependence of recirculation rate of eukaryotic initiation factor 2 (elF2) from ATP/ADP value that is created by mitochondrial bio-energetic machine.

  19. Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

    Directory of Open Access Journals (Sweden)

    Gina Nicole Wilson

    2016-11-01

    Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

  20. DUTY OF GROUNDS IN THE NEW CIVIL PROCEDURE CODE AND THE BINDING PRECEDENTS

    Directory of Open Access Journals (Sweden)

    Anderson Cortez Mendes

    2015-12-01

    Full Text Available The new Brazilian Civil Procedure Code instituted a model of binding precedents, to approach the legal system of common law countries. The legislator was already seeking the transformation of the STF and t he STJ of superior courts in supreme courts, with the transition from the exercises of the judgment control function in this case for assurance uniformity of interpretation of the law. So assumes special importance the duty of grounds, which is disciplined in article 489, allowing the management of binding system, with appropriate formation and application of the precedents. The article attempts therefore shed light on concepts inherent in the work with binding precedents, especially on those instilled in law by new Brazilian Civil Procedure Code, which are the ratio decidendi , the distinguishing and the overruling.

  1. Parallel Machine Scheduling Models with Fuzzy Parameters and Precedence Constraints: A Credibility Approach

    Institute of Scientific and Technical Information of China (English)

    HOU Fu-jun; WU Qi-zong

    2007-01-01

    A method for modeling the parallel machine scheduling problems with fuzzy parameters and precedence constraints based on credibility measure is provided.For the given n jobs to be processed on m machines, it is assumed that the processing times and the due dates are nonnegative fuzzy numbers and all the weights are positive, crisp numbers.Based on credibility measure, three parallel machine scheduling problems and a goal-programming model are formulated.Feasible schedules are evaluated not only by their objective values but also by the credibility degree of satisfaction with their precedence constraints.The genetic algorithm is utilized to find the best solutions in a short period of time.An illustrative numerical example is also given.Simulation results show that the proposed models are effective, which can deal with the parallel machine scheduling problems with fuzzy parameters and precedence constraints based on credibility measure.

  2. A lattice traffic model with consideration of preceding mixture traffic information

    Institute of Scientific and Technical Information of China (English)

    Li Zhi-Peng; Liu Fu-Qiang; Sun Jian

    2011-01-01

    In this paper,the lattice model is presented,incorporating not only site information about preceding cars but also relative currents in front.We derive the stability condition of the extended model by considering a small perturbation around the homogeneous flow solution and find that the improvement in the stability of traffic flow is obtained by taking into account preceding mixture traffic information.Direct simulations also confirm that the traffic jam can be suppressed efficiently by considering the relative currents ahead,just like incorporating site information in front.Moreover,from the nonlinear analysis of the extended models,the preceding mixture traffic information dependence of the propagating kink solutions for traffic jams is obtained by deriving the modified KdV equation near the critical point using the reductive perturbation method.

  3. Use of oral antihypertensive medication preceding blood pressure elevation in hospitalized patients

    Directory of Open Access Journals (Sweden)

    Macedo Cristiano Ricardo Bastos de

    2001-01-01

    Full Text Available OBJECTIVE: To evaluate the frequency of oral antihypertensive medication preceding the increase in blood pressure in patients in a university hospital, the drug of choice, and the maintained use of antihypertensive medication. METHODS: Data from January to June 1997 from the University Hospital Professor Edgard Santos Pharmacy concerning the prescriptions of all inpatients were used. Variables included in the analysis were: antihypertensive medication prescription preceding increase in blood pressure, type of antihypertensive medication, gender, clinical or surgical wards, and the presence of maintained antihypertensive medication. RESULTS: The hospital admitted 2,532 patients, 1,468 in surgical wards and 818 in medical wards. Antihypertensive medication prescription preceding pressure increase was observed in 578 patients (22.8%. Nifedipine was used in 553 (95.7% and captopril in 25 (4.3%. In 50.7% of patients, prescription of antihypertensive medication was not associated with maintained antihypertensive medication. Prescription of antihypertensive drugs preceding elevation of blood pressure was significantly (p<0.001 more frequent on the surgical floor (27.5%; 405/1468 than on the medical floor (14.3%; 117/818. The frequency of prescription of antihypertensive drugs preceding elevation of blood pressure without maintained antihypertensive drugs and the ratio between the number of prescriptions of nifedipine and captopril were greater in surgical wards. CONCLUSION: The use of antihypertensive medication, preceding elevation of blood pressure (22.8% observed in admitted patients is not supported by scientific evidence. The high frequency of this practice may be even greater in nonuniversity hospitals.

  4. A novel car following model considering average speed of preceding vehicles group

    Science.gov (United States)

    Sun, Dihua; Kang, Yirong; Yang, Shuhong

    2015-10-01

    In this paper, a new car following model is presented by considering the average speed effect of preceding vehicles group in cyber-physical systems (CPS) environment. The effect of this new consideration upon the stability of traffic flow is examined through linear stability analysis. A modified Korteweg-de Vries (mKdV) equation was derived via nonlinear analysis to describe the propagating behavior of traffic density wave near the critical point. Good agreement between the simulation and the analytical results shows that average speed of preceding vehicles group leads to the stabilization of traffic systems, and thus can efficiently suppress the emergence of traffic jamming.

  5. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  6. Precedent in the Sui Generis Legal Order: A Mine Run Approach

    DEFF Research Database (Denmark)

    Sadl, Urska; Hink, Sigrid

    2014-01-01

    In this article, we use case-to-case citation networks to explore the force of precedent in EU law. We introduce a novel methodology to analyse the extent to which references to past decisions act as reasons for decisions in subsequent cases and illustrate the approach on the European citizenship...... case-law citation network. We conclude that the cohesive pull of precedent in EU citizenship case-law is too weak to generate a coherent judicial doctrine, thereby confirming qualitative research on the subject. However, the incursions into competences of the Member States in areas, found only...

  7. Attention deficit hyperactivity disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Fabio de Almeida Bolognani

    2011-07-01

    Full Text Available The objective of this study, stated as Previous Notation, is to demonstrate that Attention Deficit Hyperactivity Disorder Pathology presents a differentiated condition in carriers where a significant percentage, close to 60%, present a higher level of zinc elimination by kidneys. In this study, a direct relation of Zinc Mettalicum pathogenetic symptoms, this disturbance and the elimination of this element which participates in neurotransmission process were identified, and the relation with elements from regular diet, which can act as zinc chelating agents would be involved in the evolution of this disturbance, justifying the issue of individual susceptibility, essential in homeopathic investigation

  8. Mitochondrial bioenergetics and redox state are unaltered in Trypanosoma cruzi isolates with compromised mitochondrial complex I subunit genes.

    Science.gov (United States)

    Carranza, Julio César; Kowaltowski, Alicia J; Mendonça, Marco Aurélio G; de Oliveira, Thays C; Gadelha, Fernanda R; Zingales, Bianca

    2009-06-01

    In trypanosomatids the involvement of mitochondrial complex I in NADH oxidation has long been debated. Here, we took advantage of natural Trypanosoma cruzi mutants which present conspicuous deletions in ND4, ND5 and ND7 genes coding for complex I subunits to further investigate its functionality. Mitochondrial bioenergetics of wild type and complex I mutants showed no significant differences in oxygen consumption or respiratory control ratios in the presence of NADH-linked substrates or FADH(2)-generating succinate. No correlation could be established between mitochondrial membrane potentials and ND deletions. Since release of reactive oxygen species occurs at complex I, we measured mitochondrial H(2)O(2) formation induced by different substrates. Significant differences not associated to ND deletions were observed among the parasite isolates, demonstrating that these mutations are not important for the control of oxidant production. Our data support the notion that complex I has a limited function in T. cruzi.

  9. Bioenergetic model predictions of actual growth and allometric transitions during ontogeny of juvenile blue mussels Mytilus edulis

    DEFF Research Database (Denmark)

    Larsen, Poul Scheel; Lundgreen, Kim; Riisgård, Hans Ulrik

    2013-01-01

    with predictions based on a previously developed bioenergetic growth model (BEG) for W> 10 mg (μ =aWb, a = 0.871× C – 0.986; b = –0.34, with μ in % d−1 and W in g) which explicitly takes into account the prevailing chla concentration C (μg L−1). Results for W...Wb), now with exponent b = −0.13 close to the suggested value (b ≈ −0.1) from experimentally established correlations for filtration and respiration rate of post-metamorphic mussels. Using the stated W(L)-relation for L> 10 mm the growth model has been expressed in terms of shell length specific growth...

  10. Environmental effects on sprat (Sprattus sprattus) physiology and growth at the distribution frontier: A bioenergetic modelling approach

    DEFF Research Database (Denmark)

    Frisk, Christina; Andersen, Ken Haste; Temming, A.;

    2015-01-01

    role in the ecosystem. However, the population is sensitive to small changes in environmental conditions. In this paper, we set up a bioenergetic model of Baltic sprat and evaluate how variability and seasonal changes in the physical environment affects the physiology and growth of individual sprat....... The model is dynamic and seasonally resolved. It is parameterised based on sprat from the Bornholm Basin. Our model results suggest that the optimal temperature for sprat growth is 17.5. °C, which is only observed in the Central Baltic Sea in the top water layer during a short period in summer. During 41....../2 winter months individual sprat do not grow and utilize stored energy from the previous growth season. We analysed the maximum attainable individual body size as a function of temperature. The model predicted reduced maximum body sizes with increasing temperature. The model can be used for studying...

  11. Bioenergetic response by steelhead to variation in diet, thermal habitat, and climate in the north Pacific Ocean

    Science.gov (United States)

    Atcheson, Margaret E.; Myers, Katherine W.; Beauchamp, David A.; Mantua, Nathan J.

    2012-01-01

    Energetic responses of steelhead Oncorhynchus mykiss to climate-driven changes in marine conditions are expected to affect the species’ ocean distribution, feeding, growth, and survival. With a unique 18-year data series (1991–2008) for steelhead sampled in the open ocean, we simulated interannual variation in prey consumption and growth efficiency of steelhead using a bioenergetics model to evaluate the temperature-dependent growth response of steelhead to past climate events and to estimate growth potential of steelhead under future climate scenarios. Our results showed that annual ocean growth of steelhead is highly variable depending on prey quality, consumption rates, total consumption, and thermal experience. At optimal growing temperatures, steelhead can compensate for a low-energy diet by increasing consumption rates and consuming more prey, if available. Our findings suggest that steelhead have a narrow temperature window in which to achieve optimal growth, which is strongly influenced by climate-driven changes in ocean temperature.

  12. Bioenergetic model predictions of actual growth and allometric transitions during ontogeny of juvenile blue mussels Mytilus edulis

    DEFF Research Database (Denmark)

    Larsen, Poul Scheel; Lundgreen, Kim; Riisgård, Hans Ulrik

    2013-01-01

    The growth rates of blue mussels Mytilusedulis on ropes in the Great Belt (Denmark) have been studied during the growth season of one year, from settling to about 30 mm shell length mussels, covering >4 decades of body mass. Measured shell length (L, mm) and dry weight of soft parts (W, μg) for L...... > 10 mm followed a power-law (W = 2.15L3.40) which supplemented an existing power-law for L ... with predictions based on a previously developed bioenergetic growth model (BEG) for W> 10 mg (μ =aWb, a = 0.871× C – 0.986; b = –0.34, with μ in % d−1 and W in g) which explicitly takes into account the prevailing chla concentration C (μg L−1). Results for Wlaw (μ =a...

  13. Mitochondrial bioenergetic alterations in mouse neuroblastoma cells infected with Sindbis virus: implications to viral replication and neuronal death.

    Directory of Open Access Journals (Sweden)

    Leandro Silva da Costa

    Full Text Available The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal

  14. Roles of sirtuins in the regulation of antioxidant defense and bioenergetic function of mitochondria under oxidative stress.

    Science.gov (United States)

    Wu, Y-T; Wu, S-B; Wei, Y-H

    2014-09-01

    In addition to serving as the power house of mammalian cells, mitochondria are crucial for the maintenance of cellular homeostasis in response to physiological or environmental changes. Several lines of evidence suggest that posttranslational modification (PTM) of proteins plays a pivotal role in the regulation of the bioenergetic function of mitochondria. Among them, reversible lysine acetylation of mitochondrial proteins has been established as one of the key mechanisms in cellular response to energy demand by modulating the flux of a number of key metabolic pathways. In this article, we focus on the role of Sirt3-mediated deacetylation in: (1) flexibility of energy metabolism, (2) activation of antioxidant defense, and (3) maintenance of cellular redox status in response to dietary challenge and oxidative stress. We suggest that oxidative stress-elicited down-regulation of Sirt3 plays a role in the pathophysiology of diabetes, cardiac hypotrophy, mitochondrial diseases, and age-related diseases. Besides, the physiological role of newly identified lysine acylation mediated by Sirt5 and its biochemical effects on oxidative metabolism are also discussed. Moreover, we have integrated the regulatory function of several protein kinases that are involved in the phosphorylation of mitochondrial enzymes during oxidative stress. Finally, the functional consequence of the synergistic regulation through diverse protein modifications is emphasized on the maintenance of the bioenergetic homeostasis and metabolic adaptation of the animal and human cells. Together, we have provided an updated review of PTM in mitochondrial biology and their implications in aging and human diseases through an intricate regulation of energy metabolism under oxidative stress.

  15. Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure.

    Science.gov (United States)

    Selfridge, J Eva; Wilkins, Heather M; E, Lezi; Carl, Steven M; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H

    2015-04-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain's aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated.

  16. The Determinants of Public Deficit Volatility

    OpenAIRE

    2009-01-01

    This paper empirically analyzes the political, institutional and economic sources of public deficit volatility. Using the system-GMM estimator for linear dynamic panel data models and a sample of 125 countries analyzed from 1980 to 2006, we show that higher public deficit volatility is typically associated with higher levels of political instability and less democracy. In addition, public deficit volatility tends to be magnified for small countries, in the outcome of hyper-inflation episodes ...

  17. Contributions from eye movement potentials to stimulus preceding negativity during anticipation of auditory stimulation

    DEFF Research Database (Denmark)

    Engdahl, Lis; Bjerre, Vicky K; Christoffersen, Gert R J

    2007-01-01

    Cognitive anticipation of a stimulus has been associated with an ERP called "stimulus preceding negativity" (SPN). A new auditory delay task without stimulus-related motor activity demonstrated a prefrontal SPN, present during attentive anticipation of sounds with closed eyes, but absent during...

  18. Self-Efficacy, Goal Orientations and Learning Strategies as Mediators between Preceding and Subsequent Academic Achievement

    Science.gov (United States)

    Diseth, Age

    2011-01-01

    High school grade point average (HSGPA), self-efficacy, goal orientations, learning strategies, and examination grade were measured in a sample of Norwegian undergraduate psychology students in order to investigate motives and strategies as mediators between preceding and subsequent academic achievement. Correlation analysis showed strong…

  19. Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat

    NARCIS (Netherlands)

    Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik J.; de Zeeuw, Dick; Provoost, Abraham P.; van Dokkum, Richard P. E.

    2010-01-01

    Ochodnicky P, Henning RH, Buikema HJ, de Zeeuw D, Provoost AP, van Dokkum RP. Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat. Am J Physiol Renal Physiol 298: F625-F633, 2010. First published December 9, 2009; doi:10.1152/ajprenal.00289.2009.-I

  20. List scheduling in a parallel machine environment with precedence constraints and setup times

    NARCIS (Netherlands)

    Hurink, J.L.; Knust, S.

    2000-01-01

    We present complexity results which have influence on the strength of list scheduling in a parallel machine environment where additionally precedence constraints and sequence-dependent setup times are given and the makespan has to be minimized. We show that contrary to various other scheduling probl

  1. List scheduling in a parallel machine environment with precedence constraints and setup times

    NARCIS (Netherlands)

    Hurink, Johann; Knust, Sigrid

    2001-01-01

    We present complexity results which have influence on the strength of list scheduling in a parallel machine environment where additionally precedence constraints and sequence-dependent setup times are given and the makespan has to be minimized. We show that contrary to various other scheduling probl

  2. Reduced Activation of Left Orbitofrontal Cortex Precedes Blocked Vocalization: A Magnetoencephalographic Study

    Science.gov (United States)

    Sowman, Paul F.; Crain, Stephen; Harrison, Elisabeth; Johnson, Blake W.

    2012-01-01

    While stuttering is known to be characterized by anomalous brain activations during speech, very little data is available describing brain activations during stuttering. To our knowledge there are no reports describing brain activations that precede blocking. In this case report we present magnetoencephalographic data from a person who stutters…

  3. From Function to Context to Form: Precedents and Focus Shifts in the Form Creation Process

    DEFF Research Database (Denmark)

    Restrepo-Giraldo, John Dairo

    2005-01-01

    In design, the form creation process involves imagining, seeing and drawing. Translating the vague and imprecise initial ideas into sketches requires significant ability, and in this process, images of existing products (precedents) are a welcomed aid. Searching for them, however, is difficult, b...

  4. Ancient Uses of Meteoritic Metals as Precedent for Modern In-Situ Asteroid Mining

    Science.gov (United States)

    Mardon, Austin A.; Fawcett, Brett; Krispin, Daniel

    2016-05-01

    Given the strain on earth's supply of metal and the meteoritic content of meteorites, a prudent course would be to pursue in-situ asteroid mining of meteors for metal. There is a precedent for this going back to ancient Egypt; humans have always used the meteoritic content of meteorites to fashion everything from weapons to cosmetics.

  5. 5 CFR 870.801 - Order of precedence and payment of benefits.

    Science.gov (United States)

    2010-01-01

    ... specific person or persons to receive life insurance benefits upon the death of an insured individual... the individual(s) entitled to receive Basic life insurance benefits under the statutory order of... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES' GROUP LIFE INSURANCE PROGRAM Order of Precedence...

  6. A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

    Science.gov (United States)

    McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

    2011-01-01

    Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

  7. Attentional deficits in patients with persisting postconcussive complaints: a general deficit or specific component deficit?

    Science.gov (United States)

    Chan, Raymond C K

    2002-12-01

    This study aimed to examine attentional performance in patients with persisting postconcussive complaints, using a multi-componential perspective. Comparisons of attentional performances of 92 patients with postconcussive complaints and 86 normal controls were conducted using tests of sustained attention (Sustained Attention to Response Task; Digit Backward Span), selective attention (Stroop Word-Color Test; Color Trails Test), divided attention (Paced Auditory Serial Addition Test; Symbol Digit Modalities Test), and attentional control processing (Six Elements Test; Tower of Hanoi). Questionnaires on daily life inattentive behaviour were also administered to all participants and their significant others. A MANOVA indicated that patients with persisting postconcussive complaints demonstrated a general deficit in attentional performance as compared with their normal controls, F(18, 145) = 7.939, p = .005. These patterns still persisted when measures of emotional disturbance were controlled, F(18, 143) = 5.159, p = .005. Moreover, for sustained attention and selective attention, we were able to statistically control for speed and the differences remained. Future research should be conducted to better control the potential confound of speed for all the attentional components in order to differentiate any specific component deficits in these patients.

  8. Poor Reading: A Deficit in Skill-Automatization or a Phonological Deficit?

    Science.gov (United States)

    Wimmer, Heinz; Mayringer, Heinz; Landerl, Karin.

    1998-01-01

    Examines whether the characteristic reading speed impairment of German dyslexic children resulted from a general skill-automatization deficit or a phonological deficit. Tests a dyslexic and nondyslexic group of boys in grade 2. Concludes that difficulties in learning to read are due phonological deficit and not a general skill-automatization…

  9. Timing deficits in attention-deficit/hyperactivity disorder (ADHD) : Evidence from neurocognitive and neuroimaging studies

    NARCIS (Netherlands)

    Noreika, Valdas; Falter, Christine M.; Rubia, Katya

    2013-01-01

    Relatively recently, neurocognitive and neuroimaging studies have indicated that individuals with attention-deficit/hyperactivity disorder (ADHD) may have deficits in a range of timing functions and their underlying neural networks. Despite this evidence, timing deficits in ADHD are still somewhat n

  10. Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington’s disease

    Science.gov (United States)

    Bragg, Robert M.; Coffey, Sydney R.; Weston, Rory M.; Ament, Seth A.; Cantle, Jeffrey P.; Minnig, Shawn; Funk, Cory C.; Shuttleworth, Dominic D.; Woods, Emily L.; Sullivan, Bonnie R.; Jones, Lindsey; Glickenhaus, Anne; Anderson, John S.; Anderson, Michael D.; Dunnett, Stephen B.; Wheeler, Vanessa C.; MacDonald, Marcy E.; Brooks, Simon P.; Price, Nathan D.; Carroll, Jeffrey B.

    2017-01-01

    We investigated the appearance and progression of disease-relevant signs in the B6.HttQ111/+ mouse, a genetically precise model of the mutation that causes Huntington’s disease (HD). We find that B6.HttQ111/+ mice are healthy, show no overt signs of central or peripheral inflammation, and no gross motor impairment as late as 12 months of age. Behaviorally, we find that 4–9 month old B6.HttQ111/+ mice have normal activity levels and show no clear signs of anxiety or depression, but do show clear signs of reduced motivation. The neuronal density, neuronal size, synaptic density and number of glia is normal in B6.HttQ111/+ striatum, the most vulnerable brain region in HD, up to 12 months of age. Despite this preservation of the synaptic and cellular composition of the striatum, we observe clear progressive, striatal-specific transcriptional dysregulation and accumulation of neuronal intranuclear inclusions (NIIs). Simulation studies suggest these molecular endpoints are sufficiently robust for future preclinical studies, and that B6.HttQ111/+ mice are a useful tool for modeling disease-modifying or neuroprotective strategies for disease processes before the onset of overt phenotypes. PMID:28176805

  11. Cognitive Deficits in the Pathogenesis of Autism.

    Science.gov (United States)

    Rutter, M.

    1983-01-01

    Reports empirical findings indicating that autistic children have a basic cognitive deficit that is not a secondary consequence of social withdrawal. The precise nature of the deficit is discussed, as are studies of autistic children's general intelligence, language abnormalities, and social impairments. (RH)

  12. Kognitive deficit ved skizofreni og andre psykoser

    DEFF Research Database (Denmark)

    Fagerlund, Birgitte; Glenthøj, Birte Y

    2008-01-01

    and there is considerable incentive to develop treatments that can improve these deficits. The current brief review summarizes the relevance of cognitive deficits for the pathogenesis and prognosis of psychotic disorders, and identifies pertinent issues within the research field Udgivelsesdato: 2008/11/10...

  13. Global precedence, spatial frequency channels, and the statistics of natural images.

    Science.gov (United States)

    Hughes, H C; Nozawa, G; Kitterle, F

    1996-01-01

    A great deal of evidence suggests that early in processing, retinal images are filtered by parallel, spatial frequency selective channels. We attempt to incorporate this view of early vision with the principle of global precedence, which holds that Gestalt-like processes sensitive to global image configurations tend to dominate local feature processing in human pattern perception. Global precedence is inferred from the pattern of reaction times observed when visual patterns contain multiple cues at different levels of spatial scale. Specifically, it is frequently observed that global processing times are largely unaffected by conflicting local cues, but local processing times are substantially lengthened by conflicting global cues. The asymmetry of these effects suggests the dominant role of global configurations. Since global spatial information is effectively represented by low spatial frequencies, global precedence potentially implies a low frequency dominance. The thesis is that low spatial frequencies tend to be available before information carried by higher frequency bands, producing a coarse-to-fine temporal order in visual spatial perception. It is suggested that a variety of factors contribute to the "prior entry" of low frequency information, including the high contrast gain of the magnocellular pathway, the amplitude spectra typical of natural images, and inhibitory interactions between the parallel frequency-tuned channels. Evidence suggesting a close relationship between global precedence and spatial frequency channels is provided by observations that the essential features of the global precedence effect are obtained using patterns consisting of low and high frequency sinusoids. The hypothesis that these asymmetric interference effects are due to interactions between parallel spatial channels is supported by an analysis of reaction times (RTs), which shows that RTs to redundant low and high frequency cues produce less facilitation than predictions

  14. Anomalous transport in fluid field with random waiting time depending on the preceding jump length

    Science.gov (United States)

    Zhang, Hong; Li, Guo-Hua

    2016-11-01

    Anomalous (or non-Fickian) transport behaviors of particles have been widely observed in complex porous media. To capture the energy-dependent characteristics of non-Fickian transport of a particle in flow fields, in the present paper a generalized continuous time random walk model whose waiting time probability distribution depends on the preceding jump length is introduced, and the corresponding master equation in Fourier-Laplace space for the distribution of particles is derived. As examples, two generalized advection-dispersion equations for Gaussian distribution and lévy flight with the probability density function of waiting time being quadratic dependent on the preceding jump length are obtained by applying the derived master equation. Project supported by the Foundation for Young Key Teachers of Chengdu University of Technology, China (Grant No. KYGG201414) and the Opening Foundation of Geomathematics Key Laboratory of Sichuan Province, China (Grant No. scsxdz2013009).

