WorldWideScience

Sample records for brain emerging mechanisms

  1. The Emerging Scholarly Brain

    CERN Document Server

    Kurtz, Michael J

    2010-01-01

    It is now a commonplace observation that human society is becoming a coherent super-organism, and that the information infrastructure forms its emerging brain. Perhaps, as the underlying technologies are likely to become billions of times more powerful than those we have today, we could say that we are now building the lizard brain for the future organism.

  2. Brain-Derived neurotrophic factor and suicide in schizophrenia: Critical role of neuroprotective mechanisms as an emerging hypothesis

    Directory of Open Access Journals (Sweden)

    Amresh Shrivastava

    2016-01-01

    Full Text Available Suicide is a common occurrence in psychiatric disorders and is a cause of increased healthcare utilization worldwide. Schizophrenia is one of the most common psychiatric disorders worldwide and posited to be seen in 1% of the population worldwide. Suicide is a common occurrence in schizophrenia with 25%–30% patients with schizophrenia attempting suicide and 8%–10% completing it. There is a need for valid biological markers to help clinicians identify patients with schizophrenia that may be at a risk of suicide and thus help in them receiving better care and interventions at the earliest even before a suicide attempt occurring. There are clear neurobiological changes at a genetic, neuroimaging, and neurochemical level that occurs in patients with schizophrenia that attempt suicide. There is a new theory that postulates neuronal plasticity and neuroprotection to have a role in the biological changes that ensue when suicidal thoughts and feelings occur in patients with schizophrenia. Neurotrophic growth factors like brain-derived neurotrophic factor (BDNF have been documented to play a role in the protection of neurons and in the prevention of neurobiological changes that may lead to suicide both in schizophrenia and depression. The present paper presents a commentary that looks at the role of BDNF as a protective factor and neurobiological marker for suicide in schizophrenia.

  3. Mechanical Containment in Emergency

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    Nerea Carcoba Rubio

    2012-09-01

    Full Text Available The restraint is a therapeutic measure aimed at blocking partial or widespread in most of the body of a patient to try to ensure the safety of himself or others. In most cases it forces to act against their will, and in a common context of urgency; in such a way that its use applies a therapeutic plan without the consent of the patient and is temporally deprived of freedom of movement. A literature review of the issue has been performed consulting surveillance systems and protocols developed at hospitals in several spanish cities. Also the current legal regulations on health matters relating to the subject are checked.After the analysis of data and evidence, is created a protocol of restraint in emergency and the various functions of the components of the team, to address the situation with greater efficiency and safe as possible.

  4. [Mechanic reinfusion in emergency surgery].

    Science.gov (United States)

    Ermolov, A S; Khvatov, V B; Kobzeva, E N; Valetova, V V; Makarov, M S

    2012-01-01

    The article highlights techniques and effects of intraoperative mechanic blood reinfusion in patients with trauma and intraabdominal bleeding in extend, exceeding the self circulating blood volume. The high efficacy of the self blood reinfusion during the emergency operation allowed the 2-fold decrease of the hospital and overall mortality. The mechanic blood reinfusion proved to be a safe and clinically effective method of the globular blood volume deficiency compensation, especially in emergency surgery.

  5. The scalable mammalian brain: Emergent distributions of glia and neurons

    NARCIS (Netherlands)

    Jehee, J.F.M.; Murre, J.M.J.

    2008-01-01

    In this paper, we demonstrate that two characteristic properties of mammalian brains emerge when scaling-up modular, cortical structures. Firstly, the glia-to-neuron ratio is not constant across brains of different sizes: large mammalian brains have more glia per neuron than smaller brains. Our anal

  6. Possible Brain Mechanisms of Creativity.

    Science.gov (United States)

    Heilman, Kenneth M

    2016-06-01

    Creativity is the new discovery, understanding, development and expression of orderly and meaningful relationships. Creativity has three major stages: preparation, the development (nature and nurture) of critical knowledge and skills; innovation, the development of a creative solution; and creative production. Successful preparation requires a basic level of general intelligence and domain specific knowledge and skills and highly creative people may have anatomic alterations of specific neocortical regions. Innovation requires disengagement and divergent thinking primarily mediated by frontal networks. Creative people are often risk-takers and novelty seekers, behaviors that activate their ventral striatal reward system. Innovation also requires associative and convergent thinking, activities that are dependent on the integration of highly distributed networks. People are often most creative when they are in mental states associated with reduced levels of brain norepinephrine, which may enhance the communication between distributed networks. We, however, need to learn more about the brain mechanisms of creativity.

  7. [Mild brain injuries in emergency medicine].

    Science.gov (United States)

    Liimatainen, Suvi; Niskakangas, Tero; Ohman, Juha

    2011-01-01

    Diagnostics and correct classification of mild brain injuries is challenging. Problems caused by insufficient documentation at the acute phase become more obvious in situations in which legal insurance issues are to be considered. A small proportion of patients with mild brain injury suffer from prolonged symptoms. Medical recording and classification of the brain injury at the initial phase should therefore be carried out in a structured manner. The review deals with the diagnostic problems of mild brain injuries and presents a treatment protocol for adult patients at the acute phase, aiming at avoiding prolonged problems.

  8. Mechanical behavior of emerging materials

    Directory of Open Access Journals (Sweden)

    Challapalli Suryanarayana

    2012-11-01

    Full Text Available Nanocrystalline and glassy materials, especially the bulk metallic glasses are of relatively recent origin and exhibit high strength, but lack sufficient plasticity. A clear understanding of the mechanical behavior of these novel materials is essential before these can be seriously considered for structural applications. A great deal of research has been conducted over the past couple of decades and a vast amount of data has been generated. Here, results on strength, ductility, and deformation behavior of these novel materials have been reviewed. Recent results have been highlighted and problems, wherever they exist, have been pointed out. New directions for enhancing the understanding of the mechanical behavior of these interesting materials have been suggested.

  9. Brain mechanisms of flavor learning

    Directory of Open Access Journals (Sweden)

    Takashi eYamamoto

    2011-09-01

    Full Text Available Once the flavor of the ingested food (conditioned stimulus, CS is associated with a preferable (e.g., good taste or nutritive satisfaction or aversive (e.g., malaise with displeasure signal (unconditioned stimulus, US, animals react to its subsequent exposure by increasing or decreasing ingestion to the food. These two types of association learning (preference learning vs. aversion learning are known as classical conditioned reactions which are basic learning and memory phenomena, leading selection of food and proper food intake. Since the perception of flavor is generated by interaction of taste and odor during food intake, taste and/or odor are mainly associated with bodily signals in the flavor learning. After briefly reviewing flavor learning in general, brain mechanisms of conditioned taste aversion is described in more detail. The CS-US association leading to long-term potentiation in the amygdala, especially in its basolateral nucleus, is the basis of establishment of conditioned taste aversion. The novelty of the CS detected by the cortical gustatory area may be supportive in CS-US association. After the association, CS input is conveyed through the amygdala to different brain regions including the hippocampus for contextual fear formation, to the supramammilary and thalamic paraventricular nuclei for stressful anxiety or memory dependent fearful or stressful emotion, to the reward system to induce aversive expression to the CS, or hedonic shift from positive to negative, and to the CS-responsive neurons in the gustatory system to enhance the responsiveness to facilitate to detect the harmful stimulus.

  10. Collaboration mechanism of intercity emergency rescue ecosystem

    Institute of Scientific and Technical Information of China (English)

    Jiang Yiping; Zhao Lindu

    2009-01-01

    With the development of metropolitan regions and the appearance of urban agglomerations,cities have been more closely related.For the restricted emergency rescue resource in a single city,it has become more and more imminent for the demand of the intercity collaborative resistance to major accident,so as to improve the protection capacity of urban security.In order to find an effective intercity emergency rescue collaborative system,this paper introduces the concept and analysis method of ecosystem theory into intercity emergency rescue.Based on theanalysis of the formation-process of emergency rescue individual,population and community,a three-level intercity emergency rescue collaborative system is constructed according to the characteristics of dynamics and structure of intercity emergency rescue ecosystem,then the collaboration mechanism of information,resource and process in the intercity emergency rescue ecosystem is also studied in this paper,so as to offer available strategy and method for the ecosystem theory applied to intercity emergency rescue.Through the studies of intercity emergency rescue eco,system,it illuminates that the proposed emergency system can not only cope with the major accident more timely and effectively,but also integrate the intercity information resources and emergency rescue resource and process optimi,zation.

  11. Barrier Mechanisms in the Developing Brain

    OpenAIRE

    Saunders, Norman R.; Liddelow, Shane A.; Dziegielewska, Katarzyna M.

    2012-01-01

    The adult brain functions within a well-controlled stable environment, the properties of which are determined by cellular exchange mechanisms superimposed on the diffusion restraint provided by tight junctions at interfaces between blood, brain and cerebrospinal fluid (CSF). These interfaces are referred to as “the” blood–brain barrier. It is widely believed that in embryos and newborns, this barrier is immature or “leaky,” rendering the developing brain more vulnerable to drugs or toxins ent...

  12. Entropy, Topological Theories and Emergent Quantum Mechanics

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    D. Cabrera

    2017-02-01

    Full Text Available The classical thermostatics of equilibrium processes is shown to possess a quantum mechanical dual theory with a finite dimensional Hilbert space of quantum states. Specifically, the kernel of a certain Hamiltonian operator becomes the Hilbert space of quasistatic quantum mechanics. The relation of thermostatics to topological field theory is also discussed in the context of the approach of the emergence of quantum theory, where the concept of entropy plays a key role.

  13. [Brain mechanisms of male sexual function].

    Science.gov (United States)

    Wang, Ying; Dou, Xin; Li, Jun-Fa; Luo, Yan-Lin

    2011-08-01

    In this paper, we reviewed the brain imaging studies of male sexual function in recent years from three aspects: the brain mechanism of normal sexual function, the brain mechanism of sexual dysfunction, and the mechanism of drug therapy for sexual dysfunction. Studies show that the development stages of male sexual activities, such as the excitement phase, plateau phase and orgasm phase, are controlled by different neural networks. The mesodiencephalic transition zone may play an important role in the start up of male ejaculation. There are significant differences between sexual dysfunction males and normal males in activation patterns of the brain in sexual arousal. The medial orbitofrontal cortex and inferior frontal gyrus in the abnormal activation pattern are correlated with sexual dysfunction males in sexual arousal. Serum testosterone and morphine are commonly used drugs for male sexual dysfunction, whose mechanisms are to alter the activating levels of the medial orbitofrontal cortex, insula, claustrum and inferior temporal gyrus.

  14. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    Science.gov (United States)

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-09-02

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases.

  15. Brain mechanisms underlying human communication.

    Science.gov (United States)

    Noordzij, Matthijs L; Newman-Norlund, Sarah E; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  16. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  17. The biological significance of brain barrier mechanisms

    DEFF Research Database (Denmark)

    Saunders, Norman R; Habgood, Mark D; Møllgård, Kjeld

    2016-01-01

    , but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor......Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain's internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses....... In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal...

  18. The Emergent Copenhagen Interpretation of Quantum Mechanics

    CERN Document Server

    Hollowood, Timothy J

    2013-01-01

    We introduce a new and conceptually simple interpretation of quantum mechanics based on reduced density matrices of sub-systems from which the standard Copenhagen interpretation emerges as an effective description of macroscopically large systems. Wave function collapse is seen to be a useful but fundamentally unnecessary piece of prudent book keeping which is only valid for macro-systems. The new interpretation lies in a class of modal interpretations in that it applies to quantum systems that interact with a much larger environment. However, we show that it does not suffer from the problems that have plagued similar modal interpretations like macroscopic superpositions and rapid flipping between macroscopically distinct states. We describe how the interpretation fits neatly together with fully quantum formulations of statistical mechanics and that a measurement process can be viewed as a process of ergodicity breaking analogous to a phase transition. The key feature of the new interpretation is that joint p...

  19. Heparanase Mechanisms in Melanoma Brain Metastasis

    Science.gov (United States)

    2015-10-01

    with HPSE- mediated cell signaling and actions, and ultimately affecting the modulation of BMM. Accordingly, this, by employing the pINDUCER lentiviral...found that HPSE plays important roles in mechanisms modulating BMM onset. A new molecular mechanism was also identified by which HPSE mediates an... mediated by enzymatically active heparanase. Our work has implicated heparanase as a promoter of brain metastasis since the enzyme is most active in cells

  20. Recovery after Brain Injury: Mechanisms and Principles

    Directory of Open Access Journals (Sweden)

    Randolph J. Nudo

    2013-12-01

    Full Text Available The past 20 years have represented an important period in the development of principles underlying neuroplasticity, especially as they apply to recovery from neurological injury. It is now generally accepted that acquired brain injuries, such as occur in stroke or trauma, initiate a cascade of regenerative events that last for at least several weeks, if not months. Many investigators have pointed out striking parallels between post-injury plasticity and the molecular and cellular events that take place during normal brain development. As evidence for the principles and mechanisms underlying post-injury neuroplasticity has been gleaned from both animal models and human populations, novel approaches to therapeutic intervention have been proposed. One important theme has persisted as the sophistication of clinicians and scientists in their knowledge of neuroplasticity mechanisms has grown: Behavioral experience is the most potent modulator of brain plasticity. While there is substantial evidence for this principle in normal, healthy brains, the injured brain is particularly malleable. Based on the quantity and quality of motor experience, the brain can be reshaped after injury in either adaptive or maladaptive ways. This paper reviews selected studies that have demonstrated the neurophysiological and neuroanatomical changes that are triggered by motor experience, by injury, and the interaction of these processes. In addition, recent studies using new and elegant techniques are providing novel perspectives on the events that take place in the injured brain, providing a real-time window into post-injury plasticity. These new approaches are likely to accelerate the pace of basic research, and provide a wealth of opportunities to translate basic principles into therapeutic methodologies.

  1. MONETARY POLICY TRANSMISSION MECHANISM IN EMERGING COUNTRIES

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    Andreea ROŞOIU

    2013-06-01

    Full Text Available The transmission channels of monetary policy are used by central banks to accomplish the main objective of price stability in the context of sustainable economic growth. The importance of interest rate and exchange rate channels for the emerging countries Romania, Poland, Czech Republic and Hungary is analyzed by using Bayesian VAR approach with Diffuse priors over 1998Q1-2012Q3. Main result of the empirical study is that both channels are effective for the monetary policy transmission mechanism in Hungary and Czech Republic. In Romania and Poland they do not exhibit puzzles, but the impact of the macroeconomic variables is not very significant and shows very high volatility. In the context of monetary integration, exchange rate channel will become irrelevant when these countries adopt Euro currency. This change will lead instead to a powerful interest rate channel.

  2. The role of mechanics during brain development

    Science.gov (United States)

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2014-12-01

    Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated with neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism.

  3. The role of mechanics during brain development.

    Science.gov (United States)

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2014-12-01

    Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated to neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von-Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism.

  4. The neuroprotective mechanism of brain ischemic preconditioning

    Institute of Scientific and Technical Information of China (English)

    Xiao-qian LIU; Rui SHENG; Zheng-hong QIN

    2009-01-01

    Brain ischemia is one of the most common causes of death and the leading cause of adult disability in the world. Brain ischemic pre- conditioning (BIP) refers to a transient, sublethal ischemia which results in tolerance to later, otherwise lethal, cerebral ischemia. Many attempts have been made to understand the molecular and cellular mechanisms underlying the neuroprotection offered by ischemic preconditioning. Many studies have shown that neuroprotective mechanisms may involve a series of molecular regulatory pathways including activation of the N-methyI-D-aspartate (NMDA) and adenosine receptors; activation of intracellular signaling pathways such as mitogen activated protein kinases (MAPK) and other protein kinases; upregulation of Bcl-2 and heat shock proteins (HSPs); and activation of the ubiquitin-proteasome pathway and the autophagic-lysosomal pathway. A better understanding of the processes that lead to cell death after stroke as well as of the endogenous neuroprotective mechanisms by which BIP protects against brain ischemic insults could help to develop new therapeutic strategies for this devastating neurological disease. The purpose of the present review is to summarize the neuroprotective mechanisms of BIP and to discuss the possibility of mimicking ischemic preconditioning as a new strategy for preventive treatment of ischemia.

  5. Emergent Endotracheal Intubation and Mortality in Traumatic Brain Injury

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    Fine, Philip R

    2008-11-01

    Full Text Available Objective: To determine the relationship between emergent intubation (emergency department and field intubation cases combined and mortality in patients with traumatic brain injury (TBI while controlling for injury severity.Methods: Retrospective observational study of 981 (35.2% intubated, 64.8% not intubated patients with TBI evaluating the association between intubation status and mortality. Logistic regression was used to analyze the data. Injury severity measures included Head/Neck Abbreviated Injury Scale (H-AIS, systolic blood pressure, type of head injury (blunt vs. penetrating, and a propensity score combining the effects of several other potential confounding variables. Age was also included in the model.Results: The simple association of emergent endotracheal intubation with death had an odds ratio (OR of 14.3 (95% CI = 9.4 – 21.9. The logistic regression model including relevant covariates and a propensity score that adjusted for injury severity and age yielded an OR of 5.9 (95% CI = 3.2 – 10.9.Conclusions: This study indicates that emergent intubation is associated with increased risk of death after controlling for a number of injury severity indicators. We discuss the need for optimal paramedic training, and an understanding of the factors that guide patient selection and the decision to intubate in the field. [WestJEM.2008;9:184-189

  6. Antioxidative defense mechanisms in the aging brain

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    Jovanović Zorica

    2014-01-01

    Full Text Available Aging is an extremely complex, multifactorial process that is characterized by a gradual and continuous loss of physiological functions and responses, particularly marked in the brain. A common hallmark in aging and age-related diseases is an increase in oxidative stress and the failure of antioxidant defense systems. Current knowledge indicates that the level of glutathione progressively declines during aging. Because nerve cells are the longest-living cells that exhibit a high consumption rate of oxygen throughout an individual’s lifetime, the brain may be especially vulnerable to oxidative damage and this vulnerability increases during aging. In addition, the brain contains high concentrations of polyunsaturated fatty acids and transition metals and low antioxidative defense mechanisms. Although aging is an inevitable event, a growing volume of data confirms that antioxidant supplementation in combination with symptomatic drug treatments reduces oxidative stress and improves cognitive function in aging and age-related diseases. The present review discusses the neuroprotective effects of antioxidants in the aging brain.

  7. Biophysical mechanisms of traumatic brain injuries.

    Science.gov (United States)

    Young, Lee Ann; Rule, Gregory T; Bocchieri, Robert T; Burns, Jennie M

    2015-02-01

    Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.

  8. Molecular Mechanisms of Neonatal Brain Injury

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    Claire Thornton

    2012-01-01

    Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.

  9. Developing Attention: Behavioral and Brain Mechanisms

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    Michael I. Posner

    2014-01-01

    Full Text Available Brain networks underlying attention are present even during infancy and are critical for the developing ability of children to control their emotions and thoughts. For adults, individual differences in the efficiency of attentional networks have been related to neuromodulators and to genetic variations. We have examined the development of attentional networks and child temperament in a longitudinal study from infancy (7 months to middle childhood (7 years. Early temperamental differences among infants, including smiling and laughter and vocal reactivity, are related to self-regulation abilities at 7 years. However, genetic variations related to adult executive attention, while present in childhood, are poor predictors of later control, in part because individual genetic variation may have many small effects and in part because their influence occurs in interaction with caregiver behavior and other environmental influences. While brain areas involved in attention are present during infancy, their connectivity changes and leads to improvement in control of behavior. It is also possible to influence control mechanisms through training later in life. The relation between maturation and learning may allow advances in our understanding of human brain development.

  10. P300 brain computer interface: current challenges and emerging trends

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    Reza eFazel-Rezai

    2012-07-01

    Full Text Available A brain-computer interface (BCI enables communication without movement based on brain signals measured with electroencephalography (EEG. BCIs usually rely on one of three types of signals: the P300 and other components of the event-related potential (ERP, steady state visual evoked potential (SSVEP, or event related desynchronization (ERD. Although P300 BCIs were introduced over twenty years ago, the past few years have seen a strong increase in P300 BCI research. This closed-loop BCI approach relies on the P300 and other components of the event-related potential (ERP, based on an oddball paradigm presented to the subject. In this paper, we overview the current status of P300 BCI technology, and then discuss new directions: paradigms for eliciting P300s; signal processing methods; applications; and hybrid BCIs. We conclude that P300 BCIs are quite promising, as several emerging directions have not yet been fully explored and could lead to improvements in bit rate, reliability, usability, and flexibility.

  11. Brain mechanisms of drug reward and euphoria.

    Science.gov (United States)

    Wise, R A; Bozarth, M A

    1985-01-01

    Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate

  12. Dissecting molecular mechanisms in the living brain of dementia patients.

    Science.gov (United States)

    Barrio, Jorge R; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Petric, Andrej; Small, Gary W; Kepe, Vladimir

    2009-07-21

    Understanding the molecular mechanisms associated with the development of dementia is essential for designing successful interventions. Dementia, like cancer and cardiovascular disease, requires early detection to potentially arrest or prevent further disease progression. By the time a neurologist begins to manage clinical symptoms, the disease has often damaged the brain significantly. Because successful treatment is the logical goal, detecting the disease when brain damage is still limited is of the essence. The role of chemistry in this discovery process is critical. With the advent of molecular imaging, the understanding of molecular mechanisms in human neurodegenerative diseases has exploded. Traditionally, knowledge of enzyme and neurotransmitter function in humans has been extrapolated from animal studies, but now we can acquire data directly from both healthy and diseased human subjects. In this Account, we describe the use of molecular imaging probes to elucidate the biochemical and cellular bases of dementia (e.g., Alzheimer's disease) and the application of these discoveries to the design of successful therapeutic interventions. Molecular imaging permits observation and evaluation of the basic molecular mechanisms of disease progression in the living brains of patients. 2-Deoxy-2-[(18)F]fluoro-d-glucose is used to assess the effect of Alzheimer's disease progression on neuronal circuits projecting from and to the temporal lobe (one of the earliest metabolic signs of the disease). Recently, we have developed imaging probes for detection of amyloid neuropathology (both tau and beta-amyloid peptide deposits) and neuronal losses. These probes allow us to visualize the development of pathology in the living brain of dementia patients and its consequences, such as losses of critical neurons associated with memory deficits and other neuropsychiatric impairments. Because inflammatory processes are tightly connected to the brain degenerative processes

  13. Reduced Use of Emergency Care and Hospitalization in Patients with Traumatic Brain Injury Receiving Acupuncture Treatment

    Directory of Open Access Journals (Sweden)

    Chun-Chuan Shih

    2013-01-01

    Full Text Available Background. Little research exists on acupuncture treatment’s effect on patients with traumatic brain injury (TBI. Methods. Using Taiwan’s National Health Insurance Research Database, we conducted a cohort study to compare the use of emergency care and hospitalization in TBI patients with and without acupuncture treatment in the first year after TBI. The adjusted relative risks (RRs and 95% confidence intervals (CIs of high use of emergency care and hospitalization associated with acupuncture treatment were calculated in multivariate Poisson regression models with generalized estimating equation. Results. The means of medical visits of emergency care and hospitalization were lower in TBI patients with acupuncture treatment than in those without acupuncture treatment. After adjustment, acupuncture treatment was associated with decreased risk of high emergency care visits (beta = −0.0611, P=0.0452 and hospitalization (beta = −0.0989, P<0.0001. The RRs of high medical visits and expenditure for hospitalization associated with acupuncture treatment were 0.62 (95% CI = 0.50–0.76 and 0.66 (95% CI = 0.53–0.83, respectively. Conclusion. Patients with TBI who receive acupuncture treatment have reduced the use of emergency care and hospitalization in the first year after injury. The mechanisms of effects of acupuncture on TBI warrant further investigations.

  14. Mechanical aberrations in hypetrophic cardiomyopathy: emerging concepts.

    Directory of Open Access Journals (Sweden)

    Dimitrios eNtelios

    2015-08-01

    Full Text Available Hypertrophic cardiomyopathy is the most common monogenic disorder in cardiology. Despite important advances in understanding disease pathogenesis, it is not clear how flaws in individual sarcomere components are responsible for the observed phenotype. The aim of this article is to provide a brief interpretative analysis of some currently proposed pathophysiological mechanisms of hypertrophic cardiomyopathy, with a special emphasis on alterations in the cardiac mechanical properties.

  15. Emerging evidence of ozone metabolic effects and potential mechanisms

    Science.gov (United States)

    SOT 2014 Abstract: Invitational Emerging evidence of ozone metabolic effects and potential mechanisms U.P. Kodavanti NHEERL, USEPA, Research Triangle Park, NC Recent evidence suggests that air pollutants are linked to metabolic syndrome and impact several key metabolic proce...

  16. Emergence and mechanism in the fractional quantum Hall effect

    Science.gov (United States)

    Bain, Jonathan

    2016-11-01

    For some authors, an adequate notion of emergence must include an account of a mechanism by means of which emergent behavior is realized. This appeal to mechanism is problematic in the case of the fractional quantum Hall effect (FQHE). There is a consensus among physicists that the FQHE exhibits emergent phenomena, but there are at least four alternative explanations of the latter that, arguably, appeal to ontologically distinct mechanisms, both at the microphysics level and at the level of general organizing principles. In light of this underdetermination of mechanism, one is faced with the following options: (I) deny that emergence is present in the FQHE; (II) argue for the priority of one mechanistic explanation over the others; or (III) temper the desire for a mechanism-centric account of emergence. I will argue that there are good reasons to reject (I) and (II) and accept (III). In particular, I will suggest that a law-centric account of emergence does just fine in explaining the emergent phenomena associated with the FQHE.

  17. Marijuana use and brain immune mechanisms.

    Science.gov (United States)

    Cabral, Guy A; Jamerson, Melissa

    2014-01-01

    The recreational smoking of marijuana, or Cannabis sativa, has become widespread, including among adolescents. Marijuana contains a class of compounds known as phytocannabinoids that include cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC). THC is the major psychoactive component in marijuana, but also exhibits immunosuppressive activity. CBD, while not psychotropic, also modulates immune function, but its mechanism of action appears to differ from that of THC. Since both compounds are highly lipophilic, they readily passage the blood-brain barrier and access the central nervous system. Since CBD is not psychotropic, it has been considered as a candidate therapeutic compound for ablating neuropathological processes characterized by hyperinflammation. However, an unresolved question centers around the impact of these compounds on immune-competent cells within the CNS in relation to susceptibility to infection. There are accumulating data indicating that THC inhibits the migratory capability of macrophage-like cells resident in the CNS, such as microglia, toward nodes of microbial invasion. Furthermore, phytocannabinoids have been reported to exert developmental and long-term effects on the immune system suggesting that exposure to these substances during an early stage in life has the potential to alter the fundamental neuroimmune response to select microbial agents in the adult.

  18. Hominins and the emergence of the modern human brain.

    Science.gov (United States)

    de Sousa, Alexandra; Cunha, Eugénia

    2012-01-01

    Evidence used to reconstruct the morphology and function of the brain (and the rest of the central nervous system) in fossil hominin species comes from the fossil and archeological records. Although the details provided about human brain evolution are scarce, they benefit from interpretations informed by interspecific comparative studies and, in particular, human pathology studies. In recent years, new information has come to light about fossil DNA and ontogenetic trajectories, for which pathology research has significant implications. We briefly describe and summarize data from the paleoarcheological and paleoneurological records about the evolution of fossil hominin brains, including behavioral data most relevant to brain research. These findings are brought together to characterize fossil hominin taxa in terms of brain structure and function and to summarize brain evolution in the human lineage.

  19. The biological significance of brain barrier mechanisms

    DEFF Research Database (Denmark)

    Saunders, Norman R; Habgood, Mark D; Møllgård, Kjeld;

    2016-01-01

    that prevent the entry of many drugs of therapeutic potential into the brain. We outline those that have been tried and discuss why they may so far have been largely unsuccessful. Currently, a promising approach appears to be focal, reversible disruption of the blood-brain barrier using focused ultrasound...

  20. Brain enabled mechanized speech synthesizer using Brain Mobile Interface

    Directory of Open Access Journals (Sweden)

    N.R.Raajan

    2013-02-01

    Full Text Available Communication is easily evoked when the necessity to carry out the thoughts and vision arises. As the communication technology developed it cultivated the threats of information security, on the otherhand physically challenged people have no possibility to communicate freely hence the urge for development in the field of communication is necessary in present scenario. Aim of this work is to propose a system that improves the present communication system. Here we had put forward the concept of Brain Mobile Interface (BMI from the basis of Brain Computer Interface (BCI. BMI serves as a device to translate human thoughts about speech without the need of physical movement. Wireless EEG headsets are used to acquire the speech signals directly from the brain and after signal processing it is given to the mobile which consist of inbuilt speller application. With the help of speller application the message to be conveyed is acquired as text which is then converted into speech by means of text to speech converter.

  1. Brain restoration as an emerging field in neurology and neuroscience.

    Science.gov (United States)

    Bola, Michał; Prilloff, Sylvia; Matzke, Steffi; Henrich-Noack, Petra

    2013-01-01

    Restoration of brain function was long thought to be impossible. However, as the publications in the journal Restorative Neurology and Neuroscience (RNN) for more than 20 years attest, clinically useful improvement can be achieved after damage or diseases of the brain, the retina, and the peripheral nervous system. By reviewing both pre-clinical studies and clinical work, we explore what advancements can be made today and what to expect going forward. For example, in the last few years we have seen a clinical focus in the area of non-invasive brain stimulations and rehabilitation training trials. In basic animal research multi-modal approaches have been presented to restore brain function with a combination of different treatments. We think that this is an exciting time in the area of restoration of brain function with many new strategies aimed at helping recovering their impaired neurological functions.

  2. Brain mechanisms in early language acquisition.

    Science.gov (United States)

    Kuhl, Patricia K

    2010-09-09

    The last decade has produced an explosion in neuroscience research examining young children's early processing of language. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. The phonetic level of language is especially accessible to experimental studies that document the innate state and the effect of learning on the brain. The neural signatures of learning at the phonetic level can be documented at a remarkably early point in development. Continuity in linguistic development from infants' earliest brain responses to phonetic stimuli is reflected in their language and prereading abilities in the second, third, and fifth year of life, a finding with theoretical and clinical impact. There is evidence that early mastery of the phonetic units of language requires learning in a social context. Neuroscience on early language learning is beginning to reveal the multiple brain systems that underlie the human language faculty.

  3. Severe Traumatic Brain Injury In Children: An Evidence-Based Review Of Emergency Department Management.

    Science.gov (United States)

    Morrissey, Kirsten; Fairbrother, Hilary

    2016-10-01

    More than 1.7 million traumatic brain injuries occur in adults and children each year in the United States, with approximately 30% occurring in children aged blood pressure in the emergency department to improve neurologic outcomes following pediatric severe traumatic brain injury.

  4. Barrier mechanisms in the Drosophila blood-brain barrier

    OpenAIRE

    Samantha Jane Hindle; Roland Jerome Bainton

    2014-01-01

    The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated funct...

  5. NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress.

    Science.gov (United States)

    Sarnico, Ilenia; Branca, Caterina; Lanzillotta, Annamaria; Porrini, Vanessa; Benarese, Marina; Spano, Pier Franco; Pizzi, Marina

    2012-10-02

    Brain cells display an amazing ability to respond to several different types of environmental stimuli and integrate this response physiologically. Some of these responses can outlive the original stimulus by days, weeks or even longer. Long-lasting changes in both physiological and pathological conditions occurring in response to external stimuli are almost always mediated by changes in gene expression. To effect these changes, cells have developed an impressive repertoire of signaling systems designed to modulate the activity of numerous transcription factors and epigenetic mechanisms affecting the chromatin structure. Since its initial characterization in the nervous system, NF-κB has shown to respond to multiple signals and elicit pleiotropic activities suggesting that it may play a pivotal role in integration of different types of information within the brain. Ample evidence demonstrates that NF-κB factors are engaged in and necessary for neuronal development and synaptic plasticity, but they also regulate brain response to environmental noxae. By focusing on the complexity of NF-κB transcriptional activity in neuronal cell death, it emerged that the composition of NF-κB active dimers finely tunes the neuronal vulnerability to brain ischemia. Even though we are only beginning to understand the contribution of distinct NF-κB family members to the regulation of gene transcription in the brain, an additional level of regulation of NF-κB activity has emerged as operated by the epigenetic mechanisms modulating histone acetylation. We will discuss NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress and useful drug targets for restoration of brain function. This article is part of a Special Issue entitled: Brain Integration.

  6. Vocal Emotion of Humanoid Robots: A Study from Brain Mechanism

    Directory of Open Access Journals (Sweden)

    Youhui Wang

    2014-01-01

    Full Text Available Driven by rapid ongoing advances in humanoid robot, increasing attention has been shifted into the issue of emotion intelligence of AI robots to facilitate the communication between man-machines and human beings, especially for the vocal emotion in interactive system of future humanoid robots. This paper explored the brain mechanism of vocal emotion by studying previous researches and developed an experiment to observe the brain response by fMRI, to analyze vocal emotion of human beings. Findings in this paper provided a new approach to design and evaluate the vocal emotion of humanoid robots based on brain mechanism of human beings.

  7. Pathophysiologic mechanisms of brain-body associations in ruptured brain aneurysms: A systematic review

    Directory of Open Access Journals (Sweden)

    Benjamin W. Y. Lo

    2015-01-01

    Conclusions: This systematic review synthesizes the most current evidence of underlying mechanisms of brain related associations with body systems in aneurysmal subarachnoid hemorrhage. Results gained from these studies are clinically useful and shed light on how ruptured brain aneurysms affect the cardiopulmonary system. Subsequent neuro-cardio-endocrine responses then interact with other body systems as part of the secondary responses to primary injury.

  8. Subjective visual perception: from local processing to emergent phenomena of brain activity.

    Science.gov (United States)

    Panagiotaropoulos, Theofanis I; Kapoor, Vishal; Logothetis, Nikos K

    2014-05-05

    The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.

  9. Brain Behavior Evolution during Learning: Emergence of Hierarchical Temporal Memory

    Science.gov (United States)

    2013-08-30

    ORGANIZATION NAMES AND ADDRESSES U.S. Army Research Office P.O. Box 12211 Research Triangle Park , NC 27709-2211 15. SUBJECT TERMS brain model, Hopfield... topological organization that is commonly found in several complex systems. As an organization tool, it detects and measures significant features...nodes that are already highly connected are more likely to receive one of the new connections [5]. These networks reflect a theme described as “the

  10. Your Brain on Art: Emergent Cortical Dynamics During Aesthetic Experiences.

    Science.gov (United States)

    Kontson, Kimberly L; Megjhani, Murad; Brantley, Justin A; Cruz-Garza, Jesus G; Nakagome, Sho; Robleto, Dario; White, Michelle; Civillico, Eugene; Contreras-Vidal, Jose L

    2015-01-01

    The brain response to conceptual art was studied with mobile electroencephalography (EEG) to examine the neural basis of aesthetic experiences. In contrast to most studies of perceptual phenomena, participants were moving and thinking freely as they viewed the exhibit The Boundary of Life is Quietly Crossed by Dario Robleto at the Menil Collection-Houston. The brain activity of over 400 subjects was recorded using dry-electrode and one reference gel-based EEG systems over a period of 3 months. Here, we report initial findings based on the reference system. EEG segments corresponding to each art piece were grouped into one of three classes (complex, moderate, and baseline) based on analysis of a digital image of each piece. Time, frequency, and wavelet features extracted from EEG were used to classify patterns associated with viewing art, and ranked based on their relevance for classification. The maximum classification accuracy was 55% (chance = 33%) with delta and gamma features the most relevant for classification. Functional analysis revealed a significant increase in connection strength in localized brain networks while subjects viewed the most aesthetically pleasing art compared to viewing a blank wall. The direction of signal flow showed early recruitment of broad posterior areas followed by focal anterior activation. Significant differences in the strength of connections were also observed across age and gender. This work provides evidence that EEG, deployed on freely behaving subjects, can detect selective signal flow in neural networks, identify significant differences between subject groups, and report with greater-than-chance accuracy the complexity of a subject's visual percept of aesthetically pleasing art. Our approach, which allows acquisition of neural activity "in action and context," could lead to understanding of how the brain integrates sensory input and its ongoing internal state to produce the phenomenon which we term aesthetic experience.

  11. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle

    2014-12-01

    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  12. Emerging potential of exosomes for treatment of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ye Xiong

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs. miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.

  13. Emerging potential of exosomes for treatment of traumatic brain injury

    Science.gov (United States)

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2017-01-01

    Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.

  14. Bohmian mechanics, collapse models and the emergence of classicality

    Science.gov (United States)

    Toroš, Marko; Donadi, Sandro; Bassi, Angelo

    2016-09-01

    We discuss the emergence of classical trajectories in Bohmian mechanics, when a macroscopic object interacts with an external environment. We show that in such a case the conditional wave function of the system follows a dynamics which, under reasonable assumptions, corresponds to that of the Ghirardi-Rimini-Weber (GRW) collapse model. As a consequence, Bohmian trajectories evolve classically. Our analysis also shows how the GRW (istantaneous) collapse process can be derived by an underlying continuous interaction of a quantum system with an external agent, thus throwing a light on how collapses can emerge from a deeper level theory.

  15. Emerging Frontiers of Neuroengineering: A Network Science of Brain Connectivity

    OpenAIRE

    Bassett, Danielle S.; Ankit N Khambhati; Grafton, Scott T.

    2016-01-01

    Neuroengineering is faced with unique challenges in repairing or replacing complex neural systems that are composed of many interacting parts. These interactions form intricate patterns over large spatiotemporal scales, and produce emergent behaviors that are difficult to predict from individual elements. Network science provides a particularly appropriate framework in which to study and intervene in such systems, by treating neural elements (cells, volumes) as nodes in a graph and neural int...

  16. The emerging quantum the physics behind quantum mechanics

    CERN Document Server

    Pena, Luis de la; Valdes-Hernandez, Andrea

    2014-01-01

    This monograph presents the latest findings from a long-term research project intended to identify the physics behind Quantum Mechanics. A fundamental theory for quantum mechanics is constructed from first physical principles, revealing quantization as an emergent phenomenon arising from a deeper stochastic process. As such, it offers the vibrant community working on the foundations of quantum mechanics an alternative contribution open to discussion. The book starts with a critical summary of the main conceptual problems that still beset quantum mechanics.  The basic consideration is then introduced that any material system is an open system in permanent contact with the random zero-point radiation field, with which it may reach a state of equilibrium. Working from this basis, a comprehensive and self-consistent theoretical framework is then developed. The pillars of the quantum-mechanical formalism are derived, as well as the radiative corrections of nonrelativistic QED, while revealing the underlying physi...

  17. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  18. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    represents the most devastating and feared consequence of breast cancer . BCBM is usually fatal and is increasing in frequency with occult brain...metastatic breast cancer (stage IV) patients with or without clinically diagnosed BCBM employing multiparametric flow cytometry (FACS; ARIA IIID system)(10...AWARD NUMBER: W81XWH-14-1-0214 TITLE: Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis PRINCIPAL INVESTIGATOR: Dario

  19. Neuronal survival in the brain: neuron type-specific mechanisms.

    Science.gov (United States)

    Pfisterer, Ulrich; Khodosevich, Konstantin

    2017-03-02

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  20. PHILOSOPHY OF MIND; THEORETICAL AND EXPERIMENTAL CONTRIBUTION TO THE EMERGING VISION OF MIND-BRAIN INTERACTION.

    Directory of Open Access Journals (Sweden)

    Paul Ruiz Santos

    2011-12-01

    Full Text Available This work aims to contribute to the discussion of mind-brain interactions from an emergentism point of view of the Philosophy of Mind, using some of the naturalized theories. Some proposed bridges between mind and brain based on experimental naturalization are neuro-psychoanalysis, mirror neurons, and psychosomatics, among others. Naturalization can be achieved by earching for the link between psychological and biological processes. This biological-based approach can be developed avoiding mplification and reductionism of psychological processes. We discuss the access to new insights about the mind-brain relationship and its implications through neurophenomenology, from an emerging and interactionist point of view.

  1. [Neuroprotective mechanisms of cannabinoids in brain ischemia and neurodegenerative disorders].

    Science.gov (United States)

    Osuna-Zazuetal, Marcela Amparo; Ponce-Gómez, Juan Antonio; Pérez-Neri, Iván

    2015-06-01

    One of the most important causes of morbidity and mortality is neurologic dysfunction; its high incidence has led to an intense research of the mechanisms that protect the central nervous system from hypoxia and ischemia. The mayor challenge is to block the biochemical events leading to neuronal death. This may be achieved by neuroprotective mechanisms that avoid the metabolic and immunologic cascades that follow a neurological damage. When it occurs, several pathophysiological events develop including cytokine release, oxidative stress and excitotoxicity. Neuroprotective effects of cannabinoids to all those mechanisms have been reported in animal models of brain ischemia, excitotoxicity, brain trauma and neurodegenerative disorders. Some endocannabinoid analogs are being tested in clinical studies (I-III phase) for acute disorders involving neuronal death (brain trauma and ischemia). The study of the cannabinoid system may allow the discovery of effective neuroprotective drugs for the treatment of neurological disorders.

  2. Quantum mechanics emerging from stochastic dynamics of virtual particles

    CERN Document Server

    Tsekov, R

    2015-01-01

    It is demonstrated how quantum mechanics emerges from the stochastic dynamics of force-carriers. It is shown that the quantum Moyal equation corresponds to some dynamic correlations between the momentum of a real particle and the position of a virtual particle, which are not present in classical mechanics. The new concept throws light on the physical meaning of quantum theory, showing that the Planck constant square is a second-second cross-cumulant. The novel approach to quantum systems is extended to the relativistic case and an expression is derived for the relativistic mass in the Wigner quantum phase-space.

  3. Quantum mechanics, strong emergence and ontological non-reducibility

    CERN Document Server

    Gambini, Rodolfo; Pullin, Jorge

    2015-01-01

    We show that a new interpretation of quantum mechanics, in which the notion of event is defined without reference to measurement or observers, allows to construct a quantum general ontology based on systems, states and events. Unlike the Copenhagen interpretation, it does not resort to elements of a classical ontology. The quantum ontology in turn allows us to recognize that a typical behavior of quantum systems exhibits strong emergence and ontological non-reducibility. Such phenomena are not exceptional but natural, and are rooted in the basic mathematical structure of quantum mechanics.

  4. Mechanical origins of rightward torsion in early chick brain development

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  5. Conscious perception of emotional stimuli: brain mechanisms.

    Science.gov (United States)

    Mitchell, Derek G V; Greening, Steven G

    2012-08-01

    Emotional stimuli are thought to gain rapid and privileged access to processing resources in the brain. The structures involved in this enhanced access are thought to support subconscious, reflexive processes. Whether these pathways contribute to the phenomenological experience of emotional visual awareness (i.e., conscious perception) is unclear. In this review, it is argued that subcortical networks associated with the rapid detection of emotionally salient stimuli also play a key role in shaping awareness. This proposal is based on the idea that awareness of visual stimuli should be considered along a continuum, having intermediate levels, rather than as an all-or-none construct. It is also argued that awareness of emotional stimuli requires less input from frontoparietal structures that are often considered crucial for visual awareness. Evidence is also presented that implicates a region of the medial prefrontal cortex, involved in emotion regulation, in modulating amygdala output to determine awareness of emotional visual stimuli; when emotional stimuli are present, the conscious perception of alternative stimuli requires greater regulatory influences from cortical structures. Thus, emotional stimuli are privileged not only for neuronal representation and impact on subconscious processes, but also for awareness, allowing humans to deal flexibly rather than merely reflexively to biologically significant stimuli.

  6. Reduced Use of Emergency Care and Hospitalization in Patients with Traumatic Brain Injury Receiving Acupuncture Treatment

    OpenAIRE

    Chun-Chuan Shih; Hsun-Hua Lee; Ta-Liang Chen; Chin-Chuan Tsai; Hsin-Long Lane; Wen-Ta Chiu; Chien-Chang Liao

    2013-01-01

    Background. Little research exists on acupuncture treatment's effect on patients with traumatic brain injury (TBI). Methods. Using Taiwan's National Health Insurance Research Database, we conducted a cohort study to compare the use of emergency care and hospitalization in TBI patients with and without acupuncture treatment in the first year after TBI. The adjusted relative risks (RRs) and 95% confidence intervals (CIs) of high use of emergency care and hospitalization associated with acupunct...

  7. Mental states as macrostates emerging from brain electrical dynamics

    Science.gov (United States)

    Allefeld, Carsten; Atmanspacher, Harald; Wackermann, Jiří

    2009-03-01

    Psychophysiological correlations form the basis for different medical and scientific disciplines, but the nature of this relation has not yet been fully understood. One conceptual option is to understand the mental as "emerging" from neural processes in the specific sense that psychology and physiology provide two different descriptions of the same system. Stating these descriptions in terms of coarser- and finer-grained system states (macro- and microstates), the two descriptions may be equally adequate if the coarse-graining preserves the possibility to obtain a dynamical rule for the system. To test the empirical viability of our approach, we describe an algorithm to obtain a specific form of such a coarse-graining from data, and illustrate its operation using a simulated dynamical system. We then apply the method to an electroencephalographic recording, where we are able to identify macrostates from the physiological data that correspond to mental states of the subject.

  8. Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid.

    Science.gov (United States)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen H; Bunch, Lennart; Pickering, Darryl S

    2015-03-01

    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy.

  9. Mechanisms and effects of seizures in the immature brain.

    Science.gov (United States)

    Nardou, Romain; Ferrari, Diana C; Ben-Ari, Yehezkel

    2013-08-01

    The developing immature brain is not simply a small adult brain but rather possesses unique physiological properties. These include neuronal ionic currents that differ markedly from those in the adult brain, typically being longer-lasting and less selective. This enables immature heterogeneous neurons to connect and fire together but at the same time, along with other features may contribute to the enhanced propensity of the developing brain to become epileptic. Indeed, immature neurons tend to readily synchronize and thus generate seizures. Here, we review the differences between the immature and adult brain, with particular focus on the developmental sequence of γ-aminobutyric acid that excites immature neurons while being inhibitory in the normal adult brain. We review the mechanisms underlying the developmental changes to intracellular chloride levels, as well as how epileptiform activity can drive pathologic changes to chloride balance in the brain. We show that regulation of intracellular chloride is one important factor that underlies both the ease with which seizures can be generated and the facilitation of further seizures. We stress in particular the importance of understanding normal developmental sequences and how they are interrupted by seizures and other insults, and how this knowledge has led to the identification of potential novel treatments for conditions such as neonatal seizures.

  10. Operational Mechanism and Evaluation System for Emergency Logistics Risks

    Directory of Open Access Journals (Sweden)

    Qi Cheng

    2010-12-01

    Full Text Available Lots of risks existed in the operating process of emergency logistics especially when natural disasters happened. Both operating mechanism and evaluation system research on Emergency Logistics Risks (ELR are the basis of effective recognizing, preventing and responding to risks, so it’s of great theoretical and practical significance to study the formation and influence mechanism and to establish an evaluating index system for ELR. Firstly, some foundation research about ELR was carried out, including definition, characteristics and classification of ELR. The formation and influence mechanism of ELR were discussed. The research of questionnaire survey offered an objective support for theoretical mechanism and index system establishment. Then, the evaluating index system for ELR was established. This system was a multi-level index system, and mainly evaluated by the decision-making risk, dispatching and commanding risk, organizing and coordinating risk, executing and controlling risk, resources supporting risk and their sub index. The establishment principles and significance of the index system were discussed. Then, the fuzzy comprehensive evaluation and Delphi method were used to confirm the index weight and value. Finally, a case analysis on ELR of Yushu earthquake was conducted to demonstrate the evaluating index system and to evaluate the actual risk level.

  11. Emerging Molecular Targets for Brain Repair after Stroke

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    Jerzy Krupinski

    2013-01-01

    Full Text Available The field of neuroprotection generated consistent preclinical findings of mechanisms of cell death but these failed to be translated into clinics. The approaches that combine the modulation of the inhibitory environment together with the promotion of intrinsic axonal outgrowth needs further work before combined therapeutic strategies will be transferable to clinic trials. It is likely that only when some answers have been found to these issues will our therapeutic efforts meet our expectations. Stroke is a clinically heterogeneous disease and combinatorial treatments require much greater work in pharmacological and toxicological testing. Advances in genetics and results of the Whole Human Genome Project (HGP provided new unknown information in relation to stroke. Genetic factors are not the only determinants of responses to some diseases. It was recognized early on that “epigenetic” factors were major players in the aetiology and progression of many diseases like stroke. The major players are microRNAs that represent the best-characterized subclass of noncoding RNAs. Epigenetic mechanisms convert environmental conditions and physiological stresses into long-term changes in gene expression and translation. Epigenetics in stroke are in their infancy but offer great promise for better understanding of stroke pathology and the potential viability of new strategies for its treatment.

