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Sample records for bioenergetic deficit precedes

  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. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  3. Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  4. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Bioenergetics of aquatic animals

    National Research Council Canada - National Science Library

    Lucas, A

    1996-01-01

    .... Bioenergetics can provide answers to the problems of aquaculture in marine and fresh water - practical solutions are thus supplied to the management of farmed and wild fish stocks, for example...

  6. 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.

  7. Oxygen Deficit: The Bio-energetic Pathophysiology

    Directory of Open Access Journals (Sweden)

    ABHAY KUMAR PANDEY

    2014-09-01

    Full Text Available Scarcity of oxygen in humans arises via three modes. The environment may have low oxygen to breath. There can be disease in respiratory system causing hindrance to uptake of oxygen from environment and the circulatory system may be sluggish to supply to body parts that starve for oxygen. Thirdly the chemico-cellular components of blood which carry oxygen may be lowered or defective. In reference to body cells several limiting sites and mechanisms affect the amount of oxygen delivered to them, and these are under regulatory control of several functional and metabolic systems.

  8. Bioenergetics of mammalian sperm capacitation.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    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.

  9. 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.

  10. Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach?

    Science.gov (United States)

    Ostojic, Sergej M

    2017-07-01

    A confined absorption of exogenous creatine through creatine transporter (CRT1) seems to hamper its optimal uptake in bioenergetical deficits. Co-administration of guanidinoacetic acid (GAA) along with creatine could target other transport channels besides CRT1, and supremely improve cellular levels of creatine. This innovative approach might tackle tissues difficult to reach with conventional creatine interventions, providing a potentially more effective and safe mixture in clinical pharmacology and therapeutics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. 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.

  12. Information, Precedent, and Statute

    NARCIS (Netherlands)

    O. Yalnazov (Orlin)

    2017-01-01

    textabstractI compare precedent and statute in cost-effectiveness terms. To make laws, a lawmaker needs information. Information has a cost. That cost is sensitive to the choice of law production technology. The orthodoxy is that the courts acquire information more cheaply. Litigants volunteer it in

  13. Conditions precedent and indemnities

    International Nuclear Information System (INIS)

    Nielsen, A.D.

    1999-01-01

    The use of certain conditions which allow purchase and sale agreements to be voided without any liability to either the vendor or purchaser are discussed. The drafting issues that arise when preparing these conditions are described and some common types of conditions precedent found in oil and gas purchase and sale transactions are explained. A 'conditions precedent' was defined as being something which must happen before an interest can vest or grow or before an obligation can be performed. Vendors and purchasers use conditions precedent to provide protection against having to conclude a transaction in circumstances that are not acceptable to them. The manner in which indemnity provisions in an oil and gas purchase and sale agreement work, is also explained. These usually relate to breaches of the contract by either vendors or purchasers. Indemnity clauses are used to allocate risk between the vendor and the purchaser and to set out the mechanics by which either party may make a claim against the other. Ways in which to prepare indemnity clauses are described. 2 refs

  14. 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. © The Author(s) 2015.

  15. 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...

  16. A full lifecycle bioenergetic model for bluefin tuna.

    NARCIS (Netherlands)

    Jusup, M.; Klanjscek, T.; Matsuda, H.; 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

  17. Muscle Bioenergetic Considerations for Intrinsic Laryngeal Skeletal Muscle Physiology

    Science.gov (United States)

    Sandage, Mary J.; Smith, Audrey G.

    2017-01-01

    Purpose: Intrinsic laryngeal skeletal muscle bioenergetics, the means by which muscles produce fuel for muscle metabolism, is an understudied aspect of laryngeal physiology with direct implications for voice habilitation and rehabilitation. The purpose of this review is to describe bioenergetic pathways identified in limb skeletal muscle 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. Analysis of regional brain mitochondrial bioenergetics and susceptibility to mitochondrial inhibition utilizing a microplate based system

    Science.gov (United States)

    Sauerbeck, Andrew; Pandya, Jignesh; Singh, Indrapal; Bittman, Kevin; Readnower, Ryan; Bing, Guoying; Sullivan, Patrick

    2012-01-01

    The analysis of mitochondrial bioenergetic function typically has required 50–100 μg of protein per sample and at least 15 min per run when utilizing a Clark-type oxygen electrode. In the present work we describe a method utilizing the Seahorse Biosciences XF24 Flux Analyzer for measuring mitochondrial oxygen consumption simultaneously from multiple samples and utilizing only 5 μg of protein per sample. Utilizing this method we have investigated whether regionally based differences exist in mitochondria isolated from the cortex, striatum, hippocampus, and cerebellum. Analysis of basal mitochondrial bioenergetics revealed that minimal differences exist between the cortex, striatum, and hippocampus. However, the cerebellum exhibited significantly slower basal rates of Complex I and Complex II dependent oxygen consumption (p < 0.05). Mitochondrial inhibitors affected enzyme activity proportionally across all samples tested and only small differences existed in the effect of inhibitors on oxygen consumption. Investigation of the effect of rotenone administration on Complex I dependent oxygen consumption revealed that exposure to 10 pM rotenone led to a clear time dependent decrease in oxygen consumption beginning 12 min after administration (p < 0.05). These studies show that the utilization of this microplate based method for analysis of mitochondrial bioenergetics is effective at quantifying oxygen consumption simultaneously from multiple samples. Additionally, these studies indicate that minimal regional differences exist in mitochondria isolated from the cortex, striatum, or hippocampus. Furthermore, utilization of the mitochondrial inhibitors suggests that previous work indicating regionally specific deficits following systemic mitochondrial toxin exposure may not be the result of differences in the individual mitochondria from the affected regions. PMID:21402103

  20. Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Isaac G Onyango

    2018-01-01

    Full Text Available Alzheimer's disease (AD is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

  1. Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Zhongbo Liu

    2018-01-01

    Full Text Available One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF that improved glucose utilization in high fat diet (HFD-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle. These data revealed that MGF increased glycolytic metabolites that were further augmented as glycolysis proceeded from the early to the late steps. Consistent with an MGF-stimulation of glycolytic flux there was a concomitant increase in the expression of enzymes catalyzing glycolysis. MGF also increased important metabolites in the tricarboxylic acid (TCA cycle, such as α-ketoglutarate and fumarate. Interestingly however, there was a reduction in succinate, a metabolite that also feeds into the electron transport chain to produce energy. MGF increased succinate clearance by enhancing the expression and activity of succinate dehydrogenase, leading to increased ATP production. At the transcriptional level, MGF induced mRNAs of mitochondrial genes and their transcriptional factors. Together, these data suggest that MGF upregulates mitochondrial oxidative capacity that likely drives the acceleration of glycolysis flux.

  2. The Evolution of the Bioenergetic Processes

    International Nuclear Information System (INIS)

    Broda, E.

    1976-01-01

    On the basis of an analysis of the bioenergetic processes in extant organisms, a hypothesis on their evolution is developed. It is suggested that the first organisms (bacteria) made useful energy (in the form of adenosine triphosphate, ATP) by (nonphotosynthetic) fermentation of components of the primeval oceans. The first photosynthesizers (also bacteria) used the energy of light only for the production of ATP. Later, processes were evolved through which the reducing power of sulfides, together with the energy stored in ATP, was used for the assimilation of C02. After the exhaustion of the sulfides, they were replaced as electron donors by water. This step was taken by the blue-green algae, and necessitated the use of 2 quanta in succession per electron. In the oxygenic atmosphere, due to the activities of the algae, respiration developed through conversion of the structures serving photosynthesis. All advanced organisms use respiration. In the higher cells, probably formed through endosymbiotic uptake of bacteria and blue-green algae, the mechanisms for photosynthesis and respiration are housed in separate compartments, namely mitochondria and chloroplasts, respectively. A plea is made for an intensified study of photosynthesis as a precondition of the use of photochemical method for the technical utilization of solar energy. (author)

  3. 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

  4. Microbial bioenergetics of coral-algal interactions

    Directory of Open Access Journals (Sweden)

    Ty N.F. Roach

    2017-06-01

    Full Text Available Human impacts are causing ecosystem phase shifts from coral- to algal-dominated reef systems on a global scale. As these ecosystems undergo transition, there is an increased incidence of coral-macroalgal interactions. Mounting evidence indicates that the outcome of these interaction events is, in part, governed by microbially mediated dynamics. The allocation of available energy through different trophic levels, including the microbial food web, determines the outcome of these interactions and ultimately shapes the benthic community structure. However, little is known about the underlying thermodynamic mechanisms involved in these trophic energy transfers. This study utilizes a novel combination of methods including calorimetry, flow cytometry, and optical oxygen measurements, to provide a bioenergetic analysis of coral-macroalgal interactions in a controlled aquarium setting. We demonstrate that the energetic demands of microbial communities at the coral-algal interaction interface are higher than in the communities associated with either of the macroorganisms alone. This was evident through higher microbial power output (energy use per unit time and lower oxygen concentrations at interaction zones compared to areas distal from the interface. Increases in microbial power output and lower oxygen concentrations were significantly correlated with the ratio of heterotrophic to autotrophic microbes but not the total microbial abundance. These results suggest that coral-algal interfaces harbor higher proportions of heterotrophic microbes that are optimizing maximal power output, as opposed to yield. This yield to power shift offers a possible thermodynamic mechanism underlying the transition from coral- to algal-dominated reef ecosystems currently being observed worldwide. As changes in the power output of an ecosystem are a significant indicator of the current state of the system, this analysis provides a novel and insightful means to quantify

  5. A bioenergetics systems evaluation of ketogenic diet liver effects.

    Science.gov (United States)

    Hutfles, Lewis J; Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Selfridge, J Eva; Tan, Eephie; Thyfault, John P; Slawson, Chad; Fenton, Aron W; Zhu, Hao; Swerdlow, Russell H

    2017-09-01

    Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

  6. PRECEDENCE AS A PSYCHOLINGUISTIC CATEGORY

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    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

  7. 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.

  8. Precedent Phenomena in Quebecois Linguistic World View

    Directory of Open Access Journals (Sweden)

    Ксения Эдуардовна Болотина

    2016-12-01

    Full Text Available This article is devoted to the linguocultural analysis of precedent phenomena as parts of Quebecois’ cognitive base. Precedent phenomena being cultural facts are one of the key issues in modern linguistic and cognitive studies. By precedent phenomena we mean, according to Y.E. Prohorov, such entities when verbalized in discourse that refer to a certain cultural fact behind them. In the article the precedent phenomena such as precedent text, precedent situation, precedent utterance, and precedent name are analyzed. The main theses of the precedence theory given in the article (Y.N. Karaulov, Y.E. Prohorov, V.V. Krasnyh, D.B. Gudkov are at the heart of precedence studies on the basis of different languages. However, a complex analysis of precedent phenomena in the Quebec national variant of French is new to Russian linguistics. The study of precedent phenomena enables us to elicit features of their functioning in ethnospecific discourse and determine cultural dominants existing in Quebecois’ linguistic world view. Given the fact that the size of the article is limited, we undertooke the analysis of eight phenomena precedent of the bearers of Quebec linguoculture. The choice of phenomena is determined by the frequency of their use in discourse. The facts analyzed are of national character, i.e. known to all members of the linguocultural community. A certain cultural fact is at the very core of each precedent phenomenon given in the article. To get the whole picture we analysed historic, political, and cultural context connected to the precedent phenomena in question. The study enables us to elicit distinctive features that are at the core of each phenomenon. The results are backed with the supportive material drawn from analysis of different types of discourse. The analysis of precedent phenomena undertaken in this article allows us to reconstruct, to a certain extent, Quebec cultural space and is a stepping stone to the reconstruction of the

  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. Precedent Names of Chinese National Culture

    Directory of Open Access Journals (Sweden)

    Валентина Алексеевна Ленинцева

    2015-12-01

    Full Text Available The article presents an analysis of precedent names as symbols of precedent phenomena in the material and spiritual culture of the Chinese. An evaluation of daily events and the attitude of the Chinese towards the world are reflected in the vocabulary of their language. The symbols of precedent phenomena can be proper names (anthroponomy, names of places, the date, as well as figurative and expressive means of language (idioms, sayings. Precedent names as symbols of precedent phenomena vividly and accurately capture the above-mentioned points, and encompass almost all spheres of life, history and spiritual development. The subject of our study are national precedent phenomena that define the ethno-cultural specificity, reflecting the history and culture of the Chinese people and their national character. Representatives of different cultures have different perceptions of the same precedent phenomena. Inadequate understanding of national invariants of precedent phenomena is often the source of communication failures. The aim of this paper is to highlight precedent names as a symbol of precedent phenomena in the discourse of the Chinese linguocultural community. For this purpose a classification of precedent names in Chinese was carried out. Precedent names which play an important role in shaping the Chinese national consciousness were taken from the Chinese-Russian Dictionary.

  12. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.

    Directory of Open Access Journals (Sweden)

    Lisa Mosconi

    Full Text Available After advanced age, female sex is the major risk factor for Alzheimer's disease (AD. The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15, perimenopause (PERI, n = 14 and postmenopause (MENO, n = 14. All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG-Positron Emission Tomography (PET FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's<0.001. A gradient in biomarker abnormalities was most pronounced in MENO, intermediate in PERI, and lowest in CNT (p<0.001. Biomarkers correlated with immediate and delayed memory scores (Pearson's 0.26≤r≤0.32, p≤0.05. These findings validate earlier preclinical findings and indicate emergence of bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that the optimal window of

  13. Caffeine and acetaminophen association: Effects on mitochondrial bioenergetics.

    Science.gov (United States)

    Gonçalves, Débora F; de Carvalho, Nelson R; Leite, Martim B; Courtes, Aline A; Hartmann, Diane D; Stefanello, Sílvio T; da Silva, Ingrid K; Franco, Jéferson L; Soares, Félix A A; Dalla Corte, Cristiane L

    2018-01-15

    Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice. Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30minutes, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated. Hepatic cellular oxygen consumption was evaluated by high-resolution respirometry (HRR). APAP treatment decreased cellular oxygen consumption and mitochondrial complex activities in the livers of mice. Additionally, treatment with APAP increased swelling of isolated mitochondria from mice livers. On the other hand, caffeine administered with APAP was able to improve hepatic mitochondrial bioenergetic function. Treatment with APAP increased lipid peroxidation and reactive oxygen species (ROS) production and decreased glutathione levels in the livers of mice. Caffeine administered with APAP was able to prevent lipid peroxidation and the ROS production in mice livers, which may be associated with the improvement of mitochondrial function caused by caffeine treatment. We suggest that the antioxidant effects of caffeine and/or its interactions with mitochondrial bioenergetics may be involved in its beneficial effects against APAP hepatotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

    Science.gov (United States)

    Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa S; Santos, Roberto C V; Leipnitz, Guilhian; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Baldisserotto, Bernardo

    2017-10-01

    It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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. © 2016 Elsevier Ltd. All rights reserved.

  16. Brown Adipose Tissue Bioenergetics: A New Methodological Approach

    Science.gov (United States)

    Calderon‐Dominguez, María; Alcalá, Martín; Sebastián, David; Zorzano, Antonio; Viana, Marta; Serra, Dolors

    2017-01-01

    The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b‐adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy. PMID:28435771

  17. Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research.

    Science.gov (United States)

    George, Mitchell J; Bynum, James; Nair, Prajeeda; Cap, Andrew P; Wade, Charles E; Cox, Charles S; Gill, Brijesh S

    2018-07-01

    The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction. Platelet function devices like thromboelastography, thromboelastometry, and aggregometry measure these biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the activity of antiplatelet drugs alters measures of platelet function. However, the specific mechanisms governing these alterations in platelet function and how they relate to platelet bioenergetics are still under investigation.

  18. 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...

  19. Rethinking Energy in Parkinsonian Motor Symptoms: A Potential Role for Neural Metabolic Deficits

    Directory of Open Access Journals (Sweden)

    Shinichi eAmano

    2015-01-01

    Full Text Available Parkinson’s disease (PD is characterized as a chronic and progressive neurodegenerative disorder that results in a variety of debilitating symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. Research spanning several decades has emphasized basal ganglia dysfunction, predominantly resulting from dopaminergic cell loss, as the primarily cause of the aforementioned parkinsonian features. But, why those particular features manifest themselves remains an enigma. The goal of this paper is to develop a theoretical framework that parkinsonian motor features are behavioral consequence of a long-term adaptation to their inability (inflexibility or lack of capacity to meet energetic demands, due to neural metabolic deficits arising from mitochondrial dysfunction associated with PD. Here, we discuss neurophysiological changes that are generally associated with PD, such as selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, in conjunction with metabolic and mitochondrial dysfunction. We then characterize the cardinal motor symptoms of PD, bradykinesia, resting tremor, rigidity and gait disturbance, reviewing literature to demonstrate how these motor patterns are actually energy efficient from a metabolic perspective. We will also develop three testable hypotheses: (1 neural metabolic deficits precede the increased rate of neurodegeneration and onset of behavioral symptoms in PD, (2 motor behavior of persons with PD are more sensitive to changes in metabolic/bioenergetic state, and (3 improvement of metabolic function could lead to better motor performance in persons with PD. These hypotheses are designed to introduce a novel viewpoint that can elucidate the connections between metabolic, neural and motor function in PD.

  20. Syntactic Idioms and Precedent Phenomena: Intersection Zones

    Directory of Open Access Journals (Sweden)

    Hanna Sytar

    2016-08-01

    Full Text Available Background: One examined mainly structural and semantic features of syntactic idioms so far. The pragmatic dimension of these original units that are on the verge of syntax and phraseology, has not been highlighted properly in the scientific literature, so it needs theoretical understanding. The combination of syntactic idiom and phraseological phenomenon refers to the communication techniques impacting on message recipient. Purpose: to analyze the intersection zones of syntactic idioms and precedent phenomena. Results: Analysis of the collected factual material allows to distinguish two areas of interpenetration of syntactic idioms and precedent units: 1 construction of expression according to the phraseologized model, within which the position of variable component is filled by the precedent name or precedent expression; 2 the model of sentence itself is precedent, and lexical content does not comply with generally known one that does not affect on understanding of model content by recipient. With a combination of syntactic idiom and precedent phenomena speakers provide drawing of recipients’ attention, carry out a hidden influence on them, express their own attitude to the realities, so that perform phatic, manipulative and expressive-evaluative functions. The modifications and transformations of precedent expressions and names appeared to be regular in such interpenetrations. Discussion: The obtained results reflect the general trend towards transform (transformation, modification, variation, etc. of precedent, as well as phraseological units, and can be used for the analysis of patterns of their formation and modifications. Further research phase implies tracing patterns of syntactic idioms combination with other means of expressive syntax.

  1. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. Mandatory Vaccinations: Precedent and Current Laws

    National Research Council Canada - National Science Library

    Welborn, Angie A

    2005-01-01

    This report discusses the history legal precedent for mandatory vaccination laws and provides a brief overview of state laws that require certain individuals or populations to be vaccinated against...

  6. 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.

  7. Mitochondrial bioenergetics decay in aging: beneficial effect of melatonin.

    Science.gov (United States)

    Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

    2017-11-01

    Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.

  8. The Bioenergetic Health Index: a new concept in mitochondrial translational research.

    Science.gov (United States)

    Chacko, Balu K; Kramer, Philip A; Ravi, Saranya; Benavides, Gloria A; Mitchell, Tanecia; Dranka, Brian P; Ferrick, David; Singal, Ashwani K; Ballinger, Scott W; Bailey, Shannon M; Hardy, Robert W; Zhang, Jianhua; Zhi, Degui; Darley-Usmar, Victor M

    2014-09-01

    Bioenergetics has become central to our understanding of pathological mechanisms, the development of new therapeutic strategies and as a biomarker for disease progression in neurodegeneration, diabetes, cancer and cardiovascular disease. A key concept is that the mitochondrion can act as the 'canary in the coal mine' by serving as an early warning of bioenergetic crisis in patient populations. We propose that new clinical tests to monitor changes in bioenergetics in patient populations are needed to take advantage of the early and sensitive ability of bioenergetics to determine severity and progression in complex and multifactorial diseases. With the recent development of high-throughput assays to measure cellular energetic function in the small number of cells that can be isolated from human blood these clinical tests are now feasible. We have shown that the sequential addition of well-characterized inhibitors of oxidative phosphorylation allows a bioenergetic profile to be measured in cells isolated from normal or pathological samples. From these data we propose that a single value-the Bioenergetic Health Index (BHI)-can be calculated to represent the patient's composite mitochondrial profile for a selected cell type. In the present Hypothesis paper, we discuss how BHI could serve as a dynamic index of bioenergetic health and how it can be measured in platelets and leucocytes. We propose that, ultimately, BHI has the potential to be a new biomarker for assessing patient health with both prognostic and diagnostic value.

  9. INTEGRATED APPROACH TO GENERATION OF PRECEDENCE RELATIONS AND PRECEDENCE GRAPHS FOR ASSEMBLY SEQUENCE PLANNING

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An integrated approach to generation of precedence relations and precedence graphs for assembly sequence planning is presented, which contains more assembly flexibility. The approach involves two stages. Based on the assembly model, the components in the assembly can be divided into partially constrained components and completely constrained components in the first stage, and then geometric precedence relation for every component is generated automatically. According to the result of the first stage, the second stage determines and constructs all precedence graphs. The algorithms of these two stages proposed are verified by two assembly examples.

  10. 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

  11. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    Science.gov (United States)

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519

  12. 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.

  13. Page JUDICIAL PRECEDENT IN THE NIGERIAN LEGAL SYSTEM

    African Journals Online (AJOL)

    Fr. Ikenga

    Judicial precedent is a basic principle of the administration of justice in .... precedent assume a natural position that is not different from any other ... L. Alexander, Precedent in a Companion to Philosophy of Law and Legal Theory 503-513,.

  14. Cochlear contributions to the precedence effect

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Bianchi, Federica; Dau, Torsten

    2013-01-01

    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...... of the precedence effect....

  15. 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

  16. Ontogeny of muscle bioenergetics in Adelie penguin chicks (Pygoscelis adeliae).

    Science.gov (United States)

    Fongy, Anaïs; Romestaing, Caroline; Blanc, Coralie; Lacoste-Garanger, Nicolas; Rouanet, Jean-Louis; Raccurt, Mireille; Duchamp, Claude

    2013-11-01

    The ontogeny of pectoralis muscle bioenergetics was studied in growing Adélie penguin chicks during the first month after hatching and compared with adults using permeabilized fibers and isolated mitochondria. With pyruvate-malate-succinate or palmitoyl-carnitine as substrates, permeabilized fiber respiration markedly increased during chick growth (3-fold) and further rose in adults (1.4-fold). Several markers of muscle fiber oxidative activity (cytochrome oxidase, citrate synthase, hydroxyl-acyl-CoA dehydrogenase) increased 6- to 19-fold with age together with large rises in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial content (3- to 5-fold) and oxidative activities (1.5- to 2.4-fold). The proportion of IMF relative to SS mitochondria increased with chick age but markedly dropped in adults. Differences in oxidative activity between mitochondrial fractions were reduced in adults compared with hatched chicks. Extrapolation of mitochondrial to muscle respirations revealed similar figures with isolated mitochondria and permeabilized fibers with carbohydrate-derived but not with lipid-derived substrates, suggesting diffusion limitations of lipid substrates with permeabilized fibers. Two immunoreactive fusion proteins, mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), were detected by Western blots on mitochondrial extracts and their relative abundance increased with age. Muscle fiber respiration was positively related with Mfn2 and OPA1 relative abundance. Present data showed by two complementary techniques large ontogenic increases in muscle oxidative activity that may enable birds to face thermal emancipation and growth in childhood and marine life in adulthood. The concomitant rise in mitochondrial fusion protein abundance suggests a role of mitochondrial networks in the skeletal muscle processes of bioenergetics that enable penguins to overcome harsh environmental constraints.

  17. Bioenergetics of lung tumors: Alteration of mitochondrial biogenesis and respiratory kapacity

    Czech Academy of Sciences Publication Activity Database

    Bellance, N.; Benard, G.; Furt, F.; Begueret, H.; Smolková, Katarína; Passerieux, E.; Delage, J.P.; Baste, J.M.; Moreau, P.; Rossignol, R.

    2009-01-01

    Roč. 41, č. 12 (2009), s. 2566-2577 ISSN 1357-2725 Institutional research plan: CEZ:AV0Z50110509 Keywords : tumors * bioenergetics * biogenesis Subject RIV: ED - Physiology Impact factor: 4.887, year: 2009

  18. 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 ...

  19. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    OpenAIRE

    Noa Kirschner Peretz; Sofia Segal; Limor Arbel-Ganon; Ronen Ben Jehuda; Ronen Ben Jehuda; Yuval Shemer; Yuval Shemer; Binyamin Eisen; Binyamin Eisen; Moran Davoodi; Ofer Binah; Ofer Binah; Yael Yaniv

    2017-01-01

    Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM), which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells w...

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

    OpenAIRE

    Huber, Heinrich J.; Dussmann, Heiko; Kilbride, Sean M.; Rehm, Markus; Prehn, Jochen H. M.

    2011-01-01

    How can cells cope with a bioenergetic crisis? In particular, how can cancer cells survive the bioenergetic consequences of cyt-c release that are often induced by chemotherapeutic agents, and that lead to depolarisation of the mitochondrial membrane potential ΔΨm, result in loss of ionic homeostasis and induce cell death? Is there an inherent population heterogeneity that can lead to a non-synchronous response to above cell death stimuli, thereby aggravating treatment and contributing to cli...

  1. Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

    DEFF Research Database (Denmark)

    Hopkinson, Branden M; Madsen, Claus Desler; Kalisz, Mark

    2017-01-01

    Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells...... of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction...

  2. [The mechanism of phenoptosis: 2. Hayflick limit is caused by the programmed attenuation of bioenergetics].

    Science.gov (United States)

    Trubitsin, A G

    2010-01-01

    This article continues earlier started theme on a substantiation of the programmed aging mechanism (phenoptosis). The concept underlying this mechanism is that the life represents a lot of the interconnected physical and chemical processes moving by the bioenergetics. The gradual programmed decrease of the level of bioenergetics causes the slow and coordinated attenuation of all physiological functions, i.e. aging. For a convincing substantiation of such mechanism it is necessary to show, how attenuation of bioenergetics causes the basic nocuous processes accompanying aging. It is shown earlier that the age dependent decrease in level of bioenergetics causes increase in production of reactive oxygen species by mitochondria and decrease in overall level of protein synthesis. The proof that Hayflick limit is also caused by the decrease in level of bioenergetics is presented in this article. Decrease in level of bioenergetics below certain critical level deprives a cell the ability to pass the restriction point of G1-phase of proliferative cycle. The inhibitor of cyclin-dependent kinase, p27, prevents the passage through this critical point in all normal cells. During division of normal somatic cells p27 is removed by cyclin E-Cdk2 complex. Interaction p27 with cyclin E-Cdk2 complex can have two consequences. At the normal physiological level of bioenergetics the cyclin E-Cdk2 phosphorylates p27, then the latter is destroyed by proteolytic enzymes--the cell enters in S-phase. When the programme decreases the bioenergetics level below certain value the cyclin E-Cdk2 becomes the target for p27. As a result the inhibitor evacuation stops and restriction point becomes closed--a cell enters irreversible proliferative rest.

  3. Safe specification of operator precedence rules

    NARCIS (Netherlands)

    Afroozeh, A.; Brand, van den M.G.J.; Johnstone, A.; Scott, E.; Vinju, J.J.; Erwig, M.; Paige, R.F.; Van Wyk, E.

    2013-01-01

    In this paper we present an approach to specifying operator precedence based on declarative disambiguation constructs and an implementation mechanism based on grammar rewriting. We identify a problem with existing generalized context-free parsing and disambiguation technology: generating a correct

  4. Safe Specification of Operator Precedence Rules

    NARCIS (Netherlands)

    A. Afroozeh (Ali); M.G.J. van den Brand (Mark); A. Johnstone; E. Scott; J.J. Vinju (Jurgen); K. Czarnecki; G. Hedin

    2013-01-01

    htmlabstractIn this paper we present an approach to specifying opera- tor precedence based on declarative disambiguation constructs and an implementation mechanism based on grammar rewriting. We identify a problem with existing generalized context-free parsing and disambigua- tion technology:

  5. A new approach to sperm preservation based on bioenergetic theory.

    Science.gov (United States)

    Froman, D P; Feltmann, A J

    2010-04-01

    To date, attempts to preserve chicken sperm have been based on a trial-and-error experimental approach. The present work outlines the development of an alternative approach based on empiricism and bioenergetic theory. In previous work, we found fowl sperm motility to be dependent on mitochondrial calcium cycling, phospholipase A(2), and long-chain fatty acids as an endogenous energy source. It is noteworthy that fowl sperm reside within the sperm storage tubules (SST) of the oviduct over an interval of days to weeks after insemination. In this regard, a model for in vivo sperm storage was developed and tested in additional previous research. Sperm penetration of the SST, sperm residence within the SST, and sperm egress from the SST can be explained in terms mitochondrial function. Understanding sperm function and longevity in terms of bioenergetics presented the possibility that sperm could be inactivated by disrupting mitochondrial calcium cycling and could thereby be preserved. However, this possibility also posed a problem: maintenance of the inner membrane potential of the mitochondrion within inactivated sperm. This report describes a series of experiments in which fowl sperm were inactivated by treatment with the calcium chelator tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, and then reactivated by treatment with calcium ions. The effect of tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid on mitochondrial calcium cycling was confirmed by flow cytometry and confocal microscopy. When treated sperm were cooled to 10 degrees C, inactivated sperm could be reactivated throughout a 5-h storage interval. When stored sperm were held for 3 h before reactivation and insemination, fertility was 88% of the control. Storage did not affect hatchability. In summary, short-term storage was realized by manipulating mitochondrial function. We propose that 1) complex V consumes ATP within inactivated sperm and, by doing so, maintains

  6. Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults

    Directory of Open Access Journals (Sweden)

    Emily K. Calton

    2016-12-01

    Conclusions: Inadequate vitamin D status adversely influenced bioenergetic parameters of PBMCs obtained from adults, in a pattern consistent with increased oxidative metabolism and activation of these cells.

  7. Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention.

    Directory of Open Access Journals (Sweden)

    Mingming Yang

    Full Text Available Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.

  8. Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages

    Directory of Open Access Journals (Sweden)

    Bryan J. Neth

    2017-10-01

    Full Text Available Metabolic dysfunction is a well-established feature of Alzheimer’s disease (AD, evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D, hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. This association may in part be due to the systemic mitochondrial dysfunction that is common to these pathologies. Accumulating evidence suggests that mitochondrial dysfunction is a significant feature of AD and may play a fundamental role in its pathogenesis. In fact, aging itself presents a unique challenge due to inherent mitochondrial dysfunction and prevalence of chronic metabolic disease. Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.

  9. 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.

  10. Oral lichen planus preceding concomitant lichen planopilaris.

    Science.gov (United States)

    Stoopler, Eric T; Alfaris, Sausan; Alomar, Dalal; Alawi, Faizan

    2016-09-01

    Lichen planus (LP) is an immune-mediated mucocutaneous disorder with a wide array of clinical presentations. Oral lichen planus (OLP) is characterized clinically by striae, desquamation, and/or ulceration. Lichen planopilaris (LPP), a variant of LP, affects the scalp, resulting in perifollicular erythema and scarring of cutaneous surfaces accompanied by hair loss. The association between OLP and LPP has been reported previously with scant information on concomitant or sequential disease presentation. We describe a patient with concomitant OLP and LPP, and to the best of our knowledge, this is the first report on OLP preceding the onset of LPP. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Bioenergetic Profile Experiment using C2C12 Myoblast Cells

    Science.gov (United States)

    Nicholls, David G.; Darley-Usmar, Victor M.; Wu, Min; Jensen, Per Bo; Rogers, George W.; Ferrick, David A.

    2010-01-01

    The ability to measure cellular metabolism and understand mitochondrial dysfunction, has enabled scientists worldwide to advance their research in understanding the role of mitochondrial function in obesity, diabetes, aging, cancer, cardiovascular function and safety toxicity. Cellular metabolism is the process of substrate uptake, such as oxygen, glucose, fatty acids, and glutamine, and subsequent energy conversion through a series of enzymatically controlled oxidation and reduction reactions. These intracellular biochemical reactions result in the production of ATP, the release of heat and chemical byproducts, such as lactate and CO2 into the extracellular environment. Valuable insight into the physiological state of cells, and the alteration of the state of those cells, can be gained through measuring the rate of oxygen consumed by the cells, an indicator of mitochondrial respiration - the Oxygen Consumption Rate - or OCR. Cells also generate ATP through glycolysis, i.e.: the conversion of glucose to lactate, independent of oxygen. In cultured wells, lactate is the primary source of protons. Measuring the lactic acid produced indirectly via protons released into the extracellular medium surrounding the cells, which causes acidification of the medium provides the Extra-Cellular Acidification Rate - or ECAR. In this experiment, C2C12 myoblast cells are seeded at a given density in Seahorse cell culture plates. The basal oxygen consumption (OCR) and extracellular acidification (ECAR) rates are measured to establish baseline rates. The cells are then metabolically perturbed by three additions of different compounds (in succession) that shift the bioenergetic profile of the cell. This assay is derived from a classic experiment to assess mitochondria and serves as a framework with which to build more complex experiments aimed at understanding both physiologic and pathophysiologic function of mitochondria and to predict the ability of cells to respond to stress and

  12. 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.

  13. 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.

  14. Bio-energetic rehabilitation of human health with use of therapeutic fasting

    International Nuclear Information System (INIS)

    Kechutkina, E.M.; Inyushin, V.M.; Asanov, D.R.

    2000-01-01

    The work devoted to study of mothers' and children's coming from ecologically unfavorable regions rehabilitation measures effectiveness and health improvement in condition of sanatorium-resort conditions. Comprehensive approach was developed in this direction. The approach includes of bio-energetic, psychologic, clearing measures in combination with weight-out faltering and observation of health status with help of electro-physiological methods. In result of conducted study and following analysis positive influence of hunger (in complex with resonance photoactivation bio-energetic excesses, psycho-training) process of bio-energetic rehabilitation of human health. It is concluded that most powerful energizing of reserve opportunities of body takes place at complete refusal from food and transition on internal nourishment (endogenous) that was confirm at 7-day festering by indexes of homeostasis shift

  15. 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.

  16. Bioenergetics modeling of the annual consumption of zooplankton by pelagic fish feeding in the Northeast Atlantic

    DEFF Research Database (Denmark)

    Bachiller, Eneko; Utne, Kjell Rong; Jansen, Teunis

    2018-01-01

    The present study uses bioenergetics modeling to estimate the annual consumption of the main zooplankton groups by some of the most commercially important planktivorous fish stocks in the Northeast Atlantic, namely Norwegian spring-spawning (NSS) herring (Clupea harengus), blue whiting (Micromesi......The present study uses bioenergetics modeling to estimate the annual consumption of the main zooplankton groups by some of the most commercially important planktivorous fish stocks in the Northeast Atlantic, namely Norwegian spring-spawning (NSS) herring (Clupea harengus), blue whiting...

  17. [Wide QRS tachycardia preceded by pacemaker spikes].

    Science.gov (United States)

    Romero, M; Aranda, A; Gómez, F J; Jurado, A

    2014-04-01

    The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  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

    International Nuclear Information System (INIS)

    Alsuwaidi, Ahmed R.; Albawardi, Alia; Almarzooqi, Saeeda; Benedict, Sheela; Othman, Aws R.; Hartwig, Stacey M.; Varga, Steven M.; Souid, Abdul-Kader

    2014-01-01

    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 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. Late-onset Alzheimer's disease is associated with inherent changes in bioenergetics profiles.

    Science.gov (United States)

    Sonntag, Kai-C; Ryu, Woo-In; Amirault, Kristopher M; Healy, Ryan A; Siegel, Arthur J; McPhie, Donna L; Forester, Brent; Cohen, Bruce M

    2017-10-25

    Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal aging and disturbed bioenergetics may be an important contributing mechanism underlying late-onset Alzheimer's disease (LOAD). We investigated the bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as a function of age and disease. LOAD cells exhibited an impaired mitochondrial metabolic potential and an abnormal redox potential, associated with reduced nicotinamide adenine dinucleotide metabolism and altered citric acid cycle activity, but not with disease-specific changes in mitochondrial mass, production of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD fibroblasts demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to IGF-1. The increase of glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to be inherent, as they were disease- and not age-specific. Our findings support the hypothesis that impairment in multiple interacting components of bioenergetic metabolism may be a key mechanism contributing to the risk and pathophysiology of LOAD.