  15. Investigating the build-up of precedence effect using reflection masking

    DEFF Research Database (Denmark)

    Hartcher-O'Brien, Jessica; Buchholz, Jörg

    2006-01-01

    The auditory processing level involved in the build-up of precedence [Freyman et al., J. Acoust. Soc. Am. 90, 874–884 (1991)] has been investigated here by employing reflection masked threshold (RMT) techniques. Given that RMT techniques are generally assumed to address lower levels of the auditory...... signal processing, such an approach represents a bottom-up approach to the buildup of precedence. Three conditioner configurations measuring a possible buildup of reflection suppression were compared to the baseline RMT for four reflection delays ranging from 2.5–15 ms. No buildup of reflection...... suppression was observed for any of the conditioner configurations. Buildup of template (decrease in RMT for two of the conditioners), on the other hand, was found to be delay dependent. For five of six listeners, with reflection delay=2.5 and 15 ms, RMT decreased relative to the baseline. For 5- and 10-ms...

  16. Evidence for a neural source of the precedence effect in sound localization

    OpenAIRE

    Brown, Andrew D.; Jones, Heath G.; Kan, Alan; Thakkar, Tanvi; Stecker, G. Christopher; Goupell, Matthew J.; Litovsky, Ruth Y.

    2015-01-01

    Normal-hearing human listeners and a variety of studied animal species localize sound sources accurately in reverberant environments by responding to the directional cues carried by the first-arriving sound rather than spurious cues carried by later-arriving reflections, which are not perceived discretely. This phenomenon is known as the precedence effect (PE) in sound localization. Despite decades of study, the biological basis of the PE remains unclear. Though the PE was once widely attribu...

  17. Organizational precedents for ownership and management of decentralized renewable-energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Meunier, R.; Silversmith, J.A.

    1981-03-01

    Three existing organizational types that meet the decentralization criteria of local consumer ownership and control - cooperatives, Rural Electric Cooperatives, and municipal utilities - are examined. These three organizational precedents are analyzed in terms of their histories, structures, legal powers, sources of capital, and social and political aspects. Examples of related experiments with renewable energy technologies are given, and inferences are drawn regarding the organizations' suitability as vehicles for future implementation of decentralized renewable energy systems.

  18. Factors preceding CRM readiness in small- and medium-sized tourism enterprises

    OpenAIRE

    Dinesh Vallabh; Laetitia Radder; Danie Venter

    2015-01-01

    Orientation: Customer relationship management (CRM) is important to organisations striving for competitive advantage through building relationships with their customers.Research purpose: This study identified the factors preceding CRM and assessed selected South African small- and medium-sized tourism enterprises’ (SMTEs) readiness for CRM.Motivation: CRM is likely to enhance SMTEs’ competitiveness. However, successful adoption and implementation of CRM is unlikely unless the organisation is ...

  19. DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos

    OpenAIRE

    2016-01-01

    DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γ...

  20. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis

    OpenAIRE

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-01-01

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recogni...

  1. A single bio-energetics growth and reproduction model for the oyster Crassostrea gigas in six Atlantic ecosystems

    Science.gov (United States)

    Alunno-Bruscia, Marianne; Bourlès, Yves; Maurer, Danièle; Robert, Stéphane; Mazurié, Joseph; Gangnery, Aline; Goulletquer, Philippe; Pouvreau, Stéphane

    2011-11-01

    Many studies based on bioenergetics growth models have investigated the effects of environmental factors on oyster ( Crassostrea gigas) growth and physiology. However, most of these models are site-specific and cannot be applied to other culture sites without the re-estimation of parameters or re-formulation of some processes. We aimed to develop a generic growth model suitable for application in contrasting environments, with a constant set of parameters. We tested the oyster-DEB model (Bourlès et al. 2009) for the stimulation of C. gigas growth in different cohorts (spats and adults) at major shellfish culture sites in France, in several years: Arcachon (1993-1994); Marennes-Oléron (2007); Quiberon (1999, 2000, 2001); Brest Harbour (2008); Mont-Saint-Michel Bay (2003); Baie-des-Veys (2002). These different ecosystems offer a wide range of values for the two forcing variables of the model: water temperature (range: 6-24 °C) and phytoplankton concentration (annual average: 110-700 × 10 3 cell L -1). The validation data (dry flesh mass of C. gigas) were obtained from various growth surveys carried out by IFREMER. The oyster-DEB model simulated the oyster growth dynamics of both spat and adult stages of C. gigas accurately over time at the various culture sites. The model captures: i) the active spring growth; ii) the timing and amplitude of spawning events; and iii) the lean periods ( i.e. loss of dry flesh mass) in autumn and winter. The half-saturation coefficient Xk is the only model parameter that varied between sites and years. This environment-specific coefficient reflects variability in the food of the oysters: quantitative and qualitative effects of the inorganic material and of the phytoplankton species on the feeding response of C. gigas. With a single set of parameters (other than for Xk), this is thus the first bio-energetic growth model for C. gigas robust enough and of a sufficiently generic nature for the accurate simulation of oyster growth in

  2. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Claudia V.; Oliveira, Paulo J. [CNC—Center for Neuroscience and Cell Biology, University of Coimbra (Portugal); Will, Yvonne [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States); Nadanaciva, Sashi, E-mail: sashi.nadanaciva@pfizer.com [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)

    2012-10-15

    Mitochondrial DNA (mtDNA) variations including single nucleotide polymorphisms (SNPs) have been proposed to be involved in idiosyncratic drug reactions. However, current in vitro and in vivo models lack the genetic diversity seen in the human population. Our hypothesis is that different cell strains with distinct mtDNA SNPs may have different mitochondrial bioenergetic profiles and may therefore vary in their response to drug-induced toxicity. Therefore, we used an in vitro system composed of four strains of mouse embryonic fibroblasts (MEFs) with mtDNA polymorphisms. We sequenced mtDNA from embryonic fibroblasts isolated from four mouse strains, C57BL/6J, MOLF/EiJ, CZECHII/EiJ and PERA/EiJ, with the latter two being sequenced for the first time. The bioenergetic profile of the four strains of MEFs was investigated at both passages 3 and 10. Our results showed that there were clear differences among the four strains of MEFs at both passages, with CZECHII/EiJ having a lower mitochondrial robustness when compared to C57BL/6J, followed by MOLF/EiJ and PERA/EiJ. Seven drugs known to impair mitochondrial function were tested for their effect on the ATP content of the four strains of MEFs in both glucose- and galactose-containing media. Our results showed that there were strain-dependent differences in the response to some of the drugs. We propose that this model is a useful starting point to study compounds that may cause mitochondrial off-target toxicity in early stages of drug development, thus decreasing the number of experimental animals used. -- Highlights: ► mtDNA SNPs may be linked to individual predisposition to drug-induced toxicity. ► CZECHII/EiJ and PERA/EiJ mtDNA was sequenced for the first time in this study. ► Strain-dependent mitochondrial capacity differences were measured. ► Strain-dependent differences in response to mitochondrial toxicants were observed.

  3. Effect of high-intensity interval training on body composition and bioenergetic indices in boys - futsal players

    Directory of Open Access Journals (Sweden)

    Fatemeh Balbasi

    2016-10-01

    Full Text Available Background: High-intensity interval trainings (HIIT can result in the best improvement of body fitness among athletes in the shortest possible time. The impact of HIIT on bioenergetic factors of futsal players has not been studied extensively. The objective of the present study was to investigate the effect of 3-week HIIT on body composition indices, maximum aerobic power, and maximum anaerobic power, anaerobic power among boys - futsal players. Material: 30 boys - futsal players (mean± SD age, 13.49±1.03 years; BMI, 20.95±1.78 kg/m2 participated in the study voluntarily. They were randomly assigned to experimental (n=15 and control (n=15 groups. HIIT lasted for three weeks, three sessions a week for 12-36 minutes on treadmill. Weight, body mass index (BMI, waist to hip ratio (WHR, thickness of body fat, maximal aerobic power, and maximum anaerobic power were recorded before intervention and 48 hours after the final training session. Aerobic power was measured with 20-m shuttle run, and maximum anaerobic power was measured with RAST test. Paired sample t-test was used to determine pretest-posttest differences, and independent t-test was used to determine between-group differences. The significance level was set to P < 0.05. Results: Significant differences were found in weight, BMI, thickness of body fat, maximum aerobic power and maximum anaerobic power in experimental group (P = 0.001 before and after training intervention, but the change in WHR was not significant (P < 0.05. No significant differences were observed in selected body composition between experimental and control groups, but they exhibited significant differences in maximum aerobic power and maximum anaerobic power (P = 0.001. Conclusion: According to the results, HIIT can be an effective training program for improving the performance of bioenergetic indices of futsal players. Also, it is recommended to study the effect of similar trainings with longer durations on other

  4. Measuring Algorithm for the Distance to a Preceding Vehicle on Curve Road Using On-Board Monocular Camera

    Science.gov (United States)

    Yu, Guizhen; Zhou, Bin; Wang, Yunpeng; Wun, Xinkai; Wang, Pengcheng

    2015-12-01

    Due to more severe challenges of traffic safety problems, the Advanced Driver Assistance Systems (ADAS) has received widespread attention. Measuring the distance to a preceding vehicle is important for ADAS. However, the existing algorithm focuses more on straight road sections than on curve measurements. In this paper, we present a novel measuring algorithm for the distance to a preceding vehicle on a curve road using on-board monocular camera. Firstly, the characteristics of driving on the curve road is analyzed and the recognition of the preceding vehicle road area is proposed. Then, the vehicle detection and distance measuring algorithms are investigated. We have verified these algorithms on real road driving. The experimental results show that this method proposed in the paper can detect the preceding vehicle on curve roads and accurately calculate the longitudinal distance and horizontal distance to the preceding vehicle.

  5. Postural control deficits identify lingering post-concussion neurological deficits

    Institute of Scientific and Technical Information of China (English)

    Thomas A. Buckley; Jessie R. Oldham; Jaclyn B. Caccese

    2016-01-01

    Concussion, or mild traumatic brain injury, incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom. The purpose of this review is to provide an overview of the linear and non-linear assessments of post-concussion postural control. The current acute evaluation for concussion utilizes the subjective balance error scoring system (BESS) to assess postural control. While the sensitivity of the overall test battery is high, the sensitivity of the BESS is unacceptably low and, with repeat administration, is unable to accurately identify recovery. Sophisticated measures of postural control, utilizing traditional linear assessments, have identified impairments in postural control well beyond BESS recovery. Both assessments of quiet stance and gait have identified lingering impairments for at least 1 month post-concussion. Recently, the application of non-linear metrics to concussion recovery have begun to receive limited attention with the most commonly utilized metric being approximate entropy (ApEn). ApEn, most commonly in the medial-lateral plane, has successfully identified impaired postural control in the acute post-concussion timeframe even when linear assessments of instrumented measures are equivalent to healthy pre-injury values;unfortunately these studies have not gone beyond the acute phase of recovery. One study has identified lingering deficits in postural control, utilizing Shannon and Renyi entropy metrics, which persist at least through clinical recovery and return to participation. Finally, limited evidence from two studies suggest that individuals with a previous history of a single concussion, even months or years prior, may display altered ApEn metrics. Overall, non-linear metrics provide a fertile area for future study to further the understanding of postural control impairments acutely post-concussion and address the current challenge of sensitive identification of recovery.

  6. Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xiuhua Li

    Full Text Available Parkinson's disease (PD is a neurodegenerative disorder primarily characterized by progressive loss of dopamine neurons, leading to loss of motor coordination. However, PD is associated with a high rate of non-motor neuropsychiatric comorbities that often develop before the onset of movement symptoms. The MitoPark transgenic mouse model is the first to recapitulate the cardinal clinical features, namely progressive neurodegeneration and death of neurons, loss of motor function and therapeutic response to L-DOPA. To investigate whether MitoPark mice exhibit early onset of cognitive impairment, a non-motor neuropsychiatric comorbidity, we measured performance on a spatial learning and memory task before (∼8 weeks or after (∼20 weeks the onset of locomotor decline in MitoPark mice or in littermate controls. Consistent with previous studies, we established that a progressive loss of spontaneous locomotor activity began at 12 weeks of age, which was followed by progressive loss of body weight beginning at 16-20 weeks. Spatial learning and memory was measured using the Barnes Maze. By 20 weeks of age, MitoPark mice displayed a substantial reduction in overall locomotor activity that impaired their ability to perform the task. However, in the 8-week-old mice, locomotor activity was no different between genotypes, yet MitoPark mice took longer, traveled further and committed more errors than same age control mice, while learning to successfully navigate the maze. The modest between-day learning deficit of MitoPark mice was characterized by impaired within-day learning during the first two days of testing. No difference was observed between genotypes during probe trials conducted one or twelve days after the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited impaired novel object recognition when compared to control mice. Together, these data establish that mild cognitive impairment precedes the loss of motor function in a novel

  7. Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble - Applications for Bioenergetic Research

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2009-03-01

    Full Text Available We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed.

  8. Sex-specific mitonuclear epistasis and the evolution of mitochondrial bioenergetics, ageing, and life history in seed beetles.

    Science.gov (United States)

    Đorđević, Mirko; Stojković, Biljana; Savković, Uroš; Immonen, Elina; Tucić, Nikola; Lazarević, Jelica; Arnqvist, Göran

    2017-02-01

    The role of mitochondrial DNA for the evolution of life-history traits remains debated. We examined mitonuclear effects on the activity of the multisubunit complex of the electron transport chain (ETC) involved in oxidative phosphorylation (OXPHOS) across lines of the seed beetle Acanthoscelides obtectus selected for a short (E) or a long (L) life for more than >160 generations. We constructed and phenotyped mitonuclear introgression lines, which allowed us to assess the independent effects of the evolutionary history of the nuclear and the mitochondrial genome. The nuclear genome was responsible for the largest share of divergence seen in ageing. However, the mitochondrial genome also had sizeable effects, which were sex-specific and expressed primarily as epistatic interactions with the nuclear genome. The effects of mitonuclear disruption were largely consistent with mitonuclear coadaptation. Variation in ETC activity explained a large proportion of variance in ageing and life-history traits and this multivariate relationship differed somewhat between the sexes. In conclusion, mitonuclear epistasis has played an important role in the laboratory evolution of ETC complex activity, ageing, and life histories and these are closely associated. The mitonuclear architecture of evolved differences in life-history traits and mitochondrial bioenergetics was sex-specific.

  9. Bioenergetics assessment of fish and crayfish consumption by river otter (Lontra canadensis): integrating prey availability, diet, and field metabolic rate

    Science.gov (United States)

    Dekar, Matthew P.; Magoulick, Daniel D.; Beringer, J.

    2010-01-01

    River otters (Lontra canadensis) are important predators in aquatic ecosystems, but few studies quantify their prey consumption. We trapped crayfish monthly as an index of availability and collected otter scat for diet analysis in the Ozark Mountains of northwestern Arkansas, USA. We measured otter daily energy expenditure (DEE) with the doubly labeled water method to develop a bioenergetics model for estimating monthly prey consumption. Meek's crayfish (Orconectes meeki) catch-per-unit-effort was positively related to stream temperature, indicating that crayfish were more available during warmer months. The percentage frequency of occurrence for crayfish in scat samples peaked at 85.0% in summer and was lowest (42.3%) in winter. In contrast, the percentage occurrence of fish was 13.3% in summer and 57.7% in winter. Estimates of DEE averaged 4738 kJ·day-1 for an otter with a body mass of 7842 g. Total biomass consumption ranged from 35 079 to 52 653 g·month-1 (wet mass), corresponding to a high proportion of fish and crayfish in the diet, respectively. Otter consumption represents a large fraction of prey production, indicating potentially strong effects of otters on trophic dynamics in stream ecosystems.

  10. Spatially-explicit bioenergetics of Pacific sardine in the Southern California Bight: are mesoscale eddies areas of exceptional prerecruit production?

    Science.gov (United States)

    Logerwell, Elizabeth A.; Lavaniegos, Bertha; Smith, Paul E.

    Previous research shows that offshore mesoscale eddies in the Southern California Bight region are areas where sardine larval abundance is significantly increased relative to inshore, slope and surrounding offshore waters. In order for mesoscale eddies to be a mechanism linking climate and sardine population variability they must be areas of exceptional prerecruit production. Temperature and prey data from various Southern California Bight (SCB) habitats, including offshore eddies, were applied to a spatially-explicit bioenergetic model which predicts sardine prerecruit growth potential. Growth potential was similar in inshore, slope, and eddy regions (11% and 12% day -1), and was lower in the offshore region, 9% day -1. To estimate production in eddy and non-eddy habitats, growth potential was multiplied by habitat-specific estimates of sardine larval biomass from at-sea surveys. A production index, a measure of potential production resulting from individual growth rate potential and local abundance, was greater in the model cyclonic eddy than in all other regions by more than an order of magnitude. In fact, the production index in the eddy was four times greater than in all other regions combined.

  11. Bioenergetic modeling reveals that Chinese green tree vipers select postprandial temperatures in laboratory thermal gradients that maximize net energy intake.

    Science.gov (United States)

    Tsai, Tein-Shun; Lee, How-Jing; Tu, Ming-Chung

    2009-11-01

    With bioenergetic modeling, we tested the hypothesis that reptiles maximize net energy gain by postprandial thermal selection. Previous studies have shown that Chinese green tree vipers (Trimeresurus s. stejnegeri) have postprandial thermophily (mean preferred temperature T(p) for males =27.8 degrees C) in a linear thigmothermal gradient when seclusion sites and water existed. With some published empirical models of digestion associated factors for this snake, we calculated the average rate (E(net)) and efficiency (K(net)) of net energy gain from possible combinations of meal size, activity level, and feeding frequency at each temperature. The simulations consistently revealed that E(net) maximizes at the T(p) of these snakes. Although the K(net) peaks at a lower temperature than E(net), the value of K(net) remains high (>=0.85 in ratio to maximum) at the peak temperature of E(net). This suggested that the demands of both E(net) and K(net) can be attained by postprandial thermal selection in this snake. In conclusion, the data support our prediction that postprandial thermal selection may maximize net energy gain.

  12. Altered p53 and NOX1 activity cause bioenergetic defects in a SCA7 polyglutamine disease model.

    Science.gov (United States)

    Ajayi, Abiodun; Yu, Xin; Wahlo-Svedin, Carolina; Tsirigotaki, Galateia; Karlström, Victor; Ström, Anna-Lena

    2015-01-01

    Spinocerebellar ataxia type 7 (SCA7) is one of the nine neurodegenerative disorders caused by expanded polyglutamine (polyQ) domains. Common pathogenic mechanisms, including bioenergetics defects, have been suggested for these so called polyQ diseases. However, the exact molecular mechanism(s) behind the metabolic dysfunction is still unclear. In this study we identified a previously unreported mechanism, involving disruption of p53 and NADPH oxidase 1 (NOX1) activity, by which the expanded SCA7 disease protein ATXN7 causes metabolic dysregulation. The NOX1 protein is known to promote glycolytic activity, whereas the transcription factor p53 inhibits this process and instead promotes mitochondrial respiration. In a stable inducible PC12 model of SCA7, p53 and mutant ATXN7 co-aggregated and the transcriptional activity of p53 was reduced, resulting in a 50% decrease of key p53 target proteins, like AIF and TIGAR. In contrast, the expression of NOX1 was increased approximately 2 times in SCA7 cells. Together these alterations resulted in a decreased respiratory capacity, an increased reliance on glycolysis for energy production and a subsequent 20% reduction of ATP in SCA7 cells. Restoring p53 function, or suppressing NOX1 activity, both reversed the metabolic dysfunction and ameliorated mutant ATXN7 toxicity. These results hence not only enhance the understanding of the mechanisms causing metabolic dysfunction in SCA7 disease, but also identify NOX1 as a novel potential therapeutic target in SCA7 and possibly other polyQ diseases.

  13. Landscape scale measures of steelhead (Oncorhynchus mykiss) bioenergetic growth rate potential in Lake Michigan and comparison with angler catch rates

    Science.gov (United States)

    Hook, T.O.; Rutherford, E.S.; Brines, Shannon J.; Geddes, C.A.; Mason, D.M.; Schwab, D.J.; Fleischer, G.W.

    2004-01-01

    The relative quality of a habitat can influence fish consumption, growth, mortality, and production. In order to quantify habitat quality, several authors have combined bioenergetic and foraging models to generate spatially explicit estimates of fish growth rate potential (GRP). However, the capacity of GRP to reflect the spatial distributions of fishes over large areas has not been fully evaluated. We generated landscape scale estimates of steelhead (Oncorhynchus mykiss) GRP throughout Lake Michigan for 1994-1996, and used these estimates to test the hypotheses that GRP is a good predictor of spatial patterns of steelhead catch rates. We used surface temperatures (measured with AVHRR satellite imagery) and acoustically measured steelhead prey densities (alewife, Alosa pseudoharengus) as inputs for the GRP model. Our analyses demonstrate that potential steelhead growth rates in Lake Michigan are highly variable in both space and time. Steelhead GRP tended to increase with latitude, and mean GRP was much higher during September 1995, compared to 1994 and 1996. In addition, our study suggests that landscape scale measures of GRP are not good predictors of steelhead catch rates throughout Lake Michigan, but may provide an index of interannual variation in system-wide habitat quality.

  14. Climate regimes and water temperature changes in the Columbia River: bioenergetic implications for predators of juvenile salmon

    Science.gov (United States)

    Petersen, J.H.; Kitchell, J.F.

    2001-01-01

    We examined how climatic regime shifts may have affected predation rates on juvenile Pacific salmonids (Oncorhynchus spp.) by northern squawfish (Ptychocheilus oregonensis, also called northern pikeminnow), smallmouth bass (Micropterus dolomieu), and walleye (Stizostedion vitreum) in the Columbia River. During 1933-1996, oceanic, coastal, and freshwater indices of climate were highly correlated, and an index for the Columbia River Basin suggested that climate shifts may have occurred about 1946, 1958, 1969, and 1977. Summer water temperature varied as much as 2??C between climate periods. We used a bioenergetics model for northern squawfish, the most important piscivore, to predict that predation on salmonids would have been 26-31% higher during two periods with relatively warm spring-summer water temperatures (1933-1946, 1978-1996) than during an extremely cold period (1947-1958). Predicted predation rates of northern squawfish were 68-96% higher in the warmest year compared with the coldest year. Predation rates of smallmouth bass and walleye on juvenile salmonids varied among climate periods similar to rates predicted for northern squawfish. Climatic effects need to be understood in both freshwater and nearshore marine habitats, since growth rates of salmon populations are especially sensitive to mortality during early life stages.

  15. BIOENERGETIC DIFFERENCES DURING WALKING AND RUNNING IN TRANSFEMORAL AMPUTEE RUNNERS USING ARTICULATING AND NON-ARTICULATING KNEE PROSTHESES

    Science.gov (United States)

    Highsmith, M. Jason; Kahle, Jason T.; Miro, Rebecca M.; Mengelkoch, Larry J.

    2016-01-01

    Transfemoral amputation (TFA) patients require considerably more energy to walk and run than non-amputees. The purpose of this study was to examine potential bioenergetic differences (oxygen uptake (VO2), heart rate (HR), and ratings of perceived exertion (RPE)) for TFA patients utilizing a conventional running prosthesis with an articulating knee mechanism versus a running prosthesis with a non-articulating knee joint. Four trained TFA runners (n = 4) were accommodated to and tested with both conditions. VO2 and HR were significantly lower (p ≤ 0.05) in five of eight fixed walking and running speeds for the prosthesis with an articulating knee mechanism. TFA demonstrated a trend for lower RPE at six of eight walking speeds using the prosthesis with the articulated knee condition. A trend was observed for self-selected walking speed, self-selected running speed, and maximal speed to be faster for TFA subjects using the prosthesis with the articulated knee condition. Finally, all four TFA participants subjectively preferred running with the prosthesis with the articulated knee condition. These findings suggest that, for trained TFA runners, a running prosthesis with an articulating knee prosthesis reduces ambulatory energy costs and enhances subjective perceptive measures compared to using a non-articulating knee prosthesis. PMID:28066524

  16. Philosophical basis and some historical aspects of systems biology: from Hegel to Noble - applications for bioenergetic research.

    Science.gov (United States)

    Saks, Valdur; Monge, Claire; Guzun, Rita

    2009-03-01

    We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed.

  17. Did goethe describe attention deficit hyperactivity disorder?

    Science.gov (United States)

    Bonazza, Sara; Scaglione, Cesa; Poppi, Massimo; Rizzo, Giovanni

    2011-01-01

    As early as 1846, the typical symptoms of attention deficit hyperactivity disorder (ADHD) were described by Heinrich Hoffmann (1809-1894). However, in Goethe's masterpiece Faust (1832), the character of Euphorion strongly suggests ADHD diagnosis.

  18. Attention-Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... of ADHD behaviors and problems can cause low self-esteem and problems with relationships. Individual counseling and support ... was contributed by: familydoctor.org editorial staff Tags: Adolescent, adult, Attention Deficit Hyperactivity, child, Neurologic, Overview Family ...

  19. Deficits and Growth from Romania's Perspective

    Directory of Open Access Journals (Sweden)

    Bogdan Andrei MOLDOVAN

    2009-06-01

    Full Text Available In the last eight years Romania has encountereda significant growth of the GDP. However,the economy does not seem capable to value thisgrowth by balancing the budget and reducing thecurrent account deficit, problems that are persistentduring the last period.In 2008 the Romanian economy had thehighest level of budget deficit since the 90’s. Thereis an important debate between the economistson this issue and we have to see if there is anyreason to worry, having in mind the current globalfinancial crisis.This paper tries to analyze the problemsof budgetary deficit, current account deficit andeconomic growth. We will take a look on last periodstatistics and on specific literature, see how thosevariables evolved over time and in different casesand we will try to identify possible connectionsbetween them.