  12. Emergent patterns of growth controlled by multicellular form and mechanics

    Science.gov (United States)

    Nelson, Celeste M.; Jean, Ronald P.; Tan, John L.; Liu, Wendy F.; Sniadecki, Nathan J.; Spector, Alexander A.; Chen, Christopher S.

    2005-01-01

    Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using microfabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth. PMID:16049098

  13. [Intestinal-brain axis. Neuronal and immune-inflammatory mechanisms of brain and intestine pathology].

    Science.gov (United States)

    Bondarenko, V M; Riabichenko, E V

    2013-01-01

    Mutually directed connections between intestine and brain are implemented by endocrine, neural and immune systems and nonspecific natural immunity. Intestine micro flora as an active participant of intestine-brain axis not only influences intestine functions but also stimulates the development of CNS in perinatal period and interacts with higher nervous centers causing depression and cognitive disorders in pathology. A special role belongs to intestine microglia. Apart from mechanic (protective) and trophic functions for intestine neurons, glia implements neurotransmitter, immunologic, barrier and motoric functions in the intestine. An interconnection between intestine barrier function and hematoencephalic barrier regulation exists. Chronic endotoxinemia as a result of intestine barrier dysfunction forms sustained inflammation state in periventricular zone of the brain with consequent destabilization of hematoencephalic barriers and spread oF inflammation to other parts of the brain resulting in neurodegradation development.

  14. Decision-making mechanisms in the brain

    Science.gov (United States)

    Deco, Gustavo; Rolls, Edmund T.

    2007-02-01

    Behavioral, neurophysiological, and theoretical studies are converging to a common theory of decision-making that assumes an underlying diffusion process which integrates both the accumulation of perceptual and cognitive evidence for making the decision and motor choice in one unifying neural network. In particular, neuronal activity in the ventral premotor cortex (VPC) is related to decision-making while trained monkeys compare two mechanical vibrations applied sequentially to the tip of a finger to report which of the two stimuli have the higher frequency (Romo et al. 2004, Neuron 41: 165). In particular, neurons were found whose response depended only on the difference between the two applied frequencies, the sign of that difference being the determining factor for correct task performance. We describe an integrate-and-fire attractor model with realistic synaptic dynamics including AMPA, NMDA and GABA synapses which can reproduce the decision-making related response selectivity of VPC neurons during the comparison period of the task. Populations of neurons for each decision in the biased competition attractor receive a bias input that depends on the firing rates of neurons in the VPC that code for the two vibrotactile frequencies. It was found that if the connectivity parameters of the network are tuned, using mean-field techniques, so that the network has two possible stable stationary final attractors respectively related to the two possible decisions, then the firing rate of the neurons in whichever attractor wins reflects the sign of the difference in the frequencies being compared but not the absolute frequencies. Thus Weber's law for frequency comparison is not encoded by the firing rate of the neurons in these attractors. An analysis of the nonstationary evolution of the dynamics of the network model shows that Weber's law is implemented in the probability of transition from the initial spontaneous firing state to one of the two possible attractor states

  15. The mechanism of the emergence of distinct overstretched DNA states

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, You-Liang; Sun, Zhao-Yan, E-mail: zysun@ciac.ac.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Lu, Zhong-Yuan [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China)

    2016-01-14

    Although multiple overstretched DNA states were identified in experiments, the mechanism of the emergence of distinct states is still unclear. Molecular dynamics simulation is an ideal tool to clarify the mechanism, but the force loading rates in stretching achieved by conventional all-atom DNA models are much faster, which essentially affect overstretching states. We employed a modified coarse-grained DNA model with an unprecedented low loading rate in simulations to study the overstretching transitions of end-opened double-stranded DNA. We observed two-strand peeling off for DNA with low stability and the S-DNA with high stability under tension. By introducing a melting-forbidden model which prevents base-pair breaking, we still observed the overstretching transition induced by the formation of S-DNA due to the change of dihedral angle. Hence, we confirmed that the competition between the two strain-softening manners, i.e., base-pair breaking and dihedral angle variation, results in the emergence of distinct overstretched DNA states.

  16. Corticonic models of brain mechanisms underlying cognition and intelligence

    Science.gov (United States)

    Farhat, Nabil H.

    The concern of this review is brain theory or more specifically, in its first part, a model of the cerebral cortex and the way it: (a) interacts with subcortical regions like the thalamus and the hippocampus to provide higher-level-brain functions that underlie cognition and intelligence, (b) handles and represents dynamical sensory patterns imposed by a constantly changing environment, (c) copes with the enormous number of such patterns encountered in a lifetime by means of dynamic memory that offers an immense number of stimulus-specific attractors for input patterns (stimuli) to select from, (d) selects an attractor through a process of “conjugation” of the input pattern with the dynamics of the thalamo-cortical loop, (e) distinguishes between redundant (structured) and non-redundant (random) inputs that are void of information, (f) can do categorical perception when there is access to vast associative memory laid out in the association cortex with the help of the hippocampus, and (g) makes use of “computation” at the edge of chaos and information driven annealing to achieve all this. Other features and implications of the concepts presented for the design of computational algorithms and machines with brain-like intelligence are also discussed. The material and results presented suggest, that a Parametrically Coupled Logistic Map network (PCLMN) is a minimal model of the thalamo-cortical complex and that marrying such a network to a suitable associative memory with re-entry or feedback forms a useful, albeit, abstract model of a cortical module of the brain that could facilitate building a simple artificial brain. In the second part of the review, the results of numerical simulations and drawn conclusions in the first part are linked to the most directly relevant works and views of other workers. What emerges is a picture of brain dynamics on the mesoscopic and macroscopic scales that gives a glimpse of the nature of the long sought after brain code

  17. PREFACE: EmQM13: Emergent Quantum Mechanics 2013

    Science.gov (United States)

    2014-04-01

    These proceedings comprise the invited lectures of the second international symposium on Emergent Quantum Mechanics (EmQM13), which was held at the premises of the Austrian Academy of Sciences in Vienna, Austria, 3-6 October 2013. The symposium was held at the ''Theatersaal'' of the Academy of Sciences, and was devoted to the open exploration of emergent quantum mechanics, a possible ''deeper level theory'' that interconnects three fields of knowledge: emergence, the quantum, and information. Could there appear a revised image of physical reality from recognizing new links between emergence, the quantum, and information? Could a novel synthesis pave the way towards a 21st century, ''superclassical'' physics? The symposium provided a forum for discussing (i) important obstacles which need to be overcome as well as (ii) promising developments and research opportunities on the way towards emergent quantum mechanics. Contributions were invited that presented current advances in both standard as well as unconventional approaches to quantum mechanics. The EmQM13 symposium was co-organized by Gerhard Grössing (Austrian Institute for Nonlinear Studies (AINS), Vienna), and by Jan Walleczek (Fetzer Franklin Fund, USA, and Phenoscience Laboratories, Berlin). After a very successful first conference on the same topic in 2011, the new partnership between AINS and the Fetzer Franklin Fund in producing the EmQM13 symposium was able to further expand interest in the promise of emergent quantum mechanics. The symposium consisted of two parts, an opening evening addressing the general public, and the scientific program of the conference proper. The opening evening took place at the Great Ceremonial Hall (Grosser Festsaal) of the Austrian Academy of Sciences, and it presented talks and a panel discussion on ''The Future of Quantum Mechanics'' with three distinguished speakers: Stephen Adler (Princeton), Gerard 't Hooft (Utrecht) and Masanao Ozawa (Nagoya). The articles contained in

  18. The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury

    OpenAIRE

    2015-01-01

    Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus r...

  19. Development of brain mechanisms for processing affective touch

    Directory of Open Access Journals (Sweden)

    Malin eBjornsdotter

    2014-02-01

    Full Text Available Affective tactile stimulation plays a key role in the maturation of neural circuits, but the development of brain mechanisms processing touch is poorly understood. We therefore used functional magnetic resonance imaging (fMRI to study brain responses to soft brush stroking of both glabrous (palm and hairy (forearm skin in healthy children (5-13 years, adolescents (14-17 years and adults (25-35 years. Adult-defined regions-of-interests in the primary somatosensory cortex (SI, secondary somatosensory cortex (SII, insular cortex and right posterior superior temporal sulcus (pSTS were significantly and similarly activated in all age groups. Whole-brain analyses revealed that responses in the ipsilateral SII were positively correlated with age in both genders, and that responses in bilateral regions near the pSTS correlated significantly and strongly with age in females but not in males. These results suggest that brain mechanisms associated with both sensory-discriminative and affective-motivational aspects of touch are largely established in school-aged children, and that there is a general continuing maturation of SII and a female-specific increase in pSTS sensitivity with age. Our work establishes a groundwork for future comparative studies of tactile processing in developmental disorders characterized by disrupted social perception such as autism.

  20. Molecular Mechanisms of Cannabis Signaling in the Brain.

    Science.gov (United States)

    Ronan, Patrick J; Wongngamnit, Narin; Beresford, Thomas P

    2016-01-01

    Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative.

  1. Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity

    Directory of Open Access Journals (Sweden)

    Stern Stephan T

    2012-06-01

    Full Text Available Abstract The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.

  2. Brain Mechanisms of Altered Consciousness in Generalised Seizures

    Directory of Open Access Journals (Sweden)

    Stefano Seri

    2011-01-01

    Full Text Available In spite of the inherent difficulties in achieving a biologically meaningful definition of consciousness, recent neurophysiological studies are starting to provide some insight in fundamental mechanisms associated with impaired consciousness in neurological disorders. Generalised seizures are associated with disruption of the default state network, a functional network of discrete brain areas, which include the fronto-parietal cortices. Subcortical contribution through activation of thalamocortical structures, as well as striate nuclei are also crucial to produce impaired consciousness in generalised seizures.

  3. Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms.

    Science.gov (United States)

    Kankaanranta, Hannu; Kauppi, Paula; Tuomisto, Leena E; Ilmarinen, Pinja

    2016-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2), and cardiac and psychiatric diseases. Their role as risk factors for incident asthma and whether they affect clinical asthma are evaluated. Obesity, independently or as a part of metabolic syndrome, DM2, and depression are risk factors for incident asthma. In contrast, the effects of comorbidities on clinical asthma are less well-known and mostly studies are lacking. Cross-sectional studies in obese asthmatics suggest that they may have less well controlled asthma and worse lung function. However, no long-term clinical follow-up studies with these comorbidities and asthma were identified. These emerging comorbidities often occur in the same multimorbid adult patient and may have in common metabolic pathways and inflammatory or other alterations such as early life exposures, systemic inflammation, inflammasome, adipokines, hyperglycemia, hyperinsulinemia, lung mechanics, mitochondrial dysfunction, disturbed nitric oxide metabolism, and leukotrienes.

  4. Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms

    Directory of Open Access Journals (Sweden)

    Hannu Kankaanranta

    2016-01-01

    Full Text Available Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2, and cardiac and psychiatric diseases. Their role as risk factors for incident asthma and whether they affect clinical asthma are evaluated. Obesity, independently or as a part of metabolic syndrome, DM2, and depression are risk factors for incident asthma. In contrast, the effects of comorbidities on clinical asthma are less well-known and mostly studies are lacking. Cross-sectional studies in obese asthmatics suggest that they may have less well controlled asthma and worse lung function. However, no long-term clinical follow-up studies with these comorbidities and asthma were identified. These emerging comorbidities often occur in the same multimorbid adult patient and may have in common metabolic pathways and inflammatory or other alterations such as early life exposures, systemic inflammation, inflammasome, adipokines, hyperglycemia, hyperinsulinemia, lung mechanics, mitochondrial dysfunction, disturbed nitric oxide metabolism, and leukotrienes.

  5. Crash Simulator: Brain-and-Spine Injury Mechanics

    Science.gov (United States)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    Recently, the first author has proposed a new coupled loading-rate hypothesis as a unique cause of both brain and spinal injuries, which states that they are both caused by a Euclidean jolt, an impulsive loading that strikes head and spine (or, any other part of the human body)- in several coupled degrees-of-freedom simultaneously. Injury never happens in a single direction only, nor is it ever caused by a static force. It is always an impulsive translational plus rotational force. The Euclidean jolt causes two basic forms of brain, spine and other musculo-skeletal injuries: (i) localized translational dislocations; and (ii) localized rotational disclinations. In the present Chapter, we first review this unique mechanics of a general human mechanical injury, and then describe how it can be predicted and controlled by a crash simulator toolbox. This rigorous Matlab toolbox has been developed using an existing thirdparty toolbox DiffMan, for accurately solving differential equations on smooth manifolds and mechanical Lie groups. The present crash simulator toolbox performs prediction/control of brain and spinal injuries within the framework of the Euclidean group SE(3) of rigid motions in our natural 3-dimensional space.

  6. Brain. Conscious and Unconscious Mechanisms of Cognition, Emotions, and Language

    Directory of Open Access Journals (Sweden)

    Roman Ilin

    2012-12-01

    Full Text Available Conscious and unconscious brain mechanisms, including cognition, emotions and language are considered in this review. The fundamental mechanisms of cognition include interactions between bottom-up and top-down signals. The modeling of these interactions since the 1960s is briefly reviewed, analyzing the ubiquitous difficulty: incomputable combinatorial complexity (CC. Fundamental reasons for CC are related to the Gödel’s difficulties of logic, a most fundamental mathematical result of the 20th century. Many scientists still “believed” in logic because, as the review discusses, logic is related to consciousness; non-logical processes in the brain are unconscious. CC difficulty is overcome in the brain by processes “from vague-unconscious to crisp-conscious” (representations, plans, models, concepts. These processes are modeled by dynamic logic, evolving from vague and unconscious representations toward crisp and conscious thoughts. We discuss experimental proofs and relate dynamic logic to simulators of the perceptual symbol system. “From vague to crisp” explains interactions between cognition and language. Language is mostly conscious, whereas cognition is only rarely so; this clarifies much about the mind that might seem mysterious. All of the above involve emotions of a special kind, aesthetic emotions related to knowledge and to cognitive dissonances. Cognition-language-emotional mechanisms operate throughout the hierarchy of the mind and create all higher mental abilities. The review discusses cognitive functions of the beautiful, sublime, music.

  7. Inferring brain-computational mechanisms with models of activity measurements.

    Science.gov (United States)

    Kriegeskorte, Nikolaus; Diedrichsen, Jörn

    2016-10-01

    High-resolution functional imaging is providing increasingly rich measurements of brain activity in animals and humans. A major challenge is to leverage such data to gain insight into the brain's computational mechanisms. The first step is to define candidate brain-computational models (BCMs) that can perform the behavioural task in question. We would then like to infer which of the candidate BCMs best accounts for measured brain-activity data. Here we describe a method that complements each BCM by a measurement model (MM), which simulates the way the brain-activity measurements reflect neuronal activity (e.g. local averaging in functional magnetic resonance imaging (fMRI) voxels or sparse sampling in array recordings). The resulting generative model (BCM-MM) produces simulated measurements. To avoid having to fit the MM to predict each individual measurement channel of the brain-activity data, we compare the measured and predicted data at the level of summary statistics. We describe a novel particular implementation of this approach, called probabilistic representational similarity analysis (pRSA) with MMs, which uses representational dissimilarity matrices (RDMs) as the summary statistics. We validate this method by simulations of fMRI measurements (locally averaging voxels) based on a deep convolutional neural network for visual object recognition. Results indicate that the way the measurements sample the activity patterns strongly affects the apparent representational dissimilarities. However, modelling of the measurement process can account for these effects, and different BCMs remain distinguishable even under substantial noise. The pRSA method enables us to perform Bayesian inference on the set of BCMs and to recognize the data-generating model in each case.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  8. β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms.

    Science.gov (United States)

    Achanta, Lavanya B; Rae, Caroline D

    2017-01-01

    β-Hydroxybutyrate (βOHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain βOHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point. βOHB possesses an intrinsic high heat of combustion, making it an efficient mitochondrial fuel, where it can alter the NAD(+)/NADH and Q/QH2 couples and reduce production of mitochondrial reactive oxygen species. It can directly interact as a signalling molecule influencing opening of K(+) channels and regulation of Ca(2+) channels. βOHB is an inhibitor of histone deacetylases resulting in upregulation of genes involved in protection against oxidative stress and regulation of metabolism. It interacts with an inflammasome in immune cells to reduce production of inflammatory cytokines and reduce inflammation. Use of βOHB as an efficient neurotherapeutic relies on increasing blood βOHB levels so as to encourage entry of βOHB to the brain. While use of βOHB as a sole therapeutic is currently limited, with employment of a ketogenic diet a more widely used approach, recent development and testing of esterified forms of βOHB have shown great promise, with the approach elevating plasma βOHB while allowing consumption of normal diet. An improved understanding of the mechanisms by which βOHB acts will allow better design of both diet and supplemental interventions.

  9. Inferring brain-computational mechanisms with models of activity measurements

    Science.gov (United States)

    Diedrichsen, Jörn

    2016-01-01

    High-resolution functional imaging is providing increasingly rich measurements of brain activity in animals and humans. A major challenge is to leverage such data to gain insight into the brain's computational mechanisms. The first step is to define candidate brain-computational models (BCMs) that can perform the behavioural task in question. We would then like to infer which of the candidate BCMs best accounts for measured brain-activity data. Here we describe a method that complements each BCM by a measurement model (MM), which simulates the way the brain-activity measurements reflect neuronal activity (e.g. local averaging in functional magnetic resonance imaging (fMRI) voxels or sparse sampling in array recordings). The resulting generative model (BCM-MM) produces simulated measurements. To avoid having to fit the MM to predict each individual measurement channel of the brain-activity data, we compare the measured and predicted data at the level of summary statistics. We describe a novel particular implementation of this approach, called probabilistic representational similarity analysis (pRSA) with MMs, which uses representational dissimilarity matrices (RDMs) as the summary statistics. We validate this method by simulations of fMRI measurements (locally averaging voxels) based on a deep convolutional neural network for visual object recognition. Results indicate that the way the measurements sample the activity patterns strongly affects the apparent representational dissimilarities. However, modelling of the measurement process can account for these effects, and different BCMs remain distinguishable even under substantial noise. The pRSA method enables us to perform Bayesian inference on the set of BCMs and to recognize the data-generating model in each case. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574316

  10. Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms.

    Directory of Open Access Journals (Sweden)

    Sonia eLevi

    2014-05-01

    Full Text Available Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of Neurodegeneration with Brain Iron Accumulation (NBIA. So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: Neuroferritinopathy, associated to mutations in the FTL gene and Aceruloplasminaemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, COASY,Pla2G6, C19orf12, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

  11. MOLECULAR MECHANISMS REGULATING LPS-INDUCED INFLAMMATION IN THE BRAIN

    Directory of Open Access Journals (Sweden)

    Olena eLykhmus

    2016-03-01

    Full Text Available Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the 7 nicotinic acetylcholine receptor (7 nAChR. We previously showed that either bacterial lipopolysaccharide (LPS or immunization with the 7(1-208 nAChR fragment decrease 7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease. To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of 7 nAChR RNA and protein and of acetylcholinesterase (AChE RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding 7(1-208-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining 7 nAChR/AChE decreases. In U373 cells, 7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that 7 nAChR down-regulation limits this pathway, and that 7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration.

  12. Molecular Mechanisms Regulating LPS-Induced Inflammation in the Brain

    Science.gov (United States)

    Lykhmus, Olena; Mishra, Nibha; Koval, Lyudmyla; Kalashnyk, Olena; Gergalova, Galyna; Uspenska, Kateryna; Komisarenko, Serghiy; Soreq, Hermona; Skok, Maryna

    2016-01-01

    Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the α7 nicotinic acetylcholine receptor (α7 nAChR). We previously showed that either bacterial lipopolysaccharide (LPS) or immunization with the α7(1–208) nAChR fragment decrease α7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease (AD). To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of α7 nAChR RNA and protein and of acetylcholinesterase (AChE) RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding α7(1–208)-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining α7 nAChR/AChE decreases. In U373 cells, α7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that α7 nAChR down-regulation limits this pathway, and that α7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration. PMID:27013966

  13. Mechanical Loading of Neurons and Astrocytes with Application to Blast Traumatic Brain Injury

    Science.gov (United States)

    2010-01-01

    traumatic brain injury ( TBI ). Neurons and astrocytes are susceptible to damage mechanisms arising from various...further developments may be pursued to unravel the key mechanical pathways potentially involved in TBI . 1. INTRODUCTION Traumatic brain injury ... injury mechanisms at the cellular level. This is especially important when studying traumatic brain injury ( TBI ). Neurons and astrocytes

  14. Behavioral robustness: an emergent phenomenon by means of distributed mechanisms and neurodynamic determinacy.

    Science.gov (United States)

    Fernandez-Leon, Jose A

    2012-01-01

    Theoretical discussions and computational models of bio-inspired embodied and situated agents are introduced in this article capturing in simplified form the dynamical essence of robust, yet adaptive behavior. This article analyzes the general problem of how the dynamical coupling between internal control (brain), body and environment is used in the generation of specific behaviors. Based on the Evolutionary Robotics (ER) paradigm, four computational models are described to support discussions including descriptions on performance after a series of structural, sensorimotor or mutational perturbations, or are developed in the absence of them. Experimental results suggest that 'dynamic determinacy' - i.e. the continuous presence of a unique dynamical attractor that must be chased during functional behaviors - is a common dynamic phenomenon in the analyzed robust and adaptive agents. These agents show dynamical states that are definitely and unequivocally characterized via transient dynamics toward a unique, yet moving attractor at neural level for coherent actions. This determinacy emerges as a control strategy rooted on behavioral couplings and relies on mechanisms that are distributed on brain, body and environment. Different ways to induce further distribution of behavioral mechanisms are also discussed in this paper from a bio-inspired ER perspective.

  15. Serotonergic mechanisms in the migraine brain - a systematic review

    DEFF Research Database (Denmark)

    Deen, Marie; Christensen, Casper Emil; Hougaard, Anders

    2017-01-01

    role of brain serotonergic mechanisms remains a matter of controversy. METHODS: We systematically searched PubMed for studies investigating the serotonergic system in the migraine brain by either molecular neuroimaging or electrophysiological methods. RESULTS: The literature search resulted in 59......BACKGROUND: Migraine is one of the most common and disabling of all medical conditions, affecting 16% of the general population, causing huge socioeconomic costs globally. Current available treatment options are inadequate. Serotonin is a key molecule in the neurobiology of migraine, but the exact...... papers, of which 13 were eligible for review. The reviewed papers collectively support the notion that migraine patients have alterations in serotonergic neurotransmission. Most likely, migraine patients have a low cerebral serotonin level between attacks, which elevates during a migraine attack...

  16. Mechanisms of CCK signaling from gut to brain.

    Science.gov (United States)

    Raybould, Helen E

    2007-12-01

    Following the observation that exogenous peripheral injection of CCK could inhibit food intake, the mechanisms by which CCK influences the gut-brain pathway have been the subject of intense study for nearly 30 years. Recently, it has become evident that the system is more complex and that the consequences of CCK's action on the gut-brain pathway are more far reaching than previously recognized. This review will examine the recent evidence showing the role of CCK and CCK1Rs in modulating expression of other receptors for orexigenic and anorexigenic regulatory peptides at the level of vagal afferent neurons. In addition, new evidence showing the importance of the action of CCK at the level of the vagus nerve in the regulation of food intake, body weight, and in activation of an anti-inflammatory pathway will be reviewed.

  17. Emergence of Quantum Mechanics from a Sub-Quantum Statistical Mechanics

    Science.gov (United States)

    Grössing, Gerhard

    2015-10-01

    A research program within the scope of theories on "Emergent Quantum Mechanics" is presented, which has gained some momentum in recent years. Via the modeling of a quantum system as a non-equilibrium steady-state maintained by a permanent throughput of energy from the zero-point vacuum, the quantum is considered as an emergent system. We implement a specific "bouncer-walker" model in the context of an assumed sub-quantum statistical physics, in analogy to the results of experiments by Couder and Fort on a classical wave-particle duality. We can thus give an explanation of various quantum mechanical features and results on the basis of a "21st century classical physics", such as the appearance of Planck's constant, the Schrödinger equation, etc. An essential result is given by the proof that averaged particle trajectories' behaviors correspond to a specific type of anomalous diffusion termed "ballistic" diffusion on a sub-quantum level...

  18. Boundaries as Mechanisms for Learning in Emergency Exercises with Students from Emergency Service Organisations

    Science.gov (United States)

    Andersson, Annika

    2016-01-01

    To prepare emergency response organisations for collaborative work in unpredictable and dynamic situations, various types of exercises are widely used. Still, our knowledge of collaboration exercises with emergency response students is limited. This study aimed to contribute to this field by exploring boundaries that emerged between collaborating…

  19. Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes.

    Science.gov (United States)

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2013-11-01

    Recent advances in brain energy metabolism support the notion that glycogen in astrocytes is necessary for the clearance of neuronally-released K(+) from the extracellular space. However, how the multiple metabolic pathways involved in K(+)-induced increase in glycogen turnover are regulated is only partly understood. Here we summarize the current knowledge about the mechanisms that control glycogen metabolism during enhanced K(+) uptake. We also describe the action of the ubiquitous Na(+)/K(+) ATPase for both ion transport and intracellular signaling cascades, and emphasize its importance in understanding the complex relation between glycogenolysis and K(+) uptake.

  20. Emergent Semiclassical Time in Quantum Gravity. I. Mechanical Models

    CERN Document Server

    Anderson, E

    2006-01-01

    Strategies intended to resolve the problem of time in quantum gravity by means of emergent or hidden timefunctions are considered in the arena of relational particle toy models. In situations with `heavy' and `light' degrees of freedom, two notions of emergent semiclassical WKB time emerge; these are furthermore equivalent to two notions of emergent classical `Leibniz--Mach--Barbour' time. I futhermore study the semiclassical approach, in a geometric phase formalism, extended to include linear constraints, and with particular care to make explicit those approximations and assumptions used. I propose a new iterative scheme for this in the cosmologically-motivated case with one heavy degree of freedom. I find that the usual semiclassical quantum cosmology emergence of time comes hand in hand with the emergence of other qualitatively significant terms, including back-reactions on the heavy subsystem and second time derivatives. I illustrate my analysis by taking it further for relational particle models with lin...

  1. [Brain mechanisms of imagination during verbal creative problem solving].

    Science.gov (United States)

    Rodionov, A R

    2013-01-01

    In the present study, EEG spectral analysis was used to examine the brain mechanisms of imagination in student actors and student non-actors under three experimental conditions: when subjects created a coherent story based on a presented picture (STORY), listed the details of the presented picture (DETAIL) and executed simple calculation while they looked at neutral background (COUNT). Statistical comparison of STORY and DETAIL conditions revealed significantly higher spectral power in alpha1 (7.5-10 Hz) and alpha2 (10-12.5 Hz) bands in the most of investigated cortical areas in actors and non-actors. By contrast, in comparisons STORY-COUNT and DETAIL-COUNT significantly lower spectral power in the same frequency bands in all investigated cortical areas in both groups was obtained. The most prominent differences in comparison STORY-DETAIL were revealed over the central parietal area. The most prominent differences in comparisons STORY-COUNT and DETAIL-COUNT were revealed mainly over the occipital areas. These EEG changes were found in both groups of subjects. Taking this fact into account we consider parietal areas to be stable element of the brain system which maintain verbal creativity in actors and non-actors. The discussion of our results with respect to those obtained in previous studies leads to conclusion that parietal areas are involved into the mechanism of selective inhibition of visual information processing during imagination.

  2. Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

    Directory of Open Access Journals (Sweden)

    Marianna E. Jung

    2010-07-01

    Full Text Available Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2, interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors. The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17

  3. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents

    Science.gov (United States)

    Swartz, Johnna R.

    2016-01-01

    Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step towards developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear if differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging, and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status predict changes in risk-related brain function. Specifically, we find that lower socioeconomic status during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention amongst high-risk individuals. PMID:27217150

  4. Developmental modes and developmental mechanisms can channel brain evolution

    Directory of Open Access Journals (Sweden)

    Christine J Charvet

    2011-02-01

    Full Text Available Anseriform birds (ducks and geese as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own, parrots and songbirds are altricial (e.g., hatchlings are fed by their parents. We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

  5. Developmental Modes and Developmental Mechanisms can Channel Brain Evolution.

    Science.gov (United States)

    Charvet, Christine J; Striedter, Georg F

    2011-01-01

    Anseriform birds (ducks and geese) as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own), parrots and songbirds are altricial (e.g., hatchlings are fed by their parents). We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

  6. Brain mechanisms of altered conscious states during epileptic seizures.

    Science.gov (United States)

    Cavanna, Andrea Eugenio; Monaco, Francesco

    2009-05-01

    Impaired consciousness has long been considered the hallmark of epileptic seizures. Both generalized seizures and complex partial seizures are characterized by a multifaceted spectrum of altered conscious states, in terms of the general level of awareness and the subjective contents of consciousness. Complete loss of consciousness occurs when epileptic activity involves both cortical and subcortical structures, as in tonic-clonic seizures and absence seizures. Medial temporal lobe discharges can selectively impair experience in complex partial seizures (with affected responsiveness) and certain simple partial seizures (with unaffected responsiveness). Electrical stimulation of temporal lobe structures has been shown to evoke similar subjective experiences. Findings from neurophysiological and brain-imaging studies in epilepsy have now demonstrated that involvement of the bilateral thalamus and upper brainstem leads to selective impairment of frontoparietal association cortices and midline 'default mode' networks, which results in ictal loss of consciousness. The spread of epileptic discharges from the medial temporal lobe to the same subcortical structures can ultimately cause impairment in the level of consciousness in the late ictal and immediate postictal phase of complex partial seizures. This paper reviews novel insights into the brain mechanisms that underlie alterations of consciousness during epileptic seizures and the implications for clinical practice in terms of diagnosis and management.

  7. Brain mechanisms for simple perception and bistable perception.

    Science.gov (United States)

    Wang, Megan; Arteaga, Daniel; He, Biyu J

    2013-08-27

    When faced with ambiguous sensory inputs, subjective perception alternates between the different interpretations in a stochastic manner. Such multistable perception phenomena have intrigued scientists and laymen alike for over a century. Despite rigorous investigations, the underlying mechanisms of multistable perception remain elusive. Recent studies using multivariate pattern analysis revealed that activity patterns in posterior visual areas correlate with fluctuating percepts. However, increasing evidence suggests that vision--and perception at large--is an active inferential process involving hierarchical brain systems. We applied searchlight multivariate pattern analysis to functional magnetic resonance imaging signals across the human brain to decode perceptual content during bistable perception and simple unambiguous perception. Although perceptually reflective activity patterns during simple perception localized predominantly to posterior visual regions, bistable perception involved additionally many higher-order frontoparietal and temporal regions. Moreover, compared with simple perception, both top-down and bottom-up influences were dramatically enhanced during bistable perception. We further studied the intermittent presentation of ambiguous images--a condition that is known to elicit perceptual memory. Compared with continuous presentation, intermittent presentation recruited even more higher-order regions and was accompanied by further strengthened top-down influences but relatively weakened bottom-up influences. Taken together, these results strongly support an active top-down inferential process in perception.

  8. Natural Defense Mechanisms of the Human Brain against Chronic Ischemia

    Directory of Open Access Journals (Sweden)

    A. V. Sergeev

    2015-01-01

    Full Text Available Objective: to study the structural bases of natural defense mechanisms of the human brain against chronic ischemia. Materials and methods. To accomplish this, histological, immunohistochemical (NSE, calbindin, NPY, p38 and morphometric examinations of intraoperative biopsy specimens were performed to determine the reorganization of excitatory and inhibitory neurons in the ischemic penumbra of the temporal cerebral cortex (CC. Morphometric analysis was made using the specially developed algorithms to verify neurons and their elements in the ImageJ 1.46 program. Results. The reduction in the total numerical density of neurons and synapses in chronic ischemia was ascertained to be accompanied by the compensatorily enhanced expression of NSE, calbindin, p38, and NPY in the remaining CC neurons. There were signs of hypertrophy of inhibitory CC interneurons and growth of their processes. In consequence, the impact of inhibitory CC interneurons on excitatory neurons was likely to enhance. Conclusion. In chronic ischemia, the human brain is anticipated to respond to damage to some cells via compensatory excitatory and inhibitory neuronal reorganization directed towards its natural defense against excitatory damage and towards better conditions for compensatory recovery of the structure and function of CC. 

  9. A Scalable Communication Mechanism in Service Emergence Based on Bio-network

    Institute of Scientific and Technical Information of China (English)

    SUN Hong-bin; DING Yong-sheng

    2008-01-01

    A scalable communication mechanism is proposed for service emergence based on bio-network. Service emergence is a novel model inspired by the characteristics of emergence and self-evolution in biological neuroendocrine and ininlune system,emergent conununication means a group conununication of mobile bio-entities. A series of protocol and algorithm are presented within frequently bioentities migration and failure,it includes distribution and parailelization of message propagation method,a token-ring protocol that considerably improves the performance of emergence,and failure detection mechanisms.Experiment results show the desired capability via the proposed solution.

  10. Gut to Brain Dysbiosis: Mechanisms Linking Western Diet Consumption, the Microbiome, and Cognitive Impairment

    Science.gov (United States)

    Noble, Emily E.; Hsu, Ted M.; Kanoski, Scott E.

    2017-01-01

    Consumption of a Western Diet (WD) that is high in saturated fat and added sugars negatively impacts cognitive function, particularly mnemonic processes that rely on the integrity of the hippocampus. Emerging evidence suggests that the gut microbiome influences cognitive function via the gut-brain axis, and that WD factors significantly alter the proportions of commensal bacteria in the gastrointestinal tract. Here we review mechanisms through which consuming a WD negatively impacts neurocognitive function, with a particular focus on recent evidence linking the gut microbiome with dietary- and metabolic-associated hippocampal impairment. We highlight evidence linking gut bacteria to altered intestinal permeability and blood brain barrier integrity, thus making the brain more vulnerable to the influx of deleterious substances from the circulation. WD consumption also increases production of endotoxin by commensal bacteria, which may promote neuroinflammation and cognitive dysfunction. Recent findings also show that diet-induced alterations in gut microbiota impair peripheral insulin sensitivity, which is associated with hippocampal neuronal derrangements and associated mnemonic deficits. In some cases treatment with specific probiotics or prebiotics can prevent or reverse some of the deleterious impact of WD consumption on neuropsychological outcomes, indicating that targeting the microbiome may be a successful strategy for combating dietary- and metabolic-associated cognitive impairment. PMID:28194099

  11. Androgen modulation of social decision making mechanisms in the brain: an integrative and embodied perspective

    Directory of Open Access Journals (Sweden)

    Rui F Oliveira

    2014-07-01

    Full Text Available Apart from their role in reproduction androgens also respond to social challenges and this response has been seen as a way to regulate the expression of behaviour according to the perceived social environment (Challenge hypothesis, Wingfield et al. 1990. This hypothesis implies that social decision-making mechanisms localized in the central nervous system (CNS are open to the influence of peripheral hormones that ultimately are under the control of the CNS through the hypothalamic-pituitary-gonadal axis. Therefore, two puzzling questions emerge at two different levels of biological analysis: (1 Why does the brain, which perceives the social environment and regulates androgen production in the gonad, need feedback information from the gonad to adjust its social decision-making processes? (2 How does the brain regulate gonadal androgen responses to social challenges and how do these feedback into the brain? In this paper, we will address these two questions using the integrative approach proposed by Niko Tinbergen, who proposed that a full understanding of behaviour requires its analysis at both proximate (physiology, ontogeny and ultimate (ecology, evolution levels.

  12. Electric power emergency management mechanism considering the access of new energy and renewable energy

    Science.gov (United States)

    Zhang, Baoqun; Ma, Longfei; Gong, Cheng; Jiao, Ran; Shi, Rui; Chi, Zhongjun; Ding, Yifeng

    2017-01-01

    Scholars at home and abroad have had a thorough research about the theory system and the frame of emergency management on the background of traditional grid, but for the improvement of the emergency mechanism when new energy and renewable energy access the grid, more work should be done. This paper will summarize the predecessors' work on emergency management, discuss the impact of emergency management while new energy and renewable energy access the grid and some suggestions are given.

  13. Invasion mechanisms among emerging food-borne protozoan parasites.

    Science.gov (United States)

    Yoshida, Nobuko; Tyler, Kevin M; Llewellyn, Martin S

    2011-10-01

    Food-borne parasitic diseases, many known to be more prevalent in poor countries with deficient sanitary conditions, are becoming common worldwide. Among the emerging protozoan parasites, the most prominent is Trypanosoma cruzi, rarely reported in the past to be transmitted by the oral route but currently responsible for frequent outbreaks of acute cases of Chagas disease contracted orally and characterized by high mortality. Several other food-borne protozoans considered emerging include the apicomplexans Toxoplasma gondii and Cryptosporidium, as well as Giardia and Entamoeba histolytica. Here, the interactions of these protozoans with the mucosal epithelia of the host are discussed.

  14. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

    NARCIS (Netherlands)

    Griep, L.M.; Wolbers, F.; Wagenaar, de B.; Braak, ter P.M.; Weksler, B.B.; Romero, A.; Couraud, P.O.; Vermes, I.; Meer, van der A.D.; Berg, van den A.

    2013-01-01

    The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understo

  15. Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms

    OpenAIRE

    2016-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2), and cardiac and psychiatric diseases. Their role as risk factors for incident ...

  16. Emerging Security Mechanisms for Medical Cyber Physical Systems.

    Science.gov (United States)

    Kocabas, Ovunc; Soyata, Tolga; Aktas, Mehmet K

    2016-01-01

    The following decade will witness a surge in remote health-monitoring systems that are based on body-worn monitoring devices. These Medical Cyber Physical Systems (MCPS) will be capable of transmitting the acquired data to a private or public cloud for storage and processing. Machine learning algorithms running in the cloud and processing this data can provide decision support to healthcare professionals. There is no doubt that the security and privacy of the medical data is one of the most important concerns in designing an MCPS. In this paper, we depict the general architecture of an MCPS consisting of four layers: data acquisition, data aggregation, cloud processing, and action. Due to the differences in hardware and communication capabilities of each layer, different encryption schemes must be used to guarantee data privacy within that layer. We survey conventional and emerging encryption schemes based on their ability to provide secure storage, data sharing, and secure computation. Our detailed experimental evaluation of each scheme shows that while the emerging encryption schemes enable exciting new features such as secure sharing and secure computation, they introduce several orders-of-magnitude computational and storage overhead. We conclude our paper by outlining future research directions to improve the usability of the emerging encryption schemes in an MCPS.

  17. Fracture mechanics of concrete: Will applications start to emerge?

    NARCIS (Netherlands)

    Van Mier, J.G.M.

    1995-01-01

    Fracture mechanics of concrete has developed into an active field of research in the past decades. It promises a rational solution technique to structural problems in reinforced concrete in the limit state. Numerical tools have been developed on the basis of fracture mechanics theories. The question

  18. The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries.

    Science.gov (United States)

    Chang, Lee C; Raty, Sally R; Ortiz, Jaime; Bailard, Neil S; Mathew, Sanjay J

    2013-06-01

    Traditionally, the use of ketamine for patients with traumatic brain injuries is contraindicated due to the concern of increasing intracranial pressure (ICP). These concerns, however, originated from early studies and case reports that were inadequately controlled and designed. Recently, the concern of using ketamine in these patients has been challenged by a number of published studies demonstrating that the use of ketamine was safe in these patients. This article reviews the current literature in regards to using ketamine in patients with traumatic brain injuries in different clinical settings associated with anesthesia, as well as reviews the potential mechanisms underlying the neuroprotective effects of ketamine. Studies examining the use of ketamine for induction, maintenance, and sedation in patients with TBI have had promising results. The use of ketamine in a controlled ventilation setting and in combination with other sedative agents has demonstrated no increase in ICP. The role of ketamine as a neuroprotective agent in humans remains inconclusive and adequately powered; randomized controlled trials performed in patients undergoing surgery for traumatic brain injury are necessary.

  19. Mortality and blood pressure in emergency patients with traumatic brain injury: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Pizza-Restrepo, María Juliana

    2016-10-01

    Full Text Available Introduction: Blood pressure is of special relevance in patients with traumatic brain injury (TBI at admission to emergency services, since it is the basis of cerebral perfusion pressure. The purpose of this research was to estimate the association between blood pressure values measured on admission and hospital mortality in patients with TBI. Methods: Retrospective cohort study in patients older than 18 years admitted with TBI to Hospital Pablo Tobón Uribe, in Medellín (Colombia between January 2012 and January 2014. A multivariate logistic regression model was performed to estimate the independent effect of blood pressure values on mortality. Results: 582 patients with a median age of 36 years (IQR = 25-59 77.1 % of them males (n = 449 were evaluated. Mortality according to categories of systolic blood pressure at admission (150 mmHg was as follows: 34.6 % (18/52, 13.3 % (56/421 and 29.4 % (32/109, respectively. Univariate analysis showed that blood pressure less than 100 or greater than 150 mm Hg were associated with hospital mortality, but that association lost magnitude and statistical significance (OR = 1.81; 95 % CI = 0.94-3.48 and OR = 1.91; 95 % CI = 0.86-4.54, respectively after adjustment by Glasgow coma scale, oxygen saturation and cerebral edema. Conclusions: We did not demonstrate a statistically significant association between blood pressure values at admission to the emergency service and mortality in patients with TBI.

  20. The emergence of mind and brain: an evolutionary, computational, and philosophical approach.

    Science.gov (United States)

    Mainzer, Klaus

    2008-01-01

    Modern philosophy of mind cannot be understood without recent developments in computer science, artificial intelligence (AI), robotics, neuroscience, biology, linguistics, and psychology. Classical philosophy of formal languages as well as symbolic AI assume that all kinds of knowledge must explicitly be represented by formal or programming languages. This assumption is limited by recent insights into the biology of evolution and developmental psychology of the human organism. Most of our knowledge is implicit and unconscious. It is not formally represented, but embodied knowledge, which is learnt by doing and understood by bodily interacting with changing environments. That is true not only for low-level skills, but even for high-level domains of categorization, language, and abstract thinking. The embodied mind is considered an emergent capacity of the brain as a self-organizing complex system. Actually, self-organization has been a successful strategy of evolution to handle the increasing complexity of the world. Genetic programs are not sufficient and cannot prepare the organism for all kinds of complex situations in the future. Self-organization and emergence are fundamental concepts in the theory of complex dynamical systems. They are also applied in organic computing as a recent research field of computer science. Therefore, cognitive science, AI, and robotics try to model the embodied mind in an artificial evolution. The paper analyzes these approaches in the interdisciplinary framework of complex dynamical systems and discusses their philosophical impact.

  1. Blast and the Consequences on Traumatic Brain Injury-Multiscale Mechanical Modeling of Brain

    Science.gov (United States)

    2011-02-17

    brain and spinal cord injury, is the largest contributor to a poor neurological outcome in survivors of brain and spinal cord trauma. Microscale...anatomical features of a 50th percentile male head, including the brain, falx and tentorium, cerebral spinal fluid (CSF), duramater, piamater, facial...discretized finite elements. (b) Sections of the head model; the right half of the head model is shown with the brain, the meningeal layers (dura

  2. Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis

    Science.gov (United States)

    Weng, Shinuo; Shao, Yue; Chen, Weiqiang; Fu, Jianping

    2016-09-01

    Mechanical homeostasis--a fundamental process by which cells maintain stable states under environmental perturbations--is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs). Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths through either relaxation or reinforcement. Pharmacological perturbations of the cytoskeleton and molecularly modulated integrin catch-slip bonds biased the rheostasis and induced non-homeostasis of FAs, but not of cytoskeleton tension, suggesting a unique sensitivity of FAs in regulating homeostasis. Theoretical modelling revealed myosin-mediated cytoskeleton contractility and catch-slip-bond-like behaviours in FAs and the cytoskeleton as sufficient and necessary mechanisms for quantitatively recapitulating mechanosensitive rheostasis. Our findings highlight the previously underappreciated physical nature of the mechanical homeostasis of cells.

  3. Theory of brain function, quantum mechanics and superstrings

    CERN Document Server

    Nanopoulos, Dimitri V

    1995-01-01

    Recent developments/efforts to understand aspects of the brain function at the {\\em sub-neural} level are discussed. MicroTubules (MTs) participate in a wide variety of dynamical processes in the cell especially in bioinformation processes such as learning and memory, by possessing a well-known binary error-correcting code with 64 words. In fact, MTs and DNA/RNA are unique cell structures that possess a code system. It seems that the MTs' code system is strongly related to a kind of ``Mental Code" in the following sense. The MTs' periodic paracrystalline structure make them able to support a superposition of coherent quantum states, as it has been recently conjectured by Hameroff and Penrose, representing an external or mental order, for sufficient time needed for efficient quantum computing. Then the quantum superposition collapses spontaneously/dynamically through a new, string-derived mechanism for collapse proposed recently by Ellis, Mavromatos, and myself. At the moment of collapse, organized quantum exo...

  4. Brain Mechanisms of Social Threat Effects on Working Memory.

    Science.gov (United States)

    van Ast, V A; Spicer, J; Smith, E E; Schmer-Galunder, S; Liberzon, I; Abelson, J L; Wager, T D

    2016-02-01

    Social threat can have adverse effects on cognitive performance, but the brain mechanisms underlying its effects are poorly understood. We investigated the effects of social evaluative threat on working memory (WM), a core component of many important cognitive capabilities. Social threat impaired WM performance during an N-back task and produced widespread reductions in activation in lateral prefrontal cortex and intraparietal sulcus (IPS), among other regions. In addition, activity in frontal and parietal regions predicted WM performance, and mediation analyses identified regions in the bilateral IPS that mediated the performance-impairing effects of social threat. Social threat also decreased connectivity between the IPS and dorsolateral prefrontal cortex, while increasing connectivity between the IPS and the ventromedial prefrontal cortex, a region strongly implicated in the generation of autonomic and emotional responses. Finally, cortisol response to the stressor did not mediate WM impairment but was rather associated with protective effects. These results provide a basis for understanding interactions between social and cognitive processes at a neural systems level.

  5. How Does Quantum Uncertainty Emerge from Deterministic Bohmian Mechanics?

    Science.gov (United States)

    Solé, A.; Oriols, X.; Marian, D.; Zanghì, N.

    2016-10-01

    Bohmian mechanics is a theory that provides a consistent explanation of quantum phenomena in terms of point particles whose motion is guided by the wave function. In this theory, the state of a system of particles is defined by the actual positions of the particles and the wave function of the system; and the state of the system evolves deterministically. Thus, the Bohmian state can be compared with the state in classical mechanics, which is given by the positions and momenta of all the particles, and which also evolves deterministically. However, while in classical mechanics it is usually taken for granted and considered unproblematic that the state is, at least in principle, measurable, this is not the case in Bohmian mechanics. Due to the linearity of the quantum dynamical laws, one essential component of the Bohmian state, the wave function, is not directly measurable. Moreover, it turns out that the measurement of the other component of the state — the positions of the particles — must be mediated by the wave function; a fact that in turn implies that the positions of the particles, though measurable, are constrained by absolute uncertainty. This is the key to understanding how Bohmian mechanics, despite being deterministic, can account for all quantum predictions, including quantum randomness and uncertainty.

  6. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  7. Effects of physician-based emergency medical service dispatch in severe traumatic brain injury on prehospital run time

    NARCIS (Netherlands)

    Franschman, G.; Verburg, N.; Brens-Heldens, V.; Andriessen, T. M. J. C.; Van der Naalt, J.; Peerdeman, S. M.; Hoogerwerf, N.; Greuters, S.; Schober, P.; Vos, P. E.; Christiaans, H. M. T.; Boer, C.; Valk, J.P.

    2012-01-01

    Introduction: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch o

  8. Effects of physician-based emergency medical service dispatch in severe traumatic brain injury on prehospital run time

    NARCIS (Netherlands)

    Franschman, G.; Verburg, N.; Brens-Heldens, V.; Andriessen, T.M.J.C.; Naalt, J. van der; Peerdeman, S.M.; Valk, J.P.M. van der; Hoogerwerf, N.; Greuters, S.; Schober, P.; Vos, P.E.; Christiaans, H.M.; Boer, C.