  1. 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.

  2. Bioenergetic components of reproductive effort in viviparous snakes: costs of vitellogenesis exceed costs of pregnancy.

    Science.gov (United States)

    Van Dyke, James U; Beaupre, Steven J

    2011-12-01

    Reproductive effort has been defined as the proportion of an organism's energy budget that is allocated to reproduction over a biologically meaningful time period. Historically, studies of reproductive bioenergetics considered energy content of gametes, but not costs of gamete production. Although metabolic costs of vitellogenesis (MCV) fundamentally reflect the primary bioenergetic cost of reproductive allocation in female reptiles, the few investigations that have considered costs of reproductive allocation have focused on metabolic costs of pregnancy (MCP) in viviparous species. We define MCP as energetic costs incurred by pregnant females, including all costs of maintaining gestation conditions necessary for embryogenesis. MCP by our definition do not include fetal costs of embryogenesis. We measured metabolic rates in five species of viviparous snakes (Agkistrodon contortrix, Boa constrictor, Eryx colubrinus, Nerodia sipedon, and Thamnophis sirtalis) during vitellogenesis and pregnancy in order to estimate MCV and MCP. Across all species, MCV were responsible for 30% increases in maternal metabolism. Phylogenetically-independent contrasts showed that MCV were significantly greater in B. constrictor than in other species, likely because B. constrictor yolk energy content was greater than that of other species. Estimates of MCP were not significantly different from zero in any species. In viviparous snakes, MCV appear to represent significant bioenergetic expenditures, while MCP do not. We suggest that MCV, together with yolk energy content, represent the most significant component of reptilian reproductive effort, and therefore deserve greater attention than MCP in studies of reptilian reproductive bioenergetics. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. 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--> ...

  4. 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.

  5. Measuring the bioenergetic cost of fish activity in situ using a globally dispersed radiotracer (137Cs)

    International Nuclear Information System (INIS)

    Rowan, D.J.; Rasmussen, J.B.

    1996-01-01

    The energetic cost of activity is an important component of the bioenergetic budget of fish, yet this parameter has rarely been quantified for wild populations. Using a 137 Cs mass balance approach, we estimated the annual bioenergetic budgets for individual age-classes of 19 species of North American freshwater fish. Immature fish have low activity-related metabolic costs that agree with estimates based on swimming speed or integer multipliers. Mature fish have 2- to 4-fold higher activity than immature fish and 2- to 4-fold higher activity than estimates based on swimming speed or integer multipliers. The higher activity in mature fish may be due to reproductive efforts. Underestimation of activity in conventional bioenergetics models leads to underestimation of consumption rates. Thus, our in situ and age-specific estimates of activity costs provide a means to improve bioenergetic predictions. Although our analysis was done on an annual basis, it is possible to use the 137 Cs technique over shorter intervals (weeks). The 137 Cs method has general applicability to aquatic systems because 137 Cs is globally dispersed and can be accurately measured in all aquatic organisms using gamma spectrometry. (author). 62 refs., 4 tabs., 4 figs

  6. Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Emily K. Calton

    2017-08-01

    Full Text Available Background: Vitamin D status [25(OHD] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs. No study has tracked the seasonal variation of 25(OHD and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Material and methods: Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test was performed using the Seahorse XFe96 flux analyser. 25(OHD was assessed using the Architect immunoassay method. Results: 25(OHD increased by a median (IQR of 14.40 (20.13 nmol/L (p75 nmol/L. The absolute change in 25(OHD was not associated with altered bioenergetics. Conclusion: Seasonal improvements in 25(OHD was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OHD in winter. The data warrants confirmation through cause and effect study designs. Keywords: Peripheral blood mononuclear cells, Bioenergetics, Vitamin D, Season, Inflammation, Insulin sensitivity

  7. 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

  8. Segmentation precedes face categorization under suboptimal conditions

    Directory of Open Access Journals (Sweden)

    Carlijn eVan Den Boomen

    2015-05-01

    Full Text Available Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG. Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  9. NEIGHBORHOOD TEST DESIGN BASED ON HISTORIC PRECEDENTS

    Directory of Open Access Journals (Sweden)

    Besim S. Hakim

    2012-07-01

    Full Text Available There have been various attempts to emulate traditional architecture and to experiment with the form and aesthetics of building design. However, learning from precedents of urban morphology is rare. This design study is a test at the neighborhood level using the pattern of traditional courtyard housing that is prevalent in the majority of historic towns and cities of North Africa and the Middle East. The study is undertaken at five levels of design enquiry: dwelling types, dwelling groups, neighborhood segment and community center. All of which are synthesized into a full prototype neighborhood comprising of 428 dwelling units covering an area that includes circulation and the community center, of 17.6 hectares. The test demonstrates that the traditional pattern of neighborhoods that are based on the typology of the courtyard dwelling as the initial generator of urban form may be used to develop a contemporary settlement pattern that is compatible with current necessities of lifestyle, vehicular circulation,  including parking and infrastructure achieving an attractive livable environment with an overall gross density, that includes a community center, of about 24 dwelling units per hectare.

  10. Segmentation precedes face categorization under suboptimal conditions.

    Science.gov (United States)

    Van Den Boomen, Carlijn; Fahrenfort, Johannes J; Snijders, Tineke M; Kemner, Chantal

    2015-01-01

    Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  11. Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration.

    Science.gov (United States)

    Laliberté, Alex M; MacPherson, Thomas C; Micks, Taft; Yan, Alex; Hill, Kathleen A

    2011-12-01

    Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p retina (p retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

    Science.gov (United States)

    Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

    2016-04-01

    Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress and influence of mutation-type.

    Directory of Open Access Journals (Sweden)

    Katie Richardson

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. Substantial evidence implicates oxidative stress and mitochondrial dysfunction as early events in disease progression. Our aim was to ascertain whether mutation of the SOD1 protein increases metabolic functional susceptibility to oxidative stress. Here we used a motor neuron-like cell line (NSC34 stably transfected with various human mutant SOD1 transgenes (G93A, G37R, H48Q to investigate the impact of oxidative stress on cell viability and metabolic function within intact cells. NSC34 cells expressing mutant SOD1 showed a dose dependent reduction in cell viability when exposed to oxidative stress induced by hydrogen peroxide, with variation between mutations. The G93A transfectants showed greater cell death and LDH release compared to cells transfected with the other SOD1 mutations, and H48Q showed an accelerated decline at later time points. Differences in mitochondrial bioenergetics, including mitochondrial respiration, coupling efficiency and proton leak, were identified between the mutations, consistent with the differences observed in viability. NSC34 cells expressing G93A SOD1 displayed reduced coupled respiration and mitochondrial membrane potential compared to controls. Furthermore, the G93A mutation had significantly increased metabolic susceptibility to oxidative stress, with hydrogen peroxide increasing ROS production, reducing both cellular oxygen consumption and glycolytic flux in the cell. This study highlights bioenergetic defects within a cellular model of ALS and suggests that oxidative stress is not only detrimental to oxygen consumption but also glycolytic flux, which could lead to an energy deficit in the cell.

  14. Can monaural temporal masking explain the ongoing precedence effect?

    Science.gov (United States)

    Freyman, Richard L; Morse-Fortier, Charlotte; Griffin, Amanda M; Zurek, Patrick M

    2018-02-01

    The precedence effect for transient sounds has been proposed to be based primarily on monaural processes, manifested by asymmetric temporal masking. This study explored the potential for monaural explanations with longer ("ongoing") sounds exhibiting the precedence effect. Transient stimuli were single lead-lag noise burst pairs; ongoing stimuli were trains of 63 burst pairs. Unlike with transients, monaural masking data for ongoing sounds showed no advantage for the lead, and are inconsistent with asymmetric audibility as an explanation for ongoing precedence. This result, along with supplementary measurements of interaural time discrimination, suggests different explanations for transient and ongoing precedence.

  15. 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.

  16. 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

  17. Power Measures and Solutions for Games Under Precedence Constraints

    NARCIS (Netherlands)

    Algaba, Encarnación; van den Brink, René; Dietz, Chris

    2017-01-01

    Games under precedence constraints model situations, where players in a cooperative transferable utility game belong to some hierarchical structure, which is represented by an acyclic digraph (partial order). In this paper, we introduce the class of precedence power solutions for games under

  18. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 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.

  20. First principles design of a core bioenergetic transmembrane electron-transfer protein

    Energy Technology Data Exchange (ETDEWEB)

    Goparaju, Geetha; Fry, Bryan A.; Chobot, Sarah E.; Wiedman, Gregory; Moser, Christopher C.; Leslie Dutton, P.; Discher, Bohdana M.

    2016-05-01

    Here we describe the design, Escherichia coli expression and characterization of a simplified, adaptable and functionally transparent single chain 4-α-helix transmembrane protein frame that binds multiple heme and light activatable porphyrins. Such man-made cofactor-binding oxidoreductases, designed from first principles with minimal reference to natural protein sequences, are known as maquettes. This design is an adaptable frame aiming to uncover core engineering principles governing bioenergetic transmembrane electron-transfer function and recapitulate protein archetypes proposed to represent the origins of photosynthesis. 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. Complexity Analysis of Precedence Terminating Infinite Graph Rewrite Systems

    Directory of Open Access Journals (Sweden)

    Naohi Eguchi

    2015-05-01

    Full Text Available The general form of safe recursion (or ramified recurrence can be expressed by an infinite graph rewrite system including unfolding graph rewrite rules introduced by Dal Lago, Martini and Zorzi, in which the size of every normal form by innermost rewriting is polynomially bounded. Every unfolding graph rewrite rule is precedence terminating in the sense of Middeldorp, Ohsaki and Zantema. Although precedence terminating infinite rewrite systems cover all the primitive recursive functions, in this paper we consider graph rewrite systems precedence terminating with argument separation, which form a subclass of precedence terminating graph rewrite systems. We show that for any precedence terminating infinite graph rewrite system G with a specific argument separation, both the runtime complexity of G and the size of every normal form in G can be polynomially bounded. As a corollary, we obtain an alternative proof of the original result by Dal Lago et al.

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

    Science.gov (United States)

    2015-05-01

    AWARD NUMBER: W81XWH-13-1-0149 TITLE: “Real-Time Measurement of Host Bioenergetics During Mycobacterium Tuberculosis Infection...successfully adapted metabolic flux analysis using a Seahorse XF96 metabolic flux analyzer to study Mycobacterium tuberculosis energy metabolism in an...Mycobacterium tuberculosis function. In: Systems Biology of Tuberculosis . Editors: J McFadden, D Beste and A Kierzek. 2013. Springer, New York, NY. 2

  3. 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.

  4. Bioenergetic reprogramming plasticity under nitrogen depletion by the unicellular green alga Scenedesmus obliquus.

    Science.gov (United States)

    Papazi, Aikaterini; Korelidou, Anna; Andronis, Efthimios; Parasyri, Athina; Stamatis, Nikolaos; Kotzabasis, Kiriakos

    2018-03-01

    Simultaneous nitrogen depletion and 3,4-dichlorophenol addition induce a bioenergetic microalgal reprogramming, through strong Cyt b 6 f synthesis, that quench excess electrons from dichlorophenol's biodegradation to an overactivated photosynthetic electron flow and H 2 -productivity. Cellular energy management includes "rational" planning and operation of energy production and energy consumption units. Microalgae seem to have the ability to calculate their energy reserves and select the most profitable bioenergetic pathways. Under oxygenic mixotrophic conditions, microalgae invest the exogenously supplied carbon source (glucose) to biomass increase. If 3,4-dichlorophenol is added in the culture medium, then glucose is invested more to biodegradation rather than to growth. The biodegradation yield is enhanced in nitrogen-depleted conditions, because of an increase in the starch accumulation and a delay in the establishment of oxygen-depleted conditions in a closed system. In nitrogen-depleted conditions, starch cannot be invested in PSII-dependent and PSII-independent pathways for H 2 -production, mainly because of a strong decrease of the cytochrome b 6 f complex of the photosynthetic electron flow. For this reason, it seems more profitable for the microalga under these conditions to direct the metabolism to the synthesis of lipids as cellular energy reserves. Nitrogen-depleted conditions with exogenously supplied 3,4-dichlorophenol induce reprogramming of the microalgal bioenergetic strategy. Cytochrome b 6 f is strongly synthesized (mainly through catabolism of polyamines) to manage the electron bypass from the dichlorophenol biodegradation procedure to the photosynthetic electron flow (at the level of PQ pool) and consequently through cytochrome b 6 f and PSI to hydrogenase and H 2 -production. All the above showed that the selection of the appropriate cultivation conditions is the key for the manipulation of microalgal bioenergetic strategy that leads to

  5. Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation.

    Science.gov (United States)

    Connolly, Niamh M C; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen H M

    2014-07-30

    Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, and subsequent neuronal injury. We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contribution of effects of non-neuronal cells. Hence, we here characterized bioenergetics during transient excitotoxicity in rat and mouse primary neurons at the single-cell level using fluorescent sensors for intracellular glucose, ATP, and activation of the energy sensor AMP-activated protein kinase (AMPK). We identified ATP depletion and recovery to energetic homeostasis, along with AMPK activation, as surprisingly rapid and plastic responses in two excitotoxic injury paradigms. We observed rapid recovery of neuronal ATP levels also in the absence of extracellular glucose, or when glycolytic ATP production was inhibited, but found mitochondria to be critical for fast and complete energetic recovery. Using an injury model of oxygen and glucose deprivation, we identified a similarly rapid bioenergetics response, yet with incomplete ATP recovery and decreased AMPK activity. Interestingly, excitotoxicity also induced an accumulation of intracellular glucose, providing an additional source of energy during and after excitotoxicity-induced energy depletion. We identified this to originate from extracellular, AMPK-dependent glucose uptake and from intracellular glucose mobilization. Surprisingly, cells recovering their elevated glucose levels faster to baseline survived longer, indicating that the plasticity of neurons to adapt to bioenergetic challenges is a key indicator of neuronal viability. Copyright © 2014 the authors 0270-6474/14/3410192-14$15.00/0.

  6. Single-Cell Imaging of Bioenergetic Responses to Neuronal Excitotoxicity and Oxygen and Glucose Deprivation

    OpenAIRE

    Connolly, Niamh M; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen HM

    2014-01-01

    Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca2+/Na+ influx into neurons, energetic stress, and subsequent neuronal injury.We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contributio...

  7. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    Directory of Open Access Journals (Sweden)

    Noa Kirschner Peretz

    2017-08-01

    Full Text Available Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM, which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells were maintained in culture for 24 h in a medium enriched with a myofilament contraction inhibitor, BDM. The morphology and volume of the cells, including their ability to contract in response to 1–3 Hz electrical pacing, was maintained at the same level as fresh cells. Importantly, the cells could be successfully infected with a GFP adenovirus. Action potentials, Ca2+ transients, and local Ca2+ spark parameters were similar in the cultured and in fresh cells. Finally, these cultured cells' flavoprotein autofluorescence was maintained at a constant level in response to electrical pacing, a response similar to that of fresh cells. Thus, eliminating contraction during the culture period preserves the bioelectric, biophysical and bioenergetic properties of rabbit atrial myocytes. This method therefore has the potential to further improve our understanding of energetic and biochemical regulation in the atria.

  8. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

    Science.gov (United States)

    Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

    2017-09-01

    Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons

    Directory of Open Access Journals (Sweden)

    Matthew Redmann

    2017-04-01

    Full Text Available Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics. To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. We found that both bafilomycin and chloroquine could significantly increase the autophagosome marker LC3-II and inhibit key parameters of mitochondrial function, and increase mtDNA damage. Furthermore, we observed significant alterations in TCA cycle intermediates, particularly those downstream of citrate synthase and those linked to glutaminolysis. Taken together, these data demonstrate a significant impact of bafilomycin and chloroquine on cellular bioenergetics and metabolism consistent with decreased mitochondrial quality associated with inhibition of autophagy.

  11. 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 pestle homogenization protocol is the technique of choice for studying bioenergetic enzyme activity in skeletal muscle.

  12. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

    Science.gov (United States)

    Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

    2017-01-01

    The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

  13. Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

    Science.gov (United States)

    Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

    2017-07-01

    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

    Science.gov (United States)

    Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

    2013-10-15

    Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

  15. Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

    Science.gov (United States)

    Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

    2013-01-01

    Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

  16. 10 CFR 205.11 - Order of precedence.

    Science.gov (United States)

    2010-01-01

    ... precedence. (a) If there is any conflict or inconsistency between the provisions of this part and any other... prenotification and reporting and subpart J of part 212 of this chapter shall control with respect to accounting...

  17. Routing Cooperating Vehicles to Perform Precedence-Linked Tasks

    National Research Council Canada - National Science Library

    Vakhutinsky, Andrew; Wu, Cynara

    2005-01-01

    The problem of scheduling cooperating vehicles is a generalization of the classical vehicle routing problem where certain tasks are linked by precedence constraints and vehicles have varying constrained resources...

  18. Ludic Function of Precedent-Related Phenomena in Media Discourse

    Directory of Open Access Journals (Sweden)

    Yu. M. Velykoroda

    2016-12-01

    Full Text Available The aim of this paper is to determine the ludic function of precedent-related phenomena as a type of intertextuality. The analysis is done on the basis of relevance theoretic approach, through which we aim to show the additional cognitive effect which is created by precedent-related phenomena in media discourse, and this comic effect serves as a foundation for the ludic function of these units.

  19. Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats

    Directory of Open Access Journals (Sweden)

    Rodrigo L. Castillo

    2018-01-01

    Full Text Available Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE against the damage induced by a high-cholesterol (HC diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio, prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

  20. 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.

  1. Derangements of liver tissue bioenergetics in concanavalin A-induced hepatitis.

    Science.gov (United States)

    Al-Shamsi, Mariam; Shahin, Allen; Mensah-Brown, Eric P K; Souid, Abdul-Kader

    2013-01-12

    A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption) in mice treated with concanavalin A (Con A). This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. C57Bl/6 and C57Bl/6 IFN-γ-/- mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ) and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pactivity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ-/- mice treated with ConA. Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

  2. Derangements of liver tissue bioenergetics in Concanavalin A-induced hepatitis

    Directory of Open Access Journals (Sweden)

    Al-Shamsi Mariam

    2013-01-01

    Full Text Available Abstract Background A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption in mice treated with concanavalin A (Con A. This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. Methods C57Bl/6 and C57Bl/6 IFN-γ−/− mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. Results In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pp=0.005 was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3+NKT+ cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ−/− mice treated with ConA. Conclusions Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

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

    International Nuclear Information System (INIS)

    Módis, Katalin; Asimakopoulou, Antonia; Coletta, Ciro; Papapetropoulos, Andreas; Szabo, Csaba

    2013-01-01

    Highlights: •Oxidative stress impairs 3-MST-derived H 2 S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H 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 2 S), as well as endogenous, intramitochondrial production of H 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 2 S pathway in vitro. Hydrogen peroxide (H 2 O 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 2 O 2 (50–500 μM) caused a concentration-dependent decrease in production of H 2 S from 3-MP. In cultured murine hepatoma cells H 2 O 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 2 O 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 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

  4. Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

    OpenAIRE

    Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.

    2013-01-01

    Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear backgr...

  5. 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.

  6. 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.

  7. 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; Danesh, Farhad R

    2016-11-01

    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.

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

    Science.gov (United States)

    Chausse, Bruno; Vieira-Lara, Marcel A; Sanchez, Angélica B; Medeiros, Marisa H G; Kowaltowski, Alicia J

    2015-01-01

    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.

  9. 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.

  10. Down-regulating overexpressed human Lon in cervical cancer suppresses cell proliferation and bioenergetics.

    Directory of Open Access Journals (Sweden)

    Xiaobo Nie

    Full Text Available The human mitochondrial ATP-dependent Lon protease functions in regulating the metabolism and quality control of proteins and mitochondrial DNA (mtDNA. However, the role of Lon in cancer is not well understood. Therefore, this study was undertaken to investigate the importance of Lon in cervical cancer cells from patients and in established cell lines. Microarray analysis from 30 cancer and 10 normal cervical tissues were analyzed by immunohistochemistry for Lon protein levels. The expression of Lon was also examined by immunoblotting 16 fresh cervical cancer tissues and their respective non-tumor cervical tissues. In all cases, Lon expression was significantly elevated in cervical carcinomas as compared to normal tissues. Augmented Lon expression in tissue microarrays did not vary between age, tumor-node-metastasis grades, or lymph node metastasis. Knocking down Lon in HeLa cervical cancer cells by lentivrial transduction resulted in a substantial decrease in both mRNA and protein levels. Such down-regulation of Lon expression significantly blocked HeLa cell proliferation. In addition, knocking down Lon resulted in decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using the Seahorse XF24 extracellular flux analyzer. Together, these data demonstrate that Lon plays a potential role in the oncogenesis of cervical cancer, and may be a useful biomarker and target in the treatment of cervical cancer. Lon; immunohistochemistry; cervical cancer; cell proliferation; cellular bioenergetics.

  11. Influence of regular proprioceptive and bioenergetic physical activities on balance control in elderly women.

    Science.gov (United States)

    Gauchard, Gérome C; Gangloff, Pierre; Jeandel, Claude; Perrin, Philippe P

    2003-09-01

    Balance disorders increase considerably with age due to a decrease in posture regulation quality, and are accompanied by a higher risk of falling. Conversely, physical activities have been shown to improve the quality of postural control in elderly individuals and decrease the number of falls. The aim of this study was to evaluate the impact of two types of exercise on the visual afferent and on the different parameters of static balance regulation. Static postural control was evaluated in 44 healthy women aged over 60 years. Among them, 15 regularly practiced proprioceptive physical activities (Group I), 12 regularly practiced bioenergetic physical activities (Group II), and 18 controls walked on a regular basis (Group III). Group I participants displayed lower sway path and area values, whereas Group III participants displayed the highest, both in eyes-open and eyes-closed conditions. Group II participants displayed intermediate values, close to those of Group I in the eyes-open condition and those of Group III in the eyes-closed condition. Visual afferent contribution was more pronounced for Group II and III participants than for Group I participants. Proprioceptive exercise appears to have the best impact on balance regulation and precision. Besides, even if bioenergetic activity improves postural control in simple postural tasks, more difficult postural tasks show that this type of activity does not develop a neurosensorial proprioceptive input threshold as well, probably on account of the higher contribution of visual afferent.

  12. The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.

    Directory of Open Access Journals (Sweden)

    Jae Ho Seo

    2016-07-01

    Full Text Available Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer.

  13. Improvement in the bioenergetics system of plants under metal stress environment via seaweeds

    International Nuclear Information System (INIS)

    Azmat, R.; Askari, S.

    2015-01-01

    The effects of Hg and its remediation through seaweeds on seedlings were escorted in a greenhouse experiment in a randomized block design. The effects of Hg were monitored in relation with bioenergetics system of Trigonella foenumgraecum plant at test site scale. Plants that were exposed to Hg, showed affect in diverse ways, including affinity to suffer in morphological as well as on sugar metabolism. The stress imposed by Hg exposure also extends to chloroplast pigments that lead to the distorted photosynthetic apparatus. The outcomes of reduced contents of photosynthetic machinery related with reduced contents of glucose, sucrose, total soluble sugars and carbohydrate contents of plants. These contents plays vital rule for providing bioenergy to the plant growth regulation. It was suggested that Hg is lethal for plant bioenergetics system due to which plants fail to survive under stress. The lethal effects of Hg were tried to remediate through green seaweeds (Codium iyengrii). It was observed that seaweeds successfully controlled the mobility of Hg metal and improves the plant growth regulatory system at lower applied dose only. While at higher dose of Hg, seaweeds were also effective but to a certain limits. It was established that continuous addition of Hg in soil and aquatic resources execute to the plant productivity. It is demand of time to develop alternative eco-friendly remediation technologies for controlling, cleaning Hg-polluted zones. (author)

  14. Ancient Systems of Sodium/Potassium Homeostasis as Predecessors of Membrane Bioenergetics.

    Science.gov (United States)

    Dibrova, D V; Galperin, M Y; Koonin, E V; Mulkidjanian, A Y

    2015-05-01

    Cell cytoplasm of archaea, bacteria, and eukaryotes contains substantially more potassium than sodium, and potassium cations are specifically required for many key cellular processes, including protein synthesis. This distinct ionic composition and requirements have been attributed to the emergence of the first cells in potassium-rich habitats. Different, albeit complementary, scenarios have been proposed for the primordial potassium-rich environments based on experimental data and theoretical considerations. Specifically, building on the observation that potassium prevails over sodium in the vapor of inland geothermal systems, we have argued that the first cells could emerge in the pools and puddles at the periphery of primordial anoxic geothermal fields, where the elementary composition of the condensed vapor would resemble the internal milieu of modern cells. Marine and freshwater environments generally contain more sodium than potassium. Therefore, to invade such environments, while maintaining excess of potassium over sodium in the cytoplasm, primordial cells needed means to extrude sodium ions. The foray into new, sodium-rich habitats was the likely driving force behind the evolution of diverse redox-, light-, chemically-, or osmotically-dependent sodium export pumps and the increase of membrane tightness. Here we present a scenario that details how the interplay between several, initially independent sodium pumps might have triggered the evolution of sodium-dependent membrane bioenergetics, followed by the separate emergence of the proton-dependent bioenergetics in archaea and bacteria. We also discuss the development of systems that utilize the sodium/potassium gradient across the cell membranes.

  15. Bioenergetics models to estimate numbers of larval lampreys consumed by smallmouth bass in Elk Creek, Oregon

    Science.gov (United States)

    Schultz, Luke; Heck, Michael; Kowalski, Brandon M; Eagles-Smith, Collin A.; Coates, Kelly C.; Dunham, Jason B.

    2017-01-01

    Nonnative fishes have been increasingly implicated in the decline of native fishes in the Pacific Northwest. Smallmouth Bass Micropterus dolomieu were introduced into the Umpqua River in southwest Oregon in the early 1960s. The spread of Smallmouth Bass throughout the basin coincided with a decline in counts of upstream-migrating Pacific Lampreys Entosphenus tridentatus. This suggested the potential for ecological interactions between Smallmouth Bass and Pacific Lampreys, as well as freshwater-resident Western Brook Lampreys Lampetra richardsoni. To evaluate the potential effects of Smallmouth Bass on lampreys, we sampled diets of Smallmouth Bass and used bioenergetics models to estimate consumption of larval lampreys in a segment of Elk Creek, a tributary to the lower Umpqua River. We captured 303 unique Smallmouth Bass (mean: 197 mm and 136 g) via angling in July and September. We combined information on Smallmouth Bass diet and energy density with other variables (temperature, body size, growth, prey energy density) in a bioenergetics model to estimate consumption of larval lampreys. Larval lampreys were found in 6.2% of diet samples, and model estimates indicated that the Smallmouth Bass we captured consumed 925 larval lampreys in this 2-month study period. When extrapolated to a population estimate of Smallmouth Bass in this segment, we estimated 1,911 larval lampreys were consumed between July and September. Although the precision of these estimates was low, this magnitude of consumption suggests that Smallmouth Bass may negatively affect larval lamprey populations.

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

    Science.gov (United States)

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

    2018-01-01

    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.

  17. Notes on the Altazor case (preceded by a theoretical drifting

    Directory of Open Access Journals (Sweden)

    Daniel Glaydson Ribeiro

    2012-06-01

    Full Text Available Precede by a brief theoretical drifting about the great poet and the conditions of its appearance (mythic and/or mythological - and also a differential hypothesis about the lyric and the epic -, this is an essay engaged in comprehending the narrative entitled Altazor, eighty years after its publication.

  18. 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...

  19. Solon of Athens as a precedent for Plutarch's authorial persona

    NARCIS (Netherlands)

    Klooster, Julia

    2018-01-01

    Solon is the subject of both a Plutarchan biography (Solon) and a philosophical dialogue (Convivium septem sapientium). In this article I argue that Plutarch creates a precedent for his authorial persona of wise but modest adviser of the ruling class under the Roman empire in the figure of the

  20. 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. (c) 2015 APA, all rights reserved.

  1. Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction.

    Science.gov (United States)

    Ferguson, Michael A; Sutton, Robert M; Karlsson, Michael; Sjövall, Fredrik; Becker, Lance B; Berg, Robert A; Margulies, Susan S; Kilbaugh, Todd J

    2016-06-01

    Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics. To determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg. platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P respiration through Complex II (OXPHOSCII, P respiration was not due to uncoupling, as the LEAKCI + CII respiration (mitochondrial respiration independent of ATP-production) was unchanged after CA/ROSC. Larger increases in platelet mitochondrial respiratory control ratio (RCR) compared to pre-CA RCR were significantly correlated with lower RCRs in the cortex (P respiration. Platelet mitochondrial respiration is significantly increased four hours after ROSC. Future studies will identify mechanistic relationships between this serum biomarker and altered cerebral bioenergetics function following cardiac arrest.

  2. 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.

  3. 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

  4. Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

    Science.gov (United States)

    Hoff, Paula; Maschmeyer, Patrick; Gaber, Timo; Schütze, Tabea; Raue, Tobias; Schmidt-Bleek, Katharina; Dziurla, René; Schellmann, Saskia; Lohanatha, Ferenz Leonard; Röhner, Eric; Ode, Andrea; Burmester, Gerd-Rüdiger; Duda, Georg N; Perka, Carsten; Buttgereit, Frank

    2013-01-01

    The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma. PMID:23396474

  5. 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.

  6. PAH-induced sublethal narcosis alters the bioenergetics and bioaccumulation of Fundulus heteroclitus

    Energy Technology Data Exchange (ETDEWEB)

    Merten, A. [NOAA Office of Response and Restoration, Hazardous Materials and Response, Seattle (United States); Beard, E.; Baker, B. [Univ. of Maryland, Solomons (United States)

    2004-09-15

    Accumulation of non-polar narcotic chemicals in organisms alters their metabolic rates and, therefore their energetic demands. Since exposure of these hydrophobic chemicals is primarily through the diet, we hypothesize that decreasing metabolic rates caused by accumulation of narcotics reduces feeding which, in turn, decreases further exposure to the narcotic. Thus, dietary exposure to and accumulation of narcotics may cause a negative feedback, reducing net bioaccumulation. The purpose of this short paper is to discuss the results of a long-term fish contaminant exposure study and to describe a fish bioenergetics model coupled to a PCBbioaccumulation model. The laboratory component consisted of exposing the estuarine fish Fundulus heteroclitus to environmentally-relevant levels of hydrophobic organic contaminants (HOCs) through their diet. We developed the model to further examine and understand the consequences of sublethal narcosis at both the individual and population levels of Fundulus heteroclitus.

  7. Reasoning with Previous Decisions: Beyond the Doctrine of Precedent

    DEFF Research Database (Denmark)

    Komárek, Jan

    2013-01-01

    in different jurisdictions use previous judicial decisions in their argument, we need to move beyond the concept of precedent to a wider notion, which would embrace practices and theories in legal systems outside the Common law tradition. This article presents the concept of ‘reasoning with previous decisions...... law method’, but they are no less rational and intellectually sophisticated. The reason for the rather conceited attitude of some comparatists is in the dominance of the common law paradigm of precedent and the accompanying ‘case law method’. If we want to understand how courts and lawyers......’ as such an alternative and develops its basic models. The article first points out several shortcomings inherent in limiting the inquiry into reasoning with previous decisions by the common law paradigm (1). On the basis of numerous examples provided in section (1), I will present two basic models of reasoning...

  8. 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

  9. 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.

  10. Extended precedence preservative crossover for job shop scheduling problems

    Science.gov (United States)

    Ong, Chung Sin; Moin, Noor Hasnah; Omar, Mohd

    2013-04-01

    Job shop scheduling problems (JSSP) is one of difficult combinatorial scheduling problems. A wide range of genetic algorithms based on the two parents crossover have been applied to solve the problem but multi parents (more than two parents) crossover in solving the JSSP is still lacking. This paper proposes the extended precedence preservative crossover (EPPX) which uses multi parents for recombination in the genetic algorithms. EPPX is a variation of the precedence preservative crossover (PPX) which is one of the crossovers that perform well to find the solutions for the JSSP. EPPX is based on a vector to determine the gene selected in recombination for the next generation. Legalization of children (offspring) can be eliminated due to the JSSP representation encoded by using permutation with repetition that guarantees the feasibility of chromosomes. The simulations are performed on a set of benchmarks from the literatures and the results are compared to ensure the sustainability of multi parents recombination in solving the JSSP.

  11. 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....

  12. Experimental Evidence for a Cochlear Source of the Precedence Effect

    DEFF Research Database (Denmark)

    Bianchi, Federica; Verhulst, Sarah; Dau, Torsten

    2013-01-01

    The precedence effect (PE) refers to the dominance of directional information carried by a direct sound (lead) over the spatial information contained in its multiple reflections (lags) in sound localization. Although the processes underlying the PE have been largely investigated, the extent...... to which peripheral versus central auditory processes contribute to this perceptual phenomenon has remained unclear. The present study investigated the contribution of peripheral processing to the PE through a comparison of physiological and psychoacoustical data in the same human listeners...

  13. Radiation protection: precedents, principles and practices - a regulatory viewpoint

    International Nuclear Information System (INIS)

    Jennekens, J.H.

    1986-06-01

    Radiation protection in its broadest sense is a multidisciplinary human function exemplifying in all meaningful respects the innate ability of dedicated persons to apply with both general and specialized expertise knowledge derived from a great many scientific and technical fields. The aim of this address is to outline from a regulatory viewpoint the precedents, principles and practices of radiation protection, a very essential human function

  14. Money laundering: The question of precedent relevant criminal fact

    Directory of Open Access Journals (Sweden)

    Fernando ANDRADE FERNANDES

    2014-07-01

    Full Text Available The article aims to make a more detailed analysis on the problem of the autonomy of money laundering crime. The rationale for the study is the existence of an understanding that defends the autonomy of the money laundering crime, despite the linkages she has with the precedent crime, of which result the illicit assets. The issue of autonomy of money laundering crime is analyzed in the perspective of the Criminal Law and Criminal Procedure.

  15. 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.

  16. 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

  17. Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S.; Rouchka, Eric C.; Hill, Bradford G.; Klinge, Carolyn M.

    2016-01-01

    Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

  18. Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S. [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Rouchka, Eric C. [Bioinformatics and Biomedical Computing Laboratory, Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292 (United States); Hill, Bradford G. [Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Klinge, Carolyn M., E-mail: carolyn.klinge@louisville.edu [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States)

    2016-09-10

    Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

  19. Evolutionary, kinetic and thermodynamic aspects on the bioenergetics of inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP)

    International Nuclear Information System (INIS)

    Baltscheffsky, H.; Baltscheffsky, M.

    1995-01-01

    Energy barriers for energy carriers are of fundamental significance for the successful operation of the bioenergetic reactions in living cells. PPi and ATP are outstanding ''energy-rich'' examples of molecular ''energy currencies'' in biological systems, with kinetic barriers preventing excessively fast thermodynamically feasible hydrolysis from occurring. The barriers may be considered to facilitate the energy coupling roles of these phosphate compounds, which are to secure growth and maintain numerous other energy requiring functions. The enzymes involved in overcoming the energies of activation of the bioenergetic reactions have evolved to be very well tuned for their roles. Three aspects will be discussed in some detail. The first is the fact that ATP at neutral pH is considerably more energy-rich than PPi, which thus has been called a ''poor man's ATP''. This is exemplified by the kinetic and thermodynamic differences observed between the requirements for the photosynthetic formation of PPi and ATP in certain photobacterial chromatophores by varying levels of energy supply. At lower pH, PPi and ATP are equally energy-rich, which may be of significance for acidophiles. The second concerns the possible evolutionary significance of the finding that, in the dark, a pH gradient suffices to drive extensive PPi synthesis, whereas ATP synthesis requires both a pH gradient and a membrane potential (Strid et al, Biochim. Biophys. Acta 892 (1987) 236-244). Thirdly, PPi as the most plausible predecessor to ATP in the origin and early evolution of life, will be discussed. (author). Abstract only

  20. 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.

  1. Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells.