  20. Neuropsychological deficits in patients with Lyme borreliosis

    OpenAIRE

    Katja Pruša

    2001-01-01

    Slovenia is an endemic area for Lyme borreliosis, a disease that affects many organic systems. Decline in cognitive abilities and emotional changes can appear in acute and chronic stage of the disease beside somatic difficulties. Early antibiotic therapy is of great importance in recovery. Attention and concentration deficits, memory deficits, impaired executive functioning, depression and other symptoms reduce work efficiency and life quality of people with Lyme borreliosis. Neuropsychologic...

  1. Dissociations between developmental dyslexias and attention deficits

    OpenAIRE

    Limor eLukov; Naama eFriedmann; Lilach eShalev; Lilach eKhentov-Kraus; Nir eShalev; Rakefet eLorber; Revital eGuggenheim

    2015-01-01

    We examine whether attention deficits underlie developmental dyslexia, or certain types of dyslexia, by presenting double dissociations between the two. We took into account the existence of distinct types of dyslexia and of attention deficits, and focused on dyslexias that may be thought to have an attentional basis: letter position dyslexia (LPD), in which letters migrate within words, attentional dyslexia (AD), in which letters migrate between words, neglect dyslexia, in which letters on o...

  2. Attention deficit in children: a multiprofessional approach

    OpenAIRE

    2015-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavior disorder in children characterized by attention deficit, overactivity and impulsivity, which may persist into adolescence and adulthood. It is often complicated with multiple comorbid disorders which when undiagnosed or untreated significantly affects the children on aspects like academic skills, peer relationship, social life and difficulty in leading productive lives. This report presents a case of 12 year old male ...

  3. Orbitofrontal cortex abnormality and deficit schizophrenia.

    Science.gov (United States)

    Kanahara, Nobuhisa; Sekine, Yoshimoto; Haraguchi, Tadashi; Uchida, Yoshitaka; Hashimoto, Kenji; Shimizu, Eiji; Iyo, Masaomi

    2013-02-01

    Deficit syndrome, which is characterized by primary and enduring negative symptoms, is a homogeneous subtype within schizophrenia. Negative symptoms in schizophrenia are currently considered to be closely linked with frontal lobe impairment. However, the etiology in the frontal lobe of people with deficit syndrome is not fully understood. We measured regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) in 33 patients with deficit syndrome, 40 patients with nondeficit syndrome, and 45 healthy controls, and we compared groups using the voxel-wise method. Schizophrenia combined group, the deficit syndrome and the nondeficit syndrome presented hypoperfusion in mainly the medial and lateral prefrontal cortices. The deficit syndrome group showed a significant decrease in rCBF in the right orbitofrontal cortex (OFC) compared to the nondeficit group. These results demonstrated that at-rest hypofrontality was a common feature within the disease group and suggested that the OFC might play an important role in the development of severe negative symptoms in people with deficit syndrome.

  4. Interferon-Stimulated Gene 15 Upregulation Precedes the Development of Blood-Brain Barrier Disruption and Cerebral Edema after Traumatic Brain Injury in Young Mice.

    Science.gov (United States)

    Rossi, Janet L; Todd, Tracey; Daniels, Zachary; Bazan, Nicolas G; Belayev, Ludmila

    2015-07-15

    Recent studies show that myosin light chain kinase (MLCK) plays a pivotal role in development of cerebral edema, a known complication following traumatic brain injury (TBI) in children and a contributing factor to worsened neurologic recovery. Interferon-stimulated gene 15 (ISG15) is upregulated after cerebral ischemia and is neuroprotective. The significant role of ISG15 after TBI has not been studied. Postnatal Day (PND) 21 and PND24 mice were subjected to lateral closed-skull injury with impact depth of 2.0 or 2.25 mm. Behavior was examined at 7 d using two-object novel recognition and Wire Hang tests. Mice were sacrificed at 6 h, 12 h, 24 h, 48 h, 72 h, and 7 d. ISG15 and MLCK were analyzed by Western blot and immunohistochemistry, blood-brain barrier (BBB) disruption with Evans Blue (EB), and cerebral edema with wet/dry weights. EB extravasation and edema peaked at 72 h in both ages. PND21 mice had more severe neurological deficits, compared with PND24 mice. PND24 mice showed peak ISG15 expression at 6 h, and PND21 mice at 72 h. MLCK peaked in both age groups at 12 h and co-localized with ISG15 on immunohistochemistry and co-immunoprecipitation. These studies provide evidence, ISG15 is elevated following TBI in mice, preceding MLCK elevation, development of BBB disruption, and cerebral edema.

  5. Third chromosome candidate genes for conspecific sperm precedence between D. simulans and D. mauritiana

    Directory of Open Access Journals (Sweden)

    Brouwers Barb

    2010-04-01

    Full Text Available Abstract Background Male - female incompatibilities can be critical in keeping species as separate and discrete units. Premating incompatibilities and postzygotic hybrid sterility/inviability have been widely studied as isolating barriers between species. In recent years, a number of studies have brought attention to postmating prezygotic barriers arising from male - male competition and male - female interactions. Yet little is known about the genetic basis of postmating prezygotic isolation barriers between species. Results Using D. simulans lines with mapped introgressions of D. mauritiana into their third chromosome, we find at least two D. mauritiana introgressions causing male breakdown in competitive paternity success. Eighty one genes within the mapped introgressed regions were identified as broad-sense candidates on the basis of male reproductive tract expression and male-related function. The list of candidates was narrowed down to five genes based on differences in male reproductive tract expression between D. simulans and D. mauritiana. Another ten genes were confirmed as candidates using evidence of adaptive gene coding sequence diversification in the D. simulans and/or D. mauritiana lineage. Our results show a complex genetic basis for conspecific sperm precedence, with evidence of gene interactions between at least two third chromosome loci. Pleiotropy is also evident from correlation between conspecific sperm precedence and female induced fecundity and the identification of candidate genes that might exert an effect through genetic conflict and immunity. Conclusions We identified at least two loci responsible for conspecific sperm precedence. A third of candidate genes within these two loci are located in the 89B cytogenetic position, highlighting a possible major role for this chromosome position during the evolution of species specific adaptations to postmating prezygotic reproductive challenges.

  6. Transient autonomic dysfunction precedes ST-segment depression in patients with syndrome X.

    Science.gov (United States)

    Ponikowski, P; Rosano, G M; Amadi, A A; Collins, P; Coats, A J; Poole-Wilson, P A; Kaski, J C

    1996-05-01

    Increased sympathetic drive has been suggested to play a role in the pathogenesis of syndrome X (angina pectoris, positive exercise testing, and angiographically normal coronary arteries). Heart rate variability (HRV) studies have shown that patients with syndrome X have an imbalance in autonomic nervous system activity (sympathetic predominance). However, it is not known if transient ST-segment depression which occurs in syndrome X during daily activities is related to this autonomic nervous system dysfunction. This study investigates the relation between the response of the autonomic nervous system, as assessed by HRV analysis, and the occurrence of transient ST-segment depression during 24-hour ambulatory electrocardiographic monitoring in 23 patients (4 men and 19 women, mean age 55 +/- 6 years) with syndrome X. The frequency-domain variables of HRV low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.40 Hz) power were measured at 6-minute intervals during the 30 minutes preceding the onset of transient ST-segment depression. Fourteen patients (61%) had > or = 1 episode of ST-segment depression in the 24 hours, whereas the remaining 9 patients (39%) had no significant ST-segment change. HRV measures differed according to whether or not ST-segment depression was associated with increased heart rate. Episodes of ST-segment depression associated with increased heart rate were preceded by a reduction of high-frequency power and an increase in the low-frequency--high-frequency ratio, whereas episodes of ST-segment depression not associated with increased heart rate showed no significant HRV changes. Low-frequency power remained unchanged irrespective of heart rate. Thus, in patients with syndrome X, a sympathovagal imbalance (sympathetic predominance due to vagal tone withdrawal) precedes episodes of ST-segment depression that are associated with an increased heart rate.

  7. Factors preceding CRM readiness in small- and medium-sized tourism enterprises

    Directory of Open Access Journals (Sweden)

    Dinesh Vallabh

    2015-02-01

    Full Text Available Orientation: Customer relationship management (CRM is important to organisations striving for competitive advantage through building relationships with their customers.Research purpose: This study identified the factors preceding CRM and assessed selected South African small- and medium-sized tourism enterprises’ (SMTEs readiness for CRM.Motivation: CRM is likely to enhance SMTEs’ competitiveness. However, successful adoption and implementation of CRM is unlikely unless the organisation is ready for it.Research design, approach and method: A quantitative research approach and survey questionnaire yielded primary data from 332 respondent organisations selected by systematic sampling. Exploratory factor analysis was used to identify the latent factors preceding CRM readiness. Organisational CRM readiness was assessed based on CRM maturity in terms of data collection, use and sharing throughout the organisation.Main findings: Respondent-organisations performed well on the four factors preceding CRM readiness − business strategy, customer strategy, touch points and competencies, skills and technology and also on data collections and use, but not on data sharing.Practical/Managerial implications: CRM practice is believed to assist organisations in tailoring products and services to customers’ needs, providing customer satisfaction, enhancing customer retention and ultimately improving the organisation’s competitiveness and profitability. CRM might fail if SMTEs do not have CRM-enabling conditions in place and a CRM readiness audit should therefore be performed.Contribution: The study contributes to a largely under-researched area concerning CRM in SMTEs by providing an improved understanding of the factors that will enable SMTEs to engage in CRM activities.

  8. Behaviour of coconut mites preceding take-off to passive aerial dispersal.

    Science.gov (United States)

    Melo, J W S; Lima, D B; Sabelis, M W; Pallini, A; Gondim, M G C

    2014-12-01

    For more than three decades the coconut mite Aceria guerreronis Keifer is one of the most important pests of coconut palms and has recently spread to many coconut production areas worldwide. Colonization of coconut palms is thought to arise from mites dispersing aerially after take-off from other plants within the same plantation or other plantations. The underlying dispersal behaviour of the mite at take-off, in the airborne state and after landing is largely unknown and this is essential to understand how they spread from tree to tree. In this article we studied whether take-off to aerial dispersal of coconut mites is preceded by characteristic behaviour, whether there is a correlation between the body position preceding aerial dispersal and the direction of the wind, and whether the substrate (outer surface of coconut bracts or epidermis) and the wind speed matter to the decision to take-off. We found that take-off can sometimes be preceded by a raised body stance, but more frequently take-off occurs while the mite is walking or resting on its substrate. Coconut mites that become airborne assumed a body stance that had no relation to the wind direction. Take-off was suppressed on a substrate providing food to coconut mites, but occurred significantly more frequently on the outer surface of coconut bracts than on the surface of the fruit. For both substrates, take-off frequency increased with wind speed. We conclude that coconut mites have at least some degree of control over take-off for aerial dispersal and that there is as yet no reason to infer that a raised body stance is necessary to become airborne.

  9. Optimal Parallel Algorithms for Two Processor Scheduling with Tree Precedence Constraints

    OpenAIRE

    Ernst W. Mayr; Hans Stadtherr

    2016-01-01

    Consider the problem of finding a minimum length schedule for an unit execution time tasks on m processors with tree-like precedence constraints. A sequential algorithm can solve this problem in linear time. The fastest known parallel algorithm needs O(log n) time using n^2 processors. For the case m=2 we present two work optimal parallel algorithms that produce greedy optimal schedules for intrees and outtrees. Both run in O(log n) time using n/(log n) processors of an EREW PRAM.

  10. Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report.

    Science.gov (United States)

    Georgiades, F; Demosthenous, S; Braimi, M; Tsitskari, T; Psarelis, S

    2015-11-01

    Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up.

  11. Paraneoplastic (non-metastatic) adrenal insufficiency preceded the onset of primary lung cancer by 12 weeks.

    Science.gov (United States)

    Shantha, Ghanshyam Palamaner Subash; Kumar, Anita A; Jeyachandran, Vijay; Rajamanickam, Deepan; Bhaskar, Emmanuel; Paniker, Vinod K; Abraham, Georgi

    2009-01-01

    Clinically evident adrenal insufficiency associated with lung cancer is a rare entity. Among reported cases, adrenal insufficiency has occurred with or succeeded the primary lung cancer. Adrenal insufficiency has also been secondary to metastasis to the adrenal gland. The present report concerns a 61-year-old man, a chronic smoker, who presented to us with symptomatic adrenal insufficiency. He had no evidence of lung cancer during this visit. The primary lung cancer was only identified 12 weeks later. Additionally, his adrenals showed no evidence of metastasis. Hence his adrenal insufficiency had been a paraneoplastic manifestation of the lung cancer, and it had also preceded the primary by 12 weeks.

  12. Onset of Bonding Plasmon Hybridization Preceded by Gap Modes in Dielectric Splitting of Metal Disks

    DEFF Research Database (Denmark)

    Frederiksen, Maj; Bochenkov, Vladimir; Ogaki, Ryosuke;

    2013-01-01

    Dielectric splitting of nanoscale disks was studied experimentally and via finite-difference time-domain (FDTD) simulations through systematic introduction of multiple ultrathin dielectric layers. Tunable, hybridized dark bonding modes were seen with first-order gap modes preceding the appearance...... of bonding dipole−dipole disk modes. The observed bright dipolar mode did not show the energy shift expected from plasmon hybridization but activated dark higher order gap modes. Introducing lateral asymmetry was shown to remodel the field distribution resulting in 3D asymmetry that reoriented the dipole...

  13. Solving a large-scale precedence constrained scheduling problem with elastic jobs using tabu search

    DEFF Research Database (Denmark)

    Pedersen, C.R.; Rasmussen, R.V.; Andersen, Kim Allan

    2007-01-01

    This paper presents a solution method for minimizing makespan of a practical large-scale scheduling problem with elastic jobs. The jobs are processed on three servers and restricted by precedence constraints, time windows and capacity limitations. We derive a new method for approximating the server...... exploitation of the elastic jobs and solve the problem using a tabu search procedure. Finding an initial feasible solution is in general -complete, but the tabu search procedure includes a specialized heuristic for solving this problem. The solution method has proven to be very efficient and leads...

  14. Executive functioning in boys with ADHD: primarily an inhibition deficit?

    NARCIS (Netherlands)

    Scheres, A.P.J.; Oosterlaan, J.; Geurts, H.M.; Morein-Zamir, S.; Meiran, N.; Vlasveld, L.; Sergeant, J.A.

    2004-01-01

    This study was aimed at: (1) testing whether boys with Attention Deficit/Hyperactivity Disorder (ADHD) demonstrate a deficit in response inhibition and deficits in other executive functions (EF), or alternatively, demonstrate a deficit in only response inhibition; (2) investigating which role associ

  15. Analysis of Budget deficit in Romania during 2000-2013

    OpenAIRE

    2014-01-01

    Worldwide, over time, the years of economic crisis were defined by significant increases in the levels of budget deficits. Discussions on sizing budget deficits, financing, especially the volume of public debt became more intense, both politically and academically. The impact of budget deficit on economic growth is a common theme found in the economic policies adopted. The present paper aims to analyze the evolution of budget deficit and the structural budget deficit in Romania during 2000-20...

  16. Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas.

    Science.gov (United States)

    Goldstein, Neal S; Bhanot, Punam; Odish, Eva; Hunter, Susan

    2003-06-01

    We compared hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas to incidental hyperplastic polyps to identify distinguishing morphologic criteria. The study group included 106 hyperplastic-like, nonadenomatous, serrated polyps, most from the ascending colon in 91 patients; the control group included 106 rectosigmoid hyperplastic polyps from 106 patients in whom adenocarcinoma did not develop. Study group polyps had an expanded crypt proliferative zone, a serrated architectural outline that became apparent in the basilar crypt regions, basilar crypt dilation, inverted crypts, and a predominance of dysmaturational crypts (crypts with minimal cell maturation). In contrast, control group polyps had a proliferative zone confined to the basal crypt region, serrated architecture that became apparent in the superficial crypt region, rare to no basilar crypt dilation, and rare or no dysmaturational crypts. Hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas had a distinctive constellation of morphologic features related to altered and decreased cell function and control that resulted in dysmaturational crypts. Dysmaturation constitutes a range of morphologic alterations, some of which overlap with incidental-type innocuous hyperplastic polyps. The morphologic features described herein provide initial guidelines to identify this potentially important subset of premalignant serrated-like polyps.

  17. Upland rice under no-tillage preceded by crops for soil cover and nitrogen fertilization

    Directory of Open Access Journals (Sweden)

    Edemar Moro

    2013-12-01

    Full Text Available The grain yield of upland rice under no-tillage has been unsatisfactory and one reason could be the nitrate/ammonium balance in the soil. Cover crops and nitrogen fertilization can be used to change the nitrate/ammonium relation in the soil and improve conditions for the development of upland rice in the no-tillage (NT system. The aim was to study the effect of cover crops and nitrogen sources on grain yield of upland rice under no tillage. The study was carried out on the Fazenda Experimental Lageado, in Botucatu, State of São Paulo, Brazil, in an Oxisol area under no-tillage for six years. The experiment was arranged in a randomized block split-plot design with four replications. The plots consisted of six cover crop species (Brachiaria brizantha, B. decumbens, B. humidicola, B. ruziziensis, Pennisetum americanum, and Crotalaria spectabilis and the split-plots of seven forms of N fertilizer management. Millet is the best cover crop to precede upland rice under NT. The best form of N application, as nitrate, is in split rates or total rate at topdressing or an ammonium source with or without a nitrification inhibitor, in split doses. When the cover crops C. spectabilis, B. brizantha, B. decumbens, B. humidicola, and B. ruziziensis preceded rice, they induced the highest grain yield when rice was fertilized with N as ammonium sulfate source + nitrification inhibitor in split rates or total dose at topdressing.

  18. Left ventricle expands maximally preceding end-diastole. Radionuclide ventriculography study

    Energy Technology Data Exchange (ETDEWEB)

    Horinouchi, Osamu [Kagoshima Univ. (Japan). Faculty of Medicine

    2002-05-01

    It has been considered that left ventricle (LV) expands maximally at the end-diastole. However, is it exactly coincident with this point? This study was aimed to determine whether the maximal expansion of LV coincides with the peak of R wave on electrocardiogram. Thirty-three angina pectoris patients with normal LV motion were examined using radionuclide ventriculography. Data were obtained from every 30 ms backward frame from the peak of R wave. All patients showed the time of maximal expansion preceded the peak of R wave. The intervals from the peak of R wave and the onset of P wave to maximal expansion of LV was 105{+-}29 ms and 88{+-}25 ms, respectively. This period corresponds to the timing of maximal excurtion of mitral valve by atrial contraction, and the centripetal motion of LV without losing its volume before end-diastole may be interpreted on account of the movement of mitral valve toward closure. These findings suggest that LV expands maximally between P and R wave after atrial contraction, preceding the peak of R wave thought conventionally as the end-diastole. (author)

  19. Aseismic Slips Preceding Ruptures Assumed for Anomalous Seismicities and Crustal Deformations

    Science.gov (United States)

    Ogata, Y.

    2007-12-01

    If aseismic slips occurs on a fault or its deeper extension, both seismicity and geodetic records around the source should be affected. Such anomalies are revealed to have occurred during the last several years leading up to the October 2004 Chuetsu Earthquake of M6.8, the March 2007 Noto Peninsula Earthquake of M6.9, and the July 2007 Chuetsu-Oki Earthquake of M6.8, which occurred successively in the near-field, central Japan. Seismic zones of negative and positive increments of the Coulomb failure stress, assuming such slips, show seismic quiescence and activation, respectively, relative to the predicted rate by the ETAS model. These are further supported by transient crustal movement around the source preceding the rupture. Namely, time series of the baseline distance records between a numbers of the permanent GPS stations deviated from the predicted trend, with the trend of different slope that is basically consistent with the horizontal displacements of the stations due to the assumed slips. References Ogata, Y. (2007) Seismicity and geodetic anomalies in a wide area preceding the Niigata-Ken-Chuetsu Earthquake of October 23, 2004, central Japan, J. Geophys. Res. 112, in press.

  20. BRIEF HYPOXIA PRECEDING E. COLI BACTEREMIA DOWNREGULATES HEPATIC TNF-α PRODUCTION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Hepatic TNF-α production following gram-negative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF-α expression may be modified by the manner in which the hepatic O2 supply is reduced and equally important, its timing relative to bacteremia. Brief secondary hypoxic stress of buffer-perfused rat livers downregulates E. Coli (EC)-induced TNF-α expression whereas low-flow ischemia preceding EC increases subsequent TNF-α production owing to reactive O2 species (ROS). Here we determined whether 30 min of constant-flow hypoxia preceding 109 intraportal EC likewise increases antigenic and bioactive TNF-α protein concentrations during reoxygenation via production of ROS. Multiple groups (n=38) were studied over 180 minutes, circulation antigenic TNF-α decreased in H/R+EC vs. EC controls (1 939±640 vs. 12 407±2 476 μg/L at t=180 min; P<0.01, along with TNF-α bioactivity). TNF-α protein were not restored to control levels in ALLO+H/R+EC. Thus, EC-induced hepatic TNF-α production and export is strongly O2-dependent in intact liver regardless of the generation of ROS or the sequence of bacteremia and modest hypoxic stress.

  1. Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz

    2009-01-01

    The evaluation of the cognitive control in children with attention-deficit hyperactivity disorder through the use of oculomotor tests reveal that this group showed susceptibility to peripheral distractors and deficits in response inhibition. All subjects were found to have intact sensorimotor function and working memory.

  2. Readings on Attention Deficit Disorder or Attention Deficit/Hyperactivity Disorder. ERIC Mini-Bib.

    Science.gov (United States)

    Sorenson, Barbara, Comp.

    This annotated bibliography identifies 17 readings, 3 videotapes, and 8 children's books concerned with attention deficit disorder or attention deficit/hyperactivity disorder. Items include guides for parents, teachers, and students; analyses of issues in the field; practical teaching guides; investigations into etiology; and resource guides.…

  3. Story Comprehension and Academic Deficits in Children with Attention Deficit Hyperactivity Disorder: What Is the Connection?

    Science.gov (United States)

    Berthiaume, Kristen S.

    2006-01-01

    Based on the reliable findings that children with attention deficit hyperactivity disorder (ADHD) have both attentional and academic difficulties, it is assumed that the attentional deficit contributes to the academic problems. In this article, existing support for a link between the attentional and academic difficulties experienced by children…

  4. Multiple Deficits in ADHD: Executive Dysfunction, Delay Aversion, Reaction Time Variability, and Emotional Deficits

    Science.gov (United States)

    Sjowall, Douglas; Roth, Linda; Lindqvist, Sofia; Thorell, Lisa B.

    2013-01-01

    Background: The notion that ADHD constitutes a heterogeneous disorder is well accepted. However, this study contributes with new important knowledge by examining independent effects of a large range of neuropsychological deficits. In addition, the study investigated whether deficits in emotional functioning constitute a dissociable component of…

  5. Bioenergetics of Nutrient Reserves and Metabolism in Spiny Lobster Juveniles Sagmariasus verreauxi: Predicting Nutritional Condition from Hemolymph Biochemistry.

    Science.gov (United States)

    Simon, C J; Fitzgibbon, Q P; Battison, A; Carter, C G; Battaglene, S C

    2015-01-01

    The nutritional condition of cultured Sagmariasus verreauxi juveniles over the molt and during starvation was investigated by studying their metabolism, bioenergetics of nutrient reserves, and hemolymph biochemistry. Juveniles were shown to downregulate standard metabolic rate by as much as 52% within 14 d during starvation. Hepatopancreas (HP) lipid was prioritized as a source of energy, but this reserve represented only between 1% and 13% of the total measured energy reserve and was used quickly during starvation, especially in the immediate postmolt period when as much as 60% was depleted within 3 d. Abdominal muscle (AM) protein represented between 74% and 90% of the total measured energy reserve in juvenile lobsters, and as much as 40% of available AM protein energy was used over 28 d of starvation after the molt. Carbohydrate reserves represented less than 2% of the measured total energy reserve in fed intermolt lobsters and provided negligible energy during starvation. Eighteen hemolymph parameters were measured to identify a nondestructive biomarker of condition that would reflect accurately the state of energy reserves of the lobster. Among these, the hemolymph Brix index was the most accurate and practical method to predict HP lipid and the total energy content of both the HP and the AM in juvenile S. verreauxi. The Brix index was strongly correlated with hemolymph proteins, triglyceride, cholesterol, calcium, and phosphorus concentrations, as well as lipase activity; all were useful in predicting condition. Electrolytes such as chloride, magnesium, and potassium and metabolites such as glucose and lactate were poor indicators of nutritional condition. Uric acid and the "albumin"-to-"globulin" ratio provided complementary information to the Brix index, which may assist in determining nutritional condition of wild juvenile lobsters of unknown intermolt development. This study will greatly assist future ecological studies examining the nutritional condition

  6. Anticancer/antiviral agent Akt inhibitor-IV massively accumulates in mitochondria and potently disrupts cellular bioenergetics.