    2012-01-01

    INTRODUCTION: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch o

  9. Physician-based emergency medical service deployment characteristics in severe traumatic brain injury : A Dutch multicenter study

    NARCIS (Netherlands)

    Franschman, G.; Andriessen, T. M. J. C.; Boer, C.; Van der Naalt, J.; Horn, J.; Haitsma, I.; Vos, P. E.

    2013-01-01

    Introduction: Prehospital guidelines advise advanced life support in all patients with severe traumatic brain injury (TBI). In the Netherlands, it is recommended that prehospital advanced life support is particularly provided by a physician-based helicopter emergency medical service (P-HEMS) in addi

  10. Parsing the Behavioral and Brain Mechanisms of Third-Party Punishment

    Science.gov (United States)

    Bonnie, Richard J.; Hoffman, Morris B.; Shen, Francis X.; Simons, Kenneth W.

    2016-01-01

    The evolved capacity for third-party punishment is considered crucial to the emergence and maintenance of elaborate human social organization and is central to the modern provision of fairness and justice within society. Although it is well established that the mental state of the offender and the severity of the harm he caused are the two primary predictors of punishment decisions, the precise cognitive and brain mechanisms by which these distinct components are evaluated and integrated into a punishment decision are poorly understood. Using fMRI, here we implement a novel experimental design to functionally dissociate the mechanisms underlying evaluation, integration, and decision that were conflated in previous studies of third-party punishment. Behaviorally, the punishment decision is primarily defined by a superadditive interaction between harm and mental state, with subjects weighing the interaction factor more than the single factors of harm and mental state. On a neural level, evaluation of harms engaged brain areas associated with affective and somatosensory processing, whereas mental state evaluation primarily recruited circuitry involved in mentalization. Harm and mental state evaluations are integrated in medial prefrontal and posterior cingulate structures, with the amygdala acting as a pivotal hub of the interaction between harm and mental state. This integrated information is used by the right dorsolateral prefrontal cortex at the time of the decision to assign an appropriate punishment through a distributed coding system. Together, these findings provide a blueprint of the brain mechanisms by which neutral third parties render punishment decisions. SIGNIFICANCE STATEMENT Punishment undergirds large-scale cooperation and helps dispense criminal justice. Yet it is currently unknown precisely how people assess the mental states of offenders, evaluate the harms they caused, and integrate those two components into a single punishment decision. Using a

  11. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

    Science.gov (United States)

    Rogers, G B; Keating, D J; Young, R L; Wong, M-L; Licinio, J; Wesselingh, S

    2016-01-01

    The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies. PMID:27090305

  12. Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Ricardo M. Santos

    2012-01-01

    Full Text Available During the last decades nitric oxide (•NO has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain. •NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how •NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamics in vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological •NO concentration and what constitutes a pathological one and how is •NO concentration regulated. The ambient •NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of •NO synthesis, but the inactivation pathways of •NO has been almost completely ignored. We have recently addressed these issues in vivo on basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement •NO concentration dynamics in the brain.

  13. Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Sylvia Wagner

    Full Text Available BACKGROUND: The blood-brain barrier (BBB represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. CONCLUSIONS/SIGNIFICANCE: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

  14. Metazoan Hsp70-based protein disaggregases: Emergence and mechanisms

    Directory of Open Access Journals (Sweden)

    Nadinath Bandara Nillegoda

    2015-10-01

    Full Text Available Proteotoxic stresses and ageing cause breakdown of cellular protein homeostasis, allowing misfolded proteins to form aggregates, which dedicated molecular machines have evolved to solubilize. In bacteria, fungi, protozoa and plants protein disaggregation involves an Hsp70-J-protein chaperone system, which loads and activates a powerful AAA+ ATPase (Hsp100 disaggregase onto protein aggregate substrates. Metazoans lack cytosolic and nuclear Hsp100 disaggregases but still eliminate protein aggregates. This longstanding puzzle of protein quality control is now resolved. Robust protein disaggregation activity recently shown for the metazoan Hsp70-based disaggregases relies instead on a crucial cooperation between two J-protein classes and interaction with the Hsp110 co-chaperone. An expanding multiplicity of Hsp70 and J-protein family members in metazoan cells facilitates different configurations of this Hsp70-based disaggregase allowing unprecedented versatility and specificity in protein disaggregation. Here we review the architecture, operation and adaptability of the emerging metazoan disaggregation system and discuss how this evolved.

  15. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

    Institute of Scientific and Technical Information of China (English)

    Justin; D; Glenn; Katharine; A; Whartenby

    2014-01-01

    Mesenchymal stem cells(MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

  16. Experimental research of mechanical behavior of porcine brain tissue under rotational shear stress.

    Science.gov (United States)

    Li, Gang; Zhang, Jianhua; Wang, Kan; Wang, Mingyu; Gao, Changqing; Ma, Chao

    2016-04-01

    The objective of this paper is to investigate mechanical behavior of porcine brain tissue with a series of rotational shear stress control experiments. To this end, several experiments including stress sweep tests, frequency sweep tests and quasi-static creep tests were designed and conducted with a standard rheometer (HAAKE RheoStress6000). The effects of the loading stress rates to mechanical properties of brain tissue were also studied in stress sweep tests. The results of stress sweep tests performed on the same brain showed that brain tissue had an obvious regional inhomogeneity and the mechanical damage occurred at the rotational shear stress of 10-15Pa. The experimental data from three different loading stress rates demonstrated that the mechanical behavior of porcine brain tissue was loading stress rate dependent. With the decrease of loading stress rate, a stiffer mechanical characteristic of brain tissue was observed and the occurrence of mechanical damage can be delayed to a higher stress. From the results of frequency sweep tests we found that brain tissue had almost completely elastic properties at high frequency area. The nonlinear creep response under the rotational shear stress of 1, 3, 5, 7 and 9Pa was shown in results of creep tests. A new nonlinear viscoelastic solid model was proposed for creep tests and matched well with the test data. Considering the regional differences, loading stress rates and test conditions effects, loss tangent tan δ in porcine brain tissue showed a high uniformity of 0.25-0.45.

  17. Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Seyed

    2014-01-01

    Full Text Available The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2, a natural occurring styryl-lactone. Therefore, it includes (i the source of GTN and other metabolites; (ii isolation, purification, and (iii the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.

  18. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...

  19. The mechanical activation of mTOR signaling: an emerging role for late endosome/lysosomal targeting.

    Science.gov (United States)

    Jacobs, Brittany L; Goodman, Craig A; Hornberger, Troy A

    2014-02-01

    It is well recognized that mechanical signals play a critical role in the regulation of skeletal muscle mass, and the maintenance of muscle mass is essential for mobility, disease prevention and quality of life. Furthermore, over the last 15 years it has become established that signaling through a protein kinase called the mammalian (or mechanistic) target of rapamycin (mTOR) is essential for mechanically-induced changes in protein synthesis and muscle mass, however, the mechanism(s) via which mechanical stimuli regulate mTOR signaling have not been defined. Nonetheless, advancements are being made, and an emerging body of evidence suggests that the late endosome/lysosomal (LEL) system might play a key role in this process. Therefore, the purpose of this review is to summarize this body of evidence. Specifically, we will first explain why the Ras homologue enriched in brain (Rheb) and phosphatidic acid (PA) are considered to be direct activators of mTOR signaling. We will then describe the process of endocytosis and its involvement in the formation of LEL structures, as well as the evidence which indicates that mTOR and its direct activators (Rheb and PA) are all enriched at the LEL. Finally, we will summarize the evidence that has implicated the LEL in the regulation of mTOR by various growth regulatory inputs such as amino acids, growth factors and mechanical stimuli.

  20. Shifting gears: seeking new approaches for mind/brain mechanisms.

    Science.gov (United States)

    Gazzaniga, Michael S

    2013-01-01

    Using an autobiographical approach, I review several animal and human split-brain studies that have led me to change my long-term view on how best to understand mind/brain interactions. Overall, the view is consistent with the idea that complex neural systems, like other complex information processing systems, are highly modular. At the same time, how the modules come to interact and produce unitary goals is unknown. Here, I review the importance of self-cueing in that process of producing unitary goals from disparate functions. The role of self-cueing is demonstrably evident in the human neurologic patient and especially in patients with hemispheric disconnection. When viewed in the context of modularity, it may provide insights into how a highly parallel and distributed brain locally coordinates its activities to produce an apparent unitary output. Capturing and understanding how this is achieved will require shifting gears away from standard linear models and adopting a more dynamical systems view of brain function.

  1. Is the World Local or Nonlocal? Towards an Emergent Quantum Mechanics in the 21st Century

    CERN Document Server

    Walleczek, Jan

    2016-01-01

    What defines an emergent quantum mechanics (EmQM)? Can new insight be advanced into the nature of quantum nonlocality by seeking new links between quantum and emergent phenomena as described by self-organization, complexity, or emergence theory? Could the development of a future EmQM lead to a unified, relational image of the cosmos? One key motivation for adopting the concept of emergence in relation to quantum theory concerns the persistent failure in standard physics to unify the two pillars in the foundations of physics: quantum theory and general relativity theory (GRT). The total contradiction in the foundational, metaphysical assumptions that define orthodox quantum theory versus GRT might render inter-theoretic unification impossible. On the one hand, indeterminism and non-causality define orthodox quantum mechanics, and, on the other hand, GRT is governed by causality and determinism. How could these two metaphysically-contradictory theories ever be reconciled? The present work argues that metaphysic...

  2. The Affective Brain : Novel insights into the biological mechanisms of motivation and emotion

    NARCIS (Netherlands)

    Schutter, D.J.L.G.

    2004-01-01

    Affective neuroscience is a new emerging doctrine in the brain sciences, which studies the neurobiological correlates of motivation and emotion. The research reported in this thesis starts with discussing empirical studies on the lateralized involvement of the prefrontal cortex in affective processi

  3. Evolving the Language-Ready Brain and the Social Mechanisms that Support Language

    Science.gov (United States)

    Arbib, Michael A.

    2009-01-01

    We first review the mirror-system hypothesis on the evolution of the language-ready brain, stressing the important role of imitation and protosign in providing the scaffolding for protospeech. We then assess the role of social interaction and non-specific knowledge of language in the emergence of new sign languages in deaf communities (focusing on…

  4. Mechanical response of infant brain to manually inflicted shaking.

    Science.gov (United States)

    Couper, Z; Albermani, F

    2010-01-01

    Shaken baby syndrome (SBS) is a contentious issue on both biomechanical and medical fronts, primarily due to a lack of understanding of the loading-injury relationship of infant shaking and the parameters that are deterministic to its nature. In order to address this lack, a finite element (FE) representation of a three month infant head was developed to apply kinematics derived from physical testing with an anthropomorphic infant surrogate. The FE mesh was derived from a three-dimensional geometric basis, allowing for mesh size grading in regions of high importance, and future patient-specific adaptation. Cerebrospinal fluid (CSF) was represented through static pressure equilibration in combination with a locally based squeezing resistance. The results of the simulation indicate that anteroposterior shaking will lead to specific patterns of brain matter motion, increased likelihood of focal axonal injury at contact locations and deep brain structures, and a capacity for the development of subdural hematomas (SDH) due to rupture of central bridging veins.

  5. Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

    DEFF Research Database (Denmark)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré;

    2015-01-01

    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research...... volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy....

  6. Brain mechanisms for representing what another person sees.

    Science.gov (United States)

    Heyda, Ratha D; Green, Steven R; Vander Wyk, Brent C; Morris, James P; Pelphrey, Kevin A

    2010-04-01

    We used functional magnetic resonance imaging (fMRI) and a naturalistic joint attention scenario to evaluate two, alternative hypotheses concerning the social brain. The first, Content Specific Attribution hypothesis, was that core regions previously identified as being involved in social cognition also participate in representing the contents of another mind. The second, Dual Role hypothesis, was that extrastriate, category-specific visual regions respond to a visible stimulus of a specific category and to the same stimulus occluded, but when it appears to be the focus of another person's visual attention. Participants viewed category-specific stimuli (Place and Body images) to localize the extrastriate body area (EBA) and parahippocampal place area (PPA). Then, they observed a computerized character viewing each stimulus category, occluded from the participant's view. In support of the Content Specific Attribution hypothesis, whole-brain analyses revealed that viewing someone else looking at an occluded picture of a body activated brain regions previously associated with components of social cognition more than viewing someone else looking at an occluded picture of a place. Counter to the Dual Role hypothesis, functional region of interest (ROI) analyses revealed that the EBA and PPA were not clearly involved in representing what the character was seeing.

  7. Insect brains use image interpolation mechanisms to recognise rotated objects.

    Directory of Open Access Journals (Sweden)

    Adrian G Dyer

    Full Text Available Recognising complex three-dimensional objects presents significant challenges to visual systems when these objects are rotated in depth. The image processing requirements for reliable individual recognition under these circumstances are computationally intensive since local features and their spatial relationships may significantly change as an object is rotated in the horizontal plane. Visual experience is known to be important in primate brains learning to recognise rotated objects, but currently it is unknown how animals with comparatively simple brains deal with the problem of reliably recognising objects when seen from different viewpoints. We show that the miniature brain of honeybees initially demonstrate a low tolerance for novel views of complex shapes (e.g. human faces, but can learn to recognise novel views of stimuli by interpolating between or 'averaging' views they have experienced. The finding that visual experience is also important for bees has important implications for understanding how three dimensional biologically relevant objects like flowers are recognised in complex environments, and for how machine vision might be taught to solve related visual problems.

  8. [Molecular-cellular and hormonal mechanisms of induced brain tolerance of extreme factors].

    Science.gov (United States)

    Samoĭlov, M O; Rybnikova, E A

    2012-01-01

    This review includes results of own studies and literature data on the topical problem of neurobiology and medicine: discovery of the mechanisms of increased brain resistance to extreme exposures. The emphasis is made on the molecular-cellular and hormonal mechanisms of hypoxic preconditioning-induced brain tolerance to injurious hypoxia, psychoemotional and traumatic stress. A role of basic hormonal and intracellular cascade pro-adaptive processes mediating the neuroprotective action of hypoxic preconditioning is reviewed. A dynamics of the mechanisms of development of induced susceptible brain areas (hippocampus, neocortex) tolerance which includes phases of induction, transformation and expression, is presented. New data on preconditioning-induced cross-tolerance providing increased brain resistance not only to hypoxia but also to other stresses are reported. For the first time neuroprotective effects of hypoxic postconditioning are described.

  9. A Thoracic Mechanism of Mild Traumatic Brain Injury Due to Blast Pressure Waves

    CERN Document Server

    Courtney, Amy; 10.1016/j.mehy.2008.08.015

    2008-01-01

    The mechanisms by which blast pressure waves cause mild to moderate traumatic brain injury (mTBI) are an open question. Possibilities include acceleration of the head, direct passage of the blast wave via the cranium, and propagation of the blast wave to the brain via a thoracic mechanism. The hypothesis that the blast pressure wave reaches the brain via a thoracic mechanism is considered in light of ballistic and blast pressure wave research. Ballistic pressure waves, caused by penetrating ballistic projectiles or ballistic impacts to body armor, can only reach the brain via an internal mechanism and have been shown to cause cerebral effects. Similar effects have been documented when a blast pressure wave has been applied to the whole body or focused on the thorax in animal models. While vagotomy reduces apnea and bradycardia due to ballistic or blast pressure waves, it does not eliminate neural damage in the brain, suggesting that the pressure wave directly affects the brain cells via a thoracic mechanism. ...

  10. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    Directory of Open Access Journals (Sweden)

    Sarah Kathleen Bourne

    2012-06-01

    Full Text Available Deep brain stimulation (DBS has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD, which is characterized by recurrent unwanted thoughts or ideas (obsessions and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions. Abnormal activity in cortico-striato-thalamo-cortical (CSTC circuits including the orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mediodorsal thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule, ventral capsule/ventral striatum, ventral caudate nucleus, subthalamic nucleus, nucleus accumbens, and the inferior thalamic peduncle have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  11. Fuel reduction at a Spanish heathland by prescribed fire and mechanical shredding: effects on seedling emergence.

    Science.gov (United States)

    Fernández, Cristina; Vega, José A; Fonturbel, Teresa

    2013-11-15

    Traditional heathland burning has declined in Spain, leading to fuel accumulation and fuel reduction treatments have become common for severe wildfire hazard reduction. These methods need to maintain the botanical composition of those shrub communities. Prescribed fire has been widely used in the past, but we need to compare mechanical fuel reduction with prescribed fire because it is easier and safer to carry out in a wide range of weather conditions. This information could be particularly useful in flammable ecosystems all over the world where traditional anthropogenic burning has declined. In this study, we compared the effects of prescribed burning and mechanical shredding on the seedling emergence and its relation to the mature vegetation in a fire-prone heathland dominated by Erica australis L. and Pterospartum tridentatum (L.) Willk., in Galicia (NW Spain). We combined a greenhouse experiment with periodic field inventories of seedling emergence. In the greenhouse study, the seedling emergence was significantly higher in the soil samples after burning (383 seedlings m(-2)) than in samples before burning (242 seedlings m(-2)). In contrast, there was no significant difference in seedling density before and after mechanical shredding (243 compared with 261 seedlings m(-2)). Also, the number of seedlings that emerged after burning was significantly higher than that emerged after mechanical shredding. The maximum temperatures at the soil organic layer surface during burning were significantly and positively related to the density of Halimium lasianthum ssp. alyssoides and P. tridentatum seedlings. In the field study, the observed seedling density was very low both after prescribed burning and mechanical shredding. There was a high degree of similarity between emerged seedlings and mature vegetation in both the treated and in the untreated soils, which was probably a consequence of the dominance of resprouting species. Some consequences for the management of

  12. Intravenous versus inhalational techniques for rapid emergence from anaesthesia in patients undergoing brain tumour surgery: A Cochrane systematic review

    Directory of Open Access Journals (Sweden)

    Hemanshu Prabhakar

    2017-01-01

    Full Text Available Background: Early and rapid emergence from anaesthesia is desirable for most neurosurgical patients. With the availability of newer intravenous and inhalational anaesthetic agents, all of which have inherent advantages and disadvantages, we remain uncertain as to which technique may result in more rapid early recovery from anaesthesia. The objective of this review was to assess the effects of intravenous versus inhalational techniques for rapid emergence from anaesthesia in patients undergoing brain tumour surgery. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 6 in The Cochrane Library, MEDLINE via Ovid SP (1966 to June 2014 and EMBASE via Ovid SP (1980 to June 2014. We also searched specific websites, such as www.indmed.nic.in, www.cochrane-sadcct.org and www.clinicaltrials.gov (October 2014. We included randomised controlled trials (RCTs that compared the use of intravenous anaesthetic agents such as propofol and thiopentone with inhalational anaesthetic agents such as isoflurane and sevoflurane for maintenance of general anaesthesia during brain tumour surgery. Primary outcomes were emergence from anaesthesia (assessed by time to follow verbal commands, in minutes and adverse events during emergence, such as haemodynamic changes, agitation, desaturation, muscle weakness, nausea and vomiting, shivering and pain. Secondary outcomes were time to eye opening, recovery from anaesthesia using the Aldrete or modified Aldrete score (i.e., time to attain score ≥9, in minutes, opioid consumption, brain relaxation (as assessed by the surgeon on a 4- or 5-point scale and complications of anaesthetic techniques, such as intraoperative haemodynamic instability in terms of hypotension or hypertension (mmHg, increased or decreased heart rate (beats/min and brain swelling. We used standardised methods in conducting the systematic review, as described by the Cochrane Handbook for Systematic Reviews of

  13. Brain illness and creativity: mechanisms and treatment risks.

    Science.gov (United States)

    Flaherty, Alice W

    2011-03-01

    Brain diseases and their treatment may help or hurt creativity in ways that shape quality of life. Increased creative drive is associated with bipolar disorder, depression, psychosis, temporal lobe epilepsy, frontotemporal dementia, Parkinson disease treatments, and autism. Creativity depends on goal-driven approach motivation from midbrain dopaminergic systems. Fear-driven avoidance motivation is of less aid to creativity. When serotonin and norepinephrine lower motivation and flexible behaviour, they can inhibit creativity. Hemispheric lateralization and frontotemporal connections must interact to create new ideas and conceptual schemes. The right brain and temporal lobe contribute skill in novelty detection, while the left brain and frontal lobe foster approach motivation and more easily generate new patterns of action from the novel perceptions. Genes and phenotypes that increase plasticity and creativity in tolerant environments with relaxed selection pressure may confer risk in rigorous environments. Few papers substantively address this important but fraught topic. Antidepressants (ADs) that inhibit fear-driven motivation, such as selective serotonin reuptake inhibitors, sometimes inhibit goal-oriented motivation as well. ADs that boost goal-directed motivation, such as bupropion, may remediate this effect. Benzodiazepines and alcohol may be counterproductive. Although dopaminergic agonists sometimes stimulate creativity, their doing so may inappropriately disinhibit behaviour. Dopamine antagonists may suppress creative motivation; lithium and anticonvulsant mood stabilizers may do so less. Physical exercise and REM sleep may help creativity. Art therapy and psychotherapy are not well studied. Preserving creative motivation can help creativity and other aspects of well-being in all patients, not just artists or researchers.

  14. Dissociable brain mechanisms for processing social exclusion and rule violation.

    Science.gov (United States)

    Bolling, Danielle Z; Pitskel, Naomi B; Deen, Ben; Crowley, Michael J; McPartland, James C; Mayes, Linda C; Pelphrey, Kevin A

    2011-02-01

    Social exclusion inherently involves an element of expectancy violation, in that we expect other people to follow the unwritten rule to include us in social interactions. In this functional magnetic resonance imaging (fMRI) study, we employed a unique modification of an interactive virtual ball-tossing game called "Cyberball" (Williams et al., 2000) and a novel paradigm called "Cybershape," in which rules are broken in the absence of social exclusion, to dissociate brain regions that process social exclusion from rule violations more generally. Our Cyberball game employed an alternating block design and removed evoked responses to events when the participant was throwing the ball in inclusion to make this condition comparable to exclusion, where participants did not throw. With these modifications, we replicated prior findings of ventral anterior cingulate cortex (vACC), insula, and posterior cingulate cortex activity evoked by social exclusion relative to inclusion. We also identified exclusion-evoked activity in the hippocampi, left ventrolateral prefrontal cortex, and left middle temporal gyrus. Comparing social exclusion and rule violation revealed a functional dissociation in the active neural systems as well as differential functional connectivity with vACC. Some overlap was observed in regions differentially modulated by social exclusion and rule violation, including the vACC and lateral parietal cortex. These overlapping brain regions showed different activation during social exclusion compared to rule violation, each relative to fair play. Comparing activation patterns to social exclusion and rule violation allowed for the dissociation of brain regions involved in the experience of exclusion versus expectancy violation.

  15. Age-related hearing loss: ear and brain mechanisms.

    Science.gov (United States)

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  16. Emerging interpretations of quantum mechanics and recent progress in quantum measurement

    Science.gov (United States)

    Clarke, M. L.

    2014-01-01

    The focus of this paper is to provide a brief discussion on the quantum measurement process, by reviewing select examples highlighting recent progress towards its understanding. The areas explored include an outline of the measurement problem, the standard interpretation of quantum mechanics, quantum to classical transition, types of measurement (including weak and projective measurements) and newly emerging interpretations of quantum mechanics (decoherence theory, objective reality, quantum Darwinism and quantum Bayesianism).

  17. Skull Flexure from Blast Waves: A Mechanism for Brain Injury with Implications for Helmet Design

    Energy Technology Data Exchange (ETDEWEB)

    Moss, W C; King, M J; Blackman, E G

    2009-04-30

    Traumatic brain injury [TBI] has become a signature injury of current military conflicts, with debilitating, costly, and long-lasting effects. Although mechanisms by which head impacts cause TBI have been well-researched, the mechanisms by which blasts cause TBI are not understood. From numerical hydrodynamic simulations, we have discovered that non-lethal blasts can induce sufficient skull flexure to generate potentially damaging loads in the brain, even without a head impact. The possibility that this mechanism may contribute to TBI has implications for injury diagnosis and armor design.

  18. Set up national emergency-response mechanism to scientifically cope with natural disasters

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The establishment of a national emergency management mechanism will enable China to promptly respond to and scientifically cope with natural disasters. This is a lesson we draw from the 2008 winter storms," notes a panel of the CAS Academic Divisions, China's top advisory body in science and technology in a recent proposal forwarded to State policy-makers.

  19. Emerging subspecialties in neurology: deep brain stimulation and electrical neuro-network modulation.

    Science.gov (United States)

    Hassan, Anhar; Okun, Michael S

    2013-01-29

    Deep brain stimulation (DBS) is a surgical therapy that involves the delivery of an electrical current to one or more brain targets. This technology has been rapidly expanding to address movement, neuropsychiatric, and other disorders. The evolution of DBS has created a niche for neurologists, both in the operating room and in the clinic. Since DBS is not always deep, not always brain, and not always simply stimulation, a more accurate term for this field may be electrical neuro-network modulation (ENM). Fellowships will likely in future years evolve their scope to include other technologies, and other nervous system regions beyond typical DBS therapy.

  20. Emerging Techniques in Brain Tumor Imaging: What Radiologists Need to Know

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Minjae; Kim, Ho Sung [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505 (Korea, Republic of)

    2016-11-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response.

  1. Emerging techniques in brain tumor imaging: What radiologists need to know

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Jae; Kim, Ho Sung [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2016-09-15

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response.

  2. Multisensory brain mechanisms of bodily self-consciousness.

    Science.gov (United States)

    Blanke, Olaf

    2012-07-18

    Recent research has linked bodily self-consciousness to the processing and integration of multisensory bodily signals in temporoparietal, premotor, posterior parietal and extrastriate cortices. Studies in which subjects receive ambiguous multisensory information about the location and appearance of their own body have shown that these brain areas reflect the conscious experience of identifying with the body (self-identification (also known as body-ownership)), the experience of where 'I' am in space (self-location) and the experience of the position from where 'I' perceive the world (first-person perspective). Along with phenomena of altered states of self-consciousness in neurological patients and electrophysiological data from non-human primates, these findings may form the basis for a neurobiological model of bodily self-consciousness.

  3. Human Brain Networks: Spiking Neuron Models, Multistability, Synchronization, Thermodynamics, Maximum Entropy Production, and Anesthetic Cascade Mechanisms

    Directory of Open Access Journals (Sweden)

    Wassim M. Haddad

    2014-07-01

    theoretical foundation for general anesthesia using the network properties of the brain. Finally, we present some key emergent properties from the fields of thermodynamics and electromagnetic field theory to qualitatively explain the underlying neuronal mechanisms of action for anesthesia and consciousness.

  4. Knowing When to Stop: The Brain Mechanisms of Chasing Losses

    DEFF Research Database (Denmark)

    Campbell-Meiklejohn, Daniel; Woolrich, Mark; Passingham, Dick;

    2008-01-01

    Background Continued gambling to recover previous losses (“loss-chasing”) is central to pathological gambling. However, very little is known about the neural mechanisms that mediate this behavior.MethodsWe used functional magnetic resonance imaging (fMRI) to examine neural activity while healthy ...... in pathological gambling might involve a failure to appropriately balance activity within neural systems coding conflicting motivational states. Similar mechanisms might underlie the loss-of-control over appetitive behaviors in other impulse control disorders....

  5. Mechanisms linking brain insulin resistance to Alzheimer's disease

    OpenAIRE

    Maria Niures P.S. Matioli; Ricardo Nitrini

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dy...

  6. [Metallothionein-I/II in brain injury repair mechanism and its application in forensic medicine].

    Science.gov (United States)

    Li, Dong; Li, Ru-bo; Lin, Ju-li

    2013-10-01

    Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.

  7. Intracranial mechanisms for preserving brain blood flow in health and disease.

    Science.gov (United States)

    McBryde, F D; Malpas, S C; Paton, J F R

    2017-01-01

    The brain is an exceptionally energetically demanding organ with little metabolic reserve, and multiple systems operate to protect and preserve the brain blood supply. But how does the brain sense its own perfusion? In this review, we discuss how the brain may harness the cardiovascular system to counter threats to cerebral perfusion sensed via intracranial pressure (ICP), cerebral oxygenation and ischaemia. Since the work of Cushing over 100 years ago, the existence of brain baroreceptors capable of eliciting increases in sympathetic outflow and blood pressure has been hypothesized. In the clinic, this response has generally been thought to occur only in extremis, to perfuse the severely ischaemic brain as cerebral autoregulation fails. We review evidence that pressor responses may also occur with smaller, physiologically relevant increases in ICP. The incoming brain oxygen supply is closely monitored by the carotid chemoreceptors; however, hypoxia and other markers of ischaemia are also sensed intrinsically by astrocytes or other support cells within brain tissue itself and elicit reactive hyperaemia. Recent studies suggest that astrocytic oxygen signalling within the brainstem may directly affect sympathetic nerve activity and blood pressure. We speculate that local cerebral oxygen tension is a major determinant of the mean level of arterial pressure and discuss recent evidence that this may be the case. We conclude that intrinsic intra- and extra-cranial mechanisms sense and integrate information about hypoxia/ischaemia and ICP and play a major role in determining the long-term level of sympathetic outflow and arterial pressure, to optimize cerebral perfusion.

  8. A Principle for Describing and Verifying Brain Mechanisms Using Ongoing Activity

    Science.gov (United States)

    Eriksson, David

    2017-01-01

    Not even the most informed scientist can setup a theory that takes all brain signals into account. A neuron not only receives neuronal short range and long range input from all over the brain but a neuron also receives input from the extracellular space, astrocytes and vasculature. Given this complexity, how does one describe and verify a typical brain mechanism in vivo? Common to most described mechanisms is that one focuses on how one specific input signal gives rise to the activity in a population of neurons. This can be an input from a brain area, a population of neurons or a specific cell type. All remaining inputs originating from all over the brain are lumped together into one background input. The division into two inputs is attractive since it can be used to quantify the relative importance of either input. Here we have chosen to extract the specific and the background input by means of recording and inhibiting the specific input. We summarize what it takes to estimate the two inputs on a single trial level. The inhibition should not only be strong but also fast and the specific input measurement has to be tailor-made to the inhibition. In essence, we suggest ways to control electrophysiological experiments in vivo. By applying those controls it may become possible to describe and verify many brain mechanisms, and it may also allow the study of the integration of spontaneous and ongoing activity, which in turn governs cognition and behavior. PMID:28174523

  9. The mechanisms of regional branching: An investigation of the emerging fuel cell industry

    DEFF Research Database (Denmark)

    Tanner, Anne Nygaard

    ?regional branching?. What is still lacking, however, is a more thorough understanding of the mechanisms through which regional branching operates: firm diversification, spinoffs, labor mobility, and social networking. This paper analyzes which mechanisms dominate the current regional branching process......The growth of evolutionary thinking in economic geography has brought about the proposition that new industries are place dependent and tend to develop in regions where the pre-existing industry is technologically related to the knowledge base of the new industry, a phenomena that is termed...... of the emerging fuel cell (FC) industry and the degree to which the underlying logic of these mechanisms is technologically related. It is concluded that the actors currently dominating the emerging FC industry are either large incumbent multinational enterprises (MNEs) or smaller dedicated FC system developers...

  10. TBI ADAPTER: traumatic brain injury assessment diagnosis advocacy prevention and treatment from the emergency room--a prospective observational study.

    Science.gov (United States)

    Ganti, Latha; Daneshvar, Yasamin; Bodhit, Aakash; Ayala, Sarah; Patel, Pratik S; Lottenberg, Lawrence L; York, Donna; Counsell, Colleen; Peters, Keith R

    2015-04-01

    There is no standard treatment algorithm for patients who present to the emergency department (ED) with acute traumatic brain injury (TBI). This is in part because of the heterogeneity of the injury pattern and the patient profile, and the lack of evidence-based guidelines, especially for mild TBI in adults. As TBI is seen more and more frequently in the ED, a standardized assessment would be beneficial in terms of efficiency. The authors present their ED approach to mild TBI evaluation in the ED, along with results to date. These data represent a prospective observational cohort study, where each patient provided individual, written informed consent.

  11. A mechanical model predicts morphological abnormalities in the developing human brain

    Science.gov (United States)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  12. The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Borisova, Ekaterina; Abakumov, Maxim; Gorin, Dmitry; Avramov, Latchezar; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Serov, Alexander; Pavlov, Alexey; Zinchenko, Ekaterina; Lychagov, Vlad; Navolokin, Nikita; Shirokov, Alexander; Maslyakova, Galina; Zhu, Dan; Luo, Qingming; Chekhonin, Vladimir; Tuchin, Valery; Kurths, Jürgen

    2016-01-01

    In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health. PMID:27378933

  13. Emerging role of functional brain MRI in low-grade glioma surgery

    DEFF Research Database (Denmark)

    Friismose, Ancuta; Traise, Peter; Markovic, Ljubo

    Learning objectives 1. To describe the use of functional MRI (fMRI) in cranial surgery planning for patients with low-grade gliomas (LGG). 2. To show the increasing importance of fMRI in the clinical setting. Background LGG include brain tumors classified by the World Health Organization as grade I...... be used to map eloquent cortex areas, thus minimizing postoperative deficits and improving surgical performance. Findings and procedure details Patients diagnosed with low-grade gliomas located in eloquent brain areas undergo fMRI prior to surgery. The exams are performed on a 3T MR system (Achieva TX....... Language comprehension and visual tasks can be added to visualize Wernicke’s area or the visual cortex. Diffusion tensor imaging (DTI) is used to map nerve tract course relative to the tumour. Conclusion FMRI has proven its clinical utility in locating eloquent brain areas with relation to tumor site...

  14. Circulating endothelial progenitor cells in traumatic brain injury: an emerging therapeutic target?

    Institute of Scientific and Technical Information of China (English)

    WEI Hui-jie; JIANG Rong-cai; LIU Li; ZHANG Jian-ning

    2010-01-01

    Traumatic brain injury (TBI) is a major cause ofmortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations.In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBl in the future.

  15. Targeting Epigenetic Mechanisms in Pain Due to Trauma and Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2015-10-01

    Pain  ( nociceptive ) sensitization was followed using the von Frey method. Those measures were continued until  the resolution of sensitization. We...AWARD NUMBER: W81XWH-14-1-0579 TITLE: Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) PRINCIPAL...SUBTITLE Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0579 5c

  16. How neurons make meaning: brain mechanisms for embodied and abstract-symbolic semantics.

    Science.gov (United States)

    Pulvermüller, Friedemann

    2013-09-01

    How brain structures and neuronal circuits mechanistically underpin symbolic meaning has recently been elucidated by neuroimaging, neuropsychological, and neurocomputational research. Modality-specific 'embodied' mechanisms anchored in sensorimotor systems appear to be relevant, as are 'disembodied' mechanisms in multimodal areas. In this paper, four semantic mechanisms are proposed and spelt out at the level of neuronal circuits: referential semantics, which establishes links between symbols and the objects and actions they are used to speak about; combinatorial semantics, which enables the learning of symbolic meaning from context; emotional-affective semantics, which establishes links between signs and internal states of the body; and abstraction mechanisms for generalizing over a range of instances of semantic meaning. Referential, combinatorial, emotional-affective, and abstract semantics are complementary mechanisms, each necessary for processing meaning in mind and brain.

  17. Working toward exposure thresholds for blast-induced traumatic brain injury: thoracic and acceleration mechanisms

    CERN Document Server

    Courtney, Michael; 10.1016/j.neuroimage.2010.05.025

    2011-01-01

    Research in blast-induced lung injury resulted in exposure thresholds that are useful in understanding and protecting humans from such injury. Because traumatic brain injury (TBI) due to blast exposure has become a prominent medical and military problem, similar thresholds should be identified that can put available research results in context and guide future research toward protecting warfighters as well as diagnosis and treatment. At least three mechanical mechanisms by which the blast wave may result in brain injury have been proposed - a thoracic mechanism, head acceleration and direct cranial transmission. These mechanisms need not be mutually exclusive. In this study, likely regions of interest for the first two mechanisms based on blast characteristics (positive pulse duration and peak effective overpressure) are developed using available data from blast experiments and related studies, including behind-armor blunt trauma and ballistic pressure wave studies. These related studies are appropriate to in...

  18. Mechanism Interpretation of the Biological Brain Cooling and Its Inspiration on Bionic Engineering

    Institute of Scientific and Technical Information of China (English)

    Xu Xue; Jing Liu

    2011-01-01

    The brain is one of the most important organs in a biological body which can only work in a relatively stable temperature range. However, many environmental factors in biosphere would cause cerebral temperature fluctuations. To sustain and regulate the brain temperature, many mechanisms of biological brain cooling have been evolved, including Selective Brain Cooling (SBC), cooling through surface water evaporation, respiration, behavior response and using special anatomical appendages. This article is dedicated to present a summarization and systematic interpretation on brain cooling strategies developed in animals by classifying and comparatively analyzing each typical biological brain cooling mechanism from the perspective of bio-heat transfer. Meanwhile, inspirations from such cooling in nature were proposed for developing advanced bionic engineering technologies especially with two focuses on therapeutic hypothermia and computer chip cooling areas. It is expected that many innovations can be achieved along this way to find out new cooling methodologies for a wide variety of industrial applications which will be highly efficient, energy saving, flexible or even intelligent.

  19. Mapping climatic mechanisms likely to favour the emergence of novel communities

    Science.gov (United States)

    Ordonez, Alejandro; Williams, John W.; Svenning, Jens-Christian

    2016-12-01

    Climatic conditions are changing at different rates and in different directions, potentially causing the emergence of novel species assemblages. Here we identify areas where recent (1901-2013) changes in temperature and precipitation are likely to be producing novel species assemblages through three distinct mechanisms: emergence of novel climatic combinations, rapid displacement of climatic isoclines and local divergences between temperature and precipitation vectors. Novel climates appear in the tropics, while displacement is faster at higher latitudes and divergence is high in the subtropics and mountainous regions. Globally, novel climate combinations so far are rare (3.4% of evaluated cells), mean displacement is 3.7 km decade-1 and divergence is high (>60°) for 67% of evaluated cells. Via at least one of the proposed mechanisms, novel species assemblages are likely to be forming in the North American Great Plains and temperate forests, Amazon, South American grasslands, Australia, boreal Asia and Africa. In these areas, temperature- and moisture-sensitive species may be affected by new climates emerging, differential biotic lags to rapidly changing climates or by being pulled in opposite directions along local spatial gradients. These results provide spatially explicit hypotheses about where and why novel communities are likely to emerge due to recent climate change.

  20. Windows on the brain: the emerging role of atlases and databases in neuroscience

    Science.gov (United States)

    Van Essen, David C.; VanEssen, D. C. (Principal Investigator)

    2002-01-01

    Brain atlases and associated databases have great potential as gateways for navigating, accessing, and visualizing a wide range of neuroscientific data. Recent progress towards realizing this potential includes the establishment of probabilistic atlases, surface-based atlases and associated databases, combined with improvements in visualization capabilities and internet access.

  1. Topic Repetitiveness after Traumatic Brain Injury: An Emergent, Jointly Managed Behaviour

    Science.gov (United States)

    Body, Richard; Parker, Mark

    2005-01-01

    Topic repetitiveness is a common component of pragmatic impairment and a powerful contributor to social exclusion. Despite this, description, characterization and intervention remain underdeveloped. This article explores the nature of repetitiveness in traumatic brain injury (TBI). A case study of one individual after TBI provides the basis for a…

  2. Infants' Emerging Sensitivity to Emotional Body Expressions: Insights from Asymmetrical Frontal Brain Activity

    Science.gov (United States)

    Missana, Manuela; Grossmann, Tobias

    2015-01-01

    Sensitive responding to others' emotional body expressions is an essential social skill in humans. Using event-related brain potentials, it has recently been shown that the ability to discriminate between emotional body expressions develops between 4 and 8 months of age. However, it is not clear whether the perception of emotional body expressions…

  3. Strength analysis and optimization of welding robot mechanism in emergency stop state

    Directory of Open Access Journals (Sweden)

    Zdeněk Poruba

    2016-03-01

    Full Text Available The contribution deals with the strength analysis and optimization of the welding robot mechanism in emergency stop state. The common operational positioning of the welding robot is characterized by smooth course of speeds in the time. The resulting load does not differ significantly from the static loading. However the safety requirements given by the norm require the ability of emergency stop function. Since the course of speed in time is rather steep the higher values of acceleration and thus higher excitation force is expected. The dynamical simulation performed describes the response of the robot mechanism in the form of stress course in time, quantifies the peak values of the stress caused by the dynamical component of loading and highlights the potential risks associated with this phenomenon.

  4. Emergence and resilience of cooperation in the spatial Prisoner's Dilemma via a reward mechanism

    CERN Document Server

    Jimenez, Raul; Cuesta, Jose A; Sanchez, Angel

    2007-01-01

    We study the problem of the emergence of cooperation in the spatial Prisoner's Dilemma. The pioneering work by Nowak and May showed that large initial populations of cooperators can survive and sustain cooperation in a square lattice with imitate-the-best evolutionary dynamics. We revisit this problem in a cost-benefit formulation suitable for a number of biological applications. We show that if a fixed-amount reward is established for cooperators to share, a single cooperator can invade a population of defectors and form structures that are resilient to re-invasion even if the reward mechanism is turned off. We discuss analytically the case of the invasion by a single cooperator and present agent-based simulations for small initial fractions of cooperators. Large cooperation levels, in the sustainability range, are found. In the conclusions we discuss possible applications of this model as well as its connections with other mechanisms proposed to promote the emergence of cooperation.

  5. Effect of dexmedetomidine on mechanical pain threshold and emergence agitation after laparoscopic myomectomy

    Institute of Scientific and Technical Information of China (English)

    Tao Qin; Xiao-Mei Liu

    2016-01-01

    Objective:To study the effect of dexmedetomidine on mechanical pain threshold and emergence agitation after laparoscopic myomectomy.Methods:Random number table was used to divide 82 cases of patients who received laparoscopic myomectomy in our hospital from May 2012 to October 2014 into dexmedetomidine group (Dex group) and control group (Con group), and postoperative mechanical pain threshold and emergence agitation extent were assessed.Results: 4 h, 8 h, 12 h and 24 h after operation, mechanical pain threshold of both Dex group and Con group were significantly lower than those before operation (P<0.05) and mechanical pain threshold of Dex group 4 h, 8 h, 12 h and 24 h after operation were significantly higher than those of Con group (P<0.05); both incidence and average grade of emergence agitation of Dex group were significantly lower than those of Con group (P<0.05); serum melatonin content of Dex group in recovery period were not significantly different from those in anesthesia induction period, serum melatonin content of Con group in recovery period were significantly lower than those in anesthesia induction period, and serum melatonin content of Dex group in recovery period were significantly higher than those of Con group (P<0.05); serum cortisol content of both Dex group and Con group in recovery period were significantly higher than those before anesthesia induction and cortisol content of Dex group in recovery period was significantly lower than that of Con group (P<0.05).Conclusions:Dexmedetomidine for laparoscopic myomectomy can reduce postoperative hyperalgesia and prevent emergence agitation, and it has positive clinical value.

  6. Functional complexity emerging from anatomical constraints in the brain: the significance of network modularity and rich-clubs

    Science.gov (United States)

    Zamora-López, Gorka; Chen, Yuhan; Deco, Gustavo; Kringelbach, Morten L.; Zhou, Changsong

    2016-12-01

    The large-scale structural ingredients of the brain and neural connectomes have been identified in recent years. These are, similar to the features found in many other real networks: the arrangement of brain regions into modules and the presence of highly connected regions (hubs) forming rich-clubs. Here, we examine how modules and hubs shape the collective dynamics on networks and we find that both ingredients lead to the emergence of complex dynamics. Comparing the connectomes of C. elegans, cats, macaques and humans to surrogate networks in which either modules or hubs are destroyed, we find that functional complexity always decreases in the perturbed networks. A comparison between simulated and empirically obtained resting-state functional connectivity indicates that the human brain, at rest, lies in a dynamical state that reflects the largest complexity its anatomical connectome can host. Last, we generalise the topology of neural connectomes into a new hierarchical network model that successfully combines modular organisation with rich-club forming hubs. This is achieved by centralising the cross-modular connections through a preferential attachment rule. Our network model hosts more complex dynamics than other hierarchical models widely used as benchmarks.

  7. Emerging complexity in a simple model of the mechanical behaviour of rocks

    CERN Document Server

    Amitrano, David

    2004-01-01

    We propose a mechanical model for the behaviour of rocks based on progressive damage at the elementary scale and elastic interaction. It allows us to simulate several experimental observations: mechanical behaviour ranging from brittle to ductile, fractal structure of the damage, powerlaw distribution of the damage avalanches. These macroscopic properties are not incorporated at the elementary scale, but are the results of the interaction between elements. This emerging complexity permits us to consider the strain rock process as a complex system characterized by non-linear dynamics.

  8. Brain mechanisms in religion and spirituality: An integrative predictive processing framework.

    Science.gov (United States)

    van Elk, Michiel; Aleman, André

    2017-02-01

    We present the theory of predictive processing as a unifying framework to account for the neurocognitive basis of religion and spirituality. Our model is substantiated by discussing four different brain mechanisms that play a key role in religion and spirituality: temporal brain areas are associated with religious visions and ecstatic experiences; multisensory brain areas and the default mode network are involved in self-transcendent experiences; the Theory of Mind-network is associated with prayer experiences and over attribution of intentionality; top-down mechanisms instantiated in the anterior cingulate cortex and the medial prefrontal cortex could be involved in acquiring and maintaining intuitive supernatural beliefs. We compare the predictive processing model with two-systems accounts of religion and spirituality, by highlighting the central role of prediction error monitoring. We conclude by presenting novel predictions for future research and by discussing the philosophical and theological implications of neuroscientific research on religion and spirituality.

  9. The radical-pair mechanism as a paradigm for the emerging science of quantum biology

    CERN Document Server

    Kominis, I K

    2015-01-01

    The radical-pair mechanism was introduced in the 1960's to explain anomalously large EPR and NMR signals in chemical reactions of organic molecules. It has evolved to the cornerstone of spin chemistry, the study of the effect electron and nuclear spins have on chemical reactions, with the avian magnetic compass mechanism and the photosynthetic reaction center dynamics being prominent biophysical manifestations of such effects. In recent years the radical-pair mechanism was shown to be an ideal biological system where the conceptual tools of quantum information science can be fruitfully applied. We will here review recent work making the case that the radical-pair mechanism is indeed a major driving force of the emerging field of quantum biology.

  10. Atypical Brain Mechanisms of Prediction According to Uncertainty in Autism

    Science.gov (United States)

    Thillay, Alix; Lemaire, Mathieu; Roux, Sylvie; Houy-Durand, Emmanuelle; Barthélémy, Catherine; Knight, Robert T.; Bidet-Caulet, Aurélie; Bonnet-Brilhault, Frédérique

    2016-01-01

    Resistance to change is often reported in autism and may arise from an inability to predict events in uncertain contexts. Using EEG recorded in 12 adults with autism and age-matched controls performing a visual target detection task, we characterized the influence of a certain context (targets preceded by a predictive sequence of three distinct stimuli) or an uncertain context (random targets) on behavior and electrophysiological markers of predictive processing. During an uncertain context, adults with autism were faster than controls to detect targets. They also had an enhancement in CNV amplitude preceding all random stimuli—indexing enhanced preparatory mechanisms, and an earlier N2 to targets—reflecting faster information processing—compared to controls. During a certain context, both controls and adults with autism presented an increase in P3 amplitude to predictive stimuli—indexing information encoding of the predictive sequence, an enhancement in CNV amplitude preceding predictable targets—corresponding to the deployment of preparatory mechanisms, and an earlier P3 to predictable targets—reflecting efficient prediction building and implementation. These results suggest an efficient extraction of predictive information to generate predictions in both controls and adults with autism during a certain context. However, adults with autism displayed a failure to decrease mu power during motor preparation accompanied by a reduced benefit in reaction times to predictable targets. The data reveal that patients with autism over-anticipate stimuli occurring in an uncertain context, in accord with their sense of being overwhelmed by incoming information. These results suggest that adults with autism cannot flexibly modulate cortical activity according to changing levels of uncertainty. PMID:27458337

  11. Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training

    Science.gov (United States)

    Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D.; Resnick, Neil M.