    Science.gov (United States)

    Calton, Emily K; Keane, Kevin N; Raizel, Raquel; Rowlands, Jordan; Soares, Mario J; Newsholme, Philip

    2017-08-01

    Vitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XF e 96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method. 25(OH)D increased by a median (IQR) of 14.40 (20.13)nmol/L (pwinter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (winter 25(OH)D concentrations of 50-75nmol/L or >75nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics. Seasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants

  2. The precedence effect for lateralization at low sensation levels.

    Science.gov (United States)

    Goverts, S T; Houtgast, T; van Beek, H H

    2000-10-01

    Using dichotic signals presented by headphone, stimulus onset dominance (the precedence effect) for lateralization at low sensation levels was investigated for five normal hearing subjects. Stimuli were based on 2400-Hz low pass filtered 5-ms noise bursts. We used the paradigm, as described by Aoki and Houtgast (Hear. Res., 59 (1992) 25-30) and Houtgast and Aoki (Hear. Res., 72 (1994) 29-36), in which the stimulus is divided into a leading and a lagging part with opposite lateralization cues (i.e. an interaural time delay of 0.2 ms). The occurrence of onset dominance was investigated by measuring lateral perception of the stimulus, with fixed equal duration of leading and lagging part, while decreasing absolute signal level or adding a filtered white noise with the signal level set at 65 dBA. The dominance of the leading part was quantified by measuring the perceived lateral position of the stimulus as a function of the relative duration of the leading (and thus the lagging) part. This was done at about 45 dB SL without masking noise and also at a signal-to-noise ratio resulting in a sensation level of 10 dB. The occurrence and strength of the precedence effect was found to depend on sensation level, which was decreased either by lowering the signal level or by adding noise. With the present paradigm, besides a decreased lateralization accuracy, a decrease in the precedence effect was found for sensation levels below about 30-40 dB. In daily-life conditions, with a sensation level in noise of typically 10 dB, the onset dominance was still manifest, albeit degraded to some extent.

  3. 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.

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

    OpenAIRE

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

    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 ...

  5. Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

    Science.gov (United States)

    Chen, Li-You; Renn, Ting-Yi; Liao, Wen-Chieh; Mai, Fu-Der; Ho, Ying-Jui; Hsiao, George; Lee, Ai-Wei; Chang, Hung-Ming

    2017-09-01

    Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [ 14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from

  6. 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.

  7. Human behavior preceding dog bites to the face.

    Science.gov (United States)

    Rezac, P; Rezac, K; Slama, P

    2015-12-01

    Facial injuries caused by dog bites pose a serious problem. The aims of this study were to determine human behavior immediately preceding a dog bite to the face and to assess the effects of victim age and gender and dog sex and size on the location of the bite to the face and the need for medical treatment. Complete data on 132 incidents of bites to the face were analysed. A human bending over a dog, putting the face close to the dog's face, and gazing between victim and dog closely preceded a dog bite to the face in 76%, 19% and 5% of cases, respectively. More than half of the bites were directed towards the central area of the victim's face (nose, lips). More than two thirds of the victims were children, none of the victims was an adult dog owner and only adult dogs bit the face. Victim's age and gender and dog's sex and size did not affect the location of the bite on the face. People who were bitten by large dogs sought medical treatment more often than people who were bitten by small dogs (P face close to the dog's face and gazing between human and dog should be avoided, and children should be carefully and constantly supervised when in the presence of dogs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. Linking functional response and bioenergetics to estimate juvenile salmon growth in a reservoir food web

    Science.gov (United States)

    Haskell, Craig A.; Beauchamp, David A.; Bollens, Stephen M.

    2017-01-01

    Juvenile salmon (Oncorhynchus spp.) use of reservoir food webs is understudied. We examined the feeding behavior of subyearling Chinook salmon (O. tshawytscha) and its relation to growth by estimating the functional response of juvenile salmon to changes in the density of Daphnia, an important component of reservoir food webs. We then estimated salmon growth across a broad range of water temperatures and daily rations of two primary prey, Daphnia and juvenile American shad (Alosa sapidissima) using a bioenergetics model. Laboratory feeding experiments yielded a Type-II functional response curve: C = 29.858 P *(4.271 + P)-1 indicating that salmon consumption (C) of Daphnia was not affected until Daphnia densities (P) were < 30 · L-1. Past field studies documented Daphnia densities in lower Columbia River reservoirs of < 3 · L-1 in July but as high as 40 · L-1 in August. Bioenergetics modeling indicated that subyearlings could not achieve positive growth above 22°C regardless of prey type or consumption rate. When feeding on Daphnia, subyearlings could not achieve positive growth above 20°C (water temperatures they commonly encounter in the lower Columbia River during summer). At 16–18°C, subyearlings had to consume about 27,000 Daphnia · day-1 to achieve positive growth. However, when feeding on juvenile American shad, subyearlings had to consume 20 shad · day-1 at 16–18°C, or at least 25 shad · day-1 at 20°C to achieve positive growth. Using empirical consumption rates and water temperatures from summer 2013, subyearlings exhibited negative growth during July (-0.23 to -0.29 g · d-1) and August (-0.05 to -0.07 g · d-1). By switching prey from Daphnia to juvenile shad which have a higher energy density, subyearlings can partially compensate for the effects of higher water temperatures they experience in the lower Columbia River during summer. However, achieving positive growth as piscivores requires subyearlings to feed at

  11. Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and locomotor behavior in larval zebrafish (Danio rerio).

    Science.gov (United States)

    Zhang, Ji-Liang; Laurence Souders, Christopher; Denslow, Nancy D; Martyniuk, Christopher J

    2017-07-15

    Quercetin is a natural product that is sold as a supplement in health food stores. While there are reported benefits for this flavonoid as a dietary supplement due to antioxidant properties, the full scope of its biological interactions has not been fully addressed. To learn more about the mechanisms of action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and 10μg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to 10μg/L did not induce significant mortality in developing fish, but did increase prevalence of an upward-curved dorsal plane in hatched larvae. To determine whether this developmental defect was potentially related to mitochondrial bioenergetics during development, we measured oxygen consumption rate in whole embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP-linked respiration were decreased at 1 and 10μg/L quercetin, and maximal respiration was decreased at 10μg/L quercetin, suggesting that quercetin impairs mitochondrial bioenergetics. This is proposed to be related to the deformities observed during development. Due to the fact that ATP production was affected by quercetin, larval behaviors related to locomotion were investigated, as well as transcriptional responses of six myogenesis transcripts. Quercetin at 10μg/L significantly reduced the swimming velocity of zebrafish larvae. The expression levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also altered by quercetin. Mstna, an inhibitory factor for myogenesis, was significantly increased at 1μg/L quercetin exposure, while myoD, a stimulatory factor for myogenesis, was significantly increased at 10μg/L quercetin exposure. There were no changes in transcripts related to apoptosis (bcl2, bax, casp3, casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish exposed to each dose, supporting an oxidative stress response. Our data support the hypothesis that quercetin may affect

  12. The Alteration of Emotion Regulation Precedes the Deficits in Interval Timing in the BACHD Rat Model for Huntington Disease

    Directory of Open Access Journals (Sweden)

    Daniel Garces

    2018-05-01

    Full Text Available Huntington disease (HD is an autosomal dominantly inherited, progressive neurodegenerative disorder which is accompanied by executive dysfunctions and emotional alteration. The aim of the present study was to assess the impact of emotion/stress on on-going highly demanding cognitive tasks, i.e., temporal processing, as a function of age in BACHD rats (a “full length” model of HD. Middle-aged (4–6 months and old (10–12 months rats were first trained on a 2 vs. 8-s temporal discrimination task, and then exposed to a series of bisection tests under normal and stressful (10 mild unpredictable foot-shocks conditions. The animals were then trained on a peak interval task, in which reinforced fixed-interval (FI 30-s trials were randomly intermixed with non-reinforced probe trials. After training, the effect of stress upon time perception was again assessed. Sensitivity to foot-shocks was also assessed independently. The results show effects of both age and genotype, with largely greater effects in old BACHD animals. The older BACHD animals had impaired learning in both tasks, but reached equivalent levels of performance as WT animals at the end of training in the temporal discrimination task, while remaining impaired in the peak interval task. Whereas sensitivity to foot-shock did not differ between BACHD and WT rats, delivery of foot-shocks during the test sessions had a disruptive impact on temporal behavior in WT animals, an effect which increased with age. In contrast, BACHD rats, independent of age, did not show any significant disruption under stress. In conclusion, BACHD rats showed a disruption in temporal learning in late symptomatic animals. Age-related modification in stress-induced impairment of temporal control of behavior was also observed, an effect which was greatly reduced in BACHD animals, thus confirming previous results suggesting reduced emotional reactivity in HD animals. The results suggest a staggered onset in cognitive and emotional alterations in HD, with emotional alteration being the earliest, possibly related to different time courses of degeneration in cortico-striatal and amygdala circuits.

  13. Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Maruyama, Hitoshi; Takahashi, Masanori; Ishibashi, Hiroyuki; Okabe, Shinichiro; Yoshikawa, Masaharu; Yokosuka, Osamu

    2010-01-01

    Purpose: To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC). Materials and methods: This prospective study enrolled 10 patients with histologically proven HCC (14.4-39.0 mm, 26.1 ± 7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22-0.25) during the vascular phase (agent injection to 1 min) and late phase (15 min) following the injection of Sonazoid TM (0.0075 ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced. Results: Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules. Conclusion: Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid.

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

    Science.gov (United States)

    Sánchez-Aragó, María; Cuezva, José M

    2011-02-08

    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). 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. 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. Overall, we suggest that the determination of the bioenergetic signature of colon carcinomas could

  15. Bioenergetic profiling of Trypanosoma cruzi life stages using Seahorse extracellular flux technology.

    Science.gov (United States)

    Shah-Simpson, Sheena; Pereira, Camila F A; Dumoulin, Peter C; Caradonna, Kacey L; Burleigh, Barbara A

    2016-08-01

    Energy metabolism is an attractive target for the development of new therapeutics against protozoan pathogens, including Trypanosoma cruzi, the causative agent of human Chagas disease. Despite emerging evidence that mitochondrial electron transport is essential for the growth of intracellular T. cruzi amastigotes in mammalian cells, fundamental knowledge of mitochondrial energy metabolism in this parasite life stage remains incomplete. The Clark-type electrode, which measures the rate of oxygen consumption, has served as the traditional tool to study mitochondrial energetics and has contributed to our understanding of it in T. cruzi. Here, we evaluate the Seahorse XF(e)24 extracellular flux platform as an alternative method to assess mitochondrial bioenergetics in isolated T. cruzi parasites. We report optimized assay conditions used to perform mitochondrial stress tests with replicative life cycle stages of T. cruzi using the XF(e)24 instrument, and discuss the advantages and potential limitations of this methodology, as applied to T. cruzi and other trypanosomatids. Copyright © 2016 Elsevier B.V. All rights reserved.

  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. Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

    Science.gov (United States)

    Bartesaghi, Stefano; Betts-Henderson, Joanne; Cain, Kelvin; Dinsdale, David; Zhou, Xiaoshan; Karlsson, Anna; Salomoni, Paolo; Nicotera, Pierluigi

    2010-05-01

    Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated with progressive myopathy, hepatopathy and/or encephalopathy, depending in part on the underlying nuclear genetic defect. Mutations of TK2 have previously been associated with an isolated myopathic form of MDS (OMIM 609560). However, more recently, neurological phenotypes have been demonstrated in patients carrying TK2 mutations, thus suggesting that loss of TK2 results in neuronal dysfunction. Here, we directly address the role of TK2 in neuronal homeostasis using a knockout mouse model. We demonstrate that in vivo loss of TK2 activity leads to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain. In TK2-deficient cerebellar neurons, these abnormalities are associated with impaired mitochondrial bioenergetic function, aberrant mitochondrial ultrastructure and degeneration of selected neuronal types. Overall, our findings demonstrate that TK2 deficiency leads to neuronal dysfunction in vivo, and have important implications for understanding the mechanisms of neurological impairment in MDS.

  18. 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.

  19. Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

    Science.gov (United States)

    Rana, P; Sripathy, G; Varshney, A; Kumar, P; Devi, M Memita; Marwaha, R K; Tripathi, R P; Khushu, S

    2012-02-01

    Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

  20. Huntingtin Protein is Essential for Mitochondrial Metabolism, Bioenergetics and Structure in Murine Embryonic Stem Cells

    Science.gov (United States)

    Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S.; Brivanlou, Ali H.

    2014-01-01

    Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt-/- mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3,700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt-/-, extended poly-Q (Htt-Q140/7), and wildtype mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells, did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt-/- mESCs, including: (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt-/- early embryonic lethality. PMID:24780625

  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. Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer.

    Science.gov (United States)

    van der Windt, Gerritje J W; Chang, Chih-Hao; Pearce, Erika L

    2016-04-01

    This unit contains several protocols to determine the energy utilization of T cells in real-time using a Seahorse Extracellular Flux Analyzer (http://www.seahorsebio.com). The advantages to using this machine over traditional metabolic assays include the simultaneous measurement of glycolysis and mitochondrial respiration, in real-time, on relatively small numbers of cells, without any radioactivity. The Basic Protocol describes a standard mitochondrial stress test on the XF(e) 96, which yields information about oxidative phosphorylation and glycolysis, two energy-generating pathways. The alternate protocols provide examples of adaptations to the Basic Protocol, including adjustments for the use of the XF(e) 24. A protocol for real-time bioenergetic responses to T cell activation allows for the analysis of immediate metabolic changes after T cell receptor stimulation. Specific substrate utilization can be determined by the use of differential assay media, or the injection of drugs that specifically affect certain metabolic processes. Accurate cell numbers, purity, and viability are critical to obtain reliable results. Copyright © 2016 John Wiley & Sons, Inc.

  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. 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.

  5. Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

    Science.gov (United States)

    Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

    2009-12-01

    Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

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

    Science.gov (United States)

    Trksak, George H.; Bracken, Bethany K.; Jensen, J. Eric; Plante, David T.; Penetar, David M.; Tartarini, Wendy L.; Maywalt, Melissa A.; Dorsey, Cynthia M.; Renshaw, Perry F.; Lukas, Scott E.

    2013-01-01

    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. PMID:24250276

  7. Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Vanfleteren Jacques R

    2010-06-01

    Full Text Available Abstract Background The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. Results We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370 adult animals. The increase in daf-2(e1370 mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370 animals. Conclusions We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.

  8. Effects of Aluminium on Rat Brain Mitochondria Bioenergetics: an In vitro and In vivo Study.

    Science.gov (United States)

    Iglesias-González, Javier; Sánchez-Iglesias, Sofía; Beiras-Iglesias, Andrés; Méndez-Álvarez, Estefanía; Soto-Otero, Ramón

    2017-01-01

    Numerous studies have highlighted the potential of aluminium as an aetiological factor for some neurodegenerative disorders, particularly Alzheimer's disease and Parkinson's disease. Our previous studies have shown that aluminium can cause oxidative stress, reduce the activity of some antioxidant enzymes, and enhance the dopaminergic neurodegeneration induced by 6-hydroxydopamine in an experimental model of Parkinson's disease in rats. We now report a study on the effects caused by aluminium on mitochondrial bioenergetics following aluminium addition and after its chronic administration to rats. To develop our study, we used a high-resolution respirometry to test the mitochondrial respiratory capacities under the conditions of coupling, uncoupling, and non-coupling. Our study showed alterations in leakiness, a reduction in the maximum capacity of complex II-linked respiratory pathway, a decline in the respiration efficiency, and a decrease in the activities of complexes III and V in both models studied. The observed effects also included both an alteration in mitochondrial transmembrane potential and a decrease in oxidative phosphorylation capacity when relatively high concentrations of aluminium were added to the isolated mitochondria. These findings contribute to explain both the ability of aluminium to generate oxidative stress and its suggested potential to act as an etiological factor by promoting the progression of neurodegenerative disorders such as Parkinson's disease.

  9. Respiromics – An integrative analysis linking mitochondrial bioenergetics to molecular signatures

    Directory of Open Access Journals (Sweden)

    Ellen Walheim

    2018-03-01

    Full Text Available Objective: Energy metabolism is challenged upon nutrient stress, eventually leading to a variety of metabolic diseases that represent a major global health burden. Methods: Here, we combine quantitative mitochondrial respirometry (Seahorse technology and proteomics (LC-MS/MS-based total protein approach to understand how molecular changes translate to changes in mitochondrial energy transduction during diet-induced obesity (DIO in the liver. Results: The integrative analysis reveals that significantly increased palmitoyl-carnitine respiration is supported by an array of proteins enriching lipid metabolism pathways. Upstream of the respiratory chain, the increased capacity for ATP synthesis during DIO associates strongest to mitochondrial uptake of pyruvate, which is routed towards carboxylation. At the respiratory chain, robust increases of complex I are uncovered by cumulative analysis of single subunit concentrations. Specifically, nuclear-encoded accessory subunits, but not mitochondrial-encoded or core units, appear to be permissive for enhanced lipid oxidation. Conclusion: Our integrative analysis, that we dubbed “respiromics”, represents an effective tool to link molecular changes to functional mechanisms in liver energy metabolism, and, more generally, can be applied for mitochondrial analysis in a variety of metabolic and mitochondrial disease models. Keywords: Mitochondria, Respirometry, Proteomics, Mitochondrial pyruvate carrier, Liver disease, Bioenergetics, Obesity, Diabetes

  10. CD133 is a marker of bioenergetic stress in human glioma.

    Directory of Open Access Journals (Sweden)

    Corinne E Griguer

    Full Text Available Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed rho(0 or rho(0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these rho(0 cells display the ability to form "tumor spheroids" in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, rho(0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to rho(0 cells resulting in stable trans-mitochondrial "cybrid" clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia and mitochondrial dysfunction (genetic and chemical. Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised.

  11. 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.…

  12. Self-potential variations preceding earthquakes in central california

    International Nuclear Information System (INIS)

    Corwin, R.F.; Morrison, H.G.

    1977-01-01

    Two earthquakes in central California were preceded by anomalous variations in the horizontal electric field (self-potential) of the earth. The first variation was an anomaly of 90 mV amplitude across electrode dipoles of 630 and 640 m, which began 55 days before an earthquake of M=5, located 37 km NW of the dipoles. The second variation had an amplitude of 4 mV across a 300 m dipole, and began 110 hours before an event of M=2.4 located on the San Andreas fault, 2.5 km from the dipole. Streaming potentials generated by the flow of groundwater into a dilatant zone are proposed as a possible mechanism for the observed variations

  13. Progression of disease preceding lower extremity amputation in Denmark

    DEFF Research Database (Denmark)

    Jensen, Pia Søe; Petersen, Janne; Kirketerp-Møller, Klaus

    2017-01-01

    OBJECTIVES: Patients with non-traumatic lower extremity amputation are characterised by high age, multi-morbidity and polypharmacy and long-term complications of atherosclerosis and diabetes. To ensure early identification of patients at risk of amputation, we need to gain knowledge about...... the progression of diseases related to lower extremity amputations during the years preceding the amputation. DESIGN: A retrospective population-based national registry study. SETTING: The study includes data on demographics, diagnoses, surgery, medications and healthcare services from five national registries....... Data were retrieved from 14 years before until 1 year after the amputation. Descriptive statistics were used to describe the progression of diseases and use of medication and healthcare services. PARTICIPANTS: An unselected cohort of patients (≥50 years; n=2883) subjected to a primary non...

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

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Sorensen, Inge J

    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.......4; 95% CI 1.1, 38) based on two patients, who developed testis cancer >10 years before WG. The overall prevalence of malignancies diagnosed time...... 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...

  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 ...

  16. 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...... 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...

  17. 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 la...... in institutions and experts. It suggests that an interdisciplinary, contextualised and psychologically sound approach to the study of risk is needed.......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...

  18. Attention Deficit Hyperactivity Disorder

    OpenAIRE

    Jaime O. Oliver

    2017-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is considered as among the most common yet serious brain disorders significant number of children are subjected to; the seriousness of which manifests in the ability of the disorder to continue to show up even after the childhood years, during the period of adolescence as well as adulthood. Considering the findings delivered by Brain Imaging Studies conducted on youth, it is revealed that people suffering from ADHD experiences del...

  19. Attention deficits and divorce.

    Science.gov (United States)

    Bouchard, Geneviève; Saint-Aubin, Jean

    2014-09-01

    Building on previous work on the role of attention deficits associated with the regulation of executive control in psychiatric disorders, we examine whether these attention deficits are related to an interpersonal disturbance, the experience of divorce. Attentional capacities of 95 randomly selected couples from the general population were measured with a well-established task, the Attentional Network Task, which assesses the efficiency of 3 attention networks (that is, alerting, orienting, and executive control). Among the 190 participants, 32 had experienced a divorce in the past. ANCOVAs were used to compare divorced people in marital or cohabiting unions with people in first unions in their performance on this purely cognitive task. Our findings indicate that divorced people who are currently living in a cohabiting relationship show significantly lower executive control than other adults living as couples, after controlling for sex, age, income, and education. This subgroup of divorced people not only exhibit greater difficulty in responding to some stimuli while ignoring irrelevant ones but also manifest cognitive deficits in conflict resolution. This study highlights the links between attention and the long-term maintenance of intimate relationships. Our results may have important implications for the identification of people at risk for divorce.

  20. Ballistic deficit correction

    International Nuclear Information System (INIS)

    Duchene, G.; Moszynski, M.; Curien, D.

    1991-01-01

    The EUROGAM data-acquisition has to handle a large number of events/s. Typical in-beam experiments using heavy-ion fusion reactions assume the production of about 50 000 compound nuclei per second deexciting via particle and γ-ray emissions. The very powerful γ-ray detection of EUROGAM is expected to produce high-fold event rates as large as 10 4 events/s. Such high count rates introduce, in a common dead time mode, large dead times for the whole system associated with the processing of the pulse, its digitization and its readout (from the preamplifier pulse up to the readout of the information). In order to minimize the dead time the shaping time constant τ, usually about 3 μs for large volume Ge detectors has to be reduced. Smaller shaping times, however, will adversely affect the energy resolution due to ballistic deficit. One possible solution is to operate the linear amplifier, with a somewhat smaller shaping time constant (in the present case we choose τ = 1.5 μs), in combination with a ballistic deficit compensator. The ballistic deficit can be corrected in different ways using a Gated Integrator, a hardware correction or even a software correction. In this paper we present a comparative study of the software and hardware corrections as well as gated integration

  1. Increasing Northern Hemisphere water deficit

    Science.gov (United States)

    McCabe, Gregory J.; Wolock, David M.

    2015-01-01

    A monthly water-balance model is used with CRUTS3.1 gridded monthly precipitation and potential evapotranspiration (PET) data to examine changes in global water deficit (PET minus actual evapotranspiration) for the Northern Hemisphere (NH) for the years 1905 through 2009. Results show that NH deficit increased dramatically near the year 2000 during both the cool (October through March) and warm (April through September) seasons. The increase in water deficit near 2000 coincides with a substantial increase in NH temperature and PET. The most pronounced increases in deficit occurred for the latitudinal band from 0 to 40°N. These results indicate that global warming has increased the water deficit in the NH and that the increase since 2000 is unprecedented for the 1905 through 2009 period. Additionally, coincident with the increase in deficit near 2000, mean NH runoff also increased due to increases in P. We explain the apparent contradiction of concurrent increases in deficit and increases in runoff.

  2. 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.

  3. 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

  4. Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users

    Science.gov (United States)

    Parrott, A.C.

    2009-01-01

    Aims 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. Methods The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. Results Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. Conclusions The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage. PMID:19893332

  5. Bioenergetics during calvarial osteoblast differentiation reflect strain differences in bone mass.

    Science.gov (United States)

    Guntur, Anyonya R; Le, Phuong T; Farber, Charles R; Rosen, Clifford J

    2014-05-01

    Osteoblastogenesis is the process by which mesenchymal stem cells differentiate into osteoblasts that synthesize collagen and mineralize matrix. The pace and magnitude of this process are determined by multiple genetic and environmental factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in peak bone mass and bone formation. Although all the heritable factors that differ between these strains have not been elucidated, a recent F1 hybrid expression panel (C3H × B6) revealed major genotypic differences in osteoblastic genes related to cellular respiration and oxidative phosphorylation. Thus, we hypothesized that the metabolic rate of energy utilization by osteoblasts differed by strain and would ultimately contribute to differences in bone formation. In order to study the bioenergetic profile of osteoblasts, we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) first in a preosteoblastic cell line MC3T3-E1C4 and subsequently in primary calvarial osteoblasts from C3H and B6 mice at days 7, 14, and 21 of differentiation. During osteoblast differentiation in media containing ascorbic acid and β-glycerophosphate, all 3 cell types increased their oxygen consumption and extracellular acidification rates compared with the same cells grown in regular media. These increases are sustained throughout differentiation. Importantly, C3H calvarial osteoblasts had greater oxygen consumption rates than B6 consistent with their in vivo phenotype of higher bone formation. Interestingly, osteoblasts utilized both oxidative phosphorylation and glycolysis during the differentiation process although mature osteoblasts were more dependent on glycolysis at the 21-day time point than oxidative phosphorylation. Thus, determinants of oxygen consumption reflect strain differences in bone mass and provide the first evidence that during collagen synthesis osteoblasts use both glycolysis and oxidative phosphorylation to synthesize and

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

    Science.gov (United States)

    Konigsberg, M; Pérez, V I; Ríos, C; Liu, Y; Lee, S; Shi, Y; Van Remmen, H

    2013-01-01

    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.

  7. Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Bryan Leaw

    2017-07-01

    Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

  8. Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio).

    Science.gov (United States)

    Wang, Xiao H; Souders, Christopher L; Zhao, Yuan H; Martyniuk, Christopher J

    2018-01-01

    The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos. Maximal respiration of embryos exposed to 100 μM paraquat for 24 h was reduced by more than 70%, suggesting that paraquat negatively impacts mitochondrial bioenergetics in early development. Based upon this evidence for mitochondrial dysfunction, transcriptional responses of oxidative stress- and apoptosis-related genes were measured. Fish exposed to 1 μM paraquat showed higher expression levels of superoxide dismutase 2, heat shock protein 70, Bcl-2-associated X protein, and B-cell CLL/lymphoma 2a compared to control fish. No differences among groups were detected in larvae exposed to 10 and 100 μM paraquat, suggesting a non-monotonic response. We also measured endpoints related to larval behavior and dopaminergic signaling as paraquat is associated with degeneration of dopamine neurons. Locomotor activity was stimulated with 100 μM paraquat and dopamine transporter and dopamine receptor 3 mRNA levels were increased in larvae exposed to 1 μM paraquat, interpreted to be a compensatory response at lower concentrations. This study improves mechanistic understanding into the toxic actions of paraquat on early developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Lissette C. Sánchez-Aranguren

    2018-03-01

    Full Text Available Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1. sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia. Endothelial cells (ECs and first-trimester trophoblast (HTR-8/SVneo were treated with serum from preeclamptic women rich in sFlt-1 or with the recombinant protein. sFlt-1, dose-dependently inhibited ECs respiration and acidification rates indicating a metabolic phenotype switch enhancing glycolytic flux. HTR-8/SVneo displayed a strong basal glycolytic metabolism, remaining less sensitive to sFlt-1-induced mitochondrial impairment. Moreover, results obtained in ECs exposed to serum from preeclamptic subjects demonstrated that increased sFlt-1 leads to metabolic perturbations accountable for mitochondrial dysfunction observed in preeclampsia. sFlt-1 exacerbated mitochondrial reactive oxygen species (ROS formation and mitochondrial membrane potential dissipation in ECs and trophoblasts exposed to serum from preeclamptic women. Forcing oxidative metabolism by culturing cells in galactose media, further sensitized cells to sFlt-1. This approach let us establish that sFlt-1 targets mitochondrial function in ECs. Effects of sFlt-1 on HTR-8/SVneo cells metabolism were amplified in galactose, demonstrating that sFlt-1 only target cells that rely mainly on oxidative metabolism. Together, our results establish the early metabolic perturbations induced by sFlt-1 and the resulting endothelial and mitochondrial dysfunction

  10. 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.

  11. Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer's disease.

    Science.gov (United States)

    Olajide, Olayemi Joseph; Yawson, Emmanuel Olusola; Gbadamosi, Ismail Temitayo; Arogundade, Tolulope Timothy; Lambe, Ezra; Obasi, Kosisochukwu; Lawal, Ismail Tayo; Ibrahim, Abdulmumin; Ogunrinola, Kehinde Yomi

    2017-03-01

    Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl 3 )-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl 3 (100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl 3. Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural

  12. Precedents For Authorization Of Contents Using Dose Rate Measurements

    International Nuclear Information System (INIS)

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

    2012-01-01

    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.

  13. The Kosovo Precedent in the Secession and Recognition of Crimea

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Elvina Jusufaj

    2015-06-01

    Full Text Available Crimea’s secession from Ukraine and its annexation to the Russian Federation invoked Kosovo precedent, in its declaration of independence, as an argument for secession. The territorial referendum in the Autonomous Republic of Crimea, only five days after the declaration of independence, was an attempt to justify the secession based on the right to selfdetermination of the people of Crimea. It is overwhelmingly considered illegal and its outcome has not been accepted and recognized by states, regional and international organizations. The comparative elements of statehood and secession between Kosovo and Crimea are reflected through analyzing the declarations of independence, international recognition and Russia’s role as a third-state factor in external selfdetermination. Essential distinctions are highlighted. Kosovo is widely acknowledged and accepted a sui generis case. Its declaration of independence came as result of a long monitored comprehensive process; not to legitimize the right for self-determination but as the final option for stability and peace in the region. Crimea seceded in violation of international law through the use of force. While Kosovo is a democratic, multi-ethnic new state and recognized by 107 states, the secession of Crimea and its annexation to the Russian Federation is considered illegal and endangers the existing international order.

  14. Neurological evidence linguistic processes precede perceptual simulation in conceptual processing.

    Science.gov (United States)

    Louwerse, Max; Hutchinson, Sterling

    2012-01-01

    There is increasing evidence from response time experiments that language statistics and perceptual simulations both play a role in conceptual processing. In an EEG experiment we compared neural activity in cortical regions commonly associated with linguistic processing and visual perceptual processing to determine to what extent symbolic and embodied accounts of cognition applied. Participants were asked to determine the semantic relationship of word pairs (e.g., sky - ground) or to determine their iconic relationship (i.e., if the presentation of the pair matched their expected physical relationship). A linguistic bias was found toward the semantic judgment task and a perceptual bias was found toward the iconicity judgment task. More importantly, conceptual processing involved activation in brain regions associated with both linguistic and perceptual processes. When comparing the relative activation of linguistic cortical regions with perceptual cortical regions, the effect sizes for linguistic cortical regions were larger than those for the perceptual cortical regions early in a trial with the reverse being true later in a trial. These results map upon findings from other experimental literature and provide further evidence that processing of concept words relies both on language statistics and on perceptual simulations, whereby linguistic processes precede perceptual simulation processes.

  15. The association between preceding drought occurrence and heat waves in the Mediterranean

    Science.gov (United States)

    Russo, Ana; Gouveia, Célia M.; Ramos, Alexandre M.; Páscoa, Patricia; Trigo, Ricardo M.

    2017-04-01

    A large number of weather driven extreme events has occurred worldwide in the last decade, namely in Europe that has been struck by record breaking extreme events with unprecedented socio-economic impacts, including the mega-heatwaves of 2003 in Europe and 2010 in Russia, and the large droughts in southwestern Europe in 2005 and 2012. The last IPCC report on extreme events points that a changing climate can lead to changes in the frequency, intensity, spatial extent, duration, and timing of weather and climate extremes. These, combined with larger exposure, can result in unprecedented risk to humans and ecosystems. In this context it is becoming increasingly relevant to improve the early identification and predictability of such events, as they negatively affect several socio-economic activities. Moreover, recent diagnostic and modelling experiments have confirmed that hot extremes are often preceded by surface moisture deficits in some regions throughout the world. In this study we analyze if the occurrence of hot extreme months is enhanced by the occurrence of preceding drought events throughout the Mediterranean area. In order to achieve this purpose, the number of hot days in the regions' hottest month will be associated with a drought indicator. The evolution and characterization of drought was analyzed using both the Standardized Precipitation Evaporation Index (SPEI) and the Standardized Precipitation Index (SPI), as obtained from CRU TS3.23 database for the period 1950-2014. We have used both SPI and SPEI for different time scales between 3 and 9 months with a spatial resolution of 0.5°. The number of hot days and nights per month (NHD and NHN) was determined using the ECAD-EOBS daily dataset for the same period and spatial resolution (dataset v14). The NHD and NHN were computed, respectively, as the number of days with a maximum or minimum temperature exceeding the 90th percentile. Results show that the most frequent hottest months for the Mediterranean

  16. 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

    > 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 Wpower-law (μ =a...

  17. Enhanced canopy growth precedes senescence in 2005 and 2010 Amazonian droughts

    KAUST Repository

    Liu, Yi Y.

    2018-04-09

    Unprecedented droughts hit southern Amazonia in 2005 and 2010, causing a sharp increase in tree mortality and carbon loss. To better predict the rainforest\\'s response to future droughts, it is necessary to understand its behavior during past events. Satellite observations provide a practical source of continuous observations of Amazonian forest. Here we used a passive microwave-based vegetation water content record (i.e., vegetation optical depth, VOD), together with multiple hydrometeorological observations as well as conventional satellite vegetation measures, to investigate the rainforest canopy dynamics during the 2005 and 2010 droughts. During the onset of droughts in the wet-to-dry season (May–July) of both years, we found large-scale positive anomalies in VOD, leaf area index (LAI) and enhanced vegetation index (EVI) over the southern Amazonia. These observations are very likely caused by enhanced canopy growth. Concurrent below-average rainfall and above-average radiation during the wet-to-dry season can be interpreted as an early arrival of normal dry season conditions, leading to enhanced new leaf development and ecosystem photosynthesis, as supported by field observations. Our results suggest that further rainfall deficit into the subsequent dry season caused water and heat stress during the peak of 2005 and 2010 droughts (August–October) that exceeded the tolerance limits of the rainforest, leading to widespread negative VOD anomalies over the southern Amazonia. Significant VOD anomalies were observed mainly over the western part in 2005 and mainly over central and eastern parts in 2010. The total area with significant negative VOD anomalies was comparable between these two drought years, though the average magnitude of significant negative VOD anomalies was greater in 2005. This finding broadly agrees with the field observations indicating that the reduction in biomass carbon uptake was stronger in 2005 than 2010. The enhanced canopy growth

  18. 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.

  19. Enhanced canopy growth precedes senescence in 2005 and 2010 Amazonian droughts

    KAUST Repository

    Liu, Yi Y.; van Dijk, Albert I.J.M.; Miralles, Diego G.; McCabe, Matthew; Evans, Jason P.; de Jeu, Richard A.M.; Gentine, Pierre; Huete, Alfredo; Parinussa, Robert M.; Wang, Lixin; Guan, Kaiyu; Berry, Joe; Restrepo-Coupe, Natalia

    2018-01-01

    Unprecedented droughts hit southern Amazonia in 2005 and 2010, causing a sharp increase in tree mortality and carbon loss. To better predict the rainforest's response to future droughts, it is necessary to understand its behavior during past events. Satellite observations provide a practical source of continuous observations of Amazonian forest. Here we used a passive microwave-based vegetation water content record (i.e., vegetation optical depth, VOD), together with multiple hydrometeorological observations as well as conventional satellite vegetation measures, to investigate the rainforest canopy dynamics during the 2005 and 2010 droughts. During the onset of droughts in the wet-to-dry season (May–July) of both years, we found large-scale positive anomalies in VOD, leaf area index (LAI) and enhanced vegetation index (EVI) over the southern Amazonia. These observations are very likely caused by enhanced canopy growth. Concurrent below-average rainfall and above-average radiation during the wet-to-dry season can be interpreted as an early arrival of normal dry season conditions, leading to enhanced new leaf development and ecosystem photosynthesis, as supported by field observations. Our results suggest that further rainfall deficit into the subsequent dry season caused water and heat stress during the peak of 2005 and 2010 droughts (August–October) that exceeded the tolerance limits of the rainforest, leading to widespread negative VOD anomalies over the southern Amazonia. Significant VOD anomalies were observed mainly over the western part in 2005 and mainly over central and eastern parts in 2010. The total area with significant negative VOD anomalies was comparable between these two drought years, though the average magnitude of significant negative VOD anomalies was greater in 2005. This finding broadly agrees with the field observations indicating that the reduction in biomass carbon uptake was stronger in 2005 than 2010. The enhanced canopy growth

  20. 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.