    Science.gov (United States)

    Meinig, J Matthew; Peterson, Blake R

    2015-02-20

    Inhibitors of the PI3-kinase/Akt (protein kinase B) pathway are under investigation as anticancer and antiviral agents. Akt inhibitor-IV (ChemBridge 5233705, CAS 681281-88-9, AKTIV), a small molecule reported to inhibit this pathway, exhibits potent anticancer and broad-spectrum antiviral activity. However, depending on concentration, this cationic benzimidazole derivative exhibits paradoxical positive or negative effects on the phosphorylation of Akt that are not well understood. To elucidate its mechanism of action, we investigated its spectroscopic properties. This compound proved to be sufficiently fluorescent (excitation λmax = 388 nm, emission λmax = 460 nm) to enable examination of its uptake and distribution in living mammalian cells. Despite a low quantum yield of 0.0016, imaging of HeLa cells treated with AKTIV (1 μM, 5 min) by confocal laser scanning microscopy, with excitation at 405 nm, revealed extensive accumulation in mitochondria. Treatment of Jurkat lymphocytes with 1 μM AKTIV for 15 min caused accumulation to over 250 μM in these organelles, whereas treatment with 5 μM AKTIV yielded concentrations of over 1 mM in mitochondria, as analyzed by flow cytometry. This massive loading resulted in swelling of these organelles, followed by their apparent disintegration. These effects were associated with profound disruption of cellular bioenergetics including mitochondrial depolarization, diminished mitochondrial respiration, and release of reactive oxygen species. Because mitochondria play key roles in both cancer proliferation and viral replication, we conclude that the anticancer and antiviral activities of AKTIV predominantly result from its direct and immediate effects on the structure and function of mitochondria.

  7. Zebra mussels (Dreissena polymorpha) limit food for larval fish (Pimephales promelas) in turbulent systems: A bioenergetics analysis

    Science.gov (United States)

    Bartsch, L.A.; Richardson, W.B.; Sandheinrich, M.B.

    2003-01-01

    We conducted a factorial experiment, in outdoor mesocosms, on the effects of zebra mussels and water column mixing (i.e., turbulence) on the diet, growth, and survival of larval fathead minnows (Pimephales promelas). Significant (P zebra mussels, whereas mortality was 37% in treatment with turbulence and 17% and 18% in the zebra mussels treatment, and the control, respectively. The size of individual fish was significantly different among treatments at the end of the experiment and was inversely related to survival. Levels of trophic resources (i.e., phyto and zooplankton) varied among treatments and were treatment specific. Turbulent mixing facilitated removal of phytoplankton by zebra mussels by making the entire water column of the tanks available to these benthic filter feeders. Early in the experiment (Day = 0 to 14) the physical process of turbulent mixing likely caused a reduction in standing stocks of zooplankton. The interactive effect of turbulence and mussels reduced copepod and rotifer stocks, through physical processes and through filtration by zebra mussels, relative to the turbulence treatment. The reductions in the number of total zooplankton in the turbulent mixing mesocosms and the further reduction of rotifer and copepod in the turbulence and mussels treatment coincided with a period of increased reliance of larval fathead minnows on these prey. Estimates of consumption from bioenergetics modeling and measured prey standing stocks indicated caloric resources of suitable prey in turbulence treatments during the early weeks of the experiment were insufficient to prevent starvation. Early mortality in the turbulence and mussels treatment likely released surviving fish from intense intraspecific competition and resulted in higher individual growth rates. A combination of high abundance of zebra mussels in an environment with a well-mixed water column can have significant effects on larval fish survival and growth.

  8. Bioenergetic trade-offs in the sea cucumber Apostichopus japonicus (Echinodermata: Holothuroidea) in response to CO2-driven ocean acidification.

    Science.gov (United States)

    Yuan, Xiutang; Shao, Senlin; Yang, Xiaolong; Yang, Dazuo; Xu, Qinzeng; Zong, Humin; Liu, Shilin

    2016-05-01

    Ocean acidification (OA) caused by excessive CO2 is a potential ecological threat to marine organisms. The impacts of OA on echinoderms are well-documented, but there has been a strong bias towards sea urchins, and limited information is available on sea cucumbers. This work examined the effect of medium-term (60 days) exposure to three pH levels (pH 8.06, 7.72, and 7.41, covering present and future pH variability) on the bioenergetic responses of the sea cucumber, Apostichopus japonicus, an ecologically and economically important holothurian in Asian coasts. Results showed that the measured specific growth rate linearly decreased with decreased pH, leading to a 0.42 %·day(-1) decrease at pH 7.41 compared with that at pH 8.06. The impacts of pH on physiological energetics were variable: measured energy consumption and defecation rates linearly decreased with decreased pH, whereas maintenance energy in calculated respiration and excretion were not significantly affected. No shift in energy allocation pattern was observed in A. japonicus upon exposure to pH 7.72 compared with pH 8.06. However, a significant shift in energy budget occurred upon exposure to pH 7.41, leading to decreased energy intake and increased percentage of energy that was lost in feces, thereby resulting in a significantly lowered allocation into somatic growth. These findings indicate that adult A. japonicus is resilient to the OA scenario at the end of the twenty-first century, but further acidification may negatively influence the grazing capability and growth, thereby influencing its ecological functioning as an "ecosystem engineer" and potentially harming its culture output.

  9. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.

    Science.gov (United States)

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2015-08-20

    We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise

  10. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons.

    Science.gov (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique

    2008-01-01

    This study examines the role of c-jun N-terminal kinase (JNK) in mitochondrial signaling and bioenergetics in primary cortical neurons and isolated rat brain mitochondria. Exposure of neurons to either anisomycin (an activator of JNK/p38 mitogen-activated protein kinases) or H2O2 resulted in activation (phosphorylation) of JNK (mostly p46(JNK1)) and its translocation to mitochondria. Experiments with mitochondria isolated from either rat brain or primary cortical neurons and incubated with proteinase K revealed that phosphorylated JNK was associated with the outer mitochondrial membrane; this association resulted in the phosphorylation of the E(1alpha) subunit of pyruvate dehydrogenase, a key enzyme that catalyzes the oxidative decarboxylation of pyruvate and that links two major metabolic pathways: glycolysis and the tricarboxylic acid cycle. JNK-mediated phosphorylation of pyruvate dehydrogenase was not observed in experiments carried out with mitoplasts, thus suggesting the requirement of intact, functional mitochondria for this effect. JNK-mediated phosphorylation of pyruvate dehydrogenase was associated with a decline in its activity and, consequently, a shift to anaerobic pyruvate metabolism: the latter was confirmed by increased accumulation of lactic acid and decreased overall energy production (ATP levels). Pyruvate dehydrogenase appears to be a specific phosphorylation target for JNK, for other kinases, such as protein kinase A and protein kinase C did not elicit pyruvate dehydrogenase phosphorylation and did not decrease the activity of the complex. These results suggest that JNK mediates a signaling pathway that regulates metabolic functions in mitochondria as part of a network that coordinates cytosolic and mitochondrial processes relevant for cell function.

  11. A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.

    Science.gov (United States)

    Chatton, J Y; Marquet, P; Magistretti, P J

    2000-11-01

    The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.

  12. Bioenergetics-based matrix population modeling enhances life-cycle toxicity assessment of tilapia Oreochromis mossambicus exposed to arsenic.

    Science.gov (United States)

    Liao, Chung-Min; Chiang, Kuo-Chih; Tsai, Jeng-Wei

    2006-04-01

    The objective of this study was to integrate a bioenergetics-based modeling approach into a population stage structure to enhance life-cycle toxicity assessments of the effects of waterborne arsenic (As) on the population dynamics of the tilapia Oreochromis mossambicus. The proposed mathematical model links a Leslie matrix population model and a universal ontogenetic growth model embedding the population-level growth rate and stage-specific modes of toxic action. We present data analyses of key parameters and distributions and discuss the processes of data capture and analysis and the impact of acute/chronic As toxicity responses on population-level effects. We employed a three-parameter Hill equation model to describe the relationship between tilapia whole-body burden and mortality in order to estimate the probability of stage-specific vital rate of survival. Using the DEBtox theory, we distinguished three modes of toxic action (MOA): direct effects on growth and indirect effects via maintenance and food consumption on inhibition by arsenic of the growth of a tilapia population. The asymptotic population growth rate decreased from lambda = 1.0027 for the control group to lambda = 0.9935 for tilapia population exposed to 4 microg mL(-1) As, indicating a potential risk of population intrinsic growth rates for tilapia exposed to higher levels of waterborne As. Our results estimated that an As concentration of 1.02 microg mL(-1) would cause a 50% reduction in the tilapia population. We found that the interplay between external stressors of waterborne As concentration and internally generated modes of action decreasing feeding in the juvenile stage and increasing the maintenance cost in the adult stage had a pronounced influence on the population stage structure of tilapia.

  13. Applying Dynamic Energy Budget (DEB) theory to simulate growth and bio-energetics of blue mussels under low seston conditions

    Science.gov (United States)

    Rosland, R.; Strand, Ø.; Alunno-Bruscia, M.; Bacher, C.; Strohmeier, T.

    2009-08-01

    A Dynamic Energy Budget (DEB) model for simulation of growth and bioenergetics of blue mussels ( Mytilus edulis) has been tested in three low seston sites in southern Norway. The observations comprise four datasets from laboratory experiments (physiological and biometrical mussel data) and three datasets from in situ growth experiments (biometrical mussel data). Additional in situ data from commercial farms in southern Norway were used for estimation of biometrical relationships in the mussels. Three DEB parameters (shape coefficient, half saturation coefficient, and somatic maintenance rate coefficient) were estimated from experimental data, and the estimated parameters were complemented with parameter values from literature to establish a basic parameter set. Model simulations based on the basic parameter set and site specific environmental forcing matched fairly well with observations, but the model was not successful in simulating growth at the extreme low seston regimes in the laboratory experiments in which the long period of negative growth caused negative reproductive mass. Sensitivity analysis indicated that the model was moderately sensitive to changes in the parameter and initial conditions. The results show the robust properties of the DEB model as it manages to simulate mussel growth in several independent datasets from a common basic parameter set. However, the results also demonstrate limitations of Chl a as a food proxy for blue mussels and limitations of the DEB model to simulate long term starvation. Future work should aim at establishing better food proxies and improving the model formulations of the processes involved in food ingestion and assimilation. The current DEB model should also be elaborated to allow shrinking in the structural tissue in order to produce more realistic growth simulations during long periods of starvation.

  14. Growth of juvenile steelhead Oncorhynchus mykiss under size-selective pressure limited by seasonal bioenergetic and environmental constraints

    Science.gov (United States)

    Thompson, Jamie N.; Beauchamp, David A.

    2016-01-01

    Increased freshwater growth of juvenile steelhead Oncorhynchus mykiss improved survival to smolt and adult stages, thus prompting an examination of factors affecting growth during critical periods that influenced survival through subsequent life stages. For three tributaries with contrasting thermal regimes, a bioenergetics model was used to evaluate how feeding rate and energy density of prey influenced seasonal growth and stage-specific survival of juvenile O. mykiss. Sensitivity analysis examined target levels for feeding rate and energy density of prey during the growing season that improved survival to the smolt and adult stages in each tributary. Simulated daily growth was greatest during warmer months (1 July to 30 September), whereas substantial body mass was lost during cooler months (1 December to 31 March). Incremental increases in annual feeding rate or energy density of prey during summer broadened the temperature range at which faster growth occurred and increased the growth of the average juvenile to match those that survived to smolt and adult stages. Survival to later life stages could be improved by increasing feeding rate or energy density of the diet during summer months, when warmer water temperatures accommodated increased growth potential. Higher growth during the summer period in each tributary could improve resiliency during subsequent colder periods that lead to metabolic stress and weight loss. As growth and corresponding survival rates in fresh water are altered by shifting abiotic regimes, it will be increasingly important for fisheries managers to better understand the mechanisms affecting growth limitations in rearing habitats and what measures might maintain or improve growth conditions and survival.

  15. Bioenergetics of three aquatic insects determined by radioisotopic analyses. [/sup 51/Cr and /sup 14/C tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    McCullough, D.A.

    1975-08-01

    The bioenergetics of Simulium spp. and Cheumatopsyche analis from Rattlesnake Springs and Snively Creek, respectively, Benton County, Washington and Tricorthodes minutus from Deep Creek, Oneida County, Idaho were studied using a variety of techniques. Ingestion rates were measured using food sources (diatoms, finely ground watercress, bacteria, and blue-green algae) labelled with /sup 51/Cr and /sup 14/C. Theoretical ingestion rates were calculated from analyses of gut weights and digestion times. Assimilation efficiencies (AE) were determined using the /sup 14/C and dual-label (/sup 51/Cr, /sup 14/C) methods and the ash-ratio technique. The dual-label method provided reliable results when leaching of isotopes from food and feces were not significant. Provided the /sup 51/Cr activity density of food is sufficient, the time required for digestion can also be more accurately determined with /sup 51/Cr than with /sup 14/C. The ash-ratio method provided a wide range of AE values and is not as reliable as the dual-label method because mineral assimilationis unpredictable. Assimilation rates were derived for these animals using the ingestion rate and AE, by several methods employing /sup 14/C uptake curves, and by differences in /sup 51/Cr- and /sup 14/C-derived accumulation values. Methods used to measure other energy budget components are also given. A system was developed for combusting biological samples containing /sup 14/C and determining cpm /sup 14/C and total carbon from a single sample. This method employs Van Slyke wet oxidation, forced circulation and scrubbing of the gases of combustion, and collection of CO/sub 2/ in ethanolamine. Radioactivity in this system was determined by scintillation counting and total carbon by a gravimetric precipitation method. (auth)

  16. High dose methylphenidate treatment in adult attention deficit hyperactivity disorder: a case report

    Directory of Open Access Journals (Sweden)

    Liebrenz Michael

    2012-05-01

    Full Text Available Abstract Introduction Stimulant medication improves hyperactivity, inattention, and impulsivity in both pediatric and adult populations with Attention Deficit Hyperactivity Disorder (ADHD. However, data regarding the optimal dosage in adults is still limited. Case presentation We report the case of a 38-year-old Caucasian patient who was diagnosed with Attention Deficit Hyperactivity Disorder when he was nine years old. He then received up to 10 mg methylphenidate (Ritalin® and 20 mg sustained-release methylphenidate (Ritalin SR® daily. When he was 13, his medication was changed to desipramine (Norpramin®, and both Ritalin® and Ritalin SR® were discontinued; and at age 18, when he developed obsessive-compulsive symptoms, his medication was changed to clomipramine (Anafranil® 75 mg daily. Still suffering from inattention and hyperactivity, the patient began college when he was 19, but did not receive stimulant medication until three years later, when Ritalin® 60 mg daily was re-established. During the 14 months that followed, he began to use Ritalin® excessively, both orally and rectally, in dosages from 4800-6000 mg daily. Four years ago, he was referred to our outpatient service, where his Attention Deficit Hyperactivity Disorder was re-evaluated. At that point, the patient’s daily Ritalin® dosage was reduced to 200 mg daily orally, but he still experienced pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage was raised again. The patient’s plasma levels consistently remained between 60–187 nmol/l—within the recommended range—and signs of his obsessive-compulsive symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378 mg extended-release methylphenidate (Concerta®, his symptoms of Attention Deficit Hyperactivity Disorder have improved dramatically and no further use of methylphenidate has been recorded during the 24 months preceding this report. Conclusions Symptoms of

  17. Neuropsychological deficits in patients with Lyme borreliosis

    Directory of Open Access Journals (Sweden)

    Katja Pruša

    2001-09-01

    Full Text Available Slovenia is an endemic area for Lyme borreliosis, a disease that affects many organic systems. Decline in cognitive abilities and emotional changes can appear in acute and chronic stage of the disease beside somatic difficulties. Early antibiotic therapy is of great importance in recovery. Attention and concentration deficits, memory deficits, impaired executive functioning, depression and other symptoms reduce work efficiency and life quality of people with Lyme borreliosis. Neuropsychological deficits can be explained with central nervous system impairment and partly also with reactive psychological factors. On account of symptomatic complexity, broad differential diagnostic and unreliable diagnostic technology neuropsychological evaluation can help to correctly diagnose and accurately treat this disease, and thus to enable appropriate cognitive rehabilitation and psychotherapeutic assistance.

  18. Timing deficits in attention-deficit/hyperactivity disorder (ADHD): evidence from neurocognitive and neuroimaging studies.

    Science.gov (United States)

    Noreika, Valdas; Falter, Christine M; Rubia, Katya

    2013-01-01

    Relatively recently, neurocognitive and neuroimaging studies have indicated that individuals with attention-deficit/hyperactivity disorder (ADHD) may have deficits in a range of timing functions and their underlying neural networks. Despite this evidence, timing deficits in ADHD are still somewhat neglected in the literature and mostly omitted from reviews on ADHD. There is therefore a lack of integrative reviews on the up-to-date evidence on neurocognitive and neurofunctional deficits of timing in ADHD and their significance with respect to other behavioural and cognitive deficits. The present review provides a synthetic overview of the evidence for neurocognitive and neurofunctional deficits in ADHD in timing functions, and integrates this evidence with the cognitive neuroscience literature of the neural substrates of timing. The review demonstrates that ADHD patients are consistently impaired in three major timing domains, in motor timing, perceptual timing and temporal foresight, comprising several timeframes spanning milliseconds, seconds, minutes and longer intervals up to years. The most consistent impairments in ADHD are found in sensorimotor synchronisation, duration discrimination, reproduction and delay discounting. These neurocognitive findings of timing deficits in ADHD are furthermore supported by functional neuroimaging studies that show dysfunctions in the key inferior fronto-striato-cerebellar and fronto-parietal networks that mediate the timing functions. Although there is evidence that these timing functions are inter-correlated with other executive functions that are well established to be impaired in the disorder, in particular working memory, attention, and to a lesser degree inhibitory control, the key timing deficits appear to survive when these functions are controlled for, suggesting independent cognitive deficits in the temporal domain. There is furthermore strong evidence for an association between timing deficits and behavioural

  19. Foreshock Patterns Preceding Great Earthquakes in the Subduction Zone of Chile

    Science.gov (United States)

    Papadopoulos, G. A.; Minadakis, G.

    2016-10-01

    Foreshock activity is considered as one of the most promising precursory changes for the main shock prediction in the short term. Averaging over several foreshock sequences has shown that foreshocks are characterized by distinct 3D patterns: their epicenters move towards the main shock epicenter, event count accelerates, and b-value drops. However, these space-time-size patterns were verified so far only in a very few individual cases mainly due to inadequate seismicity catalogue data. We have investigated 3D foreshock patterns before the M w 8.8 Maule in 27 February 2010, M w 8.1 Iquique in 1 April 2014, and M w 8.4 Illapel in 16 September 2015 great earthquakes in the Chile subduction zone. To avoid biased results, no a priori spatiotemporal definitions of foreshocks were inserted. The procedure was based on pattern recognition from statistically significant seismicity changes in the three domains. The pattern recognition in one domain was independent of the pattern recognition in another domain. We found and verified with two independent catalogue data sets (CSN, IPOC) that within a critical area of ca. 65 km from the main shock epicenter, the 2014 event was preceded by distinct foreshock 3D patterns. A nearly weak foreshock stage (20 January-14 March 2014) was followed by a main-strong stage (15 March-1 April 2014) highly significant in all domains, although foreshock activity slightly decreased in about the last 5 days. Seismic moment release also accelerated in the last stage due to the occurrence of a cluster of very strong foreshock events. Foreshock activity very likely occurred in the hanging-wall fault domain on the South American Plate overriding Nazca Plate. The 2014 foreshock activity was quite similar to the one preceding the 6 Apr. 2009 L' Aquila (Italy) M w 6.3 earthquake associated with normal faulting. Using the 2014 earthquake as a reference event, we observed that similar foreshock 3D patterns preceded the 2010 and 2015 earthquakes within

  20. Apoptosis Mediated by HIV Protease is Preceded by Cleavage of Bcl-2

    Science.gov (United States)

    Strack, Peter R.; West Frey, Michelle; Rizzo, Christopher J.; Cordova, Beverly; George, Henry J.; Meade, Raymond; Ho, Siew Peng; Corman, Jeanne; Tritch, Radonna; Korant, Bruce D.

    1996-09-01

    Expression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor α . We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NFkappa B, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.

  1. a Revised Stochastic Optimal Velocity Model Considering the Velocity Gap with a Preceding Vehicle

    Science.gov (United States)

    Shigaki, Keizo; Tanimoto, Jun; Hagishima, Aya

    The stochastic optimal velocity (SOV) model, which is a cellular automata model, has been widely used because of its good reproducibility of the fundamental diagram, despite its simplicity. However, it has a drawback: in SOV, a vehicle that is temporarily stopped takes a long time to restart. This study proposes a revised SOV model that suppresses this particular defect; the basic concept of this model is derived from the car-following model, which considers the velocity gap between a particular vehicle and the preceding vehicle. A series of simulations identifies the model parameters and clarifies that the proposed model can reproduce the three traffic phases: free, jam, and even synchronized phases, which cannot be achieved by the conventional SOV model.

  2. A Hybrid Genetic Algorithm to Minimize Total Tardiness for Unrelated Parallel Machine Scheduling with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Chunfeng Liu

    2013-01-01

    Full Text Available The paper presents a novel hybrid genetic algorithm (HGA for a deterministic scheduling problem where multiple jobs with arbitrary precedence constraints are processed on multiple unrelated parallel machines. The objective is to minimize total tardiness, since delays of the jobs may lead to punishment cost or cancellation of orders by the clients in many situations. A priority rule-based heuristic algorithm, which schedules a prior job on a prior machine according to the priority rule at each iteration, is suggested and embedded to the HGA for initial feasible schedules that can be improved in further stages. Computational experiments are conducted to show that the proposed HGA performs well with respect to accuracy and efficiency of solution for small-sized problems and gets better results than the conventional genetic algorithm within the same runtime for large-sized problems.

  3. Nephrotic syndrome due to immunoglobulin M mesangial glomerulonephritis preceding juvenile idiopathic arthritis.

    Science.gov (United States)

    Voyer, Luis E; Alvarado, Caupolican; Cuttica, Rubén J; Balestracci, Alejandro; Zardini, Marta; Lago, Néstor

    2013-05-21

    The association between nephrotic syndrome and juvenile idiopathic arthritis have rarely been described in pediatric patients. We report a child with steroid-responsive nephrotic syndrome, with frequent relapses, who presented with a new relapse of nephrotic syndrome associated with arthritis and uveitis at 21 months in remission after treatment with chlorambucil. Juvenile idiopathic arthritis was diagnosed and kidney biopsy examination showed mesangial glomerulonephritis with immunoglobulin M deposits. To our knowledge, only 2 cases of nephrotic syndrome preceding juvenile idiopathic arthritis have been reported, one without histopathology assessment and the other with minimal change disease. Although mesangial glomerulonephritis with nephrotic syndrome and juvenile idiopathic arthritis could have been coincidental, the immune pathogenic mechanism accepted for both diseases suggests they could be related.

  4. An investigation into the precedents of modern drug treatment in psychiatry.

    Science.gov (United States)

    Moncrieff, J

    1999-12-01

    This paper examines some of the factors associated with the introduction of a range of new drug treatments into psychiatry in the 1950s and 1960s. The nature of psychiatry in the United Kingdom in preceding decades is examined and a continuous emphasis on biological explanations and treatments of mental disorder is revealed. Physical treatment procedures such as insulin coma therapy and shock treatment received most attention. Older drug treatments, although widely used, excited little interest during this time. The new drug treatments by contrast received much attention and began to be regarded as having specific effects on different mental disorders. It is suggested that a combination of long-standing professional concerns and commercial factors helped to account for the rapid acceptance and employment of the new drugs. In turn, these drugs helped to strenghten the hegemony of the medical approach to mental illness.

  5. Rapid genetic adaptation precedes the spread of an exotic plant species.

    Science.gov (United States)

    Vandepitte, Katrien; de Meyer, Tim; Helsen, Kenny; van Acker, Kasper; Roldán-Ruiz, Isabel; Mergeay, Joachim; Honnay, Olivier

    2014-05-01

    Human activities have increasingly introduced plant species far outside their native ranges under environmental conditions that can strongly differ from those originally met. Therefore, before spreading, and potentially causing ecological and economical damage, non-native species may rapidly evolve. Evidence of genetically based adaptation during the process of becoming invasive is very scant, however, which is due to the lack of knowledge regarding the historical genetic makeup of the introduced populations and the lack of genomic resources. Capitalizing on the availability of old non-native herbarium specimens, we examined frequency shifts in genic SNPs of the Pyrenean Rocket (Sisymbrium austriacum subsp. chrysanthum), comparing the (i) native, (ii) currently spreading non-native and (iii) historically introduced gene pool. Results show strong divergence in flowering time genes during the establishment phase, indicating that rapid genetic adaptation preceded the spread of this species and possibly assisted in overcoming environmental constraints.

  6. The tailings dam failure of 5 November 2015 in SE Brazil and its preceding seismic sequence

    Science.gov (United States)

    Agurto-Detzel, H.; Bianchi, M.; Assumpção, M.; Schimmel, M.; Collaço, B.; Ciardelli, C.; Barbosa, J. R.; Calhau, J.

    2016-05-01

    The collapse of a mine tailings dam and subsequent flood in SE Brazil on 5 November 2015 was preceded by a small-magnitude seismic sequence. In this report, we explore the spatiotemporal associations between the seismic events and the accident and discuss their possible connection. We also analyze the signals generated by the turbulent mudflow, as recorded by the Brazilian Seismographic Network (RSBR). In light of our observations, we propose as possible contributing factor for the dam collapse either ground shaking and/or soil liquefaction triggered by the earthquakes. The possibility of such a small-magnitude earthquake contributing to the collapse of a tailings dam raises important concerns regarding safety and related legislation of dams in Brazil and the world.

  7. The chemistry that preceded life's origin: a study guide from meteorites.

    Science.gov (United States)

    Pizzarello, Sandra

    2007-04-01

    Carbonaceous meteorites are rare fragments of asteroids that contain organic carbon of diverse composition, various complexity, and whose lineage can in several instances be traced back to pre-solar environments. Their analyses offer a unique glimpse into the chemistry of the solar system that preceded life and may have been available to its emergence on the early Earth. While the heterogeneity of the organic materials of meteorites is indicative of random synthetic processes for their formation, some of their components have identical counterparts in the biosphere, and a group of meteoritic amino acids were found to display chiral asymmetry, a property known since the time of Pasteur to be inextricably linked to life's processes. The ability of these amino acids to act as asymmetric catalysts, as well as indications that molecular asymmetry in meteorites may not be limited to these compounds, encourage the suggestion of possible involvement of meteoritic material in the induction of selective traits in molecular evolution.

  8. Noble metal nanoclusters and nanoparticles precede mineral formation in magmatic sulphide melts.

    Science.gov (United States)

    Helmy, Hassan M; Ballhaus, Chris; Fonseca, Raúl O C; Wirth, Richard; Nagel, Thorsten; Tredoux, Marian

    2013-01-01

    In low temperature aqueous solutions, it has long been recognized by in situ experiments that many minerals are preceded by crystalline nanometre-sized particles and non-crystalline nanophases. For magmatic systems, nanometre-sized precursors have not yet been demonstrated to exist, although the suggestion has been around for some time. Here we demonstrate by high temperature quench experiments that platinum and arsenic self-organize to nanoparticles, well before the melt has reached a Pt-As concentration at which discrete Pt arsenide minerals become stable phases. If all highly siderophile elements associate to nanophases in undersaturated melts, the distribution of the noble metals between silicate, sulphide and metal melts will be controlled by the surface properties of nano-associations, more so than by the chemical properties of the elements.

  9. Enhancement of visual attention precedes the emergence of novel metaphor interpretations

    Science.gov (United States)

    Terai, Asuka; Nakagawa, Masanori; Kusumi, Takashi; Koike, Yasuharu; Jimura, Koji

    2015-01-01

    Emergence of creative ideas often involves sudden linking of unrelated ideas. Here we demonstrate that the production of insights about novel metaphor was preceded by prolonged visual inspection of metaphorical sentences. The participants made free spoken responses in a task requiring the generation of semantic interpretations about visually presented sentences, where gaze locations were continuously monitored. We found that creative interpretations were primarily generated from novel metaphorical expressions, rather than from conventional expressions. Moreover, presented words within novel metaphors were visually inspected for longer periods specifically before creative interpretations were produced. Interestingly, prolonged gazes occurred several seconds (∼8 s) prior to the generation of creative interpretations, particularly, in the case of the topic word within the metaphor. These results demonstrate latent cognitive process meditating the emergence of insights, and suggest that the prior visual inspection prompted the semantic representation of the metaphorical sentences, which eventually facilitates creative ideas. PMID:26167155

  10. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys.

    Science.gov (United States)

    Gonzales, Lauren A; Benefit, Brenda R; McCrossin, Monte L; Spoor, Fred

    2015-07-03

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently.

  11. Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy.

    Science.gov (United States)

    Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi

    2017-01-01

    It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

  12. Foreshock patterns preceding large earthquakes in the subduction zone of Chile

    Science.gov (United States)

    Minadakis, George; Papadopoulos, Gerassimos A.

    2016-04-01

    Some of the largest earthquakes in the globe occur in the subduction zone of Chile. Therefore, it is of particular interest to investigate foreshock patterns preceding such earthquakes. Foreshocks in Chile were recognized as early as 1960. In fact, the giant (Mw9.5) earthquake of 22 May 1960, which was the largest ever instrumentally recorded, was preceded by 45 foreshocks in a time period of 33h before the mainshock, while 250 aftershocks were recorded in a 33h time period after the mainshock. Four foreshocks were bigger than magnitude 7.0, including a magnitude 7.9 on May 21 that caused severe damage in the Concepcion area. More recently, Brodsky and Lay (2014) and Bedford et al. (2015) reported on foreshock activity before the 1 April 2014 large earthquake (Mw8.2). However, 3-D foreshock patterns in space, time and size were not studied in depth so far. Since such studies require for good seismic catalogues to be available, we have investigated 3-D foreshock patterns only before the recent, very large mainshocks occurring on 27 February 2010 (Mw 8.8), 1 April 2014 (Mw8.2) and 16 September 2015 (Mw8.4). Although our analysis does not depend on a priori definition of short-term foreshocks, our interest focuses in the short-term time frame, that is in the last 5-6 months before the mainshock. The analysis of the 2014 event showed an excellent foreshock sequence consisting by an early-weak foreshock stage lasting for about 1.8 months and by a main-strong precursory foreshock stage that was evolved in the last 18 days before the mainshock. During the strong foreshock period the seismicity concentrated around the mainshock epicenter in a critical area of about 65 km mainly along the trench domain to the south of the mainshock epicenter. At the same time, the activity rate increased dramatically, the b-value dropped and the mean magnitude increased significantly, while the level of seismic energy released also increased. In view of these highly significant seismicity

  13. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  14. Adaptive control for a class of nonlinear time-delay systems preceded by unknown hysteresis

    Science.gov (United States)

    Zhang, Xiuyu; Lin, Yan

    2013-08-01

    In this article, a robust adaptive neural dynamic surface control is proposed for a class of time-delay nonlinear systems preceded by saturated hystereses. Compared with the present schemes of dealing with time delay and hystereses input, the main advantages of the proposed scheme are that the prespecified transient and steady-state performance of tracking error can be guaranteed, the computational burden can be greatly reduced and the explosion of complexity problem inherent in backstepping control can be eliminated. Moreover, the utilisation of saturated-type Prandtl-Ishlinskii model makes our scheme more applicable. It is proved that the new scheme can guarantee all the closed-loop signals semiglobally uniformly ultimate bounded. Simulation results are presented to demonstrate the validity of the proposed scheme.

  15. Dendritic calcium activity precedes inspiratory bursts in preBotzinger complex neurons

    DEFF Research Database (Denmark)

    Del Negro, Christopher A; Hayes, John A; Rekling, Jens C

    2011-01-01

    Medullary interneurons of the preBötzinger complex assemble excitatory networks that produce inspiratory-related neural rhythms, but the importance of somatodendritic conductances in rhythm generation is still incompletely understood. Synaptic input may cause Ca(2+) accumulation postsynaptically...... to evoke a Ca(2+)-activated inward current that contributes to inspiratory burst generation. We measured Ca(2+) transients by two-photon imaging dendrites while recording neuronal somata electrophysiologically. Dendritic Ca(2+) accumulation frequently precedes inspiratory bursts, particularly at recording...... suggest that dendritic Ca(2+) activates an inward current to electrotonically depolarize the soma, rather than propagate as a regenerative Ca(2+) wave. These data provide new evidence that respiratory rhythmogenesis may depend on dendritic burst-generating conductances activated in the context of network...

  16. Prolonged hyperpolarizing potentials precede spindle oscillations in the thalamic reticular nucleus

    Science.gov (United States)

    Fuentealba, Pablo; Timofeev, Igor; Steriade, Mircea

    2004-01-01

    The thalamic reticular (RE) nucleus is a key structure in the generation of spindles, a hallmark bioelectrical oscillation during early stages of sleep. Intracellular recordings of RE neurons in vivo revealed the presence of prolonged hyperpolarizing potentials preceding spindles in a subgroup (30%) of neurons. These hyperpolarizations (6-10 mV) lasted for 200-300 ms and were present just before the onset of spontaneously occurring spindle waves. Corticothalamic volleys also were effective in generating such hyperpolarizations followed by spindles in RE neurons. A drop of up to 40% in the apparent input resistance (Rin) was associated with these hyperpolarizing potentials, suggesting an active process rather than disfacilitation. Accordingly, the reversal potential was approximately -100 mV for both spontaneous and cortically elicited hyperpolarizations, consistent with the activation of slow K+ conductances. QX-314 in the recording pipettes decreased both the amplitude and incidence of prolonged hyperpolarizations, suggesting the participation of G protein-dependent K+ currents in the generation of hyperpolarizations. Simultaneous extracellular and intracellular recordings in the RE nucleus demonstrated that some RE neurons discharged during the hyperpolarizations and, thus, may be implicated in their generation. The prolonged hyperpolarizations preceding spindles may play a role in the transition from tonic to bursting firing of RE neurons within a range of membrane potential (-60 to -65 mV) at which they set favorable conditions for the generation of low-threshold spike bursts that initiate spindle sequences. These data are further arguments for the generation of spindles within the thalamic RE nucleus. PMID:15210981

  17. The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Borisova, Ekaterina; Abakumov, Maxim; Gorin, Dmitry; Avramov, Latchezar; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Serov, Alexander; Pavlov, Alexey; Zinchenko, Ekaterina; Lychagov, Vlad; Navolokin, Nikita; Shirokov, Alexander; Maslyakova, Galina; Zhu, Dan; Luo, Qingming; Chekhonin, Vladimir; Tuchin, Valery; Kurths, Jürgen

    2016-01-01

    In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health. PMID:27378933

  18. Impairment of adolescent hippocampal plasticity in a mouse model for Alzheimer's disease precedes disease phenotype.

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    Daniela Hartl

    Full Text Available The amyloid precursor protein (APP was assumed to be an important neuron-morphoregulatory protein and plays a central role in Alzheimer's disease (AD pathology. In the study presented here, we analyzed the APP-transgenic mouse model APP23 using 2-dimensional gel electrophoresis technology in combination with DIGE and mass spectrometry. We investigated cortex and hippocampus of transgenic and wildtype mice at 1, 2, 7 and 15 months of age. Furthermore, cortices of 16 days old embryos were analyzed. When comparing the protein patterns of APP23 with wildtype mice, we detected a relatively large number of altered protein spots at all age stages and brain regions examined which largely preceded the occurrence of amyloid plaques. Interestingly, in hippocampus of adolescent, two-month old mice, a considerable peak in the number of protein changes was observed. Moreover, when protein patterns were compared longitudinally between age stages, we found that a large number of proteins were altered in wildtype mice. Those alterations were largely absent in hippocampus of APP23 mice at two months of age although not in other stages compared. Apparently, the large difference in the hippocampal protein patterns between two-month old APP23 and wildtype mice was caused by the absence of distinct developmental changes in the hippocampal proteome of APP23 mice. In summary, the absence of developmental proteome alterations as well as a down-regulation of proteins related to plasticity suggest the disturption of a normally occurring peak of hippocampal plasticity during adolescence in APP23 mice. Our findings are in line with the observation that AD is preceded by a clinically silent period of several years to decades. We also demonstrate that it is of utmost importance to analyze different brain regions and different age stages to obtain information about disease-causing mechanisms.

  19. An increased risk of urinary tract infection precedes development of primary biliary cirrhosis

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    West Joe

    2011-08-01

    Full Text Available Abstract Background Primary Biliary Cirrhosis is known to be associated with Urinary Tract Infections (UTIs, but whether these precede or follow the liver disease is unclear. We have therefore attempted to determine whether UTIs are more common in people with Primary Biliary Cirrhosis (PBC prior to their diagnosis. Methods We conducted a case control study in the General Practice Research Database. All cases of PBC first recorded at least one year after entry to the dataset were selected along with up to 10 controls matched for age, sex. A second unmatched control group who had Chronic Liver Diseases but not PBC were chosen. The main exposures studied were the occurrence of Urinary tract infections and pyelonephritis at least one or at least five years before diagnosis. We also performed an analysis restricted to those younger than 55 at diagnosis, as we hypothesized the relationship to be stronger in the younger age group. Results PBC is associated with UTI prior to diagnosis, OR 1.50 (CI 1.26-1.78, which was similar 5 years prior to diagnosis and after adjusting for smoking. The strongest relationships were observed in pyelonephritis exposures five years before diagnosis in cases under 55 years: adjusted odds ratios were 2.60 (1.02-6.63 in comparison with matched general population controls and adjusted odds ratios were OR 2.45 (1.02-5.59 in the comparison with chronic liver disease controls. Conclusions We found that the association between urosepsis and PBC is specific to this disease and precedes the diagnosis of PBC in a manner not previously observed in human data. This is consistent with a causal relationship.

  20. Short-term seismic quiescence immediately preceding explosions during the 2011 eruption of Telica Volcano, Nicaragua

    Science.gov (United States)

    Rodgers, M.; Roman, D. C.; Geirsson, H.; La Femina, P. C.; Muñoz, A.; Tenorio, V.

    2013-12-01

    Telica Volcano, Nicaragua, experienced a VEI 2 eruptive episode from March-June 2011. The eruption consisted of numerous small to moderate ash explosions, many of which were observed visually and recorded by a local broadband seismic network (the TESAND network). Seismicity at Telica during both background and eruptive periods is characterized by generally high and variable rates of low-magnitude volcano-seismic events. Explosions at Telica are also detected seismically and distinguished from volcanic earthquakes by the length of the seismic signal, their emergent nature and 'cigar-shaped' envelope, and broadband spectral content. During the month of May 2011, we identified 16 explosion events on a seismometer located 0.5 km from the crater vent, some of which correlate with visually observed explosions. From May 1-12, ten explosions are apparent in continuous seismic data. During this period, the rate of volcano-seismic events is relatively low (0-20 events/hour with an average of 4 events per hour). Prior to eight of the 10 explosions, there were no detected seismic events within one hour of the explosion. From May 13-31, seven explosions were identified in the continuous seismic data. During this period, the rate of volcano-seismic events is relatively high (0-48 events per hour, with an average of 18 events per hour). In the hour preceding all seven explosions, there were no detected volcano-seismic events. Visual inspection of the continuous seismic data confirms that a strong decrease in the number of volcano-seismic events immediately preceded most of the 2011 explosions at Telica Volcano. We suggest that the apparent short-term decrease in seismicity before explosions at Telica is related to a cycle of pressure buildup and release in the shallow magmatic-hydrothermal system, with an increase in pressure prior to the explosions both resulting from and reflecting constriction of gas pathways.

  1. Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions.

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    Niamh M C Connolly

    Full Text Available Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK, re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult.

  2. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

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    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  3. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

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    Shanshan Sun

    2017-04-01

    Full Text Available Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD, a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

  4. Short-term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI) compromises their respiratory capacity and alters their bioenergetic signature.

    Science.gov (United States)

    Cerveira, Joana F; Sánchez-Aragó, María; Urbano, Ana M; Cuezva, José M

    2014-01-01

    Previous studies on the impact of hexavalent chromium [Cr(VI)] on mammalian cell energetics revealed alterations suggestive of a shift to a more fermentative metabolism. Aiming at a more defined understanding of the metabolic effects of Cr(VI) and of their molecular basis, we assessed the impact of a mild Cr(VI) exposure on critical bioenergetic parameters (lactate production, oxygen consumption and intracellular ATP levels). Cells derived from normal human bronchial epithelium (BEAS-2B cell line), the main in vivo target of Cr(VI) carcinogenicity, were subjected for 48 h to 1 μM Cr(VI). We could confirm a shift to a more fermentative metabolism, resulting from the simultaneous inhibition of respiration and stimulation of glycolysis. This shift was accompanied by a decrease in the protein levels of the catalytic subunit (subunit β) of the mitochondrial H(+)-ATP synthase (β-F1-ATPase) and a concomitant marked increase in those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The corresponding alteration in the β-F1-ATPase/GAPDH protein ratio (viewed as a bioenergetic signature) upon Cr(VI) exposure was in agreement with the observed attenuation of cellular respiration and enhancement of glycolytic flux. Altogether, these results constitute a novel finding in terms of the molecular mechanisms of Cr(VI) effects.

  5. Short-term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI compromises their respiratory capacity and alters their bioenergetic signature

    Directory of Open Access Journals (Sweden)

    Joana F. Cerveira

    2014-01-01

    Full Text Available Previous studies on the impact of hexavalent chromium [Cr(VI] on mammalian cell energetics revealed alterations suggestive of a shift to a more fermentative metabolism. Aiming at a more defined understanding of the metabolic effects of Cr(VI and of their molecular basis, we assessed the impact of a mild Cr(VI exposure on critical bioenergetic parameters (lactate production, oxygen consumption and intracellular ATP levels. Cells derived from normal human bronchial epithelium (BEAS-2B cell line, the main in vivo target of Cr(VI carcinogenicity, were subjected for 48 h to 1 μM Cr(VI. We could confirm a shift to a more fermentative metabolism, resulting from the simultaneous inhibition of respiration and stimulation of glycolysis. This shift was accompanied by a decrease in the protein levels of the catalytic subunit (subunit β of the mitochondrial H+-ATP synthase (β-F1-ATPase and a concomitant marked increase in those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH. The corresponding alteration in the β-F1-ATPase/GAPDH protein ratio (viewed as a bioenergetic signature upon Cr(VI exposure was in agreement with the observed attenuation of cellular respiration and enhancement of glycolytic flux. Altogether, these results constitute a novel finding in terms of the molecular mechanisms of Cr(VI effects.

  6. Environmental factors which affect growth of Japanese common squid, Todarodes pacificus, analyzed by a bioenergetics model coupled with a lower trophic ecosystem model

    Science.gov (United States)

    Kishi, Michio J.; Nakajima, Kazuto; Fujii, Masahiko; Hashioka, Taketo

    2009-09-01

    Bioenergetics model is applied to Japanese common squid, Todarodes pacificus. The temporal change of wet weight of common squid, which migrates in the Sea of Japan, is simulated. The time dependent horizontal distribution of prey is calculated a priori by 3-D coupled physical-biological model. The biological model NEMURO (North Pacific Ecosystem Model for Understanding Regional Oceanography) is used to simulate the lower-trophic ecosystem including three kinds of zooplankton biomass two of which is used as prey of common squid. A bioenergetics model reproduced appropriate growth curve of common squid, migrating in the North Pacific and the Sea of Japan. The results show that the wet weight of common squid in the northern Sea of Japan is heavier than that migrating in the central Sea of Japan, because prey density of the northern Sea of Japan is higher than that of the central Sea of Japan. We also investigate the wet weight anomaly for a global warming scenario. In this case, wet weight of common squid decreases because water temperature exceeds the optimum temperature for common squid. This result indicates that migration route and spawning area of common squid might change with global warming.

  7. A stochastic bioenergetics model based approach to translating large river flow and temperature in to fish population responses: the pallid sturgeon example

    Science.gov (United States)

    Wildhaber, Mark L.; Dey, Rima; Wikle, Christopher K.; Moran, Edward H.; Anderson, Christopher J.; Franz, Kristie J.

    2015-01-01

    In managing fish populations, especially at-risk species, realistic mathematical models are needed to help predict population response to potential management actions in the context of environmental conditions and changing climate while effectively incorporating the stochastic nature of real world conditions. We provide a key component of such a model for the endangered pallid sturgeon (Scaphirhynchus albus) in the form of an individual-based bioenergetics model influenced not only by temperature but also by flow. This component is based on modification of a known individual-based bioenergetics model through incorporation of: the observed ontogenetic shift in pallid sturgeon diet from marcroinvertebrates to fish; the energetic costs of swimming under flowing-water conditions; and stochasticity. We provide an assessment of how differences in environmental conditions could potentially alter pallid sturgeon growth estimates, using observed temperature and velocity from channelized portions of the Lower Missouri River mainstem. We do this using separate relationships between the proportion of maximum consumption and fork length and swimming cost standard error estimates for fish captured above and below the Kansas River in the Lower Missouri River. Critical to our matching observed growth in the field with predicted growth based on observed environmental conditions was a two-step shift in diet from macroinvertebrates to fish.

  8. A new bioenergetic and thermodynamic approach to batch photoautotrophic growth of Arthrospira (Spirulina) platensis in different photobioreactors and under different light conditions.

    Science.gov (United States)

    da Silva, Milena Fernandes; Casazza, Alessandro Alberto; Ferrari, Pier Francesco; Perego, Patrizia; Bezerra, Raquel Pedrosa; Converti, Attilio; Porto, Ana Lucia Figueiredo

    2016-05-01

    Photobioreactor configuration, mode of operation and light intensity are known to strongly impact on cyanobacteria growth. To shed light on these issues, kinetic, bioenergetic and thermodynamic parameters of batch Arthrospira platensis cultures were estimated along the time at photosynthetic photon flux density (PPFD) of 70μmolm(-2)s(-1) in different photobioreactors with different surface/volume ratio (S/V), namely open pond (0.25cm(-1)), shaken flask (0.48cm(-1)), horizontal photobioreactor (HoP) (1.94cm(-1)) and helicoidal photobioreactor (HeP) (3.88cm(-1)). Maximum biomass concentration and productivity remarkably increased with S/V up to 1.94cm(-1). HoP was shown to be the best-performing system throughout the whole runs, while HeP behaved better only at the start. Runs carried out in HoP increasing PPFD from 40 to 100μmolm(-2)s(-1) revealed a progressive enhancement of bioenergetics and thermodynamics likely because of favorable light distribution. HoP appeared to be a promising configuration to perform high-yield indoor cyanobacterial cultures.

  9. In vivo 31P NMR OSIRIS of bioenergetic changes in rabbit kidneys during and after ischaemia: effect of pretreatment with an indeno-indole compound.

    Science.gov (United States)

    Sørensen, V; Jonsson, O; Pettersson, S; Scherstén, T; Soussi, B

    1998-04-01

    Changes in energy phosphates of rabbit kidneys subjected to ischaemia-reperfusion have been measured in vivo with volume selective 31P NMR spectroscopy. The effects of pretreatment with a new lipid peroxidation inhibitor (indeno-indol derivate--code name H290/51) on the bioenergetic changes were analysed. The left kidney was moved to a subcutaneous pocket to facilitate exact positioning over the surface coil. A 1H NMR image was acquired and a 3.5-mL cube selected for 31P NMR spectra. 31P NMR spectra were recorded before occlusion of the left renal artery, during 1 h of ischaemia and 2 hours of reperfusion. Ischaemia induced drastic changes in the levels of inorganic phosphates and ATP as well as intracellular acidosis. A normalization was observed during reperfusion. Two hours after reperfusion significantly higher values for beta-ATP/Pi and intracellular pH were recorded in the animals pretreated with H290/51. The present technique allows quantitative analyses of changes in kidney bioenergetics in vivo during different experimental conditions. The importance of ischaemia-reperfusion induced lipid peroxidation for mitochondrial function is emphasized.

  10. Color Vision Deficits and Literacy Acquisition.

    Science.gov (United States)

    Hurley, Sandra Rollins

    1994-01-01

    Shows that color blindness, whether partial or total, inhibits literacy acquisition. Offers a case study of a third grader with impaired color vision. Presents a review of literature on the topic. Notes that people with color vision deficits are often unaware of the handicap. (RS)

  11. Linguistic coding deficits in foreign language learners.

    Science.gov (United States)

    Sparks, R; Ganschow, L; Pohlman, J

    1989-01-01

    As increasing numbers of colleges and universities require a foreign language for graduation in at least one of their degree programs, reports of students with difficulties in learning a second language are multiplying. Until recently, little research has been conducted to identify the nature of this problem. Recent attempts by the authors have focused upon subtle but ongoing language difficulties in these individuals as the source of their struggle to learn a foreign language. The present paper attempts to expand upon this concept by outlining a theoretical framework based upon a linguistic coding model that hypothesizes deficits in the processing of phonological, syntactic, and/or semantic information. Traditional psychoeducational assessment batteries of standardized intelligence and achievement tests generally are not sensitive to these linguistic coding deficits unless closely analyzed or, more often, used in conjunction with a more comprehensive language assessment battery. Students who have been waived from a foreign language requirement and their proposed type(s) of linguistic coding deficits are profiled. Tentative conclusions about the nature of these foreign language learning deficits are presented along with specific suggestions for tests to be used in psychoeducational evaluations.

  12. Working together in a deficit logic

    DEFF Research Database (Denmark)

    Matthiesen, Noomi Christine Linde

    2016-01-01

    and with parents in home–school communication. It is argued that in a society with increased focus on parental responsibility the teachers and principals draw on a deficit logic when dealing with Somali diaspora parents and children which consequently leads to teachers either transmitting their expertise...

  13. Frequency of Cognitive Deficits in Neurofibromatosis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-11-01

    Full Text Available The frequency and severity of specific cognitive deficits in 81 children with neurofibromatosis type 1 (NF1, ages 8 to 16 years, compared to 49 unaffected sibling controls, were assessed in a study at the University of Sydney, New South Wales, Australia.

  14. Detection of feigned attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Tucha, Lara; Fuermaier, Anselm B.M.; Koerts, Janneke; Groen, Yvonne; Thome, Johannes

    2015-01-01

    In recent years, there is an increasing awareness that individuals may purposely feign or exaggerate symptoms of attention deficit hyperactivity disorder (ADHD) to gain external incentives, including access to stimulant drugs or special academic accommodations. There are vast consequences of undetec

  15. Supply Deficit of m-Aminophenol

    Institute of Scientific and Technical Information of China (English)

    Wang Zaijun

    2007-01-01

    @@ Supply deficit in the domestic market China's capacity to produce maminophenol was 2.3 thousand t/a and the actual output was around 1.8 thousand tons in 2006. Most producers use the nitrobenzene sulfonation alkali-fusion process developed by Shenyang Research Institute of Chemical Industry.

  16. RAN and Double-Deficit Theory

    Science.gov (United States)

    Cronin, Virginia S.

    2013-01-01

    Lervag and Hulme’s neuro-developmental theory and Wolf and Bowers’s double-deficit hypothesis were examined in this longitudinal study. A total of 130 children were tested in preschool and followed through fifth grade, when 84 remained in the study. During preschool and kindergarten the participants were given tests of end-sound discrimination…

  17. Rethinking a Right Hemisphere Deficit in ADHD

    Science.gov (United States)

    Hale, T. Sigi; Loo, Sandra K.; Zaidel, Eran; Hanada, Grant; Macion, James; Smalley, Susan L.

    2009-01-01

    Introduction: Early observations from lesion studies suggested right hemisphere (RH) dysfunction in ADHD. However, a strictly right-lateralized deficit has not been well supported. An alternatively view suggests increased R greater than L asymmetry of brain function and abnormal interhemispheric interaction. If true, RH pathology in ADHD should…

  18. Medication Treatment for Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Ryan, Joseph B.; Katsiyannis, Antonis; Hughes, Elizabeth M.

    2011-01-01

    Attention deficit hyperactivity disorder (ADHD) has become the most commonly diagnosed psychiatric disorder among school-age children. For more than half a century, physicians have prescribed medications to help manage behaviors such as hyperactivity, impulsivity, and inattention. Today, there is a growing consensus that ADHD is a biologically…

  19. Exploring Dyslexics' Phonological Deficit II: Phonological Grammar

    Science.gov (United States)

    Szenkovits, Gayaneh; Darma, Quynliaan; Darcy, Isabelle; Ramus, Franck

    2016-01-01

    Language learners have to acquire the phonological grammar of their native language, and different levels of representations on which the grammar operates. Developmental dyslexia is associated with a phonological deficit, which is commonly assumed to stem from degraded phonological representations. The present study investigates one aspect of the…

  20. Stigma in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Müller, Kathi; Fuermaier, Anselm B M; Koerts, Janneke; Tucha, Lara

    2012-01-01

    Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of t

  1. Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

    Science.gov (United States)

    Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

    2016-01-01

    Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

  2. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  3. Primary empathy deficits in frontotemporal dementia

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    Sandra eBaez

    2014-10-01

    Full Text Available Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD. Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM, social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.

  4. Primary empathy deficits in frontotemporal dementia

    Science.gov (United States)

    Baez, Sandra; Manes, Facundo; Huepe, David; Torralva, Teresa; Fiorentino, Natalia; Richter, Fabian; Huepe-Artigas, Daniela; Ferrari, Jesica; Montañes, Patricia; Reyes, Pablo; Matallana, Diana; Vigliecca, Nora S.; Decety, Jean; Ibanez, Agustin

    2014-01-01

    Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications. PMID:25346685

  5. Oculomotor Anomalies in Attention-Deficit/Hyperactivity Disorder: Evidence for Deficits in Response Preparation and Inhibition

    Science.gov (United States)

    Mahone, E. Mark; Mostofsky, Stewart H.; Lasker, Adrian G.; Zee, David; Denckla, Martha B.

    2009-01-01

    Girls, but not boys, with attention deficit hyperactivity disorder (ADHD) have significantly longer visually guided saccades latencies. It is found that sex differences in children with ADHD extend beyond symptom presentation to the development of oculomotor control.

  6. Escrevendo um romance, primeiro capítulo: precedentes e processo decisório no STF Writing a novel, chapter one: precedents and decision process in the Brazilian Supreme Court

    Directory of Open Access Journals (Sweden)

    Adriana de Moraes Vojvodic

    2009-06-01

    Full Text Available O artigo, por meio do estudo de casos exemplificativos, procura mostrar que um dos motivos para a falta de uma cultura de respeito aos precedentes judiciais no Supremo Tribunal Federal (STF, ou para a falta de um romance em cadeia (Dworkin, é a dificuldade de formação de uma ratio decidendi comum entre os ministros nos julgamentos da corte, em virtude, por exemplo, do próprio processo decisório do Tribunal. A falta de padrões de decisão implica que cada caso seja decidido sem referência a casos previamente relacionados. Esse contexto pode colaborar para a falta de transparência decisória e para o que pode ser considerado um deficit democrático do STF.Through the analyses of landmark cases, this article argues that one reason for the tendency by the Brazilian Supreme Court (STF to disregard judicial precedents is the difficulty to create a common ratio decidendi in Court decisions and prevent the emergence od Dworkin's chain of law. This is due, in part, to the court's own decision process. The lack of a decision pattern entails that each case is decided without refecenre to previous cases. This context might foster an atmosphere in which decisions are not transparent, something which risks creating a democratic deficit on the STF.

  7. Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Attention Deficit Hyperactivity Disorder and TSC What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a common neurobehavioral disorder. It is ...

  8. Cognitive deficits in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, Ulla; Hasselbalch, Steen Gregers

    2012-01-01

    Patients with unipolar depressive disorder may present with cognitive deficits in the remitted state, and the aim of the present study was to investigate whether cognitive deficits within specific cognitive domains are present....

  9. "Foreign and Public Deficits in Greece: In Search of Causality"

    OpenAIRE

    2013-01-01

    The paper discusses the trajectories of the Greek public deficit and sovereign debt over the last three decades and its connection to the political and economic environment of the same period. We pay special attention to the causality between the public and the foreign deficit. We argue that from 1980 to 1995 causality ran from the public deficit to the foreign deficit, but that due to the European monetary unification process and the adoption of the common currency, causality has reversed si...

  10. Critical energy deficit and mortality in critically ill patients

    Directory of Open Access Journals (Sweden)

    Marcia Carolina Siqueira-Paese

    Full Text Available Objective: We investigate the influence of caloric and protein deficit on mortality and length of hospital stay of critically ill patients. Methods: A cohort prospective study including 100 consecutive patients in a tertiary intensive care unit (ICU receiving enteral or parenteral nutrition. The daily caloric and protein deficit were collected each day for a maximum of 30 days. Energy deficits were divided into critical caloric deficit (≥ 480 kcal/day and non-critical caloric deficit (≤ 480 kcal/day; and in critical protein deficit (≥ 20 g/day and non-critical protein deficit (≤ 20 g/day. The findings were correlated with hospital stay and mortality. Results: The mortality rate was 33%. Overall, the patients received 65.4% and 67.7% of the caloric and protein needs. Critical caloric deficit was found in 72% of cases and critical protein deficit in 70% of them. There was a significant correlation between length of stay and accumulated caloric deficit (R = 0.37; p < 0.001 and protein deficit (R = 0.28; p < 0.001. The survival analysis showed that mortality was greater in patients with both critical caloric (p < 0.001 and critical protein deficits (p < 0.01. The Cox regression analysis showed that critical protein deficit was associated with higher mortality (HR 0.25, 95% CI 0.07-0.93, p = 0.03. Conclusions: The incidence of caloric and protein deficit in the ICU is high. Both caloric and protein deficits increase the length of hospital stay, and protein deficit greater than 20 g/day is an independent factor for mortality in critical care unit.

  11. Wind turbine wakes; power deficit in clusters and wind farms

    DEFF Research Database (Denmark)

    Hansen, Kurt Schaldemose; Barthelmie, Rebecca

    2012-01-01

    The purpose of this presentation is to present recent power deficit analysis based on wind farm measurements. The power deficit is used to validate wind farm prediction models for different inflow conditions......The purpose of this presentation is to present recent power deficit analysis based on wind farm measurements. The power deficit is used to validate wind farm prediction models for different inflow conditions...

  12. Modeling mechanisms that contribute to the precedence effect: From auditory periphery to midbrain

    Science.gov (United States)

    Xia, Jing

    The precedence effect (PE) describes a perceptual phenomenon whereby a pair of temporally close clicks from different directions is perceived as coming from a location near that of the first-arriving sound. The objective of this thesis is to build a physiologically plausible model that predicts perceptual aspects of the PE. The project explores different mechanisms that may contribute to the PE at different levels of the auditory system. The roles of peripheral processing and frequency dominance on the PE were explored by modeling the auditory nerve fiber and using a binaural, cross-correlation model whose outputs were weighted across frequency to predict perceived location. New behavioral results confirmed model predictions that (1) lateralization of narrowband clicks is strongly influenced by the stimulus center frequency and the inter-stimulus delay (ISD) between leading and lagging clicks, and (2) decrements in the leading click level influence lateralization of wideband clicks differently at different ISDs. The role of adaptation was explored by modeling neurons in the cochlear nucleus and the medial superior olive (MSO), both of which are important in computing the localization cues of the auditory stimuli. Simulation results indicated that low-threshold potassium currents (a form of fast adaptation) can prevent jittery, subthreshold inputs from accumulating, thus enhancing synchronization. Synaptic depression (a form of slow adaptation) can produce a sustained decline of the responses after accurately encoding the stimulus onset. The role of long-lasting inhibition was explored by modeling inferior colliculus neurons with inhibitory inputs from both ipsilateral and contralateral MSOs. Psychophysical predictions were generated from a population of model neurons. The model simulated how the physiological suppression of the lagging response depends on the ISD and relative lead and lag locations, as well as behavioral results showing that the perceived location

  13. Estrogen-related and other disease diagnoses preceding Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Jeanne C Latourelle

    2010-05-01

    Full Text Available Jeanne C Latourelle1,2, Merete Dybdahl3, Anita L Destefano1,4, Richard H Myers1, Timothy L Lash2,31Department of Neurology, Boston University School of Medicine, Boston MA, USA; 2Department of Epidemiology, Boston University School of Public Health, Boston MA, USA; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Biostatistics, Boston University School of Public Health, Boston MA, USAPurpose: Estrogen exposure has been associated with the occurrence of Parkinson’s disease (PD, as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms.Patients and methods: All female Parkinson’s disease cases between 1982 and 2007 (n = 12,093 were identified from the Danish National Registry of Patients, along with 10 controls matched by years of birth and enrollment. Conditional logistic regressions (CLR were used to calculate risk of PD after diagnosis of the estrogen-related diseases, endometriosis and osteoporosis, conditioning on years of birth and enrollment. To identify novel associations between PD and any other preceding conditions, CLR was also used to calculate the odds ratios (ORs for risk of PD for 202 different categories of preceding disease diagnoses. Empirical Bayes methods were used to identify the robust associations from the over 200 associations produced by this analysis.Results: We found a positive association between osteoporosis and osteoporotic fractures and PD (OR = 1.18, 95% confidence interval [CI] of 1.08–1.28, while a lack of association was observed

  14. Preterm Infant Hippocampal Volumes Correlate with Later Working Memory Deficits

    Science.gov (United States)

    Beauchamp, Miriam H.; Thompson, Deanne K.; Howard, Kelly; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.; Anderson, Peter J.

    2008-01-01

    Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal…

  15. Word Processing in Dyslexics: An Automatic Decoding Deficit?

    Science.gov (United States)

    Yap, Regina; Van Der Leu, Aryan

    1993-01-01

    Compares dyslexic children with normal readers on measures of phonological decoding and automatic word processing. Finds that dyslexics have a deficit in automatic phonological decoding skills. Discusses results within the framework of the phonological deficit and the automatization deficit hypotheses. (RS)

  16. Human brain lesion-deficit inference remapped.

    Science.gov (United States)

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  17. The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

    2012-10-15

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive

  18. Sumoylation precedes accumulation of phosphorylated H2AX on sex chromosomes during their meiotic inactivation.

    Science.gov (United States)

    Vigodner, Margarita

    2009-01-01

    During meiosis in male mammals, X and Y chromosomes undergo the process of meiotic sex chromosome inactivation (MSCI). A crucial role in MSCI has recently been reported for BRCA1, ATR kinase, and phosphorylated histone H2AX, but the exact mechanism remains to be determined. Small ubiquitin-like modifier (SUMO) proteins have recently been shown to localize to the sex body in mouse meiotic spermatocytes, but the role they play during MSCI is unknown. In this study, in order to better understand the molecular events of MSCI, we followed dynamic changes in gammaH2AX and SUMO localization patterns during MSCI. Using confocal laser scanning microscopy (CLSM) as an analytical tool for visualizing numerous spermatocytes from the same development stage and for consecutively following the meiotic progression, we were able to demonstrate a very early appearance of SUMO-1, which preceded gammaH2AX accumulation on the sex chromosomes during their meiotic inactivation. In contrast to SUMO-1, SUMO-2/3 was undetectable in zygotene spermatocytes, suggesting a possible specific role for SUMO-1 in the initiation of MSCI.

  19. Cost estimation for solid waste management in industrialising regions--precedents, problems and prospects.

    Science.gov (United States)

    Parthan, Shantha R; Milke, Mark W; Wilson, David C; Cocks, John H

    2012-03-01

    The importance of cost planning for solid waste management (SWM) in industrialising regions (IR) is not well recognised. The approaches used to estimate costs of SWM can broadly be classified into three categories - the unit cost method, benchmarking techniques and developing cost models using sub-approaches such as cost and production function analysis. These methods have been developed into computer programmes with varying functionality and utility. IR mostly use the unit cost and benchmarking approach to estimate their SWM costs. The models for cost estimation, on the other hand, are used at times in industrialised countries, but not in IR. Taken together, these approaches could be viewed as precedents that can be modified appropriately to suit waste management systems in IR. The main challenges (or problems) one might face while attempting to do so are a lack of cost data, and a lack of quality for what data do exist. There are practical benefits to planners in IR where solid waste problems are critical and budgets are limited.

  20. Automated Discovery and Modeling of Sequential Patterns Preceding Events of Interest

    Science.gov (United States)

    Rohloff, Kurt

    2010-01-01

    The integration of emerging data manipulation technologies has enabled a paradigm shift in practitioners' abilities to understand and anticipate events of interest in complex systems. Example events of interest include outbreaks of socio-political violence in nation-states. Rather than relying on human-centric modeling efforts that are limited by the availability of SMEs, automated data processing technologies has enabled the development of innovative automated complex system modeling and predictive analysis technologies. We introduce one such emerging modeling technology - the sequential pattern methodology. We have applied the sequential pattern methodology to automatically identify patterns of observed behavior that precede outbreaks of socio-political violence such as riots, rebellions and coups in nation-states. The sequential pattern methodology is a groundbreaking approach to automated complex system model discovery because it generates easily interpretable patterns based on direct observations of sampled factor data for a deeper understanding of societal behaviors that is tolerant of observation noise and missing data. The discovered patterns are simple to interpret and mimic human's identifications of observed trends in temporal data. Discovered patterns also provide an automated forecasting ability: we discuss an example of using discovered patterns coupled with a rich data environment to forecast various types of socio-political violence in nation-states.

  1. Voltage-gated ion channel dysfunction precedes cardiomyopathy development in the dystrophic heart.

    Directory of Open Access Journals (Sweden)

    Xaver Koenig

    Full Text Available Duchenne muscular dystrophy (DMD, caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias. Recent research suggests that impaired voltage-gated ion channels in dystrophic cardiomyocytes accompany cardiac pathology. It is, however, unknown if the ion channel defects are primary effects of dystrophic gene mutations, or secondary effects of the developing cardiac pathology.To address this question, we first investigated sodium channel impairments in cardiomyocytes derived from dystrophic neonatal mice prior to cardiomyopahty development, by using the whole cell patch clamp technique. Besides the most common model for DMD, the dystrophin-deficient mdx mouse, we also used mice additionally carrying an utrophin mutation. In neonatal cardiomyocytes, dystrophin-deficiency generated a 25% reduction in sodium current density. In addition, extra utrophin-deficiency significantly altered sodium channel gating parameters. Moreover, also calcium channel inactivation was considerably reduced in dystrophic neonatal cardiomyocytes, suggesting that ion channel abnormalities are universal primary effects of dystrophic gene mutations. To assess developmental changes, we also studied sodium channel impairments in cardiomyocytes derived from dystrophic adult mice, and compared them with the respective abnormalities in dystrophic neonatal cells. Here, we found a much stronger sodium current reduction in adult cardiomyocytes. The described sodium channel impairments slowed the upstroke of the action potential in adult cardiomyocytes, and only in dystrophic adult mice, the QRS interval of the electrocardiogram was prolonged.Ion channel impairments precede pathology development in the dystrophic heart, and may thus be considered potential cardiomyopathy triggers.

  2. The worker honeybee fat body proteome is extensively remodeled preceding a major life-history transition.

    Directory of Open Access Journals (Sweden)

    Queenie W T Chan

    Full Text Available Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies have revealed extensive remodeling of brain, thorax, and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is scarce. To narrow this gap we investigated the proteomic composition of abdominal tissue in the days typically preceding the onset of foraging in honeybee workers. In order to get a broader representation of possible protein dynamics, we used workers of two genotypes with differences in the age at which they initiate foraging. This approach was combined with RNA interference-mediated downregulation of an insulin/insulin-like signaling component that is central to foraging behavior, the insulin receptor substrate (irs, and with measurements of glucose and lipid levels. Our data provide new insight into the molecular underpinnings of phenotypic plasticity in the honeybee, invoke parallels with vertebrate metabolism, and support an integrated and irs-dependent association of carbohydrate and lipid metabolism with the transition from in-nest tasks to foraging.

  3. [The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years].

    Science.gov (United States)

    Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J

    2006-01-01

    The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs

  4. Study on the variation characteristics of the geoelectric field preceding earthquakes

    Institute of Scientific and Technical Information of China (English)

    马钦忠; 冯志生; 宋治平; 赵卫国

    2004-01-01

    Earthquake events occurred in Nantong, Jiangsu Province on Nov. 3, and Dec. 25, 2001 in which the biggest mag-nitudes were ML=3.8 and ML=4.1, respectively. This paper firstly explains the principle of the eliminating noisemethod by the multi-dipole observation system of geoelectric field. Then based on the observation data of themulti-dipole observation system obtained by ZD9A telluric current monitors installed in Chongming and Nanjingstations, we study the abnormal variation of the geoelectric field preceding the earthquakes. The study shows that:a) Eliminating noise method of multi-dipole observation is an excellent method by which many kinds of geoelec-tric field noises can be eliminated successfully and the geoelectric precursor information can be recognized; b) Thegeoelectric precursor signals for the events were recorded on the NS and NE dipoles in Chongming station 42 days,20 days and 2 days before the earthquakes respectively, in which the station is near the epicenter, and the longesttime of persisting period was 9 days. The abnormal variation signals of geoelectric field observed in Nanjing sta-tion are all the noises but not the seismic electric signals, in which the station is not near the epicenter; c) Dipoledistribution method of common electrode is not good in the multi-dipole observation system of the geoelectricfield.

  5. Precedents, Patterns and Puzzles: Feminist Reflections on the First Women Lawyers

    Directory of Open Access Journals (Sweden)

    Mary Jane Mossman

    2016-10-01

    Full Text Available This paper initially examines the historical precedents established by some of the first women who entered the “gentleman’s profession” of law in different jurisdictions, as well as the biographical patterns that shaped some women’s ambitions to enter the legal professions. The paper then uses feminist methods and theories to interpret “puzzles that remain unsolved” about early women lawyers, focusing especially on two issues. One puzzle is the repeated claims on the part of many of these early women lawyers that they were “lawyers”, and not “women lawyers”, even as they experienced exclusionary practices and discrimination on the part of male lawyers and judges—a puzzle that suggests how professional culture required women lawyers to conform to existing patterns in order to succeed. A second puzzle relates to the public voices of early women lawyers, which tended to suppress disappointments, difficulties and discriminatory practices. In this context, feminist theories suggest a need to be attentive to the “silences” in women’s stories, including the stories of the lives of early women lawyers. Moreover, these insights may have continuing relevance for contemporary women lawyers because it is at least arguable that, while there have been changes in women’s experiences, there has been very little transformation in their work status in relation to men.

  6. Mechanical tension and spontaneous muscle twitching precede the formation of cross-striated muscle in vivo.

    Science.gov (United States)

    Weitkunat, Manuela; Lindauer, Martina; Bausch, Andreas; Schnorrer, Frank

    2017-02-07

    Muscle forces are produced by repetitive stereotyped acto-myosin units called sarcomeres. Sarcomeres are chained into linear myofibrils spanning the entire muscle fiber. In mammalian body muscles, myofibrils are aligned laterally resulting in their typical cross-striated morphology. Despite this detailed textbook knowledge about the adult muscle structure, it is still unclear how cross-striated myofibrils are built in vivo Here, we investigate the morphogenesis of Drosophila abdominal muscles and establish them as in vivo model for cross-striated muscle development. Using live imaging, we find that long immature myofibrils lacking a periodic acto-myosin pattern are built simultaneously in the entire muscle fiber and then align laterally to mature cross-striated myofibrils. Interestingly, laser micro-lesion experiments demonstrate that mechanical tension precedes the formation of the immature myofibrils. Moreover, these immature myofibrils do generate spontaneous Ca(2+) dependent contractions in vivo, which when chemically blocked result in cross-striation defects. Together, these results suggest a myofibrillogenesis model, in which mechanical tension and spontaneous muscle twitchings synchronise the simultaneous self-organisation of different sarcomeric protein complexes to build highly regular cross-striated myofibrils spanning throughout large muscle fibers.

  7. Inflammation and Atrophy Precede Prostatic Neoplasia in a PhIP-Induced Rat Model

    Directory of Open Access Journals (Sweden)

    Alexander D. Borowsky

    2006-09-01

    Full Text Available 2-Amino-1-methyl-6-phenylimidazo(4,5-bpyridine (PhIP has been implicated as a major mutagenic heterocyclicamine in the human diet and is carcinogenic in the rat prostate. To validate PhIP-induced rat prostatic neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow progressive changes over time. We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at the ages of 25, 45, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P = .002, > .001, and .016 for 25, 45, and 65 weeks, respectively and atrophy (P = .003, > .001, and .006 for 25, 45, and 65 weeks, respectively in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN occurred only in PhIP-treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase π immunostaining preceding the development of PIN.None of the animals in this study developed invasive carcinomas, differing from those in previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP-treated rat prostate proceeds from inflammation to postinflammatory proliferative atrophy to PIN.

  8. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa

    Science.gov (United States)

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N.; Ehrlich, Stefan

    2017-01-01

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN. PMID:28198813

  9. Optimal models with maximizing probability of first achieving target value in the preceding stages

    Institute of Scientific and Technical Information of China (English)

    林元烈; 伍从斌; 康波大

    2003-01-01

    Decision makers often face the need of performance guarantee with some sufficiently high proba-bility. Such problems can be modelled using a discrete time Markov decision process (MDP) with a probabilitycriterion for the first achieving target value. The objective is to find a policy that maximizes the probabilityof the total discounted reward exceeding a target value in the preceding stages. We show that our formula-tion cannot be described by former models with standard criteria. We provide the properties of the objectivefunctions, optimal value functions and optimal policies. An algorithm for computing the optimal policies forthe finite horizon case is given. In this stochastic stopping model, we prove that there exists an optimal deter-ministic and stationary policy and the optimality equation has a unique solution. Using perturbation analysis,we approximate general models and prove the existence of ε-optimal policy for finite state space. We give anexample for the reliability of the satellite systems using the above theory. Finally, we extend these results tomore general cases.

  10. DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos

    Science.gov (United States)

    Montero, Juan A.; Sanchez-Fernandez, Cristina; Lorda-Diez, Carlos I.; Garcia-Porrero, Juan A.; Hurle, Juan M.

    2016-01-01

    DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells γH2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of γH2AX-only cells increases after caspase inhibition while the relative number of TUNEL-only cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration. PMID:27752097

  11. Self-experienced vulnerability, prodromal symptoms and coping strategies preceding schizophrenic and depressive relapses.

    Science.gov (United States)

    Bechdolf, Andreas; Schultze-Lutter, Frauke; Klosterkötter, Joachim

    2002-11-01

    For the first time, the present study explores pre-episodic disturbances, i.e. self-experienced vulnerability and prodromal symptoms, and related coping strategies preceding schizophrenic and depressive relapses. After complete recovery from the acute episode, 27 patients with recurrent schizophrenic and 24 patients with recurrent depressive episodes were assessed retrospectively for pre-episodic disturbances and related coping strategies with the "Bonn scale for the assessment of basic symptoms-BSABS". All (100%) of the schizophrenic and 23 (96%) of the depressive patients showed pre-episodic disturbances. Patients with schizophrenia showed significantly more often an increased emotional reactivity and certain perception and thought disturbances. Depressive patients reported significantly more often an impaired tolerance to certain stress and disorders of emotion and affect. Sixty-three percent of the schizophrenics and 87% of the depressives reacted to pre-episodic disturbances with coping strategies. The pre-episodic disturbances in patients with schizophrenia could be described in terms of mild psychotic productivity, those in depressives in terms of mild depressive syndrome. Future studies will have to show if these findings can be replicated in first episode or initial prodromal state samples and if the assessment of mild psychotic productivity and mild depressive syndrome can be used for early diagnosis and early intervention in schizophrenia and depression.

  12. Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre.

    Directory of Open Access Journals (Sweden)

    Joshi J

    1993-07-01

    Full Text Available Menstrual and reproductive history of 178 women referred to the thyroid clinic was compared with 49 healthy controls. Cases were classified as euthyroid, hypothyroid or hyperthyroid after clinical examination and after serum T3, T4, TSH measurements. Reproductive history was related chronologically to symptoms and signs of thyroid dysfunction. Only 31.8% of hypothyroid and 35.3% of hyperthyroid women had normal menstrual pattern in contrast with 56.3% of Euthyroid and 87.8% of healthy controls (p < 0.001. Reproductive failure (infertility, pregnancy wastage, failure of lactation occurred in 37.5% of hypothyroid and 36.5% of hyperthyroid cases against 16.3% of euthyroid and 16.7% of healthy controls (p < 0.05. Interestingly, in 45% of cases with menstrual abnormality, the anomaly was antecedent to other clinical features by a variable period of two months to ten years. Reproductive failure and lactation failure also preceded thyroid dysfunction or goitre. Reproductive dysfunction may therefore be considered as one of the presenting symptoms of thyroid disorders in women, keeping in mind both menstrual irregularities and lactation failure may also arise from other common or idiopathic origins. Especially in women with menstrual irregularities in the perimenopausal age if thyroid dysfunction is detected, pharmacotherapy may be a superior alternative to surgical interventions like hysterectomy.

  13. Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kaoru; Koeda, Keisuke; Sato, Nobuhiro [Iwate Medical Univ., Morioka (Japan). School of Medicine] [and others

    1999-06-01

    The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student`s T test: p<0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p<0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection. (author)

  14. Light scattering change precedes loss of cerebral adenosine triphosphate in a rat global ischemic brain model.

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2009-08-14

    Measurement of intrinsic optical signals (IOSs) is an attractive technique for monitoring tissue viability in brains since it enables noninvasive, real-time monitoring of morphological characteristics as well as physiological and biochemical characteristics of tissue. We previously showed that light scattering signals reflecting cellular morphological characteristics were closely related to the IOSs associated with the redox states of cytochrome c oxidase in the mitochondrial respiratory chain. In the present study, we examined the relationship between light scattering and energy metabolism. Light scattering signals were transcranially measured in rat brains after oxygen and glucose deprivation, and the results were compared with concentrations of cerebral adenosine triphosphate (ATP) measured by luciferin-luciferase bioluminescence assay. Electrophysiological signal was also recorded simultaneously. After starting saline infusion, EEG activity ceased at 108+/-17s, even after which both the light scattering signal and ATP concentration remained at initial levels. However, light scattering started to change in three phases at 236+/-15s and then cerebral ATP concentration started to decrease at about 260s. ATP concentration significantly decreased during the triphasic scattering change, indicating that the start of scattering change preceded the loss of cerebral ATP. The mean time difference between the start of triphasic scattering change and the onset of ATP loss was about 24s in the present model. DC potential measurement showed that the triphasic scattering change was associated with anoxic depolarization. These findings suggest that light scattering signal can be used as an indicator of loss of tissue viability in brains.

  15. Temporal changes in stress preceding the 2004-2008 eruption of Mount St. Helens, Washington

    Science.gov (United States)

    Lehto, H.L.; Roman, D.C.; Moran, S.C.

    2010-01-01

    The 2004-2008 eruption of Mount St. Helens (MSH), Washington, was preceded by a swarm of shallow volcano-tectonic earthquakes (VTs) that began on September 23, 2004. We calculated locations and fault-plane solutions (FPS) for shallow VTs recorded during a background period (January 1999 to July 2004) and during the early vent-clearing phase (September 23 to 29, 2004) of the 2004-2008 eruption. FPS show normal and strike-slip faulting during the background period and on September 23; strike-slip and reverse faulting on September 24; and a mixture of strike-slip, reverse, and normal faulting on September 25-29. The orientation of ??1 beneath MSH, as estimated from stress tensor inversions, was found to be sub-horizontal for all periods and oriented NE-SW during the background period, NW-SE on September 24, and NE-SW on September 25-29. We suggest that the ephemeral ~90?? change in ??1 orientation was due to intrusion and inflation of a NE-SW-oriented dike in the shallow crust prior to the eruption onset. ?? 2010 Elsevier B.V.

  16. Glial activation precedes seizures and hippocampal neurodegeneration in measles virus-infected mice.

    Science.gov (United States)

    Lehrmann, Elin; Guidetti, Paolo; Löve, Arthur; Williamson, John; Bertram, Edward H; Schwarcz, Robert

    2008-01-01

    Intracerebral injection of hamster neurotropic (HNT) measles virus in weanling Balb/C mice leads to an encephalitis, which is characterized by glial activation, behavioral seizures, selective neurodegeneration, and, after approximately 7 days, death. To provide a better understanding of the underlying molecular pathology, we studied seizure evolution by continuously monitoring electroencephalographic (EEG) activity, examined neuroglia and neurons histologically, and measured the brain content of glia-derived neuroactive metabolites of the kynurenine pathway of tryptophan degradation. Microglia and astrocytes were activated as early as postinoculation day (PID) 1, with reactive microglia lining the extent of the alveus. This was followed by a more extensive microglial activation that specifically outlined hippocampal pyramidal neurons in areas CA1-CA3 and by increases in the hippocampal levels of the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN). These changes preceded the onset of EEG seizures, which had a mean onset of 108 h after inoculation. Prominent hippocampal cell loss, demonstrated by Nissl- and silver staining, was apparent by PID 5. Thus, we speculate that early glial reactions to HNT inoculation result in the excess formation of 3-HK and QUIN, which in turn causes subclinical seizure activity, behavioral seizures, and, eventually, neurodegeneration. In addition to its conceptual implications, our study indicates that timely interventions modulating glial activation or 3-HK/QUIN synthesis may be of benefit in preventing or arresting seizure-induced neuronal damage.

  17. A content analysis of precede-proceed constructs in stress management mobile apps

    Science.gov (United States)

    Wilkinson, Jessica; West, Joshua H.; Bernhardt, Jay M.

    2016-01-01

    Background The emergence of Apple’s iPhone provides a platform for freelance developers to design third party apps, which greatly expands the functionality and utility of mobile devices for stress management. This study provides a basic overview of the stress management apps under the health and fitness category of the Apple App store and appraises each app’s potential for influencing behavior change. Methods Data for this study came from a content analysis of health and fitness app descriptions available in the App Store on iTunes. Trained research assistants used the Precede-Proceed Model (PPM) as a framework to guide the coding of paid stress management apps and to evaluate each app’s potential for effecting health behavior change. Results Most apps were rated as being plausible (96.9%) and intending to address stress management (98.5%), but only 63.3% were rated as recommendable to others for their use. Reinforcing apps were less common than predisposing and enabling apps. Less than one percent (0.39%) of apps included all three factors (predisposing, enabling and reinforcing). Conclusions Practitioners should be cautious when promoting the use of stress management apps, as most provide only health-related information (predisposing) or suggestions for enabling behavior, but almost none include all three theoretical factors recommended for behavior change. PMID:28293583

  18. Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

    Energy Technology Data Exchange (ETDEWEB)

    Borowsky, A D; Dingley, K; Ubick, E; Turteltaub, K; Cardiff, R D; DeVere-White, R

    2006-06-01

    2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.

  19. Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy.

    Science.gov (United States)

    Moulés, Vincent; Pomier, Carole; Sibon, David; Gabet, Anne-Sophie; Reichert, Michal; Kerkhofs, Pierre; Willems, Luc; Mortreux, Franck; Wattel, Eric

    2005-02-15

    Almost all cancers are preceded by a prolonged period of clinical latency during which a combination of cellular events helps move carcinogen-exposed cells towards a malignant phenotype. Hitherto, investigating the fate of premalignant cells in vivo remained strongly hampered by the fact that these cells are usually indistinguishable from their normal counterparts. Here, for the first time, we have designed a strategy able to reconstitute the replicative history of the bona fide premalignant clone in an animal model, the sheep experimentally infected with the lymphotropic bovine leukemia virus. We have shown that premalignant clones are early and clearly distinguished from other virus-exposed cells on the basis of their degree of clonal expansion and genetic instability. Detectable as early as 0.5 month after the beginning of virus exposure, premalignant cells displayed a two-step pattern of extensive clonal expansion together with a mutation load approximately 6 times higher than that of other virus-exposed cells that remained untransformed during the life span of investigated animals. There was no fixation of somatic mutations over time, suggesting that they regularly lead to cellular death, partly contributing to maintain a normal lymphocyte count during the prolonged premalignant stage. This equilibrium was finally broken after a period of 18.5 to 60 months of clinical latency, when a dramatic decrease in the genetic instability of premalignant cells coincided with a rapid increase in lymphocyte count and lymphoma onset.

  20. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

    Science.gov (United States)

    Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

    2016-05-10

    Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

  1. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Directory of Open Access Journals (Sweden)

    Andy Martens

    Full Text Available Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  2. Terrorist Attacks Escalate in Frequency and Fatalities Preceding Highly Lethal Attacks

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G.; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates–both in the number of people killed per attack and in the frequency of attacks–leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack. PMID:24755753

  3. General practice consultations, diagnostic investigations, and prescriptions in the year preceding a lung cancer diagnosis

    DEFF Research Database (Denmark)

    Guldbrandt, Louise M; Møller, Henrik; Jakobsen, Erik;

    2017-01-01

    Patterns of general practice utilization in the period before lung cancer (LC) diagnosis may provide new knowledge to ensure timelier and earlier diagnosis of LC. This study aimed to explore the prediagnostic activity in general practice in the year preceding LC diagnosis. The activity was compared...... = 340,170). During months 12 to 1 prior to diagnosis, 92.6% of LC patients and 88.4% of comparison subjects had one or more contacts with general practice. 13.0% of LC patients and 3.3% of comparison subjects had two or more X-rays. 20.8% of LC patients and 8.5% of comparison subjects had two or more...... than COPD patients without lung cancer, but not as pronounced as compared to patients without COPD. There was a significant increase in healthcare seeking and diagnostic activity in the year prior to a LC diagnosis, regardless of stage at diagnosis. COPD may mask the symptoms of LC. This indicates...

  4. Patterns of Theta Activity in Limbic Anxiety Circuit Preceding Exploratory Behavior in Approach-Avoidance Conflict

    Science.gov (United States)

    Jacinto, Luis R.; Cerqueira, João J.; Sousa, Nuno

    2016-01-01

    Theta oscillations within the hippocampus-amygdala-medial prefrontal cortex (HPC-AMY-mPFC) circuit have been consistently implicated in the regulation of anxiety behaviors, including risk-assessment. To study if theta activity during risk-assessment was correlated with exploratory behavior in an approach/avoidance paradigm we recorded simultaneous local field potentials from this circuit in rats exploring the elevated-plus maze (EPM). Opposing patterns of power variations in the ventral hippocampus (vHPC), basolateral amygdala (BLA), and prelimbic (PrL) mPFC, but not in the dorsal hippocampus (dHPC), during exploratory risk-assessment of the open arms preceded further exploration of the open arms or retreat back to the safer closed arms. The same patterns of theta power variations in the HPC-BLA-mPFC(PrL) circuit were also displayed by animals submitted to chronic unpredictable stress protocol known to induce an anxious state. Diverging patterns of vHPC-mPFC(PrL) theta coherence were also significantly correlated with forthcoming approach or avoidance behavior in the conflict situation in both controls and stressed animals; interestingly, vHPC-BLA, and BLA-mPFC(PrL) theta coherence correlated with future behavior only in stressed animals, underlying the pivotal role of the amygdala on the stress response. PMID:27713693

  5. Patterns of Theta Activity in Limbic Anxiety Circuit Preceding Exploratory Behavior in Approach-Avoidance Conflict

    Directory of Open Access Journals (Sweden)

    Luis R Jacinto

    2016-09-01

    Full Text Available Theta oscillations within the hippocampus-amygdala-medial prefrontal cortex (HPC-AMY-mPFC(PrL circuit have been consistently implicated in the regulation of anxiety behaviors, including risk-assessment. To study if theta activity during risk-assessment was correlated with exploratory behavior in an approach/avoidance paradigm we recorded simultaneous local field potentials from this circuit in rats exploring the elevated-plus maze (EPM. Opposing patterns of power variations in the ventral hippocampus (vHPC, basolateral amygdala (BLA and prelimbic (PrL mPFC, but not in the dorsal hippocampus (dHPC, during exploratory risk-assessment of the open arms preceded further exploration of the open arms or retreat back to the safer closed arms. The same patterns of theta power variations in the HPC-BLA-mPFC(PrL circuit were also displayed by animals submitted to chronic unpredictable stress protocol known to induce an anxious state. Diverging patterns of vHPC-mPFC(PrL theta coherence were also significantly correlated with forthcoming approach or avoidance behavior in the conflict situation in both controls and stressed animals; interestingly, vHPC-BLA and BLA-mPFC(PrL theta coherence correlated with future behavior only in stressed animals, underlying the pivotal role of the amygdala on the stress response.

  6. The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years

    Directory of Open Access Journals (Sweden)

    Janković Slavko M.

    2006-01-01

    Full Text Available The perplexing and tantalizing disease of rapid eye movement (REM sleep behavior disorder (RBD is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats [1]. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication [2], and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse [3]. However, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986 [4-7]. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia [8]. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [6] in 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. [9]. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep" [2]. Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene

  7. RELATIONSHIPS BETWEEN PRECEDING PACIFIC SEA SURFACE TEMPERATURES AND SUBTROPICAL HIGH INDEXES OF MAIN RAINING SEASONS

    Institute of Scientific and Technical Information of China (English)

    YAO Yu; YAN Hua-sheng

    2009-01-01

    With correlation analysis and factor analysis methods,the effects of preceding Pacific SSTs on subtropical high indexes of main raining seasons are discussed. The results of correlation analysis show that the effects of SSTs on five subtropical high indexes differ in seasons and regions. The variation of SSTs mostly affects the area and intensity indexes of the subtropical high,followed by the western ridge index,and the effect on the ridge line index is more remarkable than on the north boundary index. The results of factor analysis reveals that the first common thctor of SST of each season reflected mainly the inverse relation of SSTs variation between the central and eastern part of equatorial Pacific and the western Pacific,which correlates better with the subtropical high indexes in the main raining seasons than other common factors of SST. The analysis of interdecadal variation indicated that the variation of SSTs was conducive to the emergence of the La Ni(n)a event before the end of 1970s,such that in the summer the subtropical high is likely to be weaker and smaller and located eastward and northward. After the 1980s,the opposite characteristics prevailed.

  8. Strong and Anomalous Thermal Expansion Precedes the Thermosalient Effect in Dynamic Molecular Crystals.

    Science.gov (United States)

    Panda, Manas K; Centore, Roberto; Causà, Mauro; Tuzi, Angela; Borbone, Fabio; Naumov, Panče

    2016-07-12

    The ability of thermosalient solids, organic analogues of inorganic martensites, to move by rapid mechanical reconfiguration or ballistic event remains visually appealing and potentially useful, yet mechanistically elusive phenomenon. Here, with a material that undergoes both thermosalient and non-thermosalient phase transitions, we demonstrate that the thermosalient effect is preceded by anomalous thermal expansion of the unit cell. The crystal explosion occurs as sudden release of the latent strain accumulated during the anisotropic, exceedingly strong expansion of the unit cell with αa = 225.9 × 10(-6) K(-1), αb = 238.8 × 10(-6) K(-1) and αc = -290.0 × 10(-6) K(-1), the latter being the largest negative thermal expansivity observed for an organic compound thus far. The results point out to the occurence of the thermosalient effect in phase transitions as means to identify new molecular materials with strong positive and/or negative thermal expansion which prior to this work could only be discovered serendipitously.

  9. Community health needs assessment with precede-proceed model: a mixed methods study

    Directory of Open Access Journals (Sweden)

    Wang Yang

    2009-10-01

    Full Text Available Abstract Background Community health services in China have developed over the last few decades. In order to use limited health resources more effectively, we conducted a community health needs assessment. This aimed to provide an understanding of the community's health problems and the range of potential factors affecting risk behaviours for the priority health problems. Methods We used the precede-proceed model for the needs assessment. Triangulation of data, methods and researchers were employed in data collection. Results Main findings include: cardiovascular diseases (CVDs were identified as the priority health problems in the study communities; risk factors associated with CVDs included smoking, physical inactivity and unhealthy eating behaviours, particularly amongst male residents with low education level; factors negatively affecting behaviours were classified into predisposing factors (limited knowledge, beliefs and lack of perceived needs, enabling factors (limited access to health promotion activities, unawareness of health promotion, lack of work-site and school health promotion, absence of health promotion related policy and reinforcing factors (culture. Policies and organization were not perfect; there were limited staff skilled in providing health promotion in the community. Conclusion CVDs were identified by the communities as priority health problems. Future health programs should focus on smoking, physical inactivity and unhealthy eating behaviours. Behaviour change strategies should take predisposing factors, enabling factors and reinforcing factors into consideration. Policies, organization and human resource need strengthening.

  10. An improved genetic algorithm for multidimensional optimization of precedence-constrained production planning and scheduling

    Science.gov (United States)

    Dao, Son Duy; Abhary, Kazem; Marian, Romeo

    2017-01-01

    Integration of production planning and scheduling is a class of problems commonly found in manufacturing industry. This class of problems associated with precedence constraint has been previously modeled and optimized by the authors, in which, it requires a multidimensional optimization at the same time: what to make, how many to make, where to make and the order to make. It is a combinatorial, NP-hard problem, for which no polynomial time algorithm is known to produce an optimal result on a random graph. In this paper, the further development of Genetic Algorithm (GA) for this integrated optimization is presented. Because of the dynamic nature of the problem, the size of its solution is variable. To deal with this variability and find an optimal solution to the problem, GA with new features in chromosome encoding, crossover, mutation, selection as well as algorithm structure is developed herein. With the proposed structure, the proposed GA is able to "learn" from its experience. Robustness of the proposed GA is demonstrated by a complex numerical example in which performance of the proposed GA is compared with those of three commercial optimization solvers.

  11. Fault Tolerant PLBGSA: Precedence Level Based Genetic Scheduling Algorithm for P2P Grid

    Directory of Open Access Journals (Sweden)

    Piyush Chauhan

    2013-01-01

    Full Text Available Due to monetary limitation, small organizations cannot afford high end supercomputers to solve highly complex tasks. P2P (peer to peer grid computing is being used nowadays to break complex task into subtasks in order to solve them on different grid resources. Workflows are used to represent these complex tasks. Finishing such complex task in a P2P grid requires scheduling subtasks of workflow in an optimized manner. Several factors play their part in scheduling decisions. The genetic algorithm is very useful in scheduling DAG (directed acyclic graph based task. Benefit of a genetic algorithm is that it takes into consideration multiple criteria while scheduling. In this paper, we have proposed a precedence level based genetic algorithm (PLBGSA, which yields schedules for workflows in a decentralized fashion. PLBGSA is compared with existing genetic algorithm based scheduling techniques. Fault tolerance is a desirable trait of a P2P grid scheduling algorithm due to the untrustworthy nature of grid resources. PLBGSA handles faults efficiently.

  12. The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Catalina Carrasco-Pozo

    2016-10-01

    Full Text Available Studying rats fed high cholesterol diet and a pancreatic β-cell line (Min6, we aimed to determine the mechanisms by which quercetin protects against cholesterol-induced pancreatic β-cell dysfunction and impairments in glycemic control. Quercetin prevented the increase in total plasma cholesterol, but only partially prevented the high cholesterol diet-induced alterations in lipid profile. Quercetin prevented cholesterol-induced decreases in pancreatic ATP levels and mitochondrial bioenergetic dysfunction in Min6 cells, including decreases in mitochondrial membrane potentials and coupling efficiency in the mitochondrial respiration (basal and maximal oxygen consumption rate (OCR, ATP-linked OCR and reserve capacity. Quercetin protected against cholesterol-induced apoptosis of Min6 cells by inhibiting caspase-3 and -9 activation and cytochrome c release. Quercetin prevented the cholesterol-induced decrease in antioxidant defence enzymes from pancreas (cytosolic and mitochondrial homogenates and Min6 cells and the cholesterol-induced increase of cellular and mitochondrial oxidative status and lipid peroxidation. Quercetin counteracted the cholesterol-induced activation of the NFκB pathway in the pancreas and Min6 cells, normalizing the expression of pro-inflammatory cytokines. Quercetin inhibited the cholesterol-induced decrease in sirtuin 1 expression in the pancreas and pancreatic β-cells. Taken together, the anti-apoptotic, antioxidant and anti-inflammatory properties of quercetin, and its ability to protect and improve mitochondrial bioenergetic function are likely to contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction, thereby preserving glucose-stimulated insulin secretion (GSIS and glycemic control. Specifically, the improvement of ATP-linked OCR and the reserve capacity are important mechanisms for protection of quercetin. In addition, the inhibition of the NFκB pathway is an important

  13. Jealousy delirium associated with memory deficits

    Directory of Open Access Journals (Sweden)

    Orazio Zanetti

    2007-09-01

    Full Text Available Alzheimer’s disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioural disturbances. A correct and early diagnosis not only allows prompt treatment but can also give the person with Alzheimer’s and his family more time to arm themselves with knowledge about this type of dementia and the best way to live with the disease. The role of Family Physician is very important in early diagnosis: dementia may be suspected if memory deficits are exhibited during the medical history and physical examination. Information from the patient’s family members, friends and caregivers may also point to signs of dementia. We report a case of a 75-years-old man who was suffering from cognitive deficits and behavioural problems: the first disease symptom was a strong feeling of jealousy towards his wife.

  14. Traumatic knee extension deficit (the locked knee)

    DEFF Research Database (Denmark)

    Helmark, I C; Neergaard, K; Krogsgaard, M R

    2007-01-01

    In the present study we investigated the validity of magnetic resonance imaging (MRI) and arthroscopy in knees with acute, traumatic extension deficit (the "locked knee"), and evaluated whether arthroscopy of knees with no mechanical pathology could be avoided by MRI evaluation. The study consisted...... of 50 patients who had an acute, traumatic extension deficit of the knee. All patients were submitted to MRI prior to arthroscopy. Following MRI and surgery, standardized forms were filled out, attempting to objectify the findings. The orthopaedic surgeon was not aware of the MRI result prior to surgery......, the following results were calculated for the overall appearance of a lesion able to cause locking: Positive predictive value = 0.85, negative predictive value = 0.77, sensitivity = 0.95, specificity = 0.53. Two knees were erroneously evaluated with no mechanical locking at MRI (one bucket-handle lesion and one...

  15. Common Cognitive Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration

    Science.gov (United States)

    Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.

    2014-01-01

    Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…

  16. Bioenergetics of halophiles

    Energy Technology Data Exchange (ETDEWEB)

    Lanyi, Janos K. [Univ. of California, Irvine, CA (United States); Balashov, Sergei [Univ. of California, Irvine, CA (United States)

    2016-02-26

    In the last grant period we explored the Na+ binding site of the recently discovered light-driven sodium ion pump. The rationale was that comparison of this novel system to the similar proton pumps and chloride ion pumps would reveal the amazingly (and unexpectedly) wide variety of structural features that govern conversion of light-energy into biologically useful transmembrane gradients and thus production of biomass. A thorough description of this system would establish the basis for continuing our funded research on these proteins.

  17. Sporadic hemiplegic migraine with permanent neurological deficits.

    Science.gov (United States)

    Schwedt, Todd J; Zhou, Jiying; Dodick, David W

    2014-01-01

    By definition, the neurologic impairments of hemiplegic migraine are reversible. However, a few cases of permanent neurologic deficits associated with hemiplegic migraine have been reported. Herein, we present the case of a patient with permanent impairments because of hemiplegic migraine despite normalization of associated brain magnetic resonance imaging abnormalities. Cases like these suggest the need to consider aggressive prophylactic therapy for patients with recurrent hemiplegic migraine attacks.

  18. Stigma in attention deficit hyperactivity disorder

    OpenAIRE

    Anna K Mueller; Fuermaier, Anselm B. M.; Koerts, Janneke; Tucha, Lara

    2012-01-01

    Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of the empirical research in the field of ADHD with regard to stigma was performed. The findings of investigations in this field were clustered in different categories, including stigma in children wit...

  19. Sensorimotor gating deficits in multiple system atrophy

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki

    2014-01-01

    Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

  20. Pollination deficits in UK apple orchards

    OpenAIRE

    Garratt, M.P.D.; Truslove, C.L.; Coston, D. J.; Evans, R. L.; Moss, E. D.; Dodson, C.; Jenner, N.; Biesmeijer, J.C.; Potts, S. G.

    2013-01-01

    Apple production in the UK is worth over £100 million per annum and this production is heavily dependent on insect pollination. Despite its importance, it is not clear which insect pollinators carry out the majority of this pollination. Furthermore, it is unknown whether current UK apple production, in terms of both yield and quality, suffers pollination deficits and whether production value could be increased through effective management of pollination services. The present study set out to ...

  1. Cognitive deficits in patients with brain tumor

    Institute of Scientific and Technical Information of China (English)

    SHEN Chao; BAO Wei-min; YANG Bo-jie; XIE Rong; CAO Xiao-yun; LUAN Shi-hai; MAO Ying

    2012-01-01

    Objective To discuss the present status and progress of clinical research on the cognitive effects caused by different types of brain tumors and common treatments.Data sources The data used in this review were mainly from PubMed articles published in English from 1990 to Febuary 2012.Research terms were "cognitive deficits" or "cognitive dysfunction".Study selection Articals including any information about brain tumor related cognitive deficits were selected.Results It is widely accepted that brain tumors and related treatments can impair cognitive function across manydomains,and can impact on patients' quality of life.Tumor localization,lateralization,surgery,drugs,radiotherapy and chemotherapy are all thought to be important factors in this process.However,some conflicting findings regarding brain tumor-related cognitive deficits have been reported.It can be difficult to determine the mechanism of these treatments,such as chemotherapy,antibiotics,antiepileptics,and steroids.Future research is needed to clarify these potential treatment effects.Conclusions Cognitive function is important for patients with brain tumor.Much more focus has been paid on this field.It should be regarded as an important prognostic index for the patients with brain tumor,and neuropsychological tests should be used in regular examinations.

  2. Pollination deficits in UK apple orchards

    Directory of Open Access Journals (Sweden)

    Michael Paul Douglas Garratt

    2014-02-01

    Full Text Available Apple production in the UK is worth over £100 million per annum and this production is heavily dependent on insect pollination. Despite its importance, it is not clear which insect pollinators carry out the majority of this pollination. Furthermore, it is unknown whether current UK apple production, in terms of both yield and quality, suffers pollination deficits and whether production value could be increased through effective management of pollination services. The present study set out to address some of these unknowns and showed that solitary bee activity is high in orchards and that they could be making a valuable contribution to pollination. Furthermore, fruit set and apple seed number were found to be suffering potential pollination deficits although these were not reflected in apple quality. Deficits could be addressed through orchard management practices to improve the abundance and diversity of wild pollinators. Such practices include provision of additional floral resources and nesting habitats as well as preservation of semi-natural areas. The cost effectiveness of such strategies would need to be understood taking into account the potential gains to the apple industry.

  3. Pollination deficits in UK apple orchards

    Directory of Open Access Journals (Sweden)

    Simon Potts

    2013-10-01

    Full Text Available Apple production in the UK is worth over £100 million per annum and this production is heavily dependent on insect pollination. Despite its importance, it is not clear which insect pollinators carry out the majority of this pollination. Furthermore, it is unknown whether current UK apple production, in terms of both yield and quality, suffers pollination deficits and whether production value could be increased through effective management of pollination services. The present study set out to address some of these unknowns and showed that solitary bee activity is high in orchards and that they could be making a valuable contribution to pollination. Furthermore, fruit set and apple seed number were found to be suffering potential pollination deficits although these were not reflected in apple quality. Deficits could be addressed through orchard management practices to improve the abundance and diversity of wild pollinators. Such practices include provision of additional floral resources and nesting habitats as well as preservation of semi-natural areas. The cost effectiveness of such strategies would need to be understood taking into account the potential gains to the apple industry.

  4. Medical Comorbidities in Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Irem Yalug

    2009-09-01

    Full Text Available Attention Deficit Hyperactivity Disorder is one of the most common developmental disorders of childhood with a reported world-wide prevalence of 8 to 12 %. In studies conducted in our country the prevalence rates in community were reported to vary between 8.6 to 8.1 % while clinical prevalence rates were reported to vary between 8.6 to 29.44 %. Fifty to eighty percent of cases were reported to continue into adolescence while thirty to fifty percent may continue into adulthood. Attention deficit hyperactivity disorder is known to accompany subtle physical anomalies, allergic and neurologic disorders, obesity and eating disorders, traumatic injuries, risky sexual behavior, sleep disorders, substance and alcohol use, axis I and II disorders, occupational, legal and academic problems and increased treatment expenditures. Though the effects of this disorder continue throughout life, create burdens to the society along with its treatment as well as disabling the affected patients through their lives, and receive increasing attention in recent years, reviews focusing on problems associated with it are lacking. Therefore, this study aimed to summarize the results of previous studies conducted about medical comorbidities in attention deficit hyperactivity disorder.

  5. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  6. Narrative discourse deficits in amyotrophic lateral sclerosis

    Science.gov (United States)

    Menaged, Anna; Olm, Christopher; McMillan, Corey T.; Boller, Ashley; Irwin, David J.; McCluskey, Leo; Elman, Lauren; Grossman, Murray

    2014-01-01

    Objective: We examined narrative discourse in amyotrophic lateral sclerosis (ALS) to assess the role of executive functioning in support of language and the neuroanatomical basis for such support. Methods: We analyzed a semistructured speech sample in 26 patients with ALS and 19 healthy seniors for narrative discourse features of coherence. Regression analyses related a measure of discourse coherence (“local connectedness”) to gray matter atrophy and reduced white matter fractional anisotropy. Results: Patients with ALS were impaired relative to controls on measures of discourse adequacy, including local connectedness and maintenance of the theme. These discourse measures were related to measures of executive functioning but not to motor functioning. Regressions related local connectedness to gray matter atrophy in ventral and dorsal prefrontal regions and to reduced fractional anisotropy in white matter tracts mediating projections between prefrontal regions. Conclusion: Patients with ALS exhibit deficits in their ability to organize narrative discourse. These deficits appear to be related in part to executive limitations. Consistent with the hypothesis that ALS is a multisystem disorder, this deficit is related to disease in prefrontal regions. PMID:24991038

  7. Cyanobacteria from the Baltic Sea and Finnish lakes as an energy source and modulators of bioenergetic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Sumathy, S.

    2012-11-01

    Cyanobacteria are a diverse group of oxygenic photosynthetic bacteria that inhabit in a wide range of environments. They are versatile and multifaceted organisms with great possibilities for different biotechnological applications. For example, cyanobacteria produce molecular hydrogen (H{sub 2}), which is one of the most important alternatives for clean and sustainable energy. Apart from being beneficial, cyanobacteria also possess harmful characteristics and may become a source of threat to human health and other living organisms, as they are able to form surface blooms that are producing a variety of toxic or bioactive compounds. The University of Helsinki Culture Collection (UHCC) maintains around 1,000 cyanobacterial strains representing a large number of genera and species isolated from the Baltic Sea and Finnish lakes. The culture collection covers different life forms such as unicellular and filamentous, N{sub 2}-fixing and non-N{sub 2}-fixing strains, and planktonic and benthic cyanobacteria. In this thesis, the UHCC has been screened to identify potential strains for sustainable biohydrogen production and also for strains that produce compounds modifying the bioenergetic pathways of other cyanobacteria or terrestrial plants. Among the 400 cyanobacterial strains screened so far, ten were identified as high H{sub 2}- producing strains. The enzyme systems involved in H2 metabolism of cyanobacteria were analyzed using the Southern hybridization approach. This revealed the presence of the enzyme nitrogenase in all strains tested, while none of them are likely to have contained alternative nitrogenases. All the strains tested, except for two Calothrix strains, XSPORK 36C and XSPORK 11A, were suggested to contain both uptake and bidirectional hydrogenases. Moreover, 55 methanol extracts of various cyanobacterial strains were screened to identify potent bioactive compounds affecting the photosynthetic apparatus of the model cyanobacterium, Synechocystis PCC 6803

  8. Different Fear-Regulation Behaviors in Toddlerhood: Relations to Preceding Infant Negative Emotionality, Maternal Depression, and Sensitivity

    Science.gov (United States)

    Gloggler, Bettina; Pauli-Pott, Ursula

    2008-01-01

    In the study presented, the development of different fear regulation behaviors and their associations with preceding maternal sensitivity and depression is addressed. A sample of 64 mother-child pairs was examined at the children's ages of 4, 12, and 30 months. Four-month negative reactivity and 12- and 30- month behavioral inhibition and fear…

  9. The Effect of an Education Program Utilising PRECEDE Model on the Quality of Life in Patients with Type 2 Diabetes

    Science.gov (United States)

    Taghdisi, M. H.; Borhani, M.; Solhi, M.; Afkari, M. E.; Hosseini, F.

    2012-01-01

    Background and objective: The problems caused by diabetes have direct and indirect impacts on the quality of life of diabetic patients. An increase of these problems means a decrease in a patient's quality of life. This study was conducted to assess the effect of the educational programme based on the precede model in promoting quality of life of…

  10. Stability in the choice of method during the period preceding a suicide attempt and in attempt repeaters

    Directory of Open Access Journals (Sweden)

    Eberhard A. Deisenhammer

    Full Text Available Background and Objectives: Understanding the mental processes preceding a suicidal act is important for the potential to intervene. This study investigates stability and possible changes of suicide methods considered during the time immediately preceding a suicide attempt. Methods: Patients who had attempted suicide were interviewed shortly thereafter with regard to whether there was a change in the conception of the method to be used during the period preceding the attempt. In addition, the course of methods applied in previous suicide attempts was assessed in attempt repeaters. Results: In total, 130 patients were included. In 63.1% one method only was envisaged during the entire suicidal crisis, in 26.9% the initial and the actual method differed. Stability rate was higher in those older than 40 years, if the duration of the suicidal crisis was ≤ 60 minutes and if a non-violent suicide method was initially intended. Of repeaters, 46.5% used the same method in all recorded attempts. Use of a non-violent method in the first suicide attempt predicted method stability in subsequent attempts. Conclusions: Focusing on one single suicide method during the time immediately preceding a suicide attempt is common. Reduced flexibility to rapidly switch mentally to another method may contribute to explain the effectiveness of limiting access to suicide means for suicide prevention.

  11. Metacognition deficits as a risk factor for prospective motivation deficits in schizophrenia spectrum disorders.

    Science.gov (United States)

    Luther, Lauren; Firmin, Ruth L; Minor, Kyle S; Vohs, Jenifer L; Buck, Benjamin; Buck, Kelly D; Lysaker, Paul H

    2016-11-30

    Although motivation deficits are key determinants of functional outcomes, little is known about factors that contribute to prospective motivation in people with schizophrenia. One candidate factor is metacognition, or the ability to form complex representations about oneself, others, and the world. This study aimed to assess whether metacognition deficits were a significant predictor of reduced prospective motivation, after controlling for the effects of baseline motivation, anticipatory pleasure, and antipsychotic medication dose. Fifty-one participants with a schizophrenia spectrum disorder completed measures of metacognition and anticipatory pleasure at baseline; participants also completed a measure of motivation at baseline and six months after the initial assessment. Baseline antipsychotic dose was obtained from medical charts. Hierarchical regression analysis revealed that lower levels of baseline metacognition significantly predicted reduced levels of motivation assessed six months later, after controlling for baseline levels of motivation, anticipatory pleasure, and antipsychotic dose. Higher baseline antipsychotic dose was also a significant predictor of reduced six month motivation. Results suggest that metacognition deficits and higher antipsychotic dose may be risk factors for the development of motivation deficits in schizophrenia. Implications include utilizing interventions to improve metacognition in conjunction with evaluating and possibly lowering antipsychotic dose for people struggling with motivation deficits.

  12. The Microbiology of Subsurface, Salt-Based Nuclear Waste Repositories: Using Microbial Ecology, Bioenergetics, and Projected Conditions to Help Predict Microbial Effects on Repository Performance

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, Juliet S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cherkouk, Andrea [Helmholtz-Zentrum Dresden-Rossendorf, Rossendorf (Germany); Arnold, Thuro [Helmholtz-Zentrum Dresden-Rossendorf, Rossendorf (Germany); Meleshyn, Artur [Gesellschaft fur Anlagen und Reaktorsicherheit, Braunschweig (Germany); Reed, Donald T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-11-17

    This report summarizes the potential role of microorganisms in salt-based nuclear waste repositories using available information on the microbial ecology of hypersaline environments, the bioenergetics of survival under high ionic strength conditions, and “repository microbiology” related studies. In areas where microbial activity is in question, there may be a need to shift the research focus toward feasibility studies rather than studies that generate actual input for performance assessments. In areas where activity is not necessary to affect performance (e.g., biocolloid transport), repository-relevant data should be generated. Both approaches will lend a realistic perspective to a safety case/performance scenario that will most likely underscore the conservative value of that case.

  13. Glycine transporter-1 inhibition preceding extinction training inhibits reacquisition of cocaine seeking.

    Science.gov (United States)

    Achat-Mendes, Cindy; Nic Dhonnchadha, Bríd Á; Platt, Donna M; Kantak, Kathleen M; Spealman, Roger D

    2012-12-01

    Cognitive enhancers that act by increasing glycine transmission might be useful adjuncts to cocaine-cue extinction training to deter relapse. The study investigated the effects of combining treatments of the glycine transporter-1 (GlyT-1) inhibitor, Org24598, with extinction training on the subsequent reacquisition of cocaine self-administration. Squirrel monkeys and rats were trained to self-administer cocaine under a second-order schedule of intravenous drug injection in which responding was maintained by cocaine injections and a cocaine-paired visual stimulus. During three weekly extinction sessions, saline was substituted for cocaine but responding still produced the cocaine-paired stimulus. Subjects were treated with Org24598 or vehicle, either before or after each extinction session. One week later, cocaine injections were restored, and reacquisition of cocaine self-administration was evaluated over 15 sessions. Compared with vehicle, administration of Org24598 (1.0 mg/kg in monkeys; 3.0 or 7.5 mg/kg in rats) before each extinction session significantly inhibited reacquisition of cocaine self-administration in each species. In contrast, administration of Org24598 (1.0 mg/kg in monkeys) following, rather than preceding, each extinction session did not affect reacquisition compared with vehicle. When extinction training was replaced by cocaine self-administration or abstinence control conditions, treatment with the same doses of Org24598 resulted in reacquisition that was significantly more rapid than the reacquisition observed when Org24598 was administered before extinction training sessions. The results support the potential clinical utility of GlyT-1 inhibitor pretreatments combined with cocaine-cue extinction training to inhibit relapse.

  14. Evidence for a neural source of the precedence effect in sound localization.

    Science.gov (United States)

    Brown, Andrew D; Jones, Heath G; Kan, Alan; Thakkar, Tanvi; Stecker, G Christopher; Goupell, Matthew J; Litovsky, Ruth Y

    2015-11-01

    Normal-hearing human listeners and a variety of studied animal species localize sound sources accurately in reverberant environments by responding to the directional cues carried by the first-arriving sound rather than spurious cues carried by later-arriving reflections, which are not perceived discretely. This phenomenon is known as the precedence effect (PE) in sound localization. Despite decades of study, the biological basis of the PE remains unclear. Though the PE was once widely attributed to central processes such as synaptic inhibition in the auditory midbrain, a more recent hypothesis holds that the PE may arise essentially as a by-product of normal cochlear function. Here we evaluated the PE in a unique human patient population with demonstrated sensitivity to binaural information but without functional cochleae. Users of bilateral cochlear implants (CIs) were tested in a psychophysical task that assessed the number and location(s) of auditory images perceived for simulated source-echo (lead-lag) stimuli. A parallel experiment was conducted in a group of normal-hearing (NH) listeners. Key findings were as follows: 1) Subjects in both groups exhibited lead-lag fusion. 2) Fusion was marginally weaker in CI users than in NH listeners but could be augmented by systematically attenuating the amplitude of the lag stimulus to coarsely simulate adaptation observed in acoustically stimulated auditory nerve fibers. 3) Dominance of the lead in localization varied substantially among both NH and CI subjects but was evident in both groups. Taken together, data suggest that aspects of the PE can be elicited in CI users, who lack functional cochleae, thus suggesting that neural mechanisms are sufficient to produce the PE.

  15. Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

    Directory of Open Access Journals (Sweden)

    Someya Nami

    2012-06-01

    Full Text Available Abstract Background To investigate the effect of preceding acute exercise on the peripheral vascular response to a mental task, we measured splanchnic and cerebral blood flow responses to performing a mental task after exercise and resting. Methods In the exercise trial, 11 males exercised for 30 min on a cycle ergometer with a workload set at 70% of the age-predicted maximal heart rate for each individual. After a 15-min recovery period, the subjects rested for 5 min for pre-task baseline measurement and then performed mental arithmetic for 5 min followed by 5 min of post-task measurement. In the resting trial, they rested for 45 min and pre-task baseline data was obtained for 5 min. Then mental arithmetic was performed for 5 min followed by post-task measurement. We measured the mean blood velocity in the middle cerebral artery and superior mesenteric artery and the mean arterial pressure. Results Mean arterial pressure and mean blood velocity in the middle cerebral artery were significantly higher than the baseline during mental arithmetic in both exercise and resting trials. Mean blood velocity in the middle cerebral artery during mental arithmetic was greater in the control trial than the exercise trial. Mean blood velocity in the superior mesenteric artery showed no significant change during mental arithmetic from baseline in both trials. Conclusion These results suggest that acute exercise can moderate the increase in cerebral blood flow induced by a mental task.

  16. Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli:A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Julia eMossbridge

    2012-10-01

    Full Text Available This meta-analysis of 26 reports published between 1978 and 2010 tests an unusal hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: 1 randomly presented arousing vs. neutral stimuli, or 2 guessing tasks with feedback (correct vs. incorrect. Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity (EEG, and blood oxygenation level dependent (BOLD activity. To avoid including data hand-picked from multiple different analyses, no post-hoc experiments are considered. The results reveal a significant overall effect with a small effect size (random effects: overall [weighted] ES=0.21, 95%CI=0.13-0.29, z=5.3, p<5.7x10-8; fixed effects: overall ES=0.21, 95%CI=0.15-0.27, z=6.9, p<2.7x10-12. Higher quality experiments produce a quantitately larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p>0.05 was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviourally relevant events. Multiple replications arising from different laboratories using the same methods are necessary to further examine this currently unexplained anticipatory activity. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones, remains to be determined.

  17. Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer's disease brain.

    Science.gov (United States)

    Kurbatskaya, Ksenia; Phillips, Emma C; Croft, Cara L; Dentoni, Giacomo; Hughes, Martina M; Wade, Matthew A; Al-Sarraj, Safa; Troakes, Claire; O'Neill, Michael J; Perez-Nievas, Beatriz G; Hanger, Diane P; Noble, Wendy

    2016-03-31

    Alterations in calcium homeostasis are widely reported to contribute to synaptic degeneration and neuronal loss in Alzheimer's disease. Elevated cytosolic calcium concentrations lead to activation of the calcium-sensitive cysteine protease, calpain, which has a number of substrates known to be abnormally regulated in disease. Analysis of human brain has shown that calpain activity is elevated in AD compared to controls, and that calpain-mediated proteolysis regulates the activity of important disease-associated proteins including the tau kinases cyclin-dependent kinase 5 and glycogen kinase synthase-3. Here, we sought to investigate the likely temporal association between these changes during the development of sporadic AD using Braak staged post-mortem brain. Quantification of protein amounts in these tissues showed increased activity of calpain-1 from Braak stage III onwards in comparison to controls, extending previous findings that calpain-1 is upregulated at end-stage disease, and suggesting that activation of calcium-sensitive signalling pathways are sustained from early stages of disease development. Increases in calpain-1 activity were associated with elevated activity of the endogenous calpain inhibitor, calpastatin, itself a known calpain substrate. Activation of the tau kinases, glycogen-kinase synthase-3 and cyclin-dependent kinase 5 were also found to occur in Braak stage II-III brain, and these preceded global elevations in tau phosphorylation and the loss of post-synaptic markers. In addition, we identified transient increases in total amyloid precursor protein and pre-synaptic markers in Braak stage II-III brain, that were lost by end stage Alzheimer's disease, that may be indicative of endogenous compensatory responses to the initial stages of neurodegeneration. These findings provide insight into the molecular events that underpin the progression of Alzheimer's disease, and further highlight the rationale for investigating novel treatment

  18. Sound localization in reverberant environments: physiological bases of the precedence effect

    Science.gov (United States)

    Paterson, Miles Andrew McLean

    Localization dominance, a phenomenon of the precedence effect, refers to the dominance of directional cues conveyed by sound arriving directly from the source over cues conveyed by reflected copies on the perception of sound source location. One theory of localization dominance is that leading sounds suppress neural responses to lagging sounds (Yin, 1994 Litovsky & Yin, 1998 a, b). Neurons in auditory nuclei respond best to a leading sound and have a reduced response to a lagging sound, supporting this hypothesis. It has been proposed that GABA-ergic or glycinergic inhibition suppresses neural responses to lagging sounds (Yin, 1994 Fitzpatrick et al. 1995 Pollack & Burger, 2002). An alternative hypothesis states that cochlear processing in low-frequency hearing animals alters directional cues conveyed by the leading and lagging sound, emphasising those present in the leading sound (Tollin, 1998 Hartung & Trahiotis 2001). Responses of single neurons in the inferior colliculus (IC) of anaesthetised guinea pigs were recorded to binaural click pair stimuli. Responses of some neurons were recorded before, during, and after iontophoresis of either the GABAa receptor antagonist gabazine, or the glycine receptor antagonist strychnine. Blocking glycine did not decrease neural suppression of the lagging click in 8/10 neurons. Blocking GAB A did not decrease neural suppression of the lagging click in 11/16 neurons. The neural representation of directional cues in the output of low-frequency neurons to the leading click of a binaural click pair differed from those actually conveyed by the stimulus in 20/20 neurons. Examination of the responses of several such neurons indicated responses to the leading click represented a direction between that conveyed by the leading and lagging click. The results supported the hypothesis that cochlear processing of binaural click pairs alters directional cues conveyed by the stimulus. Limited support was also found for the hypothesis that

  19. Preliminary analysis of surface temperature anomalies that preceded the two major Emilia 2012 earthquakes (Italy

    Directory of Open Access Journals (Sweden)

    Kai Qin

    2012-10-01

    Full Text Available In the 1980's, from an analysis of satellite images, Russian scientists reported on a short-term thermal infrared radiation enhancement that occurred before some medium-to-large earthquakes in central Asia [Gorny et al. 1988]. Since then, many researchers have been studying earthquake thermal anomalies with satellite remote sensing data [Qiang et al. 1991, Tronin 1996, Tramutoli et al. 2001, Ouzounov and Freund 2004, Saraf and Choudhury 2004, Aliano et al. 2008, Blackett et al. 2011]. Recently, abnormal surface latent heat flux [Dey and Singh 2003, Cervone et al. 2005, Qin et al. 2009, Qin et al. 2011, Qin et al. 2012], outgoing long-wave radiation [Ouzounov et al. 2007] and microwave radiation [Takashi and Tadashi 2010] have also been shown to precede earthquakes. To investigate the possible physical mechanisms of such satellite thermal anomalies, some studies conducted a series of detecting experiments on rock loaded to fracturing [Wu et al. 2000, Freund 2002, Wu et al. 2002, Wu et al. 2006a, Wu et al. 2006b, Freund et al. 2007], and some hypotheses have been proposed. These have included: leaking of pore-gas, and hence the resulting greenhouse effect [Qiang et al. 1995]; activating and recombining of p-holes during rock deformation [Freund 2002]; release of latent heat due to near-surface air ionization [Pulinets et al. 2006], and stress-induced thermal effects due to friction and fluids [Wu and Liu 2009]. […] In this study, the long-term temperature data from both satellite and ground (with greater emphasis on the satellite data have been used to determine whether there were thermal anomalies associated with this Emilia 2012 seismic sequence. In particular, the next section will be dedicated to describing both the data and the method of analysis. In Section 3, we provide the more significant results, which we discuss in Section 4, together with the main conclusions. […

  20. Hepatic glucose intolerance precedes hepatic steatosis in the male aromatase knockout (ArKO mouse.

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    Michelle L Van Sinderen

    Full Text Available Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation and subsequent replacement in males on whole body glucose metabolism, three- and six-month-old male ArKO mice were subjected to whole body glucose, insulin and pyruvate tolerance tests and analyzed for ensuing metabolic changes in liver, adipose tissue, and skeletal muscle. Estrogen-deficient male ArKO mice showed increased gonadal adiposity which was significantly reduced upon 17β-estradiol (E2 treatment. Concurrently, elevated ArKO serum leptin levels were significantly reduced upon E2 treatment and lowered serum adiponectin levels were restored to wild type levels. Three-month-old male ArKO mice were hyperglycemic, and both glucose and pyruvate intolerant. These phenotypes continued through to 6 months of age, highlighting a loss of glycemic control. ArKO livers displayed changes in gluconeogenic enzyme expression, and in insulin signaling pathways upon E2 treatment. Liver triglycerides were increased in the ArKO males only after 6 months of age, which could be reversed by E2 treatment. No differences were observed in insulin-stimulated ex vivo muscle glucose uptake nor changes in ArKO adipose tissue and muscle insulin signaling pathways. Therefore, we conclude that male ArKO mice develop hepatic glucose intolerance by the age of 3 months which precedes the sex-specific development of hepatic steatosis. This can be reversed upon the administration of exogenous E2.