    2016-01-01

    Purpose Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Materials and Methods Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Results Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. Conclusions In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate

  12. Skull Flexure from Blast Waves: A New Mechanism for Brain Injury with Implications for Helmet Design

    CERN Document Server

    Moss, William C; Blackman, Eric G

    2008-01-01

    Traumatic brain injury [TBI] has become the signature injury of current military conflicts. The debilitating effects of TBI on society are long-lasting and costly. Although the mechanisms by which impacts cause TBI have been well researched, the mechanisms by which blasts cause TBI are not understood. Various mechanisms, including impacts caused by the blast, have been investigated, but blast-induced deformation of the skull has been neglected. Through the use of hydrodynamical numerical simulations, we have discovered that non-lethal blasts can induce sufficient flexure of the skull to generate potentially damaging loads in the brain, even if no impact occurs. This mechanism has implications for the diagnosis of TBI in soldiers and the design of protective equipment such as helmets.

  13. Development traumatic brain injury computer user interface for disaster area in Indonesia supported by emergency broadband access network.

    Science.gov (United States)

    Sutiono, Agung Budi; Suwa, Hirohiko; Ohta, Toshizumi; Arifin, Muh Zafrullah; Kitamura, Yohei; Yoshida, Kazunari; Merdika, Daduk; Qiantori, Andri; Iskandar

    2012-12-01

    Disasters bring consequences of negative impacts on the environment and human life. One of the common cause of critical condition is traumatic brain injury (TBI), namely, epidural (EDH) and subdural hematoma (SDH), due to downfall hard things during earthquake. We proposed and analyzed the user response, namely neurosurgeon, general doctor/surgeon and nurse when they interacted with TBI computer interface. The communication systems was supported by TBI web based applications using emergency broadband access network with tethered balloon and simulated in the field trial to evaluate the coverage area. The interface consisted of demography data and multi tabs for anamnesis, treatment, follow up and teleconference interfaces. The interface allows neurosurgeon, surgeon/general doctors and nurses to entry the EDH and SDH patient's data during referring them on the emergency simulation and evaluated based on time needs and their understanding. The average time needed was obtained after simulated by Lenovo T500 notebook using mouse; 8-10 min for neurosurgeons, 12-15 min for surgeons/general doctors and 15-19 min for nurses. By using Think Pad X201 Tablet, the time needed for entry data was 5-7 min for neurosurgeon, 7-10 min for surgeons/general doctors and 12-16 min for nurses. We observed that the time difference was depending on the computer type and user literacy qualification as well as their understanding on traumatic brain injury, particularly for the nurses. In conclusion, there are five data classification for simply TBI GUI, namely, 1) demography, 2) specific anamnesis for EDH and SDH, 3) treatment action and medicine of TBI, 4) follow up data display and 5) teleneurosurgery for streaming video consultation. The type of computer, particularly tablet PC was more convenient and faster for entry data, compare to that computer mouse touched pad. Emergency broadband access network using tethered balloon is possible to be employed to cover the communications systems in

  14. Research progress in mechanism of traumatic brain injury affecting speed of fracture healing

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-gang; ZHAO Guang-feng; MA Yue-feng; JIANG Guan-yu

    2007-01-01

    @@ In patients who have sustained traumatic brain injury with associated extremity fracture, there is often a clinical perception that the rate of new bone formation around the fracture site increases. 1 An overgrowth of callus is observed and ectopic ossification even occurs in the muscle,2 but the mechanism remains unclear.

  15. Action and Language Mechanisms in the Brain: Data, Models and Neuroinformatics

    DEFF Research Database (Denmark)

    Arbib, Michael A.; Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina

    2014-01-01

    We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding - separately or together - neurocomputational models and empirical...

  16. ‘Your Brain on Art’: Emergent cortical dynamics during aesthetic experiences

    Directory of Open Access Journals (Sweden)

    Kimberly eKontson

    2015-11-01

    Full Text Available The brain response to conceptual art was studied with mobile electroencephalography (EEG to examine the neural basis of aesthetic experiences. In contrast to most studies of perceptual phenomena, participants were moving and thinking freely as they viewed the exhibit The Boundary of Life is Quietly Crossed by Dario Robleto at the Menil Collection-Houston. The brain activity of over 400 subjects was recorded using dry-electrode and one reference gel-based EEG systems over a period of 3 months. Here, we report initial findings based on the reference system. EEG segments corresponding to each art piece were grouped into one of three classes (complex, moderate, and baseline based on analysis of a digital image of each piece. Time, frequency, and wavelet features extracted from EEG were used to classify patterns associated with viewing art, and ranked based on their relevance for classification. The maximum classification accuracy was 55% (chance = 33% with delta and gamma features the most relevant for classification. Functional analysis revealed a significant increase in connection strength in localized brain networks while subjects viewed the most aesthetically pleasing art compared to viewing a blank wall. The direction of signal flow showed early recruitment of broad posterior areas followed by focal anterior activation. Significant differences in the strength of connections were also observed across age and gender. This work provides evidence that EEG, deployed on freely behaving subjects, can detect selective signal flow in neural networks, identify significant differences between subject groups, and report with greater-than-chance accuracy the complexity of a subject’s visual percept of aesthetically pleasing art. Our approach, which allows acquisition of neural activity ‘in action and context’, could lead to understanding of how the brain integrates sensory input and its ongoing internal state to produce the phenomenon which we term

  17. Emergency Interventions After Severe Traumatic Brain Injury in Rats: Effect on Neuropatholgy and Functional Outcome.

    Science.gov (United States)

    1999-01-01

    brain of male Long-Evans rats (225-250 gm) via intracerebroventricular infusion. The distribution of bio-rncfosriis was detected using antibodies...Please check one: □ A. Administration /Education D B. Burns/Trauma D C. CPR D D. Cardiovascular O E. Computers/Technology O F. Ethics □ G. Immunology...therapies. Dietrich et aP reported that combination of 3 hours of moderate hypothermia with sustained administration of the glu- tamate antagonist

  18. The neural sociometer: brain mechanisms underlying state self-esteem.

    Science.gov (United States)

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  19. Management of critically ill patients receiving noninvasive and invasive mechanical ventilation in the emergency department

    Directory of Open Access Journals (Sweden)

    Rose L

    2012-03-01

    Full Text Available Louise RoseLawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, CanadaAbstract: Patients requiring noninvasive and invasive ventilation frequently present to emergency departments, and may remain for prolonged periods due to constrained critical care services. Emergency clinicians often do not receive the same education on management of mechanical ventilation or have similar exposure to these patients as do their critical care colleagues. The aim of this review was to synthesize the evidence on management of patients requiring noninvasive and invasive ventilation in the emergency department including indications, clinical applications, monitoring priorities, and potential complications. Noninvasive ventilation is recommended for patients with acute exacerbation of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. Less evidence supports its use in asthma and other causes of acute respiratory failure. Use of noninvasive ventilation in the prehospital setting is relatively new, and some evidence suggests benefit. Monitoring priorities for noninvasive ventilation include response to treatment, respiratory and hemodynamic stability, noninvasive ventilation tolerance, detection of noninvasive ventilation failure, and identification of air leaks around the interface. Application of injurious ventilation increases patient morbidity and mortality. Lung-protective ventilation with low tidal volumes based on determination of predicted body weight and control of plateau pressure has been shown to reduce mortality in patients with acute respiratory distress syndrome, and some evidence exists to suggest this strategy should be used in patients without lung injury. Monitoring of the invasively ventilated patient should focus on assessing response to mechanical ventilation and other interventions, and avoiding complications, such as ventilator-associated pneumonia. Several key aspects of management of noninvasive

  20. Plausible mechanisms for brain structural and size changes in human evolution.

    Science.gov (United States)

    Blazek, Vladimir; Brùzek, Jaroslav; Casanova, Manuel F

    2011-09-01

    Encephalization has many contexts and implications. On one hand, it is concerned with the transformation of eating habits, social relationships and communication, cognitive skills and the mind. Along with the increase in brain size on the other hand, encephalization is connected with the creation of more complex brain structures, namely in the cerebral cortex. It is imperative to inquire into the mechanisms which are linked with brain growth and to find out which of these mechanisms allow it and determine it. There exist a number of theories for understanding human brain evolution which originate from neurological sciences. These theories are the concept of radial units, minicolumns, mirror neurons, and neurocognitive networks. Over the course of evolution, it is evident that a whole range of changes have taken place in regards to heredity. These changes include new mutations of genes in the microcephalin complex, gene duplications, gene co-expression, and genomic imprinting. This complex study of the growth and reorganization of the brain and the functioning of hereditary factors and their external influences creates an opportunity to consider the implications of cultural evolution and cognitive faculties.

  1. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain.

    Science.gov (United States)

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  2. Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.

    Science.gov (United States)

    Feldstein Ewing, Sarah W; Chung, Tammy

    2013-06-01

    Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors.

  3. PREFACE: DICE 2008 - From Quantum Mechanics through Complexity to Spacetime: the role of emergent dynamical structures

    Science.gov (United States)

    Diósi, Lajos; Elze, Hans-Thomas; Fronzoni, Leone; Halliwell, Jonathan; Vitiello, Giuseppe

    2009-07-01

    Pasquini, which - with its beautiful surroundings, overlooking a piece of Tuscany's coast, and with splendid weather throughout - was conducive to the success of the meeting. The 5-day program was grouped according to the following topics: Quantum Physics and Some Important Questions it Raises Emergent Dynamics, from Quantum to Brain and Beyond Exploring Quantum Mechanics Atomistic Theories of Spacetime Quantum-Entanglement/Gravity/Cosmology A Public Roundtable Discussion formed an integral part of the program under the theme ``Dialoghi sulla complessita' - dall' atomo all' Universo'' and with the participation of physicists and philosophers: F T Arecchi (Firenze), L Fronzoni (Pisa), A M Iacono (Pisa), F Luccio (Pisa) and G Vitiello (Salerno, coordinator). This event drew a large audience, who participated in the lively discussions until late in the evening. The workshop has been organized by L Diósi (Budapest), H-T Elze (Pisa, chair), L Fronzoni (Pisa), J Halliwell (London) and G Vitiello (Salerno), with great help from our conference secretaries M Pesce-Rollins (Siena) and L Baldini (Pisa) and from our students F Caravelli and E Di Nardo, both from Pisa. Several institutions and sponsors generously supported the workshop and their representatives and, in particular, the citizens of Rosignano/Castiglioncello are deeply thanked for the help and kind hospitality: Comune di Rosignano A Nenci (Sindaco di Rosignano), S Scarpellini (Segreteria sindaco), D Del Seppia (Assessore allo Sviluppo Economico del Comune di Rosignano), A Franchi (Assessore al turismo del Comune di Rosignano/Presidente dell' associazione Armunia), A Corsini (Ufficio economato del Comune di Rosignano). REA Rosignano Energia Ambiente s.p.a. F Ghelardini (Presidente della REA), A Cecchini (Ufficio - Responsabile stampa della REA). Solvay Chimica Italia s.a. Dott S Piccoli (Responsabile Relazioni Esterne, Solvay Rosignano), G Becherucci (Comunicazione e Relazioni Esterne). Associazione Armunia M Paganelli

  4. Transport and regulation mechanism of the colloidal gold liposomes in the brain microvascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    WANG Lipeng; CHANG Yanzhong

    2015-01-01

    Objective:Blood-brain barrier is the key barrier of brain in the innate immune. It can prevent the harmful substances from the blood into the brain. In order to keep the brain in a relatively stable environment and maintain the normal function of the nervous system, it can also pump harmful substances or excess substances outside the brain selectively. Among them, brain microvascular endothelial cell tissue is a key part in the blood-brain barrier's function. The number of the patients with central nervous system ( CNS) diseases increased year by year. The therapeutic drug is usually inhibited by the blood-brain barrier and is difficult to work. Therefore, how to modify the drug and to make it easier to cross the blood brain barrier is the key point to cure CNS. At present, more than 95% research focus only on how nano drugs can enter the cell, the way and efficiency to enter the cell and the research of effect of nano drug etc. For the process of drug carrier in endocytosis, intracellular transport and release and regulation of research are rarely reported. Clathrin and P-glycoprotein are related protein in endo-cytosis and exocytosis with nano drug. Clathrin is located on the plasma membrane. It participates in endocytosis of some nutrients, and maybe the entry into the cell of some drugs. P-glycoprotein is located in the membrane of cer-ebral capillary endothelial cells. It can efflux drugs relying on ATP. Although there is a certain understanding of the cell in the inner swallow and efflux. But the process of the liposome drug is not clear. To solve the above prob-lems, using colloidal gold liposome nano materials to trace liposome's transport and regulation mechanism in brain microvascular endothelial cells, and study endocytosis, release, distribution and regulation mechanism of nano lipo-somes in brain microvascular. The solution of this problem can guide to construct reasonable drug carrier, and look forward to clarifing the molecular basis and mechanism of

  5. The Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

    Directory of Open Access Journals (Sweden)

    P. Justin eRossi

    2016-04-01

    Full Text Available This review summarizes the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized; these advances were presented at the 3rd Annual Deep Brain Stimulation Think Tank. The Think Tank’s contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

  6. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design

    Energy Technology Data Exchange (ETDEWEB)

    Moss, W C; King, M J; Blackman, E G

    2009-04-14

    Traumatic brain injury [TBI] has become a signature injury of current military conflicts. The debilitating effects of TBI are long-lasting and costly. Although the mechanisms by which impacts cause TBI have been well researched, the mechanisms by which blasts cause TBI are not understood. Various possibilities have been investigated, but blast-induced deformation of the skull has been neglected. From numerical hydrodynamic simulations, we have discovered that nonlethal blasts can induce sufficient flexure of the skull to generate potentially damaging loads in the brain, even if no impact occurs. The possibility that this mechanism may contribute to TBI has implications for the diagnosis of soldiers and the design of protective equipment such as helmets.

  7. Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.

    Science.gov (United States)

    Holmes, Jeffrey W; Laksman, Zachary; Gepstein, Lior

    2016-01-01

    Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases

  8. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

    Directory of Open Access Journals (Sweden)

    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  9. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead......Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation...... to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the brain iron homeostasis. Moreover, the uptake routes of iron and copper overlap each other which affect the interplay between the concentrations of the two metals in the brain. The divalent metal transporter-1 (DMT1...

  10. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    Science.gov (United States)

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  11. Neurotransmitter mechanisms of the action of the antihistamine dimebon on the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shadurskaya, S.K.; Khomenko, A.I.; Pereverzev, V.A.; Balakeevskii, A.I.

    1986-11-01

    To discover the possible mechanism of the stimulating effect of dimebon on the CNS, the action of the drug was studied on catecholamine concentrations and turnover and activity of forms of monoamine oxidase (MAO), differing in the substrate metabolized, in brain structures involved in the regulation of the emotional state and in the regulation of motor activity in rats. /sup 3/H-serotonin creatinine-sulfate, /sup 3/H-dopamine hydrochloride, and /sup 14/C- benzylamine hydrochloride were used as substrates. The results show that dimebon can inhibit MAO activity in the basal ganglia and other brain structures both in vitro and in vivo, and can cause changes in DA and NA metabolism and in functional activity of catecholaminergic neuronal structures of the brain.

  12. Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can Disrupt Brain Development

    Directory of Open Access Journals (Sweden)

    John W. Olney

    2013-07-01

    Full Text Available Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD, which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances. There is compelling evidence that exposure to alcohol during early embryogenesis (4th week of gestation can cause excessive death of cell populations that are essential for normal development of the face and brain. While this can explain craniofacial malformations and certain structural brain anomalies that sometimes accompany FASD, in many cases these features are absent, and the FASD syndrome manifests primarily as neurobehavioral disorders. It is not clear from the literature how alcohol causes these latter manifestations. In this review we will describe a growing body of evidence documenting that alcohol triggers widespread apoptotic death of neurons and oligodendroglia (OLs in the developing brain when administered to animals, including non-human primates, during a period equivalent to the human third trimester of gestation. This cell death reaction is associated with brain changes, including overall or regional reductions in brain mass, and long-term neurobehavioral disturbances. We will also review evidence that many drugs used in pediatric and obstetric medicine, including general anesthetics (GAs and anti-epileptics (AEDs, mimic alcohol in triggering widespread apoptotic death of neurons and OLs in the third trimester-equivalent animal brain, and that human children exposed to GAs during early infancy, or to AEDs during the third trimester of gestation, have a significantly increased incidence of FASD-like neurobehavioral disturbances. These findings provide evidence that exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. We propose that the mechanism by which

  13. The Protective Effect of Rosuvastatin on Ischemic Brain Injury and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To study the protective effect of rosuvastatin on ischemic brain injury and its mechanism,in on ischemic brain injury and its mechanism,focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery (MCA)-luminal filament technique. The cerebral blood flow was monitored with laser-Doppler flowmetry (LDF). The slices of brain tissue were stained with cresyl-violet. The cerebral e quantified with ImageJ software. The expressions of endothelial NO synthase (eNOS) and activated caspase-3 were detected with Western blot. The inducible NO were immunohistochemically observed. The results demonstrated that rosuvastatin (20 mg/kg) could remarkably decrease infarct volume and cerebral edema after MCAO ots showed that the expression of eNOS in cerebral cortex before and after ischemia was (100±43.3) %, (1668.9±112.2) % respectively (P<0.001), rosuvastatin gulated the expression of eNOS in non-ischemic cortex (P<0.001), whereas in ischemic cortex of rosuvastatin group the expression of eNOS was (1678.8±121.3) %. There was no hemic cortex, nonetheless the expression of activated caspase-3 increased after ischemia, and rosuvastatin significantly diminished it (P<0.01). Immunoaled no iNOS-positive cells in non-ischemic brain area, while in ischemic brain area the number of iNOS positive cells went up, and rosuvastatin could significantly reduced them.'s neural protection on ischemic brain injury are to enhance expression of eNOS, to inhibit expression of iNOS and activated caspase-3.mia/reperfusion; NOS; caspase-3

  14. The 3rd International Conference on Continental Earthquakes, Mechanism, Prediction, Emergency Management & Insurance

    Institute of Scientific and Technical Information of China (English)

    Dr.HuangJing

    2004-01-01

    The 3rd International Conference on Continental Earthquakes, Mechanism, Prediction, Emergency Management & Insurance (the 3rd ICCE) was held on July 9-14, 2004 in Beijing, China. The ICCE has been held every decade since it was launched over twenty years ago. The first ICCE, with the title """"International Symposium on Continental Seismicity and Earthquake Prediction""""(ISCSEP), had international sponsorship and was supported by e.g., UNESCO and hosted by the Seismological Society of China (SSC)in Beijing in 1982. In 1992 in response to the initiatives from the UN's International Decade for Natural Disaster Reduction (IDNDR),

  15. Emergent Structural Mechanisms for High-Density Collective Motion Inspired by Human Crowds

    CERN Document Server

    Bottinelli, Arianna; Silverberg, Jesse L

    2016-01-01

    Collective motion of large human crowds often depends on their density. In extreme cases like heavy metal concerts and Black Friday sales events, motion is dominated by physical interactions instead of conventional social norms. Here, we study an active matter model inspired by situations when large groups of people gather at a point of common interest. Our analysis takes an approach developed for jammed granular media and identifies Goldstone modes, soft spots, and stochastic resonance as structurally-driven mechanisms for potentially dangerous emergent collective motion.

  16. Emergent Structural Mechanisms for High-Density Collective Motion Inspired by Human Crowds

    Science.gov (United States)

    Bottinelli, Arianna; Sumpter, David T. J.; Silverberg, Jesse L.

    2016-11-01

    Collective motion of large human crowds often depends on their density. In extreme cases like heavy metal concerts and black Friday sales events, motion is dominated by physical interactions instead of conventional social norms. Here, we study an active matter model inspired by situations when large groups of people gather at a point of common interest. Our analysis takes an approach developed for jammed granular media and identifies Goldstone modes, soft spots, and stochastic resonance as structurally driven mechanisms for potentially dangerous emergent collective motion.

  17. Emergency CT brain: preliminary interpretation with a tablet device: image quality and diagnostic performance of the Apple iPad.

    LENUS (Irish Health Repository)

    Mc Laughlin, Patrick

    2012-04-01

    Tablet devices have recently been used in radiological image interpretation because they have a display resolution comparable to desktop LCD monitors. We identified a need to examine tablet display performance prior to their use in preliminary interpretation of radiological images. We compared the spatial and contrast resolution of a commercially available tablet display with a diagnostic grade 2 megapixel monochrome LCD using a contrast detail phantom. We also recorded reporting discrepancies, using the ACR RADPEER system, between preliminary interpretation of 100 emergency CT brain examinations on the tablet display and formal review on a diagnostic LCD. The iPad display performed inferiorly to the diagnostic monochrome display without the ability to zoom. When the software zoom function was enabled on the tablet device, comparable contrast detail phantom scores of 163 vs 165 points were achieved. No reporting discrepancies were encountered during the interpretation of 43 normal examinations and five cases of acute intracranial hemorrhage. There were seven RADPEER2 (understandable) misses when using the iPad display and 12 with the diagnostic LCD. Use of software zoom in the tablet device improved its contrast detail phantom score. The tablet allowed satisfactory identification of acute CT brain findings, but additional research will be required to examine the cause of "understandable" reporting discrepancies that occur when using tablet devices.

  18. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  19. Meta-Analyses of Developing Brain Function in High-Risk and Emerged Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Moon-Soo eLee

    2014-11-01

    Full Text Available Objectives: Identifying early markers of brain function among those at high risk for pediatric bipolar disorder (PBD could serve as a screening measure when children and adolescents present with sub-syndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at high risk (HR have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity towards that goal. Methods: An activation likelihood estimation meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was completed. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR and typically developing (TD groups.Results: The HR group showed significantly greater activation relative to the TD group in the right DLPFC-insular-parietal-cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC.Conclusions: The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion processing regions, such as the DLPFC, insula and parietal cortex. In contrast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process.

  20. Integrating early life experience, gene expression, brain development, and emergent phenotypes: unraveling the thread of nature via nurture.

    Science.gov (United States)

    Weaver, Ian C G

    2014-01-01

    Adaptation to environmental changes is based on the perpetual generation of new phenotypes. Modern biology has focused on the role of epigenetic mechanisms in facilitating the adaptation of organisms to changing environments through alterations in gene expression. Inherited and/or acquired epigenetic factors are relatively stable and have regulatory roles in numerous genomic activities that translate into phenotypic outcomes. Evidence that dietary and pharmacological interventions have the potential to reverse environment-induced modification of epigenetic states (e.g., early life experience, nutrition, medication, infection) has provided an additional stimulus for understanding the biological basis of individual differences in cognitive abilities and disorders of the brain. It has been suggested that accurate quantification of the relative contribution of heritable genetic and epigenetic variation is essential for understanding phenotypic divergence and adaptation in changing environments, a process requiring stable modulation of gene expression. The main challenge for epigenetics in psychology and psychiatry is to determine how experiences and environmental cues, including the nature of our nurture, influence the expression of neuronal genes to produce long-term individual differences in behavior, cognition, personality, and mental health. To this end, focusing on DNA and histone modifications and their initiators, mediators and readers may provide new inroads for understanding the molecular basis of phenotypic plasticity and disorders of the brain. In this chapter, we review recent discoveries highlighting epigenetic aspects of normal brain development and mental illness, as well as discuss some future directions in the field of behavioral epigenetics.

  1. Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies

    Directory of Open Access Journals (Sweden)

    Agnese eLupo

    2012-01-01

    Full Text Available The environment, and especially fresh water, constitutes a reactor where the evolution and the rise of new resistances occur. In rivers or streams, bacteria from different sources such as urban, industrial and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: First, the contamination of water by antibiotics or other pollutants lead to the rise of resistance due to selection processes. For instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. Moreover, further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to assess the risk of spread of antibiotic resistances via water bodies.

  2. Equilibration, thermalisation, and the emergence of statistical mechanics in closed quantum systems

    Science.gov (United States)

    Gogolin, Christian; Eisert, Jens

    2016-05-01

    We review selected advances in the theoretical understanding of complex quantum many-body systems with regard to emergent notions of quantum statistical mechanics. We cover topics such as equilibration and thermalisation in pure state statistical mechanics, the eigenstate thermalisation hypothesis, the equivalence of ensembles, non-equilibration dynamics following global and local quenches as well as ramps. We also address initial state independence, absence of thermalisation, and many-body localisation. We elucidate the role played by key concepts for these phenomena, such as Lieb-Robinson bounds, entanglement growth, typicality arguments, quantum maximum entropy principles and the generalised Gibbs ensembles, and quantum (non-)integrability. We put emphasis on rigorous approaches and present the most important results in a unified language.

  3. Equilibration, thermalisation, and the emergence of statistical mechanics in closed quantum systems.

    Science.gov (United States)

    Gogolin, Christian; Eisert, Jens

    2016-05-01

    We review selected advances in the theoretical understanding of complex quantum many-body systems with regard to emergent notions of quantum statistical mechanics. We cover topics such as equilibration and thermalisation in pure state statistical mechanics, the eigenstate thermalisation hypothesis, the equivalence of ensembles, non-equilibration dynamics following global and local quenches as well as ramps. We also address initial state independence, absence of thermalisation, and many-body localisation. We elucidate the role played by key concepts for these phenomena, such as Lieb-Robinson bounds, entanglement growth, typicality arguments, quantum maximum entropy principles and the generalised Gibbs ensembles, and quantum (non-)integrability. We put emphasis on rigorous approaches and present the most important results in a unified language.

  4. Mechanisms of brain evolution: regulation of neural progenitor cell diversity and cell cycle length.

    Science.gov (United States)

    Borrell, Victor; Calegari, Federico

    2014-09-01

    In the last few years, several studies have revisited long-held assumptions in the field of brain development and evolution providing us with a fundamentally new vision on the mechanisms controlling its size and shape, hence function. Among these studies, some described hitherto unforeseeable subtypes of neural progenitors while others reinterpreted long-known observations about their cell cycle in alternative new ways. Most remarkably, this knowledge combined has allowed the generation of mammalian model organisms in which brain size and folding has been selectively increased giving us the means to understand the mechanisms underlying the evolution of the most complex and sophisticated organ. Here we review the key findings made in this area and make a few conjectures about their evolutionary meaning including the likelihood of Martians conquering our planet.

  5. Altered brain-gut axis in autism: comorbidity or causative mechanisms?

    Science.gov (United States)

    Mayer, Emeran A; Padua, David; Tillisch, Kirsten

    2014-10-01

    The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors.

  6. Boron neutron capture therapy of brain tumors: an emerging therapeutic modality.

    Science.gov (United States)

    Barth, R F; Soloway, A H; Goodman, J H; Gahbauer, R A; Gupta, N; Blue, T E; Yang, W; Tjarks, W

    1999-03-01

    Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must be absorbed by the 10B atoms to sustain a lethal 10B (n, alpha) lithium-7 reaction. There is a growing interest in using BNCT in combination with surgery to treat patients with high-grade gliomas and possibly metastatic brain tumors. The present review covers the biological and radiobiological considerations on which BNCT is based, boron-containing low- and high-molecular weight delivery agents, neutron sources, clinical studies, and future areas of research. Two boron compounds currently are being used clinically, sodium borocaptate and boronophenylalanine, and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These are discussed, as is optimization of their delivery. Nuclear reactors currently are the only source of neutrons for BNCT, and the fission reaction within the core produces a mixture of lower energy thermal and epithermal neutrons, fast or high-energy neutrons, and gamma-rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams now are being used in the United States and Europe because of their superior tissue-penetrating properties. Currently, there are clinical trials in progress in the United States, Europe, and Japan using a combination of debulking surgery and then BNCT to treat patients with glioblastomas. The American and European studies are Phase I trials using boronophenylalanine and sodium borocaptate, respectively

  7. The emergence of grammar in a language-ready brain. Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib

    Science.gov (United States)

    Hawkins, John A.

    2016-03-01

    Arbib makes the interesting proposal [3, §1.6] that the first Homo sapiens could have been "language-ready", without possessing the kind of rich lexicon, grammar and compositional semantics that we see in the world's languages today. This early language readiness would have consisted of a set of "protolanguage" abilities, which he enumerates (1-7 in §1.6), supported by brain mechanisms unique to humans. The transition to full "language" (properties 8-11 in §1.6 and §3) would have required no changes in the genome, he argues, but could have resulted from cultural evolution plus some measure of Baldwinian evolution favoring offspring with greater linguistic skill. The full picture is set out in [1].

  8. Sphingolipids and Brain Resident Macrophages in Neuroinflammation: An Emerging Aspect of Nervous System Pathology

    Directory of Open Access Journals (Sweden)

    Emma Assi

    2013-01-01

    Full Text Available Sphingolipid metabolism is deeply regulated along the differentiation and development of the central nervous system (CNS, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system. Microglia are resident macrophages of the CNS involved in general maintenance of neural environment. Modulations in microglia phenotypes may contribute to pathogenic forms of inflammation. Since defects in macrophage/microglia activity contribute to neurodegenerative diseases, it will be essential to systematically identify the components of the microglial cell response that contribute to disease progression. In such complex processes, the sphingolipid systems have recently emerged to play important roles, thus appearing as a key new player in CNS disorders. This review provides a rationale for harnessing the sphingolipid metabolic pathway as a potential target against neuroinflammation.

  9. Vagal stimulation modulates inflammation through a ghrelin mediated mechanism in traumatic brain injury

    OpenAIRE

    Bansal, V; Ryu, SY; Lopez, N; Allexan, S; Krzyzaniak, M; Eliceiri, B; Baird, A.; Coimbra, R

    2012-01-01

    Traumatic brain injury (TBI) releases a cascade of inflammatory cytokines. Vagal nerve stimulation (VNS) and ghrelin have known anti-inflammatory effects; furthermore, ghrelin release is stimulated by acetylcholine. We hypothesized VNS decreases post-TBI inflammation through a ghrelin-mediated mechanism. TBI was created in five groups of mice: sham, TBI, TBI/ghrelin, TBI/VNS, and TBI/VNS/ghrelin receptor antagonist (GRa). Serum and tissue ghrelin, and serum TNF-αwere measured. Ghrelin increas...

  10. Shaping and reshaping the aesthetic brain: Emerging perspectives on the neurobiology of embodied aesthetics.

    Science.gov (United States)

    Kirsch, Louise P; Urgesi, Cosimo; Cross, Emily S

    2016-03-01

    Less than two decades after its inception, the burgeoning field of neuroaesthetics continues to grow in interest and momentum. Despite the biological and social importance of the human body and the attention people pay to its appearance in daily life, only recently has neuroaesthetic inquiry turned its attention to questions concerning the aesthetic appraisal of the human body. We review evidence illustrating that the complexity of aesthetic experience is reflected by dynamic interplay between brain systems involved in reward, perceptual and motor processing, with a focus on aesthetic perception involving the human body. We then evaluate work demonstrating how these systems are modulated by beholders' expertise or familiarity. Finally, we discuss seminal studies revealing the plasticity of behavioural and neural responses to beauty after perceptual and motor training. This research highlights the rich potential for neuroaesthetic inquiry to extend beyond its typical realm of the fine arts to address important questions regarding the relationship between embodiment, aesthetics and performing arts. We conclude by considering some of the criticisms and limitations of neuroaesthetics, and highlight several outstanding issues for future inquiry.

  11. Large-scale brain networks emerge from dynamic processing of musical timbre, key and rhythm.

    Science.gov (United States)

    Alluri, Vinoo; Toiviainen, Petri; Jääskeläinen, Iiro P; Glerean, Enrico; Sams, Mikko; Brattico, Elvira

    2012-02-15

    We investigated the neural underpinnings of timbral, tonal, and rhythmic features of a naturalistic musical stimulus. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while listening to a stimulus with a rich musical structure, a modern tango. We correlated temporal evolutions of timbral, tonal, and rhythmic features of the stimulus, extracted using acoustic feature extraction procedures, with the fMRI time series. Results corroborate those obtained with controlled stimuli in previous studies and highlight additional areas recruited during musical feature processing. While timbral feature processing was associated with activations in cognitive areas of the cerebellum, and sensory and default mode network cerebrocortical areas, musical pulse and tonality processing recruited cortical and subcortical cognitive, motor and emotion-related circuits. In sum, by combining neuroimaging, acoustic feature extraction and behavioral methods, we revealed the large-scale cognitive, motor and limbic brain circuitry dedicated to acoustic feature processing during listening to a naturalistic stimulus. In addition to these novel findings, our study has practical relevance as it provides a powerful means to localize neural processing of individual acoustical features, be it those of music, speech, or soundscapes, in ecological settings.

  12. The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

    Directory of Open Access Journals (Sweden)

    Y Vodovotz

    2009-01-01

    Full Text Available Traumatic injury/hemorrhagic shock (T/HS elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI. Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherentlydetrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partiallypropagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP’s.DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and nonhumanprimates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS andTBI in the near future.

  13. Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design.

    Science.gov (United States)

    Prodanov, Dimiter; Delbeke, Jean

    2016-01-01

    Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it.

  14. Brain mechanisms for emotional influences on perception and attention: what is magic and what is not.

    Science.gov (United States)

    Pourtois, Gilles; Schettino, Antonio; Vuilleumier, Patrik

    2013-03-01

    The rapid and efficient selection of emotionally salient or goal-relevant stimuli in the environment is crucial for flexible and adaptive behaviors. Converging data from neuroscience and psychology have accrued during the last decade to identify brain systems involved in emotion processing, selective attention, and their interaction, which together act to extract the emotional or motivational value of sensory events and respond appropriately. An important hub in these systems is the amygdala, which may not only monitor the emotional value of stimuli, but also readily project to several other areas and send feedback to sensory pathways (including striate and extrastriate visual cortex). This system generates saliency signals that modulate perceptual, motor, as well as memory processes, and thus in turn regulate behavior appropriately. Here, we review our current views on the function and properties of these brain systems, with an emphasis on their involvement in the rapid and/or preferential processing of threat-relevant stimuli. We suggest that emotion signals may enhance processing efficiency and competitive strength of emotionally significant events through gain control mechanisms similar to those of other (e.g. endogenous) attentional systems, but mediated by distinct neural mechanisms in amygdala and interconnected prefrontal areas. Alterations in these brain mechanisms might be associated with psychopathological conditions, such as anxiety or phobia. We conclude that attention selection and awareness are determined by multiple attention gain control systems that may operate in parallel and use different sensory cues but act on a common perceptual pathway.

  15. Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms?

    Science.gov (United States)

    Kiviniemi, Vesa; Wang, Xindi; Korhonen, Vesa; Keinänen, Tuija; Tuovinen, Timo; Autio, Joonas; LeVan, Pierre; Keilholz, Shella; Zang, Yu-Feng; Hennig, Jürgen; Nedergaard, Maiken

    2016-06-01

    The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.

  16. The impact of acute brain dysfunction in the outcomes of mechanically ventilated cancer patients.

    Directory of Open Access Journals (Sweden)

    Isabel C T Almeida

    Full Text Available INTRODUCTION: Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV cancer patients, but no studies evaluated delirium and coma (acute brain dysfunction. The present study evaluated the frequency and impact of acute brain dysfunction on mortality. METHODS: The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality. RESULTS: 170 patients were included. 73% had solid tumors, age 65 [53-72 (median, IQR 25%-75%] years. SAPS II score was 54[46-63] points and SOFA score was (7 [6-9] points. Median duration of MV was 13 (6-21 days and ICU stay was 14 (7.5-22 days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%. Survivors had more delirium/coma-free days [4(1,5-6 vs 1(0-2, p<0.001]. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality [0.771 (0.681 to 0.873, p<0.001]. CONCLUSIONS: Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.

  17. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.

    Science.gov (United States)

    Borre, Yuliya E; Moloney, Rachel D; Clarke, Gerard; Dinan, Timothy G; Cryan, John F

    2014-01-01

    There is increasing evidence that host-microbe interactions play a key role in maintaining homeostasis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition, establishing the critical importance of the bi-directional pathway of communication between the microbiota and the brain in health and disease. Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism. Bacterial colonization of the gut is central to postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Moreover, there is now expanding evidence for the view that enteric microbiota plays a role in early programming and later response to acute and chronic stress. This view is supported by studies in germ-free mice and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics. Although communication between gut microbiota and the CNS are not fully elucidated, neural, hormonal, immune and metabolic pathways have been suggested. Thus, the concept of a microbiome-brain-gut axis is emerging, suggesting microbiota-modulating strategies may be a tractable therapeutic approach for developing novel treatments for CNS disorders.

  18. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  19. Brain mechanisms for predictive control by switching internal models: implications for higher-order cognitive functions.

    Science.gov (United States)

    Imamizu, Hiroshi; Kawato, Mitsuo

    2009-07-01

    Humans can guide their actions toward the realization of their intentions. Flexible, rapid and precise realization of intentions and goals relies on the brain learning to control its actions on external objects and to predict the consequences of this control. Neural mechanisms that mimic the input-output properties of our own body and other objects can be used to support prediction and control, and such mechanisms are called internal models. We first summarize functional neuroimaging, behavioral and computational studies of the brain mechanisms related to acquisition, modular organization, and the predictive switching of internal models mainly for tool use. These mechanisms support predictive control and flexible switching of intentional actions. We then review recent studies demonstrating that internal models are crucial for the execution of not only immediate actions but also higher-order cognitive functions, including optimization of behaviors toward long-term goals, social interactions based on prediction of others' actions and mental states, and language processing. These studies suggest that a concept of internal models can consistently explain the neural mechanisms and computational principles needed for fundamental sensorimotor functions as well as higher-order cognitive functions.

  20. Deep brain stimulation mechanisms: the control of network activity via neurochemistry modulation.

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    McIntyre, Cameron C; Anderson, Ross W

    2016-10-01

    Deep brain stimulation (DBS) has revolutionized the clinical care of late-stage Parkinson's disease and shows promise for improving the treatment of intractable neuropsychiatric disorders. However, after over 25 years of clinical experience, numerous questions still remain on the neurophysiological basis for the therapeutic mechanisms of action. At their fundamental core, the general purpose of electrical stimulation therapies in the nervous system are to use the applied electric field to manipulate the opening and closing of voltage-gated sodium channels on neurons, generate stimulation induced action potentials, and subsequently, control the release of neurotransmitters in targeted pathways. Historically, DBS mechanisms research has focused on characterizing the effects of stimulation on neurons and the resulting impact on neuronal network activity. However, when electrodes are placed within the central nervous system, glia are also being directly (and indirectly) influenced by the stimulation. Mounting evidence shows that non-neuronal tissue can play an important role in modulating the neurochemistry changes induced by DBS. The goal of this review is to evaluate how DBS effects on both neuronal and non-neuronal tissue can potentially work together to suppress oscillatory activity (and/or information transfer) between brain regions. These resulting effects of ~ 100 Hz electrical stimulation help explain how DBS can disrupt pathological network activity in the brain and generate therapeutic effects in patients. Deep brain stimulation is an effective clinical technology, but detailed therapeutic mechanisms remain undefined. This review provides an overview of the leading hypotheses, which focus on stimulation-induced disruption of network oscillations and integrates possible roles for non-neuronal tissue in explaining the clinical response to therapeutic stimulation. This article is part of a special issue on Parkinson disease.

  1. A meta-analysis of brain mechanisms of placebo analgesia: consistent findings and unanswered questions.

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    Atlas, Lauren Y; Wager, Tor D

    2014-01-01

    Placebo treatments reliably reduce pain in the clinic and in the lab. Because pain is a subjective experience, it has been difficult to determine whether placebo analgesia is clinically relevant. Neuroimaging studies of placebo analgesia provide objective evidence of placebo-induced changes in brain processing and allow researchers to isolate the mechanisms underlying placebo-based pain reduction. We conducted formal meta-analyses of 25 neuroimaging studies of placebo analgesia and expectancy-based pain modulation. Results revealed that placebo effects and expectations for reduced pain elicit reliable reductions in activation during noxious stimulation in regions often associated with pain processing, including the dorsal anterior cingulate, thalamus, and insula. In addition, we observed consistent reductions during painful stimulation in the amygdala and striatum, regions implicated widely in studies of affect and valuation. This suggests that placebo effects are strongest on brain regions traditionally associated with not only pain, but also emotion and value more generally. Other brain regions showed reliable increases in activation with expectations for reduced pain. These included the prefrontal cortex (including dorsolateral, ventromedial, and orbitofrontal cortices), the midbrain surrounding the periaqueductal gray, and the rostral anterior cingulate. We discuss implications of these findings as well as how future studies can expand our understanding of the precise functional contributions of the brain systems identified here.

  2. Effect of growth hormone and melatonin on the brain: from molecular mechanisms to structural changes.

    Science.gov (United States)

    Kireev, Roman A; Cuesta, Sara; Vara, Elena; Tresguerres, Jesus A F

    2011-10-01

    Aging of the brain causes important reductions in quality of life and has wide socio-economic consequences. An increase in oxidative stress, and the associated inflammation and apoptosis, could be responsible for the pathogenesis of aging associated brain lesions. Melatonin has neuroprotective effects, by limiting the negative effects of oxygen and nitrogen free radicals. Growth hormone (GH) might exert additional neuro-protective and or neurogenic effects on the brain. The molecular mechanisms of the protective effects of GH and melatonin on the aging brain have been investigated in young and old Wistar rats. A reduction in the total number of neurons in the hilus of the dentate gyrus was evident at 24 months of age and was associated with a significant increase in inflammation markers as well as in pro-apoptotic parameters, confirming the role of apoptosis in its reduction. Melatonin treatment was able to enhance neurogenesis in old rats without modification of the total number of neurons, whereas GH treatment increased the total number of neurons without enhancing neurogenesis. Both GH and melatonin were able to reduce inflammation and apoptosis in the hippocampus. In conclusion, neuroprotective effects demonstrated by GH and melatonin in the hippocampus were exerted by decreasing inflammation and apoptosis.

  3. Mechanical Characterization of Brain Tissue in Compression at Dynamic Strain Rates

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.01.022

    2013-01-01

    Traumatic brain injury (TBI) occurs when local mechanical load exceeds certain tolerance levels for brain tissue. Extensive research has been done previously for brain matter experiencing compression at quasistatic loading; however, limited data is available to model TBI under dynamic impact conditions. In this research, an experimental setup was developed to perform unconfined compression tests and stress relaxation tests at strain rates < 90/s. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the compressive nominal stress at 30% strain was 8.83 +/- 1.94, 12.8 +/- 3.10 and 16.0 +/- 1.41 kPa (mean +/- SD) at strain rates of 30, 60 and 90/s, respectively. Relaxation tests were also conducted at 10%-50% strain with the average rise time of 10 ms, which can be used to derive time dependent parameters. Numerical simulations were performed using one-term Ogden model with initial shear modulus mu_0 = 6.06 +/- 1.44, 9.44 +/-...

  4. Imaging social motivation: distinct brain mechanisms drive effort production during collaboration versus competition.

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    Le Bouc, Raphaël; Pessiglione, Mathias

    2013-10-01

    Collaborative and competitive interactions have been investigated extensively so as to understand how the brain makes choices in the context of strategic games, yet such interactions are known to influence a more basic dimension of behavior: the energy invested in the task. The cognitive mechanisms that motivate effort production in social situations remain poorly understood, and their neural counterparts have not been explored so far. A dominant idea is that the motivation provided by the social context is reducible to the personal utility of effort production, which decreases in collaboration and increases in competition. Using functional magnetic resonance imaging, we scanned human participants while they produced a physical effort in a collaborative or competitive context. We found that motivation was indeed primarily driven by personal utility, which was reflected in brain regions devoted to reward processing (the ventral basal ganglia). However, subjects who departed from utility maximization, working more in collaborative situations, showed greater functional activation and anatomical volume in a brain region implicated previously in social cognition (the temporoparietal junction). Therefore, this region might mediate a purely pro-social motivation to produce greater effort in the context of collaboration. More generally, our findings suggest that the individual propensity to invest energy in collaborative work might have an identifiable counterpart in the brain functional architecture.

  5. Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

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    Dallakyan Sargis

    2008-08-01

    Full Text Available Abstract Background Gram-negative bacteria use periplasmic-binding proteins (bPBP to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo and closed (ligated conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding. Results We use a distance constraint model (DCM to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network. Conclusion Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect

  6. Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance.

    Science.gov (United States)

    Hawkins, Nichola J; Cools, Hans J; Sierotzki, Helge; Shaw, Michael W; Knogge, Wolfgang; Kelly, Steven L; Kelly, Diane E; Fraaije, Bart A

    2014-07-01

    Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

  7. Emerging of massive gauge particles in inhomogeneous local gauge transformations: replacement of Higgs mechanism

    CERN Document Server

    Struckmeier, Jürgen

    2013-01-01

    A generalized theory of gauge transformations is presented on the basis of the covariant Hamiltonian formalism of field theory, for which the covariant canonical field equations are equivalent to the Euler-Lagrange field equations. Similar to the canonical transformation theory of point dynamics, the canonical transformation rules for fields are derived from generating functions. Thus---in contrast to the usual Lagrangian description---the covariant canonical transformation formalism automatically ensures the mappings to preserve the action principle, and hence to be {\\em physical}. On that basis, we work out the theory of inhomogeneous local gauge transformations that generalizes the conventional local SU(N) gauge transformation theory. It is shown that massive gauge bosons naturally emerge in this description, which thus could supersede the Higgs mechanism.

  8. PREFACE: EmerQuM 11: Emergent Quantum Mechanics 2011 (Heinz von Foerster Congress)

    Science.gov (United States)

    Grössing, Gerhard

    2012-05-01

    These proceedings comprise the plenary lectures and poster contributions of the 'Heinz von Foerster Conference 2011' on Emergent Quantum Mechanics (EmerQuM11), which was held at the University of Vienna, 11-13 November 2011. With the 5th International Heinz von Foerster Conference convened at the occasion of von Foerster's 100th birthday, the organizers opted for a twin conference to take place at the Large and Small Ceremonial Halls of the University's main building, respectively. The overall topic was chosen as 'Self-Organization and Emergence', a topic to which von Foerster was an early contributor. While the first conference ('Self-Organization and Emergence in Nature and Society') addressed a more general audience, the second one ('Emergent Quantum Mechanics') was intended as a specialist meeting with a contemporary topic that could both serve as an illustration of von Foerster's intellectual heritage and, more generally, point towards future directions in physics. We thus intended to bring together many of those physicists who are interested in or are working on attempts to understand quantum mechanics as emerging from a suitable classical (or, more generally, deeper level) physics. EmerQuM11 was organized by the Austrian Institute for Nonlinear Studies (AINS), with essential support from the Wiener Institute for Social Science Documentation and Methodology (WISDOM), the Department of Contemporary History at the University of Vienna, and the Heinz von Foerster-Gesellschaft. There were a number of individuals who contributed to the smooth course of our meeting and whom I would like to sincerely thank: Christian Bischof, Thomas Elze, Marianne Ertl, Gertrud Hafner, Werner Korn, Angelika Krawanja, Florian Krug and his team, Sonja Lang, Albert Müller, Ilse Müller, Irene Müller, Karl Müller, Armin Reautschnig, Marion Schirrmacher, Anton Staudinger, Roman Zlabinger, and, last but not least, my AINS colleagues Siegfried Fussy, Herbert Schwabl and Johannes Mesa

  9. Exploring uncoupling proteins and antioxidant mechanisms under acute cold exposure in brains of fish.

    Directory of Open Access Journals (Sweden)

    Yung-Che Tseng

    Full Text Available Exposure to fluctuating temperatures accelerates the mitochondrial respiration and increases the formation of mitochondrial reactive oxygen species (ROS in ectothermic vertebrates including fish. To date, little is known on potential oxidative damage and on protective antioxidative defense mechanisms in the brain of fish under cold shock. In this study, the concentration of cellular protein carbonyls in brain was significantly increased by 38% within 1 h after cold exposure (from 28 °C to 18 °C of zebrafish (Danio rerio. In addition, the specific activity of superoxide dismutase (SOD and the mRNA level of catalase (CAT were increased after cold exposure by about 60% (6 h and by 60%-90% (1 and 24 h, respectively, while the specific glutathione content as well as the ratio of glutathione disulfide to glutathione remained constant and at a very low level. In addition, cold exposure increased the protein level of hypoxia-inducible factor (HIF by about 50% and the mRNA level of the glucose transporter zglut3 in brain by 50%-100%. To test for an involvement of uncoupling proteins (UCPs in the cold adaptation of zebrafish, five UCP members were annotated and identified (zucp1-5. With the exception of zucp1, the mRNA levels of the other four zucps were significantly increased after cold exposure. In addition, the mRNA levels of four of the fish homologs (zppar of the peroxisome proliferator-activated receptor (PPAR were increased after cold exposure. These data suggest that PPARs and UCPs are involved in the alterations observed in zebrafish brain after exposure to 18°C. The observed stimulation of the PPAR-UCP axis may help to prevent oxidative damage and to maintain metabolic balance and cellular homeostasis in the brains of ectothermic zebrafish upon cold exposure.