  1. Oral Hygiene Behaviors and Caries Experience in Northwest PRECEDENT Patients

    Science.gov (United States)

    Rothen, Marilynn; Cunha-Cruz, Joana; Zhou, Lingmei; Mancl, Lloyd; Jones, Jackie S.; Berg, Joel

    2014-01-01

    Objectives To investigate the association between oral hygiene behaviors (toothbrushing, water rinsing after brushing, interproximal cleaning, and adjunctive use of fluoride products) and recent caries (past 24 months) in a random sample of patients in Northwest PRECEDENT practices. Methods Practitioner-members of Northwest PRECEDENT dental Practice-based Research Network (PBRN) conducted a longitudinal study on caries risk assessment. At baseline patients completed a questionnaire on oral self-care, snacking, health, and socio-demographics. A dental exam recorded readily-visible heavy plaque and DMFT; chart review captured new caries and treatments in the previous 24 months. Bivariate and multiple GEE log-linear regression models stratified by age groups were used to relate oral hygiene behaviors to the primary outcome of mean dental caries in the past 24 months on data from 1400 patients in 63 practices. The primary exposure of interest was fluoride toothbrushing frequency. Results Fluoride toothbrushing once per day or more by patients 9-17 was significantly associated with a 50% lower mean caries rate compared to fluoride toothbrushing less than once per day, after adjustment for age, gender, race, education, income, between-meal carbohydrate snacks, sugar-added beverages, alcohol consumption, smoking, BMI, exercise, stimulated salivary pH, number of teeth, and all other oral hygiene behaviors captured [Rate Ratio (RR)=0.5; 95% confidence interval (CI)=0.3-0.8]. After adjustment, for patients 18-64 fluoride toothbrushing two or more times per day was significantly associated with a 40% lower recent mean caries rate (RR=0.6; 95%CI=0.4-0.9); in patients 65+, twice a day or more fluoride toothbrushing was not associated with lower caries rates (RR=1.1; 95%CI=0.7-1.8). Of the other oral hygiene variables, after adjustment, patients 18-64 who rinsed with water after brushing had a 40% lower mean caries rate compared to no rinsing (RR=0.6; 95%CI=0.4-0.9) and the

  2. 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.

  3. Integrated Vehicle Ground Vibration Testing of Manned Spacecraft: Historical Precedent

    Science.gov (United States)

    Lemke, Paul R.; Tuma, Margaret L.; Askins, Bruce R.

    2008-01-01

    For the first time in nearly 30 years, NASA is developing a new manned space flight launch system. The Ares I will carry crew and cargo to not only the International Space Station, but onward for the future exploration of the Moon and Mars. The Ares I control system and structural designs use complex computer models for their development. An Integrated Vehicle Ground Vibration Test (IVGVT) will validate the efficacy of these computer models. The IVGVT will reduce the technical risk of unexpected conditions that could place the vehicle or crew in jeopardy. The Ares Project Office's Flight and Integrated Test Office commissioned a study to determine how historical programs, such as Saturn and Space Shuttle, validated the structural dynamics of an integrated flight vehicle. The study methodology was to examine the historical record and seek out members of the engineering community who recall the development of historic manned launch vehicles. These records and interviews provided insight into the best practices and lessons learned from these historic development programs. The information that was gathered allowed the creation of timelines of the historic development programs. The timelines trace the programs from the development of test articles through test preparation, test operations, and test data reduction efforts. These timelines also demonstrate how the historical tests fit within their overall vehicle development programs. Finally, the study was able to quantify approximate staffing levels during historic development programs. Using this study, the Flight and Integrated Test Office was able to evaluate the Ares I Integrated Vehicle Ground Vibration Test schedule and workforce budgets in light of the historical precedents to determine if the test had schedule or cost risks associated with it.

  4. Citrobacter freundii impairs the phosphoryl transfer network in the gills of Rhamdia quelen: Impairment of bioenergetics homeostasis.

    Science.gov (United States)

    Baldissera, Matheus D; Souza, Carine F; Junior, Guerino B; Moreira, Karen Luise S; da Veiga, Marcelo L; da Rocha, Maria Izabel U M; Baldisserotto, Bernardo

    2018-04-01

    The precise coupling of spatially separated intracellular adenosine triphosphate (ATP)-producing and ATP-consuming, catalyzed by creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), is a critical process in the bioenergetics of tissues with high energy demand, such as the branchial tissue. The effects of Citrobacter freundii infection on gills remain poorly understood, limited only to histopathological studies. Thus, the aim of this study was to evaluate whether experimental infection by C. freundii impairs the enzymes of the phosphoryl transfer network in gills of silver catfish (Rhamdia quelen). The CK (cytosolic and mitochondrial) and AK activities decreased in infected compared to uninfected animals, while the PK activity did not differ between groups. The gill histopathology of infected animals revealed extensive degeneration with fusion and necrosis of secondary lamellae, detachment of superficial epithelium, aneurysm, vessel congestion and inflammatory process. Based on these evidences, the inhibition and absence of an efficient communication between CK compartments caused the impairment of the branchial bioenergetics homeostasis, which was not compensated by the augmentation on branchial AK activity in an attempt to restore energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to branchial tissue in animals infected with C. freundii. Copyright © 2018. Published by Elsevier Ltd.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

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

  7. Hunt warm, rest cool: bioenergetic strategy underlying diel vertical migration of a benthic shark.

    Science.gov (United States)

    Sims, David W; Wearmouth, Victoria J; Southall, Emily J; Hill, Jacqueline M; Moore, Pippa; Rawlinson, Kate; Hutchinson, Neil; Budd, Georgina C; Righton, David; Metcalfe, Julian D; Nash, Jon P; Morritt, David

    2006-01-01

    -choice scenarios indicated dogfish adopting a 'hunt warm - rest cool' strategy could lower daily energy costs by just over 4%. Our results provide the first clear evidence that are consistent with the hypothesis that a benthic marine-fish predator utilizes DVM as an energy conservation strategy that increases bioenergetic efficiency.

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

    International Nuclear Information System (INIS)

    Sappal, Ravinder; MacDonald, Nicole; Fast, Mark; Stevens, Don; Kibenge, Fred; Siah, Ahmed; Kamunde, Collins

    2014-01-01

    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 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, Cu

  9. 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

  10. Research Results of Bioenergetics Factors Influence on Crop Production Yields Increase

    Directory of Open Access Journals (Sweden)

    A. P. Grishin

    2018-01-01

    Full Text Available The results of a fundamental research is presented confirming two hypotheses concerning the process of a crop harvest forming and transpiration as the two main bio-energetic factors of fertility. Transpiration is a thermodynamic process in an open self-organizing system, which has a dissipative random character. Transpiration consumes about 95 percent of the water consumed by the plant. (Purpose of research The research objective is to obtain results confirming two hypotheses, according to which the efficiency of the process of crop formation is due to transpiration as a bio-energy factor of fertility and its components: photosynthetic exergy and thermal exergy. (Methods and materials The basic principles of thermodynamic systems self-organization, as well as methods of experimental studies of the principle of subordination to the parameter of the order in which the system control variable is dependent on parameter of the order. The relation of the order parameter (thermal exergy of solar radiation (SR and the variable control (transpiration was determined. The values of the correlation coefficients of these two processes have a value close to one. This confirms that transpiration is a dissipative self-organizing process underlying the transpiration irrigation mechanism. It is revealed that a fractal dimension of a time series of transpiration of cucumber with natural light, a potato is artificial, and their probability haracteristics: the mathematical expectation, standard deviation and variance. (Results and discussion We received confirmation of the scientific hypothesis about the influence of limiting climatic factors on the theoretical limit of plant productivity and fractal dimension of transpiration as an indicator of production processes in crop production. (Conclusions We put forward supplemental scientific hypothesis about the influence of limiting climatic factors on the theoretical limit of plant productivity. It was showed that

  11. Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents.

    Science.gov (United States)

    Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J; Morgan, David E; Bledsoe, Amber D; Jessop, Jacob E; Amann, Markus; Richardson, Russell S

    2017-12-01

    The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation. Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (P-MRS). The magnitude of metabolic perturbation was significantly greater in FENT compared with CTRL for [Pi] (37.8 ± 16.8 vs 28.6 ± 8.6 mM), [H2PO4] (24.3 ± 12.2 vs 17.9 ± 7.1 mM), and [ATP] (75.8% ± 17.5% vs 81.9% ± 15.8% of baseline), whereas there was no significant difference in [PCr] (4.5 ± 2.4 vs 4.4 ± 2.3 mM) or pH (6.51 ± 0.10 vs 6.54 ± 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4], and pH was significantly faster in FENT compared with CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than in CTRL, resulting in a significantly greater ATP cost of contraction (0.049 ± 0.016 vs 0.038 ± 0.010 mM·min·N). Group III/IV muscle afferents not only constrain the magnitude of perturbation in intramuscular Pi, H2PO4, and ATP during small muscle mass exercise but also seem to play a role in maintaining efficient skeletal muscle contractile function in men.

  12. Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Matthews, Marguerite; Nigg, Joel T.

    2014-01-01

    Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder’s pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID:24214656

  13. 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

    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

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

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    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

  15. [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.

  16. Zebrafish: a model animal for analyzing the impact of environmental pollutants on muscle and brain mitochondrial bioenergetics.

    Science.gov (United States)

    Bourdineaud, Jean-Paul; Rossignol, R; Brèthes, D

    2013-01-01

    Mercury, anthropogenic release of uranium (U), and nanoparticles constitute hazardous environmental pollutants able to accumulate along the aquatic food chain with severe risk for animal and human health. The impact of such pollutants on living organisms has been up to now approached by classical toxicology in which huge doses of toxic compounds, environmentally irrelevant, are displayed through routes that never occur in the lifespan of organisms (for instance injecting a bolus of mercury to an animal although the main route is through prey and fish eating). We wanted to address the effect of such pollutants on the muscle and brain mitochondrial bioenergetics under realistic conditions, at unprecedented low doses, using an aquatic model animal, the zebrafish Danio rerio. We developed an original method to measure brain mitochondrial respiration: a single brain was put in 1.5 mL conical tube containing a respiratory buffer. Brains were gently homogenized by 13 strokes with a conical plastic pestle, and the homogenates were immediately used for respiration measurements. Skinned muscle fibers were prepared by saponin permeabilization. Zebrafish were contaminated with food containing 13 μg of methylmercury (MeHg)/g, an environmentally relevant dose. In permeabilized muscle fibers, we observed a strong inhibition of both state 3 mitochondrial respiration and cytochrome c oxidase activity after 49 days of MeHg exposure. We measured a dramatic decrease in the rate of ATP release by skinned muscle fibers. Contrarily to muscles, brain mitochondrial respiration was not modified by MeHg exposure although brain accumulated twice as much MeHg than muscles. When zebrafish were exposed to 30 μg/L of waterborne U, the basal mitochondrial respiratory control ratio was decreased in muscles after 28 days of exposure. This was due to an increase of the inner mitochondrial membrane permeability. The impact of a daily ration of food containing gold nanoparticles of two sizes (12 and

  17. Skeletal muscle bioenergetics during all-out exercise: mechanistic insight into the oxygen uptake slow component and neuromuscular fatigue.

    Science.gov (United States)

    Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J; Amann, Markus; Richardson, Russell S

    2017-05-01

    Although all-out exercise protocols are commonly used, the physiological mechanisms underlying all-out exercise performance are still unclear, and an in-depth assessment of skeletal muscle bioenergetics is lacking. Therefore, phosphorus magnetic resonance spectroscopy ( 31 P-MRS) was utilized to assess skeletal muscle bioenergetics during a 5-min all-out intermittent isometric knee-extensor protocol in eight healthy men. Metabolic perturbation, adenosine triphosphate (ATP) synthesis rates, ATP cost of contraction, and mitochondrial capacity were determined from intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (P i ), diprotonated phosphate ([Formula: see text]), and pH. Peripheral fatigue was determined by exercise-induced alterations in potentiated quadriceps twitch force (Q tw ) evoked by supramaximal electrical femoral nerve stimulation. The oxidative ATP synthesis rate (ATP OX ) attained and then maintained peak values throughout the protocol, despite an ~63% decrease in quadriceps maximal force production. ThusATP OX normalized to force production (ATP OX gain) significantly increased throughout the exercise (1st min: 0.02 ± 0.01, 5th min: 0.04 ± 0.01 mM·min -1 ·N -1 ), as did the ATP cost of contraction (1st min: 0.048 ± 0.019, 5th min: 0.052 ± 0.015 mM·min -1 ·N -1 ). Additionally, the pre- to postexercise change in Q tw (-52 ± 26%) was significantly correlated with the exercise-induced change in intramuscular pH ( r = 0.75) and [Formula: see text] concentration ( r = 0.77). In conclusion, the all-out exercise protocol utilized in the present study elicited a "slow component-like" increase in intramuscular ATP OX gain as well as a progressive increase in the phosphate cost of contraction. Furthermore, the development of peripheral fatigue was closely related to the perturbation of specific fatigue-inducing intramuscular factors (i.e., pH and [Formula: see text] concentration). NEW & NOTEWORTHY The physiological mechanisms

  18. Hydrometeorological conditions preceding wildfire, and the subsequent burning of a fen watershed in Fort McMurray, Alberta, Canada

    Science.gov (United States)

    Elmes, Matthew C.; Thompson, Dan K.; Sherwood, James H.; Price, Jonathan S.

    2018-01-01

    The destructive nature of the ˜ 590 000 ha Horse river wildfire in the Western Boreal Plain (WBP), northern Alberta, in May of 2016 motivated the investigation of the hydrometeorological conditions that preceded the fire. Historical climate and field hydrometeorological data from a moderate-rich fen watershed were used to (a) identify whether the spring 2016 conditions were outside the range of natural variability for WBP climate cycles, (b) explain the observed patterns in burn severity across the watershed, and (c) identify whether fall and winter moisture signals observed in peatlands and lowland forests in the region are indicative of wildfire. Field hydrometeorological data from the fen watershed confirmed the presence of cumulative moisture deficits prior to the fire. Hydrogeological investigations highlighted the susceptibility of fen and upland areas to water table and soil moisture decline over rain-free periods (including winter), due to the watershed's reliance on supply from localized flow systems originating in topographic highs. Subtle changes in topographic position led to large changes in groundwater connectivity, leading to greater organic soil consumption by fire in wetland margins and at high elevations. The 2016 spring moisture conditions measured prior to the ignition of the fen watershed were not illustrated well by the Drought Code (DC) when standard overwintering procedures were applied. However, close agreement was found when default assumptions were replaced with measured duff soil moisture recharge and incorporated into the overwintering DC procedure. We conclude that accumulated moisture deficits dating back to the summer of 2015 led to the dry conditions that preceded the fire. The infrequent coinciding of several hydrometeorological conditions, including low autumn soil moisture, a modest snowpack, lack of spring precipitation, and high spring air temperatures and winds, ultimately led to the Horse river wildfire spreading widely and

  19. Pragmatic communication deficits in children with epilepsy

    NARCIS (Netherlands)

    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

  20. Alkaliphilic bacteria with impact on industrial applications, concepts of early life forms and bioenergetics of ATP synthesis

    Directory of Open Access Journals (Sweden)

    Laura ePreiss

    2015-06-01

    Full Text Available Alkaliphilic bacteria typically grow well at pH 9, with the most extremophilic strains growing up to pH values as high as pH 12-13. Interest in extreme alkaliphiles arises because they are sources of useful, stable enzymes, and the cells themselves can be used for biotechnological and other applications at high pH. In addition, alkaline hydrothermal vents represent an early evolutionary niche for alkaliphiles and novel extreme alkaliphiles have also recently been found in alkaline serpentinizing sites. A third focus of interest in alkaliphiles is the challenge raised by the use of proton-coupled ATP synthases for oxidative phosphorylation by non-fermentative alkaliphiles. This creates a problem with respect to tenets of the chemiosmotic model that remains the core model for the bioenergetics of oxidative phosphorylation. Each of these facets of alkaliphilic bacteria will be discussed with a focus on extremely alkaliphilic Bacillus strains. These alkaliphilic bacteria have provided a cogent experimental system to probe adaptations that enable their growth and oxidative phosphorylation at high pH. Adaptations are clearly needed to enable secreted or partially exposed enzymes or protein complexes to function at the high external pH. Also, alkaliphiles must maintain a cytoplasmic pH that is significantly lower than the pH of the outside medium. This protects cytoplasmic components from an external pH that is alkaline enough to impair their stability or function. However, the pH gradient across the cytoplasmic membrane, with its orientation of more acidic inside than outside, is in the reverse of the productive orientation for bioenergetic work. The reversed gradient reduces the trans-membrane proton motive force available to energize ATP synthesis. Multiple strategies are hypothesized to be involved in enabling alkaliphiles to circumvent the challenge of a low bulk proton-motive force energizing proton-coupled ATP synthesis at high pH.

  1. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

    Science.gov (United States)

    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  2. 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.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

    2014-01-01

    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. PMID:25104046

  3. Precedent approach to the formation of programs for cyclic objects control

    Science.gov (United States)

    Kulakov, S. M.; Trofimov, V. B.; Dobrynin, A. S.; Taraborina, E. N.

    2018-05-01

    The idea and procedure for formalizing the precedent method of formation of complex control solutions (complex control programs) is discussed with respect to technological or organizational objects, the operation of which is organized cyclically. A typical functional structure of the system of precedent control by complex technological unit is developed, including a subsystem of retrospective optimization of actually implemented control programs. As an example, the problem of constructing replaceable planograms for the operation of the link of a heading-and-winning machine on the basis of precedents is considered.

  4. An improved car-following model accounting for the preceding car's taillight

    Science.gov (United States)

    Zhang, Jian; Tang, Tie-Qiao; Yu, Shao-Wei

    2018-02-01

    During the deceleration process, the preceding car's taillight may have influences on its following car's driving behavior. In this paper, we propose an extended car-following model with consideration of the preceding car's taillight. Two typical situations are used to simulate each car's movement and study the effects of the preceding car's taillight on the driving behavior. Meanwhile, sensitivity analysis of the model parameter is in detail discussed. The numerical results show that the proposed model can improve the stability of traffic flow and the traffic safety can be enhanced without a decrease of efficiency especially when cars pass through a signalized intersection.

  5. Plasma 3-methoxy-4-hydroxyphenylglycol and homovanillic acid measurements in deficit and nondeficit forms of schizophrenia.

    Science.gov (United States)

    Thibaut, F; Ribeyre, J M; Dourmap, N; Ménard, J F; Dollfus, S; Petit, M

    1998-01-01

    Discrepancies in the biochemical research on negative symptoms in schizophrenia may be ascribed to the lack of differentiation into primary and secondary negative symptoms. We have used Carpenter's criteria to define the deficit syndrome of schizophrenia as the presence of enduring and primary negative symptoms and measured catecholaminergic parameters in deficit as compared with nondeficit schizophrenics. We have investigated plasma homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG) concentrations in 34 DSM-III-R neuroleptic-treated schizophrenic patients who were classified into deficit (n = 14) and nondeficit (n = 20) forms of schizophrenia. All these patients were in a stable clinical and therapeutic status for the preceding 12 months. The 14 deficit schizophrenic patients had lower plasma levels of pHVA and higher plasma concentrations of pMHPG from 9 AM to 12 AM as compared with the 20 nondeficit schizophrenic patients. The two groups did not differ on any demographic, therapeutic, or clinical variable considered. Our data are consistent with the postulated distinct pathophysiological basis for the deficit syndrome of schizophrenia and suggest that opposite alterations in the pHVA or pMHPG levels may reflect specific changes in noradrenergic and dopaminergic functions in these deficit patients.

  6. Visual search deficits in amblyopia.

    Science.gov (United States)

    Tsirlin, Inna; Colpa, Linda; Goltz, Herbert C; Wong, Agnes M F

    2018-04-01

    Amblyopia is a neurodevelopmental disorder defined as a reduction in visual acuity that cannot be corrected by optical means. It has been associated with low-level deficits. However, research has demonstrated a link between amblyopia and visual attention deficits in counting, tracking, and identifying objects. Visual search is a useful tool for assessing visual attention but has not been well studied in amblyopia. Here, we assessed the extent of visual search deficits in amblyopia using feature and conjunction search tasks. We compared the performance of participants with amblyopia (n = 10) to those of controls (n = 12) on both feature and conjunction search tasks using Gabor patch stimuli, varying spatial bandwidth and orientation. To account for the low-level deficits inherent in amblyopia, we measured individual contrast and crowding thresholds and monitored eye movements. The display elements were then presented at suprathreshold levels to ensure that visibility was equalized across groups. There was no performance difference between groups on feature search, indicating that our experimental design controlled successfully for low-level amblyopia deficits. In contrast, during conjunction search, median reaction times and reaction time slopes were significantly larger in participants with amblyopia compared with controls. Amblyopia differentially affects performance on conjunction visual search, a more difficult task that requires feature binding and possibly the involvement of higher-level attention processes. Deficits in visual search may affect day-to-day functioning in people with amblyopia.

  7. 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.

  8. A Proper Perspective on the Twin Deficits

    Science.gov (United States)

    1989-05-01

    deficit twins, the relation between them, and their consanguine parentage. The trade deficit or, to be more accurate, the current account deficit, is...In general, there is a small negative, but statistically significant, relationship between the size of the federal deficit in one year and the

  9. Preceding diagnoses to young adult bipolar disorder and schizophrenia in a nationwide study

    Science.gov (United States)

    2013-01-01

    Background The aim of this comparative study was to investigate the type and frequency of diagnoses preceding adult bipolar disorder (BD) and schizophrenia (SZ). Methods A follow-back study of all preceding diagnoses in all patients aged 21–34 years with a primary, first time diagnosis of BD (N = 784) or SZ (N = 1667) in 2008 to 2010. Data were taken from the Danish Psychiatric Central Research Register (DPCRR) including ICD-10 and ICD-8 diagnoses. Results The numbers of patients with any preceding diagnoses amounted to 69.3% in BD and 76.6% in SZ with affective disorders (excluding BD) being the most frequent preceding diagnosis (46.6 vs. 28.0%), followed by psychoses (PSY) other than SZ (14.2 vs. 41.5%, p adolescence. Overall patients with SZ had a minor but statistically significant earlier onset of any psychiatric disorder compared to BD (mean age: 23.3 vs. 22.5, p < .001). Regression analyses indicated that BD was associated with an increased risk of having experienced preceding affective disorders and ADHD, while SZ was associated with an increased risk of preceding substance use disorders, psychosis, anxiety disorders, and personality disorders. Conclusions Specific developmental trajectories of preceding disorders were delineated for BD and SZ with affective disorders being more specific for BD and both SUD and PSY more specific to SZ. There are different patterns of vulnerability in terms of preceding diagnosis in young adults with BD and SZ. PMID:24359146

  10. Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

    Science.gov (United States)

    Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

    2015-05-01

    The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

  11. 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.

  12. General contrast effects in speech perception: effect of preceding liquid on stop consonant identification.

    Science.gov (United States)

    Lotto, A J; Kluender, K R

    1998-05-01

    When members of a series of synthesized stop consonants varying acoustically in F3 characteristics and varying perceptually from /da/ to /ga/ are preceded by /al/, subjects report hearing more /ga/ syllables relative to when each member is preceded by /ar/ (Mann, 1980). It has been suggested that this result demonstrates the existence of a mechanism that compensates for coarticulation via tacit knowledge of articulatory dynamics and constraints, or through perceptual recovery of vocal-tract dynamics. The present study was designed to assess the degree to which these perceptual effects are specific to qualities of human articulatory sources. In three experiments, series of consonant-vowel (CV) stimuli varying in F3-onset frequency (/da/-/ga/) were preceded by speech versions or nonspeech analogues of /al/ and /ar/. The effect of liquid identity on stop consonant labeling remained when the preceding VC was produced by a female speaker and the CV syllable was modeled after a male speaker's productions. Labeling boundaries also shifted when the CV was preceded by a sine wave glide modeled after F3 characteristics of /al/ and /ar/. Identifications shifted even when the preceding sine wave was of constant frequency equal to the offset frequency of F3 from a natural production. These results suggest an explanation in terms of general auditory processes as opposed to recovery of or knowledge of specific articulatory dynamics.

  13. Effectiveness of the PRECEDE model in obese patients undergoing primary care nurses follow-up

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    Inés Maria Barrio Cantalejo

    2004-04-01

    Full Text Available Obesity is a serious problem in western modern countries. Primary care nurses has to follow up these patients but often with poor results. The PRECEDE model (Green L.W try to help patients to identify factors that predispose, make easier or reinforce their relationship with food and physical exercise. Objectives: To evaluate if PRECEDE makes easier the adherence of obese patients to a new style of feeding and exercise that reduces their BMI. Metodology: Experimental design, community randomised study. We analysed two samples of two different interventions: in one we applied the PRECEDE, in the other one the conventional advice about diet and exercise. Measures at 12 and 18 months. Both samples were homogeneous. The relationship between qualitative data has been studied through the Pearson x2 test and the comparison of quantitative data between two groups through the Student T test for independent samples. Results: a The PRECEDE intervention group lost more weigh than control at 12ª month, but this difference is almost null at 18º month. b The BMI difference has low clinical value because in both cases the final BMI is >30. Conclusions: a PRECEDE model shows a major capacity to reduce the BMI than the conventional model at short time. b To conclude that the PRECEDE weigh reduction is clinically effective we should have to extend our educational intervention longer time.

  14. Evolution of the F0F1 ATP synthase complex in light of the patchy distribution of different bioenergetic pathways across prokaryotes.

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    Vassiliki Lila Koumandou

    2014-09-01

    Full Text Available Bacteria and archaea are characterized by an amazing metabolic diversity, which allows them to persist in diverse and often extreme habitats. Apart from oxygenic photosynthesis and oxidative phosphorylation, well-studied processes from chloroplasts and mitochondria of plants and animals, prokaryotes utilize various chemo- or lithotrophic modes, such as anoxygenic photosynthesis, iron oxidation and reduction, sulfate reduction, and methanogenesis. Most bioenergetic pathways have a similar general structure, with an electron transport chain composed of protein complexes acting as electron donors and acceptors, as well as a central cytochrome complex, mobile electron carriers, and an ATP synthase. While each pathway has been studied in considerable detail in isolation, not much is known about their relative evolutionary relationships. Wanting to address how this metabolic diversity evolved, we mapped the distribution of nine bioenergetic modes on a phylogenetic tree based on 16S rRNA sequences from 272 species representing the full diversity of prokaryotic lineages. This highlights the patchy distribution of many pathways across different lineages, and suggests either up to 26 independent origins or 17 horizontal gene transfer events. Next, we used comparative genomics and phylogenetic analysis of all subunits of the F0F1 ATP synthase, common to most bacterial lineages regardless of their bioenergetic mode. Our results indicate an ancient origin of this protein complex, and no clustering based on bioenergetic mode, which suggests that no special modifications are needed for the ATP synthase to work with different electron transport chains. Moreover, examination of the ATP synthase genetic locus indicates various gene rearrangements in the different bacterial lineages, ancient duplications of atpI and of the beta subunit of the F0 subcomplex, as well as more recent stochastic lineage-specific and species-specific duplications of all subunits. We

  15. The Extracts and Major Compounds Derived from Astragali Radix Alter Mitochondrial Bioenergetics in Cultured Cardiomyocytes: Comparison of Various Polar Solvents and Compounds

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    Yun Huang

    2018-05-01

    Full Text Available Astragali Radix (AR is a widely used “Qi-invigorating” herb in China for its tonic effects in strengthening biological tissues. The extract of AR contains abundant antioxidants, including astragalosides and isoflavonoids. However, very few reports have systematically measured the effects of the major components of AR on cell mitochondrial bioenergetics. Here, a systemic approach employing an extracellular flux analyzer was developed to evaluate mitochondrial respiration in cultured cardiomyocyte cells H9C2. The effects of different polar extractives, as well as of the major compounds of AR, were compared. The contents of astragaloside IV, calycosin, formononetin, and genistein in the AR extracts obtained by using water, 50% ethanol, and 90% ethanol were measured by liquid chromatograph-mass spectrometer (LC–MS. The antioxidant activities of the AR extracts, as well as of their major compounds, were determined by measuring the free radical scavenging activity and protective effects in tert-butyl hydroperoxide (tBHP-treated H9C2 cells. By monitoring the real-time oxygen consumption rate (OCR in tBHP-treated cardiomyocytes with a Seahorse extracellular flux analyzer, the tonic effects of the AR extracts and of their main compounds on mitochondrial bioenergetics were evaluated. AR water extracts possessed the strongest antioxidant activity and protective effects in cardiomyocytes exposed to oxidative stress. The protection was proposed to be mediated via increasing the spare respiratory capacity and mitochondrial ATP production in the stressed cells. The major compounds of AR, astragaloside IV and genistein, showed opposite effects in regulating mitochondrial bioenergetics. These results demonstrate that highly polar extracts of AR, especially astragaloside-enriched extracts, possess better tonic effects on mitochondrial bioenergetics of cultured cardiomyocytes than extracts with a lower polarity.

  16. PRAGMATIC DEFICITS OF ASPERGER SYNDROME

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    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.

  17. Energy metabolism disorders in rare and common diseases. Toward bioenergetic modulation therapy and the training of a new generation of European scientists.

    Science.gov (United States)

    Rossignol, Rodrigue

    2015-06-01

    Energy metabolism alterations are found in a large number of rare and common diseases of genetic or environmental origin. The number of patients that could benefit from bioenergetic modulation therapy (BIOMET) is therefore very important and includes individuals with pathologies as diverse as mitochondrial diseases, acute coronary syndrome, chronic kidney disease, asthma or even cancer. Although, the alteration of energy metabolism is disease specific and sometimes patient specific, the strategies for BIOMET could be common and target a series of bioenergetic regulatory mechanisms discussed in this article. An excellent training of scientists in the field of energy metabolism, related human diseases and drug discovery is also crucial to form a young generation of MDs, PHDs and Pharma or CRO-group leaders who will discover novel personalized bioenergetic medicines, through pharmacology, genetics, nutrition or adapted exercise training. The Mitochondrial European Educational Training (MEET) consortium was created to pursue this goal, and we dedicated here a special issue of Organelle in Focus (OiF) to highlight their objectives. A total of 10 OiFs articles constitute this Directed Issue on Mitochondrial Medicine. As part of this editorial article, we asked timely questions to the PR. Jan W. Smeitink, professor of Mitochondrial Medicine and CEO of Khondrion, a mitochondrial medicine company. He shared with us his objectives and strategies for the study of mitochondrial diseases and the identification of future treatments. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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    Balbasi Fatemeh

    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

  19. Automatic Deficits can lead to executive deficits in ADHD

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    Gabriella Martino

    2017-12-01

    Full Text Available It has been well documented an executive dysfunction in children with Attention Deficit Hyperactivity Disorder (ADHD and with Reading Disorder (RD. The purpose of the present study was to test an alternative hypothesis that deficits in executive functioning within ADHD may be partially due to an impairment of the automatic processing. In addition, since the co-occurrence between ADHD and RD, we tested the hypothesis that the automatic processing may be  a possible common cognitive factor between ADHD and RD. We investigated the automatic processing of selective visual attention through two experiments. 12 children with ADHD, 17 with ADHD+RD and 29 typically developing children, matched for age and gender, performed two tasks: Visual Information Processing Task and Clock Test. As expected, ADHD and ADHD+RD groups differed from the control group in controlled process task, suggesting a deficit in executive functioning. All clinical subjects also exhibited a lower performance in automatic processes, compared to control group. The results of this study suggest that executive deficits within ADHD can be partially due to an impairment of automatic processing.

  20. No evidence of conpopulation sperm precedence between allopatric populations of house mice.

    Directory of Open Access Journals (Sweden)

    Renée C Firman

    Full Text Available Investigations into the evolution of reproductive barriers have traditionally focused on closely related species, and the prevalence of conspecific sperm precedence. The effectiveness of conspecific sperm precedence at limiting gene exchange between species suggests that gametic isolation is an important component of reproductive isolation. However, there is a paucity of tests for evidence of sperm precedence during the earlier stages of divergence, for example among isolated populations. Here, we sourced individuals from two allopatric populations of house mice (Mus domesticus and performed competitive in vitro fertilisation assays to test for conpopulation sperm precedence specifically at the gametic level. We found that ova population origin did not influence the outcome of the sperm competitions, and thus provide no evidence of conpopulation or heteropopulation sperm precedence. Instead, we found that males from a population that had evolved under a high level of postcopulatory sexual selection consistently outcompeted males from a population that had evolved under a relatively lower level of postcopulatory sexual selection. We standardised the number of motile sperm of each competitor across the replicate assays. Our data therefore show that competitive fertilizing success was directly attributable to differences in sperm fertilizing competence.

  1. No evidence of conpopulation sperm precedence between allopatric populations of house mice.

    Science.gov (United States)

    Firman, Renée C; Simmons, Leigh W

    2014-01-01

    Investigations into the evolution of reproductive barriers have traditionally focused on closely related species, and the prevalence of conspecific sperm precedence. The effectiveness of conspecific sperm precedence at limiting gene exchange between species suggests that gametic isolation is an important component of reproductive isolation. However, there is a paucity of tests for evidence of sperm precedence during the earlier stages of divergence, for example among isolated populations. Here, we sourced individuals from two allopatric populations of house mice (Mus domesticus) and performed competitive in vitro fertilisation assays to test for conpopulation sperm precedence specifically at the gametic level. We found that ova population origin did not influence the outcome of the sperm competitions, and thus provide no evidence of conpopulation or heteropopulation sperm precedence. Instead, we found that males from a population that had evolved under a high level of postcopulatory sexual selection consistently outcompeted males from a population that had evolved under a relatively lower level of postcopulatory sexual selection. We standardised the number of motile sperm of each competitor across the replicate assays. Our data therefore show that competitive fertilizing success was directly attributable to differences in sperm fertilizing competence.

  2. Study on Determination of Preceding Vehicle Motion State at the Traffic Lights Intersection

    Directory of Open Access Journals (Sweden)

    Cailin Wu

    2014-10-01

    Full Text Available In order to enhance the security of automotive safety systems and reduce traffic accidents in traffic lights intersection, In view of this, it is proposed to apply the distance measurement technology of binocular vision ranging in determination of preceding vehicle motion state at the traffic lights intersection, We study the determination of preceding vehicle motion state at the traffic lights intersection based on binocular vision. The system, which is divided into four steps, adopts the theory combining the binocular stereo vision principle and the triangulation principle. First of all, from different angles, image information with preceding vehicles and traffic lights, collected by two CCD cameras, is processed and positioned. Next, two pairs of corresponding feature matching points is obtained by using the stereo matching method. Furthermore, the distance between the cameras and the preceding vehicle, and the distance between the cameras and the traffic lights are determined, according to the camera calibration technique, the parallax disparity principle and the triangulation principle. Finally, the determination about the motion state of traffic lights intersection is determined according to the distance difference principle. Experimental results show that the design, with high measurement accuracy and application value, realize the determination of preceding vehicle’s motion state at traffic lights intersection.

  3. 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.

  4. 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.

  5. 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

    2009-01-01

    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. PMID:19399243

  6. A dynamic bioenergetic model for coral-Symbiodinium symbioses and coral bleaching as an alternate stable state.

    Science.gov (United States)

    Cunning, Ross; Muller, Erik B; Gates, Ruth D; Nisbet, Roger M

    2017-10-27

    Coral reef ecosystems owe their ecological success - and vulnerability to climate change - to the symbiotic metabolism of corals and Symbiodinium spp. The urgency to understand and predict the stability and breakdown of these symbioses (i.e., coral 'bleaching') demands the development and application of theoretical tools. Here, we develop a dynamic bioenergetic model of coral-Symbiodinium symbioses that demonstrates realistic steady-state patterns in coral growth and symbiont abundance across gradients of light, nutrients, and feeding. Furthermore, by including a mechanistic treatment of photo-oxidative stress, the model displays dynamics of bleaching and recovery that can be explained as transitions between alternate stable states. These dynamics reveal that "healthy" and "bleached" states correspond broadly to nitrogen- and carbon-limitation in the system, with transitions between them occurring as integrated responses to multiple environmental factors. Indeed, a suite of complex emergent behaviors reproduced by the model (e.g., bleaching is exacerbated by nutrients and attenuated by feeding) suggests it captures many important attributes of the system; meanwhile, its modular framework and open source R code are designed to facilitate further problem-specific development. We see significant potential for this modeling framework to generate testable hypotheses and predict integrated, mechanistic responses of corals to environmental change, with important implications for understanding the performance and maintenance of symbiotic systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  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. 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.

  9. Rhythm Deficits in "Tone Deafness"

    Science.gov (United States)

    Foxton, Jessica M.; Nandy, Rachel K.; Griffiths, Timothy D.

    2006-01-01

    It is commonly observed that "tone deaf" individuals are unable to hear the beat of a tune, yet deficits on simple timing tests have not been found. In this study, we investigated rhythm processing in nine individuals with congenital amusia ("tone deafness") and nine controls. Participants were presented with pairs of 5-note sequences, and were…

  10. Hemodynamic deterioration precedes onset of ventricular tachyarrhythmia after Heartmate II implantation.

    Science.gov (United States)

    Yaksh, Ameeta; Kik, Charles; Knops, Paul; Zwiers, Korinne; van Ettinger, Maarten J B; Manintveld, Olivier C; de Wijs, Marcel C J; van der Kemp, Peter; Bogers, Ad J J C; de Groot, Natasja M S

    2016-07-08

    Early postoperative ventricular tachyarrhythmia (PoVT) after left ventricular assist device (LVAD) implantation are common and associated with higher mortality-rates. At present, there is no data on initiation of these PoVT and the role of alterations in cardiac hemodynamics. A LVAD was implanted in a patient with end-stage heart failure due to a ischemic cardiomyopathy. Alterations in cardiac rhythm and hemodynamics preceding PoVT-episodes during the first five postoperative days were examined by using continuous recordings of cardiac rhythm and various hemodynamic parameters. All PoVT (N=120) were monomorphic, most often preceded by short-long-short-sequences or regular SR and initiated by ventricular runs. Prior to PoVT, mean arterial pressure decreased; heart rate and ST-segments deviations increased. PoVT are caused by different underlying electrophysiological mechanisms. Yet, they are all monomorphic and preceded by hemodynamic deterioration due to myocardial ischemia.

  11. Global precedence effects account for individual differences in both face and object recognition performance.

    Science.gov (United States)

    Gerlach, Christian; Starrfelt, Randi

    2018-03-20

    There has been an increase in studies adopting an individual difference approach to examine visual cognition and in particular in studies trying to relate face recognition performance with measures of holistic processing (the face composite effect and the part-whole effect). In the present study we examine whether global precedence effects, measured by means of non-face stimuli in Navon's paradigm, can also account for individual differences in face recognition and, if so, whether the effect is of similar magnitude for faces and objects. We find evidence that global precedence effects facilitate both face and object recognition, and to a similar extent. Our results suggest that both face and object recognition are characterized by a coarse-to-fine temporal dynamic, where global shape information is derived prior to local shape information, and that the efficiency of face and object recognition is related to the magnitude of the global precedence effect.

  12. 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

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

    Science.gov (United States)

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

    2014-06-30

    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 recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

  14. 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.

  15. Global precedence effects account for individual differences in both face and object recognition performance

    DEFF Research Database (Denmark)

    Gerlach, Christian; Starrfelt, Randi

    2018-01-01

    examine whether global precedence effects, measured by means of non-face stimuli in Navon's paradigm, can also account for individual differences in face recognition and, if so, whether the effect is of similar magnitude for faces and objects. We find evidence that global precedence effects facilitate...... both face and object recognition, and to a similar extent. Our results suggest that both face and object recognition are characterized by a coarse-to-fine temporal dynamic, where global shape information is derived prior to local shape information, and that the efficiency of face and object recognition...

  16. Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

    Science.gov (United States)

    Bora, E; Binnur Akdede, B; Alptekin, K

    2017-10-01

    Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

  17. Perception in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Fuermaier, Anselm B.M.; Hüpen, Philippa; De Vries, Stefanie M.; Müller, Morgana; Kok, Francien M.; Koerts, Janneke; Heutink, Joost; Tucha, Lara; Gerlach, Manfred; Tucha, Oliver

    A large body of research demonstrated that individuals with attention deficit hyperactivity disorder (ADHD) suffer from various neuropsychological deficits. In contrast, less is known and only divergent evidence exists on perceptual functions of individuals with ADHD. This is problematic as

  18. Focusing on ADHD - Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    ... September 2014 Print this issue Focusing on ADHD Attention Deficit Hyperactivity Disorder En español Send us your comments ... might be signs of a developmental disorder called attention deficit hyperactivity disorder, or ADHD. ADHD is a common ...

  19. Attention-Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... Tube DysfunctionStrep ThroatAnemiaHyperthyroidismOpioid AddictionDiabetesCroup Home Diseases and Conditions Attention-Deficit Hyperactivity Disorder (ADHD) Condition Attention-Deficit Hyperactivity Disorder ( ...

  20. Adult Attention-Deficit / Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    Adult attention-deficit/hyperactivity disorder (ADHD) Overview Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that includes a combination of persistent problems, such as difficulty paying attention, ...

  1. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. 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 Tables ...

  3. 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…

  4. 48 CFR 11.101 - Order of precedence for requirements documents.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Order of precedence for... A-119, “Federal Participation in the Development and Use of Voluntary Consensus Standards and in... of 1995, Pub. L. 104-113 (15 U.S.C. 272 note), agencies must use voluntary consensus standards, when...

  5. Last mated male sperm precedence in doubly mated females is not ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 92; Issue 2. Last mated male sperm precedence in doubly mated females is not ubiquitous: evidence from sperm competition in laboratory populations of Drosophila nasuta nasuta and Drosophila nasuta albomicans. B. Shruthi S. R. Ramesh. Research Note Volume 92 Issue 2 ...

  6. In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

    NARCIS (Netherlands)

    Baltus, Andrew E.; Menke, Douglas B.; Hu, Yueh-Chiang; Goodheart, Mary L.; Carpenter, Anne E.; de Rooij, Dirk G.; Page, David C.

    2006-01-01

    The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions. We present genetic evidence of an analogous decision

  7. 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 d...

  8. 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

    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...

  9. Tiered Auctions for Multi-Agent Coordination in Domains with Precedence Constraints

    National Research Council Canada - National Science Library

    Jones, E. G; Dias, M. B; Stentz, Anthony

    2008-01-01

    .... In this work we focus on precedence-constrained emergency response. In this domain a group of fire trucks agents attempt to navigate through a city in order to extinguish a set of fires that have occurred in the wake of a large...

  10. 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...

  11. Use and adaptation of precedents in architectural design. Toward an evolutionary design model

    NARCIS (Netherlands)

    Moraes Zarzar, K.

    2003-01-01

    For centuries, architects have re-used design precedents in the conception of new design solutions. Whether explicitly - as in the case of Le Corbusier, James Stirling and Jo Coenen - or implicitly - as with J.J.P. Oud, Aldo van Eyk, and Santiago Calatrava - this practice has led to very

  12. Strategy Precedes Operational Effectiveness: Aligning High Graduation Rankings with Competitive Graduation Grade Point Averages

    Science.gov (United States)

    Apprey, Maurice; Bassett, Kimberley C.; Preston-Grimes, Patrice; Lewis, Dion W.; Wood, Beverly

    2014-01-01

    Two pivotal and interconnected claims are addressed in this article. First, strategy precedes program effectiveness. Second, graduation rates and rankings are insufficient in any account of academic progress for African American students. In this article, graduation is regarded as the floor and not the ceiling, as it were. The ideal situation in…

  13. Attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Meek, D C

    1990-09-01

    The attention-deficit hyperactivity disorder is a common chronic disorder of childhood. No precise definition or approach to treatment is universally accepted; however, an extensive literature exists on which to base a rational approach to management. Symptomatic treatment with stimulant medication in selected patients is effective and safe, but not curative. Successful outcome depends on multimodality therapy, involving parents, teachers, and other professionals. Associated conditions, including learning disorders and emotional disturbance, must be identified and dealt with.

  14. High Health Care Utilization Preceding Diagnosis of Systemic Lupus Erythematosus in Youth.

    Science.gov (United States)

    Chang, Joyce C; Mandell, David S; Knight, Andrea M

    2017-12-01

    Childhood-onset systemic lupus erythematosus (SLE) is associated with high risk for organ damage, which may be mitigated by early diagnosis and treatment. We characterized health care utilization for youth in the year preceding SLE diagnosis compared to controls. Using Clinformatics ™ DataMart (OptumInsight, Eden Prairie, MN) de-identified administrative data from 2000 to 2013, we identified 682 youth ages 10-24 years with new-onset SLE (≥3 International Classification of Diseases, Ninth Revision (ICD-9) codes for SLE 710.0, each >30 days apart), and 1,364 age and sex-matched healthy controls. We compared the incidence of ambulatory, emergency, and inpatient visits 12 months before SLE diagnosis, and frequency of primary diagnoses. We examined subject characteristics associated with utilization preceding SLE diagnosis. Youth with SLE had significantly more visits in the year preceding diagnosis than controls across ambulatory (incidence rate ratio (IRR) 2.48, p<0.001), emergency (IRR 3.42, p<0.001) and inpatient settings (IRR 3.02, p<0.001). The most frequent acute care diagnoses and median days to SLE diagnosis were: venous thromboembolism (313, interquartile range (IQR) 18-356), thrombocytopenia (278, IQR 39-354), chest pain (73, IQR 29.5-168), fever (52, IQR 17-166), and acute kidney failure (14, IQR 5-168). Having a psychiatric diagnosis prior to SLE diagnosis was strongly associated with increased utilization across all settings. Youth with SLE have high health care utilization throughout the year preceding SLE diagnosis. Examining variable diagnostic trajectories of youth presenting for acute care preceding SLE diagnosis, and increased attention to psychiatric morbidity may help improve care for youth with new-onset SLE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. No evidence for a bioenergetic advantage from forced swimming in rainbow trout under a restrictive feeding regime

    Directory of Open Access Journals (Sweden)

    Peter Vilhelm Skov

    2015-02-01

    Full Text Available Sustained swimming at moderate speeds is considered beneficial in terms of the productive performance of salmonids, but the causative mechanisms have yet to be unequivocally established. In the present study, the effects of moderate exercise on the bioenergetics of rainbow trout were assessed during a 15 week growth experiment, in which fish were reared at three different current speeds: 1 BL s-1, 0.5 BL s-1 and still water (≈ 0 BL s-1. Randomly selected groups of 100 fish were distributed among twelve 600 L tanks and maintained on a restricted diet regime. Specific growth rate (SGR and feed conversion ratio (FCR were calculated from weight and length measurements every three weeks. Routine metabolic rate (RMR was measured every hour as rate of oxygen consumption in the tanks, and was positively correlated with swimming speed. Total ammonia nitrogen (TAN excretion rates showed a tendency to decrease with increasing swimming speeds, yet neither they nor the resulting nitrogen quotients (NQ indicated that swimming significantly reduced the fraction of dietary protein used to fuel metabolism. Energetic budgets revealed a positive correlation between energy expenditure and the current speed at which fish were reared, fish that were forced to swim and were fed restrictively consequentially had poorer growth and feed utilization. The results show that for rainbow trout, water current can negatively affect growth despite promoting minor positive changes in substrate utilization. We hypothesize that this may be the result of either a limited dietary energy supply from diet restriction being insufficient for both covering the extra costs of swimming and supporting enhanced growth.

  16. 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.

  17. 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.

  18. A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study.

    Science.gov (United States)

    Raider, Kayla; Ma, Delin; Harris, Janna L; Fuentes, Isabella; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M; Stanford, John A

    2016-07-01

    Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions

    Science.gov (United States)

    Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

    2013-01-01

    Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy. PMID:24260552

  20. 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.

  1. 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.

  2. Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Deborah A. Ferrington

    2017-10-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo. Using the Seahorse Extracellular Flux Analyzer to measure bioenergetics, we observed RPE from donors with AMD exhibited reduced mitochondrial and glycolytic function compared with healthy donors. RPE from AMD donors were also more resistant to oxidative inactivation of these two energy-producing pathways and were less susceptible to oxidation-induced cell death compared with cells from healthy donors. Investigation of the potential mechanism responsible for differences in bioenergetics and resistance to oxidative stress showed RPE from AMD donors had increased PGC1α protein as well as differential expression of multiple genes in response to an oxidative challenge. Based on our data, we propose that cultured RPE from donors phenotyped for the presence or absence of AMD provides an excellent model system for studying “AMD in a dish”. Our results are consistent with the ideas that (i a bioenergetics crisis in the RPE contributes to AMD pathology, and (ii the diseased environment in vivo causes changes in the cellular profile that are retained in vitro.

  3. Association between the attention deficits and delinquency

    Directory of Open Access Journals (Sweden)

    Robert Opora

    2011-12-01

    Full Text Available In the society we can find a lot of prejudices concerning AD/HD. The article contains facts and evidence based on research presenting that the delinquency is very often a distant complication of attention deficits but it doesn’t mean that a child with attention deficits has to be delinquent. The article describes the association between the attention deficits and delinquency. There are presented some risk factors coming from the attention deficits and protective factors which let the child follow the social norms. The research was based on 108 delinquent juveniles staying under the probation supervision. The purpose of the research was to evaluate the frequency of the attention deficits among delinquent juveniles staying under supervision. The research findings concern also the association between the attention deficit and external behavioural disorders. In the summary several conditions are described which are important to protect children with attention deficit from delinquency.

  4. H2S-induced S-sulfhydration of lactate dehydrogenase a (LDHA) stimulates cellular bioenergetics in HCT116 colon cancer cells.

    Science.gov (United States)

    Untereiner, Ashley A; Oláh, Gabor; Módis, Katalin; Hellmich, Mark R; Szabo, Csaba

    2017-07-15

    Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H 2 S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H 2 S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line HCT116. Low concentrations of GYY4137 (a slow-releasing H 2 S donor) enhanced mitochondrial function (oxygen consumption, ATP production, and spare respiratory capacity) and glycolysis in HCT116 cells. SiRNA-mediated transient silencing of LDHA attenuated the GYY4137-induced stimulation of mitochondrial respiration, but not of glycolysis. H 2 S induced the S-sulfhydration of Cys163 in recombinant LDHA, and stimulated LDHA activity. The H 2 S-induced stimulation of LDHA activity was absent in C163A LDHA. As shown in HCT116 cell whole extracts, in addition to LDHA activation, GYY4137 also stimulated LDHB activity, although to a smaller extent. Total cellular lactate and pyruvate measurements showed that in HCT116 cells LDHA catalyzes the conversion of pyruvate to lactate. Total cellular lactate levels were increased by GYY4137 in wild-type cells (but not in cells with LDHA silencing). LDHA silencing sensitized HCT116 cells to glucose oxidase (GOx)-induced oxidative stress; this was further exacerbated with GYY4137 treatment. Treatment with low concentrations of GYY4137 (0.3mM) or GOx (0.01U/ml) significantly increased the proliferation rate of HCT116 cells; the effect of GOx, but not the effect of GYY4137 was attenuated by LDHA silencing. The current report points to the involvement of LDHA in the stimulatory effect of H 2 S on mitochondrial respiration in colon

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

    International Nuclear Information System (INIS)

    Zhang Hong; Li Guo-Hua

    2016-01-01

    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. (paper)

  6. 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).

  7. Validity and QOL of neck dissection preceding radiation therapy for hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Uemura, Hirokazu; Yoshino, Kunitoshi; Fujii, Takashi; Suzuki, Motoyuki

    2009-01-01

    Thirty-one cases of hypopharyngeal cancer with neck dissection preceding radiation and 16 cases of hypopharyngeal cancer with neck dissection for locoregional recurrences after radiation were reviewed in order to make comparative evaluations of difficulty in surgical operation, postoperative complications, laryngeal preservation rate, and cause specific 5-year survival rate retrospectively. And quality of life (QOL) after neck dissection was additionally evaluated through the questionnaire. Since neck dissection preceding radiation for hypopharyngeal cancer may be superior to neck dissection for radiation failure, with easy surgical approach an non-lymphoid tissue preservation, that modality can be a reasonable choice of treatment for patients with nodal lesions, which are probably difficult to treat with radiation alone. Even though further investigation on QOL questionnaire is necessary, this modality can make a contribution to the neck and shoulder condition after neck dissection. (author)

  8. Will the judgment in the Hague trial constitute a precedent in international law

    Directory of Open Access Journals (Sweden)

    Bojanić Petar

    2006-01-01

    Full Text Available On the great crime (mala in se; scelus infandum and sovereignty In this text we are attempting to think the International Criminal Tribunal for the former Yugoslavia together, and always with its necessary connection to the International Court of Justice and International Criminal Court. By paraphrasing the title of another work, the long forgotten Hans Kelsen text from 1947 (today usually used by detractors of the Tribunal "Will the Judgment in the Nuremberg Trial constitute a Precedent in International Law?", I wish to distinguish between the two Tribunals (as well as The Treaty of Versaille,and in so doing treat international law as legislative history or judicial precedents (and their recognition.

  9. Influence of Sound Source Location on the Behavior and Physiology of the Precedence Effect in Cats

    OpenAIRE

    Dent, Micheal L.; Tollin, Daniel J.; Yin, Tom C. T.

    2009-01-01

    Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from ∼0.4 to 10 ms, summing localization for |ISDs| 10 ms, which is the appro...

  10. Legal precedents regarding use and defensibility of risk assessment in Federal transportation of SNF and HLW

    International Nuclear Information System (INIS)

    Bentz, E.J. Jr.; Bentz, C.B.; O'Hora, T.D.; Chen, S.Y.

    1997-01-01

    Risk assessment has become an increasingly important and essential tool in support of Federal decision-making regarding the handling, storage, disposal, and transportation of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). This paper analyzes the current statutory and regulatory framework and related legal precedents with regard to SNF and HLW transportation. The authors identify key scientific and technical issues regarding the use and defensibility of risk assessment in Federal decision-making regarding anticipated shipments

  11. 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.

  12. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

    Science.gov (United States)

    Sones, Jennifer L; Merriam, Audrey A; Seffens, Angelina; Brown-Grant, Dex-Ann; Butler, Scott D; Zhao, Anna M; Xu, Xinjing; Shawber, Carrie J; Grenier, Jennifer K; Douglas, Nataki C

    2018-05-01

    Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF 164 expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

  13. Medical records documentation of constipation preceding Parkinson disease: A case-control study.

    Science.gov (United States)

    Savica, R; Carlin, J M; Grossardt, B R; Bower, J H; Ahlskog, J E; Maraganore, D M; Bharucha, A E; Rocca, W A

    2009-11-24

    Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year). Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.

  14. 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...

  15. Designing a community engagement strategy for Limerick Smarter travel using focus groups and precedent studies

    OpenAIRE

    Cullinane, Kathleen Clair

    2012-01-01

    peer-reviewed This research aims to create a rational basis for designing and implementing a plan for Limerick Smarter Travel. This plan will pay particular attention to community engagement. This research establishes a rationale for a community engagement strategy. Precedent studies also provide direct guidance for this rationale. The objective of the plan is to develop a local culture of Smarter Travel in Limerick communities using best international practice, and thereby achieving behav...

  16. Quiet Periods in Edge Turbulence Preceding the L-H Transition in NSTX

    International Nuclear Information System (INIS)

    Zweben, S.; Maqueda, R.J.; Hager, R.; Hallatschek, K.; Kaye, S.M.; Munsat, T.; Poli, F.M.; Roquemore, A.L.; Sechrest, Y.; Stotler, D.P.

    2010-01-01

    This paper describes the first observations in NSTX of 'quiet periods' in the edge turbulence preceding the L-H transition, as diagnosed by the GPI diagnostic near the outer midplane separatrix. During these quiet periods the GPI D light emission pattern was transiently similar to that seen during Hmode, i.e. with a relatively small fraction of the GPI light emission located outside the separatrix. These quiet periods had a frequency of ∼3 kHz for at least 30 msec before the L-H transition, and were correlated with changes in the direction of the local poloidal velocity. The GPI turbulence images were also analyzed to obtain an estimate for the dimensionless poloidal shearing S =(dVp/dr)(Lr/Lp). The values of S were strongly modulated by the quiet periods, but not otherwise varying for at least 30 msec preceding the L-H transition. Since neither the quiet periods nor the shear flow increased significantly immediately preceding the L-H transition, neither of these appears to be the trigger for this transition, at least for these cases in NSTX.

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

    Directory of Open Access Journals (Sweden)

    Dinesh Vallabh

    2015-07-01

    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.

  18. The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer.

    Science.gov (United States)

    Somasekar, A; James, L; Stephenson, B M; Thompson, I W; Vellacott, K D; Allison, M C

    2009-09-01

    To review all preceding 'negative' large bowel investigations in patients with a final diagnosis of colorectal cancer, and to examine whether delayed diagnosis was associated with worse outcome. Details were gathered on all patients with a new diagnosis of colorectal adenocarcinoma presenting over 4.5 years. For each patient the hospital's clinical workstation and radiology and endoscopy databases were interrogated for all flexible sigmoidoscopies, colonoscopies and barium enemas during the 5 years prior to diagnosis. Among the 570 patients, 28 (5%) had undergone colonoscopy and/or flexible sigmoidoscopy that had not shown colorectal cancer during the 5 years preceding final diagnosis, and a further 28 (5%) had undergone 'negative' barium enemas. Polyp surveillance might have missed four lesions destined to become malignant. Correspondingly there were three patients undergoing IBD surveillance found to have CRC, having had a negative complete colonoscopy within the preceding 5 years. Among patients undergoing de novo colonoscopy for diagnosis the true miss rate was only one patient per year. At August 2007, 29 (58%) of those with delayed diagnosis were still alive, compared with 216 (42%) of those diagnosed during initial investigation (chi2 = 5.04, P auditing the quality assurance of lower gastrointestinal diagnostic services. Despite the delay, late diagnosis was found to be associated with improved survival and a lower likelihood of metastatic disease.

  19. The Response of Durum Wheat to the Preceding Crop in a Mediterranean Environment

    Directory of Open Access Journals (Sweden)

    Laura Ercoli

    2014-01-01

    Full Text Available Crop sequence is an important management practice that may affect durum wheat (Triticum durum Desf. production. Field research was conducted in 2007-2008 and 2008-2009 seasons in a rain-fed cold Mediterranean environment to examine the impact of the preceding crops alfalfa (Medicago sativa L., maize (Zea mays L., sunflower (Helianthus annuus L., and bread wheat (Triticum aestivum L. on yield and N uptake of four durum wheat varieties. The response of grain yield of durum wheat to the preceding crop was high in 2007-2008 and was absent in the 2008-2009 season, because of the heavy rainfall that negatively impacted establishment, vegetative growth, and grain yield of durum wheat due to waterlogging. In the first season, durum wheat grain yield was highest following alfalfa, and was 33% lower following wheat. The yield increase of durum wheat following alfalfa was mainly due to an increased number of spikes per unit area and number of kernels per spike, while the yield decrease following wheat was mainly due to a reduction of spike number per unit area. Variety growth habit and performance did not affect the response to preceding crop and varieties ranked in the order Levante > Saragolla = Svevo > Normanno.

  20. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

    Directory of Open Access Journals (Sweden)

    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  1. Dominant Species in Subtropical Forests Could Decrease Photosynthetic N Allocation to Carboxylation and Bioenergetics and Enhance Leaf Construction Costs during Forest Succession.

    Science.gov (United States)

    Xiao, Yihua; Liu, Shirong; Tong, Fuchun; Chen, Bufeng; Kuang, Yuanwen

    2018-01-01

    It is important to understand how eco-physiological characteristics shift in forests when elucidating the mechanisms underlying species replacement and the process of succession and stabilization. In this study, the dominant species at three typical successional stages (early-, mid-, and late-succession) in the subtropical forests of China were selected. At each stage, we compared the leaf construction costs (CC), payback time (PBT), leaf area based N content ( N A ), maximum CO 2 assimilation rate ( P max ), specific leaf area (SLA), photosynthetic nitrogen use efficiency (PNUE), and leaf N allocated to carboxylation ( N C ), and to bioenergetics ( N B ). The relationships between these leaf functional traits were also determined. The results showed that the early-succession forest is characterized with significantly lower leaf CC, PBT, N A , but higher P max , SLA, PNUE, N C , and N B , in relation to the late-succession forest. From the early- to the late-succession forests, the relationship between P max and leaf CC strengthened, whereas the relationships between N B , N C , PNUE, and leaf CC weakened. Thus, the dominant species are able to decrease the allocation of the photosynthetic N fraction to carboxylation and bioenergetics during forest succession. The shift in these leaf functional traits and their linkages might represent a fundamental physiological mechanism that occurs during forest succession and stabilization.

  2. The effect of AgNO3 on the bioenergetic processes and the ultrastructure of Chlorella and Dunaliella cells exposed to different saline conditions

    International Nuclear Information System (INIS)

    Loseva, N.L.; Alyabyev, A.Ju.; Gordon, L.Kh.; Andreyeva, I.N.; Kolesnikov, O.P.; Ponomareva, A.A.; Kemp, R.B.

    2007-01-01

    The effect of AgNO 3 , an inhibitor of the H + pump in the plasma membrane, on the bioenergetic processes and on the ultrastructure of the microalgae Chlorella vulgaris (salt sensitive) and Dunaliella maritima (salt resistant) was examined under varying salt concentrations. Differences between them were observed in changes of the cellular energy metabolism depending on their salt sensitivity and the inhibition of the H + pump activity. A decrease was observed in the rates of heat production (about 45%), O 2 uptake (greater than 40-50% of the control) and particularly photosynthesis (more than 80%) in Chlorella cells under the simultaneous action of NaCl and AgNO 3 . Dunaliella cells showed small to moderate rate increases for heat production (less than 7%), O 2 uptake (10-15%) and O 2 evolution (40%) in higher salt concentrations and under the action of AgNO 3 . The production of active oxygen species was studied as an early unspecific response of microalgal cells to possible unfavorable conditions, including salt stress. The amount of superoxide formed by the Dunaliella cells was higher than that by the Chlorella cells. However, Ag + ions increased the generation rate of superoxide radicals considerably in both Chlorella and Dunaliella cells. The electron microscopy showed that changes of the algal ultrastructure of cells exposed to the action of Ag + ions were connected with the observed physiological changes and to a large extent with the alteration of the bioenergetic processes in them

  3. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

    Directory of Open Access Journals (Sweden)

    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. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.

    Science.gov (United States)

    Sun, Shanshan; Hu, Fangyuan; Wu, Jihong; Zhang, Shenghai

    2017-04-01

    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 XF e 24 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. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. 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.

  6. 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

  7. Budget Deficits Effects on Economic Growth

    Directory of Open Access Journals (Sweden)

    L.C.Risti

    2013-06-01

    Full Text Available The budget deficit can not be analyzed autarchically, as it affects all the macroeconomic processes and, is itself influenced by all other macroeconomic indicators. Most analyses and studies on public finance and budget balance measure the impact that budgetary deficits accumulation has on economy. Therefore, the present paper aims at following and analyzing the mutual impact between budget deficit and another economic macro indicator, namely the economic growth.

  8. Neurocognitive Deficits in Borderline Personality Disorder

    DEFF Research Database (Denmark)

    Thomsen, Marianne Skovgaard; Ruocco, Anthony C; Carcone, Dean

    2017-01-01

    completed a comprehensive battery of neurocognitive tests, a retrospective questionnaire on early life trauma and a dimensional measure of personality psychopathology. Patients with BPD primarily showed deficits in verbal comprehension, sustained visual attention, working memory and processing speed...... suggest that patients with BPD display deficits mainly in higher-order thinking abilities that may be exacerbated by PTSD and substantial early life trauma. Potential relationships between neurocognitive deficits and dimensions of personality psychopathology in BPD need further examination....

  9. The deficit of current account balances and budgetary deficit in countries in transition

    OpenAIRE

    Sandra Krtalic; Ines Kersan

    1998-01-01

    In restructuring process of their own economies, countries in transition deal with many common problems. One of the problems that transition brought to those countries is deficit in current account, as well as budget deficit. Deficits represent limit to a healthy and fast economic development and progress. Balance in balance of payments, as well as balanced budget are components of macroeconomic system. The authors will give an review of activities on deficits in countries in transition, and ...

  10. Measuring Working Memory Deficits in Aphasia

    Science.gov (United States)

    Mayer, Jamie F.; Murray, Laura L.

    2012-01-01

    Purpose: Many adults with aphasia demonstrate concomitant deficits in working memory (WM), but such deficits are difficult to quantify because of a lack of validated measures as well as the complex interdependence between language and WM. We examined the feasibility, reliability, and internal consistency of an "n"-back task for…

  11. Traumatic brain injury and olfactory deficits

    DEFF Research Database (Denmark)

    Fortin, Audrey; Lefebvre, Mathilde Beaulieu; Ptito, Maurice

    2010-01-01

    . Between 40-44% of the patients showing olfactory impairments were not aware of their deficit. CONCLUSIONS: Since a significant proportion of the patients showing olfactory impairments were not aware of their deficit, it is recommended than clinicians systematically evaluate olfactory functions using...

  12. Sentinel Events Preceding Youth Firearm Violence An Investigation of Administrative Data in Delaware

    Science.gov (United States)

    Sumner, Steven A.; Maenner, Matthew J.; Socias, Christina M.; Mercy, James A.; Silverman, Paul; Medinilla, Sandra P.; Martin, Steven S.; Xu, Likang; Hillis, Susan D.

    2018-01-01

    Introduction Accurately identifying youth at highest risk of firearm violence involvement could permit delivery of focused, comprehensive prevention services. This study explored whether readily available city and state administrative data covering life events before youth firearm violence could elucidate patterns preceding such violence. Methods Four hundred twenty-one individuals arrested for homicide, attempted homicide, aggravated assault, or robbery with a firearm committed in Wilmington, Delaware, from January 1, 2009 to May 21, 2014, were matched 1:3 to 1,259 Wilmington resident controls on birth year and sex. In 2015, descriptive statistics and a conditional logistic regression model using Delaware healthcare, child welfare, juvenile services, labor, and education administrative data examined associations between preceding life events and subsequent firearm violence. Results In a multivariable adjusted model, experiencing a prior gunshot wound injury (AOR=11.4, 95% CI=2.7, 48.1) and being subject to community probation (AOR=13.2, 95% CI=5.7, 30.3) were associated with the highest risk of subsequent firearm violence perpetration, though multiple other sentinel events were informative. The mean number of sentinel events experienced by youth committing firearm violence was 13.0 versus 1.9 among controls (pviolence. Conclusions Youth who commit firearm violence have preceding patterns of life events that markedly differ from youth not involved in firearm violence. This information is readily available from administrative data, demonstrating the potential of data sharing across city and state institutions to focus prevention strategies on those at greatest risk. PMID:27742157

  13. 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.

  14. Development of a Rheumatoid Arthritis Education Program using the PRECEDE_PROCEED Model

    Directory of Open Access Journals (Sweden)

    Kaveh Bahmanpour

    2011-12-01

    Full Text Available Background: In order to help rheumatoid arthritis (RA patients in carrying out and attaining relevant self-care behaviors and adaptation to the physical limitations of this disease and, conse-quently, promoting their level of health status, an education program based on the PRECEDE component of the PRECEDE–PROCEED model targeting patients with RA was developed. This paper describes the planning of a RA Patient Education Program (RAPEP designed to promote their quality of life.Methods: The development of the program began with a comprehensive review of the literature. This included a review of the signs and symptoms of RA, accompanying functional disabilities, previous educational programs and the effect of the disease on the patient’s quality of life. Be-sides, in order to help inform RAPEP program development, and organize the survey according to the factors identified in the PRECEDE model a cross-sectional survey was applied on a non-prob-ability sample of 181 outpatients in Yazd, center of Iran.Results: The quality of life (QOL problem identified was the considerable low role functioning, health perception and physical functioning due to chronic pain. One of the most significant modi-fiable behavioral factors impacting pain and functional limitations was self-care behaviors in RA patients. Higher level of knowledge, attitude, self-efficacy, enabling factors and social support is associated with better self-care behavior.Conclusions: The PRECEDE component of the PRECEDE–PROCEED model provided a com-prehensive conceptual framework for the development of RAPEP aiming at RA patients in Yazd. Further research to evaluate this educational program is suggested.

  15. Characteristics of Precedent : The Case Law of the European Court of Justice in Three Dimensions

    OpenAIRE

    Derlén, Mattias; Lindholm, Johan

    2015-01-01

    The case law of the Court of Justice of the European Union (CJEU) is one of the most important sources of European Union law. However, case law’s role in EU law is not uniform. By empirically studying how the Court uses its own case law as a source of law, we explore the correlation between, on the one hand, the characteristics of a CJEU case— type of action, actors involved, and area of law—and, on the other hand, the judgment’s “embeddedness” in previous case law and value as a precedent in...

  16. The Preceding Voltage Pulse and Separation Welding Mechanism of Electrical Contacts

    DEFF Research Database (Denmark)

    Yang, Xiao Cheng; Huang, Jiang; Li, Zhen Biao

    2016-01-01

    In order to obtain a better understanding of the welding mechanism in contact separation, electrical endurance tests were conducted with AgSnO2 and AgNi contacts on a simulation test device. Waveforms of contact displacement, contact voltage, and current were recorded with LabVIEW during the tests......, and changes in a contact gap and heights of pips with increases in operation cycles were observed through charge-coupled device cameras. The resultant test results show that welding in separation is accompanied with a preceding voltage pulse which represents arc rather than contact bounce arc....

  17. Urinary Tract Infection Associated with a Celiac Crisis: A Preceding or Precipitating Event?

    Science.gov (United States)

    Tiwari, Abhinav; Qamar, Khola; Sharma, Himani; Almadani, Sameh Bashar

    2017-01-01

    Celiac crisis is a rare life-threatening presentation of celiac disease that manifests as profuse diarrhea, hypoproteinemia, and severe metabolic disturbances. It may be precipitated by a general immune stimulus such as surgery, infection, or pregnancy. We report the case of a 26-year-old woman who presented with a celiac crisis, potentially triggered by a preceding urinary tract infection. Metabolic derangement is caused by malabsorption and profuse diarrhea, which can be unremitting unless the celiac crisis is recognized, and treatment with gluten restriction is initiated.

  18. An Adaptive Evolutionary Algorithm for Traveling Salesman Problem with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Jinmo Sung

    2014-01-01

    Full Text Available Traveling sales man problem with precedence constraints is one of the most notorious problems in terms of the efficiency of its solution approach, even though it has very wide range of industrial applications. We propose a new evolutionary algorithm to efficiently obtain good solutions by improving the search process. Our genetic operators guarantee the feasibility of solutions over the generations of population, which significantly improves the computational efficiency even when it is combined with our flexible adaptive searching strategy. The efficiency of the algorithm is investigated by computational experiments.

  19. Preventive aspects in children's caries treatments preceding dental care under general anaesthesia.

    Science.gov (United States)

    Savanheimo, Nora; Vehkalahti, Miira M

    2008-03-01

    In Helsinki Public Dental Service (PDS) the Special Oral Health Care Unit (SOHCU) provides comprehensive dental treatments under general anaesthesia (GA). For the present study, all dental treatment given under GA for generally healthy children (n = 102) below 16 years of age (range 2.3-15.8) during a 1-year period and dental treatment and visits of these children in the preceding 2 years in Helsinki PDS was recorded in detail. These children were referred to the SOHCU because of serious difficulties in dental care due to large treatment needs or failures in psychological and chemical management, including sedation. To describe treatments given to generally healthy children under GA and to evaluate preventive aspects of their dental care in the preceding 2 years. The study was cross-sectional and retrospective. Data came from the patients' individual records. Treatments under GA included an average of 6.0 restorations (SD = 2.7, range 0-12) and 1.7 extractions (SD = 2.1, range 0-10). In the 2 preceding years, these children had visited dentist an average of 5.1 times (SD = 2.7, range 1-14) with an average of 2.4 restorations (SD = 1.9, range 0-12) and 0.5 extractions (SD = 1.4, range 0-10). Of the restorations made, 36% were temporary. Of all visits, those with an operative approach accounted for 35%, preventive for 37%, operative and preventive for 5%, and visits with total uncooperation for 23%. Of the children, 90% had at least one preventive visit. Children treated under conscious sedation in the preceding 2 years received less prevention (P = 0.02). Remaining without preventive measures was most likely for those children exhibiting visits with total uncooperation (odds ratio = 4.6; P = 0.004) and for those receiving numerous temporary fillings (odds ratio = 4.1; P = 0.0005). The uncooperative high-caries children pose a demanding challenge to PDS. The early identification of high-caries risk and efforts of intensive preventive care are in key position to

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

    DEFF Research Database (Denmark)

    Hartcher-O'Brien, Jessica; Buchholz, Jörg

    2006-01-01

    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...

  1. 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

    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......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...... to a significant decrease in makespan compared to the strategy currently implemented....

  2. 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...

  3. Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

    Science.gov (United States)

    Surapaneni, Dinesh Kumar; Adapa, Sree Rama Shiva Shanker; Preeti, Kumari; Teja, Gangineni Ravi; Veeraragavan, Muruganandam; Krishnamurthy, Sairam

    2012-08-30

    Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities. The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit. CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively. Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities. The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and

  4. Neurologic deficit after resection of the sacrum.

    Science.gov (United States)

    Biagini, R; Ruggieri, P; Mercuri, M; Capanna, R; Briccoli, A; Perin, S; Orsini, U; Demitri, S; Arlecchini, S

    1997-01-01

    The authors describe neurologic deficit (sensory, motor, and sphincteral) resulting from sacrifice of the sacral nerve roots removed during resection of the sacrum. The anatomical and functional bases of sphincteral continence and the amount of neurologic deficit are discussed based on level of sacral resection. A large review of the literature on the subject is reported and discussed. The authors emphasize how the neurophysiological bases of sphincteral continence (rectum and bladder) and of sexual ability are still not well known, and how the literature reveals disagreement on the subject. A score system is proposed to evaluate neurologic deficit. The clinical model of neurologic deficit caused by resection of the sacrum may be extended to an evaluation of post-traumatic deficit.

  5. Taurine, glutathione and bioenergetics

    DEFF Research Database (Denmark)

    Hansen, Svend Høime; Grunnet, Niels

    2013-01-01

    the mitochondrial inner-membrane. The very high concentration of taurine in oxidative tissue has recently led to discussions on the role of taurine in the mitochondria, e.g. with taurine acting as a pH buffer in the mitochondrial matrix. A very important consequence of the slightly alkaline pH is the fact...... 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...

  6. The bioenergetics of denitrification

    NARCIS (Netherlands)

    Stouthamer, A.H.; Boogerd, F C; van Verseveld, H W

    1982-01-01

    In anaerobically grown Paracoccus denitrificans the dissimilatory nitrate reductase is linked to the respiratory chain at the level of cytochromes b. Electron transport to nitrite and nitrous oxide involves c-type cytochromes. During electron transport from NADH to nitrate one phosphorylation site

  7. Population dynamics and bioenergetics of a fossorial herbivore, Thomomys talpoides (Rodentia: Geomyidae), in a spruce-fir sere

    Science.gov (United States)

    Andersen, Douglas C.; MacMahon, James A.

    1981-01-01

    Studies of the bioenergetics of the northern pocket gopher, Thomomys talpoides, are coupled with data on demography, activity budgets, and microclimates to model the energy requirements of individuals and populations in the Wasatch Mountains of Utah during 1976-1979. Metabolic rates during rest increased linearly with decreasing ambient temperature, but burrowing metabolic rates (16.3 mL O2 • h-1 • g-9.75) were independent of both temperature and physical properties of the soil. Radio-telemetry studies indicated that free-ranging gophers are active =50% of each day. Conservative estimates of true energy consumption were calculated using estimates of habitat-specific minimum daily burrowing requirements. Rates of burrowing measured in the laboratory were either ∞ 0.0 or ∞ 2.0 cm/min. The low burrowing rate was observed when the soil was frozen or saturated with water, as would occur in the field in early winter and in spring, respectively. Gophers burrowed through soil at the study site at an average rate of ∞ 1.5 cm/min. Belowground food energy densities at gopher foraging depth declined from 24.6 to 3.2 J/cm3 along a successional gradient (subalpine forb meadow to Engelmann spruce dominated forest). We conclude that individual gophers are food limited within the climax spruce seral stage. Further, daily energy costs associated with reproduction in females may exceed the belowground energy supply available in intermediate seral stages (aspen and subalpine fir). Reduction of burrowing rates for any reason will affect gophers in the late seral stages proportionately more than those resident in the meadow. The peak gopher densities recorded (from 62 individuals/ha in the meadow to 2 individuals/ha in spruce forest) support these inferences. Detailed demographic information was obtained only in the meadow seral stage. Adult survivorship was lower in winter than in summer and varied greatly between years (0.18-0.70 yr-1). Juvenile survivorship from weaning

  8. 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

  9. The upper spatial limit for perception of displacement is affected by preceding motion.

    Science.gov (United States)

    Stefanova, Miroslava; Mateeff, Stefan; Hohnsbein, Joachim

    2009-03-01

    The upper spatial limit D(max) for perception of apparent motion of a random dot pattern may be strongly affected by another, collinear, motion that precedes it [Mateeff, S., Stefanova, M., &. Hohnsbein, J. (2007). Perceived global direction of a compound of real and apparent motion. Vision Research, 47, 1455-1463]. In the present study this phenomenon was studied with two-dimensional motion stimuli. A random dot pattern moved alternately in the vertical and oblique direction (zig-zag motion). The vertical motion was of 1.04 degrees length; it was produced by three discrete spatial steps of the dots. Thereafter the dots were displaced by a single spatial step in oblique direction. Each motion lasted for 57ms. The upper spatial limit for perception of the oblique motion was measured under two conditions: the vertical component of the oblique motion and the vertical motion were either in the same or in opposite directions. It was found that the perception of the oblique motion was strongly influenced by the relative direction of the vertical motion that preceded it; in the "same" condition the upper spatial limit was much shorter than in the "opposite" condition. Decreasing the speed of the vertical motion reversed this effect. Interpretations based on networks of motion detectors and on Gestalt theory are discussed.

  10. Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures.

    Science.gov (United States)

    Lhatoo, Samden D; Nei, Maromi; Raghavan, Manoj; Sperling, Michael; Zonjy, Bilal; Lacuey, Nuria; Devinsky, Orrin

    2016-07-01

    To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it. We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death. Three patients (two definite and one probable) had SUDEP. They had a typical high SUDEP risk profile with longstanding intractable epilepsy and frequent generalized tonic-clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound electroencephalography (EEG) suppression. In two patients, patterns of cardiorespiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS). SUDEP almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near-SUDEP cases without a seizure have not yet been reported in literature. When nonmonitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of nonseizure SUDEP; such deaths may not be prevented by seizure detection-based devices. SUDEP risk in patients with epilepsy may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one episode of seizure ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  11. Situational Factors of Influencing Drivers to Give Precedence to Jaywalking Pedestrians at Signalized Crosswalk

    Directory of Open Access Journals (Sweden)

    Xiaobei Jiang

    2011-12-01

    Full Text Available A large number of fatalities are caused by the vehicle-pedestrian accidents. Under a potential conflict between the vehicle and jaywalking pedestrian, giving precedence to the pedestrian will be a proper decision taken by the driver to avoid collision. Field traffic data has been collected by video recording and image processing at two signalized crosswalks. Vehicle speed performance in the single vehicle-pedestrian encounter and platoon vehicle-pedestrian encounter were analyzed for understanding the driver behavior in the conflict process. Binary logic model was proposed to estimate the drivers' giving precedence influenced by the situational factors and the model was validated to predict the drivers' choices accurately. The vehicle speed, pedestrian speed, pedestrian lateral distance and the vehicle longitudinal distance to the conflict point were proved to affect the drivers' choices in platoon driving. The research results would hopefully be helpful to the design of intelligent vehicles and pedestrian protection systems by the knowledge-based decision making process.

  12. Patterns of Life Events Preceding the Suicide in Rural Young Chinese: A Case Control Study1

    Science.gov (United States)

    Zhang, Jie; Ma, Zhenyu

    2012-01-01

    Background Previous studies on the Chinese suicide found some life events prior to the suicide different from those in the West, but there is a lack of summary of the Chinese life event patterns to better understand the effects of the social structure on Chinese suicide. Aim We tried to identify the life events that precede the Chinese rural youth suicides and compare them with what found in the West, so as to find the patterns that are particularly true in the Chinese culture contexts. Methods Suicide cases were investigated with a psychological autopsy study in rural China, and local community living controls were also interviewed with the same protocol. Results We collapsed 64 negative life events into six categories: (1) Marriage/Love, (2) Family/Home, (3) Work/Business, (4) Health/Hospital, (5) Law/Legal, (6) Friend/Relationship. About 92.3% of the suicides studied had experienced at least one type of negative life events. The three most common negative life events categories in the past one year were Family/Home (60.7%), Health/Hospital (53.8%) and Marriage/Love (51.3%) in the rural young suicide victims. Conclusions Among the negative life events, those related to family relations, love affairs, and marital issues were most likely to precede a suicide of rural suicides in China, and it is especially true of rural young women. Family is an important social institution in rural China for suicide prevention efforts. PMID:22595373

  13. HIGH-RESOLUTION SIMULATIONS OF CONVECTION PRECEDING IGNITION IN TYPE Ia SUPERNOVAE USING ADAPTIVE MESH REFINEMENT

    International Nuclear Information System (INIS)

    Nonaka, A.; Aspden, A. J.; Almgren, A. S.; Bell, J. B.; Zingale, M.; Woosley, S. E.

    2012-01-01

    We extend our previous three-dimensional, full-star simulations of the final hours of convection preceding ignition in Type Ia supernovae to higher resolution using the adaptive mesh refinement capability of our low Mach number code, MAESTRO. We report the statistics of the ignition of the first flame at an effective 4.34 km resolution and general flow field properties at an effective 2.17 km resolution. We find that off-center ignition is likely, with radius of 50 km most favored and a likely range of 40-75 km. This is consistent with our previous coarser (8.68 km resolution) simulations, implying that we have achieved sufficient resolution in our determination of likely ignition radii. The dynamics of the last few hot spots preceding ignition suggest that a multiple ignition scenario is not likely. With improved resolution, we can more clearly see the general flow pattern in the convective region, characterized by a strong outward plume with a lower speed recirculation. We show that the convective core is turbulent with a Kolmogorov spectrum and has a lower turbulent intensity and larger integral length scale than previously thought (on the order of 16 km s –1 and 200 km, respectively), and we discuss the potential consequences for the first flames.

  14. An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

    Science.gov (United States)

    Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

    2015-08-15

    This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice

    International Nuclear Information System (INIS)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-01-01

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. - Highlights: • This study explore contribution of DNA damage to neurodegeneration in Parkinson's disease mice. • A53T-α-Syn MEF cells show a prolonged DNA damage repair process and senescense phenotype. • DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice. • DNA damage decrease the number of nigrostriatal dopaminergic neurons. • Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.

  16. Left ventricle expands maximally preceding end-diastole. Radionuclide ventriculography study

    International Nuclear Information System (INIS)

    Horinouchi, Osamu

    2002-01-01

    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)

  17. Stressful life events preceding the onset of depression in Asian patients with major depressive disorder.

    Science.gov (United States)

    Park, Subin; Hatim, Ahmad; Si, Tian-Mei; Jeon, Hong Jin; Srisurapanont, Manit; Bautista, Dianne; Liu, Shen-ing; Chua, Hong Choon; Hong, Jin Pyo

    2015-12-01

    Previous studies have identified the significant role of stressful life events in the onset of depressive episodes. However, there is a paucity of cross-national studies on stressful life events that precede depression. We aimed to compare types of stressful life events associated with the onset of depressive episodes in patients with major depressive disorder (MDD) in five Asian countries. A total of 507 outpatients with MDD were recruited in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and Taiwan (n = 99). All patients were assessed with the Mini-International Neuropsychiatric Interview and the List of Threatening Experiences. The prevalence of each type of stressful life events was calculated and compared between each country. The type of stressful life event that preceded the onset of a depressive episode differed between patients in China and Taiwan and those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were less likely to report interpersonal relationship problems and occupational/financial problems than patients in South Korea, Malaysia and Thailand. Understanding the nature and basis of culturally determined susceptibilities to specific stressful life events is critical for establishing a policy of depression prevention and providing effective counseling services for depressed patients. © The Author(s) 2015.

  18. A Legal Analysis of the Precedents of Medical Disputes in the Cosmetic Surgery Field.

    Science.gov (United States)

    Park, Bo Young; Kim, Min Ji; Kang, So Ra; Hong, Seung Eun

    2016-05-01

    Disputes regarding medical malpractice occur between practitioners and patients. As patients have become increasingly aware regarding medical care, an increase in the unexpected side effects of procedures has been observed, thereby leading to an increase in disputes regarding medical malpractice. In this study, we reviewed trends in precedents involving cosmetic surgery-related medical disputes, with the goal of helping to prevent unnecessary disputes in the future. We conducted a search of the judgments made in South Korean courts between 2000 and 2013 that were related to the field of plastic surgery. A total of 54 judgments were analyzed, and the selected precedents were reviewed and classified according to the kind of negligence involved. The claim amounts ranged from under 8 million KRW (6,991 USD) to 750 million KRW (629,995 USD). The most common ratio of the judgment amount to the claim amount was 20%-30%. The judgments were classified according to the following categories: violation of the duty of explanation in 17 cases (29%), violation of the duty of care in 10 cases (17%), violation of both duties in 20 cases (35%), and no violation of duty in six cases (10%). Cosmetic surgery-related suits require different approaches than general malpractice suits. The Supreme Court requires plastic surgeons to determine the type, timing, methods, and scope of their treatments when considering possible results. Therefore, practitioners should be educated on their rights and responsibilities to enable them to cope with any possible medical dispute that may arise.

  19. The Microbiology of Subsurface, Salt-Based Nuclear Waste Repositories: Using Microbial Ecology, Bioenergetics, and Projected Conditions to Help Predict Microbial Effects on Repository Performance

    International Nuclear Information System (INIS)

    Swanson, Juliet S.; Cherkouk, Andrea; Arnold, Thuro; Meleshyn, Artur; Reed, Donald T.

    2016-01-01

    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.

  20. 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.

  1. Microbial Influence on the Performance of Subsurface, Salt-Based Radioactive Waste Repositories. An Evaluation Based on Microbial Ecology, Bioenergetics and Projected Repository Conditions

    International Nuclear Information System (INIS)

    Swanson, J.S.; Reed, D.T.; Cherkouk, A.; Arnold, T.; Meleshyn, A.; Patterson, Russ

    2018-01-01

    For the past several decades, the Nuclear Energy Agency Salt Club has been supporting and overseeing the characterisation of rock salt as a potential host rock for deep geological repositories. This extensive evaluation of deep geological settings is aimed at determining - through a multidisciplinary approach - whether specific sites are suitable for radioactive waste disposal. Studying the microbiology of granite, basalt, tuff, and clay formations in both Europe and the United States has been an important part of this investigation, and much has been learnt about the potential influence of microorganisms on repository performance, as well as about deep subsurface microbiology in general. Some uncertainty remains, however, around the effects of microorganisms on salt-based repository performance. Using available information on the microbial ecology of hyper-saline environments, the bioenergetics of survival under high ionic strength conditions and studies related to repository microbiology, this report summarises the potential role of microorganisms in salt-based radioactive waste repositories

  2. QUOTEchemo: a patient-centered instrument to measure quality of communication preceding chemotherapy treatment through the patient’s eyes

    NARCIS (Netherlands)

    van Weert, J.C.M.; Jansen, J.; de Bruijn, G.J.; Noordman, J.; van Dulmen, S.

    2009-01-01

    Background: Knowing patients’ needs is a prerequisite to ensure high quality cancer care. This study describes the development and psychometric properties of a patient-centred instrument to measure needs and actual experiences with communication preceding chemotherapy treatment: QUOTEchemo.

  3. QUOTEchemo: a patient-centered instrument to measure quality of communication preceding chemotherapy treatment through the patient's eyes.

    NARCIS (Netherlands)

    Weert, J.C.M. van; Jansen, J.; Bruijn, G.J. de; Noordman, J.; Dulmen, A.M. van; Bensing, J.M.

    2009-01-01

    Background: Knowing patients’ needs is a prerequisite to ensure high quality cancer care. This study describes the development and psychometric properties of a patient-centred instrument to measure needs and actual experiences with communication preceding chemotherapy treatment: QUOTEchemo.

  4. Anomalous high-frequency wave activity flux preceding anomalous changes in the Northern polar jet

    Science.gov (United States)

    Nakamura, Mototaka; Kadota, Minoru; Yamane, Shozo

    2010-05-01

    Anomalous forcing by quasi-geostrophic (QG) waves has been reported as an important forcing factor in the Northern Annular Mode (NAM) in recent literatures. In order to shed a light on the dynamics of the NAM from a different angle, we have examined anomalous behavior of the winter jets in the upper troposphere and stratosphere by focusing our diagnosis on not the anomalous geopotential height (Z) itself, but on the anomalous change in the Z (dZ) between two successive months and preceding transient QG wave activity flux during the cold season. We calculated EOFs of dZ between two successive months at 150hPa for a 46-year period, from 1958 to 2003, using the monthly mean NCEP reanalysis data. We then formed anomaly composites of changes in Z and the zonal velocity (U), as well as the preceding and following wave activity flux, Z, U, and temperature at various heights, for both positive and negative phases of the first EOF. For the wave forcing fields, we adopted the diagnostic system for the three-dimensional QG transient wave activity flux in the zonally-varying three-dimensional mean flow developed by Plumb (1986) with a slight modification in its application to the data. Our choice of the Plumb86 is based on the fact that the winter mean flow in the Northern Hemisphere is characterized by noticeable zonal asymmetry, and has a symbiotic relationship with waves in the extra-tropics. The Plumb86 flux was calculated for high-frequency (period of 2 to 7 days) and low-frequency (period of 10 to 20 days) waves with the ultra-low-frequency (period of 30 days or longer) flow as the reference state for each time frame of the 6 hourly NCEP reanalysis data from 1958 to 2003. By replacing the mean flow with the ultra-low-frequency flow in the application of the Plumb86 formula, the flux fields were calculated as time series at 6 hour intervals. The time series of the wave activity flux was then averaged for each month. The patterns of composited anomalous dZ and dU clearly

  5. Prey size and availability limits maximum size of rainbow trout in a large tailwater: insights from a drift-foraging bioenergetics model

    Science.gov (United States)

    Dodrill, Michael J.; Yackulic, Charles B.; Kennedy, Theodore A.; Haye, John W

    2016-01-01

    The cold and clear water conditions present below many large dams create ideal conditions for the development of economically important salmonid fisheries. Many of these tailwater fisheries have experienced declines in the abundance and condition of large trout species, yet the causes of these declines remain uncertain. Here, we develop, assess, and apply a drift-foraging bioenergetics model to identify the factors limiting rainbow trout (Oncorhynchus mykiss) growth in a large tailwater. We explored the relative importance of temperature, prey quantity, and prey size by constructing scenarios where these variables, both singly and in combination, were altered. Predicted growth matched empirical mass-at-age estimates, particularly for younger ages, demonstrating that the model accurately describes how current temperature and prey conditions interact to determine rainbow trout growth. Modeling scenarios that artificially inflated prey size and abundance demonstrate that rainbow trout growth is limited by the scarcity of large prey items and overall prey availability. For example, shifting 10% of the prey biomass to the 13 mm (large) length class, without increasing overall prey biomass, increased lifetime maximum mass of rainbow trout by 88%. Additionally, warmer temperatures resulted in lower predicted growth at current and lower levels of prey availability; however, growth was similar across all temperatures at higher levels of prey availability. Climate change will likely alter flow and temperature regimes in large rivers with corresponding changes to invertebrate prey resources used by fish. Broader application of drift-foraging bioenergetics models to build a mechanistic understanding of how changes to habitat conditions and prey resources affect growth of salmonids will benefit management of tailwater fisheries.

  6. The effect of AgNO{sub 3} on the bioenergetic processes and the ultrastructure of Chlorella and Dunaliella cells exposed to different saline conditions

    Energy Technology Data Exchange (ETDEWEB)

    Loseva, N.L. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation)]. E-mail: loseva@mail.knc.ru; Alyabyev, A.Ju. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation); Gordon, L.Kh. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation); Andreyeva, I.N. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation); Kolesnikov, O.P. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation); Ponomareva, A.A. [Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan 420111 (Russian Federation); Kemp, R.B. [Institute of Biological Sciences, Edward Llwyd Building, Penglais, University of Wales, Aberystwyth SY23 3DA (United Kingdom)

    2007-06-25

    The effect of AgNO{sub 3}, an inhibitor of the H{sup +} pump in the plasma membrane, on the bioenergetic processes and on the ultrastructure of the microalgae Chlorella vulgaris (salt sensitive) and Dunaliella maritima (salt resistant) was examined under varying salt concentrations. Differences between them were observed in changes of the cellular energy metabolism depending on their salt sensitivity and the inhibition of the H{sup +} pump activity. A decrease was observed in the rates of heat production (about 45%), O{sub 2} uptake (greater than 40-50% of the control) and particularly photosynthesis (more than 80%) in Chlorella cells under the simultaneous action of NaCl and AgNO{sub 3}. Dunaliella cells showed small to moderate rate increases for heat production (less than 7%), O{sub 2} uptake (10-15%) and O{sub 2} evolution (40%) in higher salt concentrations and under the action of AgNO{sub 3}. The production of active oxygen species was studied as an early unspecific response of microalgal cells to possible unfavorable conditions, including salt stress. The amount of superoxide formed by the Dunaliella cells was higher than that by the Chlorella cells. However, Ag{sup +} ions increased the generation rate of superoxide radicals considerably in both Chlorella and Dunaliella cells. The electron microscopy showed that changes of the algal ultrastructure of cells exposed to the action of Ag{sup +} ions were connected with the observed physiological changes and to a large extent with the alteration of the bioenergetic processes in them.

  7. High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

    Science.gov (United States)

    Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

    2011-01-01

    Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

  8. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    International Nuclear Information System (INIS)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

    2017-01-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  9. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

    2017-05-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  10. Dissociations between developmental dyslexias and attention deficits

    Science.gov (United States)

    Lukov, Limor; Friedmann, Naama; Shalev, Lilach; Khentov-Kraus, Lilach; Shalev, Nir; Lorber, Rakefet; Guggenheim, Revital

    2014-01-01

    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 one side of the word are omitted or substituted, and surface dyslexia, in which words are read via the sublexical route. We tested 110 children and adults with developmental dyslexia and/or attention deficits, using extensive batteries of reading and attention. For each participant, the existence of dyslexia and the dyslexia type were tested using reading tests that included stimuli sensitive to the various dyslexia types. Attention deficit and its type was established through attention tasks assessing sustained, selective, orienting, and executive attention functioning. Using this procedure, we identified 55 participants who showed a double dissociation between reading and attention: 28 had dyslexia with normal attention and 27 had attention deficits with normal reading. Importantly, each dyslexia with suspected attentional basis dissociated from attention: we found 21 individuals with LPD, 13 AD, 2 neglect dyslexia, and 12 surface dyslexia without attention deficits. Other dyslexia types (vowel dyslexia, phonological dyslexia, visual dyslexia) also dissociated from attention deficits. Examination of 55 additional individuals with both a specific dyslexia and a certain attention deficit found no attention function that was consistently linked with any dyslexia type. Specifically, LPD and AD dissociated from selective attention, neglect dyslexia dissociated from orienting, and surface dyslexia dissociated from sustained and executive attention. These results indicate that

  11. Precedent Research on Compact Laser-plasma based Gantry for Cancer Therapy

    International Nuclear Information System (INIS)

    Hee, Park Seong; Jeong, Young Uk; Lee, Ki Tae; Kim, Kyung Nam; Cha, Young Ho

    2012-03-01

    This is the precedent R and D to develop the technology of next generation compact particle cancer treatment system based on laser-plasma interaction and to deduce a big project. The subject of this project are the survey of application technology of laser-plasma based particle beam and the design of compact laser-plasma based gantry. The survey of characteristic of particle beam for cancer therapy and present status can be adapted to develop new system. The comparison between particle beams from the existing system and new one based on laser-plasma acceleration will be important to new design and design optimization. The project includes design of multi-dimensional laser transfer beamline, minimization of laser-plasma acceleration chamber, design of effective energy separation/selection system, and radiation safety and local shielding

  12. 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.

  13. The effect of a preceding cue on the conflict solving mechanism.

    Science.gov (United States)

    Goldfarb, Liat; Henik, Avishai

    2013-01-01

    In everyday life cues and signs are used in order to improve our performance and to modify and control our behavior. This study examines whether cues can improve the performance of the mental mechanism in charge of solving conflicts when the nature of the irrelevant task remains constant. In two experiments participants performed the Stroop task in which they were asked to name the color of a stimulus while ignoring its meaning. Half the trials were preceded by a conflict-cue containing information about an upcoming conflict. In addition, conflict trial proportions were manipulated. We found that only when the probability of conflict is low can cues alter the conflict solving mechanism. These findings are discussed in the context of the nature of the control mechanism and its tendency to minimize the cost of mental resources.

  14. Body size shifts and early warning signals precede the historic collapse of whale stocks.

    Science.gov (United States)

    Clements, Christopher F; Blanchard, Julia L; Nash, Kirsty L; Hindell, Mark A; Ozgul, Arpat

    2017-06-22

    Predicting population declines is a key challenge in the face of global environmental change. Abundance-based early warning signals have been shown to precede population collapses; however, such signals are sensitive to the low reliability of abundance estimates. Here, using historical data on whales harvested during the 20th century, we demonstrate that early warning signals can be present not only in the abundance data, but also in the more reliable body size data of wild populations. We show that during the period of commercial whaling, the mean body size of caught whales declined dramatically (by up to 4 m over a 70-year period), leading to early warning signals being detectable up to 40 years before the global collapse of whale stocks. Combining abundance and body size data can reduce the length of the time series required to predict collapse, and decrease the chances of false positive early warning signals.

  15. Brain Musics: History, Precedents, and Commentary on Whalley, Mavros and Furniss

    Directory of Open Access Journals (Sweden)

    Miguel Ortiz

    2015-05-01

    Full Text Available Whalley, Mavros and Furniss explore questions of agency, control and interaction, as well as the embodied nature of musical performance in relation to the use of human-computer interaction through the work Clasp Together (beta for small ensemble and live electronics. The underlying concept of the piece focuses on direct mapping of a human neural network (embodied by a performer within the ensemble to an artificial neural network running on a computer. With our commentary, we contextualize the work within the field of Music Neuroscience. Specifically, we point at precedents in EEG-based musical practice as well as ongoing research in the field. We hope to more clearly situate Clasp Together (beta in the broad area of Brain Computer Musical Interfaces and discuss the challenges and opportunities that these technologies offer for composers.

  16. Temporal Precedence Checking for Switched Models and its Application to a Parallel Landing Protocol

    Science.gov (United States)

    Duggirala, Parasara Sridhar; Wang, Le; Mitra, Sayan; Viswanathan, Mahesh; Munoz, Cesar A.

    2014-01-01

    This paper presents an algorithm for checking temporal precedence properties of nonlinear switched systems. This class of properties subsume bounded safety and capture requirements about visiting a sequence of predicates within given time intervals. The algorithm handles nonlinear predicates that arise from dynamics-based predictions used in alerting protocols for state-of-the-art transportation systems. It is sound and complete for nonlinear switch systems that robustly satisfy the given property. The algorithm is implemented in the Compare Execute Check Engine (C2E2) using validated simulations. As a case study, a simplified model of an alerting system for closely spaced parallel runways is considered. The proposed approach is applied to this model to check safety properties of the alerting logic for different operating conditions such as initial velocities, bank angles, aircraft longitudinal separation, and runway separation.

  17. 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.

  18. Electric current precedes emergence of a lateral root in higher plants.

    Science.gov (United States)

    Hamada, S; Ezaki, S; Hayashi, K; Toko, K; Yamafuji, K

    1992-10-01

    Stable electrochemical patterns appear spontaneously around roots of higher plants and are closely related to growth. An electric potential pattern accompanied by lateral root emergence was measured along the surface of the primary root of adzuki bean (Phaseolus angularis) over 21 h using a microelectrode manipulated by a newly developed apparatus. The electric potential became lower at the point where a lateral root emerged. This change preceded the emergence of the lateral root by about 10 h. A theory is presented for calculating two-dimensional patterns of electric potential and electric current density around the primary root (and a lateral root) using only data on the one-dimensional electric potential measured near the surface of the primary root. The development of the lateral root inside the primary root is associated with the influx of electric current of about 0.7 muA.cm(-2) at the surface.

  19. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

    Science.gov (United States)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-12-02

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The market for precedent: shifting visions of the role of clinical negligence claims and trials.

    Science.gov (United States)

    Mulcahy, Linda

    2014-01-01

    This article considers the interface between the standard setting activity of the NHS Litigation Authority, and the courts and uses the clinical negligence action as a prism through which to examine it. It is suggested that despite its many disadvantages, the clinical negligence action remains an important safety valve when internal regulatory systems fail or are insufficiently transparent to gain full legitimacy. More specifically, it explores the ways in which attitudes about the usefulness of the data contained in claims against the NHS have changed in the aftermath of a number of high profile inquiries which have focused on issues of poor performance. The article concludes that while much greater use is now been made of the data contained in claims when setting standards, strategies for prompting judicial precedent as an alternative way of mobilising standard setting behaviour remain under developed. © The Author 2014. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Possible deep fault slip preceding the 2004 Parkfield earthquake, inferred from detailed observations of tectonic tremor

    Science.gov (United States)

    Shelly, David R.

    2009-01-01

    Earthquake predictability depends, in part, on the degree to which sudden slip is preceded by slow aseismic slip. Recently, observations of deep tremor have enabled inferences of deep slow slip even when detection by other means is not possible, but these data are limited to certain areas and mostly the last decade. The region near Parkfield, California, provides a unique convergence of several years of high-quality tremor data bracketing a moderate earthquake, the 2004 magnitude 6.0 event. Here, I present detailed observations of tectonic tremor from mid-2001 through 2008 that indicate deep fault slip both before and after the Parkfield earthquake that cannot be detected with surface geodetic instruments. While there is no obvious short-term precursor, I find unidirectional tremor migration accompanied by elevated tremor rates in the 3 months prior to the earthquake, which suggests accelerated creep on the fault ∼16 km beneath the eventual earthquake hypocenter.

  2. 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

  3. Static Scheduling of Periodic Hardware Tasks with Precedence and Deadline Constraints on Reconfigurable Hardware Devices

    Directory of Open Access Journals (Sweden)

    Ikbel Belaid

    2011-01-01

    Full Text Available Task graph scheduling for reconfigurable hardware devices can be defined as finding a schedule for a set of periodic tasks with precedence, dependence, and deadline constraints as well as their optimal allocations on the available heterogeneous hardware resources. This paper proposes a new methodology comprising three main stages. Using these three main stages, dynamic partial reconfiguration and mixed integer programming, pipelined scheduling and efficient placement are achieved and enable parallel computing of the task graph on the reconfigurable devices by optimizing placement/scheduling quality. Experiments on an application of heterogeneous hardware tasks demonstrate an improvement of resource utilization of 12.45% of the available reconfigurable resources corresponding to a resource gain of 17.3% compared to a static design. The configuration overhead is reduced to 2% of the total running time. Due to pipelined scheduling, the task graph spanning is minimized by 4% compared to sequential execution of the graph.

  4. Blood-brain barrier hyperpermeability precedes demyelination in the cuprizone model.

    Science.gov (United States)

    Berghoff, Stefan A; Düking, Tim; Spieth, Lena; Winchenbach, Jan; Stumpf, Sina K; Gerndt, Nina; Kusch, Kathrin; Ruhwedel, Torben; Möbius, Wiebke; Saher, Gesine

    2017-12-01

    In neuroinflammatory disorders such as multiple sclerosis, the physiological function of the blood-brain barrier (BBB) is perturbed, particularly in demyelinating lesions and supposedly secondary to acute demyelinating pathology. Using the toxic non-inflammatory cuprizone model of demyelination, we demonstrate, however, that the onset of persistent BBB impairment precedes demyelination. In addition to a direct effect of cuprizone on endothelial cells, a plethora of inflammatory mediators, which are mainly of astroglial origin during the initial disease phase, likely contribute to the destabilization of endothelial barrier function in vivo. Our study reveals that, at different time points of pathology and in different CNS regions, the level of gliosis correlates with the extent of BBB hyperpermeability and edema. Furthermore, in mutant mice with abolished type 3 CXC chemokine receptor (CXCR3) signaling, inflammatory responses are dampened and BBB dysfunction ameliorated. Together, these data have implications for understanding the role of BBB permeability in the pathogenesis of demyelinating disease.

  5. Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

    Science.gov (United States)

    Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

    2010-01-01

    Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

  6. [Hereditary factors in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Fliers, E.A.; Franke, B.

    2005-01-01

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of

  7. Patterns of life events preceding the suicide in rural young Chinese: a case control study.

    Science.gov (United States)

    Zhang, Jie; Ma, Zhenyu

    2012-10-01

    Previous studies on the Chinese suicide found some life events prior to the suicide different from those in the West, but there is a lack of summary of the Chinese life event patterns to better understand the effects of the social structure on Chinese suicide. We tried to identify the life events that precede the Chinese rural youth suicides and compare them with what are found in the West, so as to find the patterns that are particularly true in the Chinese culture contexts. Suicide cases were investigated with a psychological autopsy study in rural China, and local community living controls were also interviewed with the same protocol. We collapsed 64 negative life events into six categories: (1) Marriage/Love, (2) Family/Home, (3) Work/Business, (4) Health/Hospital, (5) Law/Legal, (6) Friend/Relationship. About 92.3% of the suicides studied had experienced at least one type of negative life events. The three most common negative life events categories in the past one year were Family/Home (60.7%), Health/Hospital (53.8%) and Marriage/Love (51.3%) in the rural young suicide victims. Among the negative life events, those related to family relations, love affairs, and marital issues were most likely to precede a suicide of rural suicides in China, and it is especially true of rural young women. Family is an important social institution in rural China for suicide prevention efforts. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Diseases that precede disability among latter-stage elderly individuals in Japan.

    Science.gov (United States)

    Naruse, Takashi; Sakai, Mahiro; Matsumoto, Hiroshige; Nagata, Satoko

    2015-08-01

    Understanding causes of disability among elderly individuals is an important public health issue, particularly because of the increasing rate of disabled elderly individuals and the social costs in a rapidly aging society. Accordingly, we aimed to describe the diseases that precede disability and investigate the types of diseases that are related to severe disability among Japanese elderly individuals aged over 75 years. Using claim data from the latter-stage elderly healthcare system and long-term care insurance system, we identified 76,265 elderly individuals over 75 years old who did not qualify as disabled on April 1, 2011. Among them, 3,715 elderly individuals who had been newly qualified as disabled between April 1, 2011 and March 31, 2012 were selected. Disease codes from the medical claim data in the 6 months prior to disability were collected. All descriptions were developed separately for six groups divided by gender and disability level (low, middle, and high). The results of the ordinal logistic analysis including sex and age revealed that men tended to have significantly higher levels of disability (β = 0.417, p disability level groups. In low-level disability groups, cancer in men (12.8%) and arthropathy and fracture in women (11.9% and 13.5%, respectively) were as common as cerebrovascular disorder (12.2% and 9.7%, in men and women, respectively). Stroke was the most common disease for all genders and disability levels. The diseases preceding low-level disability differed by gender. This study demonstrated the need to consider arthropathy and fracture as well as CVD in order to prevent disability.

  9. Impairment of adolescent hippocampal plasticity in a mouse model for Alzheimer's disease precedes disease phenotype.

    Directory of Open Access Journals (Sweden)

    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.

  10. Creating an inclusive mall environment with the PRECEDE-PROCEED model: a living lab case study.

    Science.gov (United States)

    Ahmed, Sara; Swaine, Bonnie; Milot, Marc; Gaudet, Caroline; Poldma, Tiiu; Bartlett, Gillian; Mazer, Barbara; Le Dorze, Guylaine; Barbic, Skye; Rodriguez, Ana Maria; Lefebvre, Hélène; Archambault, Philippe; Kairy, Dahlia; Fung, Joyce; Labbé, Delphine; Lamontagne, Anouk; Kehayia, Eva

    2017-10-01

    Although public environments provide opportunities for participation and social inclusion, they are not always inclusive spaces and may not accommodate the wide diversity of people. The Rehabilitation Living Lab in the Mall is a unique, interdisciplinary, and multi-sectoral research project with an aim to transform a shopping complex in Montreal, Canada, into an inclusive environment optimizing the participation and social inclusion of all people. The PRECEDE-PROCEDE Model (PPM), a community-oriented and participatory planning model, was applied as a framework. The PPM is comprised of nine steps divided between planning, implementation, and evaluation. The PPM is well suited as a framework for the development of an inclusive mall. Its ecological approach considers the environment, as well as the social and individual factors relating to mall users' needs and expectations. Transforming a mall to be more inclusive is a complex process involving many stakeholders. The PPM allows the synthesis of several sources of information, as well as the identification and prioritization of key issues to address. The PPM also helps to frame and drive the implementation and evaluate the components of the project. This knowledge can help others interested in using the PPM to create similar enabling and inclusive environments world-wide. Implication for rehabilitation While public environments provide opportunities for participation and social inclusion, they are not always inclusive spaces and may not accommodate the wide diversity of people. The PRECEDE PROCEDE Model (PPM) is well suited as a framework for the development, implementation, and evaluation of an inclusive mall. Environmental barriers can negatively impact the rehabilitation process by impeding the restoration and augmentation of function. Removing barriers to social participation and independent living by improving inclusivity in the mall and other environments positively impacts the lives of people with disabilities.

  11. A Legal Analysis of the Precedents of Medical Disputes in the Cosmetic Surgery Field

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    Bo Young Park

    2016-05-01

    Full Text Available BackgroundDisputes regarding medical malpractice occur between practitioners and patients. As patients have become increasingly aware regarding medical care, an increase in the unexpected side effects of procedures has been observed, thereby leading to an increase in disputes regarding medical malpractice. In this study, we reviewed trends in precedents involving cosmetic surgery-related medical disputes, with the goal of helping to prevent unnecessary disputes in the future.MethodsWe conducted a search of the judgments made in South Korean courts between 2000 and 2013 that were related to the field of plastic surgery. A total of 54 judgments were analyzed, and the selected precedents were reviewed and classified according to the kind of negligence involved.ResultsThe claim amounts ranged from under 8 million KRW (6,991 USD to 750 million KRW (629,995 USD. The most common ratio of the judgment amount to the claim amount was 20%–30%. The judgments were classified according to the following categories: violation of the duty of explanation in 17 cases (29%, violation of the duty of care in 10 cases (17%, violation of both duties in 20 cases (35%, and no violation of duty in six cases (10%.ConclusionsCosmetic surgery-related suits require different approaches than general malpractice suits. The Supreme Court requires plastic surgeons to determine the type, timing, methods, and scope of their treatments when considering possible results. Therefore, practitioners should be educated on their rights and responsibilities to enable them to cope with any possible medical dispute that may arise.

  12. Remediation of attention deficits in head injury.

    OpenAIRE

    Nag S; Rao S

    1999-01-01

    Head injury is associated with psychological sequelae which impair the patient′s psychosocial functioning. Information processing, attention and memory deficits are seen in head injuries of all severity. We attempted to improve deficits of focused, sustained and divided attention. The principle of overlapping sources of attention resource pools was utilised in devising the remediation programme. Tasks used simple inexpensive materials. Four head injured young adult males with post conc...

  13. Saudi Arabia: persistent but tenable deficits

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    In this article is described the economic situation of Saudi Arabia. In a first time, Saudi Arabia drew from external reserves to finance gulf war and covered its budget deficits, then the internal debts took over. The actual strategy in order to transfer from state to private national and foreign sector a great part of new projects financing is become a necessity to control the deficits in a country where state is strongly got in debt. (N.C.). 2 tabs

  14. Analysis of Budget deficit in Romania during 2000-2013

    OpenAIRE

    Moraru Camelia; Popovici Norina

    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...

  15. Color perception deficits in co-existing attention-deficit/hyperactivity disorder and chronic tic disorders

    NARCIS (Netherlands)

    Roessner, V.; Banaschewski, T.; Fillmer-Otte, A.; Becker, A.; Albrecht, B.; Uebel, H.; Sergeant, J.A.; Tannock, R.; Rothenberger, A.

    2008-01-01

    Preliminary findings suggest that color perception, particularly of blue-yellow stimuli, is impaired in attention-deficit/hyperactivity disorder (ADHD) as well as in chronic tic disorders (CTD). However, these findings have been not replicated and it is unclear what these deficits mean for the

  16. Beyond Auditory Sensory Processing Deficits: Lexical Tone Perception Deficits in Chinese Children with Developmental Dyslexia

    Science.gov (United States)

    Tong, Xiuhong; Tong, Xiuli; King Yiu, Fung

    2018-01-01

    Increasing evidence suggests that children with developmental dyslexia exhibit a deficit not only at the segmental level of phonological processing but also, by extension, at the suprasegmental level. However, it remains unclear whether such a suprasegmental phonological processing deficit is due to a difficulty in processing acoustic cues of…

  17. 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…

  18. Rethinking 'flexibilities' in the international drug control system-Potential, precedents and models for reforms.

    Science.gov (United States)

    Collins, John

    2017-01-24

    Much international drug policy debate centres on, what policies are permissible under the international drug treaties, whether member states are openly 'breaching' these treaties by changing national regulatory frameworks and shifting priorities away from a 'war on drugs' approach, and what 'flexibility' exists for policy reform and experimentation at national and local levels. Orthodox interpretations hold that the current system is a US-led 'prohibition regime' that was constructed in an extremely repressive and restrictive manner with almost no flexibility for significant national deviations. This paper challenges these orthodox interpretive frameworks and suggests no absolute and clear dichotomy between strict adherence and 'breaches' of the international treaties. This paper uses historical analysis to highlight the flaws in orthodox policy analyses, which assume a uniform interpretation, implementation and set of policy trajectories towards a 'prohibition regime' in the 20th century. It challenges some existing legal interpretations of the treaties through recourse to historical precedents of flexible interpretation and policy prioritisation. It then examines the legal justifications currently being formulated by member states to explain a shift towards policies which, until recently, have been viewed as outside the permissible scope of the conventions. It then examines a functionalist framework for understanding the likely contours of drug diplomacy in the post-UN General Assembly Special Session (UNGASS) 2016 era. The paper highlights that, contrary to current policy discourses, the international control system has always been implemented in a 'flexible' manner. It demonstrates that drug control goals were repeatedly subsumed to security, development, political stability and population welfare imperatives, or what we might now refer to under the umbrella of 'development issues.' The paper further demonstrates that policy prioritisation, inherent treaty

  19. Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

    Science.gov (United States)

    London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

    2018-04-04

    The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

  20. High dose methylphenidate treatment in adult attention deficit hyperactivity disorder: a case report

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    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

  1. THE BRAZILIAN SUPREME COURT'S PRECEDENTS AND THE CURIOUS TAXING DIFFERENCE ON THE AIR AND INLAND PASSENGER TRANSPORT

    Directory of Open Access Journals (Sweden)

    Marciano Seabra de Godoi

    2016-07-01

    Full Text Available The study aims to the taxing of transport service provision, particularly the passenger transport, as well as the odd difference of treatment created directly by the Brazilian Supreme Court’s precedents, applying distinguished regimes for air passenger and inland. It discusses the evolution of legislation on the subject and, specially, it examines critically how the Supreme Court’s case law stood on the issue, through the judgment of many direct actions of unconstitutionality (ADI. The study considers legally inconsistent these precedents, in which is unconstitutional the tax collection over the air transport, but constitutional over the inland one.

  2. Resting-state functional connectivity remains unaffected by preceding exposure to aversive visual stimuli.

    Science.gov (United States)

    Geissmann, Léonie; Gschwind, Leo; Schicktanz, Nathalie; Deuring, Gunnar; Rosburg, Timm; Schwegler, Kyrill; Gerhards, Christiane; Milnik, Annette; Pflueger, Marlon O; Mager, Ralph; de Quervain, Dominique J F; Coynel, David

    2018-02-15

    While much is known about immediate brain activity changes induced by the confrontation with emotional stimuli, the subsequent temporal unfolding of emotions has yet to be explored. To investigate whether exposure to emotionally aversive pictures affects subsequent resting-state networks differently from exposure to neutral pictures, a resting-state fMRI study implementing a two-group repeated-measures design in healthy young adults (N = 34) was conducted. We focused on investigating (i) patterns of amygdala whole-brain and hippocampus connectivity in both a seed-to-voxel and seed-to-seed approach, (ii) whole-brain resting-state networks with an independent component analysis coupled with dual regression, and (iii) the amygdala's fractional amplitude of low frequency fluctuations, all while EEG recording potential fluctuations in vigilance. In spite of the successful emotion induction, as demonstrated by stimuli rating and a memory-facilitating effect of negative emotionality, none of the resting-state measures was differentially affected by picture valence. In conclusion, resting-state networks connectivity as well as the amygdala's low frequency oscillations appear to be unaffected by preceding exposure to widely used emotionally aversive visual stimuli in healthy young adults. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia found in an atomic bomb survivor

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Y; Edagawa, J; Taniwaki, M; Ide, T; Misawa, S [Kyoto Prefectural Univ. of Medicine (Japan)

    1981-03-01

    An autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia, presumably on a sequela to the atomic bomb in Hiroshima is reported. On admission, severe anemia and thrombocytosis were found and the bone marrow aspiration showed myeloid hyperplasia without definite maturation arrest. Mild to moderate eosinophilia and basophilia continued during the course of the disease, accompaning mild monocytosis 2 years later. Furthermore, he had the radical operation for the early gastric cancer in this preleukemic stage. After the administration of methenolone acetate (25 mg/day), severe anemia has dramatically improved, but leukocytosis with profound monocytosis persisted, and subsequently acute myelocytic leukemia developed. He died from an intracerebral bleeding due to an accidental trauma on the head. Autopsy findings disclosed the systemic leukemic infiltration. Repeated chromosome analyses revealed the mosaic karyotype of 46, XY/45, XY, -16 on admission, but it was 46, XY/46, XY, del (8) (p 12) in the overt leukemic phase. The granulopoietic colony forming capacity of bone marrow cells was already low one year before the onset of overt leukemia. This finding suggested that the existence of an abnormal clone could be predictable. In addition, the possible causative effect of the exposure to the atomic bomb in leukemogenesis in this case is discussed.

  4. Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zaitunnatakhin Zamli

    2014-01-01

    Full Text Available Osteoarthritis (OA is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH and Bristol Strain 2 (BS2 guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the changes were always greater and faster in DH than BS2. In the medial side, a significant increase of chondrocyte apoptosis and cartilage degradation was observed in DH between 24 and 30 weeks of age preceded by a progressive thickening and stiffening of subchondral bone plate (Sbp. The Sbp thickness consistently increased over the 30-week study period but the bone mineral density (BMD of the Sbp gradually decreased after 16 weeks. The absence of these changes in the medial side of BS2 may indicate that the Sbp of DH was undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep zone of articular cartilage and correlated with thickness of the subchondral bone plate suggesting that cartilage degradation and chondrocyte apoptosis may be a consequence of continuous bone remodelling during the development of OA in these animal models of OA.

  5. Influence of sound source location on the behavior and physiology of the precedence effect in cats.

    Science.gov (United States)

    Dent, Micheal L; Tollin, Daniel J; Yin, Tom C T

    2009-08-01

    Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from approximately 0.4 to 10 ms, summing localization for |ISDs| 10 ms, which is the approximate echo threshold. The neural correlates to the PE have been described in both anesthetized and unanesthetized animals at many levels from auditory nerve to cortex. Single-unit recordings from the inferior colliculus (IC) and auditory cortex of cats demonstrate that neurons respond to both lead and lag sounds at ISDs above behavioral echo thresholds, but the response to the lag is reduced at shorter ISDs, consistent with localization dominance. Here the influence of the relative locations of the leading and lagging sources on the PE was measured behaviorally in a psychophysical task and physiologically in the IC of awake behaving cats. At all configurations of lead-lag stimulus locations, the cats behaviorally exhibited summing localization, localization dominance, and breakdown of fusion. Recordings from the IC of awake behaving cats show neural responses paralleling behavioral measurements. Both behavioral and physiological results suggest systematically shorter echo thresholds when stimuli are further apart in space.

  6. Barriers to Effective Doctor-Patient Relationship Based on PRECEDE PROCEED Model

    Science.gov (United States)

    Ghaffarifar, Saeideh; Ghofranipour, Fazlollah; Ahmadi, Fazlollah; Khoshbaten, Manouchehr

    2015-01-01

    Objective: This study intends to investigate interns and faculty members’ insights into constructing relationship between physicians and patients at 3 more accredited Iranian universities of medical sciences. Method: Applying PRECEDE PROCEED model, semi-structured interviews were completed with 7 interns and 14 faculty members and two themes were emerged from directed content analysis. The meaning units of the first theme, barriers to effective doctor-patient relationship, are discussed in this paper. Results: According to the participants, building doctor-patient relationship is influenced by many contextual and regulatory factors as well as content, process and perceptual skills of physicians. Conclusions: Faculty and curriculum development, as well as foundation of the department of communication skills at medical schools are recommended to eliminate the impact of poor communication on patients’ satisfaction and physicians’ self-efficacy specific to their communication skills. Practice Implications: Applying theories and models of health education and health promotion, researchers and educators can use the most predictive constructs of theories to design and implement effective interventions. PMID:26153160

  7. Cost estimation for solid waste management in industrialising regions – Precedents, problems and prospects

    International Nuclear Information System (INIS)

    Parthan, Shantha R.; Milke, Mark W.; Wilson, David C.; Cocks, John H.

    2012-01-01

    Highlights: ► We review cost estimation approaches for solid waste management. ► Unit cost method and benchmarking techniques used in industrialising regions (IR). ► Variety in scope, quality and stakeholders makes cost estimation challenging in IR. ► Integrate waste flow and cost models using cost functions to improve cost planning. - Abstract: 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.

  8. Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation.

    Science.gov (United States)

    Pennings, Nicholas; Jaber, Johnny; Ahiawodzi, Peter

    2018-05-01

    Numerous studies have examined the relationship between endogenous insulin and weight change with mixed results. This study examined the relationship between fasting insulin levels, insulin resistance (IR), and 10-year weight change by glycaemic stage. Using data from the US National Health and Nutrition Examination Survey 2011-2014, 3840 participants were divided into 6 groups based on fasting glucose and fasting insulin levels. Fasting insulin concentrations were dichotomized into <25th percentile (normal) and ≥25th percentile (elevated). Ten-year weight change associated with fasting insulin was assessed by glycaemic stage. Average weight change over a 10-year period was higher in individuals with elevated insulin levels compared to the first quartile (1.40 lbs. vs 11.12 lbs, P < .0001). Across all groups, a 1 μU increase in fasting insulin levels resulted in a 0.52-pound increase in weight (P < .0001). Similarly, an increase in HOMA-IR was associated with increase in weight (1.32 lbs per IR unit, P < .0001). Marginal increases in weight were most pronounced in the normal insulin groups compared to elevated insulin groups and diminished as glycaemic stage progressed. Elevated fasting insulin level was positively associated with weight gain. The impact of fasting insulin and IR on weight gain preceded hyperglycaemia and diminished as glycaemic stage progressed. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus

    International Nuclear Information System (INIS)

    Ishida, Kaoru; Koeda, Keisuke; Sato, Nobuhiro

    1999-01-01

    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)

  10. 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.

  11. Engineering Codes of Ethics and the Duty to Set a Moral Precedent.

    Science.gov (United States)

    Schlossberger, Eugene

    2016-10-01

    Each of the major engineering societies has its own code of ethics. Seven "common core" clauses and several code-specific clauses can be identified. The paper articulates objections to and rationales for two clauses that raise controversy: do engineers have a duty (a) to provide pro bono services and/or speak out on major issues, and (b) to associate only with reputable individuals and organizations? This latter "association clause" can be justified by the "proclamative principle," an alternative to Kant's universalizability requirement. At the heart of engineering codes of ethics, and implicit in what it is to be a moral agent, the "proclamative principle" asserts that one's life should proclaim one's moral stances (one's values, principles, perceptions, etc.). More specifically, it directs engineers to strive to insure that their actions, thoughts, and relationships be fit to offer to their communities as part of the body of moral precedents for how to be an engineer. Understanding codes of ethics as reflections of this principle casts light both on how to apply the codes and on the distinction between private and professional morality.

  12. 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.

  13. A New Car-Following Model considering Driving Characteristics and Preceding Vehicle’s Acceleration

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2017-01-01

    Full Text Available In the past decades, many improved car-following models based on the full velocity difference (FVD model have been developed. But these models do not consider the acceleration of leading vehicle. Some of them consider individual anticipation behavior of drivers, but they either do not quantitatively determine the types of driving or artificially divide the driving types rather than deriving them from actual traffic data. In this paper, driver’s driving styles are firstly categorized based on actual traffic data via data mining and clustering algorithm. Secondly, a new car-following model based on FVD model is developed, taking into account individual anticipation effects and the acceleration of leading vehicle. The effect of driving characteristics and leading vehicle’s acceleration on car-following behavior is further analyzed via numerical simulation. The results show that considering the acceleration of preceding vehicle in the model improves the stability of traffic flow and different driving characteristics have different influence on the stability of traffic flow.

  14. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma.

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D; Schlecht, Nicolas F; Einstein, Mark H; Greally, John M

    2016-09-20

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors.

  15. 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.

  16. Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    James, N D; Apperley, J F; Kam, K C; Mackinnon, S; Goldman, J M; Goolden, A W.G.; Sikora, K [Royal Postgraduate Medical School, London (UK)

    1989-03-01

    Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author).

  17. Future climate forcing potentially without precedent in the last 420 million years.

    Science.gov (United States)

    Foster, Gavin L; Royer, Dana L; Lunt, Daniel J

    2017-04-04

    The evolution of Earth's climate on geological timescales is largely driven by variations in the magnitude of total solar irradiance (TSI) and changes in the greenhouse gas content of the atmosphere. Here we show that the slow ∼50 Wm -2 increase in TSI over the last ∼420 million years (an increase of ∼9 Wm -2 of radiative forcing) was almost completely negated by a long-term decline in atmospheric CO 2 . This was likely due to the silicate weathering-negative feedback and the expansion of land plants that together ensured Earth's long-term habitability. Humanity's fossil-fuel use, if unabated, risks taking us, by the middle of the twenty-first century, to values of CO 2 not seen since the early Eocene (50 million years ago). If CO 2 continues to rise further into the twenty-third century, then the associated large increase in radiative forcing, and how the Earth system would respond, would likely be without geological precedent in the last half a billion years.

  18. 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

  19. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction.

    Science.gov (United States)

    Stanyer, Lee; Jorgensen, Wenche; Hori, Osamu; Clark, John B; Heales, Simon J R

    2008-09-01

    The accumulation of oxidatively modified proteins has been shown to be a characteristic feature of many neurodegenerative disorders and its regulation requires efficient proteolytic processing. One component of the mitochondrial proteolytic system is Lon, an ATP-dependent protease that has been shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated activity was inhibited by 45%. Treatment of mitochondria with a range of peroxynitrite concentrations (10-1000 microM) revealed that a decline in Lon protease activity preceded electron transport chain (ETC) dysfunction (complex I, II-III and IV) and that ATP-stimulated activity was approximately fivefold more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex. Taken together these findings suggest that Lon protease may be particularly vulnerable to inactivation in conditions associated with GSH depletion and elevated oxidative stress.

  20. Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

    Science.gov (United States)

    Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

    2017-09-01

    To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

  1. Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation

    International Nuclear Information System (INIS)

    Werts, E.D.; Gibson, D.P.; Knapp, S.A.; DeGowin, R.L.

    1980-01-01

    Circulation of hemopoietic stem cells into an irradiated site has been thoroughly documented, but migration of stromal cells to repair radiation damage has not. We determined the radiosensitivity of mouse bone marrow stroma and evaluated stromal and hemopoietic repopulation in x-irradiated marrow. The D 0 for growth of colonies of marrow stromal cells (MSC) was 215 to 230 rad. Total-body irradiation (TB) obliterated marrow stromal and hemopoietic cells within 3 days. In contrast, 1 day after 1000 rad leg irradiation (LI), MSC rose to 80% of normal, but fell to 34% by 3 days and recovered to 72% by 30 days. However, femoral nucleated cells diminished to 20% by 3 days and recovered to 74% of normal by 30 days. Likewise, differentiated marrow cells and hemopoietic stem cells were initially depleted. With 1000 rad LI followed 3 h later by 1000 rad to the body while shielding the leg, MSC and femoral nucleated cells recovered to values intermediate between 1000 rad TB and 1000 rad LI. We concluded that: (1) the D 0 for MSC was 215 to 230 rad, (2) stromal repopulation preceded hemopoietic recovery, and (3) immigration of stromal cells from an unirradiated sanctuary facilitated hemopoietic repopulation of a heavily irradiated site

  2. How are topics born? Understanding the research dynamics preceding the emergence of new areas

    Directory of Open Access Journals (Sweden)

    Angelo A. Salatino

    2017-06-01

    Full Text Available The ability to promptly recognise new research trends is strategic for many stakeholders, including universities, institutional funding bodies, academic publishers and companies. While the literature describes several approaches which aim to identify the emergence of new research topics early in their lifecycle, these rely on the assumption that the topic in question is already associated with a number of publications and consistently referred to by a community of researchers. Hence, detecting the emergence of a new research area at an embryonic stage, i.e., before the topic has been consistently labelled by a community of researchers and associated with a number of publications, is still an open challenge. In this paper, we begin to address this challenge by performing a study of the dynamics preceding the creation of new topics. This study indicates that the emergence of a new topic is anticipated by a significant increase in the pace of collaboration between relevant research areas, which can be seen as the ‘parents’ of the new topic. These initial findings (i confirm our hypothesis that it is possible in principle to detect the emergence of a new topic at the embryonic stage, (ii provide new empirical evidence supporting relevant theories in Philosophy of Science, and also (iii suggest that new topics tend to emerge in an environment in which weakly interconnected research areas begin to cross-fertilise.

  3. Bell’s Palsy: Symptoms Preceding and Accompanying the Facial Paresis

    Directory of Open Access Journals (Sweden)

    Daniele De Seta

    2014-01-01

    Full Text Available This individual prospective cohort study aims to report and analyze the symptoms preceding and accompanying the facial paresis in Bell’s palsy (BP. Two hundred sixty-nine patients affected by BP with a maximum delay of 48 hours from the onset were enrolled in the study. The evolution of the facial paresis expressed as House-Brackmann grade in the first 10 days and its correlation with symptoms were analyzed. At the onset, 136 patients presented postauricular pain, 114 were affected by dry eye, and 94 reported dysgeusia. Dry mouth was present in 54 patients (19.7%, facial pain, hyperlacrimation, aural fullness, and hyperacusis represented a smaller percentage of the reported symptoms. After 10 days, 39.9% of the group had a severe paresis while 10.2% reached a complete recovery. Dry mouth at the onset was correlated with severe grade of palsy and was prognostic for poor recovery in the early period. These outcomes lead to the deduction that the nervus intermedius plays an important role in the presentation of the BP and it might be responsible for most of the accompanying symptomatology of the paresis. Our findings could be of important interest to early address a BP patient to further examinations and subsequent therapy.

  4. Presentations and Preceding factors of Drug Overdose amongst adolescents admitted to a Large Regional Hospital.

    LENUS (Irish Health Repository)

    Maduemem, KE

    2018-04-01

    Suicide is the third most common cause of death among adolescents globally, and poisoning is the leading method of attempted suicide. Survival after self-poisoning or drug overdose (OD) is common, providing an opportunity for secondary prevention. The aim of this study was to highlight pattern of presentations and preceding factors of OD in an adolescent population. We retrospectively evaluated the data of 85 adolescents presenting to a large regional hospital with OD over a 3-year period. The female-to-male ratio was 4.3:1. The median age of adolescents was 15.83 (range: 11.32 – 16.98) years. History of deliberate self-harm (DSH) was documented in 44.7%. Twenty-eight (33%) patients had been under the care of the CAMHS prior to index admission. Acetaminophen was the commonest drug used. Depression was the most common cause of mental illness in the study group. Substance abuse and conduct disorder were significantly commoner in males (p<0.05). Self-poisoning including OD in adolescence is a strong predictor of suicide; understanding the probable triggers can be significant in establishing appropriate prevention strategies.

  5. Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study.

    Science.gov (United States)

    Benedetti, M D; Bower, J H; Maraganore, D M; McDonnell, S K; Peterson, B J; Ahlskog, J E; Schaid, D J; Rocca, W A

    2000-11-14

    To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

  6. Cognitive declines precede and predict functional declines in aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Laura B Zahodne

    Full Text Available To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer's disease (AD.A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study.3,443 initially non-demented older adults (612 with eventual incident dementia and 517 patients with AD.Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults or an informant (in the sample of prevalent AD patients. Data were analyzed with autoregressive cross-lagged panel analysis.Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD.Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults.

  7. Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

    Science.gov (United States)

    Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

    2017-12-01

    Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

  8. 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.

  9. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

    2018-05-01

    Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

  10. Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    James, N.D.; Apperley, J.F.; Kam, K.C.; Mackinnon, S.; Goldman, J.M.; Goolden, A.W.G.; Sikora, K.

    1989-01-01

    Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author)

  11. Genetic architecture of conspecific sperm precedence in Allonemobius fasciatus and A. socius.

    Science.gov (United States)

    Britch, Seth C; Swartout, Emma J; Hampton, Daniel D; Draney, Michael L; Chu, Jiming; Marshall, Jeremy L; Howard, Daniel J

    2007-06-01

    The evolution of barriers to gene exchange is centrally important to speciation. We used the crickets Allonemobius fasciatus and A. socius to investigate the genetic architecture of conspecific sperm precedence (CSP), a postinsemination prezygotic reproductive barrier. With amplified fragment-length polymorphism (AFLP) markers and controlled crosses we constructed linkage maps and estimated positions of QTL associated with CSP. The majority of QTL have low to moderate effects, although a few QTL exist in A. socius with large effects, and the numbers of QTL are comparable to numbers of genes accounting for species differences in other studies. The QTL are spread across many unlinked markers, yet QTL placed with linked markers are on a small number of linkage groups that could reflect the role of the large Allonemobius sex chromosome in prezygotic isolation. Although many QTL had positive effects on conspecific sperm utilization several QTL also exerted negative effects, which could be explained by intraspecific sexual conflict, sperm competition, or epistasis of introgressed genes on novel backgrounds. One unexpected outcome was that A. socius CSP alleles have a stronger effect than those from A. fasciatus in hybrid females, causing hybrids to behave like A. socius with regard to sperm utilization. Implications of this asymmetry in the Allonemobius hybrid zone are discussed.

  12. 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.

  13. [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

  14. Understanding suicide among indigenous adolescents: a review using the PRECEDE model.

    Science.gov (United States)

    Clarke, V A; Frankish, C J; Green, L W

    1997-06-01

    To use the available literature to identify the causes of suicide among indigenous adolescents. The PRECEDE model provided a framework to organize the material and identify the areas where relatively little research had been reported. The epidemiological diagnosis showed that suicide was greater in indigenous than non-indigenous populations and particularly high among adolescent males. Environments of native persons are characterized by remoteness, poverty, cultural displacement, and family disintegration. The educational and organizational diagnosis identified predisposing factors reflecting the social environments previously identified, the enabling factors of televised suicides, and firearm and alcohol availability, in conjunction with an absence of positive expectations. Finally the administrative and policy diagnosis identified a piecemeal, short term perspective, often lacking cultural sensitivity. Although there was more literature from the United States than from Canada, Australia or New Zealand, the pictures emerging were consistent, with problems being identified across continents. Literature was more abundant in relation to the epidemiological, environmental, and educational/ organizational diagnoses than in relation to policy and administration. The increased suicide rates among indigenous adolescents were not a product of their native origins, but of the social milieu in which these people generally found themselves.

  15. 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.

  16. The history of attention deficit hyperactivity disorder

    Science.gov (United States)

    Reichl, Susanne; Lange, Katharina M.; Tucha, Lara; Tucha, Oliver

    2010-01-01

    The contemporary concept of attention deficit hyperactivity disorder (ADHD) as defined in the DSM-IV-TR (American Psychiatric Association 2000) is relatively new. Excessive hyperactive, inattentive, and impulsive children have been described in the literature since the nineteenth century. Some of the early depictions and etiological theories of hyperactivity were similar to current descriptions of ADHD. Detailed studies of the behavior of hyperactive children and increasing knowledge of brain function have changed the concepts of the fundamental behavioral and neuropathological deficits underlying the disorder. This article presents an overview of the conceptual history of modern-day ADHD. PMID:21258430

  17. The deficit syndrome of schizophrenia: towards heterogeneity.

    Science.gov (United States)

    Thibaut, F; Petit, M

    1997-01-01

    Since the turn of the century, psychiatrists have been concerned with both the unity and diversity of schizophrenia. From these early descriptions until now, many authors have attempted to delineate clinically meaningful subtypes within this disorder. In this connection, negative/positive subtyping has generated great interest. Carpenter and his team have emphasized the origin of the negative symptoms observed. They have proposed that primary enduring negative symptoms should be distinguished from transient negative symptoms resulting from treatment, depression or social deprivation and should be termed deficit symptoms. The validity of this subtyping is supported by clinical, biochemical or electrophysiological studies showing differences between deficit and nondeficit patients.

  18. The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.

    Science.gov (United States)

    Tanis, Ross M; Piroli, Gerardo G; Day, Stani D; Frizzell, Norma

    2015-01-01

    While the 3T3-L1 adipocyte model is routinely used for the study of obesity and diabetes, the mitochondrial respiratory profile in normal versus high glucose has not been examined in detail. We matured adipocytes in normal (5mM) or high (30 mM) glucose and insulin and examined the mitochondrial bioenergetics. We also assessed the requirement for the Unfolded Protein Response (UPR) and ER stress under these conditions. Basal respiration was ~1.7-fold greater in adipocytes that had matured in 30 mM glucose; however, their ability to increase oxygen consumption in response to stress was impaired. Adipogenesis proceeded in both normal and high glucose with concomitant activation of the UPR, but only high glucose was associated with increased levels of ER stress and mitochondrial stress as observed by parallel increases in CHOP and protein succination. Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration. Our data suggests that mitochondrial stress, protein succination and ER stress are uniquely linked in adipocytes matured in high glucose. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

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    Wolfgang Nachbauer

    Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

  20. Bioenergetic Consequences of FLAG Tag Addition to the C-Terminus of Subunit 8 of Yeast Saccharomyces cerevisiae Mitochondrial ATP Synthase

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    I MADE ARTIKA

    2010-09-01

    Full Text Available The yeast mitochondrial F1F0-ATP synthase is a multisubunit complex that contains at least 17 different subunits. Subunit 8 of yeast mitochondrial ATP synthase is a hydrophobic protein of 48 amino acids encoded by the mitochondrial ATP8 gene. Subunit 8 has three distinct domains; an N-terminal domain, a central hydrophobic domain and a C-terminal domain. FLAG tag addition to subunit 8 protein potentially facilitate elucidation of its topology, structure, and function. It has been shown that following incorporation of FLAG tag to its C-terminus, subunit 8 still assemble into functional ATP synthase complex. In order to analyze bioenergetic consequences of the FLAG tag addition, a yeast strain expressing FLAG tagged-subunit 8 was subjected to cellular respiration assays. Results obtained showed that addition of FLAG tag to the C-terminus of subunit 8 does not impair its proper functioning. The FLAG tag system, therefore, can be employed to study subunit 8′s detailed structure, topology, and function.

  1. Gray matter-specific changes in brain bioenergetics after acute sleep deprivation: a 31P magnetic resonance spectroscopy study at 4 Tesla.

    Science.gov (United States)

    Plante, David T; Trksak, George H; Jensen, J Eric; Penetar, David M; Ravichandran, Caitlin; Riedner, Brady A; Tartarini, Wendy L; Dorsey, Cynthia M; Renshaw, Perry F; Lukas, Scott E; Harper, David G

    2014-12-01

    A principal function of sleep may be restoration of brain energy metabolism caused by the energetic demands of wakefulness. Because energetic demands in the brain are greater in gray than white matter, this study used linear mixed-effects models to examine tissue-type specific changes in high-energy phosphates derived using 31P magnetic resonance spectroscopy (MRS) after sleep deprivation and recovery sleep. Experimental laboratory study. Outpatient neuroimaging center at a private psychiatric hospital. A total of 32 MRS scans performed in eight healthy individuals (mean age 35 y; range 23-51 y). Phosphocreatine (PCr) and β-nucleoside triphosphate (NTP) were measured using 31P MRS three dimensional-chemical shift imaging at high field (4 Tesla) after a baseline night of sleep, acute sleep deprivation (SD), and 2 nights of recovery sleep. Novel linear mixed-effects models were constructed using spectral and tissue segmentation data to examine changes in bioenergetics in gray and white matter. PCr increased in gray matter after 2 nights of recovery sleep relative to SD with no significant changes in white matter. Exploratory analyses also demonstrated that increases in PCr were associated with increases in electroencephalographic slow wave activity during recovery sleep. No significant changes in β-NTP were observed. These results demonstrate that sleep deprivation and subsequent recovery-induced changes in high-energy phosphates primarily occur in gray matter, and increases in PCr after recovery sleep may be related to sleep homeostasis. © 2014 Associated Professional Sleep Societies, LLC.

  2. 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…

  3. Magnetic resonance imaging findings of mumps meningoencephalitis with bilateral hippocampal lesions without preceding acute parotitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Reum; Lee, Ha Young; Lim, Myung Kwan; Kang, Young Hye; Cho, Soon Gu; Choi, Seong Hye; Baek, Ji Hyeon [Inha University School of Medicine, Incheon (Korea, Republic of)

    2017-04-15

    Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.

  4. Self-verification strivings in children holding negative self-views: the mitigating effects of a preceding success experience

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Orobio de Castro, B.; Telch, M.J.

    2010-01-01

    Research among adults has consistently shown that people holding negative self-views prefer negative over positive feedback. The present study tested the hypothesis that this preference is less robust among pre-adolescents, such that it will be mitigated by a preceding positive event.

  5. 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…

  6. First sale doctrine on computer programs in the European Union. reiteration of the precedent or jurisprudential change?

    Directory of Open Access Journals (Sweden)

    Sergio Raúl Cardoso González

    2017-08-01

    Full Text Available Comparative analysis of rulings C-128/11 (UsedSoft of July 3, 2012 and C-166/15 (Ranks and Vasiļevičs of October 12, 2016 by the Court of Justice of the European Union, concerning first sale doctrine on computer programs. Reiteration of the precedent or jurisprudential change?

  7. Number and sequence of preceding miscarriages and maternal age for the prediction of antiphospholipid syndrome in women with recurrent miscarriage.

    NARCIS (Netherlands)

    Boogaard, E. van den; Cohn, D.M.; Korevaar, J.C.; Dawood, F.; Vissenberg, R.; Middeldorp, S.; Goddijn, M.; Farquharson, R.G.

    2013-01-01

    Objective: To investigate the relationship between the number and sequence of preceding miscarriages and antiphospholipid syndrome (APS). Design: Retrospective cohort study. Setting: Recurrent miscarriage (RM) clinic. Patient(s): Women who attended the RM clinic from 1988 to 2006. Intervention(s):

  8. Suicide and general elections in Austria: do preceding regional suicide rate differentials foreshadow subsequent voting behavior swings?