  10. Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

    Science.gov (United States)

    Ueno, S.; Matsuda, T.

    1991-04-01

    We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

  11. Infusion of Emerging Technologies and New Teaching Methods into the Mechanical Engineering Curriculum at the City College of New York

    Science.gov (United States)

    Delale, Feridun; Liaw, Benjamin M.; Jiji, Latif M.; Voiculescu, Ioana; Yu, Honghui

    2011-01-01

    From October 2003 to April 2008 a systemic reform of the Mechanical Engineering program at The City College of New York was undertaken with the goal of incorporating emerging technologies (such as nanotechnology, biotechnology, Micro-Electro-Mechanical Systems (MEMS), intelligent systems) and new teaching methodologies (such as project based…

  12. Molecular Mechanisms of Allosteric Inhibition of Brain Glycogen Phosphorylase by Neurotoxic Dithiocarbamate Chemicals.

    Science.gov (United States)

    Mathieu, Cécile; Bui, Linh-Chi; Petit, Emile; Haddad, Iman; Agbulut, Onnik; Vinh, Joelle; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2017-02-03

    Dithiocarbamates (DTCs) are important industrial chemicals used extensively as pesticides and in a variety of therapeutic applications. However, they have also been associated with neurotoxic effects and in particular with the development of Parkinson-like neuropathy. Although different pathways and enzymes (such as ubiquitin ligases or the proteasome) have been identified as potential targets of DTCs in the brain, the molecular mechanisms underlying their neurotoxicity remain poorly understood. There is increasing evidence that alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. Interestingly, recent studies with N,N-diethyldithiocarbamate suggest that brain glycogen phosphorylase (bGP) and glycogen metabolism could be altered by DTCs. Here, we provide molecular and mechanistic evidence that bGP is a target of DTCs. To examine this system, we first tested thiram, a DTC pesticide known to display neurotoxic effects, observing that it can react rapidly with bGP and readily inhibits its glycogenolytic activity (kinact = 1.4 × 10(5) m(-1) s(-1)). Using cysteine chemical labeling, mass spectrometry, and site-directed mutagenesis approaches, we show that thiram (and certain of its metabolites) alters the activity of bGP through the formation of an intramolecular disulfide bond (Cys(318)-Cys(326)), known to act as a redox switch that precludes the allosteric activation of bGP by AMP. Given the key role of glycogen metabolism in brain functions and neurodegeneration, impairment of the glycogenolytic activity of bGP by DTCs such as thiram may be a new mechanism by which certain DTCs exert their neurotoxic effects.

  13. Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle.

    Directory of Open Access Journals (Sweden)

    Kenneth S Campbell

    2009-11-01

    Full Text Available Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere.

  14. Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle.

    Science.gov (United States)

    Campbell, Kenneth S

    2009-11-01

    Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere.

  15. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression.

    Science.gov (United States)

    Hashimoto, Kenji

    2013-01-01

    Epidemiological studies have demonstrated a close relationship between depression and cardiovascular disease (CVD). Although it is known that the central nervous system (CNS) contributes to this relationship, the detailed mechanisms involved in this process remain unclear. Recent studies suggest that the endoplasmic reticulum (ER) molecular chaperone sigma-1 receptor and brain-derived neurotrophic factor (BDNF) play a role in the pathophysiology of CVD and depression. Several meta-analysis studies have showed that levels of BDNF in the blood of patients with major depressive disorder (MDD) are lower than normal controls, indicating that blood BDNF might be a biomarker for depression. Furthermore, blood levels of BDNF in patients with CVD are also lower than normal controls. A recent study using conditional BDNF knock-out mice in animal models of myocardial infarction highlighted the role of CNS-mediated mechanisms in the cardioprotective effects of BDNF. In addition, a recent study shows that decreased levels of sigma-1 receptor in the mouse brain contribute to the association between heart failure and depression. Moreover, sigma-1 receptor agonists, including the endogenous neurosteroid dehydroepiandosterone (DHEA) and the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, show potent cardioprotective and antidepressive effects in rodents, via sigma-1 receptor stimulation. Interestingly, agonist activation of sigma-1 receptors increased the secretion of mature BDNF from its precursor proBDNF via chaperone activity in the ER. Given the role of ER stress in the pathophysiology of CVD and MDD, the author will discuss the potential link between sigma-1 receptors and BDNF-TrkB pathway in the pathophysiology of these two diseases. Finally, the author will make a case for potent sigma-1 receptor agonists and TrkB agonists as new potential therapeutic drugs for depressive patients with CVD.

  16. Mechanisms of team-sport-related brain injuries in children 5 to 19 years old: opportunities for prevention.

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    Michael D Cusimano

    Full Text Available BACKGROUND: There is a gap in knowledge about the mechanisms of sports-related brain injuries. The objective of this study was to determine the mechanisms of brain injuries among children and youth participating in team sports. METHODS: We conducted a retrospective case series of brain injuries suffered by children participating in team sports. The Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP database was searched for brain injury cases among 5-19 year-olds playing ice hockey, soccer, American football (football, basketball, baseball, or rugby between 1990 and 2009. Mechanisms of injury were classified as "struck by player," "struck by object," "struck by sport implement," "struck surface," and "other." A descriptive analysis was performed. RESULTS: There were 12,799 brain injuries related to six team sports (16.2% of all brain injuries registered in CHIRPP. Males represented 81% of injuries and the mean age was 13.2 years. Ice hockey accounted for the greatest number of brain injuries (44.3%, followed by soccer (19.0% and football (12.9%. In ice hockey, rugby, and basketball, striking another player was the most common injury mechanism. Football, basketball, and soccer also demonstrated high proportions of injuries due to contact with an object (e.g., post among younger players. In baseball, a common mechanism in the 5-9 year-old group was being hit with a bat as a result of standing too close to the batter (26.1% males, 28.3% females. INTERPRETATION: Many sports-related brain injury mechanisms are preventable. The results suggest that further efforts aimed at universal rule changes, safer playing environments, and the education of coaches, players, and parents should be targeted in maximizing prevention of sport-related brain injury using a multifaceted approach.

  17. Mechanism of noradrenaline-induced stimulation of Na-K ATPase activity in the rat brain: implications on REM sleep deprivation-induced increase in brain excitability.

    Science.gov (United States)

    Mallick, Birendra Nath; Singh, Sudhuman; Singh, Abhishek

    2010-03-01

    Rapid eye movement (REM) sleep is a unique phenomenon expressed in all higher forms of animals. Its quantity varies in different species and with ageing; it is also affected in several psycho-somatic disorders. Several lines of studies showed that after REM sleep loss, the levels of noradrenaline (NA) increase in the brain. The NA in the brain modulates neuronal Na-K ATPase activity, which helps maintaining the brain excitability status. The detailed mechanism of increase in NA level after REM sleep loss and the effect of NA on stimulation of Na-K ATPase in the neurons have been discussed. The findings have been reviewed and discussed with an aim to understand the role of REM sleep in maintaining brain excitability status.

  18. Mechanism of action of ulipristal acetate for emergency contraception: a systematic review

    Directory of Open Access Journals (Sweden)

    Elena eRosato

    2016-01-01

    Full Text Available SUMMARYUlipristal acetate (UPA is now recommended as first choice hormonal Emergency Contraception (EC, due to its higher efficacy and similar safety compared to Levonogestrel - EC. Even though all trials demonstrated that the first mechanism of action is inhibition of ovulation, some authors still postulate that a post fertilization effect is also possible, raising the alert on medication and fostering the ethical debate.A Medline database search was performed in order to find recent articles related to UPA’s effects on ovulation, on fallopian tube and on endometrium. We also analyzed the effects on sperm function and pregnancy. All studies conclude that UPA is effective in inhibition of ovulation even when administered shortly before LH peak. The effects on fallopian tube are unclear: according to some authors UPA inhibits ciliar beat through an agonistic effect on progesterone receptors, according to others it antagonizes the progesterone-induced ciliar beat decrease. Concerning the action on endometrium and on embryo implantation most of the studies concluded that low dose UPA used for EC has no significant effect on the decrease of endometrial thickness and on embryo’s attachment, but these results are still matter of debate. Finally recent evidence suggests that UPA modulates human sperm functions while it has no effect on established pregnancy. To date the majority of the evidence concur in excluding a post-fertilization effect of UPA, even though more studies are needed to clarify its mechanism of action.

  19. Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models.

    Science.gov (United States)

    Buendia, Izaskun; Gómez-Rangel, Vanessa; González-Lafuente, Laura; Parada, Esther; León, Rafael; Gameiro, Isabel; Michalska, Patrycja; Laudon, Moshe; Egea, Javier; López, Manuela G

    2015-12-01

    Stopping the ischemic cascade by targeting its components is a potential strategy for acute ischemic stroke treatment. During ischemia and especially over reperfusion, oxidative stress plays a major role in causing neuronal cell death. Melatonin has been previously reported to provide neuroprotective effects in in vivo models of stroke by a mechanism that implicates melatonin receptors. In this context, this study was planned to test the potential neuroprotective effects of the novel melatonin MT1/MT2 receptor agonist, Neu-P11, against brain ischemia in in vitro and in vivo models, and to elucidate its underlying mechanism of action. Neu-P11 proved to be a good antioxidant, to protect against glutamate-induced excitotoxicity and oxygen and glucose deprivation in hippocampal slices, and to reduce infarct volume in an in vivo stroke model. Regarding its mechanism of action, the protective effect of Neu-P11 was reverted by luzindole (melatonin receptor antagonist), AG490 (JAK2 inhibitor), LY294002 (PI3/AKT inhibitor) and PD98059 (MEK/ERK1/2 inhibitor). In conclusion, Neu-P11 affords neuroprotection against brain ischemia in in vitro and in vivo models by activating a pro-survival signaling pathway that involves melatonin receptors, JAK/STAT, PI3K/Akt and MEK/ERK1/2.

  20. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  1. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    Directory of Open Access Journals (Sweden)

    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  2. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  3. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A

    2015-09-01

    Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.

  4. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    Science.gov (United States)

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  5. Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

    Directory of Open Access Journals (Sweden)

    Chadi G.

    1998-01-01

    Full Text Available The actions of fibroblast growth factors (FGFs, particularly the basic form (bFGF, have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

  6. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    Science.gov (United States)

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death.

  7. Molecular mechanisms of increased cerebral vulnerability after repeated mild blast-induced traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Alaa Kamnaksh

    2014-06-01

    Full Text Available The consequences of a mild traumatic brain injury can be especially severe if it is repeated within the period of increased cerebral vulnerability (ICV that follows the initial insult. To better understand the molecular mechanisms that contribute to ICV, we exposed rats to different levels of mild blast overpressure (5 exposures; total pressure range: 15.54–19.41 psi or 107.14–133.83 kPa at a rate of 1 per 30 min, monitored select physiological parameters, and assessed behavior. Two days post-injury or sham, we determined changes in protein biomarkers related to various pathologies in behaviorally relevant brain regions and in plasma. We found that oxygen saturation and heart rate were transiently depressed following mild blast exposure and that injured rats exhibited significantly increased anxiety- and depression-related behaviors. Proteomic analyses of the selected brain regions showed evidence of substantial oxidative stress and vascular changes, altered cell adhesion, and inflammation predominantly in the prefrontal cortex. Importantly, these pathological changes as well as indications of neuronal and glial cell loss/damage were also detected in the plasma of injured rats. Our findings illustrate some of the complex molecular changes that contribute to the period of ICV in repeated mild blast-induced traumatic brain injury. Further studies are needed to determine the functional and temporal relationship between the various pathomechanisms. The validation of these and other markers can help to diagnose individuals with ICV using a minimally invasive procedure and to develop evidence-based treatments for chronic neuropsychiatric conditions.

  8. Studies of the neural mechanisms of deep brain stimulation in rodent models of Parkinson's disease.

    Science.gov (United States)

    Chang, Jing-Yu; Shi, Li-Hong; Luo, Fei; Zhang, Wang-Ming; Woodward, Donald J

    2008-01-01

    Several rodent models of deep brain stimulation (DBS) have been developed in recent years. Electrophysiological and neurochemical studies have been performed to examine the mechanisms underlying the effects of DBS. In vitro studies have provided deep insights into the role of ion channels in response to brain stimulation. In vivo studies reveal neural responses in the context of intact neural circuits. Most importantly, recording of neural responses to behaviorally effective DBS in freely moving animals provides a direct means for examining how DBS modulates the basal ganglia thalamocortical circuits and thereby improves motor function. DBS can modulate firing rate, normalize irregular burst firing patterns and reduce low frequency oscillations associated with the Parkinsonian state. Our current efforts are focused on elucidating the mechanisms by which DBS effects on neural circuitry improve motor performance. New behavioral models and improved recording techniques will aide researchers conducting future DBS studies in a variety of behavioral modalities and enable new treatment strategies to be explored, such as closed-loop stimulations based on real time computation of ensemble neural activity.

  9. Brain mechanisms that underlie the effects of motivational audiovisual stimuli on psychophysiological responses during exercise.

    Science.gov (United States)

    Bigliassi, Marcelo; Silva, Vinícius B; Karageorghis, Costas I; Bird, Jonathan M; Santos, Priscila C; Altimari, Leandro R

    2016-05-01

    Motivational audiovisual stimuli such as music and video have been widely used in the realm of exercise and sport as a means by which to increase situational motivation and enhance performance. The present study addressed the mechanisms that underlie the effects of motivational stimuli on psychophysiological responses and exercise performance. Twenty-two participants completed fatiguing isometric handgrip-squeezing tasks under two experimental conditions (motivational audiovisual condition and neutral audiovisual condition) and a control condition. Electrical activity in the brain and working muscles was analyzed by use of electroencephalography and electromyography, respectively. Participants were asked to squeeze the dynamometer maximally for 30s. A single-item motivation scale was administered after each squeeze. Results indicated that task performance and situational motivational were superior under the influence of motivational stimuli when compared to the other two conditions (~20% and ~25%, respectively). The motivational stimulus downregulated the predominance of low-frequency waves (theta) in the right frontal regions of the cortex (F8), and upregulated high-frequency waves (beta) in the central areas (C3 and C4). It is suggested that motivational sensory cues serve to readjust electrical activity in the brain; a mechanism by which the detrimental effects of fatigue on the efferent control of working muscles is ameliorated.

  10. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    Science.gov (United States)

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  11. Tinnitus Neural Mechanisms and Structural Changes in the Brain: The Contribution of Neuroimaging Research

    Directory of Open Access Journals (Sweden)

    Simonetti, Patricia

    2015-03-01

    Full Text Available Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus.

  12. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

    Science.gov (United States)

    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  13. Exploring associations between self-regulatory mechanisms and neuropsychological functioning and driver behaviour after brain injury.

    Science.gov (United States)

    Rike, Per-Ola; Johansen, Hans J; Ulleberg, Pål; Lundqvist, Anna; Schanke, Anne-Kristine

    2016-04-11

    The objective of this prospective one-year follow-up study was to explore the associations between self-regulatory mechanisms and neuropsychological tests as well as baseline and follow-up ratings of driver behaviour. The participants were a cohort of subjects with stroke and traumatic brain injury (TBI) who were found fit to drive after a multi-disciplinary driver assessment (baseline). Baseline measures included neuropsychological tests and ratings of self-regulatory mechanisms, i.e., executive functions (Behavior Rating Inventory of Executive Function-Adult Version; BRIEF-A) and impulsive personality traits (UPPS Impulsive Behavior Scale). The participants rated pre-injury driving behaviour on the Driver Behaviour Qestionnaire (DBQ) retrospectively at baseline and after one year of post-injury driving (follow-up). Better performance on neuropsychological tests was significantly associated with more post-injury DBQ Violations. The BRIEF-A main indexes were significantly associated with baseline and follow-up ratings of DBQ Mistakes and follow-up DBQ Inattention. UPPS (lack of) Perseverance was significantly associated with baseline DBQ Inattention, whereas UPPS Urgency was significantly associated with baseline DBQ Inexperience and post-injury DBQ Mistakes. There were no significant changes in DBQ ratings from baseline (pre-injury) to follow-up (post-injury). It was concluded that neuropsychological functioning and self-regulatory mechanisms are related to driver behaviour. Some aspects of driver behaviour do not necessarily change after brain injury, reflecting the influence of premorbid driving behaviour or impaired awareness of deficits on post-injury driving behaviour. Further evidence is required to predict the role of self-regulatory mechanisms on driver behaviour and crashes or near misses.

  14. Reduced neophobia: a potential mechanism explaining the emergence of self-medicative behavior in sheep.

    Science.gov (United States)

    Egea, A Vanina; Hall, Jeffery O; Miller, James; Spackman, Casey; Villalba, Juan J

    2014-08-01

    Gastrointestinal helminths challenge ruminants in ways that reduce their fitness. In turn, ruminants have evolved physiological and behavioral adaptations that counteract this challenge. For instance, emerging behavioral evidence suggests that ruminants self-select medicinal compounds and foods that reduce parasitic burdens. However, the mechanism/s leading to self-medicative behaviors in sick animals is still unknown. We hypothesized that when homeostasis is disturbed by a parasitic infection, consumers should respond by increasing the acceptability of novel foods relative to healthy individuals. Three groups of lambs (N=10) were dosed with 0 (Control-C), 5000 (Medium-M) and 15000 (High-H) L3 stage larvae of Haemonchus contortus. When parasites had reached the adult stage, all animals were offered novel foods and flavors in pens and then novel forages at pasture. Ingestive responses by parasitized lambs were different from non-parasitized Control animals and they varied with the type of food and flavor on offer. Parasitized lambs consumed initially more novel beet pulp and less novel beet pulp mixed with tannins than Control lambs, but the pattern reversed after 9d of exposure to these foods. Parasitized lambs ingested more novel umami-flavored food and less novel bitter-flavored food than Control lambs. When offered choices of novel unflavored and bitter-flavored foods or different forage species to graze, parasitized lambs selected a more diverse array of foods than Control lambs. Reductions in food neophobia or selection of a more diverse diet may enhance the likelihood of sick herbivores encountering novel medicinal plants and nutritious forages that contribute to restore health.

  15. A mechanism for proven technology foresight for emerging fast reactor designs and concepts

    Science.gov (United States)

    Anuar, Nuraslinda; Muhamad Pauzi, Anas

    2016-01-01

    The assessment of emerging nuclear fast reactor designs and concepts viability requires a combination of foresight methods. A mechanism that allows for the comparison and quantification of the possibility of being a proven technology in the future, β for the existing fast reactor designs and concepts is proposed as one of the quantitative foresight method. The methodology starts with the identification at the national or regional level, of the factors that would affect β. The factors are then categorized into several groups; economic, social and technology elements. Each of the elements is proposed to be mathematically modelled before all of the elemental models can be combined. Once the overall β model is obtained, the βmin is determined to benchmark the acceptance as a candidate design or concept. The β values for all the available designs and concepts are then determined and compared with the βmin, resulting in a list of candidate designs that possess the β value that is larger than the βmin. The proposed methodology can also be applied to purposes other than technological foresight.

  16. A mechanism for proven technology foresight for emerging fast reactor designs and concepts

    Energy Technology Data Exchange (ETDEWEB)

    Anuar, Nuraslinda, E-mail: nuraslinda@uniten.edu.my; Muhamad Pauzi, Anas, E-mail: anas@uniten.edu.my [College of Engineering, Universiti Tenaga Nasional, Jalan IKRAM-UNITEN, 43000 Kajang, Selangor (Malaysia)

    2016-01-22

    The assessment of emerging nuclear fast reactor designs and concepts viability requires a combination of foresight methods. A mechanism that allows for the comparison and quantification of the possibility of being a proven technology in the future, β for the existing fast reactor designs and concepts is proposed as one of the quantitative foresight method. The methodology starts with the identification at the national or regional level, of the factors that would affect β. The factors are then categorized into several groups; economic, social and technology elements. Each of the elements is proposed to be mathematically modelled before all of the elemental models can be combined. Once the overall β model is obtained, the β{sub min} is determined to benchmark the acceptance as a candidate design or concept. The β values for all the available designs and concepts are then determined and compared with the β{sub min}, resulting in a list of candidate designs that possess the β value that is larger than the β{sub min}. The proposed methodology can also be applied to purposes other than technological foresight.

  17. Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

    NARCIS (Netherlands)

    Westerhout, J.

    2014-01-01

    In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in huma

  18. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Eveline Snelders

    2008-11-01

    Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more

  19. Recovery mechanisms of somatosensory function in stroke patients: implications of brain imaging studies

    Institute of Scientific and Technical Information of China (English)

    Sung Ho Jang

    2013-01-01

    Somatosensory dysfunction is associated with a high incidence of functional impairment and safety in patients with stroke.With developments in brain mapping techniques,many studies have addressed the recovery of various functions in such patients.However,relatively little is known about the mechanisms of recovery of somatosensory function.Based on the previous human studies,a review of 11 relevant studies on the mechanisms underlying the recovery of somatosensory function in stroke patients was conducted based on the following topics:(1) recovery of an injured somatosensory pathway,(2) peri-lesional reorganization,(3) contribution of the unaffected somatosensory cortex,(4) contribution of the secondary somatosensory cortex,and (5)mechanisms of recovery in patients with thalamic lesions.We believe that further studies in this field using combinations of diffusion tensor imaging,functional neuroimaging,and magnetoencephalography are needed.In addition,the clinical significance,critical period,and facilitatory strategies for each recovery mechanism should be clarified.

  20. Emerging roles for brain drug-metabolizing cytochrome P450 enzymes in neuropsychiatric conditions and responses to drugs.

    Science.gov (United States)

    Toselli, Francesca; Dodd, Peter R; Gillam, Elizabeth M J

    2016-08-01

    P450s in the human brain were originally considered unlikely to contribute significantly to the clearance of drugs and other xenobiotic chemicals, since their overall expression was a small fraction of that found in the liver. However, it is now recognized that P450s play substantial roles in the metabolism of both exogenous and endogenous chemicals in the brain, but in a highly cell type- and region-specific manner, in line with the greater functional heterogeneity of the brain compared to the liver. Studies of brain P450 expression and the characterization of the catalytic activity of specific forms expressed as recombinant enzymes have suggested possible roles for xenobiotic-metabolizing P450s in the brain. It is now possible to confirm these roles through the use of intracerebroventricular administration of selective P450 inhibitors in animal models, coupled with brain sampling techniques to measure drug concentrations in vivo, and modern neuroimaging techniques. The purpose of this review is to discuss the evidence behind the functional importance of P450s from the "xenobiotic-metabolizing" families, CYP1, CYP2 and CYP3 in the brain. Approaches used to define the quantitative and qualitative significance of these P450s in determining tissue-specific levels of xenobiotics in brain will be considered. Finally, the possible roles of these enzymes in brain biochemistry will be examined in light of the demonstrated activity of these enzymes in vitro and the association of particular P450 forms with disease states.

  1. Mechanism of the emergence of the photo-EMF upon silicon liquid crystal-single crystal contact

    Science.gov (United States)

    Budagov, K. M.; Guseinov, A. G.; Pashaev, B. G.

    2017-03-01

    The effect light has on a silicon liquid crystal-single crystal contact at different temperatures of the surface doping of silicon, and when BaTiO3 nanoparticles are added to the composition of a liquid crystal, is studied. The mechanism of the emergence of the photo-EMF in the liquid crystal-silicon structure is explained.

  2. Molecular Electrical Doping of Organic Semiconductors: Fundamental Mechanisms and Emerging Dopant Design Rules.

    Science.gov (United States)

    Salzmann, Ingo; Heimel, Georg; Oehzelt, Martin; Winkler, Stefanie; Koch, Norbert

    2016-03-15

    Today's information society depends on our ability to controllably dope inorganic semiconductors, such as silicon, thereby tuning their electrical properties to application-specific demands. For optoelectronic devices, organic semiconductors, that is, conjugated polymers and molecules, have emerged as superior alternative owing to the ease of tuning their optical gap through chemical variability and their potential for low-cost, large-area processing on flexible substrates. There, the potential of molecular electrical doping for improving the performance of, for example, organic light-emitting devices or organic solar cells has only recently been established. The doping efficiency, however, remains conspicuously low, highlighting the fact that the underlying mechanisms of molecular doping in organic semiconductors are only little understood compared with their inorganic counterparts. Here, we review the broad range of phenomena observed upon molecularly doping organic semiconductors and identify two distinctly different scenarios: the pairwise formation of both organic semiconductor and dopant ions on one hand and the emergence of ground state charge transfer complexes between organic semiconductor and dopant through supramolecular hybridization of their respective frontier molecular orbitals on the other hand. Evidence for the occurrence of these two scenarios is subsequently discussed on the basis of the characteristic and strikingly different signatures of the individual species involved in the respective doping processes in a variety of spectroscopic techniques. The critical importance of a statistical view of doping, rather than a bimolecular picture, is then highlighted by employing numerical simulations, which reveal one of the main differences between inorganic and organic semiconductors to be their respective density of electronic states and the doping induced changes thereof. Engineering the density of states of doped organic semiconductors, the Fermi

  3. The complexity of biomechanics causing primary blast-induced traumatic brain injury: a review of potential mechanisms.

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    Amy eCourtney

    2015-10-01

    Full Text Available Primary blast induced traumatic brain injury (bTBI is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs which isolate a single injury mechanism.

  4. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    Science.gov (United States)

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  5. Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation.

    Science.gov (United States)

    Guo, Wei; Robbins, Meredith T; Wei, Feng; Zou, Shiping; Dubner, Ronald; Ren, Ke

    2006-01-04

    In the adult mammalian brain, brain-derived neurotrophic factor (BDNF) is critically involved in long-term synaptic plasticity. Here, we show that supraspinal BDNF-tyrosine kinase receptor B (TrkB) signaling contributes to pain facilitation. We show that BDNF-containing neurons in the periaqueductal gray (PAG), the central structure for pain modulation, project to and release BDNF in the rostral ventromedial medulla (RVM), a relay between the PAG and spinal cord. BDNF in PAG and TrkB phosphorylation in RVM neurons are upregulated after inflammation. Intra-RVM sequestration of BDNF and knockdown of TrkB by RNA interference attenuate inflammatory pain. Microinjection of BDNF (10-100 fmol) into the RVM facilitates nociception, which is dependent on NMDA receptors (NMDARs). In vitro studies with RVM slices show that BDNF induces tyrosine phosphorylation of the NMDAR NR2A subunit in RVM via a signal transduction cascade involving IP(3), PKC, and Src. The supraspinal BDNF-TrkB signaling represents a previously unknown mechanism underlying the development of persistent pain. Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain.

  6. Oscillatory brain activity related to control mechanisms during laboratory-induced reactive aggression

    Directory of Open Access Journals (Sweden)

    Ulrike M Krämer

    2009-11-01

    Full Text Available Aggressive behavior is a common reaction in humans after an interpersonal provocation, but little is known about the underlying brain mechanisms. The present study analyzed oscillatory brain activity while participants were involved in an aggressive interaction to examine the neural processes subserving the associated decision and evaluation processes. Participants were selected from a larger sample because of their high scores in trait aggressiveness. We used a competitive reaction time task that induces aggressive behavior through provocation. Each trial is separated in a decision phase, during which the punishment for the opponent is set, and an outcome phase, during which the actual punishment is applied or received. We observed provocation-related differences during the decision phase in the theta band which differed depending on participants’ aggressive behavior: High provocation was associated with an increased frontal theta response in participants refraining from retaliation, but with reduced theta power in those who got back to the opponent. Moreover, more aggressive decisions after being punished were associated with a decrease of frontal theta power. Non-aggressive and aggressive participants differed also in their outcome-related response: Being punished led to an increased frontal theta power compared to win trials in the latter only, pointing to differences in evaluation processes associated with their different behavioral reactions. The data thus support previous evidence for a role of prefrontal areas in the control of reactive aggression and extend behavioral studies on associations between aggression or violence and impaired prefrontal functions.

  7. Persistent polar depletion of stratospheric ozone and emergent mechanisms of ultraviolet radiation-mediated health dysregulation.

    Science.gov (United States)

    Dugo, Mark A; Han, Fengxiang; Tchounwou, Paul B

    2012-01-01

    Year 2011 noted the first definable ozone "hole" in the Arctic region, serving as an indicator to the continued threat of dangerous ultraviolet radiation (UVR) exposure caused by the deterioration of stratospheric ozone in the northern hemisphere. Despite mandates of the Montreal Protocol to phase out the production of ozone-depleting chemicals (ODCs), the relative stability of ODCs validates popular notions of persistent stratospheric ozone for several decades. Moreover, increased UVR exposure through stratospheric ozone depletion is occurring within a larger context of physiologic stress and climate change across the biosphere. In this review, we provide commentaries on stratospheric ozone depletion with relative comparisons between the well-known Antarctic ozone hole and the newly defined ozone hole in the Arctic. Compared with the Antarctic region, the increased UVR exposure in the Northern Hemisphere poses a threat to denser human populations across North America, Europe, and Asia. In this context, we discuss emerging targets of UVR exposure that can potentially offset normal biologic rhythms in terms of taxonomically conserved photoperiod-dependent seasonal signaling and entrainment of circadian clocks. Consequences of seasonal shifts during critical life history stages can alter fitness and condition, whereas circadian disruption is increasingly becoming associated as a causal link to increased carcinogenesis. We further review the significance of genomic alterations via UVR-induced modulations of phase I and II transcription factors located in skin cells, the aryl hydrocarbon receptor (AhR), and the nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2), with emphasis on mechanism that can lead to metabolic shifts and cancer. Although concern for adverse health consequences due to increased UVR exposure are longstanding, recent advances in biochemical research suggest that AhR and Nrf2 transcriptional regulators are likely targets for UVR

  8. Emergence and Spread of A Plasmid-Mediated Polymyxin Resistance Mechanism, MCR-1: Are Bacteria Winning?

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    Chao Yang

    2015-12-01

    Full Text Available The report of the emergence of mcr-1, the first plasmid-mediated polymyxin resistance mechanism, in Enterobacteriaceae in November 2015 challenged our last psychological line of defense. However, we still trusted that this resistance factor had not spread globally. One month later, in December 2015, the detection of mcr-1 in an Escherichia coliisolate from a septicemic patient in Denmark and in five E. coli isolates from imported chicken meat really defeated us. The worst news was that one of the chicken meat isolates belonged to ST131, a spreading epidemic sequence type. In China, 15%-21% of E. coli strains isolated from raw meat and animals carried mcr-1, and about 1% of patient isolates carried this gene, indicating that E. coli carrying this plasmid is not a rare phenomenon. This gene is transferable by conjugation and can be maintained in Klebsiella pneumonia and Pseudomonas aeruginosa, suggesting the risk of transfer between different bacterial genera. The good news is that the strains carrying mcr-1 do not contain genes for pan-resistance profiles, although some Danish strains contain 15 different resistance genes, including genes for extended-spectrum beta-lactam antibiotics, and gene mutations leading to high-level fluoroquinolone resistance. If the mcr-1-bearing strains acquire multidrug resistance, extensive drug resistance, or pandrug resistance, no antibiotic drugs will be available with which clinicians can treat infected patients. Therefore, the use of antibiotics in both hospitals and the animal breeding industry must be strictly regulated. The origin of mcr-1 may be associated with the wide use of colistin in agriculture. There is no evidence that the Danish mcr-1 gene spread from China. Therefore, it is likely that mcr-1 genes originated in multiple sites simultaneously under the pressure of colistin use, because India and Denmark are the world’ s greatest users of this antibiotic. More surveys must be conducted in different

  9. Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans.

    Science.gov (United States)

    Ruigrok, Mitchel J R; de Lange, Elizabeth C M

    2015-05-01

    To investigate the potential added value of intranasal drug administration, preclinical studies to date have typically used the area under the curve (AUC) in brain tissue or cerebrospinal fluid (CSF) compared to plasma following intranasal and intravenous administration to calculate measures of extent like drug targeting efficiencies (%DTE) and nose-to-brain transport percentages (%DTP). However, CSF does not necessarily provide direct information on the target site concentrations, while total brain concentrations are not specific to that end either as non-specific binding is not explicitly considered. Moreover, to predict nose-to-brain transport in humans, the use of descriptive analysis of preclinical data does not suffice. Therefore, nose-to-brain research should be performed translationally and focus on preclinical studies to obtain specific information on absorption from the nose, and distinguish between the different transport routes to the brain (absorption directly from the nose to the brain, absorption from the nose into the systemic circulation, and distribution between the systemic circulation and the brain), in terms of extent as well as rate. This can be accomplished by the use of unbound concentrations obtained from plasma and brain, with subsequent advanced mathematical modeling. To that end, brain extracellular fluid (ECF) is a preferred sampling site as it represents most closely the site of action for many targets. Furthermore, differences in nose characteristics between preclinical species and humans should be considered. Finally, pharmacodynamic measurements that can be obtained in both animals and humans should be included to further improve the prediction of the pharmacokinetic-pharmacodynamic relationship of intranasally administered CNS drugs in humans.

  10. Epidemiological Trends of Traumatic Brain Injury Identified in the Emergency Department in a Publicly-Insured Population, 2002-2010.

    Directory of Open Access Journals (Sweden)

    Terence S Fu

    Full Text Available To examine epidemiological trends of Traumatic Brain Injury (TBI treated in the Emergency Department (ED, identify demographic groups at risk of TBI, and determine the factors associated with hospitalization following an ED visit for TBI.A province-wide database was used to identify all ED visits for TBI in Ontario, Canada between April 2002 and March 2010. Trends were analyzed using linear regression, and predictors of hospital admission were evaluated using logistic regression.There were 986,194 ED visits for TBI over the eight-year study period, resulting in 49,290 hospitalizations and 1,072 deaths. The age- and sex-adjusted rate of TBI decreased by 3%, from 1,013.9 per 100,000 (95% CI 1,008.3-1,010.6 to 979.1 per 100,000 (95% CI 973.7-984.4; p = 0.11. We found trends towards increasing age, comorbidity level, length of stay, and ambulatory transport use. Children and young adults (ages 5-24 sustained peak rates of motor vehicle crash (MVC and bicyclist-related TBI, but also experienced the greatest decline in these rates (p = 0.003 and p = 0.005. In contrast, peak rates of fall-related TBI occurred among the youngest (ages 0-4 and oldest (ages 85+ segments of the population, but rates remained stable over time (p = 0.52 and 0.54. The 5-24 age group also sustained the highest rates of sports-related TBI but rates remained stable (p = 0.80. On multivariate analysis, the odds of hospital admission decreased by 1% for each year over the study period (OR = 0.991, 95% CI = 0.987-0.995. Increasing age and comorbidity, male sex, and ambulatory transport were significant predictors of hospital admission.ED visits for TBI are involving older populations with increasingly complex comorbidities. While TBI rates are either stable or declining among vulnerable groups such as young drivers, youth athletes, and the elderly, these populations remain key targets for focused injury prevention and surveillance. Clinicians in the ED setting should be cognizant

  11. Benchmarking Prehospital and Emergency Department Care for Argentine Children with Traumatic Brain Injury: For the South American Guideline Adherence Group

    Science.gov (United States)

    Vavilala, Monica S.; Lujan, Silvia B.; Qiu, Qian; Petroni, Gustavo J.; Ballarini, Nicolás M.; Guadagnoli, Nahuel; Depetris, María Alejandra; Faguaga, Gabriela A.; Baggio, Gloria M.; Busso, Leonardo O.; García, Mirta E.; González Carrillo, Osvaldo R.; Medici, Paula L.; Sáenz, Silvia S.; Vanella, Elida E.; Fabio, Anthony; Bell, Michael J.

    2016-01-01

    Objective There is little information on the type of early care provided to children with traumatic brain injury (TBI) in low middle income countries. We benchmarked early prehospital [PH] and emergency department [ED] pediatric TBI care in Argentina. Methods We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with TBI. Eligible participants were patients 0–18 years, and had diagnosis of TBI (admission Glasgow Coma scale score [GCS] 0). Outcomes were transport type, transport time, PH and ED adherence to best practice, and discharge Pediatric Cerebral Performance Category Scale (PCPC) and Pediatric Overall Performance category Scale (POPC). Results Of the 366 children, mean age was 8.7 (5.0) years, 58% were male, 90% had isolated TBI and 45.4% were transported by private vehicle. 50 (34.7%) of the 144 children with severe TBI (39.3% of all TBI patients) were transported by private vehicle. Most (267; 73%) patients received initial TBI care at an index hospital prior to study center admission, including children with severe (81.9%) TBI. Transport times were shorter for those patients who were directly transported by ambulance to study center than for the whole cohort (1.4 vs.5.5 hours). Ambulance blood pressure data were recorded in 30.9%. ED guideline adherence rate was higher than PH guideline adherence rate (84.8% vs. 26.4%). For patients directly transferred from scene to study trauma centers, longer transport time was associated with worse discharge outcome (PCPC aOR 1.10 [1.04, 1.18] and (POPC aOR 1.10 [1.04, 1.18]). There was no relationship between PH or ED TBI guideline adherence rate and discharge POPC and PCPC. Conclusion This study benchmarks early pediatric TBI care in Argentina and shows that many critically injured children with TBI do not receive timely or best practice PH care, that PH guideline adherence rate is low and that longer transport time was associated with poor

  12. Molecular mechanisms associated with ALA-PDT of brain tumor cells

    Science.gov (United States)

    Alqawi, Omar; Espiritu, Myrna; Singh, Gurmit

    2009-06-01

    Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.

  13. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Tina eSkjørringe

    2012-09-01

    Full Text Available Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation is strictly regulated, and concordantly protective barriers i.e. the blood-brain barrier (BBB and the blood-cerebrospinal fluid (CSF barrier (BCB have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the brain-iron homeostasis. Moreover, the uptake routes of iron and copper overlap each other which affect the interplay between the concentrations of the two metals in the brain. The divalent metal transporter-1 (DMT1 is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1 and ferroportin, all highly involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells that express various transporters

  14. Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

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    Gang Chen

    2008-01-01

    Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

  15. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders.

  16. Effects of weak transcranial Alternating Current Stimulation on brain activity – a review of known mechanisms from animal studies

    Directory of Open Access Journals (Sweden)

    Davide eReato

    2013-10-01

    Full Text Available Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (~1 Hz and gamma oscillations (~30 Hz. We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.

  17. Emergence of Form from Function - Mechanical Engineering Approaches to Probe the Role of Stem Cell Mechanoadaptation in Sealing Cell Fate.

    Science.gov (United States)

    Knothe Tate, Melissa L; Gunning, Peter W; Sansalone, Vittorio

    2016-10-14

    Stem cell "mechanomics" refers to the effect of mechanical cues on stem cell and matrix biology, where cell shape and fate are intrinsic manifestations of form and function. Before specialization, the stem cell itself serves as a sensor and actuator; its structure emerges from its local mechanical milieu as the cell adapts over time. Coupling of novel spatiotemporal imaging and computational methods allows for linking of the energy of adaptation to the structure, biology and mechanical function of the cell. Cutting edge imaging methods enable probing of mechanisms by which stem cells' emergent anisotropic architecture and fate commitment occurs. A novel cell-scale model provides a mechanistic framework to describe stem cell growth and remodeling through mechanical feedback; making use of a generalized virtual power principle, the model accounts for the rate of doing work or the rate of using energy to effect the work. This coupled approach provides a basis to elucidate mechanisms underlying the stem cell's innate capacity to adapt to mechanical stimuli as well as the role of mechanoadaptation in lineage commitment. An understanding of stem cell mechanoadaptation is key to deciphering lineage commitment, during prenatal development, postnatal wound healing, and engineering of tissues.

  18. Emotion recognition and emergent leadership : Unraveling mediating mechanisms and boundary conditions

    NARCIS (Netherlands)

    Walter, F.; Cole, M.S.; van der Vegt, G.S.; Rubin, R.S.; Bommer, W.H.

    2012-01-01

    This study examines the complex connection between individuals' emotion recognition capability and their emergence as leaders. It is hypothesized that emotion recognition and extraversion interactively relate with an individual's task coordination behavior which, in turn, influences the likelihood o

  19. Mechanisms that Underlie Co-variation of the Brain and Face

    OpenAIRE

    Marcucio, Ralph S.; Young, Nathan M.; Hu, Diane; Hallgrimsson, Benedikt

    2011-01-01

    The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this paper we describe factors that are active between development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signal...

  20. The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: a longitudinal prospective analysis using susceptibility-weighted imaging.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Cooper, Janine M; Beare, Richard; Ditchfield, Michael; Coleman, Lee; Silk, Timothy; Crossley, Louise; Beauchamp, Miriam H; Anderson, Vicki A

    2015-05-01

    Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high-level social cognitive skills. This study aimed to examine the differential influence of age-at-insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5-9 years; n = 41); (ii) late childhood (10-11 years; n = 39); and (iii) adolescence (12-15 years; n = 32) and group-matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks postinjury and were assessed on a battery of ToM tasks at 6- and 24-months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6- and 24-months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time-dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure-function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high-level social

  1. Reward mechanisms in the brain and their role in dependence : evidence from neurophysiological and neuroimaging studies

    NARCIS (Netherlands)

    Martin-Soelch, C; Leenders, KL; Chevalley, AF; Missimer, J; Kunig, G; Magyar, S; Mino, A; Schultz, W

    2001-01-01

    This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce

  2. Evolutionary Mechanisms Involved in Emergence of Viral Haemorrhagic Septicaemia Virus (VHSV) into Cultured Rainbow Trout, Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Schönherz, Anna A.

    Viral haemorrhagic septicaemaia virus (VHSV) is an RNA virus of lower vertebrates that infects a wide range of freshwater, anadromous and marine fish species. VHSV is endemic among most marine and anadromous fish species but has emerged into cultured rainbow trout where it evolves towards high...... virulence, causing extensive losses to the aquacultre industry. Cross-species transmission and subsequent adaptation to cultured raibow trout is observed occasionally. However, the biological background facilitationg VHSV emergense has yet to be identified. In the present PhD project potential mechanisms...... facilitation VHSV emergence into cultured raibow trout were explored. In vivo infection trials and in selico based molecular analysis were performed to independently investigate the first two steps of viral emergence, namely initial introduction to- and subsequent adaptation and establishment within the new...

  3. On the emergence of quantum mechanics, diffeomorphism invariance and the weak equivalence principle from deterministic Cartan-Randers systems

    CERN Document Server

    Torromé, Ricardo Gallego

    2014-01-01

    In this work, deterministic Cartan-Randers dynamical systems, a particular class of {\\it deterministic quantum models} associated to first order ordinary differential equations are considered. Then we show that {\\it diffeomorphism invariance}, a classical and a quantum versions of a Principle of Inertia, reversibility of the effective quantum dynamics and a {\\it covariant maximal universal acceleration} emerge from deterministic Cartan-Randers models. A geometric analytic mechanism for quantum measurement processes without reduction of wave packet appears naturally. The mechanism is applied heuristically to the quantum two slit experiment. The mechanism allows for protective measurement and usual Von Neumann measurements. Furthermore, a similar geometric-analytic mechanism is discovered to produce a lower bound for physical values for the eigenvalues of Hamiltonian for matter. As a side effect of such mechanism, a natural explanation for the Weak Equivalence Principle is obtained. This fact together with the ...

  4. Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans

    OpenAIRE

    Ruigrok, M.J.R.; Lange, de, A.H.

    2015-01-01

    To investigate the potential added value of intranasal drug administration, preclinical studies to date have typically used the area under the curve (AUC) in brain tissue or cerebrospinal fluid (CSF) compared to plasma following intranasal and intravenous administration to calculate measures of extent like drug targeting efficiencies (%DTE) and nose-to-brain transport percentages (%DTP). However, CSF does not necessarily provide direct information on the target site concentrations, while tota...

  5. Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer brain and the possible mechanism

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Alzheimer disease (AD) neurofibrillary degeneration is characterized by a disruption of the cytoskeleton. The alteration of microtubule system and the microtubule-associated protein has been extensively investigated in this pathology. In the present study, we decided to explore the role of neurofilament (NF) proteins in AD neurofibrillary degeneration. We first investigated the content and the phosphorylation level of NF proteins in AD brain by using a panel of anti-NF antibodies. It was found by quantitative Western blot that the NF subunits were exclusively detected in an insoluble fraction from AD brain grey matter. The level of phosphorylated (p)-NF-H and (p)-NF-M was increased 1.5 and 1.3 times (P<0.05) respectively at phosphorylation specific antibody SMI31 epitope in AD as compared to neurological controls of Huntington disease (HD). A 1.6 fold elevation (P>0.05) of p-NF-H to another phosphate reactive antibody SMI34 was also seen in AD. The level of non-phosphorylated (np)-NF-H/M recognized by SMI33 was similar before alkaline phosphatase (ALP) treatment, but the total level of NF-H/M was 1.5 and 1.6 times (P<0.01) higher in AD than HD after dephosphorylation. Furthermore, a 1.8 fold increase of NF-M to SMI32 was observed in AD only after ALP treatment, suggesting that the NF-H/M are increased in the phosphorylated form. The amount of NF-L determined by NR-4 was 1.6 fold (P<0.01) higher in AD than HD. To our knowledge, this is the first biochemical data shown definite abnormality of NF subunits in AD brain. To understand the possible mechanism for the abnormal hyperphosphorylation and elevation of NF in AD brain, we treated human SY5Y neuroblastoma cell with protein phosphatase(PP)-2A and PP-1 inhibitor okadaic acid(OA). Then, we determined the relationship between an AD-like PP-A and PP-1 activity deficiency and NF phosphorylation as well as intracellular translocation in modeled cell system. It was demonstrated that p-NF-H/M detected by SMI31 and

  6. Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

    Science.gov (United States)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

    Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

  7. Noninvasive Brain Stimulation for Motor Recovery after Stroke: Mechanisms and Future Views

    Directory of Open Access Journals (Sweden)

    Naoyuki Takeuchi

    2012-01-01

    Full Text Available Repetitive transcranial magnetic stimulation and transcranial direct current stimulation are noninvasive brain stimulation (NIBS techniques that can alter excitability of the human cortex. Considering the interhemispheric competition occurring after stroke, improvement in motor deficits can be achieved by increasing the excitability of the affected hemisphere or decreasing the excitability of the unaffected hemisphere. Many reports have shown that NIBS application improves motor function in stroke patients by using their physiological peculiarity. For continuous motor improvement, it is important to impart additional motor training while NIBS modulates the neural network between both hemispheres and remodels the disturbed network in the affected hemisphere. NIBS can be an adjuvant therapy for developed neurorehabilitation strategies for stroke patients. Moreover, recent studies have reported that bilateral NIBS can more effectively facilitate neural plasticity and induce motor recovery after stroke. However, the best NIBS pattern has not been established, and clinicians should select the type of NIBS by considering the NIBS mechanism. Here, we review the underlying mechanisms and future views of NIBS therapy and propose rehabilitation approaches for appropriate cortical reorganization.

  8. Invasive Mechanical Ventilation in California Over 2000-2009: Implications for Emergency Medicine

    Directory of Open Access Journals (Sweden)

    Seshadri C. Mudumbai

    2015-10-01

    Full Text Available Introduction: Patients who require invasive mechanical ventilation (IMV often represent a sequence of care between the emergency department (ED and intensive care unit (ICU. Despite being the most populous state, little information exists to define patterns of IMV use within the state of California. Methods: We examined data from the masked Patient Discharge Database of California’s Office of Statewide Health Planning and Development from 2000-2009. Adult patients who received IMV during their stay were identified using the International Classification of Diseases 9th Revision and Clinical Modification procedure codes (96.70, 96.71, 96.72. Patients were divided into age strata (18-34yr, 35-64yr, and >65yr. Using descriptive statistics and regression analyses, for IMV discharges during the study period, we quantified the number of ED vs. non-ED based admissions; changes in patient characteristics and clinical outcome; evaluated the marginal costs for IMV; determined predictors for prolonged acute mechanical ventilation (PAMV, i.e. IMV>96hr; and projected the number of IMV discharges and ED-based admissions by year 2020. Results: There were 696,634 IMV discharges available for analysis. From 2000–2009, IMV discharges increased by 2.8%/year: n=60,933 (293/100,000 persons in 2000 to n=79,868 (328/100,000 persons in 2009. While ED-based admissions grew by 3.8%/year, non-ED-based admissions remained stable (0%. During 2000-2009, fastest growth was noted for 1 the 35–64 year age strata; 2 Hispanics; 3 patients with non-Medicare public insurance; and 4 patients requiring PAMV. Average total patient cost-adjusted charges per hospital discharge increased by 29% from 2000 (from $42,528 to $60,215 in 2014 dollars along with increases in the number of patients discharged to home and skilled nursing facilities. Higher marginal costs were noted for younger patients (ages 18-34yr, non-whites, and publicly insured patients. Some of the strongest predictors

  9. Evaluation of self-perception of mechanical ventilation knowledge among Brazilian final-year medical students, residents and emergency physicians

    Science.gov (United States)

    Tallo, Fernando Sabia; de Campos Vieira Abib, Simone; de Andrade Negri, Alexandre Jorgi; Filho, Paulo Cesar; Lopes, Renato Delascio; Lopes, Antônio Carlos

    2017-01-01

    OBJECTIVE: To present self-assessments of knowledge about mechanical ventilation made by final-year medical students, residents, and physicians taking qualifying courses at the Brazilian Society of Internal Medicine who work in urgent and emergency settings. METHODS: A 34-item questionnaire comprising different areas of knowledge and training in mechanical ventilation was given to 806 medical students, residents, and participants in qualifying courses at 11 medical schools in Brazil. The questionnaire’s self-assessment items for knowledge were transformed into scores. RESULTS: The average score among all participants was 21% (0-100%). Of the total, 85% respondents felt they did not receive sufficient information about mechanical ventilation during medical training. Additionally, 77% of the group reported that they would not know when to start noninvasive ventilation in a patient, and 81%, 81%, and 89% would not know how to start volume control, pressure control and pressure support ventilation modes, respectively. Furthermore, 86.4% and 94% of the participants believed they would not identify the basic principles of mechanical ventilation in patients with obstructive pulmonary disease and acute respiratory distress syndrome, respectively, and would feel insecure beginning ventilation. Finally, 77% said they would fear for the safety of a patient requiring invasive mechanical ventilation under their care. CONCLUSION: Self-assessment of knowledge and self-perception of safety for managing mechanical ventilation were deficient among residents, students and emergency physicians from a sample in Brazil.

  10. Long term ex vivo culturing of Drosophila brain as a method to live image pupal brains: insights into the cellular mechanisms of neuronal remodeling.

    Science.gov (United States)

    Rabinovich, Dana; Mayseless, Oded; Schuldiner, Oren

    2015-01-01

    Holometabolous insects, including Drosophila melanogaster, undergo complete metamorphosis that includes a pupal stage. During metamorphosis, the Drosophila nervous system undergoes massive remodeling and growth, that include cell death and large-scale axon and synapse elimination as well as neurogenesis, developmental axon regrowth, and formation of new connections. Neuronal remodeling is an essential step in the development of vertebrate and invertebrate nervous systems. Research on the stereotypic remodeling of Drosophila mushroom body (MB) γ neurons has contributed to our knowledge of the molecular mechanisms of remodeling but our knowledge of the cellular mechanisms remain poorly understood. A major hurdle in understanding various dynamic processes that occur during metamorphosis is the lack of time-lapse resolution. The pupal case and opaque fat bodies that enwrap the central nervous system (CNS) make live-imaging of the central brain in-vivo impossible. We have established an ex vivo long-term brain culture system that supports the development and neuronal remodeling of pupal brains. By optimizing culture conditions and dissection protocols, we have observed development in culture at kinetics similar to what occurs in vivo. Using this new method, we have obtained the first time-lapse sequence of MB γ neurons undergoing remodeling in up to a single cell resolution. We found that axon pruning is initiated by blebbing, followed by one-two nicks that seem to initiate a more widely spread axon fragmentation. As such, we have set up some of the tools and methodologies needed for further exploration of the cellular mechanisms of neuronal remodeling, not limited to the MB. The long-term ex vivo brain culture system that we report here could be used to study dynamic aspects of neurodevelopment of any Drosophila neuron.

  11. Social Robots, Brain Machine Interfaces and Neuro/Cognitive Enhancers: Three Emerging Science and Technology Products through the Lens of Technology Acceptance Theories, Models and Frameworks

    Directory of Open Access Journals (Sweden)

    Gregor Wolbring

    2013-06-01

    Full Text Available Social robotics, brain machine interfaces and neuro and cognitive enhancement products are three emerging science and technology products with wide-reaching impact for disabled and non-disabled people. Acceptance of ideas and products depend on multiple parameters and many models have been developed to predict product acceptance. We investigated which frequently employed technology acceptance models (consumer theory, innovation diffusion model, theory of reasoned action, theory of planned behaviour, social cognitive theory, self-determination theory, technology of acceptance model, Unified Theory of Acceptance and Use of Technology UTAUT and UTAUT2 are employed in the social robotics, brain machine interfaces and neuro and cognitive enhancement product literature and which of the core measures used in the technology acceptance models are implicit or explicit engaged with in the literature.

  12. Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention.

    Science.gov (United States)

    Witkiewitz, Katie; Lustyk, M Kathleen B; Bowen, Sarah

    2013-06-01

    Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse.

  13. Interindividual Variability and Intraindividual Reliability of Intermittent Theta Burst Stimulation-induced Neuroplasticity Mechanisms in the Healthy Brain

    NARCIS (Netherlands)

    Schilberg, Lukas; Schuhmann, Teresa; Sack, Alexander T

    2017-01-01

    We combined patterned TMS with EMG in several sessions of a within-subject design to assess and characterize intraindividual reliability and interindividual variability of TMS-induced neuroplasticity mechanisms in the healthy brain. Intermittent theta burst stimulation (iTBS) was applied over M1 to

  14. PREFACE: DICE 2012 : Spacetime Matter Quantum Mechanics - from the Planck scale to emergent phenomena

    Science.gov (United States)

    Diósi, Lajos; Elze, Hans-Thomas; Fronzoni, Leone; Halliwell, Jonathan; Prati, Enrico; Vitiello, Giuseppe; Yearsley, James

    2013-06-01

    Presented in this volume are the Invited Lectures and the Contributed Papers of the Sixth International Workshop on Decoherence, Information, Complexity and Entropy - DICE 2012, held at Castello Pasquini, Castiglioncello (Tuscany), 17-21 September 2012. These proceedings may document to the interested public and to the wider scientific community the stimulating exchange of ideas at the meeting. The number of participants has been steadily growing over the years, reflecting an increasing attraction, if not need, of such conference. Our very intention has always been to bring together leading researchers, advanced students, and renowned scholars from various areas, in order to stimulate new ideas and their exchange across the borders of specialization. In this way, the series of meetings successfully continued from the beginning with DICE 20021, followed by DICE 20042, DICE 20063, DICE 20084, and DICE 20105, Most recently, DICE 2012 brought together more than 120 participants representing more than 30 countries worldwide. It has been a great honour and inspiration to have Professor Yakir Aharonov (Tel Aviv) with us, who presented the opening Keynote Lecture 'The two-vector quantum formalism'. With the overarching theme 'Spacetime - Matter - Quantum Mechanics - from the Planck scale to emergent phenomena', the conference took place in the very pleasant and inspiring atmosphere of Castello Pasquini - in beautiful surroundings, overlooking a piece of Tuscany's coast. The 5-day program covered these major topics: Quantum Mechanics, Foundations and Quantum-Classical Border Quantum-Classical Hybrids and Many-Body Systems Spectral Geometry, Path Integrals and Experiments Quantum -/- Gravity -/- Spacetime Quantum Mechanics on all Scales? A Roundtable Discussion under the theme 'Nuovi orizzonti nella ricerca scientifica. Ci troviamo di fronte ad una rivoluzione scientifica?' formed an integral part of the program. With participation of E Del Giudice (INFN & Università di

  15. The 13th J. A. F. Stevenson memorial lecture. Sexual differentiation of the brain: possible mechanisms and implications.

    Science.gov (United States)

    Gorski, R A

    1985-06-01

    The mammalian brain appears to be inherently feminine and the action of testicular hormones during development is necessary for the differentiation of the masculine brain both in terms of functional potential and actual structure. Experimental evidence for this statement is reviewed in this discussion. Recent discoveries of marked structural sex differences in the central nervous system, such as the sexually dimorphic nucleus of the preoptic area in the rat, offer model systems to investigate potential mechanisms by which gonadal hormones permanently modify neuronal differentiation. Although effects of these steroids on neurogenesis and neuronal migration and specification have not been conclusively eliminated, it is currently believed, but not proven, that the principle mechanism of steroid action is to maintain neuronal survival during a period of neuronal death. The structural models of the sexual differentiation of the central nervous system also provide the opportunity to identify sex differences in neurochemical distribution. Two examples in the rat brain are presented: the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus and of tyrosine hydroxylase-immunoreactive fibers and cells in the anteroventral periventricular nucleus. It is likely that sexual dimorphisms will be found to be characteristic of many neural and neurochemical systems. The final section of this review raises the possibility that the brain of the adult may, in response to steroid action, be morphologically plastic, and considers briefly the likelihood that the brain of the human species is also influenced during development by the hormonal environment.

  16. When Is a Physical Concept Born? The Emergence of "Work" as a Magnitude of Mechanics

    Science.gov (United States)

    Kanderakis, Nikos Emmanouil

    2010-01-01

    The physical magnitude "work" has a long history. It emerged when two different practices, performed during the whole eighteenth century, met each other. The first was theoretical, practiced by philosophers and mathematicians, and was related mainly to the "living forces" (vires vivae). The second was empirical, practiced by engineers, and was…

  17. Chemical Genomics and Emerging DNA Technologies in the Identification of Drug Mechanisms and Drug Targets

    DEFF Research Database (Denmark)

    Olsen, Louise Cathrine Braun; Færgeman, Nils J.

    2012-01-01

    critical roles in the genomic age of biological research and drug discovery. In the present review we discuss how simple biological model organisms can be used as screening platforms in combination with emerging genomic technologies to advance the identification of potential drugs and their molecular...

  18. An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi

    2014-07-01

    There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

  19. [Acquired drives. The cortical mechanism responsible to the emergence and development of social existence].

    Science.gov (United States)

    József, Knoll

    2007-10-01

    This paper is a brief interpretation of the theory (J. Knoll: The Brain and Its Self, Springer, 2005) the main message of which is that the appearance of the mammalian brain with the ability to acquire drives ensured the development of social life, and eventually led to the evolution of the human society. In the mammalian brain capable to acquire drives, untrained cortical neurons (Group 1) possess the potentiality to change their functional state in response to practice, training, or experience in three consecutive stages, namely, by getting involved in (a) an extinguishable conditioned reflex (ECR) (Group 2), (b) an inextinguishable conditioned reflex (ICR) (Group 3), or (c)an acquired drive (Group 4). The activity of the cortical neurons belonging to Group 3 and 4 is inseparable from conscious perception. In any moment of life self is the sum of those cortical neurons that have already changed their functional significance and belong to Group 3 or 4. Metaphorically, every human being is born with a telencephalon that resembles a book with over 100 billion empty pages (untrained, naive cortical neurons, Group 1), and with the capacity to inscribe as much as possible in this book throughout life. Whenever a drive is acquired, chains of ICRs are fixed, neurons responsible for emotions are also coupled to the integral whole, thus cognitive/volitional consciousness is necessarily inseparable from an affective state of consciousness. Cortical neurons belonging to Group 3 or 4 continuously synthesize their specific enhancer substance within their capacity. This means that even in the vigilant resting state (leisure), in the absence of a dominant drive, as well as in the non-vigilant resting state (sleeping), the cortical neurons representing the totality of the already fixed ICRs and acquired drives are permanently under the influence of their specific enhancer substance. Although the level of this permanent, undulating activation remains low, it is unpredictable as to

  20. Brain-Derived Neurotrophic Factor in Alzheimer's Disease: Risk, Mechanisms, and Therapy.

    Science.gov (United States)

    Song, Jing-Hui; Yu, Jin-Tai; Tan, Lan

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) has a neurotrophic support on neuron of central nervous system (CNS) and is a key molecule in the maintenance of synaptic plasticity and memory storage in hippocampus. However, changes of BDNF level and expression have been reported in the CNS as well as blood of Alzheimer's disease (AD) patients in the last decade, which indicates a potential role of BDNF in the pathogenesis of AD. Therefore, this review aims to summarize the latest progress in the field of BDNF and its biological roles in AD pathogenesis. We will discuss the interaction between BDNF and amyloid beta (Aβ) peptide, the effect of BDNF on synaptic repair in AD, and the association between BDNF polymorphism and AD risk. The most important is, enlightening the detailed biological ability and complicated mechanisms of action of BDNF in the context of AD would provide a future BDNF-related remedy for AD, such as increment in the production or release of endogenous BDNF by some drugs or BDNF mimics.

  1. The Brain Mechanisms Underlying the Cognitive Benefits of Bilingualism may be Extraordinarily Difficult to Discover

    Directory of Open Access Journals (Sweden)

    Kenneth R. Paap

    2014-12-01

    Full Text Available The hypothesis that coordinating two or more languages leads to an enhancement in executive functioning has been intensely studied for the past decade with very mixed results. The purpose of this review and analysis is to consider why it has been (and will continue to be difficult to discover the brain mechanisms underlying any cognitive benefits to bilingualism. Six reasons are discussed: 1 the phenomenon may not actually exist; 2 the cognitive neuroscientists investigating bilingual advantages may have been studying the wrong component of executive functioning; 3 most experiments use risky small numbers of participants and are underpowered; 4 the neural differences between groups do not align with the behavioral differences; 5 neural differences sometimes suffer from valence ambiguity, that is, disagreements whether “more” implies better or worse functioning and 6 neural differences often suffer from kind ambiguity, that is, disagreements regarding what type of mental events the pattern of activation in a region-of-interest actually reflects.

  2. The role of different cues in the brain mechanism on visual spatial attention

    Institute of Scientific and Technical Information of China (English)

    SONG Weiqun; LUO Yuejia; CHI Song; JI Xunming; LING Feng; ZHAO Lun; WANG Maobin; SHI Jiannong

    2006-01-01

    The visual spatial attention mechanism in the brain was studied in 16 young subjects through the visual search paradigm of precue-target by the event-related potential (ERP) technique, with the attentive ranges cued by different scales of Chinese character and region cues. The results showed that the response time for Chinese character cues was much longer than that for region cues especially for small region cues. With the exterior interferences, the target stimuli recognition under region cues was much quicker than that under Chinese character cues. Compared with that under region cues, targets under Chinese character cues could lead to increase of the posterior P1,decrease of the N1 and increase of the P2. It should also be noted that the differences between region cues and Chinese character cues were affected by the interference types. Under exterior interferences, no significant difference was found between region cues and Chinese character cues; however, it was not the case under the interior interferences. Considering the difference between the exterior interferences and the interior interferences, we could conclude that with the increase of difficulty in target recognition there was obvious difference in the consumption of anterior frontal resources by target stimuli under the two kinds of cues.

  3. Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury.

    Science.gov (United States)

    Goeller, Jacques; Wardlaw, Andrew; Treichler, Derrick; O'Bruba, Joseph; Weiss, Greg

    2012-07-01

    Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170 kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study.

  4. The radical-pair mechanism as a paradigm for the emerging science of quantum biology

    OpenAIRE

    Kominis, I. K.

    2015-01-01

    The radical-pair mechanism was introduced in the 1960's to explain anomalously large EPR and NMR signals in chemical reactions of organic molecules. It has evolved to the cornerstone of spin chemistry, the study of the effect electron and nuclear spins have on chemical reactions, with the avian magnetic compass mechanism and the photosynthetic reaction center dynamics being prominent biophysical manifestations of such effects. In recent years the radical-pair mechanism was shown to be an idea...

  5. New insights into schizophrenia disease genes interactome in the human brain: emerging targets and therapeutic implications in the postgenomics era.

    Science.gov (United States)

    Podder, Avijit; Latha, Narayanan

    2014-12-01

    Schizophrenia, a complex neurological disorder, is comprised of interactions between multiple genetic and environmental factors wherein each of the factors individually exhibits a small effect. In this regard a network-based strategy is best suited to capture the combined effect of multiple genes with their definite pattern of interactions. Given that schizophrenia affects multiple regions of the brain, we postulated that instead of any single specific tissue, a mutual set of interactions occurs between different regions of brain in a well-defined pattern responsible for the disease phenotype. To validate, we constructed and compared tissue specific co-expression networks of schizophrenia candidate genes in twenty diverse brain tissues. As predicted, we observed a common interaction network of certain genes in all the studied brain tissues. We examined fundamental network topologies of the common network to sequester essential common candidates for schizophrenia. We also performed a gene set analysis to identify the essential biological pathways enriched by the common candidates in the network. Finally, the candidate drug targets were prioritized and scored against known available schizophrenic drugs by molecular docking studies. We distinctively identified protein kinases as the top candidates in the network that can serve as probable drug targets for the disease. Conclusively, we propose that a comprehensive study of the connectivity amongst the disease genes themselves may turn out to be more informative to understand schizophrenia disease etiology and the underlying complexity.

  6. Statistical mechanics of graph models and their implications for emergent manifolds

    CERN Document Server

    Chen, Si

    2012-01-01

    Inspired by "quantum graphity" models for spacetime, a statistical model of graphs is proposed to explore possible realizations of emergent manifolds. Graphs with given numbers of vertices and edges are considered, governed by a very general Hamiltonian that merely favors graphs with near-constant valency and local rotational symmetry. The ratio of vertices to edges controls the dimensionality of the emergent manifold. The model is simulated numerically in the canonical ensemble for a given vertex to edge ratio, where it is found that the low energy states are almost triangulations of two dimensional manifolds. The resulting manifold shows topological "handles" and surface intersections in a higher embedding space as well as non-trivial fractal dimension. The transition is first order, underlying the difficulty of graph models in describing criticality that is independent of the details of the underlying graph. Another interesting phenomenon is that the entropy of the graphs are super-extensive, a fact known ...

  7. Targeting signaling factors for degradation, an emerging mechanism for TRAF functions

    OpenAIRE

    Yang, Xiao-Dong; Sun, Shao-Cong

    2015-01-01

    Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) form a family of proteins that are best known as signaling adapters of TNFRs. However, emerging evidence suggests that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling the fate of intracellular signaling factors. A well-recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin-dependent degradation of NF-κB-inducing kinase (NIK), an action required for the control ...

  8. Predictable 'meta-mechanisms' emerge from feedbacks between transpiration and plant growth and cannot be simply deduced from short-term mechanisms.

    Science.gov (United States)

    Tardieu, François; Parent, Boris

    2016-08-29

    Growth under water deficit is controlled by short-term mechanisms but, because of numerous feedbacks, the combination of these mechanisms over time often results in outputs that cannot be deduced from the simple inspection of individual mechanisms. It can be analysed with dynamic models in which causal relationships between variables are considered at each time-step, allowing calculation of outputs that are routed back to inputs for the next time-step and that can change the system itself. We first review physiological mechanisms involved in seven feedbacks of transpiration on plant growth, involving changes in tissue hydraulic conductance, stomatal conductance, plant architecture and underlying factors such as hormones or aquaporins. The combination of these mechanisms over time can result in non-straightforward conclusions as shown by examples of simulation outputs: 'over production of abscisic acid (ABA) can cause a lower concentration of ABA in the xylem sap ', 'decreasing root hydraulic conductance when evaporative demand is maximum can improve plant performance' and 'rapid root growth can decrease yield'. Systems of equations simulating feedbacks over numerous time-steps result in logical and reproducible emergent properties that can be viewed as 'meta-mechanisms' at plant level, which have similar roles as mechanisms at cell level.

  9. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

    Directory of Open Access Journals (Sweden)

    Kristina Leuner

    2010-09-01

    Full Text Available Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g. might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential (MMP, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease (AD. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, these new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

  10. An anisotropic hyperelastic constitutive model of brain white matter in biaxial tension and structural-mechanical relationships.

    Science.gov (United States)

    Labus, Kevin M; Puttlitz, Christian M

    2016-09-01

    Computational models of the brain require accurate and robust constitutive models to characterize the mechanical behavior of brain tissue. The anisotropy of white matter has been previously demonstrated; however, there is a lack of data describing the effects of multi-axial loading, even though brain tissue experiences multi-axial stress states. Therefore, a biaxial tensile experiment was designed to more fully characterize the anisotropic behavior of white matter in a quasi-static loading state, and the mechanical data were modeled with an anisotropic hyperelastic continuum model. A probabilistic analysis was used to quantify the uncertainty in model predictions because the mechanical data of brain tissue can show a high degree of variability, and computational studies can benefit from reporting the probability distribution of model responses. The axonal structure in white matter can be heterogeneous and regionally dependent, which can affect computational model predictions. Therefore, corona radiata and corpus callosum regions were tested, and histology and transmission electron microscopy were performed on tested specimens to relate the distribution of axon orientations and the axon volume fraction to the mechanical behavior. These measured properties were implemented into a structural constitutive model. Results demonstrated a significant, but relatively low anisotropic behavior, yet there were no conclusive mechanical differences between the two regions tested. The inclusion of both biaxial and uniaxial tests in model fits improved the accuracy of model predictions. The mechanical anisotropy of individual specimens positively correlated with the measured axon volume fraction, and, accordingly, the structural model exhibited slightly decreased uncertainty in model predictions compared to the model without structural properties.

  11. Research Review: Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia

    Science.gov (United States)

    Ross, Randal G.; Stevens, Karen E.; Proctor, William R.; Leonard, Sherry; Kisley, Michael A.; Hunter, Sharon K.; Freedman, Robert; Adams, Catherine E.

    2010-01-01

    The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this…

  12. Neural Mechanisms Linking Mild Traumatic Brain Injury and Anxiety States in an Animal Model

    Science.gov (United States)

    2012-03-01

    region cortices) as defined by Paxinos and Watson (1998). The volume of each brain region of interest was measured from cresyl violet stained...Kurume Med. J. 56, 49-59. Paxinos , C., Watson, C., 1997. The Rat Brain in Stereotaxic Coordinates, 3rd ed. Academic Press, New York. 30 Ptito

  13. Mechanisms and dynamics of cooperation and competition emergence in complex networked systems

    Science.gov (United States)

    Gianetto, David A.

    Cooperative behavior is a pervasive phenomenon in human interactions and yet how it can evolve and become established, through the selfish process of natural selection, is an enduring puzzle. These behaviors emerge when agents interact in a structured manner; even so, the key structural factors that affect cooperation are not well understood. Moreover, the literature often considers cooperation a single attribute of primitive agents who do not react to environmental changes but real-world actors are more perceptive. The present work moves beyond these assumptions by evolving more realistic game participants, with memories of the past, on complex networks. Agents play repeated games with a three-part Markovian strategy that allows us to separate the cooperation phenomenon into trust, reciprocity, and forgiveness characteristics. Our results show that networks matter most when agents gain the most by acting in a selfish manner, irrespective of how much they may lose by cooperating; since the context provided by neighborhoods inhibits greedy impulses that agents otherwise succumb to in isolation. Network modularity is the most important driver of cooperation emergence in these high-stakes games. However, modularity fails to tell the complete story. Modular scale-free graphs impede cooperation when close coordination is required, partially due to the acyclic nature of scale-free network models. To achieve the highest cooperation in diverse social conditions, both high modularity, low connectivity within modules, and a rich network of long cycles become important. With these findings in hand, we study the influence of networks on coordination and competition within the federal health care insurance exchange. In this applied study, we show that systemic health care coordination is encouraged by the emergent insurance network. The network helps underpin the viability of the exchange and provides an environment of stronger competition once a critical-mass of insurers have

  14. Research on Heat-Mechanical Coupling of Ventilated Disc Brakes under the Condition of Emergency Braking

    Science.gov (United States)

    Tan, Xuelong; Zhang, Jian; Tang, Wenxian; Zhang, Yang

    Taking the ventilated disc brake in some company as research object, and using UG to build 3D models of brake disc and pad, and making use of ABAQUS/Standard to set up two parts' finite element model, via the decelerated motion of actual simulation brake disc, which gets ventilated disc brake in the case of emergency breaking in time and space distribution of conditions of temperature and stress field, summarizes the distribution of temperature field and stress field, proves complex coupling between temperature, stress, and supplies the direct basis for brake's fatigue life analysis.

  15. Emergence of overlap in ensembles of spatial multiplexes and statistical mechanics of spatial interacting networks ensembles

    CERN Document Server

    Halu, Arda; Bianconi, Ginestra

    2013-01-01

    Spatial networks range from the brain networks, to transportation networks and infrastructures. Recently interacting and multiplex networks are attracting great attention because their dynamics and robustness cannot be understood without treating at the same time several networks. Here we present maximal entropy ensembles of spatial multiplex and spatial interacting networks that can be used in order to model spatial multilayer network structures and to build null models of real datasets. We show that spatial multiplex naturally develop a significant overlap of the links, a noticeable property of many multiplexes that can affect significantly the dynamics taking place on them. Additionally, we characterize ensembles of spatial interacting networks and we analyse the structure of interacting airport and railway networks in India, showing the effect of space in determining the link probability.

  16. Resuscitation therapy for traumatic brain injury-induced coma in rats:mechanisms of median nerve electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    Zhen Feng; Ying-jun Zhong; Liang Wang; Tian-qi Wei

    2015-01-01

    In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually in-creased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our ifndings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the pre-frontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

  17. Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

    Directory of Open Access Journals (Sweden)

    Zhen Feng

    2015-01-01

    Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

  18. Speech and music shape the listening brain: evidence for shared domain-general mechanisms

    Directory of Open Access Journals (Sweden)

    Salomi S. Asaridou

    2013-06-01

    Full Text Available Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This review summarizes a large body of behavioral and neuroscientific findings which suggest that the musical experience of trained musicians does modulate speech processing, and a sparser set of data, largely on pitch processing, which suggest in addition that linguistic experience, in particular learning a tone language, modulates music processing. Although research has focused mostly on music on speech effects, we argue that both directions of influence need to be studied, and conclude that the picture which thus emerges is one of mutual interaction across domains. In particular, it is not simply that experience with spoken language has some effects on music perception, and vice versa, but that because of shared domain-general subcortical and cortical networks, experiences in both domains influence behavior in both domains.

  19. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.

    Science.gov (United States)

    Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Liu, Zhen; Masoodi, Mojgan; Bazinet, Richard P

    2013-09-01

    Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.

  20. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Helen L Hellmich

    Full Text Available Developing new pharmacotherapies for traumatic brain injury (TBI requires elucidation of the neuroprotective mechanisms of many structurally and functionally diverse compounds. To test our hypothesis that diverse neuroprotective drugs similarly affect common gene targets after TBI, we compared the effects of two drugs, metyrapone (MT and carbenoxolone (CB, which, though used clinically for noncognitive conditions, improved learning and memory in rats and humans. Although structurally different, both MT and CB inhibit a common molecular target, 11β hydroxysteroid dehydrogenase type 1, which converts inactive cortisone to cortisol, thereby effectively reducing glucocorticoid levels. We examined injury-induced signaling pathways to determine how the effects of these two compounds correlate with pro-survival effects in surviving neurons of the injured rat hippocampus. We found that treatment of TBI rats with MT or CB acutely induced in hippocampal neurons transcriptional profiles that were remarkably similar (i.e., a coordinated attenuation of gene expression across multiple injury-induced cell signaling networks. We also found, to a lesser extent, a coordinated increase in cell survival signals. Analysis of injury-induced gene expression altered by MT and CB provided additional insight into the protective effects of each. Both drugs attenuated expression of genes in the apoptosis, death receptor and stress signaling pathways, as well as multiple genes in the oxidative phosphorylation pathway such as subunits of NADH dehydrogenase (Complex1, cytochrome c oxidase (Complex IV and ATP synthase (Complex V. This suggests an overall inhibition of mitochondrial function. Complex 1 is the primary source of reactive oxygen species in the mitochondrial oxidative phosphorylation pathway, thus linking the protective effects of these drugs to a reduction in oxidative stress. The net effect of the drug-induced transcriptional changes observed here indicates that

  1. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment

    Directory of Open Access Journals (Sweden)

    Gaurav eSinghal

    2014-04-01

    Full Text Available Recent studies on environmental enrichment (EE have shown cytokines, cellular immune components (e.g. T lymphocytes, NK cells and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise, a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including IL-6 secretion from muscle fibers, reduced expression of TLR’s on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia and upregulation of MKP-1 in CNS. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and TNF-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning and EE has paved a way towards formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immuno-modulatory role of physical exercise has been evaluated extensively, more research is required to investigate neuroimmune changes associated with other enrichment methods.

  2. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment.

    Science.gov (United States)

    Singhal, Gaurav; Jaehne, Emily J; Corrigan, Frances; Baune, Bernhard T

    2014-01-01

    Recent studies on environmental enrichment (EE) have shown cytokines, cellular immune components [e.g., T lymphocytes, natural killer (NK) cells], and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise (PE), a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including interleukin (IL)-6 secretion from muscle fibers, reduced expression of Toll-like receptors on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia, and upregulation of mitogen-activated protein kinase phosphatase-1 in central nervous system. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and tumor necrosis factor-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning, and EE has paved a way toward formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immunomodulatory role of PE has been evaluated extensively, more research

  3. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    Science.gov (United States)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Larsen, Annette K.; de Almeida, Luís Neves; Escargueil, Alexandre; Clairambault, Jean

    2016-06-01

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  4. Inhibitory effect of morphine on excitatory synaptic transmission via presynaptic mechanism in rat SON neurons in brain slices

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; HU San-jue; JU Gong

    2001-01-01

    To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20 μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution ofmEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.

  5. CSL Wave Function Collapse Model as a Mechanism for the Emergence of Cosmological Asymmetries in Inflation

    CERN Document Server

    Cañate, Pedro; Sudarsky, Daniel

    2012-01-01

    As previously discussed in (D. Sudarsky, Int.J.Mod.Phys.D20:509-552, (2011); [arXiv:0906.0315]), the inflationary account for the emergence of the seeds of cosmic structure falls short of actually explaining the generation of primordial anisotropies and inhomogeneities. This description starts from a symmetric background, and invokes symmetric dynamics, so it cannot explain asymmetries. To generate asymmetries, we present an application of the Continuous Spontaneous Localization (CSL) model of wave function collapse (P. Pearle, Phys. Rev. A 39, 2277, (1989); G. C. Ghirardi, P. Pearle and A. Rimini, Phys. Rev. A42, 78 (1990)) in the context of inflation. This modification of quantum dynamics introduces a stochastic non-unitary component to the evolution of the inflaton field perturbations. This leads to passage from a homogeneous and isotropic stage to another, where the quantum uncertainties in the initial state of inflation transmute into the primordial inhomogeneities and anisotropies. We examine requiremen...

  6. Mechanisms that underlie co-variation of the brain and face.

    Science.gov (United States)

    Marcucio, Ralph S; Young, Nathan M; Hu, Diane; Hallgrimsson, Benedikt

    2011-04-01

    The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this work, we describe factors that are active between the development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signals to facial tissues to establish signaling centers that regulate patterned growth. Importantly, subtle alterations to these physical or molecular interactions may contribute to both normal and abnormal variation. These interactions are therefore critical to our understanding of how a diversity of facial morphologies can be generated both within species and across evolutionary time.

  7. Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.

    Science.gov (United States)

    Ridley, Ben; Beltramone, Marion; Wirsich, Jonathan; Le Troter, Arnaud; Tramoni, Eve; Aubert, Sandrine; Achard, Sophie; Ranjeva, Jean-Philippe; Guye, Maxime; Felician, Olivier

    2016-01-01

    Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant

  8. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Science.gov (United States)

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  9. Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

    Science.gov (United States)

    Rossi, P Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J; Elias, W Jeff; Rossi, Marvin A; Butson, Christopher L; Fox, Michael D; McIntyre, Cameron C; Pouratian, Nader; Swann, Nicole C; de Hemptinne, Coralie; Gross, Robert E; Chizeck, Howard J; Tagliati, Michele; Lozano, Andres M; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L; Akbar, Umer; Gerhardt, Greg A; Grill, Warren M; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H; Lang, Anthony E; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y; Molina, Rene; Opri, Enrico; Otto, Kevin J; Oweiss, Karim G; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A; Shih, Ludy C; Steinke, G Karl; Tröster, Alexander I; Vanegas, Nora; Zaghloul, Kareem A; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D; Okun, Michael S

    2016-01-01

    The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

  10. Evolution of time-keeping mechanisms : early emergence and adaptation to photoperiod

    NARCIS (Netherlands)

    Hut, R. A.; Beersma, D. G. M.

    2011-01-01

    Virtually all species have developed cellular oscillations and mechanisms that synchronize these cellular oscillations to environmental cycles. Such environmental cycles in biotic (e. g. food availability and predation risk) or abiotic (e. g. temperature and light) factors may occur on a daily, annu

  11. Mechanism of case processing in the brain: an fMRI study.

    Directory of Open Access Journals (Sweden)

    Satoru Yokoyama

    Full Text Available In sentence comprehension research, the case system, which is one of the subsystems of the language processing system, has been assumed to play a crucial role in signifying relationships in sentences between noun phrases (NPs and other elements, such as verbs, prepositions, nouns, and tense. However, so far, less attention has been paid to the question of how cases are processed in our brain. To this end, the current study used fMRI and scanned the brain activity of 15 native English speakers during an English-case processing task. The results showed that, while the processing of all cases activates the left inferior frontal gyrus and posterior part of the middle temporal gyrus, genitive case processing activates these two regions more than nominative and accusative case processing. Since the effect of the difference in behavioral performance among these three cases is excluded from brain activation data, the observed different brain activations would be due to the different processing patterns among the cases, indicating that cases are processed differently in our brains. The different brain activations between genitive case processing and nominative/accusative case processing may be due to the difference in structural complexity between them.

  12. The incidence and risk factors for hypotension during emergent decompressive craniotomy in children with traumatic brain injury.

    Science.gov (United States)

    Miller, Patrick; Mack, Christopher D; Sammer, Marla; Rozet, Irene; Lee, Lorri A; Muangman, Saipin; Wang, Marjorie; Hollingworth, Will; Lam, Arthur M; Vavilala, Monica S

    2006-10-01

    We conducted a retrospective cohort study in children or =4 mm predicted IH (ARR 1.67 95% CI 1.06-2.63), independent of blood loss. IH occurred frequently during emergent decompressive craniotomy in children with TBI. ED hypotension, blood loss, CT lesion volume, and CT midline shift predicted IH. Anesthesiologists can expect children with preoperative CT midline shift > or =4 mm to have IH during this procedure.

  13. Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: Relevance to depressive-like behavior.

    Science.gov (United States)

    Chabry, Joëlle; Nicolas, Sarah; Cazareth, Julie; Murris, Emilie; Guyon, Alice; Glaichenhaus, Nicolas; Heurteaux, Catherine; Petit-Paitel, Agnès

    2015-11-01

    Regulation of neuroinflammation by glial cells plays a major role in the pathophysiology of major depression. While astrocyte involvement has been well described, the role of microglia is still elusive. Recently, we have shown that Adiponectin (ApN) plays a crucial role in the anxiolytic/antidepressant neurogenesis-independent effects of enriched environment (EE) in mice; however its mechanisms of action within the brain remain unknown. Here, we show that in a murine model of depression induced by chronic corticosterone administration, the hippocampus and the hypothalamus display increased levels of inflammatory cytokines mRNA, which is reversed by EE housing. By combining flow cytometry, cell sorting and q-PCR, we show that microglia from depressive-like mice adopt a pro-inflammatory phenotype characterized by higher expression levels of IL-1β, IL-6, TNF-α and IκB-α mRNAs. EE housing blocks pro-inflammatory cytokine gene induction and promotes arginase 1 mRNA expression in brain-sorted microglia, indicating that EE favors an anti-inflammatory activation state. We show that microglia and brain-macrophages from corticosterone-treated mice adopt differential expression profiles for CCR2, MHC class II and IL-4recα surface markers depending on whether the mice are kept in standard environment or EE. Interestingly, the effects of EE were abolished when cells are isolated from ApN knock-out mouse brains. When injected intra-cerebroventricularly, ApN, whose level is specifically increased in cerebrospinal fluid of depressive mice raised in EE, rescues microglia phenotype, reduces pro-inflammatory cytokine production by microglia and blocks depressive-like behavior in corticosterone-treated mice. Our data suggest that EE-induced ApN increase within the brain regulates microglia and brain macrophages phenotype and activation state, thus reducing neuroinflammation and depressive-like behaviors in mice.

  14. The role of programmed and emergent mechanisms of coordination: How standardized care pathways contribute to coordinate care tasks in hospitals

    DEFF Research Database (Denmark)

    Prætorius, Thim

    Hospitals face substantial coordination challenges. To meet this hospitals more and more use standardized work processes such as care pathways. By drawing on recent coordination theory that increasingly emphasizes the role of lateral and emergent interactions alongside traditional, programmed...... mechanisms of coordination, this paper finds that standardized work processes such as care pathways should be considered as a bundle of coordination mechanisms—plans and rules, objects, routines, roles and proximity—rather than a mechanism of its own. The bundle builds the accountability, predictability...... and common understanding needed to coordinate standardized care tasks. The analysis lends theoretical insights to the traditional view that see standardized work processes as programmed processes. For health care workers who design, implement and use care pathways to solve care tasks, the analysis calls...

  15. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

    Science.gov (United States)

    Elshenawy, Osama H.; Shoieb, Sherif M.; Mohamed, Anwar; El-Kadi, Ayman O.S.

    2017-01-01

    Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. PMID:28230738

  16. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank - A Review of Emerging Issues and Technologies

    Directory of Open Access Journals (Sweden)

    Wissam Deeb

    2016-11-01

    Full Text Available This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual Deep Brain Stimulation Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson’s disease, essential tremor, Alzheimer’s disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year’s international Think Tank, with a view toward current and near future advancement of the field.

  17. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Osama H. Elshenawy

    2017-02-01

    Full Text Available Cytochrome P450-mediated metabolism of arachidonic acid (AA is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal 19 ischemia/reperfusion (I/R injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future.

  18. Emerging quantum mechanics: Coefficient of second-order coherence from classical random fields interacting with threshold type detectors

    Science.gov (United States)

    Khrennikov, Andrei

    2014-11-01

    This paper is a contribution to the project "emergent quantum mechanics" unifying a variety of attempts to treat quantum mechanics (QMs) as emergent from other theories pretending on finer descriptions of quantum phenomena. More concretely it is about an attempt to model detection probabilities predicted by QM for single photon states by using classical random fields interacting with detectors of the threshold type. Continuous field model, prequantum classical statistical field theory (PCSFT), was developed in recent years and its predictions about probabilities and correlations match well with QM. The main problem is to develop the corresponding measurement theory which would describe the transition from continuous fields to discrete events, "clicks of detectors". Some success was achieved and the click-probabilities for quantum observables can be derived from PCSFT by modeling interaction of fields with the threshold type detectors. However, already for the coefficient of second-order coherence g2(0) calculations are too complicated and only an estimation of g2(0) was obtained. In this paper, we present results of numerical simulation based on PCSFT and modeling of interaction with threshold type detectors. The "prequantum random field" interacting with a detector is modeled as the Brownian motion in the space of classical fields (Wiener process in complex Hilbert space). Simulation for g2(0) shows that this coefficient approaches zero with increase of the number of detections.

  19. Epigenetic mechanisms: An emerging role in pathogenesis and its therapeutic potential in systemic sclerosis.

    Science.gov (United States)

    Luo, Yangyang; Wang, Yong; Shu, Ye; Lu, Qianjin; Xiao, Rong

    2015-10-01

    Systemic sclerosis (SSc) is a heterogeneous and life-threatening autoimmune disease characterized by damage to small blood vessels, interruption of immune homeostasis and ultimately, fibrosis. Currently, the mechanisms involved in SSc pathogenesis remain unknown. An increasing amount of data shows that, via certain signaling pathways, epigenetic mechanisms, including DNA methylation, histone modification, and miRNAs, are closely related to the three primary processes that characterize SSc: vascular abnormalities, activation of immune system, and excessive extracellular matrix deposition. In the clinical setting, identification of molecules and biomarkers for determining disease severity, predicting disease progression and assessing response to treatment remains challenging. In this review, we aim to summarize the key epigenetic mechanisms involved in the pathogenesis of SSc. Certain cytokines or molecules, such as CD40, CD70, and Fli-1, are expressed at varying rates in SSc due to epigenetic modification and play important roles in SSc. It is therefore likely that these molecules may be biomarkers for SSc. In addition, epigenetic changes of certain genes, including Fli-1, BMPRII, CD11a, Foxp3, and eNOS, influence the expression of these genes to ultimately result in an anti-fibrotic effect. The influence that epigenetics has on SSc pathogenesis suggests that epigenetics-targeting drugs may have potential therapeutic effects against SSc. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

  20. Computerized cognitive training and brain derived neurotrophic factor during bed rest: mechanisms to protect individual during acute stress

    Science.gov (United States)

    Passaro, Angelina; Soavi, Cecilia; Sanz, Juana M.; Morieri, Mario L.; Dalla Nora, Edoardo; Kavcic, Voyko; Narici, Marco V.; Reggiani, Carlo; Biolo, Gianni; Zuliani, Giovanni; Lazzer, Stefano; Pišot, Rado

    2017-01-01

    Acute stress, as bed rest, was shown to increase plasma level of the neurotrophin brain-derived neurotrophic factor (BDNF) in older, but not in young adults. This increase might represent a protective mechanism towards acute insults in aging subjects. Since computerized cognitive training (CCT) is known to protect brain, herein we evaluated the effect of CCT during bed rest on BDNF, muscle mass, neuromuscular function and metabolic parameters. The subjects that underwent CCT did not show an increase of BDNF after bed rest, and showed an anti-insular modification pattern in metabolism. Neuromuscular function parameters, already shown to beneficiate from CCT, negatively correlated with BDNF in research participants undergoing CCT, while positively correlated in the control group. In conclusion, BDNF increase can be interpreted as a standardized protective mechanism taking place whenever an insult occurs; it gives low, but consistent preservation of neuromuscular function. CCT, acting as an external protective mechanism, seems to modify this standardized response, avoiding BDNF increase or possibly modifying its time course. Our results suggest the possibility of differential neuroprotective mechanisms among ill and healthy individuals, and the importance of timing in determining the effects of protective mechanisms. PMID:28161695

  1. Epigenetic mechanisms in non-alcoholic fatty liver disease:An emerging field

    Institute of Scientific and Technical Information of China (English)

    Rocío; Gallego-Durán; Manuel; Romero-Gómez

    2015-01-01

    Non-alcoholic fatty liver disease(NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to nonalcoholic steatohepatitis(NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or micro RNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

  2. Epigenetic mechanisms in non-alcoholic fatty liver disease: An emerging field.

    Science.gov (United States)

    Gallego-Durán, Rocío; Romero-Gómez, Manuel

    2015-10-28

    Non-alcoholic fatty liver disease (NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or microRNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

  3. The emergence of urban land use patterns driven by dispersion and aggregation mechanisms.

    Directory of Open Access Journals (Sweden)

    James Decraene

    Full Text Available We employ a cellular-automata to reconstruct the land use patterns of cities that we characterize by two measures of spatial heterogeneity: (a a variant of spatial entropy, which measures the spread of residential, business, and industrial activity sectors, and (b an index of dissimilarity, which quantifies the degree of spatial mixing of these land use activity parcels. A minimalist and bottom-up approach is adopted that utilizes a limited set of three parameters which represent the forces which determine the extent to which each of these sectors spatially aggregate into clusters. The dispersion degrees of the land uses are governed by a fixed pre-specified power-law distribution based on empirical observations in other cities. Our method is then used to reconstruct land use patterns for the city state of Singapore and a selection of North American cities. We demonstrate the emergence of land use patterns that exhibit comparable visual features to the actual city maps defining our case studies whilst sharing similar spatial characteristics. Our work provides a complementary approach to other measures of urban spatial structure that differentiate cities by their land use patterns resulting from bottom-up dispersion and aggregation processes.

  4. From correspondence to complementarity: The emergence of Bohr's Copenhagen interpretation of quantum mechanics

    Science.gov (United States)

    Tanona, Scott Daniel

    I develop a new analysis of Niels Bohr's Copenhagen interpretation of quantum mechanics by examining the development of his views from his earlier use of the correspondence principle in the so-called 'old quantum theory' to his articulation of the idea of complementarity in the context of the novel mathematical formalism of quantum mechanics. I argue that Bohr was motivated not by controversial and perhaps dispensable epistemological ideas---positivism or neo-Kantianism, for example---but by his own unique perspective on the difficulties of creating a new working physics of the internal structure of the atom. Bohr's use of the correspondence principle in the old quantum theory was associated with an empirical methodology that used this principle as an epistemological bridge to connect empirical phenomena with quantum models. The application of the correspondence principle required that one determine the validity of the idealizations and approximations necessary for the judicious use of classical physics within quantum theory. Bohr's interpretation of the new quantum mechanics then focused on the largely unexamined ways in which the developing abstract mathematical formalism is given empirical content by precisely this process of approximation. Significant consistency between his later interpretive framework and his forms of argument with the correspondence principle indicate that complementarity is best understood as a relationship among the various approximations and idealizations that must be made when one connects otherwise meaningless quantum mechanical symbols to empirical situations or 'experimental arrangements' described using concepts from classical physics. We discover that this relationship is unavoidable not through any sort of a priori analysis of the priority of classical concepts, but because quantum mechanics incorporates the correspondence approach in the way in which it represents quantum properties with matrices of transition probabilities, the

  5. Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats.

    Science.gov (United States)

    Krivova, Natalia A; Zaeva, Olga B; Grigorieva, Valery A

    2015-01-01

    The Morris water maze (MWM) is a tool for assessment of age-related modulations spatial learning and memory in laboratory rats. In our work was investigated the age-related decline of MWM performance in 11-month-old rats and the effect exerted by training in the MWM on the redox mechanisms in rat brain parts. Young adult (3-month-old) and aged (11-month-old) male rats were trained in the MWM. Intact animals of the corresponding age were used as the reference groups. The level of pro- and antioxidant capacity in brain tissue homogenates was assessed using the chemiluminescence method. A reduced performance in the MWM test was found in 11-month-old rats: at the first day of training they showed only 30% of successful MWM trials. However, at the last training day the percentage of successful trials was equal for young adult and aged animals. This indicates that the aged 11-month-old rats can successfully learn in MWM. Therewith, the MWM spatial learning procedure itself produces changes in different processes of redox homeostasis in 11-month-old and 3-month-old rats as compared to intact animals. Young adult rats showed a decrease in prooxidant capacity in all brain parts, while 11-month-old rats demonstrated an increase in antioxidant capacity in the olfactory bulb, pons + medulla oblongata and frontal lobe cortex. Hence, the MWM procedure activates the mechanisms that restrict the oxidative stress in brain parts. The obtained results may be an argument for further development of the animal training procedures aimed to activate the mechanisms that can prevent the age-related deterioration of performance in the learning test. This may be useful not only for the development of training procedures applicable to human patients with age-related cognitive impairments, but also for their rehabilitation.

  6. Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; SHANG Chong-zhi; HU Qun-liang

    2009-01-01

    Objective: To explore the role and function of stromal cell-derived factor- 1 (SDF- 1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF- 1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

  7. Use of biomarker S100B for traumatic brain damage in the emergency department may change observation strategy

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Bouchelouche, Pierre Nourdine

    2014-01-01

    INTRODUCTION: The revised Scandinavian Neurotrauma Committee (SNC) guidelines on management of patients with head trauma include an option for measurement of S100B in peripheral blood with 100% sensitivity for neurosurgical intervention. A medical technology assessment was conducted to evaluate any...... impact of using S100B on the use of computed tomographies (CT) of the brain and admission for observation. MATERIAL AND METHODS: Patients referred for assessment of head injury over a period of 1.5 months had their blood sampled for measurement of S100B in serum. Results were not available...... patients had their blood sampled for analysis. In all, 12 patients were excluded in pursuance of SNC guidelines, which left 27 patients for analysis. A total of 15 patients had abnormally high S100B levels. Using the SNC criteria, only eight of these qualified a priori for blood sampling. Furthermore...

  8. The Emerging Role of TPR-Domain Immunophilins in the Mechanism of Action of Steroid Receptors

    Directory of Open Access Journals (Sweden)

    G. I. Mazaira

    2014-11-01

    Full Text Available In the absence of ligand, some members of nuclear receptor family such as corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus upon ligand-binding. Other members of the family such as the estrogen receptor are mostly nuclear. Regardless of their primary location, these oligomeric proteins undergo a dynamic nuclear-cytoplasmic shuttling, and their transport through the cytoplasmic compartment has always been assumed to occur in a stochastic manner by simple diffusion. Although heuristic, this oversimplified model has never been demonstrated. Moreover, it has always been assumed that the first step related to receptor activation is the dissociation of the Hsp90-based heterocomplex, a process referred to as `transformation.' Nonetheless, recent experimental evidence indicates that the chaperone machinery is required for the retrotransport of the receptor throughout the cytoplasm and facilitates its active passage through the nuclear pore. Therefore, transformation is actually a nuclear event. A group of Hsp90-binding cochaperones belonging to the immunophilin family plays a cardinal role not only in the mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity. In this article we analyze the importance of molecular chaperones and TPR-domain immunophilins in the molecular mechanism of action of steroid receptors.