    Science.gov (United States)

    Voracek, Martin; Formann, Anton K; Fülöp, Gerhard; Sonneck, Gernot

    2003-05-01

    Suicide-epidemiological research on short-term effects of elections on national/regional suicide and parasuicide incidence has yielded contradictory evidence. Reversing the cause-effect relationship of this line of research we investigated whether preceding regional suicide rates are related to subsequent election results. For Austria's 121 districts, we regressed averaged standardized suicide rates for the preceding period (1988-1994) on political parties' subsequent electoral gains/losses (1999-to-1995) while controlling for a set of 12 domain-relevant psychosocial/economic indices. Stepwise weighted multiple regression led to a significant model. The 1999-to-1995 electoral gains/losses of two opposition parties, together with the population variation caused by migration balance and by births/deaths balance, accounted for a substantial part (30%) of the variability in preceding district-level suicide rates. Various other social indices failed to contribute further substantial increments to this model. This finding suggests that variations in preceding regional suicide incidence might be mirrored in subsequent changes in voting behavior. A speculative post hoc explanation for the finding is offered: on a community level, suicide's aftermath might produce socially and politically alienated survivors of suicide who co-shape swings towards opposition parties in subsequent general elections. The finding calls for more research on suicide's long-term aftermath. Within-country replicability and cross-national generalizability await further investigation. At present, the factor/mechanism accounting for this finding is neither well-established nor has been directly tested.

  9. “Caint na ndaoine”. The Irish Language as a Precedent for Standardisation

    Directory of Open Access Journals (Sweden)

    Carlo James Waskowski Ritchie

    2016-12-01

    Full Text Available “Caint na ndaoine”. The Irish Language as a Precedent for Standardisation Critics of the standardisation of the Irish language argue that the “modernisation” of the Irish orthography has been detrimental to the preservation of the various dialects that form native spoken Irish. The effects of standardisation on Irish consequently form an important precedent for language standardisation. The potential alienation of a language’s native speakers is an outcome of standardisation that is obviously destructive for a language community that exists in a minority. The issues that surround the movement for a standardised Plattdeutsch are similar to those faced in the standardisation of Modern Irish. Since the recognition by the European Union of Low German (Plattdeutsch as a regional language in 1998, there has been newfound momentum in the movement for its reestablishment as a unified language of Northern Germany. One of the great difficulties of this movement however is the lack of any universal orthography due to the separate nature of the language’s dialects. Given the sociolinguistic similarities of these two (albeit unrelated languages, a study of the effects of the standardisation of Irish is useful for an assessment of the possibility of a standardised Plattdeutsch.   “Caint na ndaoine”. Język irlandzki jako precedens standaryzacji Krytycy procesu standaryzacji języka irlandzkiego uważają, że „modernizacja” irlandzkiej ortografii zaszkodziła ochronie wielu dialektów składających się na oralny język natywnych Irlandczyków. Skutki standaryzacji irlandzkiego stanowią więc ważny precedens standaryzacji języków. Możliwe wyobcowanie natywnych użytkowników języka jest w oczywisty sposób destrukcyjnym dla trwania wspólnoty mniejszościowej rezultatem procesu standaryzacji. Zagadnienia towarzyszące ruchowi na rzecz standaryzacji języka dolnoniemieckiego są podobne do problemów standaryzacji, wobec kt

  10. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    International Nuclear Information System (INIS)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

    2017-01-01

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  11. Optimally growing boundary layer disturbances in a convergent nozzle preceded by a circular pipe

    Science.gov (United States)

    Uzun, Ali; Davis, Timothy B.; Alvi, Farrukh S.; Hussaini, M. Yousuff

    2017-06-01

    We report the findings from a theoretical analysis of optimally growing disturbances in an initially turbulent boundary layer. The motivation behind this study originates from the desire to generate organized structures in an initially turbulent boundary layer via excitation by disturbances that are tailored to be preferentially amplified. Such optimally growing disturbances are of interest for implementation in an active flow control strategy that is investigated for effective jet noise control. Details of the optimal perturbation theory implemented in this study are discussed. The relevant stability equations are derived using both the standard decomposition and the triple decomposition. The chosen test case geometry contains a convergent nozzle, which generates a Mach 0.9 round jet, preceded by a circular pipe. Optimally growing disturbances are introduced at various stations within the circular pipe section to facilitate disturbance energy amplification upstream of the favorable pressure gradient zone within the convergent nozzle, which has a stabilizing effect on disturbance growth. Effects of temporal frequency, disturbance input and output plane locations as well as separation distance between output and input planes are investigated. The results indicate that optimally growing disturbances appear in the form of longitudinal counter-rotating vortex pairs, whose size can be on the order of several times the input plane mean boundary layer thickness. The azimuthal wavenumber, which represents the number of counter-rotating vortex pairs, is found to generally decrease with increasing separation distance. Compared to the standard decomposition, the triple decomposition analysis generally predicts relatively lower azimuthal wavenumbers and significantly reduced energy amplification ratios for the optimal disturbances.

  12. Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli:A Meta-Analysis

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    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.

  13. Observations of increased tropical rainfall preceded by air passage over forests.

    Science.gov (United States)

    Spracklen, D V; Arnold, S R; Taylor, C M

    2012-09-13

    Vegetation affects precipitation patterns by mediating moisture, energy and trace-gas fluxes between the surface and atmosphere. When forests are replaced by pasture or crops, evapotranspiration of moisture from soil and vegetation is often diminished, leading to reduced atmospheric humidity and potentially suppressing precipitation. Climate models predict that large-scale tropical deforestation causes reduced regional precipitation, although the magnitude of the effect is model and resolution dependent. In contrast, observational studies have linked deforestation to increased precipitation locally but have been unable to explore the impact of large-scale deforestation. Here we use satellite remote-sensing data of tropical precipitation and vegetation, combined with simulated atmospheric transport patterns, to assess the pan-tropical effect of forests on tropical rainfall. We find that for more than 60 per cent of the tropical land surface (latitudes 30 degrees south to 30 degrees north), air that has passed over extensive vegetation in the preceding few days produces at least twice as much rain as air that has passed over little vegetation. We demonstrate that this empirical correlation is consistent with evapotranspiration maintaining atmospheric moisture in air that passes over extensive vegetation. We combine these empirical relationships with current trends of Amazonian deforestation to estimate reductions of 12 and 21 per cent in wet-season and dry-season precipitation respectively across the Amazon basin by 2050, due to less-efficient moisture recycling. Our observation-based results complement similar estimates from climate models, in which the physical mechanisms and feedbacks at work could be explored in more detail.

  14. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

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    Cecilie Linneberg

    2015-09-01

    Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  15. Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

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    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. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D.; Schlecht, Nicolas F.; Einstein, Mark H.; Greally, John M.

    2016-01-01

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors. PMID:27557505

  17. Increased diagnostic activity in general practice during the year preceding colorectal cancer diagnosis.

    Science.gov (United States)

    Hansen, Pernille Libach; Hjertholm, Peter; Vedsted, Peter

    2015-08-01

    Accurate diagnostic activity in general practice before colorectal cancer (CRC) diagnosis is crucial for an early detection of CRC. This study aimed to investigate the rates of daytime consultations, hemoglobin (Hb) measurements and medicine prescriptions for hemorrhoids in general practice in the year preceding CRC diagnosis. Using Danish registries, we conducted a population-based matched cohort study including CRC patients aged 40-80 years (n = 19,209) and matched references (n = 192,090). We calculated odds ratios (ORs) using a conditional logistical regression model and incidence rate ratios (IRRs) using a negative binomial regression model. The CRC patients had significantly more consultations from 9 months before diagnosis and significantly increased rates of Hb measurements from up to 17 months before diagnosis compared with references. Furthermore, up to 18 months before diagnosis, CRC patients had significantly higher rates of prescriptions for hemorrhoids; and 2 months before diagnosis, the IRR was 12.24 (95% confidence interval (CI): 10.29-14.55) for men. The positive predictive value (PPV) of CRC for having a first-time prescription for hemorrhoids was highest among men aged 70-80 years [PPV = 3.2% (95% CI: 2.8-3.7)]. High prescription rates were predominantly seen among rectal cancer patients, whereas colon cancer patients had higher rates of consultations and Hb measurements. This study revealed a significant increase in healthcare seeking and diagnostic activity in general practice in the year prior to CRC diagnosis, which indicates the presence of a "diagnostic time window" and a potential for earlier diagnosis of CRC based on clinical signs and symptoms. © 2015 UICC.

  18. Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

    Science.gov (United States)

    Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

    2009-01-01

    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

  19. A case-control study on cigarette, alcohol, and coffee consumption preceding Parkinson's disease.

    Science.gov (United States)

    Ragonese, P; Salemi, G; Morgante, L; Aridon, P; Epifanio, A; Buffa, D; Scoppa, F; Savettieri, G

    2003-01-01

    To investigate the association between cigarette smoking, alcohol drinking, coffee consumption and Parkinson's disease (PD). We selected subjects affected by idiopathic PD, with a Mini-Mental State Examination of > or =24, and controls matched 1 to 1 with cases by age (+/- 2 years) and sex. Controls were randomly selected from the resident list of the same municipality of residence of the cases. We assessed cigarette smoking, alcohol drinking, and coffee consumption preceding the onset of PD or the corresponding time for controls using a structured questionnaire, which also evaluated the duration and dose of exposure. Using conditional logistic regression analysis, we calculated adjusted OR and 95% CI. We interviewed 150 PD patients and 150 matched controls. Cigarette smoking (ever vs. never smokers OR = 0.66, 95% CI = 0.41-1.05, p = 0.08) did not show a statistically significant association with PD. We observed an inverse association between alcohol drinking (ever vs. never OR = 0.61, 95% CI = 0.39-0.97, p = 0.037) and coffee consumption (ever vs. never OR = 0.16, 95% CI 0.05-0.46, p = 0.0001) and PD. These associations remained significant after adjustment for other covariates: OR for ever vs. never alcohol consumption was 0.62 (95% CI = 0.43-0.89, p = 0.009) and that for coffee drinking 0.19 (95% CI = 0.07-0.52, p = 0.001). Heavy coffee consumption confirmed the inverse association between coffee and PD (more than 81 cup/year vs. none: OR = 0.20, 95% CI = 0.08-0.47, p coffee drinking, alcohol consumption and PD. The multiple inverse association observed may indicate a complex interaction between genetic and environmental factors. Copyright 2003 S. Karger AG, Basel

  20. Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

    Directory of Open Access Journals (Sweden)

    S Samuel Weigt

    Full Text Available Chronic Lung Allograft Dysfunction (CLAD is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL fluid samples were obtained from incipient CLAD (n = 9 and CLAD free (n = 8 lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix. Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated.The cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells. Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively into incipient CLAD and CLAD-free categories.These findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted.

  1. Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures

    Directory of Open Access Journals (Sweden)

    Oana eToader

    2013-08-01

    Full Text Available Neuronal circuit disturbances that lead to hyperexcitability in the cortico-hippocampal network are one of the landmarks of temporal lobe epilepsy. The dentate gyrus (DG network plays an important role in regulating the excitability of the entire hippocampus by filtering and integrating information received via the perforant path. Here, we investigated possible epileptogenic abnormalities in the function of the DG neuronal network in the Synapsin II (Syn II knockout mouse (Syn II-/-, a genetic mouse model of epilepsy. Syn II is a presynaptic protein whose deletion in mice reproducibly leads to generalized seizures starting at the age of two months. We made use of a high-resolution microelectrode array (4096 electrodes and patch-clamp recordings, and found that in acute hippocampal slices of young pre-symptomatic (3-6 weeks-old Syn II-/- mice excitatory synaptic output of the mossy fibers is reduced. Moreover, we showed that the main excitatory neurons present in the polymorphic layer of the DG, hilar mossy cells, display a reduced excitability. We also provide evidence of a predominantly inhibitory regulatory output from mossy cells to granule cells, through feed-forward inhibition, and show that the excitatory-inhibitory ratio is increased in both pre-symptomatic and symptomatic Syn II-/- mice. These results support the key role of the hilar mossy neurons in maintaining the normal excitability of the hippocampal network and show that the late epileptic phenotype of the Syn II-/- mice is preceded by neuronal circuitry dysfunctions. Our data provide new insights into the mechanisms of epileptogenesis in the Syn II-/- mice and open the possibility for early diagnosis and therapeutic interventions.

  2. Preoperative biliary decompression preceding pancreaticoduodenectomy with plastic or self-expandable metallic stent.

    Science.gov (United States)

    Haapamäki, C; Seppänen, H; Udd, M; Juuti, A; Halttunen, J; Kiviluoto, T; Sirén, J; Mustonen, H; Kylänpää, L

    2015-06-01

    The rainage (PBD) prior to pancreaticoduodenectomy (PD) is controversial. If PBD is required, large bore self-expandable metallic stents (SEMS) are thought to maintain better drainage and have fewer postoperative complications than plastic stents. The confirming evidence is scarce. The aim of the study was to compare outcomes of surgery in patients who underwent PBD with SEMS or plastic stents deployed at endoscopic retrograde cholangiopancreatography (ERCP). This is a retrospective study of 366 patients having had PD during 2000-2009. Preceding endoscopic PBD was performed in 191 patients and nine had had percutaneous transhepatic drainage (PTD). At the time of operation, 163 patients had a plastic stent and 28 had SEMS. Due to stent exchanges, 176 plastic stents and 29 SEMS were placed in all. The stent failure rate was 7.4% for plastic stents and 3.4% for SEMS (p = 0.697). A bilirubin level under 50 µmol/L was reached by 80% of the patients with plastic stents and by 61% of the patients with SEMS (p = 0.058). A postoperative infection complication and/or a pancreatic fistula was found in 26% while using plastic stents and in 25% using SEMS (p = 1.000). In unstented patients with biliary obstruction, the bile juice was sterile significantly more often than in endoscopically stented patients (100% vs 1%, p stented and unstented patients were compared regarding postoperative infection complications, there was no significant difference between the groups (p = 0.365). Plastic stents did not differ from SEMS regarding the stent failure rate, bilirubin level decrease, amount of bacteria in the bile juice, or postoperative complications when used for PBD. The significantly higher price of SEMS suggests their use in selected cases only. © The Finnish Surgical Society 2014.

  3. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

    Science.gov (United States)

    Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

    2017-08-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

  4. Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Yoshihisa Okuchi

    Full Text Available Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs, we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors.

  5. Influence of preceding diagnostic and therapeutic procedures on the radioiodine therapy of benign thyroid diseases

    International Nuclear Information System (INIS)

    Rendl, J.; Boerner, W.

    1991-01-01

    Before and until 3 weeks after application of nonionic CA iodine and the 20-min-technetium-thyroid-uptake was measured in serum and urine in 23 euthyroid patients, which were given intravenously nonionic CA during heart catheterization. Concerning the possible influence of iodine contamination on a subsequent radioiodine therapy the following aspects result from the study: the time interval between application of CA and therapy has to be at least 4-6 weeks to avoid dilution of the radioiodine by iodine being released from the contrast agents. The thyroid-uptake of Technetium or Iodine after administration of CA is not constant over time but reaches its original value only in a gradual way (60% of the initial value 3 weeks after the CA were given); that means, the iodine-uptake during, radioiodine therapy can be higher than it was at the time the dose was calculated. Concerning the possible influence of preceding therapeutic procedures on the therapy with radioiodine the pretreatment with antithyroid drugs plays the most important role. Antithyroid drugs of the thiourylene group have been shown by many study groups to have a radioprotective effect. Other large studies however could not demonstrate any effect of antithyroid medication on the results of radioiodine therapy. All studies so far existing have in common that they are not strongly randomized with regard to the patient groups, because generally only in severe cases of hyperthyroidism additional antithyroid drug treatment has been employed, therefore it might be the case that the radioprotective effect of antithyroid drugs may be caused only by selection artifacts. The contradictory results of the different studies justify the practical way in so far as there are no reasonable objections against the pretreatment with antithyroid drugs to restore euthyroidism before starting the therapy with radioiodine. (orig./MG) [de

  6. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Directory of Open Access Journals (Sweden)

    Catherine J Collier

    Full Text Available Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR. Shoot proliferation occurred at salinities <30 PSU, with the largest increases, up to 400% increase in shoot density, occurring at the sub-lethal salinities <15 PSU, with the specific salinity associated with peak shoot density being variable among species. Resources were not diverted away from leaf growth or shoot development to support the new shoot production. However, at sub-lethal salinities where shoots proliferated, flowering was severely reduced for H. ovalis, the only species to flower during this experiment, demonstrating a diversion of resources away from sexual reproduction to support the investment in new shoots. This SIMR response preceded mortality, which occurred at 3 PSU for H. ovalis and 6 PSU for H. uninervis, while complete mortality was not reached for Z. muelleri. This is the first study to identify a SIMR in seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress.

  7. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

    Science.gov (United States)

    Angelis, Katia De; Senador, Danielle D.; Mostarda, Cristiano; Irigoyen, Maria C.

    2012-01-01

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease. PMID:22319048

  8. Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension.

    Science.gov (United States)

    Kim, Sung-Ai; Park, Sun-Hee; Jo, Sang-Ho; Park, Kyoung-Ha; Kim, Hyun-Sook; Han, Sang-Jin; Park, Woo-Jung; Ha, Jong-Won

    2016-05-01

    Carotid intima-media thickness (cIMT) is an established surrogate marker of atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. The aim of this study was to evaluate whether vascular properties of carotid artery (CA) in patients with hypertension differ from those of patients with diabetes and controls before the progression of cIMT. Vascular properties of CA were assessed in 402 consecutive asymptomatic subjects who have normal cIMT (131 with hypertension, 151 with diabetes mellitus, and 120 controls). Conventional carotid stiffness indices calculated from vessel diameter and blood pressure, and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change (FAC), radial velocity, circumferential strain, and strain rate were measured to assess the differences between the groups. In univariate analysis, both patients with hypertension and diabetes showed higher elastic modulus, lower distensibility coefficients and FAC of VVI than those of controls. However, when adjusting for baseline covariates, only FAC (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.70-0.97, p = 0.025) and vessel area (OR = 2.84, 95% CI = 1.64-4.91, p hypertension from those of controls. Also, patients with hypertension showed larger vessel area than diabetes (OR = 2.58, 95% CI = 1.75-3.80, p hypertensive patients was stiffer than those of controls and positive remodeling preceded the wall thickening independent of baseline covariates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  10. The effects of an educational program based on PRECEDE model on depression levels in patients with coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Sayyed Mohammad Mahdi Hazavei

    2012-06-01

    Full Text Available    BACKGROUND: Depression is among the most important barriers to proper treatment of cardiac patients. It causes failure in accepting their conditions, decreases their motivation in following the therapeutic recommendations, and thus negatively affects their functionality and quality of life. The present study aimed to investigate the effects of an educational program based on Predisposing, Reinforcing, Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE model on depression level in coronary artery bypass grafting (CABG surgery patients.    METHODS: This was a quasi-experimental study in which 54 post-bypass surgery patients of Isfahan Cardiovascular Research Center were investigated. The patients were randomly divided into two groups of intervention and control. The data was collected using two questionnaires. Primarily, the cardiac depression scale was used to measure the degree of depression followed by PRECEDE model-based educational questionnaire to identify the role of the educational intervention on patients. The PRECEDE model-based intervention composed of 9 educational sessions per week (60-90 minutes each. The patients were followed up for two months post-intervention.    RESULTS: Following the educational intervention, mean scores of predisposing, enabling, and reinforcing factors, and self-helping behaviors significantly increased in the intervention group compared to the control group (P < 0.001. In addition, a significant difference in mean scores of depression was observed between the two groups following the educational intervention (P < 0.001.    CONCLUSION: The findings of the current study confirmed the practicability and effectiveness of the PRECEDE model-based educational programs on preventing or decreasing depression levels in CABG patients.         Keywords: Educational Program, PRECEDE Model, Depression, Coronary Artery Bypass Surgery.  

  11. [A core deficit in Parkinson disease?].

    Science.gov (United States)

    Benítez-Burraco, A; Herrera, E; Cuetos, F

    2016-05-01

    Parkinson disease is a neurodegenerative condition involving motor, cognitive, and linguistic deficits. It is important to know why all these different deficits co-occur in the affected people. This paper aims to clarify whether these comorbid deficits result from the selective impairment of a computational primitive, namely, a context-sensitive computational ability according to Chomsky's Hierarchy (a well-established research tool in comparative neuroscience). A total of 15 medicated subjects with Parkinson disease and 15 controls were selected. They were matched in age and education. A battery of tasks was designed to test 3 different domains (motor capacities, cognition, and language) and 2 different computational abilities (context-free and context-sensitive operations). Significant differences between groups were observed only regarding the linguistic task involving context-sensitive computations (correferences). The observed deficits in our patients with Parkinson disease cannot be explained in terms of the selective impairment of one only unspecific, low-level computational process. At the same time, differences between patients and controls are expected to be greater if the former are not medicated. Moreover, we should pursue in the search of (this kind of) computational primitives than can be selectively impaired in people with Parkinson disease, because they may help to achieve an earlier diagnosis of this condition. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Intervertebral Disc Characteristic on Progressive Neurological Deficit

    Directory of Open Access Journals (Sweden)

    Farid Yudoyono

    2017-09-01

    Full Text Available Objective: To examine the intervertebral disc characteristic on magnetic resonance imaging (MRI in lumbar herniated disc (LHD patients with progressive neurological deficit. Methods: Patients were collected retrospectively from Dr. Hasan Sadikin General Hospital Database from 2011–2013 with LHD, had neurological deficit such as radiculopathy and cauda equine syndrome for less than four weeks with a positive sign confirmed by neurological examination and confirmatory with MRI examination. Results: A total of 14 patients with lumbar herniated disc disease (10 males, 4 females suffered from progressive neurological deficit with an average age of (52.07±10.9 years old. Early disc height was 9.38±0.5 mm and progressive neurological deficit state disc height was 4.03±0.53 mm, which were significantly different statisticaly (p<0.01. Symptoms of radiculopathy were seen in 11 patients and cauda equine syndrome in three patients. Modic changes grade 1 was found in five patients, grade 2 in eight patients,grade 3 in one patient, Pfirmman grade 2 in eleven patients and grade 3 in three patients. Thecal sac compression 1/3 compression was seen in four patients and 2/3 compression in ten patients. Conclusions: Neurosurgeon should raise concerns on the characteristic changes of intervertebral disc in magnetic resonance imaging examination to avoid further neural injury in lumbar herniated disc patients.

  13. Stigma in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Müller, Kathi; Fuermaier, Anselm B M; Koerts, Janneke; Tucha, Lara

    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

  14. Nature, Nurture, and Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Faraone, Stephen V.; Biederman, Joseph

    2000-01-01

    Comments on Joseph's review of the genetics of attention deficit disorder, demonstrating errors of scientific logic and oversight of relevant research in Joseph's argument. Argues for the validity of twin studies in supporting a genetic link for ADHD and for the complementary role of nature and nurture in the etiology of the disorder. (JPB)

  15. 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…

  16. Reducing the Deficit: Spending and Revenue Options

    Science.gov (United States)

    1994-03-01

    357 B SPENDING OPTIONS BY BUDGET FUNCION ...... 363 TABLES 1. Baseline Deficit Projections, Fiscal Years 1993-2004...direct control of the Congress. abled beneficiaries and beneficiaries with end-stage renal disease. Nonhealth changes enacted in The total that is

  17. ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD)

    African Journals Online (AJOL)

    Enrique

    People who suffer from ADHD are far more likely than normal to drop out of school (32 ... secondary to learning disabilities, partial sensory deficits or even low cognitive ... bad days (Fig. 3), which can lead to frustration for teachers, parents and the child, as there is always the feeling that ... boys who often present very young.

  18. Invest to Improve: The Cybersecurity Talent Deficit

    Science.gov (United States)

    Business-Higher Education Forum, 2017

    2017-01-01

    "Invest to Improve: The Cybersecurity Talent Deficit" provides recommendations for cybersecurity stakeholders--employers, government agencies, and higher education institutions--to enable regional partnerships to meet today's cybersecurity skills needs. This report combines data from a 2017 Gallup survey of business executives and higher…

  19. 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.

  20. Financing the U.S. Trade Deficit

    National Research Council Canada - National Science Library

    Jackson, James K

    2007-01-01

    The U.S. merchandise trade deficit is a part of the overall U.S. balance of payments, a summary statement of all economic transactions between the residents of the United States and the rest of the world, during a given period of time...

  1. Attention Deficit Hyperactivity Disorder: A Parent's Perspective.

    Science.gov (United States)

    Thompson, Anna M.

    1996-01-01

    A parent and educator who has spent the past 10 years struggling to help her own ADHD (attention deficit-hyperactivity disorder) child offers suggestions for managing the challenges facing such children and enhancing the quality of their lives. Since drug regimens have limitations, parents need to read appropriate literature and receive…

  2. Primary School Teacher's knowledge towards Attention Deficit ...

    African Journals Online (AJOL)

    The work of the teacher becomes much more demanding when some learners have Attention-Deficit/Hyperactivity Disorder (ADHD), as their problems with attention span, impulse control and activity level frequently interfere with activities in the classroom and socially. This study revealed the teachers good knowledge about ...

  3. Magnesium supplementation in children with attention deficit ...

    African Journals Online (AJOL)

    Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with associated mineral deficiency. Aim: To assess magnesium level in ADHD children and compare it to the normal levels in children. Then, to detect the effect of magnesium supplementation as an add on therapy, ...

  4. 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. Copyright © 2011 S. Karger AG, Basel.

  5. Legal Sentience and the Problem of the Instant: A Critical Assessment of the Temporal Structure of Precedent and its Implications for Legal Authority

    OpenAIRE

    Wargan, Pawel

    2015-01-01

    This paper assesses the authority of precedent from a phenomenological standpoint. Phenomenology distinguishes between two temporal models. One describes time in an idealised form, as a divisible chain of instants or events. The other looks at lived temporality as fluid and indivisible duration. In the system of precedent, we witness an interaction of both models. The legal order is constructed from slices in time that become the building blocks of future judgments. Precedents are binding for...

  6. 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.

  7. When legislation precedes the state of the art in teacher training: problems and implications.

    Science.gov (United States)

    Tymitz, B L

    1980-01-01

    Passage of Public Law 94-142, the Education for all Handicapped Children Act requires the development of an Individualized Education Program (IEP) for each handicapped child served. While administration are inclined to view the IEP as a document intended to monitor the provision of special services, teachers focused on the potential instructional value of the IEP. Professionals agree that this has been one of the most difficult components of the law to implement. Policymakers designing the law posited that training technology was adequate to support the instructional requirements outlined in the legislation. The present study challenges that assumption. It is also argued that studies which attempt to integrate multiple operations to clarify findings can provide more accurate and consequently more useful data of critical value in the beginning stages of policy formation. The multiple data collection strategies employed in this study yielded increasingly specific information on the status of present training technology--particularly in relation to teacher skills related to the instructional aspects of the IEP planning process. Teacher perceptions of their training needs were compared with actual skill performances on selected IEP tasks. Data reveal the inadequacy of essential skills in formulating required goal and objective statements. Special education and regular classroom teachers show similar patterns in specific skills which are problematic. Statements from teacher interviews corroborated deficits in past training. Suggestions for future training are offered as are emphases for needed research. Implications for implementation of the IEP are also discussed.

  8. Robotic identification of kinesthetic deficits after stroke.

    Science.gov (United States)

    Semrau, Jennifer A; Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

    2013-12-01

    Kinesthesia, the sense of body motion, is essential to proper control and execution of movement. Despite its importance for activities of daily living, no current clinical measures can objectively measure kinesthetic deficits. The goal of this study was to use robotic technology to quantify prevalence and severity of kinesthetic deficits of the upper limb poststroke. Seventy-four neurologically intact subjects and 113 subjects with stroke (62 left-affected, 51 right-affected) performed a robot-based kinesthetic matching task with vision occluded. The robot moved the most affected arm at a preset speed, direction, and magnitude. Subjects were instructed to mirror-match the movement with their opposite arm (active arm). A large number of subjects with stroke were significantly impaired on measures of kinesthesia. We observed impairments in ability to match movement direction (69% and 49% impaired for left- and right-affected subjects, respectively) and movement magnitude (42% and 31%). We observed impairments to match movement speed (32% and 27%) and increased response latencies (48% and 20%). Movement direction errors and response latencies were related to clinical measures of function, motor recovery, and dexterity. Using a robotic approach, we found that 61% of acute stroke survivors (n=69) had kinesthetic deficits. Additionally, these deficits were highly related to existing clinical measures, suggesting the importance of kinesthesia in day-to-day function. Our methods allow for more sensitive, accurate, and objective identification of kinesthetic deficits after stroke. With this information, we can better inform clinical treatment strategies to improve poststroke rehabilitative care and outcomes.

  9. 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.

  10. Early functional deficit and microglial disturbances in a mouse model of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Yannick Nicolas Gerber

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any treatment. However growing evidences are in favor of the involvement, besides neurons, of several partners such as glia and muscles. To better characterize the time course of pathological events in an animal model that recapitulates human ALS symptoms, we investigated functional and cellular characteristics of hSOD1(G93A mice. METHODS AND FINDINGS: We have evaluated locomotor function of hSOD1(G93A mice through dynamic walking patterns and spontaneous motor activity analysis. We detected early functional deficits that redefine symptoms onset at 60 days of age, i.e. 20 days earlier than previously described. Moreover, sequential combination of these approaches allows monitoring of motor activity up to disease end stage. To tentatively correlate early functional deficit with cellular alterations we have used flow cytometry and immunohistochemistry approaches to characterize neuromuscular junctions, astrocytes and microglia. We show that (1 decrease in neuromuscular junction's number correlates with motor impairment, (2 astrocytes number is not altered at pre- and early-symptomatic ages but intraspinal repartition is modified at symptoms onset, and (3 microglia modifications precede disease onset. At pre-symptomatic age, we show a decrease in microglia number whereas at onset of the disease two distinct microglia sub-populations emerge. CONCLUSIONS: In conclusion, precise motor analysis updates the onset of the disease in hSOD1(G93A mice and allows locomotor monitoring until the end stage of the disease. Early functional deficits coincide with alterations of neuromuscular junctions. Importantly, we identify different sets of changes in microglia before disease onset as well as at early-symptomatic stage. This finding not only brings a new sequence of cellular

  11. Attention-Deficit / Hyperactivity Disorder (ADHD): Data and Statistics

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Note: Javascript is disabled or ... claims to understand diagnosis and treatment patterns for Attention-Deficit/Hyperactivity Disorder (ADHD). On this page you can ...

  12. Children and Adults with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    ... Renew CHADD Annual Conference Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD), is a national nonprofit organization ... ADHD community. © 2017 by Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD). All Rights Reserved. Press Privacy ...

  13. Persistence of attention deficit/hyperactivity disorder into adulthood ...

    African Journals Online (AJOL)

    Persistence of attention deficit/hyperactivity disorder into adulthood: A study conducted on parents of children diagnosed with attention deficit/hyperactivity disorder. ... 10, No 1 (2007) >. Log in or Register to get access to full text downloads.

  14. 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 ...

  15. The Double-Deficit Hypothesis in Spanish Developmental Dyslexia

    Science.gov (United States)

    Jimenez, Juan E.; Hernandez-Valle, Isabel; Rodriguez, Cristina; Guzman, Remedios; Diaz, Alicia; Ortiz, Rosario

    2008-01-01

    The double-deficit hypothesis (DDH) of developmental dyslexia was investigated in seven to twelve year old Spanish children. It was observed that the double deficit (DD) group had the greatest difficulty with reading.

  16. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

  17. A case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion.

    Science.gov (United States)

    Okuda, Kenichi; Noguchi, Satoshi; Narumoto, Osamu; Ikemura, Masako; Yamauchi, Yasuhiro; Tanaka, Goh; Takai, Daiya; Fukayama, Masashi; Nagase, Takahide

    2016-05-10

    Meigs' syndrome is defined as the presence of a benign ovarian tumor with pleural effusion and ascites that resolve after removal of the tumor. The pathogenesis of the production of ascites and pleural effusion in this syndrome remains unknown. Aside from pleural effusion and ascites, pericardial effusion is rarely observed in Meigs' syndrome. Here, we report the first case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion. An 84-year-old Japanese non-smoking woman with a history of lung cancer, treated by surgery, was admitted due to gradual worsening of dyspnea that had occurred over the previous month. She had asymptomatic and unchanging pericardial effusion and a pelvic mass, which had been detected 3 and 11 years previously, respectively. The patient was radiologically followed-up without the need for treatment. Two months before admission, the patient underwent a right upper lobectomy for localized lung adenocarcinoma and intraoperative pericardial fenestration confirmed that the pericardial effusion was not malignant. However, she began to experience dyspnea on exertion leading to admission. A chest, abdomen, and pelvis computed tomography scan confirmed the presence of right-sided pleural and pericardial effusion and ascites with a left ovarian mass. Repeated thoracentesis produced cultures that were negative for any microorganism and no malignant cells were detected in the pleural effusions. Pleural fluid accumulation persisted despite a tube thoracostomy for pleural effusion drainage. With a suspicion of Meigs' syndrome, the patient underwent surgical resection of the ovarian mass and histopathological examination of the resected mass showed ovarian fibroma. Pleural and pericardial effusion as well as ascites resolved after tumor resection, confirming a diagnosis of Meigs' syndrome. This clinical course suggests a strong association between pericardial effusion and ovarian fibroma, as well as pleural and peritoneal

  18. (-)-P7C3-S243 Protects a Rat Model of Alzheimer's Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia.

    Science.gov (United States)

    Voorhees, Jaymie R; Remy, Matthew T; Cintrón-Pérez, Coral J; El Rassi, Eli; Khan, Michael Z; Dutca, Laura M; Yin, Terry C; McDaniel, Latisha N; Williams, Noelle S; Brat, Daniel J; Pieper, Andrew A

    2017-11-06

    In addition to cognitive deficits, Alzheimer's disease (AD) is associated with other neuropsychiatric symptoms, including severe depression. Indeed, depression often precedes cognitive deficits in patients with AD. Unfortunately, the field has seen only minimal therapeutic advances, underscoring the critical need for new treatments. P7C3 aminopropyl carbazoles promote neuronal survival by enhancing nicotinamide adenine dinucleotide flux in injured neurons. Neuroprotection with P7C3 compounds has been demonstrated in preclinical models of neurodegeneration by virtue of promoting neuronal survival independently of early disease-specific pathology, resulting in protection from cognitive deficits and depressive-like behavior. We hypothesize that P7C3 compounds might be uniquely applicable to patients with AD, given the comorbid presentation of depression and cognitive deficits. Aging male and female wild-type and TgF344-AD rats, a well-characterized preclinical AD model, were administered (-)-P7C3-S243 daily for 9 and 18 months, beginning at 6 months of age. Behavioral phenotypes related to cognition and depression were assessed at 15 and 24 months, and brain pathology and biochemistry were assessed at 24 months. (-)-P7C3-S243 safely protected aging male and female wild-type and TgF344-AD rats from cognitive deficits and depressive-like behavior. Depressive-like behavior occurred earlier than cognitive deficits in TgF344-AD rats, consistent with AD in many patients. Treatment with (-)-P7C3-S243 blocked neurodegeneration in TgF344-AD rats, without altering amyloid deposition or indicators of neuroinflammation. Neuronal cell death-specific treatment approaches, such as P7C3 compounds, may represent a new treatment approach for patients experiencing the combination of cognitive deficits and depression associated with AD. Published by Elsevier Inc.

  19. The impact of a budget deficit on inflation in Zimbabwe

    OpenAIRE

    Makochekanwa, Albert

    2008-01-01

    The Zimbabwean economy is one of the many numbers of countries that has experienced a relatively high fiscal deficit for a prolonged period with the result of a high inflationary environment. This paper examines the deficit-inflation nexus in the Zimbabwean economy and establishes the causal link that runs from the budget deficit to the inflation rate using Johansen (1991, 1995) cointegration technique over the period 1980 – 2005. Due to massive monetization of the budget deficit, significant...

  20. Impact of Budget Deficit on Inflation in Zimbabwe

    OpenAIRE

    Albert Makochekanwa

    2011-01-01

    The Zimbabwean economy is one of the countries that once experienced a relatively high fiscal deficit for a prolonged period which resulted in a hyper inflationary environment. This paper examines the deficit-inflation nexus in the Zimbabwean economy and establishes the causal link that runs from the budget deficit to the inflation rate using Johansen (1991, 1995) cointegration technique over the period 1980 to 2005. Due to massive monetization of the budget deficit, significant inflationary ...