  9. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action.

    Science.gov (United States)

    Poudyal, Hemant; Panchal, Sunil K; Diwan, Vishal; Brown, Lindsay

    2011-10-01

    Epidemiological, human, animal, and cell culture studies show that n-3 fatty acids, especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n-3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n-3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n-3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n-3 and n-6 fatty acids as well as the interactions of n-3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n-3 fatty acids to reduce the risk factors of metabolic syndrome.

  10. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    Science.gov (United States)

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI.

  11. A stochastic mechanism for signal propagation in the brain: Force of rapid random fluctuations in membrane potentials of individual neurons.

    Science.gov (United States)

    Hong, Dawei; Man, Shushuang; Martin, Joseph V

    2016-01-21

    There are two functionally important factors in signal propagation in a brain structural network: the very first synaptic delay-a time delay about 1ms-from the moment when signals originate to the moment when observation on the signal propagation can begin; and rapid random fluctuations in membrane potentials of every individual neuron in the network at a timescale of microseconds. We provide a stochastic analysis of signal propagation in a general setting. The analysis shows that the two factors together result in a stochastic mechanism for the signal propagation as described below. A brain structural network is not a rigid circuit rather a very flexible framework that guides signals to propagate but does not guarantee success of the signal propagation. In such a framework, with the very first synaptic delay, rapid random fluctuations in every individual neuron in the network cause an "alter-and-concentrate effect" that almost surely forces signals to successfully propagate. By the stochastic mechanism we provide analytic evidence for the existence of a force behind signal propagation in a brain structural network caused by rapid random fluctuations in every individual neuron in the network at a timescale of microseconds with a time delay of 1ms.

  12. Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.

    Science.gov (United States)

    Huang, Xiao-Tian; Qian, Zhong-Ming; He, Xuan; Gong, Qi; Wu, Ka-Chun; Jiang, Li-Rong; Lu, Li-Na; Zhu, Zhou-Jing; Zhang, Hai-Yan; Yung, Wing-Ho; Ke, Ya

    2014-05-01

    Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease.

  13. Mechanisms of restriction of viral neuroinvasion at the blood-brain barrier.

    Science.gov (United States)

    Miner, Jonathan J; Diamond, Michael S

    2016-02-01

    The blood-brain barrier (BBB) consists of highly specialized cells including brain microvascular endothelial cells, astrocytes, microglia, pericytes, and neurons, which act in concert to restrict the entry of pathogens, immune cells, and soluble molecules into the central nervous system (CNS). If pathogens manage to cross the BBB and establish infection within the CNS, the BBB can open in a regulated manner to allow leukocyte transmigration into the CNS so that microbes, infected cells, and debris can be cleared. This review highlights how different inflammatory cytokines or signaling pathways disrupt or enhance BBB integrity in a way that regulates entry of neurotropic viruses into the CNS.

  14. Anesthetic Efficacy Study in 60 Patients with Severe Brain Trauma Emergency Surgery%60例重症颅脑外伤手术的麻醉体会

    Institute of Scientific and Technical Information of China (English)

    王丽杰

    2015-01-01

    Objective To investigate the efective anesthesia of emergency surgery in patients with severe traumatic brain injury.Methods60 cases of severe traumatic brain injury patients for the study were randomly divided into two groups, the experimental group and the control group, each of 30 cases. Patients in the experimental group were treated with total intravenous anesthesia, while patients in the control group were implemented inhalation anesthesia. The eficacy of anesthesia was compared between the two groups of patients.Results The heart rate and mean arterial pressure of the experimental group patients in incision and cut the dura were significantly lower than the control group, and the recovery time and extubation time of patients were significantly shorter than the control group (P<0.05).ConclusionPatients with severe traumatic brain injury treated with emergency surgery inhalation anesthesia can maintain a good depth of anesthesia, which has an important role in implementation of surgery.%目的:分析重症颅脑外伤手术的麻醉方法。方法选择在我院进行治疗60例重症颅脑外伤患者作为研究对象,将其随机分为对照组和观察组,每组30例,对照组接受静吸复合麻醉,观察组接受全凭静脉麻醉,比较两组患者的麻醉效果。结果和对照组患者相比较,观察组患者切皮、切硬脑膜时心率和平均动脉压都较低,患者苏醒和拔管时间也较短(P<0.05)。结论重症颅脑外伤患者进行手术时使用全凭静脉麻醉具有良好的麻醉效果且能维持患者的麻醉深度,能够促进手术的顺利进行,值得临床推广使用。

  15. The Research of Innovation Mechanism of China's Emergency Logistics System%我国应急物流体系创新机制研究

    Institute of Scientific and Technical Information of China (English)

    刘小更

    2012-01-01

    从应急物流的内涵、特点入手,提出了应急物流体系创新机制的构建,包括应急物流信息平台、应急物流快速反应机制、应急物流政府保障机制和应急物流的反馈控制机制四大模块。只有这些创新机制的协同运作。突发事件的物资供应才能得到有效保障。%From the content and the characteristics of file emergency logistics, the article is proposed building the innovative mec, hanisms of the emergency logistics system. There are four modules in the emergency logistics system, including the information platform of emergency logistics, the rapid response mechanism of emergency logistics, government safeguards mechanism and feedback control mechanism of emergency logistics to four modules. Only co-operation of these innovative mechanisms, emergency supplies can be effectively protected.

  16. Mechanism of wavelength conversion in polystyrene doped with benzoxanthene: emergence of a complex

    Science.gov (United States)

    Nakamura, Hidehito; Shirakawa, Yoshiyuki; Kitamura, Hisashi; Sato, Nobuhiro; Shinji, Osamu; Saito, Katashi; Takahashi, Sentaro

    2013-01-01

    Fluorescent guest molecules doped in polymers have been used to convert ultraviolet light into visible light for applications ranging from optical fibres to filters for the cultivation of plants. The wavelength conversion process involves the absorption of light at short wavelengths followed by fluorescence emission at a longer wavelength. However, a precise understanding of the light conversion remains unclear. Here we show light responses for a purified polystyrene base substrates doped with fluorescent benzoxanthene in concentrations varied over four orders of magnitude. The shape of the excitation spectrum for fluorescence emission changes significantly with the concentration of the benzoxanthene, indicating formation of a base substrate/fluorescent molecule complex. Furthermore, the wavelength conversion light yield increases in three stages depending on the nature of the complex. These findings identify a mechanism that will have many applications in wavelength conversion materials. PMID:23974205

  17. Renewable Energy Investment in Emerging Markets: Evaluating Improvements to the Clean Development Mechanism

    Directory of Open Access Journals (Sweden)

    Amy Tang

    2014-06-01

    Full Text Available In the past, industrialized countries have invested in or financed numerous renewable energy projects in developing countries, primarily through the Clean Development Mechanism (CDM of the Kyoto Protocol. However, critics have pointed to its bureaucratic structure, problems with additionality and distorted credit prices as ill-equipped to streamline renewable energy investment. In this paper, we simulate the impact of policy on investment decisions on whether or not to invest in wind energy infrastructure in India, Brazil and China. Data from 2,578 past projects as well as literature on investor behaviour is used to inform the model structure and parameters. Our results show that the CDM acts differently in each country and reveal that while streamlining the approval process and reconsidering additionality can lead to non-trivial increase in total investment, stabilizing policy and decreasing investment risk will do the most to spur investment.

  18. Emerging GaN-based HEMTs for mechanical sensing within harsh environments

    Science.gov (United States)

    Köck, Helmut; Chapin, Caitlin A.; Ostermaier, Clemens; Häberlen, Oliver; Senesky, Debbie G.

    2014-06-01

    Gallium nitride based high-electron-mobility transistors (HEMTs) have been investigated extensively as an alternative to Si-based power transistors by academia and industry over the last decade. It is well known that GaN-based HEMTs outperform Si-based technologies in terms of power density, area specific on-state resistance and switching speed. Recently, wide band-gap material systems have stirred interest regarding their use in various sensing fields ranging from chemical, mechanical, biological to optical applications due to their superior material properties. For harsh environments, wide bandgap sensor systems are deemed to be superior when compared to conventional Si-based systems. A new monolithic sensor platform based on the GaN HEMT electronic structure will enable engineers to design highly efficient propulsion systems widely applicable to the automotive, aeronautics and astronautics industrial sectors. In this paper, the advancements of GaN-based HEMTs for mechanical sensing applications are discussed. Of particular interest are multilayered heterogeneous structures where spontaneous and piezoelectric polarization between the interface results in the formation of a 2-dimensional electron gas (2DEG). Experimental results presented focus on the signal transduction under strained operating conditions in harsh environments. It is shown that a conventional AlGaN/GaN HEMT has a strong dependence of drain current under strained conditions, thus representing a promising future sensor platform. Ultimately, this work explores the sensor performance of conventional GaN HEMTs and leverages existing technological advances available in power electronics device research. The results presented have the potential to boost GaN-based sensor development through the integration of HEMT device and sensor design research.

  19. Face learning and the emergence of view-independent face recognition: an event-related brain potential study.

    Science.gov (United States)

    Zimmermann, Friederike G S; Eimer, Martin

    2013-06-01

    Recognizing unfamiliar faces is more difficult than familiar face recognition, and this has been attributed to qualitative differences in the processing of familiar and unfamiliar faces. Familiar faces are assumed to be represented by view-independent codes, whereas unfamiliar face recognition depends mainly on view-dependent low-level pictorial representations. We employed an electrophysiological marker of visual face recognition processes in order to track the emergence of view-independence during the learning of previously unfamiliar faces. Two face images showing either the same or two different individuals in the same or two different views were presented in rapid succession, and participants had to perform an identity-matching task. On trials where both faces showed the same view, repeating the face of the same individual triggered an N250r component at occipito-temporal electrodes, reflecting the rapid activation of visual face memory. A reliable N250r component was also observed on view-change trials. Crucially, this view-independence emerged as a result of face learning. In the first half of the experiment, N250r components were present only on view-repetition trials but were absent on view-change trials, demonstrating that matching unfamiliar faces was initially based on strictly view-dependent codes. In the second half, the N250r was triggered not only on view-repetition trials but also on view-change trials, indicating that face recognition had now become more view-independent. This transition may be due to the acquisition of abstract structural codes of individual faces during face learning, but could also reflect the formation of associative links between sets of view-specific pictorial representations of individual faces.

  20. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms

    NARCIS (Netherlands)

    van Vliet, E.A.; Otte, W.M.; Wadman, W.J.; Aronica, E.; Kooij, G.; de Vries, H.E.; Dijkhuizen, R.M.; Gorter, J.A.

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  1. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II : Potential mechanisms

    NARCIS (Netherlands)

    van Vliet, Erwin A; Otte, Wim M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  2. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury.

    NARCIS (Netherlands)

    Andriessen, T.M.J.C.; Jacobs, B.; Vos, P.E.

    2010-01-01

    Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS

  3. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury

    NARCIS (Netherlands)

    Andriessen, Teuntje M J C; Jacobs, Bram; Vos, Pieter E

    2010-01-01

    Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS

  4. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Science.gov (United States)

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

  5. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

    Science.gov (United States)

    Deeb, Wissam; Giordano, James J.; Rossi, Peter J.; Mogilner, Alon Y.; Gunduz, Aysegul; Judy, Jack W.; Klassen, Bryan T.; Butson, Christopher R.; Van Horne, Craig; Deny, Damiaan; Dougherty, Darin D.; Rowell, David; Gerhardt, Greg A.; Smith, Gwenn S.; Ponce, Francisco A.; Walker, Harrison C.; Bronte-Stewart, Helen M.; Mayberg, Helen S.; Chizeck, Howard J.; Langevin, Jean-Philippe; Volkmann, Jens; Ostrem, Jill L.; Shute, Jonathan B.; Jimenez-Shahed, Joohi; Foote, Kelly D.; Wagle Shukla, Aparna; Rossi, Marvin A.; Oh, Michael; Pourfar, Michael; Rosenberg, Paul B.; Silburn, Peter A.; de Hemptine, Coralie; Starr, Philip A.; Denison, Timothy; Akbar, Umer; Grill, Warren M.; Okun, Michael S.

    2016-01-01

    This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field. PMID:27920671

  6. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

    Science.gov (United States)

    Deeb, Wissam; Giordano, James J; Rossi, Peter J; Mogilner, Alon Y; Gunduz, Aysegul; Judy, Jack W; Klassen, Bryan T; Butson, Christopher R; Van Horne, Craig; Deny, Damiaan; Dougherty, Darin D; Rowell, David; Gerhardt, Greg A; Smith, Gwenn S; Ponce, Francisco A; Walker, Harrison C; Bronte-Stewart, Helen M; Mayberg, Helen S; Chizeck, Howard J; Langevin, Jean-Philippe; Volkmann, Jens; Ostrem, Jill L; Shute, Jonathan B; Jimenez-Shahed, Joohi; Foote, Kelly D; Wagle Shukla, Aparna; Rossi, Marvin A; Oh, Michael; Pourfar, Michael; Rosenberg, Paul B; Silburn, Peter A; de Hemptine, Coralie; Starr, Philip A; Denison, Timothy; Akbar, Umer; Grill, Warren M; Okun, Michael S

    2016-01-01

    This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.

  7. Mechanisms of social avoidance learning can explain the emergence of adaptive and arbitrary behavioral traditions in humans.

    Science.gov (United States)

    Lindström, Björn; Olsson, Andreas

    2015-06-01

    Many nonhuman animals preferentially copy the actions of others when the environment contains predation risk or other types of danger. In humans, the role of social learning in avoidance of danger is still unknown, despite the fundamental importance of social learning for complex social behaviors. Critically, many social behaviors, such as cooperation and adherence to religious taboos, are maintained by threat of punishment. However, the psychological mechanisms allowing threat of punishment to generate such behaviors, even when actual punishment is rare or absent, are largely unknown. To address this, we used both computer simulations and behavioral experiments. First, we constructed a model where simulated agents interacted under threat of punishment and showed that mechanisms' (a) tendency to copy the actions of others through social learning, together with (b) the rewarding properties of avoiding a threatening punishment, could explain the emergence, maintenance, and transmission of large-scale behavioral traditions, both when punishment is common and when it is rare or nonexistent. To provide empirical support for our model, including the 2 mechanisms, we conducted 4 experiments, showing that humans, if threatened with punishment, are exceptionally prone to copy and transmit the behavior observed in others. Our results show that humans, similar to many nonhuman animals, use social learning if the environment is perceived as dangerous. We provide a novel psychological and computational basis for a range of human behaviors characterized by the threat of punishment, such as the adherence to cultural norms and religious taboos.

  8. New mechanized system for circle spraying of oil palms seedling emergence

    Directory of Open Access Journals (Sweden)

    Darius El Pebrian

    2012-04-01

    Full Text Available A new machine system has been designed, developed and evaluated for extensive circle spraying of oil palms (Elaeis guineensis Jacq. in an effort to overcome the inefficient spraying problem with the conventional spraying system. The machine system consists of a four-wheeled drive 4WD prime mover with front mounted machine attachments for the circle spraying operation. The configuration of the circle spraying attachment consists of a hexagonal curved spray boom, lifting arm, opening-tilting mechanism unit, storage tank, spray pump, solid cone nozzles, and associate hydraulic system. Field performance tests on the machine system showed an average effective field capacity of 7.89 ha per man per day and when compared to the earlier reported effective field capacity of the walking spray-operated equipment using Serena LT16 knapsack sprayer; a difference of 1.97 time for circle spraying of mature palms grove. Reduction in the human energy expenditure of 101.28 kJ man-1 h-1 or 10.68 % but an increase in the spraying cost of 1.53 USD ha-1 or 24.9 % were obtained with the machine system against the walking spraying-operated equipment using Serena LT16 knapsack sprayer. Justification for machine system to be cost effective could be satisfied if the present effective field capacity is increased to 1.263 time with good skilled operator or if the current R&D cost is reduced to 0.41 time. This is because the improved field capacity of new machine system could not rationalize its current R&D cost. Admittedly, the machine system has great potential to overcome the limitations with the current employed machine/equipment in the circle spraying operation of oil palms in the plantation.

  9. Is beat induction innate or learned? Probing emergent meter perception in adults and newborns using event-related brain potentials.

    Science.gov (United States)

    Honing, Henkjan; Ladinig, Olivia; Háden, Gábor P; Winkler, István

    2009-07-01

    Meter is considered an important structuring mechanism in the perception and experience of rhythm in music. Combining behavioral and electrophysiological measures, in the present study we investigate whether meter is more likely a learned phenomenon, possibly a result of musical expertise, or whether sensitivity to meter is also active in adult nonmusicians and newborn infants. The results provide evidence that meter induction is active in adult nonmusicians and that beat induction is already functional right after birth.

  10. Colistin in pig production: Chemistry, Mechanism of antibacterial action, Microbial resistance emergence, and One Health Perspectives

    Directory of Open Access Journals (Sweden)

    Mohamed Rhouma

    2016-11-01

    cooperation between physicians, veterinarians, and other scientific health and environmental professionals. This review is an update on the chemistry of colistin, its applications and antibacterial mechanism of action, and on Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the One Health approach and propose guidelines for colistin resistance management.

  11. Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives

    Science.gov (United States)

    Rhouma, Mohamed; Beaudry, Francis; Thériault, William; Letellier, Ann

    2016-01-01

    , veterinarians, and other scientific health and environmental professionals. This review is an update on the chemistry of colistin, its applications and antibacterial mechanism of action, and on Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the One Health approach and propose guidelines for colistin resistance management. PMID:27891118

  12. Effect of glycyrrhizin on traumatic brain injury in rats and its mechanism

    Directory of Open Access Journals (Sweden)

    Gu Xiangjin

    2014-02-01

    Full Text Available 【Abstract】Objective: To investigate the neuroprotective effects of glycyrrhizin (Gly as well as its effect on expression of high-mobility group box 1 (HMGB1 in rats after traumatic brain injury (TBI. Methods: Male Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group. Rat TBI model was made by using the modified Feeney’s method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4 and receptor for advanced glycation end products (RAGE/nuclear factor- κB(NF- κB signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed. Results: Beam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4- positive cells and apoptotic cells were respectively 58.37%±5.06%, 54.15%±4.65%, 65.50%± 4.83%, 52.02%± 4.63% in TBI group and 39.99%±4.99%, 34.87%±5.02%, 43.33%±4.54%, 37.84%±5.16% in TBI+Gly group (all P<0.01 compared with TBI group. Conclusion: Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB - mediated inflammatory responses in the injured rat brain.

  13. Effect of glycyrrhizin on traumatic brain injury in rats and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Gu Xiangjin; Xu Jin; Ma Banyou; Chen Gong; Gu Peiyuan; Wei Dong; Hu Weixing

    2014-01-01

    Objective:To investigate the neuroprotective effects of glycyrrhizin (Gly) as well as its effect on expression of high-mobility group box 1 (HMGB 1) in rats after traumatic brain injury (TBI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:sham group,TBI group,and TBI+Gly group (n=36 per group).Rat TBI model was made by using the modified Feeney's method.In TBI+Gly group,Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI.At 24 h after TBI,motor function and brain water content were evaluated.Meanwhile,HMGB 1/HMGB 1 receptors including toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nuclear factor-κ B(NF-κ B) signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction,western blot,electrophoretic mobility shift assay and enzyme-linked immunosorbent assay.Furthermore,HMGB 1,RAGE and TLR4 immunohistochemistry and apoptosis were analyzed.Results:Beam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile,the over-expressions of HMGB 1/HMGB 1 receptors (TLR4 and RAGE)/NF-κB DNA-binding activity and inflammatory cytokines were inhibited.The percentages of HMGB 1,RAGE and TLR4positive cells and apoptotic cells were respectively 58.37%±5.06%,54.15%±4.65%,65.50%± 4.83%,52.02%± 4.63% in TBI group and 39.99%±4.99%,34.87%±5.02%,43.33%±4.54%,37.84%±5.16% in TBI+Gly group (all P<0.01 compared with TBI group).Conclusion:Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB 1/HMGB 1 receptors (TLR4 and RAGE)/NF-κ B-mediated inflammatory responses in the injured rat brain.

  14. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

    Science.gov (United States)

    Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

    2016-01-01

    The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  15. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

    Directory of Open Access Journals (Sweden)

    Chuan-Chih Yang

    2016-01-01

    Full Text Available The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation and between time points (before versus after training were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  16. Brain mechanisms of male sexual function%男性性活动相关的脑机制

    Institute of Scientific and Technical Information of China (English)

    王营; 窦鑫; 李俊发

    2011-01-01

    本文从正常性功能的脑机制、性功能障碍的脑机制以及药物治疗机制等几个方面综述了近年来男性性相关的脑成像研究.研究发现男性性活动兴奋期、平台期和高潮期由不同脑区构成的神经网络控制.其中,间脑转换区在男性射精中发挥了关键的启动作用.男性性功能障碍患者在性唤起时存在眶额回和额下回的异常激活模式.血清睾酮和脱水吗啡等药物治疗性功能障碍时,主要通过改变眶额回、脑岛、屏状核和颞下回的激活状态来发挥作用.%In this paper, we reviewed the brain imaging studies of male sexual function in recent years from three aspects: the brain mechanism of normal sexual function, the brain mechanism of sexual dysfunction, and the mechanism of drug therapy for sexual dysfunction. Studies show that the development stages of male sexual activities, such as the excitement phase, plateau phase and orgasm phase, are controlled by different neural networks. The mesodiencephalic transition zone may play an important role in the startup of male ejaculation. There are significant differences between sexual dysfunction males and normal males in activation patterns of the brain in sexual arousal. The medial orbitofrontal cortex and inferior frontal gyrus in the abnormal activation pattern are correlated with sexual dysfunction males in sexual arousal. Serum testosterone and morphine are commonly used drugs for male sexual dysfunction,whose mechanisms are to alter the activating levels of the medial orbitofrontal cortex, insula, claustrum and inferior temporal gyrus.Natl J Androl, 2011, 17 (8): 739-743

  17. Brain mechanisms of hypoxic preconditioning%低氧预适应的脑机制

    Institute of Scientific and Technical Information of China (English)

    吕国蔚; 崔秀玉; 赵兰峰; 安仰原; 高翠英

    2004-01-01

    A concept ot tissue adaptation to hypoxia( i.e. hypoxic preconditioning) was developed and its corresponding animal models were reproduced in 1966s. The methods of model reproduction in rat, rabbit, and mouse in particular and the main results are brifly introduced in this review. The tolerance to hypoxia o{ preconditioned animals is significantly increased. Regular changes in animals' behavior, neurophysiology, respiratory and circulatory physiology, neuromorphology in vivo and {unction of brain and spinal cord in vitro are briefly demonstrated. The protective effects in vivo and in vitro of homogenate extract taken from the brain o{ preconditioned animals, neurochemcals and molecular neurobiolcgical alterations are briefly presented. The essence and significance of tissue adaption to hypoxia/hypoxic preconditioning are discussed in the review in terms of evolution and practical implication.

  18. Holographic View of the Brain Memory Mechanism Based on Evanescent Superluminal Photons

    Directory of Open Access Journals (Sweden)

    Takaaki Musha

    2012-08-01

    Full Text Available D. Pollen and M. Trachtenberg proposed the holographic brain theory to help explain the existence of photographic memories in some people. They suggested that such individuals had more vivid memories because they somehow could access a very large region of their memory holograms. Hameroff suggested in his paper that cylindrical neuronal microtubule cavities, or centrioles, function as waveguides for the evanescent photons for quantum signal processing. The supposition is that microtubular structures of the brain function as a coherent fiber bundle set used to store holographic images, as would a fiber-optic holographic system. In this paper, the author proposes that superluminal photons propagating inside the microtubules via evanescent waves could provide the access needed to record or retrieve a quantum coherent entangled holographic memory.

  19. Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy after Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2013-10-01

    Implementation of post- TBI pain behavior measurements. 15. SUBJECT TERMS Traumatic brain injury, cortical spreading depression, seizure, post-traumatic...conventional recovery is complete. We test with video EEG monitoring for increased excitability, and use behavioral measures to test the pain response...months after CCI TBI (Brennan/Dudek, Months 18-36). Pending. Will be performed simultaneous with task 1.f. above. g. Perform nociception

  20. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

    Science.gov (United States)

    Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

    2015-01-01

    Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation. PMID:26582977

  1. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms.

    Science.gov (United States)

    Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

    2015-01-01

    Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation.

  2. Effect of Heavy Ion Brain Radiation on Nerve-immune System Regulation Mechanism in Rat

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; KONG; Fu-quan; SUI; Li; LEI; Run-hong; MA; Hong; DENG; Yu-lin; LI; Qiang

    2013-01-01

    High-dose ionizing irradiation can cause extensive injuries in susceptible tissues.Blood,nervous and immune systems are highly radiation-sensitive.While the nerve-immune system regulation of radiationdamage in the relevant research is rare.So the brain injury model that rats were subjected to 15 Gy of head irradiation was built.By detecting hypothalamic-pituitary-adrenal axis(HPA axis)changes,the

  3. Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and clinical implications.

    Science.gov (United States)

    d'Avella, D; Cicciarello, R; Angileri, F F; Lucerna, S; La Torre, D; Tomasello, F

    1998-01-01

    The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

  4. S-Nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats

    Directory of Open Access Journals (Sweden)

    Gilg Anne G

    2011-07-01

    Full Text Available Abstract Background Traumatic brain injury (TBI induces primary and secondary damage in both the endothelium and the brain parenchyma, collectively termed the neurovascular unit. While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury in the neurovascular unit following TBI. In activated endothelial cells, excessive superoxide reacts with nitric oxide (NO to form peroxynitrite. Peroxynitrite has been implicated in blood brain barrier (BBB leakage, altered metabolic function, and neurobehavioral impairment. S-nitrosoglutathione (GSNO, a nitrosylation-based signaling molecule, was reported not only to reduce brain levels of peroxynitrite and oxidative metabolites but also to improve neurological function in TBI, stroke, and spinal cord injury. Therefore, we investigated whether GSNO promotes the neurorepair process by reducing the levels of peroxynitrite and the degree of oxidative injury. Methods TBI was induced by controlled cortical impact (CCI in adult male rats. GSNO or 3-Morpholino-sydnonimine (SIN-1 (50 μg/kg body weight was administered orally two hours following CCI. The same dose was repeated daily until endpoints. GSNO-treated (GSNO group or SIN-1-treated (SIN-1 group injured animals were compared with vehicle-treated injured animals (TBI group and vehicle-treated sham-operated animals (Sham group in terms of peroxynitrite, NO, glutathione (GSH, lipid peroxidation, blood brain barrier (BBB leakage, edema, inflammation, tissue structure, axon/myelin integrity, and neurotrophic factors. Results SIN-1 treatment of TBI increased whereas GSNO treatment decreased peroxynitrite, lipid peroxides/aldehydes, BBB leakage, inflammation and edema in a short-term treatment (4-48 hours. GSNO also reduced brain infarctions and enhanced the levels of NO and GSH. In a long-term treatment (14 days, GSNO protected axonal integrity, maintained myelin levels, promoted synaptic plasticity

  5. Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk.

    Science.gov (United States)

    Costa, Pedro M; Fadeel, Bengt

    2016-05-15

    Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global 'omics' approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials.

  6. The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases.

    Science.gov (United States)

    Balistreri, Carmela Rita; Madonna, Rosalinda; Melino, Gerry; Caruso, Calogero

    2016-08-01

    Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until now there is a confounding evidence about the related mechanisms. Here, we discuss mechanisms through which Notch signaling acts in a very complex network of pathways, where it seems to have the crucial role of hub. Thus, we stress the possibility to use Notch pathway, the related molecules and pathways constituting this network, both as innovative (predictive, diagnostic and prognostic) biomarkers and targets for personalised treatments for age-related diseases.

  7. Short-term retrospective versus prospective memory processing as emergent properties of the mind and brain: human fMRI evidence.

    Science.gov (United States)

    Mok, L W

    2012-12-13

    demonstrated that short-term retrospection and prospection may emerge without necessarily relying on working memory-specific brain networks. Furthermore, attention may not necessarily be recruited to realize working memory. When cognitive processes are spontaneously experienced, they may be facilitated by the default brain network.

  8. There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD/ALS.

    Science.gov (United States)

    Gitler, Aaron D; Tsuiji, Hitomi

    2016-09-15

    The discovery of C9orf72 mutations as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has awakened a surge of interest in deciphering how mutations in this mysterious gene cause disease and what can be done to stop it. C9orf72 harbors a hexanucleotide repeat, GGGGCC, in a non-coding region of the gene and a massive expansion of this repeat causes ALS, FTD, or both (FTD/ALS). Many questions lie ahead. What does this gene normally do? What is the consequence of an enormous GGGGCC repeat expansion on that gene's function? Could that hexanucleotide repeat expansion have additional pathological actions unrelated to C9orf72 function? There has been tremendous progress on all fronts in the quest to define how C9orf72 mutations cause disease. Many new experimental models have been constructed and unleashed in powerful genetic screens. Studies in mouse and human patient samples, including iPS-derived neurons, have provided unprecedented insights into pathogenic mechanisms. Three major hypotheses have emerged and are still being hotly debated in the field. These include (1) loss of function owing to decrease in the abundance of C9orf72 protein and its ability to carryout its still unknown cellular role; (2) RNA toxicity from bidirectionally transcribed sense (GGGGCC) and antisense (GGCCCC) transcripts that accumulate in RNA foci and might sequester critical RNA-binding proteins; (3) proteotoxicity from dipeptide repeat proteins produced by an unconventional form of translation from the expanded nucleotide repeats. Here we review the evidence in favor and against each of these three hypotheses. We also suggest additional experiments and considerations that we propose will help clarify which mechanism(s) are most important for driving disease and therefore most critical for considering during the development of therapeutic interventions. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.

  9. Unexpected events induce motor slowing via a brain mechanism for action-stopping with global suppressive effects.

    Science.gov (United States)

    Wessel, Jan R; Aron, Adam R

    2013-11-20

    When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression.

  10. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    Science.gov (United States)

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  11. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    Dissertação de mestrado em Biologia Celular e Molecular apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sinápti...

  12. Brain hemorrhage after electrical burn injury: Case report and probable mechanism

    Science.gov (United States)

    Axayacalt, Gutierrez Aceves Guillermo; Alejandro, Ceja Espinosa; Marcos, Rios Alanis; Inocencio, Ruiz Flores Milton; Alfredo, Herrera Gonzalez Jose

    2016-01-01

    Background: High-voltage electric injury may induce lesion in different organs. In addition to the local tissue damage, electrical injuries may lead to neurological deficits, musculoskeletal damage, and cardiovascular injury. Severe vascular damage may occur making the blood vessels involved prone to thrombosis and spontaneous rupture. Case Description: Here, we present the case of a 39-year-old male who suffered an electrical burn with high tension wire causing intracranial bleeding. He presented with an electrical burn in the parietal area (entry zone) and the left forearm (exit zone). The head tomography scan revealed an intraparenchimatous bleeding in the left parietal area. In this case, the electric way was the scalp, cranial bone, blood vessels and brain, upper limb muscle, and skin. The damage was different according to the dielectric property in each tissue. The injury was in the scalp, cerebral blood vessel, skeletal muscle, and upper limb skin. The main damage was in brain’s blood vessels because of the dielectric and geometric features that lead to bleeding, high temperature, and gas delivering. Conclusion: This is a report of a patient with an electric brain injury that can be useful to elucidate the behavior of the high voltage electrical current flow into the nervous system. PMID:27904757

  13. Blood-brain barrier permeability mechanisms in view of quantitative structure-activity relationships (QSAR).

    Science.gov (United States)

    Bujak, Renata; Struck-Lewicka, Wiktoria; Kaliszan, Michał; Kaliszan, Roman; Markuszewski, Michał J

    2015-04-10

    The goal of the present paper was to develop a quantitative structure-activity relationship (QSAR) method using a simple statistical approach, such as multiple linear regression (MLR) for predicting the blood-brain barrier (BBB) permeability of chemical compounds. The "best" MLR models, comprised logP and either molecular mass (M) or isolated atomic energy (E(isol)), tested on a structurally diverse set of 66 compounds, is characterized the by correlation coefficients (R) around 0.8. The obtained models were validated using leave-one-out (LOO) cross-validation technique and the correlation coefficient of leave-one-out- R(LOO)(2) (Q(2)) was at least 0.6. Analysis of a case from legal medicine demonstrated informative value of our QSAR model. To best authors' knowledge the present study is a first application of the developed QSAR models of BBB permeability to case from the legal medicine. Our data indicate that molecular energy-related descriptors, in combination with the well-known descriptors of lipophilicity may have a supportive value in predicting blood-brain distribution, which is of utmost importance in drug development and toxicological studies.

  14. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review

    Directory of Open Access Journals (Sweden)

    David O. Kennedy

    2016-01-01

    Full Text Available The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6 that are the most prominent (but not the exclusive B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.

  15. Mechanisms of oxidative stress in brain ischemia injury%氧化应激在脑缺血损伤中的作用机制

    Institute of Scientific and Technical Information of China (English)

    赵丹洋; 吴伟康

    2004-01-01

    Oxidative stress has been implicated in brain injury after ischemia, which is a complex cascade. These oxidants produced by oxidative stress are directly involved in oxidative damage with cellular macromolecules such as lipids, proteins and nucleic acids, which lead to cell death. Oxidants are also mediators in signaling involving mitochondria pathway, DNA repair enzymes, and transcription factor that may lead to apoptosis after cerebral ischemia. Antioxidangt enzymes (such as superoxide dismutase,etc) provide useful tools in dissecting the events involving oxidative stress in signaling and damage in ischemic brain injury. This review focuses on the mechanisms of oxidative stress during brain ischemia.

  16. Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy after Brain Injury (TBI)

    Science.gov (United States)

    2015-12-01

    memantine after TBI, in this case with a focus on pain metrics. Subtask 2. Perform nociception behavior experiments (mechanical and thermal thresholds...cortex is more susceptible to spreading depolarizations, consistent with prominent sensory and pain features after TBI; 5. the effects of TBI are... nociception behavior experiments (mechanical and thermal thresholds, rotarod) on animals 3 months after CCI TBI. We have experience with both

  17. Assessing Quantitative Changes in Intrinsic Thalamic Networks in Blast and Nonblast Mild Traumatic Brain Injury: Implications for Mechanisms of Injury.

    Science.gov (United States)

    Nathan, Dominic E; Bellgowan, Julie F; Oakes, Terrence R; French, Louis M; Nadar, Sreenivasan R; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

    2016-06-01

    In the global war on terror, the increased use of improvised explosive devices has resulted in increased incidence of blast-related mild traumatic brain injury (mTBI). Diagnosing mTBI is both challenging and controversial due to heterogeneity of injury location, trauma intensity, transient symptoms, and absence of focal biomarkers on standard clinical imaging modalities. The goal of this study is to identify a brain biomarker that is sensitive to mTBI injury. Research suggests the thalamus may be sensitive to changes induced by mTBI. A significant number of connections to and from various brain regions converge at the thalamus. In addition, the thalamus is involved in information processing, integration, and regulation of specific behaviors and mood. In this study, changes in task-free thalamic networks as quantified by graph theory measures in mTBI blast (N = 186), mTBI nonblast (N = 80), and controls (N = 21) were compared. Results show that the blast mTBI group had significant hyper-connectivity compared with the controls and nonblast mTBI group. However, after controlling for post-traumatic stress symptoms (PTSS), the blast mTBI group was not different from the controls, but the nonblast mTBI group showed significant hypo-connectivity. The results suggest that there are differences in the mechanisms of injury related to mTBI as reflected in the architecture of the thalamic networks. However, the effect of PTSS and its relationship to mTBI is difficult to distinguish and warrants more research.

  18. Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?

    Science.gov (United States)

    Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu

    2013-01-01

    Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.

  19. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, F. K. [Toronto Western Research Institute, University Health Network, Krembil Discovery Tower, Toronto Western Hospital, 60 Leonard Street, 7th floor, 7KD411, Toronto, Ontario M5T 2S8 (Canada); Department of Medicine (Neurology), University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4 (Canada); Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King' s College Circle, Toronto, Ontario M5S 1A8 (Canada); Ferguson, K. A. [Toronto Western Research Institute, University Health Network, Krembil Discovery Tower, Toronto Western Hospital, 60 Leonard Street, 7th floor, 7KD411, Toronto, Ontario M5T 2S8 (Canada); Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King' s College Circle, Toronto, Ontario M5S 1A8 (Canada)

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  20. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

    Directory of Open Access Journals (Sweden)

    Valérie Wolff

    2015-01-01

    Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

  1. Updates in the pathophysiological mechanisms of Parkinson’s disease: Emerging role of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Hanaa; H; Ahmed; Ahmed; M; Salem; Hazem; M; Atta; Emad; F; Eskandar; Abdel; Razik; H; Farrag; Mohamed; A; Ghazy; Neveen; A; Salem; Hadeer; A; Aglan

    2016-01-01

    AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson’s disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

  2. Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.

    Science.gov (United States)

    Kung, H F; Blau, M

    1980-02-01

    This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

  3. Brain mechanisms of persuasion: how ‘expert power’ modulates memory and attitudes

    Science.gov (United States)

    Smidts, Ale; Fernández, Guillén

    2008-01-01

    Human behaviour is affected by various forms of persuasion. The general persuasive effect of high expertise of the communicator, often referred to as ’expert power’, is well documented. We found that a single exposure to a combination of an expert and an object leads to a long-lasting positive effect on memory for and attitude towards the object. Using functional magnetic resonance imaging, we probed the neural processes predicting these behavioural effects. Expert context was associated with distributed left-lateralized brain activity in prefrontal and temporal cortices related to active semantic elaboration. Furthermore, experts enhanced subsequent memory effects in the medial temporal lobe (i.e. in hippocampus and parahippocampal gyrus) involved in memory formation. Experts also affected subsequent attitude effects in the caudate nucleus involved in trustful behaviour, reward processing and learning. These results may suggest that the persuasive effect of experts is mediated by modulation of caudate activity resulting in a re-evaluation of the object in terms of its perceived value. Results extend our view of the functional role of the dorsal striatum in social interaction and enable us to make the first steps toward a neuroscientific model of persuasion. PMID:19015077

  4. Brain dynamic mechanisms on the visual attention scale with Chinese characters cues

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The temporal dynamics in brain evoked by the scale of visual attention with the cues of Chinese characters were studied by recording event-related potentials (ERPs). With the fixed orientation of visual attention, 14 healthy young participants performed a search task in which the search array was preceded by Chinese characters cues, "大, 中, 小" (large, medium, small). 128 channels scalp ERPs were recorded to study the role of visual attention scale played in the visual spatial attention. The results showed that there was no significant difference in the ERP components evoked by the three Chinese characters cues except the inferoposterior N2 latency. The targets evoked P2, N2 amplitudes and latency have significant differences with the different cues of large, middle and small, while P1 and N1 components had no significant difference. The results suggested that the processing of scale of visual attention was mainly concerned with P2, N2 components, while the P1, N1 components were mainly related with the processing of visual orientation information.

  5. Brain mechanisms underlying the effects of aging on different aspects of selective attention

    NARCIS (Netherlands)

    Geerligs, Linda; Saliasi, Emi; Maurits, Natasha M; Renken, Remco J; Lorist, Monicque M

    2014-01-01

    The ability to suppress irrelevant information declines with age, while the ability to enhance relevant information remains largely intact. We examined mechanisms behind this dissociation in an fMRI study, using a selective attention task in which relevant and irrelevant information appeared simulta

  6. Speech and music shape the listening brain: Evidence for shared domain-general mechanisms

    NARCIS (Netherlands)

    Asaridou, S.S.; McQueen, J.M.

    2013-01-01

    Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This r

  7. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    in patients with NMO. The degree of mechanical hyperalgesia reflecting central sensitization of nociceptive pathways seems to be controlled by the major brain endocannabinoid 2-AG.

  8. On the mechanical characterization and modeling of polymer gel brain substitute under dynamic rotational loading.

    Science.gov (United States)

    Fontenier, B; Hault-Dubrulle, A; Drazetic, P; Fontaine, C; Naceur, H

    2016-10-01

    The use of highly sensitive soft materials has become increasingly apparent in the last few years in numerous industrial fields, due to their viscous and damping nature. Unfortunately these materials remain difficult to characterize using conventional techniques, mainly because of the very low internal forces supported by these materials especially under high strain-rates of deformation. The aim of this work is to investigate the dynamic response of a polymer gel brain analog material under specific rotational-impact experiments. The selected polymer gel commercially known as Sylgard 527 has been studied using a specific procedure for its experimental characterization and numerical modeling. At first an indentation experiment was conducted at several loading rates to study the strain rate sensitivity of the Sylgard 527 gel. During the unloading several relaxation tests were performed after indentation, to assess the viscous behavior of the material. A specific numerical procedure based on moving least square approximation and response surface method was then performed to determine adequate robust material parameters of the Sylgard 527 gel. A sensitivity analysis was assessed to confirm the robustness of the obtained material parameters. For the validation of the obtained material model, a second experiment was conducted using a dynamic rotational loading apparatus. It consists of a metallic cylindrical cup filled with the polymer gel and subjected to an eccentric transient rotational impact. Complete kinematics of the cup and the large strains induced in the Sylgard 527 gel, have been recorded at several patterns by means of optical measurement. The whole apparatus was modeled by the Finite Element Method using explicit dynamic time integration available within Ls-dyna(®) software. Comparison between the physical and the numerical models of the Sylgard 527 gel behavior under rotational choc shows excellent agreements.

  9. Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy After Traumatic Brain Injury

    Science.gov (United States)

    2014-10-01

    test the pain response. We will specifically probe the glial scar and surrounding tissue for evidence of aberrant excitation. -If development of...after CCI TBI. Pending. Will be performed simultaneous with task 1.f. above. Subtask 6. Perform nociception behavior experiments (mechanical and...after TBI in both animals and humans) is associated with pain behavior and could confound results if not measured specifically. Our combined general

  10. Bio-Mechanical Model of the Brain for a Per-Operative Image-Guided Neuronavigator Compensating for "Brain-Shift" Deformations

    CERN Document Server

    Bucki, Marek; Payan, Yohan

    2007-01-01

    In this paper we present a methodology to address the problem of brain tissue deformation referred to as 'brain-shift'. This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on pre-operative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intra-operative image-guided system, we describe a procedure to generate patient specific finite element meshes of the brain and propose a biomechanical model which can take into account tissue deformations and surgical procedures that modify the brain structure, like tumour or tissue resection.

  11. Understanding complexity in the human brain.

    Science.gov (United States)

    Bassett, Danielle S; Gazzaniga, Michael S

    2011-05-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind-brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind-brain mechanisms.

  12. Driving pressure during assisted mechanical ventilation: Is it controlled by patient brain?

    Science.gov (United States)

    Georgopoulos, Dimitris; Xirouchaki, Nectaria; Tzanakis, Nikolaos; Younes, Magdy

    2016-07-01

    Tidal volume (VT) is the controlled variable during passive mechanical ventilation (CMV) in order to avoid ventilator-induced-lung-injury. However, recent data indicate that the driving pressure [ΔP; VT to respiratory system compliance (Crs) ratio] is the parameter that best stratifies the risk of death. In order to study which variable (VT or ΔP) is controlled by critically ill patients, 108 previously studied patients were assigned to receive PAV+ (a mode that estimates Crs and permits the patients to select their own breathing pattern) after CMV, were re-analyzed. When patients were switched from CMV to PAV+ they controlled ΔP without constraining VT to narrow limits. VT was increased when the resumption of spontaneous breathing was associated with an increase in Crs. When ΔP was high during CMV, the patients (n=12) decreased it in 58 out of 67 measurements. We conclude that critically ill patients control the driving pressure by sizing the tidal volume to individual respiratory system compliance using appropriate feedback mechanisms aimed at limiting the degree of lung stress.

  13. Investigations of oxidative stress effects and their mechanisms in rat brain after systemic administration of ceria engineered nanomaterials

    Science.gov (United States)

    Hardas, Sarita S.

    Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives and for therapeutic intervention as a putative antioxidant. However, the biological effects of ceria ENM exposure have yet to be fully defined. Both pro-and anti-oxidative effects of ceria ENM exposure are repeatedly reported in literature. EPA, NIEHS and OECD organizations have nominated ceria for its toxicological evaluation. All these together gave us the impetus to examine the oxidative stress effects of ceria ENM after systemic administration. Induction of oxidative stress is one of the primary mechanisms of ENM toxicity. Oxidative stress plays an important role in maintaining the redox homeostasis in the biological system. Increased oxidative stress, due to depletion of antioxidant enzymes or molecules and / or due to increased production of reactive oxygen (ROS) or nitrogen (RNS) species may lead to protein oxidation, lipid peroxidation and/or DNA damage. Increased protein oxidation or lipid peroxidation together with antioxidant protein levels and activity can serve as markers of oxidative stress. To investigate the oxidative stress effects and the mechanisms of ceria-ENM toxicity, fully characterized ceria ENM of different sizes (˜ 5nm, 15nm, 30nm, 55nm and nanorods) were systematically injected into rats intravenously in separate experiments. Three brain regions

  14. Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signaltransduction pathway in depressive disorder

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Yingquan Zhang; Mingqi Qiao

    2013-01-01

    The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.

  15. Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder.

    Science.gov (United States)

    Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

    2013-03-25

    The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.

  16. Research on quantify structural analysis of brain cisterns and emergency surgical indications%量化脑池结构分析与急诊手术指征的研究

    Institute of Scientific and Technical Information of China (English)

    林其昌; 林少华; 黄汉添; 胡子慧

    2014-01-01

    Objective To investigate the changes of brain cisterns structure caused by acute intracranial lesions,which can response emergency surgical indications more fundamentally from a compensatory spatial perspective.Methods One hundred and twenty cases of acute intracranial lesions (including traumatic brain injury,cerebral hemorrhage,cerebral ischemia,etc) were conditionally screened.Track CT scan and quantify structural analysis of brain cisterns,60 cases were classified as the conservative treatment group which had the traditional indication for surgery and the definition of brain cisterns.Another 60 cases were classified as the emergency surgery group which had no obvious intracranial spaceoccupying but brain cisterns structure disappeared.Results According to quantify brain cisterns structure analysis to guide surgical decision.Two groups both had good prognosis.Conclusions Quantify structural analysis of brain cisterns can be considered as one of the important indications for emergency surgery.%目的 探讨急性颅内病变所致的脑池结构变化,从可代偿空间角度更本质地反映急诊手术指征.方法 按条件筛选120例急性颅内病变患者(包括颅脑损伤、脑出血、脑缺血等),追踪CT扫描并作量化脑池结构分析,其中60例有明确传统手术指征但脑池结构清晰列为保守治疗组,相反另60例无明显颅内占位但脑池结构变化而行急诊手术治疗列为手术组.结果 按量化脑池结构分析指导决定手术的急缓,两组患者预后理想.结论 量化脑池结构分析可作为急诊手术指征的另一重要依据之一.

  17. The changing brain--insights into the mechanisms of neural and behavioral adaptation to the environment

    DEFF Research Database (Denmark)

    Bergersen, L H; Bramham, C R; Hugdahl, K

    2013-01-01

    in the vomero-nasal organ can switch off male-specific and switch on female-specific innate behavior of mice in response to environmental stimulation (Dulac). Innate behaviors can be stably transmitted from parent to offspring through generations even when those behaviors cannot be expressed, as illustrated...... of the Symposium presentations was the mechanisms by which animals adapt to their environment. The symposium speakers--Michael Greenberg, Erin Schuman, Chiara Cirelli, Michael Meaney, Catherine Dulac, Hopi Hoekstra, and Stanislas Dehaene--covered topics ranging from the molecular and cellular levels to the systems...... level and behavior. Thus a single amino acid change in a transcriptional repressor can disrupt gene regulation through neural activity (Greenberg). Deep sequencing analysis of the neuropil transcriptome indicates that a large fraction of the synaptic proteome is synthesized in situ in axons...

  18. Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

    Science.gov (United States)

    Chang, Alice Y W; Li, Faith C H; Huang, Chi-Wei; Wu, Julie C C; Dai, Kuang-Yu; Chen, Chang-Han; Li, Shau-Hsuan; Su, Chia-Hao; Wu, Re-Wen

    2014-11-01

    Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.

  19. The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Norman R. Saunders

    2016-03-01

    Full Text Available Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain’s internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses. In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal environment of the body. An essential morphological component of all but one of the barriers is the presence of specialized intercellular tight junctions between the cells comprising the interface: endothelial cells in the blood-brain barrier itself, cells of the arachnoid membrane, choroid plexus epithelial cells, and tanycytes (specialized glial cells in the circumventricular organs. In the ependyma lining the cerebral ventricles in the adult brain, the cells are joined by gap junctions, which are not restrictive for intercellular movement of molecules. But in the developing brain, the forerunners of these cells form the neuroepithelium, which restricts exchange of all but the smallest molecules between cerebrospinal fluid and brain interstitial fluid because of the presence of strap junctions between the cells. The intercellular junctions in all these interfaces are the physical basis for their barrier properties. In the blood-brain barrier proper, this is combined with a paucity of vesicular transport that is a characteristic of other vascular beds. Without such a diffusional restrain, the cellular transport mechanisms in the barrier interfaces would be ineffective. Superimposed on these physical structures are physiological mechanisms as the cells of the interfaces contain various metabolic transporters and efflux pumps, often ATP-binding cassette (ABC

  20. 'No time to be lost!' Ethical considerations on consent for inclusion in emergency pharmacological research in severe traumatic brain injury in the European Union

    NARCIS (Netherlands)

    E.J.O. Kompanje (Erwin)

    2007-01-01

    textabstractSevere Traumatic Brain Injury (TBI) remains a major cause of death and disability afflicting mostly young adult males and elderly people, resulting in high economic costs to society. Therapeutic approaches focus on reducing the risk on secondary brain injury. Specific ethical issues pert

  1. Brain-derived neurotrophic factor (BDNF as a potential mechanism of the effects of acute exercise on cognitive performance

    Directory of Open Access Journals (Sweden)

    Aaron T. Piepmeier

    2015-03-01

    Full Text Available The literature shows that improvements in cognitive performance may be observed following an acute bout of exercise. However, evidence in support of the biological mechanisms of this effect is still limited. Findings from both rodent and human studies suggest brain-derived neurotrophic factor (BDNF as a potential mechanism of the effect of acute exercise on memory. The molecular properties of BDNF allow this protein to be assessed in the periphery (pBDNF (i.e., blood serum, blood plasma, making measurements of acute exercise-induced changes in BDNF concentration relatively accessible. Studies exploring the acute exercise–pBDNF–cognitive performance relationship have had mixed findings, but this may be more reflective of methodological differences between studies than it is a statement about the role of BDNF. For example, significant associations have been observed between acute exercise-induced changes in pBDNF concentration and cognitive performance in studies assessing memory, and non-significant associations have been found in studies assessing non-memory cognitive domains. Three suggestions are made for future research aimed at understanding the role of BDNF as a biological mechanism of this relationship: 1 Assessments of cognitive performance may benefit from a focus on various types of memory (e.g., relational, spatial, long-term; 2 More fine-grained measurements of pBDNF will allow for the assessment of concentrations of specific isoforms of the BDNF protein (i.e., immature, mature; 3 Statistical techniques designed to test the mediating role of pBDNF in the acute exercise-cognitive performance relationship should be utilized in order to make causal inferences.

  2. Brain and behavioral evidence for altered social learning mechanisms among women with assault-related posttraumatic stress disorder.

    Science.gov (United States)

    Cisler, Josh M; Bush, Keith; Scott Steele, J; Lenow, Jennifer K; Smitherman, Sonet; Kilts, Clinton D

    2015-04-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n = 25) and control women (n = 15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically.

  3. Mechanism of blood-brain barrier impairment after mild traumatic brain injury caused by blast shock waves and its relationship with delayed nerve dysfunction

    Directory of Open Access Journals (Sweden)

    Zhao-xi XU

    2016-06-01

    Full Text Available Mild traumatic brain injury (mTBI caused by blast shock waves (BSWs is one of the most common injuries among soldiers in the war. Such mTBI can also happen in civilians if exposed to shock waves of accidental explosion disasters, bomb attacks by terrorists and so on. This injury often results in cognitive problems, memory dysfunction and emotional disorder, and these neurological deficits are closely related to the dysfunction or disruption of the blood-brain barrier (BBB. The present paper discusses mainly the relationship between dysfunction or disruption of BBB and inflammatory reaction in mild brain injury associated with explosive shock wave and effects of early intervention of oxidative stress injury, repairing the BBB and blocking inflammation on relieving delayed neurological deficits. DOI: 10.11855/j.issn.0577-7402.2016.05.15

  4. Use of non-invasive mechanical ventilation in the Emergency Department, clinical outcomes and correlates of failure

    Directory of Open Access Journals (Sweden)

    Paolo Groff

    2008-09-01

    Full Text Available

    Background: Despite several studies having been carried in this organizational context, there is an absence of information about the effectiveness of non-invasive mechanical ventilation (NIV in Emergency Departments (ED, based on a number of suitable patients with acute respiratory failure (ARF of different aetiology. In particular, it has not yet been defined as to whether the context of the ED suits the necessary requirement of quality for the correct application of the method and if the obtained results are different from those taken in other studies in general or respiratory intensive care unit. Finally there are few data related to the predictive factors to NIV failure (endotracheal intubation, in-hospital mortality when applied in the emergency setting.

    Methods: To answer these questions we have retrospectively studied a population of 210 patients (95 with COPD exsacerbation ; 92 with acute cardiogenic pulmonary oedema; 23 with severe community acquired pneumonia treated for ARF in the “critical area” of four Italian level II Emergency Departments. For all patients demographic data; some comorbidities (diabetes, dementia, sopraventricular arrhythmias, obesity; the physiological scores (Kelly, SAPS II, Apache II; the need for pharmacological sedation; vital and blood gas parameters (evaluated at entry, after one hour of treatment and before its suspension; the ventilatory modality applied (CPAP or PSV + PEEP and some parameters of in-hospital stay (duration of the hospitalization in the critical area, duration of ventilation, compliance to the treatment, patient's refusal to continue it, development of skin necrosis, need for endotracheal intubation, in-hospital mortality were considered. Finally demographic, event of death with Cox regression or to the need for ETI through linear regression analysis.

    Results: Globally, in-hospital mortality reached 13,3%, the percentage

  5. Voluntary exercise promotes beneficial anti-aging mechanisms in SAMP8 female brain.

    Science.gov (United States)

    Bayod, Sergi; Guzmán-Brambila, Carolina; Sanchez-Roige, Sandra; Lalanza, Jaume F; Kaliman, Perla; Ortuño-Sahagun, Daniel; Escorihuela, Rosa M; Pallàs, Mercè

    2015-02-01

    Regular physical exercise mediates health and longevity promotion involving Sirtuin 1 (SIRT1)-regulated pathways. The anti-aging activity of SIRT1 is achieved, at least in part, by means of fine-tuning the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway by preventing the transition of an originally pro-survival program into a pro-aging mechanism. Additionally, SIRT1 promotes mitochondrial function and reduces the production of reactive oxygen species (ROS) through regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the master controller of mitochondrial biogenesis. Here, by using senescence-accelerated mice prone 8 (SAMP8) as a model for aging, we determined the effect of wheel-running as a paradigm for long-term voluntary exercise on SIRT1-AMPK pathway and mitochondrial functionality measured by oxidative phosphorylation (OXPHOS) complex content in the hippocampus and cortex. We found differential activation of SIRT1 in both tissues and hippocampal-specific activation of AMPK. These findings correlated well with significant changes in OXPHOS in the hippocampal, but not in the cerebral cortex, area. Collectively, the results revealed greater benefits of the exercise in the wheel-running intervention in a murine model of senescence, which was directly related with mitochondrial function and which was mediated through the modulation of SIRT1 and AMPK pathways.

  6. Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.

    Science.gov (United States)

    Rapôso, Catarina; Odorissi, Paulo Alexandre Miranda; Savioli, Stefania Fioravanti; Hell, Rafaela Chitarra Rodrigues; Simões, Gustavo Ferreira; Ruela-de-Sousa, Roberta R; de Oliveira, Alexandre Leite Rodrigues; da Cruz-Höfling, Maria Alice

    2014-01-01

    Severe accidents caused by the "armed" spider Phoneutria nigriventer cause neurotoxic manifestations in victims. In experiments with rats, P. nigriventer venom (PNV) temporarily disrupts the properties of the BBB by affecting both the transcellular and the paracellular route. However, it is unclear how cells and/or proteins participate in the transient opening of the BBB. The present study demonstrates that PNV is a substrate for the multidrug resistance protein-1 (MRP1) in cultured astrocyte and endothelial cells (HUVEC) and increases mrp1 and cx43 and down-regulates glut1 mRNA transcripts in cultured astrocytes. The inhibition of nNOS by 7-nitroindazole suggests that NO derived from nNOS mediates some of these effects by either accentuating or opposing the effects of PNV. In vivo, MRP1, GLUT1 and Cx43 protein expression is increased differentially in the hippocampus and cerebellum, indicating region-related modulation of effects. PNV contains a plethora of Ca(2+), K(+) and Na(+) channel-acting neurotoxins that interfere with glutamate handling. It is suggested that the findings of the present study are the result of a complex interaction of signaling pathways, one of which is the NO, which regulates BBB-associated proteins in response to PNV interference on ions physiology. The present study provides additional insight into PNV-induced BBB dysfunction and shows that a protective mechanism is activated against the venom. The data shows that PNV has qualities for potential use in drug permeability studies across the BBB.

  7. Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats

    Science.gov (United States)

    2013-01-01

    10 mM ThioGloTM-1 (Calbiochem, SanDiego, CA), a maleimid reagent that produces a highly fluorescent product upon its reaction with thiol groups.21...GSH concentrations were determined by addition of GSH peroxidase and cumene hydro peroxide to the brain homogenates with ThioGloTM-1 working solution...cAMP, 5’- AMP, 3’-AMP, 2’-AMP, adenosine and inosine using our standard LC-MS/MS purine assay with selected reaction monitoring (SRM).24 The brain

  8. Neurophysiological mechanisms of formation of non-chemical dependence through self-stimulation of positive emotiogenic areas of rats’ brains

    Directory of Open Access Journals (Sweden)

    O. G. Berchenko

    2016-05-01

    Full Text Available The aim of our research was to study the limbic-neocortical mechanisms of addictive behaviour in rats formed throughthe arousal of intense emotions on the model of self-stimulation reaction of the brain. We carried out investigations by conducting a chronic experiment on 15 nonlinear laboratory male rats weighing 250 to 320 grams, at the ages of 5 to 6 months. As a model of receiving positive emotions we used the behaviour of animals held in a Skinner box which was formed through self stimulation of the positive emotional zones of the posterior ventrolateral hypothalamus. We registered the frequency of self-stimulation reactions of the ventrolateral hypothalamus daily for 4 days and on the 7th day after its ccessation (state of deprivation. We performed visual and spectral analysis of the electrical activity of the brain using "Neuron-spektr.net" software. We assessed the absolute spectral density of the power of rhythm signals of the following frequency bands: delta (0.5–4.0 Hz, theta (4.0–7.0 Hz, alpha (8.0–12.0 Hz and low frequency beta (14.0–20.0 Hz. The formation of behaviour dependent on receiving intense emotions as a result of self-stimulation of the positive zones of the ventrolateral hypothalamus is caused by the initial high level of need for positive emotional reinforcement and further growth in the implementation of desire and is associated with activation of emotional memory mechanisms, changes in electrogenesis in the hippocampus and the reticular formation in the form of decrease in the spectral power of rhythms of alpha and beta bands and increased spectral power of biopotentials of the delta range in the hippocampus and theta range in the reticular formation with severe manifestations of seizure and paroxysmal activity components and increased activity of the sympatho-adrenal system. The syndrome of withdrawal fromthe receiving of positive emotions in some rats with implementation of a programme of a phobic character

  9. Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.

    Directory of Open Access Journals (Sweden)

    Catarina Rapôso

    Full Text Available Severe accidents caused by the "armed" spider Phoneutria nigriventer cause neurotoxic manifestations in victims. In experiments with rats, P. nigriventer venom (PNV temporarily disrupts the properties of the BBB by affecting both the transcellular and the paracellular route. However, it is unclear how cells and/or proteins participate in the transient opening of the BBB. The present study demonstrates that PNV is a substrate for the multidrug resistance protein-1 (MRP1 in cultured astrocyte and endothelial cells (HUVEC and increases mrp1 and cx43 and down-regulates glut1 mRNA transcripts in cultured astrocytes. The inhibition of nNOS by 7-nitroindazole suggests that NO derived from nNOS mediates some of these effects by either accentuating or opposing the effects of PNV. In vivo, MRP1, GLUT1 and Cx43 protein expression is increased differentially in the hippocampus and cerebellum, indicating region-related modulation of effects. PNV contains a plethora of Ca(2+, K(+ and Na(+ channel-acting neurotoxins that interfere with glutamate handling. It is suggested that the findings of the present study are the result of a complex interaction of signaling pathways, one of which is the NO, which regulates BBB-associated proteins in response to PNV interference on ions physiology. The present study provides additional insight into PNV-induced BBB dysfunction and shows that a protective mechanism is activated against the venom. The data shows that PNV has qualities for potential use in drug permeability studies across the BBB.

  10. Discussion on Mechanical Emergency Start of Fire Pump%消防泵机械应急启泵装置探讨

    Institute of Scientific and Technical Information of China (English)

    徐建兵; 李慧

    2015-01-01

    收集整理有关消防水泵控制柜应设置机械应急启泵功能要求的国内外相关标准;介绍美国Joslyn Clark消防泵控制柜机械应急启泵装置的设置;总结电源系统及消防泵控制柜各功能组件的性能要求。%This paper collects and analyzes the international and national standards related to the requirement of mechanical emergency startup function for control cabinet of fire pump, introduces the settings of mechanical emergency starter of Joslyn Clark fire pump control cabinet, and summarizes the functional requirements for functional components of power system and control cabinet of fire pump.

  11. Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs.

    Science.gov (United States)

    Ufnal, Marcin; Skrzypecki, Janusz

    2014-04-01

    Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure.

  12. [CROSS-TALK BETWEEN 5-HT1A AND 5-HT7 RECEPTORS: ROLE IN THE AUTOREGULATION OF THE BRAIN SEROTONIN SYSTEM AND IN MECHANISM OF ANTIDEPRESSANTS ACTION].

    Science.gov (United States)

    Popova, N K; Ponimaskin, E G; Naumenko, V S

    2015-11-01

    Recent studies considerably extended our knowledge of the mechanisms and physiological role of the interaction between different receptors in the brain. Current review summarizes data on the formation of receptor complexes and the role of such complexes in the autoregulation of the brain serotonin system, behavioral abnormalities and mechanism of antidepressants action. Particular attention is paid to 5-HT1A and 5-HT7 receptor heterodimers. The results described in the present review indicate that: i) dimerization and formation of mobile receptor complexes is a common feature for the members of G-protein coupled receptor superfamily; ii) 5-HT7 receptor appears to be a modulator for 5-HT1A receptor - the key autoregulator of the brain serotonin system; iii) 5-HT1A/5-HT7 receptor complexes formation is one of the mechanisms for inactivation and desensitization of the 5-HTIA receptors in the brain; iv) differences in the 5-HT7 receptor and 5-HTIA/5-HT7 heterodimers density define different sensitivity of pre- and postsynaptic 5-HTlA receptors to chronic treatment with selective serotonin reuptake inhibitors.

  13. Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders

    Science.gov (United States)

    Radley, Jason; Morilak, David; Viau, Victor; Campeau, Serge

    2015-01-01

    Stress responses entail neuroendocrine, autonomic, and behavioral changes to promote effective coping with real or perceived threats to one’s safety. While these responses are critical for the survival of the individual, adverse effects of repeated exposure to stress are widely known to have deleterious effects on health. Thus, a considerable effort in the search for treatments to stress-related CNS disorders necessitates unraveling the brain mechanisms responsible for adaptation under acute conditions and their perturbations following chronic stress exposure. This paper is based upon a symposium from the 2014 International Behavioral Neuroscience Meeting, summarizing some recent advances in understanding the effects of stress on adaptive and maladaptive responses subserved by limbic forebrain networks. An important theme highlighted in this review is that the same networks mediating neuroendocrine, autonomic, and behavioral processes during adaptive coping also comprise targets of the effects of repeated stress exposure in the development of maladaptive states. Where possible, reference is made to the similarity of neurobiological substrates and effects observed following repeated exposure to stress in laboratory animals and the clinical features of stress-related disorders in humans. PMID:26116544

  14. The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development

    Science.gov (United States)

    Parker, Matthew O.; Annan, Leonette V.; Kanellopoulos, Alexandros H.; Brock, Alistair J.; Combe, Fraser J.; Baiamonte, Matteo; Teh, Muy-Teck; Brennan, Caroline H.

    2014-01-01

    Exposure to moderate levels of ethanol during brain development has a number of effects on social behavior but the molecular mechanisms that mediate this are not well understood. Gaining a better understanding of these factors may help to develop therapeutic interventions in the future. Zebrafish offer a potentially useful model in this regard. Here, we introduce a zebrafish model of moderate prenatal ethanol exposure. Embryos were exposed to 20 mM ethanol for seven days (48hpfs–9dpf) and tested as adults for individual social behavior and shoaling. We also tested their basal anxiety with the novel tank diving test. We found that the ethanol-exposed fish displayed reductions in social approach and shoaling, and an increase in anxiety in the novel tank test. These behavioral differences corresponded to differences in hrt1aa, slc6a4 and oxtr expression. Namely, acute ethanol caused a spike in oxtr and ht1aa mRNA expression, which was followed by down-regulation at 7dpf, and an up-regulation in slc6a4 at 72hpf. This study confirms the utility of zebrafish as a model system for studying the molecular basis of developmental ethanol exposure. Furthermore, it proposes a putative developmental mechanism characterized by ethanol-induced OT inhibition leading to suppression of 5-HT and up-regulation of 5-HT1A, which leads, in turn, to possible homeostatic up-regulation of 5-HTT at 72hpf and subsequent imbalance of the 5-HT system. PMID:24690524

  15. Study on the Characteristics of Emergency Logistics and Distribution Mechanism of Emergency Logistics in China%应急物流特点及我国应急物流配送机制研究

    Institute of Scientific and Technical Information of China (English)

    陈艺华; 李大卫

    2014-01-01

    The global large-scale public events in recent years, such as SARS, ocean tsunami, earthquake, hurricane and so on, such incidents left sad memories to people and caused huge loss. This article discusses the definition and characteristics of emergency logistics, points out the status of emergency logistics in our country, plans to establish a set of perfect emergency logistics distribution mechanism.%近几年来全球大规模发生公共事件,例如非典、大洋海啸、大地震、飓风等。类似这样的突发事件给事发地民众留下了难以忘怀的惨痛记忆并造成的巨大损失。本文章探讨了应急物流的定义、特点,指出了我们国家自然灾害救助的应急物流配送现状,设想建立一套较为完善的应急物流配送机制。

  16. The cost of brain diseases

    DEFF Research Database (Denmark)

    DiLuca, Monica; Olesen, Jes

    2014-01-01

    Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists.......Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists....

  17. Inhibition of misleading heuristics as a core mechanism for typical cognitive development: evidence from behavioural and brain-imaging studies.

    Science.gov (United States)

    Borst, Grégoire; Aïte, Ania; Houdé, Olivier

    2015-04-01

    Cognitive development is generally conceived as incremental with knowledge of increasing complexity acquired throughout childhood and adolescence. However, several studies have now demonstrated not only that infants possess complex cognitive abilities but also that older children, adolescents, and adults tend to make systematic errors even in simple logical reasoning tasks. Therefore, one of the main issues for any theory of typical cognitive development is to provide an explanation of why at some age and in some contexts children, adolescents, and adults do not express a knowledge or cognitive principle that they already acquired when they were younger. In this review, we present convergent behavioural and neurocognitive evidence that cognitive development is more similar to a non-linear dynamic system than to a linear, stage-like system. In this theoretical framework, errors can emerge in problems similar to the ones infants or young children were succeeding when older children, adolescents, and adults rely on a misleading heuristic rather than on the correct logical algorithm to solve such problems. And the core mechanism for overcoming these errors is inhibitory control (i.e. the ability to inhibit the misleading heuristics). Therefore, typical cognitive development relies not only on the ability to acquire knowledge of incremental complexity but also to inhibit previously acquired knowledge.

  18. Study of effect of oxygen/glucose-deprived culture on the brain-pancreas relative protein in PC12 cells and the mechanism

    Institute of Scientific and Technical Information of China (English)

    Yan-huaLIN; LuTIE; Ai-huaLIU; Xue-junLI

    2004-01-01

    AIM: To study the effect of oxygen/glucose-deprived (OGD)culture on the expression of a novel protein, brain-pancreas relative protein (BPRP), and the possible regulating mechanism in vitro. BPRP was a key protein found in our previous study of cerebral ischemia. METHODS: PC12 cells was selected and exposed to the Eagle's solution containing 1 mmol/L Na2S2O4 for

  19. Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain

    Science.gov (United States)

    Yufune, Shinya; Satoh, Yasushi; Akai, Ryosuke; Yoshinaga, Yosuke; Kobayashi, Yasushi; Endo, Shogo; Kazama, Tomiei

    2016-01-01

    In animal models, neonatal exposure to general anesthetics significantly increased neuronal apoptosis with subsequent behavioral deficits in adulthood. Although the underlying mechanism is largely unknown, involvement of extracellular signal-regulated kinases (ERKs) is speculated since ERK phosphorylation is decreased by neonatal anesthetic exposure. Importance of ERK phosphorylation for neuronal development is underscored by our recent finding that transient suppression of ERK phosphorylation during the neonatal period significantly increased neuronal apoptosis and induced behavioral deficits. However, it is still unknown as to what extent decreased ERK phosphorylation contributes to the mechanism underlying anesthetic-induced toxicity. Here we investigated the causal relationship of decreased ERK phosphorylation and anesthetic-induced toxicity in the developing brain. At postnatal day 6 (P6), mice were exposed to sevoflurane (2%) or the blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) (50 mg/kg). Transient suppression of ERK phosphorylation by an intraperitoneal injection of SL327 at P6 significantly increased apoptosis similar to sevoflurane-induced apoptosis. Conversely, SL327 administration at P14 or P21 did not induce apoptosis, even though ERK phosphorylation was inhibited. Restoring ERK phosphorylation by administration of molecular hydrogen ameliorated sevoflurane-induced apoptosis. Together, our results strongly suggests that suppressed ERK phosphorylation is critically involved in the mechanism underlying anesthetic-induced toxicity in the developing brain. PMID:26905012

  20. Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob diseases the common key for a free radical mechanism and oxidative stress-induced damage?

    Science.gov (United States)

    Deloncle, Roger; Guillard, Olivier

    2015-01-01

    In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases, similar pathological hallmarks have been described, one of which is brain deposition of abnormal protease-resistant proteins. For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a mechanism has been proposed that may underlie the neurodegenerative processes that occur when copper protection against free radicals is impaired. In peptide sequences, the alpha acid proton near the peptide bond is highly mobile and can be pulled out by free radicals. It will produce a trivalent α-carbon radical and induce a free radical chain process that will generate a D-amino acid configuration in the peptide sequence. Since only L-amino acids are physiologically present in mammalian (human) proteins, it may be supposed that only physiological L-peptides can be recycled by physiological enzymes such as proteases. If a D-amino acid is found in the peptide sequence subsequent to deficient copper protection against free radicals, it will not be recognized and might alter the proteasome L-amino acid recycling from brain peptides. In the brain, there will result an accumulation of abnormal protease-resistant proteins such as those observed in AD, LBD, and CJD.

  1. Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.

    Science.gov (United States)

    Smith, Maren L; Lopez, Marcelo F; Archer, Kellie J; Wolen, Aaron R; Becker, Howard C; Miles, Michael F

    2016-01-01

    Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC). In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a complex temporal

  2. Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.

    Directory of Open Access Journals (Sweden)

    Maren L Smith

    Full Text Available Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD. Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC. In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a

  3. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  4. Exercise to enhance neurocognitive function after traumatic brain injury.

    Science.gov (United States)

    Fogelman, David; Zafonte, Ross

    2012-11-01

    Vigorous exercise has long been associated with improved health in many domains. Results of clinical observation have suggested that neurocognitive performance also is improved by vigorous exercise. Data derived from animal model-based research have been emerging that show molecular and neuroanatomic mechanisms that may explain how exercise improves cognition, particularly after traumatic brain injury. This article will summarize the current state of the basic science and clinical literature regarding exercise as an intervention, both independently and in conjunction with other modalities, for brain injury rehabilitation. A key principle is the factor of timing of the initiation of exercise after mild traumatic brain injury, balancing potentially favorable and detrimental effects on recovery.

  5. New Heuristics for Interfacing Human Motor System using Brain Waves

    Directory of Open Access Journals (Sweden)

    Mohammed El-Dosuky

    2012-09-01

    Full Text Available There are many new forms of interfacing human users to machines. We persevere here electric-mechanical form of interaction between human and machine. The emergence of brain-computer interface allows mind-to-movement systems. The story of the Pied Piper inspired us to devise some new heuristics for interfacing human motor system using brain waves, by combining head helmet and LumbarMotionMonitor. For the simulation we use java GridGain. Brain responses of classified subjects during training indicates that Probe can be the best stimulus to rely on in distinguishing between knowledgeable and not knowledgeable

  6. Deep brain stimulation for cluster headache

    DEFF Research Database (Denmark)

    Grover, Patrick J; Pereira, Erlick A C; Green, Alexander L

    2009-01-01

    Cluster headache is a severely debilitating disorder that can remain unrelieved by current pharmacotherapy. Alongside ablative neurosurgical procedures, neuromodulatory treatments of deep brain stimulation (DBS) and occipital nerve simulation have emerged in the last few years as effective...... circumstances to intervene. Here we review current data on neurosurgical interventions for chronic cluster headache focusing upon DBS and occipital nerve stimulation, and discuss the indications for and putative mechanisms of DBS including translational insights from functional neuroimaging, diffusion weighted...

  7. The Mammalian Brain in the Electromagnetic Fields Designed by Man with Special Reference to Blood-Brain Barrier Function, Neuronal Damage and Possible Physical Mechanisms

    Science.gov (United States)

    Salford, L. G.; Nittby, H.; Brun, A.; Grafström, G.; Malmgren, L.; Sommarin, M.; Eberhardt, J.; Widegren, B.; Persson, B. R.

    Life on earth was formed during billions of years, exposed to,and shaped by the original physical forces such as gravitation, cosmic irradiation, atmospheric electric fields and the terrestrial magnetism. The Schumann resonances at 7.4 Hz are an example of oscillations possibly important for life. The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity, in the early 20th century long-wave radio and in the 1940-ies short-wave radio. High frequency RF was introduced in the 50-ies as FM and television and during the very last decades, microwaves of the modern communication society spread around the world. Today, however, one third of the world's population is owner of the microwave-producing mobile phones and an even larger number is exposed to the cordless RF emitting systems. To what extent are all living organisms affected by these, almost everywhere present radio freque ncy fields? And what will be the effects of many years of continuing exposure? Since 1988 our group has studied the effects upon the mammalian blood-brain barrier (BBB) in rats by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been shown to cause significantly increased leakage of the rats' own blood albumin through the BBB of exposed rats, at energy levels of 1W/kg and below, as compared to non-exposed animals in a total series of about two thousand animals.-6)} One remarkable observation is the fact that the lowest energy levels, with whole-body average power densities below 10mW/kg, give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz, at

  8. Continuous spontaneous localization wave function collapse model as a mechanism for the emergence of cosmological asymmetries in inflation

    Science.gov (United States)

    Cañate, Pedro; Pearle, Philip; Sudarsky, Daniel

    2013-05-01

    The inflationary account for the emergence of the seeds of cosmic structure falls short of actually explaining the generation of primordial anisotropies and inhomogeneities. This description starts from a symmetric background, and invokes symmetric dynamics, so it cannot explain asymmetries. To generate asymmetries, we present an application of the continuous spontaneous localization model of wave function collapse in the context of inflation. This modification of quantum dynamics introduces a stochastic nonunitary component to the evolution of the inflaton field perturbations. This leads to passage from a homogeneous and isotropic stage to another, where the quantum uncertainties in the initial state of inflation transmute into the primordial inhomogeneities and anisotropies. We show, by proper choice of the collapse-generating operator, that it is possible to achieve compatibility with the precise observations of the cosmic microwave background radiation.

  9. Diabetic Emergencies

    Science.gov (United States)

    ... Emergencies A-Z Share this! Home » Emergency 101 Diabetic Emergencies It is estimated that more than 20 ... they have it. The best way to prevent diabetic emergencies is to effectively manage the disease through ...

  10. Childhood Emergencies

    Science.gov (United States)

    ... emergency physicians. They receive comprehensive training in treating childhood emergencies and have more training in pediatric emergencies than other physicians, including pediatricians. Does Your Child's School Know About Food Allergies? - 8/10/2015 The nation's emergency physician ...

  11. Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish

    Science.gov (United States)

    Teles, Magda C.; Cardoso, Sara D.; Oliveira, Rui F.

    2016-01-01

    Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results

  12. Study on dynamic mechanism model of emergency industry development in China%我国应急产业发展动力机制模型研究

    Institute of Scientific and Technical Information of China (English)

    王建光

    2015-01-01

    调研分析了应急产业有关定义,明确了应急产业的范围;从产业内容、产业发展阶段等角度,分析了应急产业的特点;基于自组织理论和新古典经济理论,结合应急产业特点,建立了应急产业发展动力机制“内切圆”模型。模型中,应急产业的发展动力机制系统包括产业成长的外部动力因素和内部动力因素,其中,外部动力因素包括有市场需求、技术创新、产业政策、产业投资等,内部动力因素包括应急产业内相关企业间的竞争与协作、针对市场失效的产业政策。内部动力因素和外部动力因素之间存在着相互作用,在一定的条件下,外部动力可以与内部动力相互转化。内部和外部动力因素的综合作用,推动应急产业不断发展。%Some conceptions related to emergency industry were investigated .From the view of emergency manage-ment, the definition of emergency industry was analyzed and the scope was cleared .From the view of industry de-velopment phase and content of industry , the features of emergency industry were analyzed .Combining with the characteristics of emergency industry , based on the self-organization theory and the Neo-classical Economics theory , an "inscribed circle"model for development dynamic mechanism of emergency industry was established .In this model , the dynamic mechanism system of emergency industry development includes exogenous dynamic factors and endogenous dynamic factors , the exogenous factors include market demand , technological innovation , industrial policy and industrial investment , and the endogenous factors include the competition and cooperation between enter-prises, and industrial policy aiming at market failure .There is interaction between the endogenous dynamic factors and the exogenous dynamic factors .Under certain conditions , the endogenous dynamic factors and exogenous dy-namic factors can be transformed into each

  13. Granulopoietic Growth Factor Secretion in Ovarian Carcinoma as a Mechanism for the Emergence of Immune Suppressive Myeloid Subsets

    Science.gov (United States)

    2013-06-01

    Series, Dept. of Pediatrics , University of Texas M.D. Anderson Cancer Center, August 2007. Title of Seminar : “Fas Resistance Contributes to Tumor... Seminar Series, Section of General Surgery , the University of Chicago Medical Center, November 2005. Title of Seminar : “Fas-Mediated Cytotoxicity...Immunology, Chicago, IL, October 22-24, 2012. Title of Seminar : “Granulocytic myeloid-derived suppressor cell development via G-CSF-dependent mechanisms

  14. Screening of biochemical and molecular mechanisms of secondary injury and repair in the brain after experimental blast-induced traumatic brain injury in rats.

    Science.gov (United States)

    Kochanek, Patrick M; Dixon, C Edward; Shellington, David K; Shin, Samuel S; Bayır, Hülya; Jackson, Edwin K; Kagan, Valerian E; Yan, Hong Q; Swauger, Peter V; Parks, Steven A; Ritzel, David V; Bauman, Richard; Clark, Robert S B; Garman, Robert H; Bandak, Faris; Ling, Geoffrey; Jenkins, Larry W

    2013-06-01

    Abstract Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. Injury produced ∼25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2'-AMP [adenosine monophosphate], and 5'-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1α, IL-6, IL-10, and macrophage inflammatory protein 1 alpha [MIP-1α]) were increased; by 24 h, only MIP-1α remained elevated. ATP was not depleted, and adenosine correlated with 2'-cyclic AMP (cAMP), and not 5'-cAMP. Our data reveal (1) gene-array alterations similar to disorders of

  15. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods.

    Science.gov (United States)

    Osei Sekyere, J; Govinden, U; Bester, L A; Essack, S Y

    2016-09-01

    A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

  16. Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model.

    Science.gov (United States)

    Fan, Xiang; Chai, Lijuan; Zhang, Han; Wang, Yuefei; Zhang, Boli; Gao, Xiumei

    2015-11-18

    P-glycoprotein (P-gp) on brain microvascular endothelial cells (BMECs) that form the blood brain barrier (BBB), influences transportation of substances between blood and brain. The objective of this study was to characterize the effects of borneol on P-gp efflux function on BBB and explore the potential mechanisms. We established an in vitro BBB model comprised of rat BMECs and astrocytes to measure the effects of borneol on the known P-gp substrates transport across BBB, and examined the function and expression of P-gp in BMECs and the signaling pathways regulating P-gp expression. Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression. Borneol could activate nuclear factor-κB (NF-κB) and inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol. These data suggested that borneol depresses P-gp function in BMECs by a NF-κB signaling medicated mechanism in a BBB in vitro model.

  17. 血脑屏障中P-糖蛋白的调节机制%Regulatory mechanisms of P-glycoprotein at the blood-brain barrier

    Institute of Scientific and Technical Information of China (English)

    王玉璘; 王少峡; 郭虹; 胡利民

    2011-01-01

    P-糖蛋白属于ABC转运蛋白超家族.它在脑微血管中大量表达,限制毒性物质和大量治疗中枢神经系统的药物进入脑内,因此弄清P-糖蛋白在血脑屏障中的调节机制对疾病的治疗尤为重要.该文总结了P-糖蛋白基本结构、分布、功能,并讨论了P-糖蛋白在血脑屏障中调节机制的研究进展.%P-glycoprotein (P-gp) belongs to the adenosine triphosphate( ATP )-binding cassette( ABC ) proteins, which is present in the microvessels in the brain, so it can prevent cytotoxic compounds and large amount of CNS agents entering the brain. Thus, it is important to find out the mechanisms that regulate P-gp function and expression in the blood-brain barier for pharmcotherapy. In this review, the structure, tissue distribution and the function of P-glycoprotein were reviewed, focusing on the research advances of regulatory mechanisms at the bloodbrain barrier.

  18. Adsorption mechanisms of emerging micro-pollutants with a clay mineral: Case of tramadol and doxepine pharmaceutical products.

    Science.gov (United States)

    Thiebault, Thomas; Guégan, Régis; Boussafir, Mohammed

    2015-09-01

    A sodium exchanged smectite clay mineral (Mt) was used as geo-sorbent for the adsorption of tramadol and doxepin: two pharmaceutical products (PPs) defined as emerging pollutants due to their presence at significant concentration in numerous water compartments. The adsorption isotherms for both the temperatures of 20 and 40°C and the derived data determined through the fitting procedure by using Langmuir, Freundlich and Dubinin-Radushkevich equation models explicitly pointed out that the sorption of both tramadol and doxepin is mainly driven by electrostatic interaction. The studied PPs are intercalated in a monolayer arrangement within the interlayer space through a cation exchange in stoichiometric proportion with the Na(+) cations leading to adsorbed PPs amounts that match the cation exchange capacity (CEC) of Mt. Due to their hydrophobic character, additional doxepin molecules could be adsorbed by weak molecular interaction driving to an increase of the adsorbed amount beyond the CEC at low temperature (20°C). The confinement of PPs within the interlayer space of Mt confirms the use of clay minerals as potential material for the wastewater treatment as well as it drives to an amorphous or glassy state, which can find echo in biopharmaceutical applications for a controlled release of PPs.

  19. Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.

    Science.gov (United States)

    Liu, Xiaofei; Cao, Shangqing; Zhang, Xuewu

    2015-09-16

    There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

  20. Metabolism, Seizures, and Blood Flow in Brain Following Organophosphate Exposure: Mechanisms of Action and Possible Therapeutic Agents

    Science.gov (United States)

    1991-01-31

    concentration of 4 mM had no effect. In fact, Ca 2+ and Mg2 + were slightly inhibitory between concentrations of 1 and 4 mM, whereas Zn 2 + was highly...induces an acrosome reaction in spermatozoa . J. Biol. Chem. 264:9412-9419. 146. Koul, 0. and Hauser, 0. (1987) Modulation of rat brain cytosolic

  1. Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

    Directory of Open Access Journals (Sweden)

    Irune Diaz-Aparicio

    2016-01-01

    Full Text Available Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

  2. Clearing the corpses:regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

    Institute of Scientific and Technical Information of China (English)

    Irune Diaz-Aparicio; Sol Beccari; Oihane Abiega; Amanda Sierra

    2016-01-01

    Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the pa-renchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artiifcial phagocytic targetsin vitro. Nevertheless, these indirect methods present several limitations and, thus, direct obser-vation and quantiifcation of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. hTese parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inlfammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to ifnd and engulf apoptotic cells, resulting in accumulation of debris and inlfammation. Herein, we advocate that the effciency of microglial phagocytosis should be routinely tested in neurodegenerative and neuro-logical disorders, in order to determine the extent to which it contributes to apoptosis and inlfammation found in these conditions. Finally, our ifndings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inlfammation, and accelerate recovery in brain diseases.

  3. Processing of visual semantic information to concrete words: temporal dynamics and neural mechanisms indicated by event-related brain potentials

    NARCIS (Netherlands)

    Schie, H.T. van; Wijers, A.A.; Mars, R.B.; Benjamins, J.S.; Stowe, L.A.

    2005-01-01

    Event-related brain potentials were used to study the retrieval of visual semantic information to concrete words, and to investigate possible structural overlap between visual object working memory and concreteness effects in word processing. Subjects performed an object working memory task that inv

  4. Processing of visual semantic information to concrete words : temporal dynamics and neural mechanisms indicated by event-related brain potentials

    NARCIS (Netherlands)

    van Schie, HT; Wijers, AA; Mars, RB; Benjamins, JS; Stowe, LA; Mars, Ruben

    2005-01-01

    Event-related brain potentials were used to study the retrieval of visual semantic information to concrete words, and to investigate possible structural overlap between visual object working memory and concreteness effects in word processing. Subjects performed an object working memory task that inv

  5. Design and Analysis of Blast Induced Traumatic Brain Injury Mechanism Using a Surrogate Headform: Instrumentation and Outcomes

    Science.gov (United States)

    2011-05-01

    of twenty cases. London : s.n., 1961. OCLC: 603454539. 6. University of Toronto. Workshop on Brain Biomechanics . Presentation Notes. Toronto, Canada...Strain Gauge Technology; 2nd edition. New York : Springer , 1993. ISBN: 978-1-85166-864-9. 36. Vishay Micro-Measurements. MR-Series Bridge Completion...38. Books LLC (Editor). Accelerometers: Accelerometer, Piezoelectric Accelerometer, Piga Accelerometer, Gravimeter, Liquid Capacitive Inclinometers

  6. SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood-cerebrospinal fluid interface during brain development

    DEFF Research Database (Denmark)

    Liddelow, S A; Dziegielewska, K M; Møllgård, K

    2011-01-01

    Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain. The mech...

  7. Molecular modifications by regulating cAMP signaling and oxidant-antioxidant defence mechanisms, produce antidepressant-like effect: A possible mechanism of etazolate aftermaths of impact accelerated traumatic brain injury in rat model.

    Science.gov (United States)

    Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank; Pandey, Dilip

    2016-12-14

    Traumatic brain injury (TBI) is one of the leading cause of psychiatric conditions in patients, amongst which, depression and anxiety are more frequent. Despite the preclinical antidepressant-like effects, clinical development of Phospodiesterase-4 (PDE4) enzyme inhibitors has been hampered due to serious side effect profiles, such as nausea and vomiting. Etazolate (ETZ) is a new generation PDE4 inhibitor with encouraging safety and tolerance profiles. In our previous studies we have addressed that ETZ produces antidepressant-like effects in animal models of depression, however, the underlying mechanism(s) following TBI have not been completely explored. Impact accelerated TBI by weight drop method causes depression-like behavioral deficits in modified open field exploration, hyper-emotionality and sucrose consumption paradigms. TBI not only causes immediate mechanical damage to the brain, but also induces biochemical changes that lead to delayed neural cell loss leading to a secondary injury. The present study examines the antidepressant effects of ETZ on the TBI-induced depression-like behavior deficits and attempts to explore the underlying mechanism. In order to understand the underlying pathology of TBI and mechanism(s) of ETZ in TBI molecular markers namely, brain cAMP, cAMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) were estimated. Additionally, the level of oxidative (lipid peroxidation) & nitrosative (nitrite) stress markers, along with antioxidant enzymes markers, such as, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured. Furthermore, the involvement of hypothalamic-pituitary adrenal (HPA) axis activity in underlying mechanism was also investigated by measuring serum corticosterone (CORT) level. The results revealed that TBI significantly altered cAMP, pCREB and BDNF levels. Moreover, a significant increase in oxidative-nitrosative stress markers levels, while, significant

  8. Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4.

    Directory of Open Access Journals (Sweden)

    Heling Chu

    Full Text Available Vascular endothelial growth factor (VEGF has protective effects on many neurological diseases. However, whether VEGF acts on brain edema following intracerebral hemorrhage (ICH is largely unknown. Our previous study has shown aquaporin-4 (AQP4 plays an important role in brain edema elimination following ICH. Meanwhile, there is close relationship between VEGF and AQP4. In this study, we aimed to test effects of VEGF on brain edema following ICH and examine whether they were AQP4 dependent. Recombinant human VEGF165 (rhVEGF165 was injected intracerebroventricularly 1 d after ICH induced by microinjecting autologous whole blood into striatum. We detected perihemotomal AQP4 protein expression, then examined the effects of rhVEGF165 on perihemotomal brain edema at 1 d, 3 d, and 7 d after injection in wild type (AQP4(+/+ and AQP4 knock-out (AQP4(-/- mice. Furthermore, we assessed the possible signal transduction pathways activated by VEGF to regulate AQP4 expression via astrocyte cultures. We found perihemotomal AQP4 protein expression was highly increased by rhVEGF165. RhVEGF165 alleviated perihemotomal brain edema in AQP4(+/+ mice at each time point, but had no effect on AQP4(-/- mice. Perihemotomal EB extravasation was increased by rhVEGF165 in AQP4(-/- mice, but not AQP4(+/+ mice. RhVEGF165 reduced neurological deficits and increased Nissl's staining cells surrounding hemotoma in both types of mice and these effects were related to AQP4. RhVEGF165 up-regulated phospharylation of C-Jun amino-terminal kinase (p-JNK and extracellular signal-regulated kinase (p-ERK and AQP4 protein in cultured astrocytes. The latter was inhibited by JNK and ERK inhibitors. In conclusion, VEGF reduces neurological deficits, brain edema, and neuronal death surrounding hemotoma but has no influence on BBB permeability. These effects are closely related to AQP4 up-regulation, possibly through activating JNK and ERK pathways. The current study may present new insights to

  9. Nursing experience of emergency treatment for traumatic severe brain injury%外伤性重型颅脑损伤急救阶段护理体会分析

    Institute of Scientific and Technical Information of China (English)

    叶雪花

    2016-01-01

    Objective To compare the nursing effects of different nursing methods for emergency treatment of traumatic severe brain injury. Methods 126 patients with severe traumatic brain injury in our hospital were selected and divided into different groups according to emergency care approach phase. Cure effects of patients were compared. Results The rescue time, rescue expense, complication rate and death rate in observation group was much lower than those in control group (P < 0.05). Stable disease rate of observation group was much higher than that of control group (P < 0.05). Care attitude, nursing skills, mental health care and better education satisfaction rate of observation group than those of control group(P < 0.05). Conclusion Clinical nursing in the emergency treatment of traumatic severe brain injury can effectively shorten rescue time, and reduce expense and lower complication rate. At the same time, patient's condition stability rate and survival rate can be significantly improved. It is worth popularizing in clinical application.%目的:对比不同护理手段对外伤性重型颅脑损伤患者急救阶段的护理效果。方法将我院收治的126例外伤性重型颅脑损伤患者依据急救阶段护理方式差异分组,对比两组护理效果。结果观察组入院抢救时间与抢救费用、并发症率与死亡率均远低于对照组(P <0.05);观察组病情稳定率远高于对照组(P <0.05);观察组护理态度、护理技术、心理护理与健康教育满意率均较对照组更理想(P <0.05)。结论临床予以外伤性重型颅脑损伤患者急救阶段临床护理路径,可有效降低抢救时间、费用与并发症率,同时对患者的病情稳定与生存率均具明显提升作用,该法深受临床欢迎,值得推广。

  10. Orchestrating Proactive and Reactive Mechanisms for Filtering Distracting Information: Brain-Behavior Relationships Revealed by a Mixed-Design fMRI Study.

    Science.gov (United States)

    Marini, Francesco; Demeter, Elise; Roberts, Kenneth C; Chelazzi, Leonardo; Woldorff, Marty G

    2016-01-20

    Given the information overload often imparted to human cognitive-processing systems, suppression of irrelevant and distracting information is essential for successful behavior. Using a hybrid block/event-related fMRI design, we characterized proactive and reactive brain mechanisms for filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distracters might occur) and negatively with distraction-related behavioral costs (incongruent vs congruent trials), suggesting a role in coordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20% (vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction

  11. Neuroethics vs neurophysiologically and neuropsychologically uninformed influences in child-rearing, education, emerging hunter-gatherers, and artificial intelligence models of the brain.

    Science.gov (United States)

    Pontius, A A

    1993-04-01

    Potentially negative long-term consequences in four areas are emphasized, if specific neuromaturational, neurophysiological, and neuropsychological facts within a neurodevelopmental and ecological context are neglected in normal functional levels of child development and maturational lag of the frontal lobe system in "Attention Deficit Disorder," in education (reading/writing and arithmetic), in assessment of cognitive functioning in hunter-gatherer populations, specifically modified in the service of their survival, and in constructing computer models of the brain, neglecting consciousness and intentionality as criticized recently by Searle.

  12. Correlation between emergency treatment time and prognosis of acute traumatic brain injury patients caused by external violence%外部暴力所致急性颅脑创伤预后的相关性因素分析

    Institute of Scientific and Technical Information of China (English)

    杨玲昌

    2015-01-01

    Objective To explore the correlation of prognosis with emergency treatment time,gender,age and GCS score of acute traumatic brain injury patients caused by external violence.Methods 92 acute traumatic brain injury patients caused by external violence were selected.The gender,age,emergency treatment time,post-resuscita-tion GCS and GOS after 5 months were collected and analyzed.The relationship between patients′signs and emergency treatment time and prognosis were analyzed.Results The differences of prognosis between elderly patients and youn-ger patients were statistically significant(χ2 =5.30,P<0.05).The differences of prognosis in patients with different GCS scores were statistically significant(χ2 =11.97,P<0.01).The differences of prognosis in patients with different emergency treatment time were statistically significant(χ2 =15.74,P<0.01).The prognosis with age and emergency treatment time had a significant correlation(P=0.016,0.007).The prognosis of patients with different emergency treatment time had a significant difference(χ2 =28.45,P<0.01).Conclusion The age,post-resuscitation GCS and emergency treatment time are meaningful in predicating patients′mortality and prognosis.The shorter the emer-gency treatment time,the better the prognosis.%目的:探讨外部暴力所致急性颅脑创伤患者现场及院内抢救时间、性别、年龄及格拉斯哥昏迷评分(GCS评分)与预后的相关性。方法选取92例外部暴力所致急性颅脑创伤患者为研究对象,回顾性分析其临床资料。收集患者的性别、年龄、受伤到抢救的时间、入院时 GCS 及5个月后格拉斯哥预后评分(GOS),分析各征象及抢救时间与临床预后的相关性。结果高龄和低龄患者的预后差异有统计学意义(χ2=5.30,P<0.05);GCS评分不同对预后好坏的影响有统计学意义(χ2=11.97,P<0.01);伤后到抢救的时间不同亦对预后好坏产生显著性影响(χ2

  13. Schizophrenia, abnormal connection, and brain evolution.

    Science.gov (United States)

    Randall, P L

    1983-03-01

    Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslex