WorldWideScience

Sample records for brain emerging mechanisms

  1. Editorial: Music, Brain, and Rehabilitation: Emerging Therapeutic Applications and Potential Neural Mechanisms

    OpenAIRE

    Särkämö, Teppo; Altenmüller, Eckart; Rodríguez-Fornells, Antoni; Peretz, Isabelle

    2016-01-01

    Music is an important source of enjoyment, learning, and well-being in life as well as a rich, powerful, and versatile stimulus for the brain. With the advance of modern neuroimaging techniques during the past decades, we are now beginning to understand better what goes on in the healthy brain when we listen, play, think, and feel music and how the structure and function of the brain can change as a result of musical training and expertise. In the healthy brain, there is already mounting evid...

  2. Emergent quantum mechanics and emergent symmetries

    NARCIS (Netherlands)

    Hooft, G. 't

    2007-01-01

    Quantum mechanics is ‘emergent’ if a statistical treatment of large scale phenomena in a locally deterministic theory requires the use of quantum operators. These quantum operators may allow for symmetry transformations that are not present in the underlying deterministic system. Such

  3. Mechanisms of deep brain stimulation

    Science.gov (United States)

    Cheng, Jennifer J.; Eskandar, Emad N.

    2015-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756

  4. Local inhibitory plasticity tunes macroscopic brain dynamics and allows the emergence of functional brain networks.

    Science.gov (United States)

    Hellyer, Peter J; Jachs, Barbara; Clopath, Claudia; Leech, Robert

    2016-01-01

    Rich, spontaneous brain activity has been observed across a range of different temporal and spatial scales. These dynamics are thought to be important for efficient neural functioning. A range of experimental evidence suggests that these neural dynamics are maintained across a variety of different cognitive states, in response to alterations of the environment and to changes in brain configuration (e.g., across individuals, development and in many neurological disorders). This suggests that the brain has evolved mechanisms to maintain rich dynamics across a broad range of situations. Several mechanisms based around homeostatic plasticity have been proposed to explain how these dynamics emerge from networks of neurons at the microscopic scale. Here we explore how a homeostatic mechanism may operate at the macroscopic scale: in particular, focusing on how it interacts with the underlying structural network topology and how it gives rise to well-described functional connectivity networks. We use a simple mean-field model of the brain, constrained by empirical white matter structural connectivity where each region of the brain is simulated using a pool of excitatory and inhibitory neurons. We show, as with the microscopic work, that homeostatic plasticity regulates network activity and allows for the emergence of rich, spontaneous dynamics across a range of brain configurations, which otherwise show a very limited range of dynamic regimes. In addition, the simulated functional connectivity of the homeostatic model better resembles empirical functional connectivity network. To accomplish this, we show how the inhibitory weights adapt over time to capture important graph theoretic properties of the underlying structural network. Therefore, this work presents suggests how inhibitory homeostatic mechanisms facilitate stable macroscopic dynamics to emerge in the brain, aiding the formation of functional connectivity networks. Copyright © 2015 Elsevier Inc. All rights

  5. Brain mechanisms of flavor learning.

    Science.gov (United States)

    Yamamoto, Takashi; Ueji, Kayoko

    2011-01-01

    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 supramammillary 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.

  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. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Mechanisms of deep brain stimulation

    National Research Council Canada - National Science Library

    Herrington, Todd M; Cheng, Jennifer J; Eskandar, Emad N

    2016-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders...

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27598148

  9. 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.

  10. Entropy, Topological Theories and Emergent Quantum Mechanics

    Directory of Open Access Journals (Sweden)

    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.

  11. Creative innovation: possible brain mechanisms.

    Science.gov (United States)

    Heilman, Kenneth M; Nadeau, Stephen E; Beversdorf, David O

    2003-10-01

    This article reviews and develops some theories about the neurobiological basis of creative innovation (CI). CI is defined as the ability to understand and express novel orderly relationships. A high level of general intelligence, domain-specific knowledge and special skills are necessary components of creativity. Specialized knowledge is stored in specific portions of the temporal and parietal lobes. Some anatomic studies suggest that talented people might have alterations of specific regions of the posterior neocortical architecture, but further systematic studies are needed. Intelligence, knowledge and special skills, however, are not sufficient for CI. Developing alternative solutions or divergent thinking has been posited to be a critical element of CI, and clinical as well as functional imaging studies suggest that the frontal lobes are important for these activities. The frontal lobes have strong connections with the polymodal and supramodal regions of the temporal and parietal lobes where concepts and knowledge are stored. These connections might selectively inhibit and activate portions of posterior neocortex and thus be important for developing alternative solutions. Although extensive knowledge and divergent thinking together are critical for creativity they alone are insufficient for allowing a person to find the thread that unites. Finding this thread might require the binding of different forms of knowledge, stored in separate cortical modules that have not been previously associated. Thus, CI might require the co-activation and communication between regions of the brain that ordinarily are not strongly connected. The observations that CI often occurs during levels of low arousal and that many people with depression are creative suggests that alterations of neurotransmitters such as norepinephrine might be important in CI. High levels of norepinephrine, produced by high rates of locus coeruleus firing, restrict the breadth of concept representations

  12. Simulating Mechanics to Study Emergence in Games

    NARCIS (Netherlands)

    Dormans, Joris

    2011-01-01

    This paper presents the latest version of the Machinations framework. This framework uses diagrams to represent the flow of tangible and abstract resources through a game. This flow represents the mechanics that make up a game’s interbal economy and has a large impact on the emergent gameplay of

  13. Uncovering the mechanism(s) of deep brain stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y [Inspiring Technical Laboratory, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China)

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  14. The biological significance of brain barrier mechanisms

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  15. Serotonergic mechanisms in the migraine brain

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... This review suggests that novel methods of investigating the serotonergic system in the migraine brain are warranted. Uncovering the serotonergic mechanisms in migraine pathophysiology could prove useful for the development of future migraine drugs....... 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 papers...

  16. Emergency medicine residents' knowledge of mechanical ventilation.

    Science.gov (United States)

    Wilcox, Susan R; Seigel, Todd A; Strout, Tania D; Schneider, Jeffrey I; Mitchell, Patricia M; Marcolini, Evie G; Cocchi, Michael N; Smithline, Howard A; Lutfy-Clayton, Lucienne; Mullen, Marie; Ilgen, Jonathan S; Richards, Jeremy B

    2015-04-01

    Although Emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) residency curricula. The objective of this study was to quantify EM residents' education, experience, and knowledge regarding mechanical ventilation. We developed a survey of residents' educational experiences with ventilators and an assessment tool with nine clinical questions. Correlation and regression analyses were performed to evaluate the relationship between residents' scores on the assessment instrument and their training, education, and comfort with ventilation. Of 312 EM residents, 218 responded (69.9%). The overall correct response rate for the assessment tool was 73.3%, standard deviation (SD) ± 22.3. Seventy-seven percent (n = 167) of respondents reported ≤ 3 h of mechanical ventilation education in their residency curricula over the past year. Residents reported frequently caring for ventilated patients in the ED, as 64% (n = 139) recalled caring for ≥ 4 ventilated patients per month. Fifty-three percent (n = 116) of residents endorsed feeling comfortable caring for mechanically ventilated ED patients. In multiregression analysis, the only significant predictor of total test score was residents' comfort with caring for mechanically ventilated patients (F = 10.963, p = 0.001). EM residents report caring for mechanically ventilated patients frequently, but receive little education on mechanical ventilation. Furthermore, as residents' performance on the assessment tool is only correlated with their self-reported comfort with caring for ventilated patients, these results demonstrate an opportunity for increased educational focus on mechanical ventilation management in EM residency training. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Mechanisms of action of oral emergency contraception.

    Science.gov (United States)

    Gemzell-Danielsson, Kristina; Berger, Cecilia; Lalitkumar, P G

    2014-10-01

    This review gives an overview of the mechanisms of action of oral emergency contraception pills (ECPs), focusing on the levonorgestrel (LNG) and ulipristal acetate (UPA) containing ECPs. In vivo and in vitro studies have addressed the effect of EC on various possible targets. Based on these studies as well as on clinical trials it is clear that the efficacy of ECPs to prevent an unintended pregnancy depends on their mechanism of action as well as on their use in relation to the fertile window. While the main effect of both available ECPs is to prevent or delay ovulation the window of action for UPA is wider than that of LNG. This provides the biological explanation for the difference observed in clinical trials and the higher efficacy of UPA. Neither LNG nor UPA impairs endometrial receptivity or embryo implantation. Correct knowledge on the mechanism of action of ECPs is important to avoid overestimating their effectiveness and to advise women on correct use.

  18. The emergent Copenhagen interpretation of quantum mechanics

    Science.gov (United States)

    Hollowood, Timothy J.

    2014-05-01

    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. This interpretation describes a world in which definite measurement results are obtained with probabilities that reproduce the Born rule. 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 probabilities for the ergodic subsets of states of disjoint macro-systems only arise as emergent quantities. Finally we give an account of the EPR-Bohm thought experiment and show that the interpretation implies the violation of the Bell inequality characteristic of quantum mechanics but in a way that is rather novel. The final conclusion is that the Copenhagen interpretation gives a completely satisfactory phenomenology of macro-systems interacting with micro-systems.

  19. Bedaquiline resistance: Its emergence, mechanism and prevention.

    Science.gov (United States)

    Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C

    2017-11-08

    Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. Respiratory mechanics in brain-damaged patients.

    Science.gov (United States)

    Koutsoukou, Antonia; Perraki, Helen; Raftopoulou, Asimina; Koulouris, Nikolaos; Sotiropoulou, Christina; Kotanidou, Anastasia; Orfanos, Stylianos; Roussos, Charis

    2006-12-01

    To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH(2)O or zero PEEP (ZEEP). Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital. Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH(2)O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation. In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 +/- 3.8 cmH(2)O/l and 5.6 +/- 2.2 cmH(2)O/l per second, respectively); on day 5 static elastance and iso-CO(2) minimal resistance values were higher than on day 1 (21.2 +/- 4.1 cmH(2)O/l; 7.0 +/- 1.9 cmH(2)O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO(2)/FIO(2) in both groups. On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting "low lung volume" injury. Both could be prevented by administration of moderate levels of PEEP.

  1. Respiratory mechanics in brain injury: A review.

    Science.gov (United States)

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-02-04

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

  2. Emerging mechanisms of neutrophil recruitment across endothelium.

    Science.gov (United States)

    Williams, Marcie R; Azcutia, Verónica; Newton, Gail; Alcaide, Pilar; Luscinskas, Francis W

    2011-10-01

    Neutrophils are the all-terrain vehicle of the innate immune system because of their ability to gain entry into tissues and organs, and thus, play an essential role in host defense. Exactly how this marvel of nature works is still incompletely understood. In the past 2-3 years, new players and processes have been identified in the endothelial-leukocyte adhesion cascade. Novel signaling pathways have been discovered in both the endothelium and the neutrophils that regulate various steps in the recruitment process. This review focuses on these emerging pathways and the mechanisms that regulate neutrophil recruitment across endothelium. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Learning Predictive Statistics: Strategies and Brain Mechanisms.

    Science.gov (United States)

    Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew E; Kourtzi, Zoe

    2017-08-30

    When immersed in a new environment, we are challenged to decipher initially incomprehensible streams of sensory information. However, quite rapidly, the brain finds structure and meaning in these incoming signals, helping us to predict and prepare ourselves for future actions. This skill relies on extracting the statistics of event streams in the environment that contain regularities of variable complexity from simple repetitive patterns to complex probabilistic combinations. Here, we test the brain mechanisms that mediate our ability to adapt to the environment's statistics and predict upcoming events. By combining behavioral training and multisession fMRI in human participants (male and female), we track the corticostriatal mechanisms that mediate learning of temporal sequences as they change in structure complexity. We show that learning of predictive structures relates to individual decision strategy; that is, selecting the most probable outcome in a given context (maximizing) versus matching the exact sequence statistics. These strategies engage distinct human brain regions: maximizing engages dorsolateral prefrontal, cingulate, sensory-motor regions, and basal ganglia (dorsal caudate, putamen), whereas matching engages occipitotemporal regions (including the hippocampus) and basal ganglia (ventral caudate). Our findings provide evidence for distinct corticostriatal mechanisms that facilitate our ability to extract behaviorally relevant statistics to make predictions.SIGNIFICANCE STATEMENT Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. Past work has studied how humans identify repetitive patterns and associative pairings. However, the natural environment contains regularities that vary in complexity from simple repetition to complex probabilistic combinations. Here, we combine behavior and multisession fMRI to track the brain mechanisms that mediate our ability to adapt to

  4. 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.

  5. Mechanical characterization of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  6. Antioxidative defense mechanisms in the aging brain

    Directory of Open Access Journals (Sweden)

    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. Emerging Role of Epigenetic Mechanisms in Alcohol Addiction.

    Science.gov (United States)

    Berkel, Tiffani D M; Pandey, Subhash C

    2017-04-01

    Alcohol use disorder (AUD) is a complex brain disorder with an array of persistent behavioral and neurochemical manifestations. Both genetic and environmental factors are known to contribute to the development of AUD, and recent studies on alcohol exposure and subsequent changes in gene expression suggest the importance of epigenetic mechanisms. In particular, histone modifications and DNA methylation have emerged as important regulators of gene expression and associated phenotypes of AUD. Given the therapeutic potential of epigenetic targets, this review aims to summarize the role of epigenetic regulation in our current understanding of AUD by evaluating known epigenetic signatures of brain regions critical to addictive behaviors in both animal and human studies throughout various stages of AUD. More specifically, the effects of acute and chronic alcohol exposure, tolerance, and postexposure withdrawal on epigenetically induced changes to gene expression and synaptic plasticity within key brain regions and the associated behavioral phenotypes have been discussed. Understanding the contribution of epigenetic regulation to crucial signaling pathways may prove vital for future development of novel biomarkers and treatment agents in ameliorating or preventing AUD. Copyright © 2017 by the Research Society on Alcoholism.

  8. Developing Attention: Behavioral and Brain Mechanisms

    Directory of Open Access Journals (Sweden)

    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.

  9. Effect of vitro preservation on mechanical properties of brain tissue

    Science.gov (United States)

    Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

    2017-05-01

    To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

  10. Current and emerging brain applications of MR-guided focused ultrasound.

    Science.gov (United States)

    Meng, Ying; Suppiah, Suganth; Mithani, Karim; Solomon, Benjamin; Schwartz, Michael L; Lipsman, Nir

    2017-01-01

    MRI guided focused ultrasound is an emerging technique that uses acoustic energy to noninvasively treat intracranial disorders. At high frequencies, it can be used to raise tissue temperatures and ablate discrete brain targets with sub-millimeter accuracy. This application is currently under investigation for a broad range of clinical applications, including brain tumors, movement disorders, and psychiatric conditions. At low frequencies MRI guided focused ultrasound can be used to modulate neuronal activity and in conjunction with injected microbubbles, can open the blood-brain barrier to enhance the delivery of therapeutic compounds. The last decade has seen dramatic advances in the science of MRI guided focused ultrasound, helping elucidate both its mechanisms and potential in pre-clinical models, and its translational promise across myriad clinical applications. This review provides an update of current and emerging MRI guided focused ultrasound applications for intracranial disorders and describes future directions and challenges for the field.

  11. Brain mechanisms that control sleep and waking

    Science.gov (United States)

    Siegel, Jerome

    This review paper presents a brief historical survey of the technological and early research that laid the groundwork for recent advances in sleep-waking research. A major advance in this field occurred shortly after the end of World War II with the discovery of the ascending reticular activating system (ARAS) as the neural source in the brain stem of the waking state. Subsequent research showed that the brain stem activating system produced cortical arousal via two pathways: a dorsal route through the thalamus and a ventral route through the hypothalamus and basal forebrain. The nuclei, pathways, and neurotransmitters that comprise the multiple components of these arousal systems are described. Sleep is now recognized as being composed of two very different states: rapid eye movements (REMs) sleep and non-REM sleep. The major findings on the neural mechanisms that control these two sleep states are presented. This review ends with a discussion of two current views on the function of sleep: to maintain the integrity of the immune system and to enhance memory consolidation.

  12. ``the Human BRAIN & Fractal quantum mechanics''

    Science.gov (United States)

    Rosary-Oyong, Se, Glory

    In mtDNA ever retrieved from Iman Tuassoly, et.al:Multifractal analysis of chaos game representation images of mtDNA''.Enhances the price & valuetales of HE. Prof. Dr-Ing. B.J. HABIBIE's N-219, in J. Bacteriology, Nov 1973 sought:'' 219 exist as separate plasmidDNA species in E.coli & Salmonella panama'' related to ``the brain 2 distinct molecular forms of the (Na,K)-ATPase..'' & ``neuron maintains different concentration of ions(charged atoms'' thorough Rabi & Heisenber Hamiltonian. Further, after ``fractal space time are geometric analogue of relativistic quantum mechanics''[Ord], sought L.Marek Crnjac: ``Chaotic fractals at the root of relativistic quantum physics''& from famous Nottale: ``Scale relativity & fractal space-time:''Application to Quantum Physics , Cosmology & Chaotic systems'',1995. Acknowledgements to HE. Mr. H. TUK SETYOHADI, Jl. Sriwijaya Raya 3, South-Jakarta, INDONESIA.

  13. MONETARY POLICY TRANSMISSION MECHANISM IN EMERGING COUNTRIES

    National Research Council Canada - National Science Library

    Andreea ROŞOIU; Iulia ROŞOIU

    2013-01-01

    .... 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...

  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. Study on Mine Emergency Mechanism based on TARP and ICS

    Science.gov (United States)

    Xi, Jian; Wu, Zongzhi

    2018-01-01

    By analyzing the experiences and practices of mine emergency in China and abroad, especially the United States and Australia, normative principle, risk management principle and adaptability principle of constructing mine emergency mechanism based on Trigger Action Response Plans (TARP) and Incident Command System (ICS) are summarized. Classification method, framework, flow and subject of TARP and ICS which are suitable for the actual situation of domestic mine emergency are proposed. The system dynamics model of TARP and ICS is established. The parameters such as evacuation ratio, response rate, per capita emergency capability and entry rate of rescuers are set up. By simulating the operation process of TARP and ICS, the impact of these parameters on the emergency process are analyzed, which could provide a reference and basis for building emergency capacity, formulating emergency plans and setting up action plans in the emergency process.

  16. Principals' Learning Mechanisms: Exploring an Emerging Construct

    Science.gov (United States)

    Schechter, Chen; Qadach, Mowafaq

    2016-01-01

    This exploration of principal learning mechanisms (PLM) to support a learning-centered school aimed to develop, field-test, and validate a PLM-measuring instrument. Following exploratory and confirmatory factor analyses of items to examine factorial validity, the developed scale was correlated with other work-related established constructs (e.g.,…

  17. 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. 2010 Elsevier Inc. All rights reserved.

  18. Brain Mechanisms in Early Language Acquisition

    Science.gov (United States)

    Kuhl, Patricia K.

    2010-01-01

    Summary 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 pre-reading 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. PMID:20826304

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Fazel-Rezai, Reza; Allison, Brendan Z.; Guger, Christoph; Sellers, Eric W.; Kleih, Sonja C.; Kübler, Andrea

    2012-01-01

    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 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. PMID:22822397

  1. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

    Science.gov (United States)

    Hamed, Sherifa A

    2017-04-01

    Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

  2. Physical-Mechanisms Based Reliability Analysis For Emerging Technologies

    Science.gov (United States)

    2017-05-05

    AFRL-AFOSR-VA-TR-2017-0095 PHYSICAL-MECHANISMS BASED RELIABILITY ANALYSIS FOR EMERGING TECHNOLOGIES Ron Schrimpf VANDERBILT UNIVERSITY 110 21ST...SUBTITLE PHYSICAL-MECHANISMS BASED RELIABILITY ANALYSIS FOR EMERGING TECHNOLOGIES 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-11-1-0307 5c.  PROGRAM...order to ensure technical superiority for US forces, but at the same time, levels of reliability exceeding those of commercial systems are required

  3. Maturing Brain Mechanisms and Developing Behavioral Language Skills

    Science.gov (United States)

    Friedrich, Manuela; Friederici, Angela D.

    2010-01-01

    The relation between the maturation of brain mechanisms responsible for the N400 elicitation in the event-related brain potential (ERP) and the development of behavioral language skills was investigated in 12-month-old infants. ERPs to words presented in a picture-word priming paradigm were analyzed according to the infants' production and…

  4. [Brain Mechanism for Successful Memory Retrieval].

    Science.gov (United States)

    Takeda, Masaki

    2016-04-01

    Previous neuropsychological studies that investigated patients with brain injury have revealed the presense of multiple memory systems and the related brain regions. Recent functional imaging studies have identified a neuronal network including the temporal cortex and hippocampus that is responsible for the retrieval of semantic memory. This memory network was further investigated by electrophysiology using a simultaneous recording technique. This new technique revealed that a coupling of inter-area top-down signal within the temporal cortex with translaminar signal processing is required for successful memory retrieval of visual objects.

  5. Increasingly diverse brain dynamics in the developmental arc: using Pareto-optimization to infer a mechanism

    Science.gov (United States)

    Tang, Evelyn; Giusti, Chad; Baum, Graham; Gu, Shi; Pollock, Eli; Kahn, Ari; Roalf, David; Moore, Tyler; Ruparel, Kosha; Gur, Ruben; Gur, Raquel; Satterthwaite, Theodore; Bassett, Danielle

    Motivated by a recent demonstration that the network architecture of white matter supports emerging control of diverse neural dynamics as children mature into adults, we seek to investigate structural mechanisms that support these changes. Beginning from a network representation of diffusion imaging data, we simulate network evolution with a set of simple growth rules built on principles of network control. Notably, the optimal evolutionary trajectory displays a striking correspondence to the progression of child to adult brain, suggesting that network control is a driver of development. More generally, and in comparison to the complete set of available models, we demonstrate that all brain networks from child to adult are structured in a manner highly optimized for the control of diverse neural dynamics. Within this near-optimality, we observe differences in the predicted control mechanisms of the child and adult brains, suggesting that the white matter architecture in children has a greater potential to increasingly support brain state transitions, potentially underlying cognitive switching.

  6. Mechanisms of microbial traversal of the blood-brain barrier.

    Science.gov (United States)

    Kim, Kwang Sik

    2008-08-01

    Central nervous system (CNS) infections continue to be an important cause of morbidity and mortality. Microbial invasion and traversal of the blood-brain barrier is a prerequisite for CNS infections. Pathogens can cross the blood-brain barrier transcellularly, paracellularly and/or in infected phagocytes (the so-called Trojan-horse mechanism). Consequently, pathogens can cause blood-brain barrier dysfunction, including increased permeability, pleocytosis and encephalopathy. A more complete understanding of the microbial-host interactions that are involved in microbial traversal of the blood-brain barrier and the associated barrier dysfunction should help to develop new strategies to prevent CNS infections.

  7. Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis.

    Science.gov (United States)

    Bauer, Kylynda C; Huus, Kelsey E; Finlay, B Brett

    2016-05-01

    The concept of a gut microbiota-brain axis has emerged to describe the complex and continuous signalling between the gut microbiota and host nervous system. This review examines key microbial-derived neuromodulators and structural components that comprise the gut microbiota-brain axis. To conclude, we briefly identify current challenges in gut microbiota-brain research and suggest a framework to characterize these interactions. Here, we propose five emerging hallmarks of the gut microbiota-brain axis: (i) Indistinguishability, (ii) Emergence, (iii) Bidirectional Signalling, (iv) Critical Window Fluidity and (5) Neural Homeostasis. © 2016 John Wiley & Sons Ltd.

  8. 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.

  9. The emergence of functional architecture during early brain development

    NARCIS (Netherlands)

    Keunen, Kristin|info:eu-repo/dai/nl/413751953; Counsell, Serena J.; Benders, Manon J.N.L.|info:eu-repo/dai/nl/185214266

    2017-01-01

    Early human brain development constitutes a sequence of intricate processes resulting in the ontogeny of functionally operative neural circuits. Developmental trajectories of early brain network formation are genetically programmed and can be modified by epigenetic and environmental influences. Such

  10. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The Right Brain: An Emerging Frontier in Education.

    Science.gov (United States)

    Beals, Mark G.

    The main thrust of American education has been cognitively oriented. Recent research on the human brain suggests that such orientation is a general function of only one hemisphere of the brain, the left. Because of the close relationships among speech, language, thinking, reasoning, and the higher mental functions, the left brain hemisphere…

  12. 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.

  13. Modulating Effect of Cytokines on Mechanisms of Synaptic Plasticity in the Brain.

    Science.gov (United States)

    Levin, S G; Godukhin, O V

    2017-03-01

    After accumulation of data showing that resident brain cells (neurons, astrocytes, and microglia) produce mediators of the immune system, such as cytokines and their receptors under normal physiological conditions, a critical need emerged for investigating the role of these mediators in cognitive processes. The major problem for understanding the functional role of cytokines in the mechanisms of synaptic plasticity, de novo neurogenesis, and learning and memory is the small number of investigated cytokines. Existing concepts are based on data from just three proinflammatory cytokines: interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha. The amount of information in the literature on the functional role of antiinflammatory cytokines in the mechanisms of synaptic plasticity and cognitive functions of mature mammalian brain is dismally low. However, they are of principle importance for understanding the mechanisms of local information processing in the brain, since they modulate the activity of individual cells and local neural networks, being able to reconstruct the processes of synaptic plasticity and intercellular communication, in general, depending on the local ratio of the levels of different cytokines in certain areas of the brain. Understanding the functional role of cytokines in cellular mechanisms of information processing and storage in the brain would allow developing preventive and therapeutic means for the treatment of neuropathologies related to impairment of these mechanisms.

  14. Mechanics of the brain: perspectives, challenges, and opportunities.

    Science.gov (United States)

    Goriely, Alain; Geers, Marc G D; Holzapfel, Gerhard A; Jayamohan, Jayaratnam; Jérusalem, Antoine; Sivaloganathan, Sivabal; Squier, Waney; van Dommelen, Johannes A W; Waters, Sarah; Kuhl, Ellen

    2015-10-01

    The human brain is the continuous subject of extensive investigation aimed at understanding its behavior and function. Despite a clear evidence that mechanical factors play an important role in regulating brain activity, current research efforts focus mainly on the biochemical or electrophysiological activity of the brain. Here, we show that classical mechanical concepts including deformations, stretch, strain, strain rate, pressure, and stress play a crucial role in modulating both brain form and brain function. This opinion piece synthesizes expertise in applied mathematics, solid and fluid mechanics, biomechanics, experimentation, material sciences, neuropathology, and neurosurgery to address today's open questions at the forefront of neuromechanics. We critically review the current literature and discuss challenges related to neurodevelopment, cerebral edema, lissencephaly, polymicrogyria, hydrocephaly, craniectomy, spinal cord injury, tumor growth, traumatic brain injury, and shaken baby syndrome. The multi-disciplinary analysis of these various phenomena and pathologies presents new opportunities and suggests that mechanical modeling is a central tool to bridge the scales by synthesizing information from the molecular via the cellular and tissue all the way to the organ level.

  15. Academic Emergency Medicine Physicians’ Knowledge of Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Susan R. Wilcox

    2016-05-01

    Full Text Available Introduction: Although emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM education or clinical practice. The objective of this study was to quantify EM attendings’ education, experience, and knowledge regarding mechanical ventilation in the emergency department. Methods: We developed a survey of academic EM attendings’ educational experiences with ventilators and a knowledge assessment tool with nine clinical questions. EM attendings at key teaching hospitals for seven EM residency training programs in the northeastern United States were invited to participate in this survey study. We performed correlation and regression analyses to evaluate the relationship between attendings’ scores on the assessment instrument and their training, education, and comfort with ventilation. Results: Of 394 EM attendings surveyed, 211 responded (53.6%. Of respondents, 74.5% reported receiving three or fewer hours of ventilation-related education from EM sources over the past year and 98 (46% reported receiving between 0-1 hour of education. The overall correct response rate for the assessment tool was 73.4%, with a standard deviation of 19.9. The factors associated with a higher score were completion of an EM residency, prior emphasis on mechanical ventilation during one’s own residency, working in a setting where an emergency physician bears primary responsibility for ventilator management, and level of comfort with managing ventilated patients. Physicians’ comfort was associated with the frequency of ventilator changes and EM management of ventilation, as well as hours of education. Conclusion: EM attendings report caring for mechanically ventilated patients frequently, but most receive fewer than three educational hours a year on mechanical ventilation, and nearly half receive 0-1 hour. Physicians’ performance on an assessment tool for mechanical ventilation is

  16. 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

    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...

  17. Brain Mechanisms of Affective Language Comprehension in Autism Spectrum Disorders

    Science.gov (United States)

    2016-10-01

    This data will enable us to examine the general connectivity of brain structures in our population of participants with ASD compared to our control... compared to typically developing peers. As depicted in Figure 1, the current investigation aims to identify the brain mechanisms underlying difficulties...to stories inferring others emotions. In the first year, we have collected functional and structural magnetic resonance imaging ( MRI ) data from 31

  18. 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.

  19. Brain Organization into Resting State Networks Emerges at Criticality on a Model of the Human Connectome

    Science.gov (United States)

    Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.

    2013-04-01

    The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.

  20. Local mechanical properties of white matter structures in the human brain

    Science.gov (United States)

    Johnson, Curtis L; McGarry, Matthew DJ; Gharibans, Armen A; Weaver, John B; Paulsen, Keith D; Wang, Huan; Olivero, William C; Sutton, Bradley P; Georgiadis, John G

    2013-01-01

    The noninvasive measurement of the mechanical properties of brain tissue using magnetic resonance elastography (MRE) has emerged as a promising method for investigating neurological disorders. To date, brain MRE investigations have been limited to reporting global mechanical properties, though quantification of the stiffness of specific structures in the white matter architecture may be valuable in assessing the localized effects of disease. This paper reports the mechanical properties of the corpus callosum and corona radiata measured in healthy volunteers using MRE and atlas-based segmentation. Both structures were found to be significantly stiffer than overall white matter, with the corpus callosum exhibiting greater stiffness and less viscous damping than the corona radiata. Reliability of both local and global measures was assessed through repeated experiments, and the coefficient of variation for each measure was less than 10%. Mechanical properties within the corpus callosum and corona radiata demonstrated correlations with measures from diffusion tensor imaging pertaining to axonal microstructure. PMID:23644001

  1. Academic Emergency Medicine Physicians' Knowledge of Mechanical Ventilation.

    Science.gov (United States)

    Wilcox, Susan R; Strout, Tania D; Schneider, Jeffrey I; Mitchell, Patricia M; Smith, Jessica; Lutfy-Clayton, Lucienne; Marcolini, Evie G; Aydin, Ani; Seigel, Todd A; Richards, Jeremy B

    2016-05-01

    Although emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) education or clinical practice. The objective of this study was to quantify EM attendings' education, experience, and knowledge regarding mechanical ventilation in the emergency department. We developed a survey of academic EM attendings' educational experiences with ventilators and a knowledge assessment tool with nine clinical questions. EM attendings at key teaching hospitals for seven EM residency training programs in the northeastern United States were invited to participate in this survey study. We performed correlation and regression analyses to evaluate the relationship between attendings' scores on the assessment instrument and their training, education, and comfort with ventilation. Of 394 EM attendings surveyed, 211 responded (53.6%). Of respondents, 74.5% reported receiving three or fewer hours of ventilation-related education from EM sources over the past year and 98 (46%) reported receiving between 0-1 hour of education. The overall correct response rate for the assessment tool was 73.4%, with a standard deviation of 19.9. The factors associated with a higher score were completion of an EM residency, prior emphasis on mechanical ventilation during one's own residency, working in a setting where an emergency physician bears primary responsibility for ventilator management, and level of comfort with managing ventilated patients. Physicians' comfort was associated with the frequency of ventilator changes and EM management of ventilation, as well as hours of education. EM attendings report caring for mechanically ventilated patients frequently, but most receive fewer than three educational hours a year on mechanical ventilation, and nearly half receive 0-1 hour. Physicians' performance on an assessment tool for mechanical ventilation is most strongly correlated with their self-reported comfort with mechanical

  2. 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.

  3. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Emergence Of Consciousness And Qualia From A Complex Brain

    Directory of Open Access Journals (Sweden)

    Korf Jakob

    2014-12-01

    Full Text Available Qualia are private conscious experiences of which the associated feelings can be reported to other people. Whether qualia are amenable to scientific exploration has often been questioned, which is challenged by the present article. The following arguments are given: 1. the configuration of the brain changes continuously and irreversibly, because of genetic and environmental influences and interhuman communication; 2. qualia and consciousness are processes, rather than states; 3. private feelings, including those associated with qualia, should be positioned in the context of a personal brain as being developed during life; 4. consciousness and qualia should be understood in the context of general system theory, thus concluding that isolated, in vitro, properties of neurons and other brain constituents might marginally contribute to the understanding of higher brain functions, mind or qualia; 5. current in vivo approaches have too little resolution power - in terms of space and time - to delineate individual and subjective brain processes.

  5. 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...

  6. A longitudinal study of the mechanical properties of injured brain tissue in a mouse model.

    Science.gov (United States)

    Feng, Yuan; Gao, Yuan; Wang, Tao; Tao, Luyang; Qiu, Suhao; Zhao, Xuefeng

    2017-07-01

    Mechanical properties of brain tissue are crucial to understand the mechanism of traumatic brain injury (TBI). Over the past several decades, most of the studies focused on healthy brain tissues, while few of them are about the injured tissues. Therefore, limited knowledge is known about the mechanical properties of the injured brain tissues. In this study, we used an in vivo mouse model with a weight drop device to study injured brain tissues. Around the injury site, mechanical properties of the injured, neighboring, and the corresponding contralateral regions of interest (ROIs) were measured over five temporal points by indentation. Longitudinal and regional comparisons of the mechanical properties revealed that the ROI of the injured tissue had a higher elastic modulus than the contralateral counterpart one-hour post-injury. However, the elastic modulus decreased one-day post-injury and recovered to be close to the contralateral ROI in 7 days. The elastic modulus curves of the injured and the contralateral counterpart ROIs crossed at time points of 12h and 1 day post-injury, where two significant increases of glial fibrillary acidic protein (GFAP) positive cells were observed. Biological staining results indicated that both the astrocytic responses and the morphological structure could affect the mechanical properties of the injured tissue. The observed longitudinal changes of the mechanical properties at the tissue level and the morphological and biological changes at the cellular level provide insights into understanding the mechanism of TBI. Results are also meaningful for applying emerging in vivo diagnostic tools such as magnetic resonance elastography (MRE) in TBI detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Brain-kidney cross-talk: Definition and emerging evidence.

    Science.gov (United States)

    Afsar, Baris; Sag, Alan A; Yalcin, Can Ege; Kaya, Eren; Siriopol, Dimitrie; Goldsmith, David; Covic, Adrian; Kanbay, Mehmet

    2016-12-01

    Cross-talk is broadly defined as endogenous homeostatic signaling between vital organs such as the heart, kidneys and brain. Kidney-brain cross-talk remains an area with excitingly few publications despite its purported clinical relevance in the management of currently undertreated conditions such as resistant hypertension. Therefore, this review aims to establish an organ-specific definition for kidney-brain cross-talk and review the available and forthcoming literature on this topic. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  8. Brain alterations and clinical symptoms of dementia in diabetes: Abeta/tau-dependent and independent mechanisms

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2014-09-01

    Full Text Available Emerging evidence suggests that diabetes affects cognitive function and increases the incidence of dementia. However, the mechanisms by which diabetes modifies cognitive function still remains unclear. Morphologically, diabetes is associated with neuronal loss in the frontal and temporal lobes including the hippocampus, and aberrant functional connectivity of the posterior cingulate cortex and medial frontal/temporal gyrus. Clinically, diabetic patients show decreased executive function, information processing, planning, visuospatial construction, and visual memory. Therefore, in comparison with the characteristics of AD brain structure and cognition, diabetes seems to affect cognitive function through not only simple AD pathological feature-dependent mechanisms, but also independent mechanisms. As an Abeta/tau-independent mechanism, diabetes compromises cerebrovascular function, increases subcortical infarction and might alter the blood brain barrier (BBB. Diabetes also affects glucose metabolism, insulin signaling and mitochondrial function in the brain. Diabetes also modifies metabolism of Abeta and tau and causes Abeta/tau-dependent pathological changes. Moreover, there is evidence that suggests an interaction between Abeta/tau-dependent and independent mechanisms. Therefore, diabetes modifies cognitive function through Abeta/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle.

  9. Seed dormancy and germination - Emerging mechanisms and new hypotheses

    Directory of Open Access Journals (Sweden)

    Hiroyuki eNonogaki

    2014-05-01

    Full Text Available Seed dormancy has played a significant role in adaptation and evolution of seed plants. While its biological significance is clear, molecular mechanisms underlying seed dormancy induction, maintenance and alleviation still remain elusive. Intensive efforts have been made to investigate gibberellin and abscisic acid metabolism in seeds, which greatly contributed to the current understanding of seed dormancy mechanisms. Other mechanisms, which might be independent of hormones, or specific to the seed dormancy pathway, are also emerging from genetic analysis of seed dormancy mutants. These studies suggest that chromatin remodeling through histone ubiquitination, methylation and acetylation, which could lead to transcription elongation or gene silencing, may play a significant role in seed dormancy regulation. Small interfering RNA and/or long non-coding RNA might be a trigger of epigenetic changes at the seed dormancy or germination loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from genetic studies of seed dormancy, novel hypotheses are also generated from seed germination study with high throughput gene expression analysis. Recent studies on tissue-specific gene expression in tomato and Arabidopsis seeds, which suggested possible mechanosensing in the regulatory mechanisms, advanced our understanding of embryo-endosperm interaction and have potential to re-draw the traditional hypotheses or integrate them into a comprehensive scheme. The progress in basic seed science will enable knowledge translation, another frontier of research to be expanded for food and fuel production.

  10. Mechanical ventilation in emergency departments: Non invasive or invasive mechanical ventilation. Where is the answer?

    OpenAIRE

    Esquinas Rodriguez Antonio M; Cosentini Roberto; Papadakos Peter J

    2012-01-01

    The Emergency Department length of stay for patients requiring mechanical ventilation paper in this issue is very illustrative of many variables that still confound the way we treat patients that may not require endotracheal intubation (ETI) but may benefit from non-invasive mechanical ventilation (NIV) [1].

  11. [Lung-brain interaction in the mechanically ventilated patient].

    Science.gov (United States)

    López-Aguilar, J; Fernández-Gonzalo, M S; Turon, M; Quílez, M E; Gómez-Simón, V; Jódar, M M; Blanch, L

    2013-10-01

    Patients with acute lung injury or acute respiratory distress syndrome (ARDS) admitted to the ICU present neuropsychological alterations, which in most cases extend beyond the acute phase and have an important adverse effect upon quality of life. The aim of this review is to deepen in the analysis of the complex interaction between lung and brain in critically ill patients subjected to mechanical ventilation. This update first describes the neuropsychological alterations occurring both during the acute phase of ICU stay and at discharge, followed by an analysis of lung-brain interactions during mechanical ventilation, and finally explores the etiology and mechanisms leading to the neurological disorders observed in these patients. The management of critical patients requires an integral approach focused on minimizing the deleterious effects over the short, middle or long term. Copyright © 2012 Elsevier España, S.L. y SEMICYUC. All rights reserved.

  12. Mechanisms of CCK signaling from gut to brain

    OpenAIRE

    Raybould, Helen E.

    2007-01-01

    Following the observation that exogenous peripheral injection of CCK could inhibit food intake, the mechanisms by which CCK influences the gut-brain pathway has been the subject of intense study for nearly thirty 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 ex...

  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. Emergency medicine program targets "brain drain" in Ethiopia ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    15 juil. 2014 ... "brain drain" in Ethiopia. Dr Dave MacKinnon gives a demonstration on casting to medical residents in Addis Ababa. Over the last three decades, 4,000 doctors have left Ethiopia for specialized training abroad. But very few return home to practice their specialty. Now, thanks to the Toronto-Addis Ababa ...

  15. Traumatic Brain Injury in the Accident and Emergency Department of ...

    African Journals Online (AJOL)

    Background: Traumatic brain injury is a major public health problem in Nigeria, as it could be associated with long term and life long deficits. Unlike other parts of the world, in our country, motorcycles are possibly the main cause of this injury. Unfortunately, we do not have a national epidemiological data base yet. This study ...

  16. Brain mechanical property measurement using MRE with intrinsic activation

    Science.gov (United States)

    Weaver, John B.; Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

    2012-11-01

    Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed ‘intrinsic activation’, that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of six asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation

  17. Brain insulin: regulation, mechanisms of action and functions.

    Science.gov (United States)

    Gerozissis, Kyriaki; Kyriaki, Gerozissis

    2003-02-01

    1. While many questions remained unanswered, it is now well documented that, contrary to earlier views, insulin is an important neuromodulator, contributing to neurobiological processes, in particular energy homeostasis and cognition. A specific role on cognitive functions related to feeding is proposed, and it is suggested that brain insulin from different sources might be involved in the above vital functions in health and disease. 2. A molecule identical to pancreatic insulin, and specific insulin receptors, are found widely distributed in the central nervous system networks related to feeding, reproduction, or cognition. 3. The actions of insulin in the central nervous system may be under both multilevel and multifactorial controls. The amount of blood insulin reaching the brain, brain insulin stores and secretion, potential local biosynthesis and degradation of the peptide, and insulin receptors and signal transduction can be affected by metabolic factors induced by nutrients, hormones, neurotransmitters, and regulatory peptides, peripherally or in the central nervous system. 4. Glucose and serotonin regulate insulin directly in the hypothalamus and may be of importance for its biological effects. Central mechanisms regulating glucose-induced insulin secretion show some analogy with the mechanisms operating in the pancreas. 5. A cross-talk between insulin and leptin receptors has been observed in the brain, and a regulation of central insulin actions, potentially via serotonin modulation, by leptin, galanin, melancortins, and neuropeptide Y (NPY) is suggested. 6. A more complete knowledge of the biological role of insulin in brain function and dysfunction, and of the regulatory mechanisms involved in these processes, constitutes a real advancement in the understanding of the pathophysiology of metabolic and mental diseases and could lead to important medical benefits.

  18. 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. Copyright © 2016. Published by Elsevier Inc.

  19. 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

  20. Stress and the social brain: behavioural effects and neurobiological mechanisms.

    Science.gov (United States)

    Sandi, Carmen; Haller, József

    2015-05-01

    Stress often affects our social lives. When undergoing high-level or persistent stress, individuals frequently retract from social interactions and become irritable and hostile. Predisposition to antisocial behaviours - including social detachment and violence - is also modulated by early life adversity; however, the effects of early life stress depend on the timing of exposure and genetic factors. Research in animals and humans has revealed some of the structural, functional and molecular changes in the brain that underlie the effects of stress on social behaviour. Findings in this emerging field will have implications both for the clinic and for society.

  1. Physical insights into the blood-brain barrier translocation mechanisms

    Science.gov (United States)

    Theodorakis, Panagiotis E.; Müller, Erich A.; Craster, Richard V.; Matar, Omar K.

    2017-08-01

    The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.

  2. Mechanism of Deep Brain Stimulation: Inhibition, Excitation, or Disruption?

    Science.gov (United States)

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

    Deep brain stimulation (DBS), applying high-frequency electrical stimulation to deep brain structures, has now provided an effective therapeutic option for treatment of various neurological and psychiatric disorders. DBS targeting the internal segment of the globus pallidus, subthalamic nucleus, and thalamus is used to treat symptoms of movement disorders, such as Parkinson's disease, dystonia, and tremor. However, the mechanism underlying the beneficial effects of DBS remains poorly understood and is still under debate: Does DBS inhibit or excite local neuronal elements? In this short review, we would like to introduce our recent work on the physiological mechanism of DBS and propose an alternative explanation: DBS dissociates input and output signals, resulting in the disruption of abnormal information flow through the stimulation site. © The Author(s) 2015.

  3. Emergency medicine program targets "brain drain" in Ethiopia ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-04-29

    Apr 29, 2016 ... TAAAC-EM2.jpg With IDRC support, the TAAC-EM program has. retained 80% of the first graduating class of 2013 in jobs in Ethiopia's public sector; ​published 54 open access, online teaching modules; ​developed a research program focusing on evidence-based emergency care and services at AAU.

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

    Science.gov (United States)

    Perlovsky, Leonid; Ilin, Roman

    2012-01-01

    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. PMID:24961270

  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.

    Science.gov (United States)

    Perlovsky, Leonid; Ilin, Roman

    2012-12-18

    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. 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.

  8. 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.

  9. The role of programmed and emergent mechanisms of coordination

    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...

  10. Deep Brain Stimulation Emergencies: How the New Technologies Could Modify the Current Scenario.

    Science.gov (United States)

    Cossu, Giovanni; Sensi, Mariachiara

    2017-07-01

    After 25 years of deep brain stimulation (DBS) for the treatment of Parkinson's disease, it has become increasingly recognized that a range of postoperative urgent situations and emergencies may occur. In this review we describe the possible scenarios of DBS-related emergencies: perioperative (intraoperative and early postoperative) and postoperative settings and issues from suboptimal control of motor and nonmotor symptoms in the early programming phase and during long-term follow-up. We also outline potential advantages in the management of these emergencies offered by the newest devices, emerging technologies, and new possibilities in programming.

  11. Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

    Science.gov (United States)

    Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

    2011-01-01

    The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

  12. Emerging Roles of CREB-Regulated Transcription Coactivators in Brain Physiology and Pathology.

    OpenAIRE

    Saura, C.A.; Cardinaux, J R

    2017-01-01

    The brain has the ability to sense, coordinate, and respond to environmental changes through biological processes involving activity-dependent gene expression. cAMP-response element binding protein (CREB)-regulated transcription coactivators (CRTCs) have recently emerged as novel transcriptional regulators of essential biological functions, while their deregulation is linked to age-related human diseases. In the brain, CRTCs are unique signaling factors that act as sensors and integrators of ...

  13. 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

  14. Dynamic links between emerging cognitive skills and brain processes.

    Science.gov (United States)

    Molfese, Dennis L; Molfese, Victoria J; Beswick, Jennifer; Jacobi-Vessels, Jill; Molfese, Peter J; Key, Alexandra P F; Starkey, Gillian

    2008-01-01

    The goal of the present study was to investigate whether advanced cognitive skills in one domain impact the neural processing of unrelated skills in a different cognitive domain. This question is related to the broader issue of how cognitive-neurodevelopment proceeds as different skills are mastered. To address this goal, event-related brain potentials (ERPs) were used to assess linkages between cognitive skills of preschool children as reflected in their performance on a pre-reading screening test (Get Ready To Read) and their neural responses while engaged in a geometric shape matching task. Sixteen children (10 males) participated in this study. The children ranged from 46 to 60 months (SD = 4.36 months). ERPs were recorded using a 128-electrode high-density array while children attended to presentations of matched and mismatched shapes (triangles, circles, or squares). ERPs indicated that children with more advanced pre-reading skills discriminated between matched and mismatched shapes earlier than children with poorer pre-readings skills. The earlier discrimination effect observed in the advanced group was localized over the occipital electrode sites whereas in the Low Group such effects were present over frontal, parietal, and occipital sites. Modeled magnetic resonance images (MRIs) of the ERP component sources identified differences in neural generators between the two groups. Both sets of findings support the hypothesis that processing in a poorer-performing group is more distributed temporally and spatially across the scalp, and reflects the engagement of more distributed brain regions. These findings are seen as support for a theory of neural-cognitive development that is advanced in the present article.

  15. Cortical and subcortical mechanisms of brain-machine interfaces.

    Science.gov (United States)

    Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

    2017-06-01

    Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. [Mild traumatic brain injury and postconcussive syndrome: a re-emergent questioning].

    Science.gov (United States)

    Auxéméry, Y

    2012-09-01

    Blast injuries are psychologically and physically devastating. Notably, primary blast injury occurs as a direct effect of changes in atmospheric pressure caused by a blast wave. The combat-related traumatic brain injuries (TBI) resulting from exposure to explosions is highly prevalent among military personnel who have served in current wars. Traumatic brain injury is a common cause of neurological damage and disability among civilians and servicemen. Most patients with TBI suffer a mild traumatic brain injury with transient loss of consciousness. A controversial issue in the field of head injury is the outcome of concussion. Most individuals with such injuries are not admitted to emergency units and receive a variable degree of medical attention. Nevertheless, cranial traumas vary in their mechanisms (blast, fall, road accident, bullet-induced craniocerebral injury) and in their gravity (from minor to severe). The majority of subjects suffering concussion have been exposed to explosion or blast injuries, which have caused minor cranial trauma. Although some authors refuse to accept the reality of post-concussion syndrome (PCS) and confuse it with masked depression, somatic illnesses or post-traumatic stress, we have raised the question again of its existence, without denying the intricate links with other psychiatric or neurological disorders. Although the mortality rate is negligible, the traumatic sequel after mild traumatic brain injury is clear. A difference in initial somatic severity is noted between the serious somatic consequences of a severe cranial trauma compared with the apparently benign consequences of a minor cranial trauma. However, the long-term consequences of the two types of impacts are far from negligible: PCS is a source of morbidity. The prognosis for minor cranial traumas is benign at vital level but a number of patients will develop long-term complaints, which contrast with the negativity of the clinical examination and complementary

  17. 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.

  18. Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Charles J Wilson

    2011-06-01

    Full Text Available High frequency deep-brain stimulation of the subthalamic nucleus (DBS relieves many of the symptoms of Parkinson's disease in humans and animal models. Although the treatment has seen widespread use, its therapeutic mechanism remains paradoxical. The subthalamic nucleus is excitatory, so its stimulation at rates higher than its normal firing rate should worsen the disease by increasing subthalamic excitation of the globus pallidus. The therapeutic effectiveness of DBS is also frequency and intensity sensitive, and the stimulation must be periodic; aperiodic stimulation at the same mean rate is ineffective. These requirements are not adequately explained by existing models, whether based on firing rate changes or on reduced bursting. Here we report modeling studies suggesting that high frequency periodic excitation of the subthalamic nucleus may act by desynchronizing the firing of neurons in the globus pallidus, rather than by changing the firing rate or pattern of individual cells. Globus pallidus neurons are normally desynchronized, but their activity becomes correlated in Parkinson's disease. Periodic stimulation may induce chaotic desynchronization by interacting with the intrinsic oscillatory mechanism of globus pallidus neurons. Our modeling results suggest a mechanism of action of deep brain stimulation and a pathophysiology of Parkinsonism in which synchrony, rather than firing rate, is the critical pathological feature.

  19. 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.

  20. 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.

  1. Molecular mechanisms of cognitive dysfunction following traumatic brain injury.

    Science.gov (United States)

    Walker, Kendall R; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

  2. Molecular mechanisms of cognitive dysfunction following traumatic brain injury

    Science.gov (United States)

    Walker, Kendall R.; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

  3. Molecular Mechanisms of Cognitive Dysfunction following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kendall Rae Walker

    2013-07-01

    Full Text Available Traumatic brain injury (TBI results in significant disability due to cognitive deficits particularly in attention, learning and memory and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer’s disease (AD, Parkinson’s disease (PD, Amyotrophic Lateral Sclerosis (ALS and most recently chronic traumatic encephalopathy (CTE is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

  4. Memory, imprinting, and the brain: an inquiry into mechanisms

    National Research Council Canada - National Science Library

    Horn, Gabriel

    1985-01-01

    ... process, and advances in our understanding of the mechanisms by which information is stored in the brain are recent and have been made on a limited front. The purpose of writing this book is to say something about these advances. The book is not, nor is it intended to be, a general review of this field, but gives an account of work in which I have been involved, over the past two decades or so, on habituation and imprinting. During that time modest success has been achieved in analysing habituation- a common change...

  5. The Association Between Use of Brain CT for Atraumatic Headache and 30-Day Emergency Department Revisitation.

    Science.gov (United States)

    Patterson, Brian W; Pang, Peter S; AlKhawam, Lora; Hamedani, Azita G; Mendonca, Eneida A; Zhao, Ying-Qi; Venkatesh, Arjun K

    2016-12-01

    The purpose of this article is to describe the association between initial CT for atraumatic headache and repeat emergency department (ED) visitation within 30 days of ED discharge. A retrospective observational study was performed at an academic urban ED with more than 85,000 annual visits. All adult patients with a chief complaint of headache from January through December 2010 who were discharged after ED evaluation were included in the analysis. Patients were excluded if they were transferred, died in the ED, or had a diagnosis indicating a traumatic mechanism. A propensity score-matched logistic regression model was used to determine whether the use of brain CT was associated with the primary outcome of ED revisitation within 30 days, controlling for potential confounding variables. Of 80,619 total patient visits to the ED during the study period, 922 ED discharges with a chief complaint of headache were included. A total of 139 (15.1%) patients revisited within 30 days. The return rate was 11.2% among patients who underwent CT at their initial visit and 21.1% among those who did not. In the adjusted analysis, controlling for age, race, sex, insurance status, triage vital signs, laboratory values, and triage pain level, the odds ratio for revisitation given CT performance was 0.49 (95% CI, 0.27-0.86). After adjustment for clinical factors, we found that patients who underwent a brain CT examination for atraumatic headache at an initial ED visit were less likely to return to the ED within 30 days. Future appropriate use quality metrics regarding ED imaging use may need to incorporate downstream health care use.

  6. Emerging Molecular Targets for Brain Repair after Stroke

    Directory of Open Access Journals (Sweden)

    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.

  7. Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

    Science.gov (United States)

    Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela

    2017-07-12

    Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [ 11 C]DASB and [ 18 F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT 1A R, respectively. Oxytocin (1 IU in 20 μl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [ 11 C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [ 18 F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [ 11 C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT 1A R. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT 1A R receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders. SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical

  8. De Novo Emergence of Odor Category Representations in the Human Brain.

    Science.gov (United States)

    Qu, Lisa P; Kahnt, Thorsten; Cole, Sydni M; Gottfried, Jay A

    2016-01-13

    Categorization allows organisms to efficiently extract relevant information from a diverse environment. Because of the multidimensional nature of odor space, this ability is particularly important for the olfactory system. However, categorization relies on experience, and the processes by which the human brain forms categorical representations about new odor percepts are currently unclear. Here we used olfactory psychophysics and multivariate fMRI techniques, in the context of a paired-associates learning task, to examine the emergence of novel odor category representations in the human brain. We found that learning between novel odors and visual category information induces a perceptual reorganization of those odors, in parallel with the emergence of odor category-specific ensemble patterns in perirhinal, orbitofrontal, piriform, and insular cortices. Critically, the learning-induced pattern effects in orbitofrontal and perirhinal cortex predicted the magnitude of categorical learning and perceptual plasticity. The formation of de novo category-specific representations in olfactory and limbic brain regions suggests that such ensemble patterns subserve the development of perceptual classes of information, and imply that these patterns are instrumental to the brain's capacity for odor categorization. How the human brain assigns novel odors to perceptual classes and categories is poorly understood. We combined an olfactory-visual paired-associates task with multivariate pattern-based fMRI approaches to investigate the de novo formation of odor category representations within the human brain. The identification of emergent odor category codes within the perirhinal, piriform, orbitofrontal, and insular cortices suggests that these regions can integrate multimodal sensory input to shape category-specific olfactory representations for novel odors, and may ultimately play an important role in assembling each individual's semantic knowledge base of the olfactory world

  9. 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.

  10. Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

    Science.gov (United States)

    Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

    2014-01-01

    The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

  11. 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…

  12. Research on Group Decision-Making Mechanism of Internet Emergency Management

    Science.gov (United States)

    Xie, Kefan; Chen, Gang; Qian, Wu; Shi, Zhao

    With the development of information technology, internet has become a popular term and internet emergency has an intensive influence on people's life. This article offers a short history of internet emergency management. It discusses the definition, characteristics, and factor of internet emergency management. A group decision-making mechanism of internet emergency is presented based on the discussion. The authors establish a so-called Rough Set Scenario Flow Graphs (RSSFG) of group decision-making mechanism of internet emergency management and make an empirical analysis based on the RSSFG approach. The experimental results confirm that this approach is effective in internet emergency decision-making.

  13. 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.

  14. A review of glutamate's role in traumatic brain injury mechanisms

    Science.gov (United States)

    Good, Cameron H.

    2013-05-01

    Glutamate is the primary excitatory neurotransmitter used by the central nervous system (CNS) for synaptic communication, and its extracellular concentration is tightly regulated by glutamate transporters located on nearby astrocytes. Both animal models and human clinical studies have demonstrated elevated glutamate levels immediately following a traumatic brain event, with the duration and severity of the rise corresponding to prognosis. This rise in extracellular glutamate likely results from a combination of excessive neurotransmitter release from damaged neurons and down regulation of uptake mechanisms in local astrocytes. The immediate results of a traumatic event can lead to necrotic tissue in severely injured regions, while prolonged increases in excitatory transmission can cause secondary excitotoxic injury through activation of delayed apoptotic pathways. Initial TBI animal studies utilized a variety of broad glutamate receptor antagonists to successfully combat secondary injury mechanisms, but unfortunately this same strategy has proven inconclusive in subsequent human trials due to deleterious side effects and heterogeneity of injuries. More recent treatment strategies have utilized specific glutamate receptor subunit antagonists in an effort to minimize side effects and have shown promising results. Future challenges will be detecting the concentration and kinetics of the glutamate rise following injury, determining which patient populations could benefit from antagonist treatment based on their extracellular glutamate concentrations and when drugs should be administered to maximize efficacy.

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

    Directory of Open Access Journals (Sweden)

    Lisa Mosconi

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

  16. Formation mechanism of quick emergency response capability for urban rail transit: Inter-organizational collaboration perspective

    National Research Council Canada - National Science Library

    Zhang, Yanchun; Zou, Dejian; Zheng, Junwei; Fang, Xiaoping; Luo, Haijuan

    2016-01-01

    .... Based on the perspective of inter-organizational collaboration, this article examines the formation mechanism of quick emergency response capability of urban rail transit and proposes the concept...

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

    NARCIS (Netherlands)

    Schutter, D.J.L.G.

    2003-01-01

    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

  18. Formation mechanism of quick emergency response capability for urban rail transit: Inter-organizational collaboration perspective

    Directory of Open Access Journals (Sweden)

    Yanchun Zhang

    2016-06-01

    Full Text Available With the rapid development of urban rail transit in China recently, improving its quick emergency response capability is becoming an important issue. Based on the perspective of inter-organizational collaboration, this article examines the formation mechanism of quick emergency response capability of urban rail transit and proposes the concept model hypothesis, in order to highlight the inter-organizational emergency collaboration relationships and the quick emergency response capability. According to site surveys and analysis of the elements of inter-organizational collaboration in emergency rescue and the meaning of quick emergency response capability, the scale of emergency collaboration and emergency response capability is designed, and the hypothetical concept model is tested by structural equation model. The results indicate that the emergency collaboration can be realized mainly through emergency organizations, resources, plans, and information. These elements interact with each other; the quick emergency response capability includes fast reaction and emergency disposal capability, emergency decision and execution capability, and coordination and joint action capability. These capabilities restrict each other. Moreover, emergency collaboration has significant but different influence on different dimensions of quick emergency response capability. Therefore, allocating and controlling emergency elements are pivotal to realizing inter-organizational emergency collaboration and generating the quick emergency response capability of urban rail transit.

  19. Brain mechanisms of plasticity in response to treatments for core deficits in autism.

    Science.gov (United States)

    Ventola, Pamela E; Oosting, Devon; Anderson, Laura C; Pelphrey, Kevin A

    2013-01-01

    Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by social communication impairments and repetitive behaviors. Although the prevalence of ASD is estimated at 1 in 88, understanding of the neural mechanisms underlying the disorder is still emerging. Regions including the amygdala, superior temporal sulcus, orbitofrontal cortex, fusiform gyrus, medial prefrontal cortex, and insula have been implicated in social processing. Neuroimaging studies have demonstrated both anatomical and functional differences in these areas of the brain in individuals with ASD when compared to controls; however, research on the neural basis for response to treatment in ASD is limited. Results of the three studies that have examined the neural mechanisms underlying treatment response are promising; following treatment, the brains of individuals with ASD seem to "normalize," responding more similarly to those of typically developing individuals. The research in this area is in its early stages, and thus a focused effort examining the neural basis of treatment response in ASD is crucial. © 2013 Elsevier B.V. All rights reserved.

  20. Feasibility, safety, and potential demand of emergent brain magnetic resonance imaging of patients with cardiac implantable electronic devices

    Directory of Open Access Journals (Sweden)

    Maki Ono

    2017-10-01

    Conclusions: Our study found the potential demand of brain MRI of patients with CIEDs in emergency situations compared with scheduled scanning, which was shown to be feasible and safe for the diagnosis and treatment of an acute stroke.

  1. Eyes-closed task-free electroencephalography in clinical trials for Alzheimer's disease: an emerging method based upon brain dynamics

    NARCIS (Netherlands)

    van Straaten, E.C.W.; Scheltens, P.; Gouw, A.A.; Stam, C.J.

    2014-01-01

    Electroencephalography (EEG) is a longstanding technique to measure electrical brain activity and thereby an indirect measure of synaptic activity. Synaptic dysfunction accompanies Alzheimer's disease (AD) and EEG can be regarded as a potentially useful biomarker in this disease. Lately, emerging

  2. Mechanisms of blast induced brain injuries, experimental studies in rats.

    Science.gov (United States)

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  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 for loss of awareness of thought and movement.

    Science.gov (United States)

    Walsh, Eamonn; Oakley, David A; Halligan, Peter W; Mehta, Mitul A; Deeley, Quinton

    2017-05-01

    Loss or reduction of awareness is common in neuropsychiatric disorders and culturally influenced dissociative phenomena but the underlying brain mechanisms are poorly understood. fMRI was combined with suggestions for automatic writing in 18 healthy highly hypnotically suggestible individuals in a within-subjects design to determine whether clinical alterations in awareness of thought and movement can be experimentally modelled and studied independently of illness. Subjective ratings of control, ownership, and awareness of thought and movement, and fMRI data were collected following suggestions for thought insertion and alien control of writing movement, with and without loss of awareness. Subjective ratings confirmed that suggestions were effective. At the neural level, our main findings indicated that loss of awareness for both thought and movement during automatic writing was associated with reduced activation in a predominantly left-sided posterior cortical network including BA 7 (superior parietal lobule and precuneus), and posterior cingulate cortex, involved in self-related processing and awareness of the body in space. Reduced activity in posterior parietal cortices may underlie specific clinical and cultural alterations in awareness of thought and movement. Clinically, these findings may assist development of imaging assessments for loss of awareness of psychological origin, and interventions such as neurofeedback. © The Author (2017). Published by Oxford University Press.

  5. Brain mechanisms for loss of awareness of thought and movement

    Science.gov (United States)

    Oakley, David A.; Halligan, Peter W.; Mehta, Mitul A.; Deeley, Quinton

    2017-01-01

    Abstract Loss or reduction of awareness is common in neuropsychiatric disorders and culturally influenced dissociative phenomena but the underlying brain mechanisms are poorly understood. fMRI was combined with suggestions for automatic writing in 18 healthy highly hypnotically suggestible individuals in a within-subjects design to determine whether clinical alterations in awareness of thought and movement can be experimentally modelled and studied independently of illness. Subjective ratings of control, ownership, and awareness of thought and movement, and fMRI data were collected following suggestions for thought insertion and alien control of writing movement, with and without loss of awareness. Subjective ratings confirmed that suggestions were effective. At the neural level, our main findings indicated that loss of awareness for both thought and movement during automatic writing was associated with reduced activation in a predominantly left-sided posterior cortical network including BA 7 (superior parietal lobule and precuneus), and posterior cingulate cortex, involved in self-related processing and awareness of the body in space. Reduced activity in posterior parietal cortices may underlie specific clinical and cultural alterations in awareness of thought and movement. Clinically, these findings may assist development of imaging assessments for loss of awareness of psychological origin, and interventions such as neurofeedback. PMID:28338742

  6. Brain death after decompressive craniectomy: Incidence and pathophysiological mechanisms.

    Science.gov (United States)

    Salih, Farid; Finger, Tobias; Vajkoczy, Peter; Wolf, Stefan

    2017-06-01

    Patients who received decompressive craniectomy (DC) are usually not regarded to qualify for brain death (BD) as intracranial pressure (ICP) is not assumed to reach levels critical enough to cause cerebral perfusion failure. Here we investigated the incidence of BD after DC and analyzed the pathophysiological mechanisms. We searched our chart records of patients with DC for individuals who developed BD (2010-2016). We then analyzed the course of ICP and cerebral perfusion pressure (CPP) prior to BD and results from radiological tests that aim at demonstrating loss of cerebral perfusion in BD. BD was diagnosed in 12 of 164 (incidence 7.3%) patients (age=16-70years; male=7; mean longitudinal diameter: 136.2mm). Mean latency between DC and BD was 69.4h. Immediately after DC, mean ICP was 30.0mmHg (standard deviation±24.7mmHg), CPP was 56.8mmHg (±28.1). In the course to BD, ICP increased to 95.8mmHg (±16.1), CPP decreased to -9.9mmHg (±11.2). In patients in whom radiological methods were performed (n=5) loss of cerebral perfusion was demonstrated. Our study evidences that DC does not exclude BD. Even after DC, BD is preceded by a severely reduced CPP, supporting loss of cerebral perfusion as a critical step in BD pathophysiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A decade of emerging indications: deep brain stimulation in the United States.

    Science.gov (United States)

    Youngerman, Brett E; Chan, Andrew K; Mikell, Charles B; McKhann, Guy M; Sheth, Sameer A

    2016-08-01

    OBJECTIVE Deep brain stimulation (DBS) is an emerging treatment option for an expanding set of neurological and psychiatric diseases. Despite growing enthusiasm, the patterns and implications of this rapid adoption are largely unknown. National trends in DBS surgery performed for all indications between 2002 and 2011 are reported. METHODS Using a national database of hospital discharges, admissions for DBS for 14 indications were identified and categorized as either FDA approved, humanitarian device exempt (HDE), or emerging. Trends over time were examined, differences were analyzed by univariate analyses, and outcomes were analyzed by hierarchical regression analyses. RESULTS Between 2002 and 2011, there were an estimated 30,490 discharges following DBS for approved indications, 1647 for HDE indications, and 2014 for emerging indications. The volume for HDE and emerging indications grew at 36.1% annually in comparison with 7.0% for approved indications. DBS for emerging indications occurred at hospitals with more neurosurgeons and neurologists locally, but not necessarily at those with the highest DBS caseloads. Patients treated for HDE and emerging indications were younger with lower comorbidity scores. HDE and emerging indications were associated with greater rates of reported complications, longer lengths of stay, and greater total costs. CONCLUSIONS DBS for HDE and emerging indications underwent rapid growth in the last decade, and it is not exclusively the most experienced DBS practitioners leading the charge to treat the newest indications. Surgeons may be selecting younger and healthier patients for their early experiences. Differences in reported complication rates warrant further attention and additional costs should be anticipated as surgeons gain experience with new patient populations and targets.

  8. [Aquaporin water channels in the brain and molecular mechanisms of brain edema].

    Science.gov (United States)

    Sobue, Kazuya; Asai, Kiyofumi; Katsuya, Hirotada

    2006-06-01

    Aquaporins(AQPs) are a family of water selective channel. Transcripts of AQP1, AQP3, AQP4, AQP5, AQP8, and AQP9 are detected in the brain. Especially in astrocytes, AQP4 is abundantly expressed in end feet at the blood-brain barrier. Brain AQPs play important roles in the regulation of water homeostasis and the cerebro spinal fluid formation. Recently, AQP4 and AQP9 have been reported to involve in the brain water accumulation in the brain edema. Studies of transgenic mouse and brain injury models reveal that AQP4 may play a role not in the edema formation, but in the fluid elimination. Further study of AQPs functions in the brain may provide new insights into the brain edema and allow the design of novel anti edema medications.

  9. 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.

  10. Emergency care of traumatic brain injuries in Pakistan: a multicenter study.

    Science.gov (United States)

    Bhatti, Junaid; Stevens, Kent; Mir, Muhammad; Hyder, Adnan A; Razzak, Junaid

    2015-01-01

    This study assessed factors associated with emergency care outcomes and out-of-pocket treatment costs in traumatic brain injury (TBI) patients in Pakistan. Data on TBI patients were extracted from a four-month surveillance study conducted in the emergency departments (ED) of seven large teaching hospitals. Emergency care access to physicians and imaging facilities were compared with respect to ED outcomes (discharged, admitted or dead). Out-of-pocket treatment costs (in United States dollars [USD]) were compared among different patient strata. ED outcomes were available for 1,787 TBI patients. Of them, most were males (79%), aged Emergency care factors significantly associated with being admitted or died were arriving by ambulance (adjusted odds ratio [aOR] = 2.37, 95% confidence interval (CI) [95%CI] = 1.78-3.16); seen by medical officer/residents (aOR = 2.11; 95%CI = 1.49-2.99); and had CT scan (aOR = 2.93; 95%CI = 2.25-3.83). Out-of-pocket treatment costs at the ED were reported in 803 patients. Average costs were USD 8, (standard deviation [SD] = 23). Costs were twice as high in those arriving in ambulances (USD 20, SD = 49) or who underwent CT scans (USD 16, SD = 37). TBI patients' access to ambulance transport, experienced physicians, and imaging facilities during emergency care needs to be improved in Pakistan.

  11. Candida tropicalis brain abscess in a neonate: An emerging nosocomial menace

    Directory of Open Access Journals (Sweden)

    Sangeetha Yoganathan

    2014-01-01

    Full Text Available Fungi are a relatively uncommon cause of brain abscess in neonates and early infancy. They are usually associated with predisposing factors like prematurity, low birth weight, use of broad-spectrum antibiotics, and prolonged stay in the intensive care unit. Candida tropicalis (C. tropicalis is rapidly emerging as a nosocomial threat in the neonatal intensive care settings. This case report describes a neonate with C. tropicalis brain abscess who was diagnosed early and managed aggressively with a favorable outcome. Inadvertent use of intravenous antibiotics can have serious complications such as invasive fungal infection. Correct microbiological diagnosis is the key to successful treatment of deep-seated pyogenic infection. Fungal etiology should always be studied in relevant clinical settings.

  12. Compound mechanism hypothesis on +Gz induced brain injury and dysfunction of learning and memory

    Science.gov (United States)

    Sun, Xi-Qing; Li, Jin-Sheng; Cao, Xin-Sheng; Wu, Xing-Yu

    2005-08-01

    We systematically studied the effect of high- sustained +Gz on the brain and its mechanism in past ten years by animal centrifuge experiments. On the basis of the facts we observed and the more recent advances in acceleration physiology, we put forward a compound mechanism hypothesis to offer a possible explanation for +Gz-induced brain injury and dysfunction of learning and memory. It states that, ischemia during high G exposure might be the main factor accounting for +Gz-induced brain injury and dysfunction of learning and memory, including transient depression of brain energy metabolism, disturbance of ion homeostasis, increased blood-brain barrier permeability, increased brain nitric oxide synthase expression, and the protective effect of heat shock protein 70. In addition, the large rapid change of intracranial pressure and increased stress during +Gz exposure, and the hemorrheologic change after +Gz exposure might be one of the important factors accounting for +Gz-induced brain injury and dysfunction of learning and memory.

  13. Temporal Organization of the Brain: Neurocognitive Mechanisms and Clinical Implications

    Science.gov (United States)

    Dawson, Kim A.

    2004-01-01

    The synchrony between the individual brain and its environment is maintained by a system of internal clocks that together reflect the temporal organization of the organism. Extending the theoretical work of Edelman and others, the temporal organization of the brain is posited as functioning through "'re-entry" and "'temporal tagging"' and binds…

  14. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Science.gov (United States)

    Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  15. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Directory of Open Access Journals (Sweden)

    Daniel C Stewart

    Full Text Available While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  16. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

    Science.gov (United States)

    Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

  17. 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.

  18. Role of Sucrose in Emerging Mechanisms of Stomatal Aperture Regulation.

    Energy Technology Data Exchange (ETDEWEB)

    Outlaw, W. H.

    2000-09-15

    Focused on the second of 2 hypotheses that were proposed for testing that transpiration rate determines the extent to which suc accumulates in the GC wall providing a mechanism for regulating stomatal aperture size.

  19. Epigenetic Mechanisms: An Emerging Player in Plant-Microbe Interactions.

    Science.gov (United States)

    Zhu, Qian-Hao; Shan, Wei-Xing; Ayliffe, Michael A; Wang, Ming-Bo

    2016-03-01

    Plants have developed diverse molecular and cellular mechanisms to cope with a lifetime of exposure to a variety of pathogens. Host transcriptional reprogramming is a central part of plant defense upon pathogen recognition. Recent studies link DNA methylation and demethylation as well as chromatin remodeling by posttranslational histone modifications, including acetylation, methylation, and ubiquitination, to changes in the expression levels of defense genes upon pathogen challenge. Remarkably these inducible defense mechanisms can be primed prior to pathogen attack by epigenetic modifications and this heightened resistance state can be transmitted to subsequent generations by inheritance of these modification patterns. Beside the plant host, epigenetic mechanisms have also been implicated in virulence development of pathogens. This review highlights recent findings and insights into epigenetic mechanisms associated with interactions between plants and pathogens, in particular bacterial and fungal pathogens, and demonstrates the positive role they can have in promoting plant defense.

  20. 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

  1. Brain mechanisms underlying automatic and unconscious control of motor action

    Directory of Open Access Journals (Sweden)

    Kevin eD'ostilio

    2012-09-01

    Full Text Available Are we in command of our motor acts? The popular belief holds that our conscious decisions are the direct causes of our actions. However, overwhelming evidence from neurosciences demonstrates that our actions are instead largely driven by brain processes that unfold outside of our consciousness. To study these brain processes, scientists have used a range of different functional brain imaging techniques and experimental protocols, such as subliminal priming. Here, we review recent advances in the field and propose a theoretical model of motor control that may contribute to a better understanding of the pathophysiology of movement disorders such as Parkinson’s disease.

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

    Science.gov (United States)

    Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen

    2012-01-01

    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. 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. 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.

  3. The mechanisms of action of deep brain stimulation and ideas for the future development.

    Science.gov (United States)

    Udupa, Kaviraja; Chen, Robert

    2015-10-01

    Deep brain stimulation (DBS) has been used as a treatment of movement disorders such as Parkinson's disease, dystonia, and essential tremor for over twenty years, and is a promising treatment for depression and epilepsy. However, the exact mechanisms of action of DBS are still uncertain, although different theories have emerged. This review summarizes the current understanding in this field. Different modalities used to investigate DBS such as electrophysiological, imaging and biochemical studies have revealed different mechanisms of DBS. The mechanisms may also be different depending on the structure targeted, the disease condition or the animal model employed. DBS may inhibit the target neuronal networks but activate the efferent axons. It may suppress pathological rhythms or impose new rhythms associated with beneficial effects, and involves neuronal networks with widespread connections. Different neurotransmitter systems such as dopamine and GABA upregulation are involved in the effects of DBS. There are also technical advances to prolong the battery life and specific targeting based on new electrode designs with multiple contacts which have the ability to steer the current toward a specific direction. There is ongoing work in closed loop or adaptive DBS using neural oscillations to provide the feedback signals. These oscillations need to be better characterized in a wide variety of clinical settings in future studies. Individualization of DBS parameters based on neural oscillations may optimize the clinical benefits of DBS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Stemper, Brian D; Shah, Alok S; Budde, Matthew D; Olsen, Christopher M; Glavaski-Joksimovic, Aleksandra; Kurpad, Shekar N; McCrea, Michael; Pintar, Frank A

    2016-01-01

    Mild traumatic brain injury (mTBI) can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW) Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

  5. Behavioral Outcomes Differ Between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Brian D. Stemper

    2016-03-01

    Full Text Available Mild traumatic brain injury (mTBI can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time-course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

  6. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  7. Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology.

    Science.gov (United States)

    Zhan, Ming; Brooks, Craig; Liu, Fuyou; Sun, Lin; Dong, Zheng

    2013-04-01

    Mitochondria are a class of dynamic organelles that constantly undergo fission and fusion. Mitochondrial dynamics is governed by a complex molecular machinery and finely tuned by regulatory proteins. During cell injury or stress, the dynamics is shifted to fission, resulting in mitochondrial fragmentation, which contributes to mitochondrial damage and consequent cell injury and death. Emerging evidence has suggested a role of mitochondrial fragmentation in the pathogenesis of renal diseases including acute kidney injury and diabetic nephropathy. A better understanding of the regulation of mitochondrial dynamics and its pathogenic changes may unveil novel therapeutic strategies.

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

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    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......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...

  9. 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...... 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...

  10. Mechanisms of abnormal brain development leading to transsexualism (review

    Directory of Open Access Journals (Sweden)

    L. F. Kurilo

    2014-11-01

    Full Text Available Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  11. Mechanisms of abnormal brain development leading to transsexualism (review

    Directory of Open Access Journals (Sweden)

    L. F. Kurilo

    2013-01-01

    Full Text Available Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  12. Brain mechanisms of acoustic communication in humans and nonhuman primates: an evolutionary perspective.

    Science.gov (United States)

    Ackermann, Hermann; Hage, Steffen R; Ziegler, Wolfram

    2014-12-01

    Any account of "what is special about the human brain" (Passingham 2008) must specify the neural basis of our unique ability to produce speech and delineate how these remarkable motor capabilities could have emerged in our hominin ancestors. Clinical data suggest that the basal ganglia provide a platform for the integration of primate-general mechanisms of acoustic communication with the faculty of articulate speech in humans. Furthermore, neurobiological and paleoanthropological data point at a two-stage model of the phylogenetic evolution of this crucial prerequisite of spoken language: (i) monosynaptic refinement of the projections of motor cortex to the brainstem nuclei that steer laryngeal muscles, presumably, as part of a "phylogenetic trend" associated with increasing brain size during hominin evolution; (ii) subsequent vocal-laryngeal elaboration of cortico-basal ganglia circuitries, driven by human-specific FOXP2 mutations.;>This concept implies vocal continuity of spoken language evolution at the motor level, elucidating the deep entrenchment of articulate speech into a "nonverbal matrix" (Ingold 1994), which is not accounted for by gestural-origin theories. Moreover, it provides a solution to the question for the adaptive value of the "first word" (Bickerton 2009) since even the earliest and most simple verbal utterances must have increased the versatility of vocal displays afforded by the preceding elaboration of monosynaptic corticobulbar tracts, giving rise to enhanced social cooperation and prestige. At the ontogenetic level, the proposed model assumes age-dependent interactions between the basal ganglia and their cortical targets, similar to vocal learning in some songbirds. In this view, the emergence of articulate speech builds on the "renaissance" of an ancient organizational principle and, hence, may represent an example of "evolutionary tinkering" (Jacob 1977).

  13. Feasibility, safety, and potential demand of emergent brain magnetic resonance imaging of patients with cardiac implantable electronic devices.

    Science.gov (United States)

    Ono, Maki; Suzuki, Makoto; Isobe, Mitsuaki

    2017-10-01

    The feasibility, safety, and potential demand of emergent magnetic resonance imaging (MRI) of patients with a cardiac implantable electronic device (CIED) in emergency situations are unknown. We retrospectively compared emergent and scheduled MRI orders for patients with CIEDs at Kameda General Hospital, a tertiary hospital in Japan, from October 2012 to September 2016. We identified 11 emergent MRI orders via the emergency room and 38 scheduled MRI orders. Although the baseline characteristics were similar between the two groups, brain scanning was predominant in emergent scanning (p=0.002). The reasons for MRI and physicians who ordered it were also significantly different between the two groups (pMRI. The time from arrival at the emergency room to MRI was 144±29 min, and the time from the MRI order made by the cardiologist to its actual performance was 60±10 min. Four out of 9 patients had a diagnosis of acute stroke confirmed by emergent MRI, and two had emergent thrombolysis with a complete neurological recovery. All emergent scanning was conducted safely with no complications. Our study found the potential demand of brain MRI of patients with CIEDs in emergency situations compared with scheduled scanning, which was shown to be feasible and safe for the diagnosis and treatment of an acute stroke.

  14. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2017-07-01

    Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess

  15. The Epidemiology of Epilepsy and Traumatic Brain Injury: Severity, Mechanism, and Outcomes

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-2-0046 TITLE: The Epidemiology of Epilepsy and Traumatic Brain Injury: Severity, Mechanism, and Outcomes PRINCIPAL...COVERED 30 Sep 2016 – 29 SEP 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Epidemiology of Epilepsy and Traumatic Brain Injury: Severity...previous research has found that Post-9/11 Veterans with any kind of traumatic brain injury (TBI) were more likely to develop epilepsy than those without

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

    NARCIS (Netherlands)

    van Elk, Michiel; Aleman, Andre

    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

  17. Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths - United States, 2007 and 2013.

    Science.gov (United States)

    Taylor, Christopher A; Bell, Jeneita M; Breiding, Matthew J; Xu, Likang

    2017-03-17

    Traumatic brain injury (TBI) has short- and long-term adverse clinical outcomes, including death and disability. TBI can be caused by a number of principal mechanisms, including motor-vehicle crashes, falls, and assaults. This report describes the estimated incidence of TBI-related emergency department (ED) visits, hospitalizations, and deaths during 2013 and makes comparisons to similar estimates from 2007. 2007 and 2013. State-based administrative health care data were used to calculate estimates of TBI-related ED visits and hospitalizations by principal mechanism of injury, age group, sex, and injury intent. Categories of injury intent included unintentional (motor-vehicle crashes, falls, being struck by or against an object, mechanism unspecified), intentional (self-harm and assault/homicide), and undetermined intent. These health records come from the Healthcare Cost and Utilization Project's National Emergency Department Sample and National Inpatient Sample. TBI-related death analyses used CDC multiple-cause-of-death public-use data files, which contain death certificate data from all 50 states and the District of Columbia. In 2013, a total of approximately 2.8 million TBI-related ED visits, hospitalizations, and deaths (TBI-EDHDs) occurred in the United States. This consisted of approximately 2.5 million TBI-related ED visits, approximately 282,000 TBI-related hospitalizations, and approximately 56,000 TBI-related deaths. TBIs were diagnosed in nearly 2.8 million (1.9%) of the approximately 149 million total injury- and noninjury-related EDHDs that occurred in the United States during 2013. Rates of TBI-EDHDs varied by age, with the highest rates observed among persons aged ≥75 years (2,232.2 per 100,000 population), 0-4 years (1,591.5), and 15-24 years (1,080.7). Overall, males had higher age-adjusted rates of TBI-EDHDs (959.0) compared with females (810.8) and the most common principal mechanisms of injury for all age groups included falls (413.2, age

  18. The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures.

    Science.gov (United States)

    Feinstein, Douglas L; Akpa, Belinda S; Ayee, Manuela A; Boullerne, Anne I; Braun, David; Brodsky, Sergey V; Gidalevitz, David; Hauck, Zane; Kalinin, Sergey; Kowal, Kathy; Kuzmenko, Ivan; Lis, Kinga; Marangoni, Natalia; Martynowycz, Michael W; Rubinstein, Israel; van Breemen, Richard; Ware, Kyle; Weinberg, Guy

    2016-06-01

    Superwarfarins were developed following the emergence of warfarin resistance in rodents. Compared to warfarin, superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum and difenacoum were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raise the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1-2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K-dependent and -independent effects, which are not mitigated by vitamin K therapy. In this review, we summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches. © 2016 New York Academy of Sciences.

  19. Mechanisms Underlying the Emergent Properties of Gecko-like Nanostructures

    Science.gov (United States)

    Autumn, Kellar

    2010-03-01

    Imagine the difficulties a gecko would encounter if it employed a conventional pressure sensitive adhesive (PSA) on its toes. PSAs are soft viscoelastic polymers that degrade, foul, self-adhere, and attach accidentally to inappropriate surfaces. In contrast, gecko toes bear angled arrays of branched, hair-like setae formed from stiff, hydrophobic keratin that act as a bed of angled springs with similar effective stiffness to that of PSAs. We have discovered nine benchmark properties of the gecko adhesive over the past decade: 1) anisotropy, 2) strong attachment with minimal preload, 3) easy and rapid detachment, 4) material independence, 5) self-cleaning 6) anti-self-adhesion, and 7) nonadhesive default state. Most recently, we discovered 8) dynamic adhesion and 9) wear resistance. Rate dependent, wear-free friction and adhesion in a dry hard solid may emerge from uncorrelated stick-slip of the spatulae. We confirmed these predictions in a gecko-like synthetic adhesive (GSA) made from a hard silicone polymer. The GSA slid smoothly while adhering, and its velocity-dependence and stick-slip frequency matched the predictions of the model. There has been rapid progress in understanding the principles underlying these remarkable properties, and in applying the principles of gecko adhesion in the fabrication of GSAs. Properties 1-9 have all been achieved in GSAs (although not yet in a single material).

  20. Emerging anticancer potentials of goniothalamin and its molecular mechanisms.

    Science.gov (United States)

    Seyed, Mohamed Ali; Jantan, Ibrahim; Bukhari, Syed Nasir Abbas

    2014-01-01

    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.

  1. TNF biology, pathogenic mechanisms and emerging therapeutic strategies

    Science.gov (United States)

    Kalliolias, George D.; Ivashkiv, Lionel B.

    2016-01-01

    TNF is a pleiotropic cytokine with important functions in homeostasis and disease pathogenesis. Recent discoveries have provided insights into TNF biology that introduce new concepts for the development of therapeutics for TNF-mediated diseases. The model of TNF receptor signalling has been extended to include linear ubiquitination and the formation of distinct signalling complexes that are linked with different functional outcomes, such as inflammation, apoptosis and necroptosis. Our understanding of TNF-induced gene expression has been enriched by the discovery of epigenetic mechanisms and concepts related to cellular priming, tolerization and induction of ‘short-term transcriptional memory’. Identification of distinct homeostatic or pathogenic TNF-induced signalling pathways has introduced the concept of selectively inhibiting the deleterious effects of TNF while preserving its homeostatic bioactivities for therapeutic purposes. In this Review, we present molecular mechanisms underlying the roles of TNF in homeostasis and inflammatory disease pathogenesis, and discuss novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases. PMID:26656660

  2. Fluid Mechanics of the Vascular Basement Membrane in the Brain

    Science.gov (United States)

    Coloma, Mikhail; Hui, Jonathan; Chiarot, Paul; Huang, Peter; Carare, Roxana; McLeod, Kenneth; Schaffer, David

    2013-11-01

    Beta-amyloid is a normal product of brain metabolic function and is found within the interstitial fluid of the brain. Failure of the clearance of beta-amyloid from the aging brain leads to its accumulation within the walls of arteries and to Alzheimer's disease. The vascular basement membrane (VBM) within the walls of cerebral arteries surrounds the spirally arranged smooth muscle cells and represents an essential pathway for removal of beta-amyloid from the brain. This process fails with the stiffening of arterial walls associated with aging. In this study we hypothesize that the deformation of the VBM associated with arterial pulsations drives the interstitial fluid to drain in the direction opposite of the arterial blood flow. This hypothesis is theoretically investigated by modeling the VBM as a thin, coaxial, fluid-filled porous medium surrounding a periodically deforming cylindrical tube. Flow and boundary conditions required to achieve such a backward clearance are derived through a control volume analysis of mass, momentum, and energy.

  3. Screening for Post-Traumatic Stress Disorder in a Civilian Emergency Department Population with Traumatic Brain Injury.

    Science.gov (United States)

    Haarbauer-Krupa, Juliet; Taylor, Christopher A; Yue, John K; Winkler, Ethan A; Pirracchio, Romain; Cooper, Shelly R; Burke, John F; Stein, Murray B; Manley, Geoffrey T

    2017-01-01

    Post-traumatic stress disorder (PTSD) is a condition associated with traumatic brain injury (TBI). While the importance of PTSD and TBI among military personnel is widely recognized, there is less awareness of PTSD associated with civilian TBI. We examined the incidence and factors associated with PTSD 6 months post-injury in a civilian emergency department population using measures from the National Institute of Neurological Disorders and Stroke TBI Common Data Elements Outcome Battery. Participants with mild TBI (mTBI) from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with complete 6-month outcome batteries (n = 280) were analyzed. Screening for PTSD symptoms was conducted using the PTSD Checklist-Civilian Version. Descriptive measures are summarized and predictors for PTSD were examined using logistic regression. Incidence of screening positive for PTSD was 26.8% at 6 months following mTBI. Screening positive for PTSD was significantly associated with concurrent functional disability, post-concussive and psychiatric symptomatology, decreased satisfaction with life, and decreased performance in visual processing and mental flexibility. Multi-variable regression showed injury mechanism of assault (odds ratio [OR] 3.59; 95% confidence interval [CI] 1.69-7.63; p = 0.001) and prior psychiatric history (OR 2.56; 95% CI 1.42-4.61; p = 0.002) remained significant predictors of screening positive for PTSD, while education (per year OR 0.88; 95% CI 0.79-0.98; p = 0.021) was associated with decreased odds of PTSD. Standardized data collection and review of pre-injury education, psychiatric history, and injury mechanism during initial hospital presentation can aid in identifying patients with mTBI at risk for developing PTSD symptoms who may benefit from closer follow-up after initial injury care.

  4. Estrogen receptor alpha: molecular mechanisms and emerging insights.

    Science.gov (United States)

    Candelaria, Nicholes R; Liu, Ka; Lin, Chin-Yo

    2013-10-01

    Estrogen receptor alpha (ERα) is a cellular receptor for the female sex hormone estrogen and other natural and synthetic ligands and play critical roles in normal development and physiology and in the etiology and treatment of endocrine-related diseases. ERα is a member of the nuclear receptor superfamily of transcription factors and regulates target gene expression in a ligand-dependent manner. It has also been shown to interact with G-protein coupled receptors and associated signaling molecules in the cytoplasm. Transcriptionally, ERα either binds DNA directly through conserved estrogen response element sequence motifs or indirectly by tethering to other interacting transcription factors and nucleate transcriptional regulatory complexes which include an array of co-regulator proteins. Genome-scale studies of ERα transcriptional activity and localization have revealed mechanistic complexity and insights including novel interactions with several transcription factors, including FOXA1, AP-2g, GATA3, and RUNX1, which function as pioneering, collaborative, or tethering factors. The major challenge and exciting prospect moving forward is the comprehensive definition and integration of ERα complexes and mechanisms and their tissue-specific roles in normal physiology and in human diseases. Copyright © 2013 Wiley Periodicals, Inc.

  5. 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.

  6. Mechanisms of modulation of brain microvascular endothelial cells function by thrombin.

    Science.gov (United States)

    Brailoiu, Eugen; Shipsky, Megan M; Yan, Guang; Abood, Mary E; Brailoiu, G Cristina

    2017-02-15

    Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca(2+) concentration in RBMVEC via Ca(2+) release from endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors and Ca(2+) influx from extracellular space. Thrombin increases nitric oxide production; the effect is abolished by inhibition of the nitric oxide synthase or by antagonism of PAR1 receptors. In addition, thrombin increases mitochondrial and cytosolic reactive oxygen species production via PAR1-dependent mechanisms. Immunocytochemistry studies indicate that thrombin increases F-actin stress fibers, and disrupts the tight junctions. Thrombin increased the RBMVEC permeability assessed by a fluorescent flux assay. Taken together, our results indicate multiple mechanisms by which thrombin modulates the function of RBMVEC and may contribute to the blood-brain barrier dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures: The emerging threat of superwarfarins

    Energy Technology Data Exchange (ETDEWEB)

    Feinstein, Douglas L. [Department of Anesthesiology, University of Illinois, Chicago Illinois; Jesse Brown VA Medical Center, Chicago Illinois; Akpa, Belinda S. [Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh North Carolina; Ayee, Manuela A. [Department of Medicine, University of Illinois, Chicago Illinois; Boullerne, Anne I. [Department of Anesthesiology, University of Illinois, Chicago Illinois; Jesse Brown VA Medical Center, Chicago Illinois; Braun, David [Department of Anesthesiology, University of Illinois, Chicago Illinois; Brodsky, Sergey V. [Department of Pathology, the Ohio State University, Columbus Ohio; Gidalevitz, David [Department of Physics and the Center for the Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago Illinois; Hauck, Zane [Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago Illinois; Kalinin, Sergey [Department of Anesthesiology, University of Illinois, Chicago Illinois; Kowal, Kathy [Department of Anesthesiology, University of Illinois, Chicago Illinois; Kuzmenko, Ivan [X-ray Science Division, Argonne National Laboratory, Lemont Illinois; Lis, Kinga [Department of Anesthesiology, University of Illinois, Chicago Illinois; Marangoni, Natalia [Department of Anesthesiology, University of Illinois, Chicago Illinois; Martynowycz, Michael W. [Department of Physics and the Center for the Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago Illinois; X-ray Science Division, Argonne National Laboratory, Lemont Illinois; Rubinstein, Israel [Department of Anesthesiology, University of Illinois, Chicago Illinois; Department of Medicine, University of Illinois, Chicago Illinois; van Breemen, Richard [Department of Anesthesiology, University of Illinois, Chicago Illinois; Ware, Kyle [Department of Pathology, the Ohio State University, Columbus Ohio; Weinberg, Guy [Department of Anesthesiology, University of Illinois, Chicago Illinois; Jesse Brown VA Medical Center, Chicago Illinois

    2016-05-31

    Superwarfarins were developed following the emergence of warfarin resistance in rodents. Compared to warfarin, superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum and difenacoum were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raise the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1–2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K–dependent and –independent effects,which are not mitigated by vitaminKtherapy. In this review, we summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches.

  8. Motorcycle crash-related emergency department visits and hospitalizations for traumatic brain injury in North Carolina.

    Science.gov (United States)

    Harmon, Katherine J; Marshall, Stephen W; Proescholdbell, Scott K; Naumann, Rebecca B; Waller, Anna E

    2015-01-01

    To examine statewide emergency department (ED) visit data for motorcycle crash morbidity and healthcare utilization due to traumatic brain injuries (TBIs) and non-TBIs. North Carolina ED data (2010-2012) and hospital discharge data (2009-2011). Statewide ED visits and hospitalizations due to injuries from traffic-related motorcycle crashes stratified by TBI status. Descriptive study. Descriptive statistics include age, sex, mode of transport, disposition, expected source of payment, hospital length of stay, and hospital charges. Over the study period, there were 18 780 ED visits and 3737 hospitalizations due to motorcycle crashes. Twelve percent of ED visits for motorcycle crashes and 26% of hospitalizations for motorcycle crashes had a diagnosis of TBI. Motorcycle crash-related hospitalizations with a TBI diagnosis had median hospital charges that were nearly $9000 greater than hospitalizations without a TBI diagnosis. Emergency department visits and hospitalizations due to motorcycle crashes with a TBI diagnosis consumed more healthcare resources than motorcycle crash-related ED visits and hospitalizations without a TBI diagnosis. Increased awareness of motorcyclists by other road users and increased use of motorcycle helmets are 2 strategies to mitigate the incidence and severity of motorcycle crash injuries, including TBIs.

  9. 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…

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

    Science.gov (United States)

    Bourne, Sarah K; Eckhardt, Christine A; Sheth, Sameer A; Eskandar, Emad N

    2012-01-01

    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 (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) 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.

  12. 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.

  13. 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. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. An emergency call system for patients in locked-in state using an SSVEP-based brain switch.

    Science.gov (United States)

    Lim, Jeong-Hwan; Kim, Yong-Wook; Lee, Jun-Hak; An, Kwang-Ok; Hwang, Han-Jeong; Cha, Ho-Seung; Han, Chang-Hee; Im, Chang-Hwan

    2017-11-01

    Patients in a locked-in state (LIS) due to severe neurological disorders such as amyotrophic lateral sclerosis (ALS) require seamless emergency care by their caregivers or guardians. However, it is a difficult job for the guardians to continuously monitor the patients' state, especially when direct communication is not possible. In the present study, we developed an emergency call system for such patients using a steady-state visual evoked potential (SSVEP)-based brain switch. Although there have been previous studies to implement SSVEP-based brain switch system, they have not been applied to patients in LIS, and thus their clinical value has not been validated. In this study, we verified whether the SSVEP-based brain switch system can be practically used as an emergency call system for patients in LIS. The brain switch used for our system adopted a chromatic visual stimulus, which proved to be visually less stimulating than conventional checkerboard-type stimuli but could generate SSVEP responses strong enough to be used for brain-computer interface (BCI) applications. To verify the feasibility of our emergency call system, 14 healthy participants and 3 patients with severe ALS took part in online experiments. All three ALS patients successfully called their guardians to their bedsides in about 6.56 seconds. Furthermore, additional experiments with one of these patients demonstrated that our emergency call system maintains fairly good performance even up to 4 weeks after the first experiment without renewing initial calibration data. Our results suggest that our SSVEP-based emergency call system might be successfully used in practical scenarios. © 2017 Society for Psychophysiological Research.

  15. Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options.

    Science.gov (United States)

    Yousefi, Meysam; Bahrami, Tayyeb; Salmaninejad, Arash; Nosrati, Rahim; Ghaffari, Parisa; Ghaffari, Seyed H

    2017-10-01

    Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease. Here, we provide an overview of the molecular mechanisms underlying the pathogenesis of lung cancer dissemination and metastasis to the brain, as well as promising horizons for impeding lung cancer brain metastasis, including the role of cancer stem cells, the blood-brain barrier, interactions of lung cancer cells with the brain microenvironment and lung cancer-driven systemic processes, as well as the role of growth factor/receptor tyrosine kinases, cell adhesion molecules and non-coding RNAs. In addition, we provide an overview of current and novel therapeutic approaches, including radiotherapy, surgery and stereotactic radiosurgery, chemotherapy, as also targeted cancer stem cell and epithelial-mesenchymal transition (EMT)-based therapies, micro-RNA-based therapies and other small molecule or antibody-based therapies. We will also discuss the daunting potential of some combined therapies. The identification of molecular mechanisms underlying lung cancer metastasis has opened up new avenues towards their eradication and provides interesting opportunities for future research aimed at the development of novel targeted therapies.

  16. 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.

  17. 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

  18. 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

  19. Gender differences in neurological emergencies part II: a consensus summary and research agenda on traumatic brain injury.

    Science.gov (United States)

    Wright, David W; Espinoza, Tamara R; Merck, Lisa H; Ratcliff, Jonathan J; Backster, Anika; Stein, Donald G

    2014-12-01

    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There is strong evidence that gender and sex play an important role across the spectrum of TBI, from pathophysiology to clinical care. In May 2014, Academic Emergency Medicine held a consensus conference "Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." A TBI working group was formed to explore what was known about the influence of sex and gender on TBI and to identify gaps for future research. The findings resulted in four major recommendations to guide the TBI research agenda. © 2014 by the Society for Academic Emergency Medicine.

  20. Molecular mechanisms of traumatic brain injury in children. A review.

    Science.gov (United States)

    Jagannathan, Pavan; Jagannathan, Jay

    2008-10-01

    Despite advances in molecular biology and genetics, the precise pathophysiology of traumatic brain injury (TBI) in children is unknown. In this paper the authors review what is currently known about intra- and extracellular responses to pediatric TBI and relate these factors to future investigations. Although hyperemia and vascular congestion have long been thought to be the hallmarks of pediatric TBI, on a cellular level, calcium influx as well as modulation of local neurotransmitters appears to play a major role in its onset. Recent genetic and proteomic research has identified specific neurotrophic factors as well as apoptotic and antiapoptotic genes that appear to control the progression of inflammation and neuronal damage. The search for a therapeutic target will ultimately require a thorough understanding of these factors and their interplay on a proteomic, genomic, and neuromic level.

  1. Evolution, immunity and the emergence of brain superautoantigens [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Serge Nataf

    2017-02-01

    Full Text Available While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e.g. thyroid, pancreas, joints, brain or skin, a significant proportion of superautoantigens are highly expressed in the synaptic compartment of the central nervous system (CNS. Such an observation applies notably for GAD65, AchR, ribonucleoproteins, heat shock proteins, collagen IV, laminin, tyrosine hydroxylase and the acetylcholinesterase domain of thyroglobulin. It is also argued that cognitive alterations have been described in a number of autoimmune disorders, including psoriasis, rheumatoid arthritis, lupus, Crohn's disease and autoimmune thyroiditis. Finally, the present paper points out that a great majority of the "incidental" autoimmune conditions notably triggered by neoplasms, vaccinations or microbial infections are targeting the synaptic or myelin compartments. On this basis, the concept of an immunological homunculus, proposed by Irun Cohen more than 25 years ago, is extended here in a model where physiological autoimmunity against brain superautoantigens confers both: i a crucial evolutionary-determined advantage via cognition-promoting autoimmunity; and ii a major evolutionary-determined vulnerability, leading to the emergence of autoimmune disorders in Homo sapiens. Moreover, in this theoretical framework, the so called co-development/co-evolution model, both the development (at the scale of an individual and evolution (at the scale of species of the antibody and T-cell repertoires

  2. Consequences of lead exposure, and it's emerging role as an epigenetic modifier in the aging brain.

    Science.gov (United States)

    Eid, Aseel; Zawia, Nasser

    2016-09-01

    Lead exposure has primarily been a concern during development in young children and little attention has been paid to exposure outcomes as these children age, or even to exposures in adulthood. Childhood exposures have long term consequences, and adults who have been exposed to lead as children show a host of cognitive deficits. Lead has also been shown to induce latent changes in the aging brain, and has been implicated in the pathogenesis of neurodegenerative diseases, particularly Alzheimer's Disease, and Parkinson's. Recent research has shown that lead has the ability to alter DNA methylation, histone modifications, and miRNA expression in experimental models, and in humans. These findings implicate epigenetics in lead induced toxicity, and long term changes in individuals. Epigenetic modification could potentially provide us a mechanism by which the environment, and toxic exposures contribute to the increased susceptibility of adult neurodegenerative disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Molecular mechanisms of experience-dependent structural and functional plasticity in the brain.

    Science.gov (United States)

    Kondo, Makoto

    2017-01-01

    Experiences and environments have a variety of effects on brain plasticity at levels ranging from the molecular and cellular to the behavioral. Brain plasticity is one of the most important characteristics of animal survival. In particular, environmental enrichment and exercise induce many structural and functional changes in the brain, and it is noteworthy that these changes result in further beneficial effects at behavioral levels, such as improved learning behavior and antidepressant effects. The effects of enrichment and exercise, and the mechanisms involved in both, provide crucial evidence for the prevention and treatment of brain disorders. However, the enriched environment- and exercise-induced mechanisms underlying the structural and behavioral effects in the brain remain poorly understood. In this review I discuss the molecular mechanisms of environment- and experience-dependent brain plasticity based on the results of studies carried out by our research group at the Department of Neuroscience and Cell Biology, Osaka University. This review consists of three parts: first, a description of a role for the motor protein KIF1A in enhanced synaptogenesis and memory function induced by environmental enrichment; second, a discussion of the function of the 5-HT3 receptor in hippocampal neurogenesis and behavioral changes induced by exercise; third, a discussion of the role of the 5-HT3 receptor in fear extinction.

  4. Ultrasound Detection of Patellar Fracture and Evaluation of the Knee Extensor Mechanism in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Kiersten Carter

    2016-11-01

    Full Text Available Traumatic injuries to the knee are common in emergency medicine. Bedside ultrasound (US has benefits in the rapid initial detection of injuries to the patella. In addition, US can also quickly detect injuries to the entire knee extensor mechanism, including the quadriceps tendon and inferior patellar ligament, which may be difficult to diagnose with plain radiographs. While magnetic resonance imaging remains the gold standard for diagnostic evaluation of the knee extensor mechanism, this can be difficult to obtain from the emergency department. Clinicians caring for patients with orthopedic injuries of the knee would benefit from incorporating bedside musculoskeletal US into their clinical skills set.

  5. 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.

  6. Biomarkers and Brain Mechanisms of Gulf War Illness

    Science.gov (United States)

    believed to be causative of the illness. The pathobiological mechanisms of GWI are unknown; there are no validated diagnostic tests, nor are there effective...performed to obtain cerebrospinal fluid (CSF), which will be analyzed for abnormalities in biochemical compounds that may be related to GWI. The derived

  7. Brain-to-brain coupling : a mechanism for creating and sharing a social world

    NARCIS (Netherlands)

    Hasson, Uri; Ghazanfar, Asif A.; Galantucci, Bruno; Garrod, Simon; Keysers, Christian

    Cognition materializes in an interpersonal space. The emergence of complex behaviors requires the coordination of actions among individuals according to a shared set of rules. Despite the central role of other individuals in shaping one's mind, most cognitive studies focus on processes that occur

  8. Emergent Coordination Underlying Learning to Reach-to-Grasp with a Brain-Machine Interface.

    Science.gov (United States)

    Vaidya, Mukta; Balasubramanian, Karthikeyan; Southerland, Joshua; Badreldin, Islam; Eleryan, Ahmed; Shattuck, Kelsey; Gururangan, Suchin; Slutzky, Marc W; Osborne, Leslie C; Fagg, Andrew H; Oweiss, Karim G; Hatsopoulos, Nicholas G

    2017-12-13

    The development of coordinated reach to grasp has been well-studied in infants and children (Kuhtz-Buschbeck, Stolze, Jöhnk, Boczek-Funcke, & Illert, 1998; von Hofsten, 1984a). However, the role of motor cortex during this development is unclear because it is difficult to study in humans. We took the approach using a brain-machine interface (BMI) paradigm in rhesus macaques with prior therapeutic amputations to examine the emergence of novel, coordinated reach-to-grasp. Previous research has shown that after amputation, the cortical area previously involved in the control of the lost limb undergoes reorganization (Qi, Stepniewska, & Kaas, 2000; Schieber & Deuel, 1997; Wu & Kaas, 1999), but prior BMI work has largely relied on finding neurons that already encode specific movement-related information. Here, we taught macaques to cortically control a robotic arm and hand through operant conditioning using neurons that were not explicitly reach- or grasp-related. Over the course of training, stereotypical patterns emerged and stabilized in the cross-covariance between the reaching and grasping velocity profiles, between pairs of neurons involved in controlling reach and grasp, and to a comparable, but lesser, extent between other stable neurons in the network. In fact, we found evidence of this structured coordination between pairs composed of all combinations of neurons decoding reach or grasp, and other stable neurons in the network. The degree of and participation in coordination was highly correlated across all pair-types. Our approach provides a unique model for studying the development of novel, coordinated reach-to-grasp at the behavioral and cortical levels.

  9. Theory of mind--evolution, ontogeny, brain mechanisms and psychopathology.

    Science.gov (United States)

    Brüne, Martin; Brüne-Cohrs, Ute

    2006-01-01

    The ability to infer other persons' mental states and emotions has been termed 'theory of mind'. It represents an evolved psychological capacity most highly developed in humans. The evolutionary origins of theory of mind can be traced back in extant non-human primates; theory of mind probably emerged as an adaptive response to increasingly complex primate social interaction. This sophisticated 'metacognitive' ability comes, however, at an evolutionary cost, reflected in a broad spectrum of psychopathological conditions. Extensive research into autistic spectrum disorders has revealed that theory of mind may be selectively impaired, leaving other cognitive faculties intact. Recent studies have shown that observed deficits in theory of mind task performance are part of a broad range of symptoms in schizophrenia, bipolar affective disorder, some forms of dementia, 'psychopathy' and in other psychiatric disorders. This article reviews the evolutionary psychology of theory of mind including its ontogeny and representation in the central nervous system, and studies of theory of mind in psychopathological conditions.

  10. Reconsolidation of human memory: brain mechanisms and clinical relevance.

    Science.gov (United States)

    Schwabe, Lars; Nader, Karim; Pruessner, Jens C

    2014-08-15

    The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Initial emergency nursing management of patients with severe traumatic brain injury: development of an evidence-based care bundle for the Thai emergency department context.

    Science.gov (United States)

    Damkliang, Jintana; Considine, Julie; Kent, Bridie; Street, Maryann

    2014-11-01

    Thai emergency nurses play a vital role in caring for patients with severe TBI, and are an important part of the healthcare team throughout the resuscitation phase. They are also responsible for continuous physiological monitoring, and detecting deterioration associated with increased intracranial pressure and preventing secondary brain injury. However, there is known variation in Thai nurses' knowledge and care practices for patients with severe TBI. In addition, there are no specific evidence-based practice guidelines available for emergency nursing management of patients with severe TBI. The aim of this paper is to describe the development of an evidence-based care bundle for initial emergency nursing management of patients with severe TBI for use in a Thai ED context. An evidence-based care bundle focused on seven major elements: (1) establish a secure airway along with c-spine protection, (2) maintain adequacy of oxygenation and ventilation, (3) maintain circulation and fluid balance, (4) assessment of GCS, and pupil size and reactivity, (5) maintain cerebral venous outflow, (6) management of pain, agitation, and irritability, and (7) administer for urgent CT scan. A care bundle is one method of promoting consistent, evidence-based emergency nursing care of patients with severe TBI, decreasing unnecessary variations in nursing care and reducing the risk of secondary brain injury from suboptimal care. Implementation of this evidence-based care bundle developed specifically for the Thai emergency nursing context has the potential to improve the care of the patients with severe TBI. Copyright © 2014 College of Emergency Nursing Australasia Ltd. Published by Elsevier Ltd. All rights reserved.

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    adult participants decided to chase losses or decided to quit gambling to prevent further losses.ResultsChasing losses was associated with increased activity in cortical areas linked to incentive-motivation and an expectation of reward. By contrast, quitting was associated with decreased activity...... 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....

  14. Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Ari Ercole

    2017-08-01

    Full Text Available Traumatic brain injury (TBI is understood as an interplay between the initial injury, subsequent secondary injuries, and a complex host response all of which are highly heterogeneous. An understanding of the underlying biology suggests a number of windows where mechanistically inspired interventions could be targeted. Unfortunately, biologically plausible therapies have to-date failed to translate into clinical practice. While a number of stereotypical pathways are now understood to be involved, current clinical characterization is too crude for it to be possible to characterize the biological phenotype in a truly mechanistically meaningful way. In this review, we examine current and emerging technologies for fuller biochemical characterization by the simultaneous measurement of multiple, diverse biomarkers. We describe how clinically available techniques such as cerebral microdialysis can be leveraged to give mechanistic insights into TBI pathobiology and how multiplex proteomic and metabolomic techniques can give a more complete description of the underlying biology. We also describe spatially resolved label-free multiplex techniques capable of probing structural differences in chemical signatures. Finally, we touch on the bioinformatics challenges that result from the acquisition of such large amounts of chemical data in the search for a more mechanistically complete description of the TBI phenotype.

  15. Australian emergency doctors' and nurses' acceptance and knowledge regarding brain death: a national survey.

    Science.gov (United States)

    Marck, Claudia H; Weiland, Tracey J; Neate, Sandra L; Hickey, Bernadette B; Jelinek, George A

    2012-01-01

    Healthcare staff's acceptance of brain death (BD) being a valid determination of death is essential for optimized organ and tissue donation (OTD) rates. Recently, resources to increase Australian OTD rates have been aimed at emergency departments (ED) as a significant missed donor potential was discovered. A cross-sectional survey was conducted to assess Australian ED clinicians' acceptance and knowledge regarding BD. Most (86%) of the 599 medical and 212 nursing staff accepted BD, but only 60% passed a 5-item-validated BD knowledge tool. BD knowledge was related to the acceptance of BD. Accepting BD influenced attitudes toward OTD, including willingness to donate. BD acceptance and knowledge were related to education/training regarding OTD, years of experience in EDs, experience with OTD-related tasks, and increased perceived competence and comfort with OTD-related tasks. Of concern, more than half of respondents who did not pass the BD test reported feeling competent and comfortable explaining BD to next of kin; of respondents who had recent experience with this, more than a third failed the BD test. Despite being generally positive toward OTD, Australian ED clinicians do not have a sound knowledge of BD. This may be hampering efforts to increase donation rates from the ED. © 2012 John Wiley & Sons A/S.

  16. Emergency Situation Prediction Mechanism: A Novel Approach for Intelligent Transportation System Using Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    P. Ganeshkumar

    2015-01-01

    Full Text Available In Indian four-lane express highway, millions of vehicles are travelling every day. Accidents are unfortunate and frequently occurring in these highways causing deaths, increase in death toll, and damage to infrastructure. A mechanism is required to avoid such road accidents at the maximum to reduce the death toll. An Emergency Situation Prediction Mechanism, a novel and proactive approach, is proposed in this paper for achieving the best of Intelligent Transportation System using Vehicular Ad Hoc Network. ESPM intends to predict the possibility of occurrence of an accident in an Indian four-lane express highway. In ESPM, the emergency situation prediction is done by the Road Side Unit based on (i the Status Report sent by the vehicles in the range of RSU and (ii the road traffic flow analysis done by the RSU. Once the emergency situation or accident is predicted in advance, an Emergency Warning Message is constructed and disseminated to all vehicles in the area of RSU to alert and prevent the vehicles from accidents. ESPM performs well in emergency situation prediction in advance to the occurrence of an accident. ESPM predicts the emergency situation within 0.20 seconds which is comparatively less than the statistical value. The prediction accuracy of ESPM against vehicle density is found better in different traffic scenarios.

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

    Science.gov (United States)

    2015-10-01

    likely that we will be able to show that damage to specific  pain   pathways  or, more likely, specific molecular  processes like epigenetics mediate the...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

  19. 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

  20. 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.

  1. Alternative mechanisms alter the emergent properties of self-organization in mussel beds.

    Science.gov (United States)

    Liu, Quan-Xing; Weerman, Ellen J; Herman, Peter M J; Olff, Han; van de Koppel, Johan

    2012-07-22

    Theoretical models predict that spatial self-organization can have important, unexpected implications by affecting the functioning of ecosystems in terms of resilience and productivity. Whether and how these emergent effects depend on specific formulations of the underlying mechanisms are questions that are often ignored. Here, we compare two alternative models of regular spatial pattern formation in mussel beds that have different mechanistic descriptions of the facilitative interactions between mussels. The first mechanism involves a reduced mussel loss rate at high density owing to mutual protection between the mussels, which is the basis of prior studies on the pattern formation in mussels. The second mechanism assumes, based on novel experimental evidence, that mussels feed more efficiently on top of mussel-generated hummocks. Model simulations point out that the second mechanism produces very similar types of spatial patterns in mussel beds. Yet the mechanisms predict a strikingly contrasting effect of these spatial patterns on ecosystem functioning, in terms of productivity and resilience. In the first model, where high mussel densities reduce mussel loss rates, patterns are predicted to strongly increase productivity and decrease the recovery time of the bed following a disturbance. When pattern formation is generated by increased feeding efficiency on hummocks, only minor emergent effects of pattern formation on ecosystem functioning are predicted. Our results provide a warning against predictions of the implications and emergent properties of spatial self-organization, when the mechanisms that underlie self-organization are incompletely understood and not based on the experimental study.

  2. Experimental investigation of the mechanical properties of brain simulants used for cranial gunshot simulation.

    Science.gov (United States)

    Lazarjan, Milad Soltanipour; Geoghegan, Patrick Henry; Jermy, Mark Christopher; Taylor, Michael

    2014-06-01

    The mechanical properties of the human brain at high strain rate were investigated to analyse the mechanisms that cause backspatter when a cranial gunshot wound occurs. Different concentrations of gelatine and a new material (M1) developed in this work were tested and compared to bovine brain samples. Kinetic energy absorption and expansion rate of the samples caused by the impact of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22 long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high speed camera (24,000fps). The AR projectile had, in the region of interest, an average kinetic energy (Ek) of 42±1.3J. On average, the bovine brain absorbed 50±5% of Ek, and the simulants 46-58±5%. The Ek of the .22 LR was 141±3.7J. The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The expansion of the sample, after penetration, was measured. The bovine brain experienced significant plastic deformation whereas the gelatine solution exhibited a principally elastic response. The permanent damage patterns in the M1 material were much closer to those in brain tissue, than were the damage patterns in the gelatine. The results provide a first step to developing a realistic experimental simulant for the human brain which can produce the same blood backspatter patterns as a human brain during a cranial gunshot. These results can also be used to improve the 3D models of human heads used in car crash and blast trauma injury research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    Science.gov (United States)

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  4. Emergent Quantum Mechanics and the Origin of Quantum Non-local Correlations

    Science.gov (United States)

    Torromé, Ricardo Gallego

    2017-10-01

    A geometric interpretation for quantum correlations and entanglement according to a particular framework of emergent quantum mechanics is developed. The mechanism described is based on two ingredients: 1. At an hypothetical sub-quantum level description of physical systems, the dynamics has a regime where it is partially ergodic and 2. A formal projection from a two-dimensional time mathematical formalism of the emergent quantum theory to the usual one-dimensional time formalism of quantum dynamics. Observable consequences of the theory are obtained. Among them we show that quantum correlations must be instantaneous from the point of view of the spacetime description, but the spatial distance up to which they can be observed must be bounded. It is argued how our mechanism avoids Bell theorem and Kochen-Specken theorem. Evidence for non-signaling faster than the speed of light in our proposal is discussed.

  5. On the characterization of the heterogeneous mechanical response of human brain tissue.

    Science.gov (United States)

    Forte, Antonio E; Gentleman, Stephen M; Dini, Daniele

    2017-06-01

    The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.

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

  7. Blood–brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome

    Science.gov (United States)

    Ivens, Sebastian; Gabriel, Szendro; Greenberg, George; Shelef, Ilan

    2013-01-01

    Cerebral hyperperfusion syndrome (CHS) may occur as a severe complication following surgical treatment of carotid stenosis. However, the mechanism inducing neurological symptoms in CHS remains unknown. We describe a patient with CHS presenting with seizures 24 h following carotid endarterectomy. Imaging demonstrated early ipsilateral blood–brain barrier (BBB) breakdown with electroencephalographic evidence of cortical dysfunction preceding brain edema. Using in vitro experiments on rat cortical tissue, we show that direct exposure of isolated brain slices to a serum-like medium induces spontaneous epileptiform activity, and that neuronal dysfunction is triggered by albumin. We propose BBB breakdown and subsequent albumin extravasation as a novel pathogenic mechanism underlying CHS and a potential target for therapy. PMID:20361293

  8. Role of opioid peptides in brain mechanisms regulating blood pressure.

    Science.gov (United States)

    de Jong, W; Petty, M A; Sitsen, J M

    1983-02-01

    Beta-endorphin and related opioid peptides are neuropeptides which appear to play a role in cardiovascular regulation which is supported by altered nociceptive responsiveness in hypertensive animals. In spontaneously hypertensive rats the pain threshold for electric stimulation is elevated; these rats show increased response latency time in a hot plate test. The opiate antagonist naloxone reverses these values to that of the normotensive controls. In other forms of experimental hypertension, eg, renal hypertension (one-clip, two-kidney model), no change in pain sensitivity is apparent. Sinoaortic baroreceptor denervation causes a labile hypertension without changes in hot plate response. Administration of beta-endorphin into the nucleus of the solitary tract (NTS) gradually decreases blood pressure and heart rate without affecting respiratory frequency. These cardiovascular effects are blocked by naloxone as well as by an antibody to beta-endorphin. In contrast to the effects of beta-endorphin, microinjection of enkephalins into the NTS increases blood pressure and heart rate. The data suggest the existence of two separate endorphin systems at the level of the NTS, one a depressor and another a pressor system. The depressor influence of beta-endorphin may play a role in the mechanism of action of antihypertensive agents such as methyldopa and clonidine. Our data support a role of endorphins as neuropeptides involved in cardiovascular regulation, exerting a dual influence at the level of the NTS.

  9. Understanding Why Patients Return to the Emergency Department after Mild Traumatic Brain Injury within 72 Hours

    Directory of Open Access Journals (Sweden)

    Ganti, Latha

    2015-05-01

    Full Text Available Introduction: Although there are approximately 1.1 million case presentations of mild traumatic brain injury (mTBI in the emergency department (ED each year, little data is available to clinicians to identify patients who are at risk for poor outcomes, including 72-hour ED return after discharge. An understanding of patients at risk for ED return visits during the hyperacute phase following head injury would allow ED providers to develop clinical interventions that reduce its occurrence and improve outcomes. Methods: This institutional review board-approved consecutive cohort study collected injury and outcome variables on adults with the purpose of identifying positive predictors for 72-hour ED return visits in mTBI patients. Results: Of 2,787 mTBI patients, 145 (5% returned unexpectedly to the ED within 72 hours of hospital discharge. Positive predictors for ED return visits included being male (p=0.0298, being black (p=0.0456, having a lower prehospital Glasgow Coma Score (p=0.0335, suffering the injury due to a motor vehicle collision (p=0.0065, or having a bleed on head computed tomography (CT (p=0.0334. ED return visits were not significantly associated with age, fracture on head CT, or symptomology following head trauma. Patients with return visits most commonly reported post-concussion syndrome (43.1%, pain (18.7%, and recall for further clinical evaluation (14.6% as the reason for return. Of the 124 patients who returned to the ED within 72 hours, one out of five were admitted to the hospital for further care, with five requiring intensive care unit stays and four undergoing neurosurgery. Conclusion: Approximately 5% of adult patients who present to the ED for mTBI will return within 72 hours of discharge for further care. Clinicians should identify at-risk individuals during their initial visits and attempt to provide anticipatory guidance when possible. [West J Emerg Med. 2015;16(2:481–485.

  10. Microcavitation as a neuronal damage mechanism in blast -traumatic brain injury

    OpenAIRE

    Estrada, Jon; Franck, Christian

    2014-01-01

    Traumatic brain injury (TBI), usually the result of impact or blast to the head, affects about 1.5 million Americans annually. 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 armed forces exposed to concussive blasts. Cavitation damage to free surfaces has been well-studied in the field of fluid dynamics, but b...

  11. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2015-07-01

    chronic neuronal cell loss, glial activation, and chronic traumatic encephalopathy (CTE) measure of β-amyloid and hyper-phosphorylated tau protein...Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury...30 Jun 2015 4. TITLE AND SUBTITLE Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After TBI 5a. CONTRACT NUMBER W81XWH-14-1

  12. 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...

  13. Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

    Science.gov (United States)

    Bourdillon, Pierre; Apra, Caroline; Guénot, Marc; Duffau, Hugues

    2017-12-01

    To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  14. Fetal and neonatal brain injury: mechanisms, management, and the risks of practice

    National Research Council Canada - National Science Library

    Stevenson, David K; Benitz, William E; Sunshine, Philip

    2003-01-01

    ..., imaging studies, and laboratory measurements can identify the timing and severity of the injury event. Despite these advances, fetal and neonatal brain injury remains a major concern with devastating consequences. It is hoped that this definitive account will provide the clinician not only with a better understanding of the mechanisms involved but also with...

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

    Science.gov (United States)

    Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina; Kemmerer, David; MacWhinney, Brian; Nielsen, Finn Årup; Oztop, Erhan

    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 data that serve systems and cognitive neuroscience. PMID:24234916

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

    Science.gov (United States)

    Mosconi, Lisa; Berti, Valentina; Guyara-Quinn, Crystal; McHugh, Pauline; Petrongolo, Gabriella; Osorio, Ricardo S; Connaughty, Christopher; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Swerdlow, Russell H; Brinton, Roberta Diaz

    2017-01-01

    After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p'sendocrine aging process.

  17. Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases.

    Science.gov (United States)

    Phan, Chia-Wei; David, Pamela; Sabaratnam, Vikineswary

    2017-01-01

    There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their antidementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.

  18. Nanotheranostics: Emerging Strategies for Early Diagnosis and Therapy of Brain Cancer

    OpenAIRE

    Sonali,; Viswanadh, Matte Kasi; Singh, Rahul Pratap; Agrawal, Poornima; Mehata, Abhishesh Kumar; Pawde, Datta Maroti; Narendra,; Sonkar, Roshan; Muthu, Madaswamy Sona

    2018-01-01

    Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems establis...

  19. 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.

  20. [Molecular mechanism of brain regeneration and reconstruction of dopaminergic neural network in planarians].

    Science.gov (United States)

    Nishimura, Kaneyasu; Kitamura, Yoshihisa; Agata, Kiyokazu

    2008-04-01

    Recently, planarians have received much attention because of their contributions to research on the basic science of stem cell systems, neural regeneration, and regenerative medicine. Planarians can regenerate complete organs, including a well-organized central nervous system (CNS), within about 7 days. This high regenerative capacity is supported by pluripotent stem cells present in the mesenchymal space throughout the body. Interestingly, planarians can regenerate their brain via a molecular mechanism similar to that of mammalian brain development. The regeneration process of the planarian brain can be divided into five steps: (1) anterior blastema formation, (2) brain rudiment formation, (3) brain pattern formation, (4) neural network formation, and (5) functional recovery, with several kinds of genes and molecular cascades acting at each step. Recently, we have identified a planarian tyrosine hydroxylase (TH) gene, a rate-limiting enzyme for dopamine (DA) biosynthesis, and produced TH-knockdown planarians by the RNA interference technique. Studies of TH-knockdown planarians showed that DA has an important role of the modification in behavioral movement in planarians. Using monoclonal anti-planarian TH antibody, we also found that dopaminergic neurons are mainly localized in the planarian brain. When the planarian body was amputated, newly generated TH-immunopositive neurons were detected in the anterior region at day 3 of regeneration (i.e., the period of neural network formation), and the TH-immunopositive axonal and dendritic neural network in the CNS was reconstructed during day 5-7 of regeneration. In this article, recent advances in elucidating the molecular mechanism of planarian brain regeneration and dopaminergic neurons are reviewed, and its future prospects for contribution of this system to basic science and medical science research are described.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Tao Qin

    2016-08-01

    Full Text Available 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.

  3. [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

  4. 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

  5. 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

    National Research Council Canada - National Science Library

    Gregor Wolbring; Lucy Diep; Sophya Yumakulov; Natalie Ball; Dean Yergens

    2013-01-01

      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...

  6. 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. 2013 APA, all rights reserved

  7. 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.

  8. Mechanisms underlying brain monitoring during anesthesia: limitations, possible improvements, and perspectives.

    Science.gov (United States)

    Cascella, Marco

    2016-04-01

    Currently, anesthesiologists use clinical parameters to directly measure the depth of anesthesia (DoA). This clinical standard of monitoring is often combined with brain monitoring for better assessment of the hypnotic component of anesthesia. Brain monitoring devices provide indices allowing for an immediate assessment of the impact of anesthetics on consciousness. However, questions remain regarding the mechanisms underpinning these indices of hypnosis. By briefly describing current knowledge of the brain's electrical activity during general anesthesia, as well as the operating principles of DoA monitors, the aim of this work is to simplify our understanding of the mathematical processes that allow for translation of complex patterns of brain electrical activity into dimensionless indices. This is a challenging task because mathematical concepts appear remote from clinical practice. Moreover, most DoA algorithms are proprietary algorithms and the difficulty of exploring the inner workings of mathematical models represents an obstacle to accurate simplification. The limitations of current DoA monitors - and the possibility for improvement - as well as perspectives on brain monitoring derived from recent research on corticocortical connectivity and communication are also discussed.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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. © 2014 WILEY Periodicals, Inc.

  14. Pulsations with reflected boundary waves: a hydrodynamic reverse transport mechanism for perivascular drainage in the brain.

    Science.gov (United States)

    Coloma, M; Schaffer, J D; Carare, R O; Chiarot, P R; Huang, P

    2016-08-01

    Beta-amyloid accumulation within arterial walls in cerebral amyloid angiopathy is associated with the onset of Alzheimer's disease. However, the mechanism of beta-amyloid clearance along peri-arterial pathways in the brain is not well understood. In this study, we investigate a transport mechanism in the arterial basement membrane consisting of forward-propagating waves and their reflections. The arterial basement membrane is modeled as a periodically deforming annulus filled with an incompressible single-phase Newtonian fluid. A reverse flow, which has been suggested in literature as a beta-amyloid clearance pathway, can be induced by the motion of reflected boundary waves along the annular walls. The wave amplitude and the volume of the annular region govern the flow magnitude and may have important implications for an aging brain. Magnitudes of transport obtained from control volume analysis and numerical solutions of the Navier-Stokes equations are presented.

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

    Science.gov (United States)

    Hut, R A; Beersma, D G M

    2011-07-27

    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, annual or tidal time scale. Internal timing mechanisms may facilitate behavioural or physiological adaptation to such changes in environmental conditions. These timing mechanisms commonly involve an internal molecular oscillator (a 'clock') that is synchronized ('entrained') to the environmental cycle by receptor mechanisms responding to relevant environmental signals ('Zeitgeber', i.e. German for time-giver). To understand the evolution of such timing mechanisms, we have to understand the mechanisms leading to selective advantage. Although major advances have been made in our understanding of the physiological and molecular mechanisms driving internal cycles (proximate questions), studies identifying mechanisms of natural selection on clock systems (ultimate questions) are rather limited. Here, we discuss the selective advantage of a circadian system and how its adaptation to day length variation may have a functional role in optimizing seasonal timing. We discuss various cases where selective advantages of circadian timing mechanisms have been shown and cases where temporarily loss of circadian timing may cause selective advantage. We suggest an explanation for why a circadian timing system has emerged in primitive life forms like cyanobacteria and we evaluate a possible molecular mechanism that enabled these bacteria to adapt to seasonal variation in day length. We further discuss how the role of the circadian system in photoperiodic time measurement may explain differential selection pressures on circadian period when species are exposed to changing climatic conditions (e.g. global warming) or when they expand their geographical range to different latitudes or altitudes.

  16. The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks.

    Directory of Open Access Journals (Sweden)

    Sven eVanneste

    2012-05-01

    Full Text Available Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like and associated emotional components, such as distress and mood changes. Source localization of qEEG data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual, auditory cortex (primary and secondary, dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus, parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature.

  17. Functional near infrared spectroscopy (fNIRS): an emerging neuroimaging technology with important applications for the study of brain disorders.

    Science.gov (United States)

    Irani, Farzin; Platek, Steven M; Bunce, Scott; Ruocco, Anthony C; Chute, Douglas

    2007-01-01

    Functional near-infrared spectroscopy (fNIRS) is an emerging functional neuroimaging technology offering a relatively non-invasive, safe, portable, and low-cost method of indirect and direct monitoring of brain activity. Most exciting is its potential to allow more ecologically valid investigations that can translate laboratory work into more realistic everyday settings and clinical environments. Our aim is to acquaint clinicians and researchers with the unique and beneficial characteristics of fNIRS by reviewing its relative merits and limitations vis-à-vis other brain-imaging technologies such as functional magnetic resonance imaging (fMRI). We review cross-validation work between fMRI and fNIRS, and discuss possible reservations about its deployment in clinical research and practice. Finally, because there is no comprehensive review of applications of fNIRS to brain disorders, we also review findings from the few studies utilizing fNIRS to investigate neurocognitive processes associated with neurological (Alzheimer's disease, Parkinson's disease, epilepsy, traumatic brain injury) and psychiatric disorders (schizophrenia, mood disorders, anxiety disorders).

  18. THE EFFECTS OF AN INCENTIVE MECHANISM ON BRAIN DRAIN IN THE HOTEL INDUSTRY

    OpenAIRE

    Zhao, Danni

    2016-01-01

    This thesis studies the effects of incentive mechanism on brain drain in hotel industry. As for the reason why this topic is chosen, it is regarding to the author's previous working experiences in the hotel industry. After the training practice in several different hotels, it is notable that Chinese hotel industry is confronted with a severe problem of high employee turnover. While the normal human resource turnover rate should remain between 5% and 10%, the average figure for the hotel staff...

  19. 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

  20. Role of MicroRNAs in innate neuroprotection mechanisms due to preconditioning of the brain

    Directory of Open Access Journals (Sweden)

    Eva Maria Jimenez-Mateos

    2015-04-01

    Full Text Available Insults to the brain that are sub-threshold for damage activate endogenous protective pathways, which can temporarily protect the brain against a subsequent harmful episode. This mechanism has been named as tolerance and its protective effects have been shown in experimental models of ischemia and epilepsy. The preconditioning-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs.Gene-array profiling has shown that both ischemic and epileptic tolerance feature large-scale gene down-regulation but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of ~20-22 nucleotides length which regulate gene expression at a post-transcriptional level via mRNA degradation or inhibition of protein translation. MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli in the brain and to contribute to neuroprotective mechanisms. This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic preconditioning.

  1. 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

    2015-09-01

    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. 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. 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. 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 activation appears to be a consequence of the improvement

  2. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications.

    Science.gov (United States)

    Palombo, Carlo; Kozakova, Michaela

    2016-02-01

    Arterial stiffness results from a degenerative process affecting mainly the extracellular matrix of elastic arteries under the effect of aging and risk factors. Changes in extracellular matrix proteins and in the mechanical properties of the vessel wall related to arterial stiffening may activate number of mechanisms involved also in the process of atherosclerosis. Several noninvasive methods are now available to estimate large artery stiffness in the clinical setting, including carotid-femoral pulse wave velocity, the reference for aortic stiffness estimate, and local distensibility measures of superficial arteries, namely carotid and femoral. An independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in general as well as in selected populations, and reference values adjusted for age and blood pressure have been established. Thus, arterial stiffness is emerging as an interesting tissue biomarker for cardiovascular risk stratification and estimation of the individual "biological age". This paper overviews the mechanisms accounting for development and progression of arterial stiffness and for associations between arterial stiffness, atherosclerotic burden and incident cardiovascular events, summarizes the evidence and caveat for clinical use of stiffness as surrogate marker of cardiovascular risk, and briefly outlines some emerging methods for large artery stiffness characterization. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 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...

  4. The Emerging Role of Tractography in Deep Brain Stimulation: Basic Principles and Current Applications

    Directory of Open Access Journals (Sweden)

    Nelson B. Rodrigues

    2018-01-01

    Full Text Available Diffusion tensor imaging (DTI is an MRI-based technique that delineates white matter tracts in the brain by tracking the diffusion of water in neural tissue. This methodology, known as “tractography”, has been extensively applied in clinical neuroscience to explore nervous system architecture and diseases. More recently, tractography has been used to assist with neurosurgical targeting in functional neurosurgery. This review provides an overview of DTI principles, and discusses current applications of tractography for improving and helping develop novel deep brain stimulation (DBS targets.

  5. 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.

  6. 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 +/-...

  7. 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.

  8. Traumatic brain injury in the Netherlands, trends in emergency department visits, hospitalization and mortality between 1998 and 2012.

    Science.gov (United States)

    Van den Brand, Crispijn L; Karger, Lennard B; Nijman, Susanne T M; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

    2017-03-06

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. The effects of epidemiological changes such as ageing of the population and increased traffic safety on the incidence of TBI are unknown. The objective of this study was to evaluate trends in TBI-related emergency department (ED) visits, hospitalization and mortality in the Netherlands between 1998 and 2012. This was a retrospective observational, longitudinal study. The main outcome measures were TBI-related ED visits, hospitalization and mortality. Between 1998 and 2012, there were 500 000 TBI-related ED visits in the Netherlands. In the same period, there were 222 000 TBI-related admissions and 17 000 TBI-related deaths. During this period, there was a 75% increase in ED visits for TBI and a 95% increase for TBI-related hospitalization; overall mortality because of TBI did not change significantly. Despite the overall increase in TBI-related ED visits, this increase was not evenly distributed among age groups or trauma mechanisms. In patients younger than 65 years, a declining trend in ED visits for TBI caused by road traffic accidents was observed. Among patients 65 years or older, ED visits for TBI caused by a fall increased markedly. TBI-related mortality shifted from mainly young (67%) and middle-aged individuals (1998 and 2012. The conclusions of this study did not change when adjusting for changes in age, sex and overall population growth. The incidence of TBI-related ED visits and hospitalization increased markedly between 1998 and 2012 in the Netherlands. TBI-related mortality occurred at an older age. These observations are probably the result of a change in aetiology of TBI, specifically a decrease in traffic accidents and an increase in falls in the ageing population. This hypothesis is supported by our data. However, ageing of the population is not the only cause of the changes observed; the observed changes remained significant when correcting for age and sex

  9. 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

  10. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.

    Science.gov (United States)

    Carhart-Harris, Robin L; Roseman, Leor; Bolstridge, Mark; Demetriou, Lysia; Pannekoek, J Nienke; Wall, Matthew B; Tanner, Mark; Kaelen, Mendel; McGonigle, John; Murphy, Kevin; Leech, Robert; Curran, H Valerie; Nutt, David J

    2017-10-13

    Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.

  11. Cellular and molecular mechanisms triggered by Deep Brain Stimulation in depression: A preclinical and clinical approach.

    Science.gov (United States)

    Torres-Sanchez, S; Perez-Caballero, L; Berrocoso, E

    2017-02-06

    Deep Brain Stimulation (DBS) was originally developed as a therapeutic approach to manage movement disorders, in particular Parkinson's Disease. However, DBS also seems to be an effective treatment against refractory depression when patients fail to respond satisfactorily to conventional therapies. Thus, DBS targeting specific brain areas can produce an antidepressant response that improves depressive symptomatology, these areas including the subcallosal cingulate region, nucleus accumbens, ventral capsule/ventral striatum, medial forebrain bundle, the inferior thalamic peduncle and lateral habenula. Although the efficacy and safety of this therapy has been demonstrated in some clinical trials and preclinical studies, the intrinsic mechanisms underlying its antidepressant effect remain poorly understood. This review aims to provide a comprehensive overview of DBS, focusing on the molecular and cellular changes reported after its use that could shed light on the mechanisms underpinning its antidepressant effect. Several potential mechanisms of action of DBS are considered, including monoaminergic and glutamatergic neurotransmission, neurotrophic and neuroinflammatory mechanisms, as well as potential effects on certain intracellular signaling pathways. Although future studies will be necessary to determine the key molecular events underlying the antidepressant effect of DBS, the findings presented provide an insight into some of its possible modes of action. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  13. 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…

  14. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  15. 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.

  16. Brain mechanisms for social perception: lessons from autism and typical development.

    Science.gov (United States)

    Pelphrey, Kevin A; Carter, Elizabeth J

    2008-12-01

    In this review, we summarize our research program, which has as its goal charting the typical and atypical development of the social brain in children, adolescents, and adults with and without autism. We highlight recent work using virtual reality stimuli, eye tracking, and functional magnetic resonance imaging that has implicated the superior temporal sulcus (STS) region as an important component of the network of brain regions that support various aspects of social cognition and social perception. Our work in typically developing adults has led to the conclusion that the STS region is involved in social perception via its role in the visual analysis of others' actions and intentions from biological-motion cues. Our work in high-functioning adolescents and adults with autism has implicated the STS region as a mechanism underlying social perception dysfunction in this neurodevelopmental disorder. We also report novel findings from a study of biological-motion perception in young children with and without autism.

  17. Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

    Science.gov (United States)

    Jin, Byung-Ju; Smith, Alex J; Verkman, Alan S

    2016-12-01

    A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. © 2016 Jin et al.

  18. 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 × 105 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 (Cys318-Cys326), 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. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

    Science.gov (United States)

    Aragno, Manuela; Mastrocola, Raffaella

    2017-01-01

    The rapid increase in metabolic diseases, which occurred in the last three decades in both industrialized and developing countries, has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agents when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidence also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not only metabolic control, but global health. Indeed, the most recent reports on the effects of high sugar consumption and diet-derived AGEs on human health reviewed here suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities. PMID:28420091

  20. A functional architecture of the human brain: emerging insights from the science of emotion.

    Science.gov (United States)

    Lindquist, Kristen A; Barrett, Lisa Feldman

    2012-11-01

    The 'faculty psychology' approach to the mind, which attempts to explain mental function in terms of categories that reflect modular 'faculties', such as emotions, cognitions, and perceptions, has dominated research into the mind and its physical correlates. In this paper, we argue that brain organization does not respect the commonsense categories belonging to the faculty psychology approach. We review recent research from the science of emotion demonstrating that the human brain contains broadly distributed functional networks that can each be re-described as basic psychological operations that interact to produce a range of mental states, including, but not limited to, anger, sadness, fear, disgust, and so on. When compared to the faculty psychology approach, this 'constructionist' approach provides an alternative functional architecture to guide the design and interpretation of experiments in cognitive neuroscience. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Friismose, Ancuta; Traise, Peter; Markovic, Ljubo

    . 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...... 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......, Philips Healthcare, Best, The Netherlands). Blood oxygen level dependent (BOLD) contrast axial images are acquired using a T2-weighted single-shot echo planar imaging (EPI) sequence. Silent word generation and finger tapping paradigms are included in the exam to pinpoint Broca and motor cortex areas...

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

    Directory of Open Access Journals (Sweden)

    Michael D Cusimano

    Full Text Available 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.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.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.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.

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

    Science.gov (United States)

    Cusimano, Michael D; Cho, Newton; Amin, Khizer; Shirazi, Mariam; McFaull, Steven R; Do, Minh T; Wong, Matthew C; Russell, Kelly

    2013-01-01

    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. 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. 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). 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.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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. Mechanical properties of dura mater from the rat brain and spinal cord.

    Science.gov (United States)

    Maikos, Jason T; Elias, Ragi A I; Shreiber, David I

    2008-01-01

    The dura mater is the outermost and most substantial meningial layer of central nervous system (CNS) tissue that acts as a protective membrane for the brain and spinal cord. In animal models of traumatic brain injury and spinal cord injury, mechanical insults are often delivered directly to the dura to injure the underlying tissue. As such, including a description of the mechanical properties of dura mater is critical for biomechanical analyses of these models. We have characterized the mechanical response of dura mater from the rat brain and spinal cord in uniaxial tension. Testing was performed at low (0.0014 sec(-1)) and high (19.42 sec(-1)) strain rates. Both rat cranial dura and spinal dura demonstrated non-linear stress-strain responses characteristic of collagenous soft tissues. The non-linear increase in stress lagged in the spinal dura compared to the cranial dura. The slow rate data was fit to a one-term Ogden hyperelastic constitutive law, and significant differences were observed for the stiffness, G, and the parameter, alpha, which nominally introduces non-linearity. High strain rate stress-relaxation tests were performed to 10% strain, which was held for 10 sec. The relaxation was fit to a four-term Prony series exponential decay. Cranial dura and spinal dura demonstrated similar overall relaxation, but significant differences were identified in the distribution of the relaxation over the Prony series parameters, which demonstrated that cranial dura tended to relax faster. Polarized light microscopy revealed that the structural entities of spinal dura were aligned in the axial direction, whereas cranial dura did not demonstrate a preferential alignment. This was confirmed qualitatively with Masson's Tri-chrome and Verhoeff's Van Gieson staining for collagen and elastin, which also indicated greater elastin content for the spinal dura than for the cranial dura.

  7. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder

    OpenAIRE

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, D.

    2015-01-01

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a normal quality of life (QoL) after DBS. Reviewing the literature of the last 4 years, we argue that the mechanisms of action of DBS are a combination of excitatory and inhibitory as well as ...

  8. Mechanics of blast loading on the head models in the study of traumatic brain injury using experimental and computational approaches.

    Science.gov (United States)

    Ganpule, S; Alai, A; Plougonven, E; Chandra, N

    2013-06-01

    Blast waves generated by improvised explosive devices can cause mild, moderate to severe traumatic brain injury in soldiers and civilians. To understand the interactions of blast waves on the head and brain and to identify the mechanisms of injury, compression-driven air shock tubes are extensively used in laboratory settings to simulate the field conditions. The overall goal of this effort is to understand the mechanics of blast wave-head interactions as the blast wave traverses the head/brain continuum. Toward this goal, surrogate head model is subjected to well-controlled blast wave profile in the shock tube environment, and the results are analyzed using combined experimental and numerical approaches. The validated numerical models are then used to investigate the spatiotemporal distribution of stresses and pressure in the human skull and brain. By detailing the results from a series of careful experiments and numerical simulations, this paper demonstrates that: (1) Geometry of the head governs the flow dynamics around the head which in turn determines the net mechanical load on the head. (2) Biomechanical loading of the brain is governed by direct wave transmission, structural deformations, and wave reflections from tissue-material interfaces. (3) Deformation and stress analysis of the skull and brain show that skull flexure and tissue cavitation are possible mechanisms of blast-induced traumatic brain injury.

  9. 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

  10. 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.

  11. 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.

  12. Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain.

    Science.gov (United States)

    Römermann, Kerstin; Fedrowitz, Maren; Hampel, Philip; Kaczmarek, Edith; Töllner, Kathrin; Erker, Thomas; Sweet, Douglas H; Löscher, Wolfgang

    2017-05-01

    There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders. Recently, active efflux transport at the blood-brain barrier (BBB) has been suggested as a process involved in the low brain:plasma ratio of bumetanide, but it is presently not clear which transporters are involved. Understanding the processes explaining the poor brain penetration of bumetanide is needed for developing strategies to improve the brain delivery of this drug. In the present study, we administered probenecid and more selective inhibitors of active transport carriers at the BBB directly into the brain of mice to minimize the contribution of peripheral effects on the brain penetration of bumetanide. Furthermore, in vitro experiments with mouse organic anion transporter 3 (Oat3)-overexpressing Chinese hamster ovary cells were performed to study the interaction of bumetanide, bumetanide derivatives, and several known inhibitors of Oats on Oat3-mediated transport. The in vivo experiments demonstrated that the uptake and efflux of bumetanide at the BBB is much more complex than previously thought. It seems that both restricted passive diffusion and active efflux transport, mediated by Oat3 but also organic anion-transporting polypeptide (Oatp) Oatp1a4 and multidrug resistance protein 4 explain the extremely low brain concentrations that are achieved after systemic administration of bumetanide, limiting the use of this drug for targeting abnormal expression of neuronal NKCC1 in brain diseases. Copyright © 2017 Elsevier Ltd. All rights

  13. Evidence of an emerging levee failure mechanism causing disastrous floods in Italy

    Science.gov (United States)

    Orlandini, Stefano; Moretti, Giovanni; Albertson, John

    2017-04-01

    A levee failure occurred along the Secchia River, Northern Italy, on January 19, 2014, resulting in flood damage in excess of 500 Million. In response to this failure, immediate surveillance of other levees in the region led to the identification of a second breach developing on the neighboring Panaro River, where rapid mitigation efforts were successful in averting a full levee failure. The paired breach events that occurred along the Secchia and Panaro Rivers provided an excellent window on an emerging levee failure mechanism. In the Secchia River, by combining the information content of photographs taken from helicopters in the early stage of breach development and 10-cm resolution aerial photographs taken in 2010 and 2012, animal burrows were found to exist in the precise levee location where the breach originated. In the Panaro River, internal erosion was observed to occur at a location where a crested porcupine den was known to exist and this erosion led to the collapse of the levee top. This paper uses detailed numerical modeling of rainfall, river flow, and variably saturated flow in the levee to explore the hydraulic and geotechnical mechanisms that were triggered along the Secchia and Panaro Rivers by activities of burrowing animals leading to levee failures. As habitats become more fragmented and constrained along river corridors it is possible that this failure mechanism could become more prevalent and, therefore, will demand greater attention in both the design and maintenance of earthen hydraulic structures as well as in wildlife management.

  14. [Mechanisms of viral emergence and interspecies transmission: the exemple of simian foamy viruses in Central Africa].

    Science.gov (United States)

    Gessain, Antoine

    2013-12-01

    A large proportion of viral pathogens that have emerged during the last decades in humans are considered to have originated from various animal species. This is well exemplified by several recent epidemics such as those of Nipah, Severe Acute Respiratory Syndrome, Avian flu, Ebola, Monkeypox, and Hantaviruses. After the initial interspecies transmission per se, the viruses can disseminate into the human population through various and distinct mechanisms. Some of them are well characterized and understood, thus allowing a certain level of risk control and prevention. Surprisingly and in contrast, the initial steps that lead to the emergence of several viruses, and of their associated diseases, remain still poorly understood. Epidemiological field studies conducted in certain specific high-risk populations are thus necessary to obtain new insights into the early events of this emergence process. Human infections by simian viruses represent increasing public health concerns. Indeed, by virtue of their genetic andphysiological similarities, non-human primates (NHPs) are considered to be likely the sources of viruses that can infect humans and thus may pose a significant threat to human population. This is well illustrated by retroviruses, which have the ability to cross species, adapt to a new host and sometimes spread within these new species. Sequence comparison and phylogenetic studies have thus clearly showed that the emergence of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in humans have resulted from several independent interspecies transmissions of different SIV types from Chimpanzees and African monkeys (including sooty mangabeys), respectively, probably during the first part of the last century. The situation for Human T cell Lymphotropic virus type 1 (HTLV-1) is, for certain aspects, quite comparable. Indeed, the origin of most HTLV-1 subtypes appears to be linked to interspecies transmission between STLV-1-infected monkeys and humans, followed by

  15. 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.

  16. Observation of direction-dependent mechanical properties in the human brain with multi-excitation MR elastography.

    Science.gov (United States)

    Anderson, Aaron T; Van Houten, Elijah E W; McGarry, Matthew D J; Paulsen, Keith D; Holtrop, Joseph L; Sutton, Bradley P; Georgiadis, John G; Johnson, Curtis L

    2016-06-01

    Magnetic resonance elastography (MRE) has shown promise in noninvasively capturing changes in mechanical properties of the human brain caused by neurodegenerative conditions. MRE involves vibrating the brain to generate shear waves, imaging those waves with MRI, and solving an inverse problem to determine mechanical properties. Despite the known anisotropic nature of brain tissue, the inverse problem in brain MRE is based on an isotropic mechanical model. In this study, distinct wave patterns are generated in the brain through the use of multiple excitation directions in order to characterize the potential impact of anisotropic tissue mechanics on isotropic inversion methods. Isotropic inversions of two unique displacement fields result in mechanical property maps that vary locally in areas of highly aligned white matter. Investigation of the corpus callosum, corona radiata, and superior longitudinal fasciculus, three highly ordered white matter tracts, revealed differences in estimated properties between excitations of up to 33%. Using diffusion tensor imaging to identify dominant fiber orientation of bundles, relationships between estimated isotropic properties and shear asymmetry are revealed. This study has implications for future isotropic and anisotropic MRE studies of white matter tracts in the human brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Emerging Collaboration Between Palliative Care Specialists and Mechanical Circulatory Support Teams: A Qualitative Study.

    Science.gov (United States)

    Sagin, Alana; Kirkpatrick, James N; Pisani, Barbara A; Fahlberg, Beth B; Sundlof, Annika L; O'Connor, Nina R

    2016-10-01

    Despite national requirements mandating collaboration between palliative care specialists and mechanical circulatory support (MCS) teams at institutions that place destination therapy ventricular assist devices, little is known about the nature of those collaborations or outcomes for patients and families. To assess how Centers for Medicare & Medicaid Services' regulations have changed collaboration between palliative care and MCS teams and how this collaboration is perceived by MCS team members. After obtaining verbal consent, members of MCS teams were interviewed using semistructured telephone interviews. Interviews were transcribed, and content was coded and analyzed using qualitative methods. Models for collaboration varied widely between institutions. Several expected themes emerged from interviews: 1) improvements over time in the relationship between palliative care specialists and MCS teams, 2) palliative care specialists as facilitators of advance care planning, and 3) referral to hospice and ventricular assist device deactivation as specific areas for collaboration. Several unexpected themes also emerged: 4) the emergence of dedicated heart failure palliative care teams, 5) palliative care specialists as impartial voices in decision making, 6) palliative care specialists as extra support for MCS team members, and 7) the perception of improved patient and family experiences with palliative care team exposure. Although the structure of collaboration varies between institutions, collaboration between MCS teams and palliative care specialists is increasing and often preceded the Centers for Medicare & Medicaid Services requirement. Overall impressions of palliative care specialists are highly positive, with perceptions of improved patient and family experience and decreased burden on MCS team members. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  19. A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.

    Directory of Open Access Journals (Sweden)

    Stefan Auer

    2008-11-01

    Full Text Available The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention because it has been associated with a range of neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate that the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Individual beta-sheets initially form with random orientations and subsequently tend to align into protofilaments as their lengths increase. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first-order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.

  20. Analyses of Entry Mechanisms of Novel Emerging Viruses Using Pseudotype VSV System.

    Science.gov (United States)

    Tani, Hideki

    2014-06-01

    Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.

  1. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.

    Directory of Open Access Journals (Sweden)

    Derek W Cain

    Full Text Available Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis.

  2. The emergence and evolution of life in a "fatty acid world" based on quantum mechanics.

    Science.gov (United States)

    Tamulis, Arvydas; Grigalavicius, Mantas

    2011-02-01

    Quantum mechanical based electron correlation interactions among molecules are the source of the weak hydrogen and Van der Waals bonds that are critical to the self-assembly of artificial fatty acid micelles. Life on Earth or elsewhere could have emerged in the form of self-reproducing photoactive fatty acid micelles, which gradually evolved into nucleotide-containing micelles due to the enhanced ability of nucleotide-coupled sensitizer molecules to absorb visible light. Comparison of the calculated absorption spectra of micelles with and without nucleotides confirmed this idea and supports the idea of the emergence and evolution of nucleotides in minimal cells of a so-called Fatty Acid World. Furthermore, the nucleotide-caused wavelength shift and broadening of the absorption pattern potentially gives these molecules an additional valuable role, other than a purely genetic one in the early stages of the development of life. From the information theory point of view, the nucleotide sequences in such micelles carry positional information providing better electron transport along the nucleotide-sensitizer chain and, in addition, providing complimentary copies of that information for the next generation. Nucleotide sequences, which in the first period of evolution of fatty acid molecules were useful just for better absorbance of the light in the longer wavelength region, later in the PNA or RNA World, took on the role of genetic information storage.

  3. Motor imagery based brain-computer interfaces: An emerging technology to rehabilitate motor deficits.

    Science.gov (United States)

    Alonso-Valerdi, Luz Maria; Salido-Ruiz, Ricardo Antonio; Ramirez-Mendoza, Ricardo A

    2015-12-01

    When the sensory-motor integration system is malfunctioning provokes a wide variety of neurological disorders, which in many cases cannot be treated with conventional medication, or via existing therapeutic technology. A brain-computer interface (BCI) is a tool that permits to reintegrate the sensory-motor loop, accessing directly to brain information. A potential, promising and quite investigated application of BCI has been in the motor rehabilitation field. It is well-known that motor deficits are the major disability wherewith the worldwide population lives. Therefore, this paper aims to specify the foundation of motor rehabilitation BCIs, as well as to review the recent research conducted so far (specifically, from 2007 to date), in order to evaluate the suitability and reliability of this technology. Although BCI for post-stroke rehabilitation is still in its infancy, the tendency is towards the development of implantable devices that encompass a BCI module plus a stimulation system. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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    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.

  5. Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model.

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    Tsung-Hsun Hsieh

    Full Text Available Traumatic brain injury (TBI is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.The acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.Gradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.We conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.

  6. Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology.

    Science.gov (United States)

    Kulbe, Jacqueline R; Hall, Edward D

    2017-11-01

    In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Emergency Department Visits for Traumatic Brain Injury in Older Adults in the United States: 2006-08

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    William S. Pearson

    2012-08-01

    Full Text Available Introduction: Traumatic brain injury (TBI can be complicated among older adults due to age-related frailty, a greater prevalence of chronic conditions and the use of anticoagulants. We conducted this study using the latest available, nationally-representative emergency department (ED data to characterize visits for TBI among older adults.Methods: We used the 2006-2008 National Hospital Ambulatory Medical Care – Emergency Department (NHAMCS-ED data to examine ED visits for TBI among older adults. Population-level estimates of triage immediacy, receipt of a head computed tomography (CT and/or head magnetic resonance imaging (MRI, and hospital admission by type were used to characterize 1,561 sample visits, stratified by age <65 and ≥65 years of age.Results: Of ED visits made by persons ≥65 years of age, 29.1% required attention from a physician within 15 minutes of arrival; 82.1% required a head CT, and 20.9% required hospitalization. Persons≥65 years of age were 3 times more likely to receive a head CT or MRI compared to younger patients presenting with TBI (adjusted odds ratio [aOR] 3.2; 95% confidence interval [CI], 1.8-5.8, and were 4 times more likely to be admitted to an intensive care unit, step-down unit, or surgery (aOR 4.1; 95% CI 2.1-8.0 compared to younger patients presenting with TBI, while controlling for sex and race.Conclusion: Results demonstrate increased emergent service delivery for older persons presenting with TBI. As the United States population ages and continues to grow, TBI will become an even more important public health issue that will place a greater demand on the healthcare system. [West J Emerg Med. 2012;13(3:289-293.

  8. 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…

  9. GOAL ORIENTED ANAESTHETIC MANAGEMENT OF A PREGNANT PATIENT WITH BRAIN TUMOR POSTED FOR EMERGENCY CAESARIAN SECTION AND V-P SHUNT

    OpenAIRE

    Dhanveer; Srinivas

    2014-01-01

    BACKGROUND AND OBJECTIVE: Pregnant women with brain tumors are uncommon; however pregnancy itself may aggravate the natural history of an intracranial tumor and may even unmask a previously unknown diagnosis. Small studies remain an important source of knowledge and experience and hence this study aims to highlight the major issues and provide an overview to the case of the pregnant patients with brain tumor posted for emergency caesarean section including pre-anaesthetic ...

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

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    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.

  11. 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 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. © 2015 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

  12. A survey regarding acceptability of oral emergency contraception according to the posited mechanism of action.

    Science.gov (United States)

    Willetts, S J; MacDougall, M; Cameron, S T

    2017-08-01

    The objective was to determine the acceptability to women of oral emergency contraception (EC) that works by inhibiting ovulation, preventing implantation or disrupting implantation, and also to determine the characteristics of women associated with the acceptability of each posited mechanism of action. Women completed a self-administered, anonymous questionnaire asking whether they would consider using an EC pill based on each of three hypothetical mechanisms of action: inhibiting ovulation, preventing implantation or disrupting implantation. The questionnaire was distributed among women in Edinburgh, UK, (a) presenting for EC at a community pharmacy, (b) attending a clinic for insertion of intrauterine contraception (IUC) or (c) attending a clinic for an induced abortion. Descriptive analyses stratified women according to healthcare setting and personal characteristics. Univariable and multivariable analyses were used to establish factors which may predict acceptability of each EC pill's mechanism of action. Four hundred and nineteen out of 458 (91%) women responded to the survey. Overall, women reported that EC would be acceptable if it worked by inhibiting ovulation (89%), preventing implantation (83%) or disrupting implantation (75%). Among women seeking abortion, more would accept an EC pill which disrupted implantation compared to women seeking IUC (odds ratio, 2.19; 95% confidence interval, 1.30-3.69; p=.004). Based on multivariable analyses, factors associated with acceptability included previous use of EC, previously holding strong views against abortion and having had a previous abortion. For each of the posited mechanisms of action, a majority of women surveyed would be willing to consider oral EC to prevent unintended pregnancy. The scope of the study was limited, and further work on the views of women in the wider population is needed. This is important as the development of such drugs to prevent pregnancy is likely to raise political and ethical

  13. 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.

  14. 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.

  15. Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

    Directory of Open Access Journals (Sweden)

    Dustin Anderson

    2017-01-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI, in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN, the globus pallidus pars interna (GPi, and to a lesser degree the ventral intermediate nucleus (VIM of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS.

  16. Working memory as an emergent property of the mind and brain.

    Science.gov (United States)

    Postle, B R

    2006-04-28

    Cognitive neuroscience research on working memory has been largely motivated by a standard model that arose from the melding of psychological theory with neuroscience data. Among the tenets of this standard model are that working memory functions arise from the operation of specialized systems that act as buffers for the storage and manipulation of information, and that frontal cortex (particularly prefrontal cortex) is a critical neural substrate for these specialized systems. However, the standard model has been a victim of its own success, and can no longer accommodate many of the empirical findings of studies that it has motivated. An alternative is proposed: Working memory functions arise through the coordinated recruitment, via attention, of brain systems that have evolved to accomplish sensory-, representation-, and action-related functions. Evidence from behavioral, neuropsychological, electrophysiological, and neuroimaging studies, from monkeys and humans, is considered, as is the question of how to interpret delay-period activity in the prefrontal cortex.

  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. The Coherent Heart: Heart–Brain Interactions, Psychophysiological Coherence, and the Emergence of System-Wide Order

    Directory of Open Access Journals (Sweden)

    Rollin McCraty

    2009-12-01

    Full Text Available This article presents theory and research on the scientific study of emotion that emphasizes the importance of coherence as an optimal psychophysiological state. A dynamic systems view of the interrelations between psychological, cognitive and emotional systems and neural communication networks in the human organism provides a foundation for the view presented. These communication networks are examined from an information processing perspective and reveal a fundamental order in heart-brain interactions and a harmonious synchronization of physiological systems associated with positive emotions. The concept of coherence is drawn on to understand optimal functioning which is naturally reflected in the heart’s rhythmic patterns. Research is presented identifying various psychophysiological states linked to these patterns, with neurocardiological coherence emerging as having significant impacts on well being. These include psychophysiological as well as improved cognitive performance. From this, the central role of the heart is explored in terms of biochemical, biophysical and energetic interactions. Appendices provide further details and research on; psychophysiological functioning, reference previous research in this area, details on research linking coherence with optimal cognitive performance, heart brain synchronization and the energetic signature of the various psychophysiological modes.

  19. 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].

  20. 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.

  1. Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism

    Science.gov (United States)

    The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of m...

  2. Mechanism of Action of Ulipristal Acetate for Emergency Contraception: A Systematic Review

    Science.gov (United States)

    Rosato, Elena; Farris, Manuela; Bastianelli, Carlo

    2016-01-01

    Ulipristal acetate (UPA) is now recommended as first choice hormonal emergency contraception (EC), due to its higher efficacy and similar safety compared to Levonorgestrel – 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 concurs in excluding a post-fertilization effect of UPA, even though more studies are needed to clarify its mechanism of action. PMID:26793107

  3. Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014.

    Science.gov (United States)

    Liang, Wen-Juan; Liu, Hui-Ying; Duan, Guang-Cai; Zhao, Yong-Xin; Chen, Shuai-Yin; Yang, Hai-Yan; Xi, Yuan-Lin

    2017-10-26

    The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli) strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of bla NDM was 80% (4/5). The sequencing results showed that two isolates belonged to bla NDM-1 whereas other 2 isolates carried the bla NDM-5. Other carbapenemase genes including bla IMP , bla VIM , bla KPC and bla OXA-48 were not detected. The bla CTX-M-15, bla TEM-1, sul2, aad, and aac(6")-Ib-cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated bla NDM could be transferred. In conclusion, the bla NDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China. Copyright © 2017. Published by Elsevier Ltd.

  4. 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.

  5. Adaptive mechanisms of developing brain. The neuroradiologic assessment of the preterm infant.

    Science.gov (United States)

    Ment, L R; Schneider, K C; Ainley, M A; Allan, W C

    2000-06-01

    . Research aimed at discovering etiologies and mechanisms of brain injury in these high-risk infants should use the more sensitive modality MR imaging. Finally, the interesting observation that preterm infants fare as well as they do despite MR imaging-identified lesions might stimulate research studying the adaptive mechanisms of developing brain.

  6. The role of an endogenous amnesic mechanism mediated by brain beta-endorphin in memory modulation.

    Science.gov (United States)

    Izquierdo, I

    1982-07-01

    1. Post-training administration of the opiate receptor antagonist naloxone facilitates the memory consolidation of a wide variety of tasks by rats. 2. Post-training administration of subanalgesic doses of beta-endorphin causes retrograde amnesia. This effect is shared by other opiates and opioids and is competitively antagonized by naloxone. These other opiates and opioids probably act by the release of endogenous beta-endorphin. 3. During various forms of aversive and non-aversive training beta-endorphin (but not Met-enkephalin) is released in the rat brain in amounts compatible with amnestic doses of this substance. 4. A number of treatments that cause naloxone-reversible retrograde amnesia, i.e. high doses of ACTH or adrenaline, low doses of morphine or of opioids, electroconvulsive shock, release massive amounts of beta-endorphin and Met-enkephalin in the rat brain. 5. These findings point to the existence of a physiological amnesic mechanism mediated by beta-endorphin, and perhaps other opioids as well, that normally prevents memory from being as good as it could be, and when operating at an exaggerated level may cause complete amnesia. 6. This mechanism interacts with other systems that influence memory consolidation (central dopaminergic and noradrenergic pathways, ACTH, peripheral adrenaline) and is a powerful modulator of their activity. 7. One possible role of the amnesic mechanism during training is to cause the rapid forgetting of adventitious learning that may interfere with acquisition of the main tasks for which animals are being trained. 8. Either through this action, or by some direct effect, beta-endorphin facilitates retrieval of a variety of behaviors in the rat when given before a test session.

  7. 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

    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......) 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...

  8. Integrating Classical with Emerging Concepts for Better Understanding of Salinity Stress Tolerance Mechanisms in Rice

    Directory of Open Access Journals (Sweden)

    Navdeep Kaur

    2017-07-01

    Full Text Available Rice is an important cereal crop responsible for world's food security. The sensitivity of rice plants toward a range of abiotic stresses is a prime challenge for its overall growth and productivity. Among these, salinity is a major stress which results in a significant loss of global rice yield annually. For finding straightforward and strict future solutions in order to assure the food security to growing world population, understanding of the various mechanisms responsible for salt stress tolerance in rice is of paramount importance. In classical studies, identification of salt tolerant cultivars and the genetic markers linked to salt tolerance and breeding approaches have been given emphasis. It further affirmed on the identification of various pathways regulating the complex process of salt stress adaptation. However, only limited success has been achieved in these approaches as salt tolerance is a complex process and is governed by multiple factors. Hence, for better understanding of salt tolerance mechanisms, a comprehensive approach involving physiological, biochemical and molecular studies is much warranted. Modern experimental and genetic resources have provided a momentum in this direction and have provided molecular insights into different salt stress responsive pathways at the signaling and regulatory level. The integrative knowledge of classical and modern research of the understanding of salt stress adaptive pathways can help the researchers for designing effective strategies to fight against salt stress. Hence, the present review is focused on the understanding of the salt stress tolerance mechanisms in rice through the consolidative knowledge of classical and modern concepts. It further highlights the emerging new trends of salt stress adaptive pathways in rice.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  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. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Examining Emergency Department Treatment Processes in Severe Pediatric Traumatic Brain Injury.

    Science.gov (United States)

    Ajdari, Ali; Boyle, Linda Ng; Kannan, Nithya; Rowhani-Rahbar, Ali; Wang, Jin; Mink, Richard; Ries, Benjamin; Wainwright, Mark; Groner, Jonathan I; Bell, Michael J; Giza, Chris; Zatzick, Douglas F; Ellenbogen, Richard G; Mitchell, Pamela H; Rivara, Frederick P; Vavilala, Monica S

    2017-02-03

    In the treatment of pediatric traumatic brain injury (TBI), timely treatment of patients can affect the outcome. Our objectives were to examine the treatment process of acute pediatric TBI and the impact of non-value-added time (NVAT) on patient outcomes. Data for 136 pediatric trauma patients (age value stream map identified NVATs and their sources in the treatment process. Cluster and regression analysis were used to examine the relationship between NVAT, as a percentage of the patient's length of stay (LOS), and the patient outcome, measured by their corresponding Glasgow outcome scale. There were 14 distinct sources of NVAT identified. A regression analysis showed that increased NVAT was associated with less favorable outcomes (relative ratio = 1.015, confidence interval = [1.002-1.029]). Specifically, 1% increase in the NVAT-to-LOS ratio was associated with a 1.5% increase in the chance of a less favorable outcome (i.e., death or vegetative state). The NVAT has a significant impact on the outcome of pediatric TBI, and every minute spent on performing non-value-added processes can lead to an increase in the likelihood of less favorable outcomes.

  13. 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

  14. Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain.

    Science.gov (United States)

    Andriani, Grasiella A; Vijg, Jan; Montagna, Cristina

    2017-01-01

    Aneuploidy and polyploidy are a form of Genomic Instability (GIN) known as Chromosomal Instability (CIN) characterized by sporadic abnormalities in chromosome copy numbers. Aneuploidy is commonly linked to pathological states. It is a hallmark of spontaneous abortions and birth defects and it is observed virtually in every human tumor, therefore being generally regarded as detrimental for the development or the maturation of tissues under physiological conditions. Polyploidy however, occurs as part of normal physiological processes during maturation and differentiation of some mammalian cell types. Surprisingly, high levels of aneuploidy are present in the brain, and their frequency increases with age suggesting that the brain is able to maintain its functionality in the presence of high levels of mosaic aneuploidy. Because somatic aneuploidy with age can reach exceptionally high levels, it is likely to have long-term adverse effects in this organ. We describe the mechanisms accountable for an abnormal DNA content with a particular emphasis on the CNS where cell division is limited. Next, we briefly summarize the types of GIN known to date and discuss how they interconnect with CIN. Lastly we highlight how several forms of CIN may contribute to genetic variation, tissue degeneration and disease in the CNS. Copyright © 2016. Published by Elsevier B.V.

  15. 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.

  16. Glucosylceramide and glucosylsphingosine modulate calcium mobilization from brain microsomes via different mechanisms.

    Science.gov (United States)

    Lloyd-Evans, Emyr; Pelled, Dori; Riebeling, Christian; Bodennec, Jacques; de-Morgan, Aviv; Waller, Helen; Schiffmann, Raphael; Futerman, Anthony H

    2003-06-27

    We recently demonstrated that elevation of intracellular glucosylceramide (GlcCer) levels results in increased functional Ca2+ stores in cultured neurons, and suggested that this may be due to modulation of ryanodine receptors (RyaRs) by GlcCer (Korkotian, E., Schwarz, A., Pelled, D., Schwarzmann, G., Segal, M. and Futerman, A. H. (1999) J. Biol. Chem. 274, 21673-21678). We now systematically examine the effects of exogenously added GlcCer, other glycosphingolipids (GSLs) and their lyso-derivatives on Ca2+ release from rat brain microsomes. GlcCer had no direct effect on Ca2+ release, but rather augmented agonist-stimulated Ca2+ release via RyaRs, through a mechanism that may involve the redox sensor of the RyaR, but had no effect on Ca2+ release via inositol 1,4,5-trisphosphate receptors. Other GSLs and sphingolipids, including galactosylceramide, lactosylceramide, ceramide, sphingomyelin, sphingosine 1-phosphate, sphinganine 1-phosphate, and sphingosylphosphorylcholine had no effect on Ca2+ mobilization from rat brain microsomes, but both galactosylsphingosine (psychosine) and glucosylsphingosine stimulated Ca2+ release, although only galactosylsphingosine mediated Ca2+ release via the RyaR. Finally, we demonstrated that GlcCer levels were approximately 10-fold higher in microsomes prepared from the temporal lobe of a type 2 Gaucher disease patient compared with a control, and Ca2+ release via the RyaR was significantly elevated, which may be of relevance for explaining the pathophysiology of neuronopathic forms of Gaucher disease.

  17. Perinatal White Matter Injury: The Changing Spectrum of Pathology and Emerging Insights into Pathogenetic Mechanisms

    Science.gov (United States)

    Back, Stephen A.

    2006-01-01

    Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal…

  18. Mapping the mechanical heterogeneity of the brain, and why this matters (Conference Presentation)

    Science.gov (United States)

    Guck, Jochen R.

    2017-02-01

    It is increasingly recognized that cells measure and respond to the mechanics of their environment. We are especially interested in this mechanosensing during CNS development and pathologies. Using quantitative scanning force microscopy we have shown that various neural tissues are very compliant (shear modulus root of foreign body reactions. Also oligodendrocytes are mechanosensitive as their survival, proliferation, migration, and differentiation capacity in vitro depend on substrate stiffness. This finding might be linked to the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis. And finally, we have also shown retinal ganglion axon pathfinding in the early embryonic Xenopus brain development to be instructed by stiffness gradients. These results form the basis for further investigations into the mechanobiology of cell function in the CNS. Ultimately, this research could help treating previously incurable neuropathologies such as spinal cord injuries and neurodegenerative disorders.

  19. 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.

  20. 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. Published by Elsevier Inc.

  1. Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emerging Role of Lipin-1

    Science.gov (United States)

    You, Min; Jogasuria, Alvin; Lee, Kwangwon; Wu, Jiashin; Zhang, Yanqiao; Lee, Yoon Kwang; Sadana, Prabodh

    2016-01-01

    Lipin-1, a mammalian phosphatidic acid phosphatase (PAP), is a bi-functional molecule involved in various signaling pathways via its function as a PAP enzyme in the triglyceride synthesis pathway and in the nucleus as a transcriptional co-regulator. In the liver, lipin-1 is known to play a vital role in controlling the lipid metabolism and inflammation process at multiple regulatory levels. Alcoholic fatty liver disease (AFLD) is one of the earliest forms of liver injury and approximately 8–20% of patients with simple steatosis can develop into more severe forms of liver injury, including steatohepatitis, fibrosis/cirrhosis, and eventually hepatocellular carcinoma (HCC). The signal transduction mechanisms for alcohol-induced detrimental effects in liver involves alteration of complex and multiple signaling pathways largely governed by a central and upstream signaling system, namely, sirtuin 1 (SIRT1)-AMP activated kinase (AMPK) axis. Emerging evidence suggests a pivotal role of lipin-1 as a crucial downstream regulator of SIRT1-AMPK signaling system that is likely to be ultimately responsible for development and progression of AFLD. Several lines of evidence demonstrate that ethanol exposure significantly induces lipin-1 gene and protein expression levels in cultured hepatocytes and in the livers of rodents, induces lipin-1-PAP activity, impairs the functional activity of nuclear lipin-1, disrupts lipin-1 mRNA alternative splicing and induces lipin-1 nucleocytoplasmic shuttling. Such impairment in response to ethanol leads to derangement of hepatic lipid metabolism, and excessive production of inflammatory cytokines in the livers of the rodents and human alcoholics. This review summarizes current knowledge about the role of lipin-1 in the pathogenesis of AFLD and its potential signal transduction mechanisms. PMID:26278388

  2. When is a Physical Concept born? The Emergence of `Work' as a Magnitude of Mechanics

    Science.gov (United States)

    Kanderakis, Nikos Emmanouil

    2010-10-01

    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 related to the work and the effectiveness of the motor engines. In both activities, the products ‘weight (or force) multiplied by height (or displacement)’ were used for calculations. Can we regard that these products constitute a well defined physical magnitude and are anticipations of the magnitude ‘work’? Modern historians of science assert that ‘work’, as a magnitude of mechanics, was created in France, at the beginning of the nineteenth century. Why? In order to examine these issues, a brief survey into the history of the relevant ideas will be done, and a number of characteristics, acquired by the magnitude of ‘work’ through the historical process of its construction, will be presented. These characteristics may help to depict a magnitude, in general, which is autonomous and embedded in a physical theory. Finally, from the historical data concerning the history of ‘work’, some educational implications will be considered.

  3. Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis.

    Science.gov (United States)

    Alvarez-Dominguez, Juan R; Lodish, Harvey F

    2017-09-19

    Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels. Here we review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. We focus on a growing number of mechanistic studies to synthesize emerging principles of lncRNA function, emphasizing how they facilitate diversification of gene programming during development. We also survey how disrupted lncRNA function can contribute to malignant transformation, highlighting opportunities for therapeutic intervention in specific myeloid and lymphoid cancers. Finally, we discuss challenges and prospects for further elucidation of lncRNA mechanisms. Copyright © 2017 American Society of Hematology.

  4. Mechanisms Underlying the Emergence of Post-acidosis Arrhythmia at the Tissue Level: A Theoretical Study

    Science.gov (United States)

    Bai, Jieyun; Yin, Renli; Wang, Kuanquan; Zhang, Henggui

    2017-01-01

    Acidosis has complex electrophysiological effects, which are associated with a high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer modeling, this study investigated the mechanisms underlying the emergence of post-acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov ventricular model was modified to incorporate various data on acidosis-induced alterations of cellular electrophysiology and intercellular electrical coupling. The single cell models were incorporated into multicellular one-dimensional (1D) fiber and 2D sheet tissue models. Electrophysiological effects were quantified as changes of action potential profile, sink-source interactions of fiber tissue, and the vulnerability of tissue to the genesis of unidirectional conduction that led to initiation of re-entry. It was shown that acidosis-induced sarcoplasmic reticulum (SR) calcium load contributed to delayed afterdepolarizations (DADs) in single cells. These DADs may be synchronized to overcome the source-sink mismatch arising from intercellular electrotonic coupling, and produce a premature ventricular complex (PVC) at the tissue level. The PVC conduction can be unidirectionally blocked in the transmural ventricular wall with altered electrical heterogeneity, resulting in the genesis of re-entry. In conclusion, altered source-sink interactions and electrical heterogeneity due to acidosis-induced cellular electrophysiological alterations may increase susceptibility to post-acidosis ventricular arrhythmias. PMID:28424631

  5. Current and Emerging Treatments for Postsurgical Cleft Lip Scarring: Effectiveness and Mechanisms.

    Science.gov (United States)

    Papathanasiou, E; Trotman, C A; Scott, A R; Van Dyke, T E

    2017-11-01

    Cleft lip with or without cleft palate is the most common congenital malformation of the head and the third-most common birth defect. Surgical repair of the lip is the only treatment and is usually performed during the first year of life. Hypertrophic scar (HTS) formation is a frequent postoperative complication that impairs soft tissue form, function, or movement. Multiple lip revision operations are often required throughout childhood, attempting to optimize aesthetics and function. The mechanisms guiding HTS formation are multifactorial and complex. HTS is the result of dysregulated wound healing, where excessive collagen and extracellular matrix proteins are deposited within the wound area, resulting in persistent inflammation and resultant fibrosis. Many studies support the contribution of dysregulated, exaggerated inflammation in scar formation. Fibrosis and scarring result from chronic inflammation that interrupts tissue remodeling in normal wound healing. Failure of active resolution of inflammation pathways has been implicated. The management of HTS has been challenging for clinicians, since current therapies are minimally effective. Emerging evidence that specialized proresolving mediators of inflammation accelerate wound healing by preventing chronic inflammation and allowing natural uninterrupted tissue remodeling suggests new therapeutic opportunities in the prevention and management of HTS.

  6. 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

  7. Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis.

    Science.gov (United States)

    Peng, Wenjing; Zhang, Yu; Zhu, Rui; Mechref, Yehia

    2017-09-01

    Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label-free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label-free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up-regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down-regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up-regulation of integrin proteins and down-regulation of EPHA2 in brain metastasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Emergency Department Triage of Traumatic Head Injury Using a Brain Electrical Activity Biomarker: A Multisite Prospective Observational Validation Trial.

    Science.gov (United States)

    Hanley, Daniel; Prichep, Leslie S; Bazarian, Jeffrey; Huff, J Stephen; Naunheim, Rosanne; Garrett, John; Jones, Elizabeth B; Wright, David W; O'Neill, John; Badjatia, Neeraj; Gandhi, Dheeraj; Curley, Kenneth C; Chiacchierini, Richard; O'Neil, Brian; Hack, Dallas C

    2017-05-01

    A brain electrical activity biomarker for identifying traumatic brain injury (TBI) in emergency department (ED) patients presenting with high Glasgow Coma Scale (GCS) after sustaining a head injury has shown promise for objective, rapid triage. The main objective of this study was to prospectively evaluate the efficacy of an automated classification algorithm to determine the likelihood of being computed tomography (CT) positive, in high-functioning TBI patients in the acute state. Adult patients admitted to the ED for evaluation within 72 hours of sustaining a closed head injury with GCS 12 to 15 were candidates for study. A total of 720 patients (18-85 years) meeting inclusion/exclusion criteria were enrolled in this observational, prospective validation trial, at 11 U.S. EDs. GCS was 15 in 97%, with the first and third quartiles being 15 (interquartile range = 0) in the study population at the time of the evaluation. Standard clinical evaluations were conducted and 5 to 10 minutes of electroencephalogram (EEG) was acquired from frontal and frontal-temporal scalp locations. Using an a priori derived EEG-based classification algorithm developed on an independent population and applied to this validation population prospectively, the likelihood of each subject being CT+ was determined, and performance metrics were computed relative to adjudicated CT findings. Sensitivity of the binary classifier (likely CT+ or CT-) was 92.3% (95% confidence interval [CI] = 87.8%-95.5%) for detection of any intracranial injury visible on CT (CT+), with specificity of 51.6% (95% CI = 48.1%-55.1%) and negative predictive value (NPV) of 96.0% (95% CI = 93.2%-97.9%). Using ternary classification (likely CT+, equivocal, likely CT-) demonstrated enhanced sensitivity to traumatic hematomas (≥1 mL of blood), 98.6% (95% CI = 92.6%-100.0%), and NPV of 98.2% (95% CI = 95.5%-99.5%). Using an EEG-based biomarker high accuracy of predicting the likelihood of being CT+ was obtained, with

  9. 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

    2012-01-01

    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 hypoxicischemic-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 for brain disorders. PMID:22627492

  10. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Pediatric Emergency Care Applied Research Network (PECARN) prediction rules in identifying high risk children with mild traumatic brain injury.

    Science.gov (United States)

    Nakhjavan-Shahraki, B; Yousefifard, M; Hajighanbari, M J; Oraii, A; Safari, S; Hosseini, M

    2017-06-22

    Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) prognostic rules is a scoring system for prediction of the need for computed tomography (CT) scanning in children with mild TBI. However, its validation has not been assessed in developing countries. Therefore, the present study was designed to assess the value of PECARN rule in identification of children with clinically important TBI (ciTBI). In this prospective cross-sectional study, 594 children (mean age: 7.9 ± 5.3 years; 79.3% boys) with mild TBI brought to emergency ward of two healthcare centers in Tehran, Iran were assessed. PECARN checklist was filled for all patients and children were divided to three groups of low, intermediate and high risks. Patients were followed for 2 weeks by phone to assess their ciTBI status. At the end, discrimination power, calibration and overall performance of PECARN rule were assessed. PECARN had a sensitivity and specificity of 92.3 and 40.6%, respectively, in predicting ciTBI in children under 2 years and 100.0 and 57.8%, respectively, in individuals between the ages of 2 and 18. PECARN rule had a proper calibration in prediction of ciTBI and CT scan findings. Brier score (overall performance) of PECARN rule in predicting ciTBI in children under 2 and 2-18 years were 1.5 and 1.2, respectively. PECARN prediction rule has a proper validity in the prediction of ciTBI. Therefor it can be used for screening and identification of high risk children with mild TBI.

  13. 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

  14. 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

  15. 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.

  16. Neurobiological mechanisms associated with facial affect recognition deficits after traumatic brain injury.

    Science.gov (United States)

    Neumann, Dawn; McDonald, Brenna C; West, John; Keiski, Michelle A; Wang, Yang

    2016-06-01

    The neurobiological mechanisms that underlie facial affect recognition deficits after traumatic brain injury (TBI) have not yet been identified. Using functional magnetic resonance imaging (fMRI), study aims were to 1) determine if there are differences in brain activation during facial affect processing in people with TBI who have facial affect recognition impairments (TBI-I) relative to people with TBI and healthy controls who do not have facial affect recognition impairments (TBI-N and HC, respectively); and 2) identify relationships between neural activity and facial affect recognition performance. A facial affect recognition screening task performed outside the scanner was used to determine group classification; TBI patients who performed greater than one standard deviation below normal performance scores were classified as TBI-I, while TBI patients with normal scores were classified as TBI-N. An fMRI facial recognition paradigm was then performed within the 3T environment. Results from 35 participants are reported (TBI-I = 11, TBI-N = 12, and HC = 12). For the fMRI task, TBI-I and TBI-N groups scored significantly lower than the HC group. Blood oxygenation level-dependent (BOLD) signals for facial affect recognition compared to a baseline condition of viewing a scrambled face, revealed lower neural activation in the right fusiform gyrus (FG) in the TBI-I group than the HC group. Right fusiform gyrus activity correlated with accuracy on the facial affect recognition tasks (both within and outside the scanner). Decreased FG activity suggests facial affect recognition deficits after TBI may be the result of impaired holistic face processing. Future directions and clinical implications are discussed.

  17. 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. 2013 APA, all rights reserved

  18. 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

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

    Directory of Open Access Journals (Sweden)

    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

  20. Emergence of modular structure in a large-scale brain network with interactions between dynamics and connectivity

    Directory of Open Access Journals (Sweden)

    Cornelis Jan Stam

    2010-09-01

    Full Text Available A network of 32 or 64 connected neural masses, each representing a large population of interacting excitatory and inhibitory neurons and generating an EEG / MEG like output signal, was used to demonstrate how an interaction between dynamics and connectivity might explain the emergence of complex network features, in particular modularity. Network evolution was modeled by two processes: (i synchronization dependent plasticity (SDP and (ii growth dependent plasticity (GDP. In the case of SDP, connections between neural masses were strengthened when they were strongly synchronized, and were weakened when they were not. GDP was modeled as a homeostatic process with random, distance dependent outgrowth of new connections between neural masses. GDP alone resulted in stable networks with distance dependent connection strengths, typical small-world features, but no degree correlations and only weak modularity. SDP applied to random networks induced clustering, but no clear modules. Stronger modularity evolved only through an interaction of SDP and GDP, with the number and size of the modules depending on the relative strength of both processes, as well as on the size of the network. Lesioning part of the network, after a stable state was achieved, resulted in a temporary disruption of the network structure. The model gives a possible scenario to explain how modularity can arise in developing brain networks, and makes predictions about the time course of network changes during development and following acute lesions.

  1. Emergence of Modular Structure in a Large-Scale Brain Network with Interactions between Dynamics and Connectivity.

    Science.gov (United States)

    Stam, Cornelis J; Hillebrand, Arjan; Wang, Huijuan; Van Mieghem, Piet

    2010-01-01

    A network of 32 or 64 connected neural masses, each representing a large population of interacting excitatory and inhibitory neurons and generating an electroencephalography/magnetoencephalography like output signal, was used to demonstrate how an interaction between dynamics and connectivity might explain the emergence of complex network features, in particular modularity. Network evolution was modeled by two processes: (i) synchronization dependent plasticity (SDP) and (ii) growth dependent plasticity (GDP). In the case of SDP, connections between neural masses were strengthened when they were strongly synchronized, and were weakened when they were not. GDP was modeled as a homeostatic process with random, distance dependent outgrowth of new connections between neural masses. GDP alone resulted in stable networks with distance dependent connection strengths, typical small-world features, but no degree correlations and only weak modularity. SDP applied to random networks induced clustering, but no clear modules. Stronger modularity evolved only through an interaction of SDP and GDP, with the number and size of the modules depending on the relative strength of both processes, as well as on the size of the network. Lesioning part of the network, after a stable state was achieved, resulted in a temporary disruption of the network structure. The model gives a possible scenario to explain how modularity can arise in developing brain networks, and makes predictions about the time course of network changes during development and following acute lesions.

  2. Different brain mechanisms between stereotype activation and application: evidence from an ERP study.

    Science.gov (United States)

    Jia, Lei; Dickter, Cheryl L; Luo, Junlong; Xiao, Xiao; Yang, Qun; Lei, Ming; Qiu, Jiang; Zhang, Qinglin

    2012-01-01

    Stereotyping involves two processes in which first, social stereotypes are activated (stereotype activation), and then, stereotypes are applied to given targets (stereotype application). Previous behavioral studies have suggested that these two processes are independent of each other and may have different mechanisms. As few psychophysiological studies have given an integrated account of these stages in stereotyping so far, this study utilized a trait categorization task in which event-related potentials (ERPs) were used to explore the brain mechanisms associated with the processes of stereotype activation and its application. The behavioral (reaction time) and electrophysiological data showed that stereotype activation and application were elicited respectively in an affective valence identification subtask and in a semantic content judgment subtask. The electrophysiological results indicated that the categorization processes involved in stereotype activation to quickly identify stereotypic and nonstereotypic information were quite different from those involved in the application. During the process of stereotype activation, a P2 and N2 effect was observed, indicating that stereotype activation might be facilitated by an early attentional bias. Also, a late positive potential (LPP) was elicited, suggesting that social expectancy violation might be involved. During the process of the stereotype application, electrophysiological data showed a P2 and P3 effect, indicating that stereotype application might be related to the rapid social knowledge identification in semantic representation and thus may be associated with an updating of existing stereotypic contents or a motivation to resolve the inconsistent information. This research strongly suggested that different mechanisms are involved in the stereotype activation and application processes.

  3. Lyso-glycosphingolipids mobilize calcium from brain microsomes via multiple mechanisms.

    Science.gov (United States)

    Lloyd-Evans, Emyr; Pelled, Dori; Riebeling, Christian; Futerman, Anthony H

    2003-11-01

    Recently, we demonstrated that the GSL (glycosphingolipid), GlcCer (glucosylceramide), modulates Ca2+ release from intracellular stores and from microsomes by sensitizing the RyaR (ryanodine receptor), a major Ca2+-release channel of the endoplasmic reticulum, whereas the lyso derivative of GlcCer, namely GlcSph (glucosylsphingosine), induced Ca2+ release via a mechanism independent of the RyaR [Lloyd-Evans, Pelled, Riebeling, Bodennec, de-Morgan, Waller, Schiffmann and Futerman (2003) J. Biol. Chem. 278, 23594-23599]. We now systematically examine the mechanism by which GlcSph and other lyso-GSLs modulate Ca2+ mobilization from rat brain cortical and cerebellar microsomes. GlcSph, lactosylsphingosine and galactosylsphingosine all mobilized Ca2+, but at significantly higher concentrations than those required for GlcCer-mediated sensitization of the RyaR. GlcSph-induced Ca2+ mobilization was partially blocked by heparin, an inhibitor of the Ins(1,4,5) P3 receptor, and also partially blocked by thapsigargin or ADP, inhibitors of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), but completely blocked when both acted together. In contrast, neither lactosylsphingosine nor galactosylsphingosine had any effect on Ca2+ release via either the Ins(1,4,5) P3 receptor or SERCA, but acted as agonists of the RyaR. Finally, and surprisingly, all three lyso-GSLs reversed inhibition of SERCA by thapsigargin. We conclude that different lyso-GSLs modulate Ca2+ mobilization via different mechanisms, and discuss the relevance of these findings to the GSL storage diseases in which lyso-GSLs accumulate.

  4. Quality and consistency of guidelines for the management of mild traumatic brain injury in the emergency department.

    Science.gov (United States)

    Tavender, Emma J; Bosch, Marije; Green, Sally; O'Connor, Denise; Pitt, Veronica; Phillips, Kate; Bragge, Peter; Gruen, Russell L

    2011-08-01

    The objective was to provide an overview of the recommendations and quality of evidence-based clinical practice guidelines (CPGs) for the emergency management of mild traumatic brain injury (mTBI), with a view to informing best practice and improving the consistency of recommendations. Electronic searches of health databases (MEDLINE, EMBASE, The Cochrane Library, PsycINFO), CPG clearinghouse websites, CPG developer websites, and Internet search engines up to January 2010 were conducted. CPGs were included if 1) they were published in English and freely accessible, 2) their scope included the management of mTBI in the emergency department (ED), 3) the date of last search was within the past 10 years (2000 onward), 4) systematic methods were used to search for evidence, and 5) there was an explicit link between the recommendations and the supporting evidence. Four authors independently assessed the quality of the included CPGs using the Appraisal of Guidelines, Research and Evaluation (AGREE) Instrument. The authors extracted and categorized recommendations according to initial clinical assessment, imaging, management, observation, discharge planning, and patient information and follow-up. The search identified 18 potential CPGs, of which six met the inclusion criteria. The included CPGs varied in scope, target population, size, and guideline development processes. Four CPGs were assessed as "strongly recommended." The majority of CPGs did not provide information about the level of stakeholder involvement (mean AGREE standardized domain score = 57%, range = 25% to 81%), nor did they address the organizational/cost implications of applying the recommendations or provide criteria for monitoring and review of recommendations in practice (mean AGREE standardized domain score = 46.6%, range = 19% to 94%). Recommendations were mostly consistent in terms of the use of the Glasgow Coma Scale (GCS) score (adult and pediatric) to assess the level of consciousness, initial

  5. A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

    Science.gov (United States)

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

    2017-09-01

    Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

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

    Directory of Open Access Journals (Sweden)

    Dana eRabinovich

    2015-08-01

    Full Text Available 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.

  7. 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.

  8. Evaluation of Seed Emergence Uniformity of Mechanically Sown Wheat with UAV RGB Imagery

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2017-12-01

    Full Text Available The uniformity of wheat seed emergence is an important characteristic used to evaluate cultivars, cultivation mode and field management. Currently, researchers typically investigated the uniformity of seed emergence by manual measurement, a time-consuming and laborious process. This study employed field RGB images from unmanned aerial vehicles (UAVs to obtain information related to the uniformity of wheat seed emergence and missing seedlings. The calculation of the length of areas with missing seedlings in both drill and broadcast sowing can be achieved by using an area localization algorithm, which facilitated the comprehensive evaluation of uniformity of seed emergence. Through a comparison between UAV images and the results of manual surveys used to gather data on the uniformity of seed emergence, the root-mean-square error (RMSE was 0.44 for broadcast sowing and 0.64 for drill sowing. The RMSEs of the numbers of missing seedling regions for broadcast and drill sowing were 1.39 and 3.99, respectively. The RMSEs of the lengths of the missing seedling regions were 12.39 cm for drill sowing and 0.20 cm2 for broadcast sowing. The UAV image-based method provided a new and greatly improved method for efficiently measuring the uniformity of wheat seed emergence. The proposed method could provide a guideline for the intelligent evaluation of the uniformity of wheat seed emergence.

  9. Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients.

    Science.gov (United States)

    Korovesi, I; Kotanidou, A; Papadomichelakis, E; Livaditi, O; Sotiropoulou, C; Koutsoukou, A; Marczin, N; Orfanos, S E

    2016-03-02

    The inflammatory influence and biological markers of prolonged mechanical-ventilation in uninjured human lungs remains controversial. We investigated exhaled nitric oxide (NO) and carbon monoxide (CO) in mechanically-ventilated, brain-injured patients in the absence of lung injury or sepsis at two different levels of positive end-expiratory pressure (PEEP). Exhaled NO and CO were assessed in 27 patients, without lung injury or sepsis, who were ventilated with 8 ml kg(-1) tidal volumes under zero end-expiratory pressure (ZEEP group, n  =  12) or 8 cm H2O PEEP (PEEP group, n  =  15). Exhaled NO and CO was analysed on days 1, 3 and 5 of mechanical ventilation and correlated with previously reported markers of inflammation and gas exchange. Exhaled NO was higher on day 3 and 5 in both patient groups compared to day 1: (PEEP group: 5.8 (4.4-9.7) versus 11.7 (6.9-13.9) versus 10.7 (5.6-16.6) ppb (p  <  0.05); ZEEP group: 5.3 (3.8-8.8) versus 9.8 (5.3-12.4) versus 9.6 (6.2-13.5) ppb NO peak levels for days 1, 3 and 5, respectively, p  <  0.05). Exhaled CO remained stable on day 3 but significantly decreased by day 5 in the ZEEP group only (6.3 (4.3-9.0) versus 8.1 (5.8-12.1) ppm CO peak levels for day 5 versus 1, p  <  0.05). The change scores for peak exhaled CO over day 1 and 5 showed significant correlations with arterial blood pH and plasma TNF levels (r s  =  0.49, p  =  0.02 and r s  =  -0.51 p  =  0.02, respectively). Exhaled NO correlated with blood pH in the ZEEP group and with plasma levels of IL-6 in the PEEP group. We observed differential changes in exhaled NO and CO in mechanically-ventilated patients even in the absence of manifest lung injury or sepsis. These may suggest subtle pulmonary inflammation and support application of real time breath analysis for molecular monitoring in critically ill patients.

  10. Research and Improvement on Characteristics of Emergency Diesel Generating Set Mechanical Support System in Nuclear Power Plant

    Science.gov (United States)

    Zhe, Yang

    2017-06-01

    There are often mechanical problems of emergency power generation units in nuclear power plant, which bring a great threat to nuclear safety. Through analyzing the influence factors caused by mechanical failure, the existing defects of the design of mechanical support system are determined, and the design idea has caused the direction misleading in the field of maintenance and transformation. In this paper, research analysis is made on basic support design of diesel generator set, main pipe support design and important components of supercharger support design. And this paper points out the specific design flaws and shortcomings, and proposes targeted improvement program. Through the implementation of improvement programs, vibration level of unit and mechanical failure rate are reduced effectively. At the same time, it also provides guidance for design, maintenance and renovation of diesel generator mechanical support system of nuclear power plants in the future.

  11. Multiple mechanisms underlying neuroprotection by secretory phospholipase A2 preconditioning in a surgically induced brain injury rat model.

    Science.gov (United States)

    Wang, Yuechun; Sherchan, Prativa; Huang, Lei; Akyol, Onat; McBride, Devin W; Zhang, John H

    2018-02-01

    Intra-operative bleeding, post-operative brain edema and neuroinflammation are major complications in patients with surgical brain injury (SBI). Phospholipase A2 (PLA2) is the upstream enzyme which initiates the PLA2, 5-lipoxygenase (5-LOX) and leukotriene B4 (LTB4) inflammatory pathway. We hypothesized PLA2preconditioning (PPC) prior to SBI can activate endogenous anti-inflammatory responses to protect against SBI. This study evaluated if PPC can ameliorate neurosurgical complications and elucidated PPC-mediated possible protective mechanisms in a rat SBI model. Total 105 adult male Sprague Dawley rats were used for this study. SBI was induced by partial resection of the right frontal lobe. PLA2 or 0.9% NaCl was injected via rats' tail vein for 3 consecutive days prior to SBI. For mechanism study, a selective PLA2 inhibitor, Manoalide and 5-LOX inhibitor, Zileuton were injected intravenously with PPC to elucidate the role of PLA2 and 5-LOX in PPC-mediated anti-inflammatory effects. Brain water content (BWC) and lung water content, neurological tests, ELISA, western blot, immunohistochemistry, white blood cells (WBC) count, and spectrophotometric assay for intra-operative hemorrhage volume were evaluated. First, PPC reduced brain water content, intra-operative bleeding, and improved neurological function after SBI. Second, PPC decreased 5-LOX expression and brain leukocyte infiltration, while increasing glial fibrillary acidic protein (GFAP) expression in the peri-resection brain tissue after SBI. Third, PPC induced peripheral inflammation represented by mild pulmonary inflammation and increased peripheral blood WBC count and LTB4 level. Lastly, PPC increased blood glucose concentration and glucocorticoid levels after SBI. In addition, PPC mediated above-mentioned changes were partially reversed by administration of PLA2 inhibitor, Manoalide and 5-LOX inhibitor, Zileuton. PPC conferred neuroprotection against SBI via multi-target involvement induced anti

  12. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain

    Science.gov (United States)

    Stefano, George B.

    2010-01-01

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing. PMID:22371784

  13. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2010-06-30

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing.

  14. Altered Sleep Mechanisms following Traumatic Brain Injury and Relation to Waking Function

    Directory of Open Access Journals (Sweden)

    Kimberly A Cote

    2015-10-01

    Full Text Available Sleep difficulties are commonly reported following traumatic brain injury (TBI, but few studies have systematically examined the neurophysiological characteristics of sleep. Sleep EEG was quantified over multiple nights to examine mechanisms underlying sleep disruption in individuals who had sustained a TBI and to explore the relationship between sleep disruption and waking function. Sleep was recorded from 20 individuals with a TBI (18-64 years and 20 age-matched controls over two uninterrupted nights, as well as during a night where auditory stimuli were delivered. All participants underwent neuropsychological testing and waking performance assessment. Compared to controls, the TBI group had subjective complaints of falling asleep, delayed sleep onset on polysomnography (PSG, less Slow Wave (< 1 Hz and delta (1-4 Hz EEG power in non-REM sleep, fewer spontaneous and evoked k-complexes, reduced periodicity of spontaneous k-complexes, and lower amplitude of evoked k-complexes. While for controls, the density, duration and periodicity of sleep spindles diminished with deepening of non-REM as typically observed, this pattern was disrupted in the TBI group with peak spindle presentation occurring in Stage 3 sleep. Night-to-night-stability of Stage 2 spindles was high for controls but absent for the TBI group. Greater injury severity was related to fewer evoked k-complexes and lower spindle density. Greater spindle production predicted better waking function in the TBI group. Taken together, these data demonstrate impairment in sleep regulatory and inhibitory mechanisms as factors underlying sleep complaints following a TBI. Spindle generation may be adaptive or a marker of resiliency following TBI.

  15. 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.

  16. Hypokinesia upon pallidal deep brain stimulation of dystonia: support of a GABAergic mechanism

    Directory of Open Access Journals (Sweden)

    Florian eAmtage

    2013-12-01

    Full Text Available In the past, many studies have documented the beneficial effects of deep brain stimulation (DBS in the globus pallidus internus for treatment of primary segmental or generalized dystonia. Recently however, several reports focused on DBS-induced hypokinesia or freezing of gait as a side effect in these patients. Here we report on two patients suffering from freezing of gait after successful treatment of their dystonic movement disorder with pallidal high frequency stimulation (HFS. Several attempts to reduce the freezing of gait resulted in worsening of the control of dystonia. In one patient levodopa treatment was initialized which was somewhat successful to relieve freezing of gait. We discuss the possible mechanisms of hypokinetic side effects of pallidal DBS which can be explained by the hypothesis of selective GABA release as the mode of action of HFS. Pallidal HFS is also effective in treating idiopathic Parkinson’s disease as a hypokinetic disorder which at first sight seems to be a paradox. In our view, however, the GABAergic hypothesis can explain this and other clinical observations.

  17. 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.

  18. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain.

    Science.gov (United States)

    Freyberg, Zachary; Sonders, Mark S; Aguilar, Jenny I; Hiranita, Takato; Karam, Caline S; Flores, Jorge; Pizzo, Andrea B; Zhang, Yuchao; Farino, Zachary J; Chen, Audrey; Martin, Ciara A; Kopajtic, Theresa A; Fei, Hao; Hu, Gang; Lin, Yi-Ying; Mosharov, Eugene V; McCabe, Brian D; Freyberg, Robin; Wimalasena, Kandatege; Hsin, Ling-Wei; Sames, Dalibor; Krantz, David E; Katz, Jonathan L; Sulzer, David; Javitch, Jonathan A

    2016-02-16

    Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.

  19. TMS interference with primacy and recency mechanisms reveals bimodal episodic encoding in the human brain.

    Science.gov (United States)

    Innocenti, Iglis; Cappa, Stefano F; Feurra, Matteo; Giovannelli, Fabio; Santarnecchi, Emiliano; Bianco, Giovanni; Cincotta, Massimo; Rossi, Simone

    2013-01-01

    A classic finding of the psychology of memory is the "serial position effect." Immediate free recall of a word list is more efficient for items presented early (primacy effect) or late (recency effect), with respect to those in the middle. In an event-related, randomized block design, we interfered with the encoding of unrelated words lists with brief trains of repetitive TMS (rTMS), applied coincidently with the acoustic presentation of each word to the left dorsolateral pFC, the left intraparietal lobe, and a control site (vertex). Interference of rTMS with encoding produced a clear-cut double dissociation on accuracy during immediate free recall. The primacy effect was selectively worsened by rTMS of the dorsolateral pFC, whereas recency was selectively worsened by rTMS of the intraparietal lobe. These results are in agreement with the double dissociation between short-term and long-term memory observed in neuropsychological patients and provide direct evidence of distinct cortical mechanisms of encoding in the human brain.

  20. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

    Science.gov (United States)

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  1. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder.

    Science.gov (United States)

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, Damiaan

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a normal quality of life (QoL) after DBS. Reviewing the literature of the last 4 years, we argue that the mechanisms of action of DBS are a combination of excitatory and inhibitory as well as local and distal effects. Evidence from DBS animal models converges with human DBS EEG and imaging findings, in that DBS may be effective for OCD by reduction of hyperconnectivity between frontal and striatal areas. This is achieved through reduction of top-down-directed synchrony and reduction of frontal low-frequency oscillations. DBS appears to counteract striatal dysfunction through an increase in striatal dopamine and through improvement of reward processing. DBS affects anxiety levels through reduction of stress hormones and improvement of fear extinction.

  2. Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms.

    Science.gov (United States)

    Somayaji, Mahadevabharath R; Mahadevabharath, R; Przekwas; Andrzej, J; Gupta; Raj, K

    2017-08-28

    Traumatic brain injury (TBI) is a major healthcare problem that affects millions of people worldwide. Despite advances in understanding and developing preventative and treatment strategies using preclinical animal models, clinical trials to date have failed, and a "magic bullet" for effectively treating TBI-induced damage does not exist. Thus, novel pharmacological strategies to effectively manipulate the complex and heterogeneous pathophysiology of secondary injury mechanisms are needed. Given that goal, this paper discusses the relevance and advantages of combination therapies (COMTs) for "multi-target manipulation" of the injury cascade by administering multiple drugs to achieve an optimal therapeutic window of opportunity (e.g., temporally broad window) and compares these regimens to monotherapies that manipulate a single target with a single drug at a time. Furthermore, we posit that integrated mechanistic multiscale models that combine primary biomechanics, secondary injury mechano-/neurobiology, pharmacology and mathematical programming techniques could account for vast differences in the biological space and time scales and help to accelerate drug development, optimize combination pharmacotherapy protocols and improve treatment outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. 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

  4. Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms

    Science.gov (United States)

    Fink, John K.

    2014-01-01

    , SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. For recent review of HSP including historical descriptions, differential diagnosis, and additional references see [78]. PMID:23897027

  5. 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

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

    Science.gov (United States)

    Mudumbai, Seshadri C; Barr, Juli; Scott, Jennifer; Mariano, Edward R; Bertaccini, Edward; Nguyen, Hieu; Memtsoudis, Stavros G; Cason, Brian; Phibbs, Ciaran S; Wagner, Todd

    2015-09-01

    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. 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 (18-34 yr, 35-64 yr, and >65 yr). 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>96 hr); and projected the number of IMV discharges and ED-based admissions by year 2020. 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 18-34 yr), non-whites, and publicly insured patients. Some of the strongest predictors for PAMV were age 35-64 years (OR=1

  7. 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; Cesar, Paulo; Lopes, Renato Delascio; Lopes, Antônio Carlos

    2017-02-01

    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. 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. 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. 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.

  8. The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

    Science.gov (United States)

    Tian, Shan; Zhu, Fengping; Hu, Ruiping; Tian, Song; Chen, Xingxing; Lou, Dan; Cao, Bing; Chen, Qiulei; Li, Bai; Li, Fang; Bai, Yulong; Wu, Yi; Zhu, Yulian

    2018-01-01

    Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

    Science.gov (United States)

    Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

    2012-04-01

    Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

  10. InteractInteraction mechanism of emergency response in geological hazard perception and risk management: a case study in Zhouqu county

    Science.gov (United States)

    Qi, Yuan; Zhao, Hongtao

    2017-04-01

    China is one of few several natural disaster prone countries, which has complex geological and geographical environment and abnormal climate. On August 8, 2010, a large debris flow disaster happened in Zhouqu Country, Gansu province, resulting in more than 1700 casualties and more than 200 buildings damaged. In order to percept landslide and debris flow, an early warning system was established in the county. Spatial information technologies, such as remote sensing, GIS, and GPS, play core role in the early warning system, due to their functions in observing, analyzing, and locating geological disasters. However, all of these spatial information technologies could play an important role only guided by the emergency response mechanism. This article takes the establishment of Zhouqu Country's Disaster Emergency Response Interaction Mechanism (DERIM) as an example to discuss the risk management of country-level administrative units. The country-level risk management aims to information sharing, resources integration, integrated prevention and unified command. Then, nine subsystems support DERIM, which included disaster prevention and emergency data collection and sharing system, joint duty system, disaster verification and evaluation system, disaster consultation system, emergency warning and information release system, emergency response system, disaster reporting system, plan management system, mass prediction and prevention management system. At last, an emergency command platform in Zhouqu Country built up to realize DERIM. The core mission of the platform consists of daily management of disaster, monitoring and warning, comprehensive analysis, information release, consultation and decision-making, emergency response, etc. Five functional modules, including module of disaster information management, comprehensive monitoring module (geological monitoring, meteorological monitoring, water conservancy and hydrological monitoring), alarm management module, emergency

  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. Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

    Science.gov (United States)

    2017-10-01

    electrode technology , and wireless enclosure have significant interest and applications outside of PTE. There are many free roaming large animal...Electrophysiology Diffuse brain injury Focal brain injury Axonal pathology Epilepsy monitoring unit Chronic Implantation Wireless telemetry...Conclusions: A) Contusion injury validation and neuropathology B) Grid electrode development and testing C) Wireless Large Animal Custom Enclosure

  13. The adolescent brain : unraveling the neural mechanisms of cognitive and affective development

    NARCIS (Netherlands)

    Peters, Sabine

    2016-01-01

    Adolescence is often characterized as a period of increased risk taking and impulsive behavior. Researchers have constructed brain-based models to explain the higher prevalence of risk taking during adolescence. It has been hypothesized that brain regions for cognitive control develop relatively

  14. Bjork-Shiley convexoconcave valves: Susceptibility artifacts at brain MR imaging and mechanical valve fractures

    NARCIS (Netherlands)

    van Gorp, Maarten J.; van der Graaf, Yolanda; de Mol, Bas A. J. M.; Bakker, Chris J. G.; Witkamp, Theo D.; Ramos, Lino M. P.; Mali, Willem P. T. M.

    2004-01-01

    PURPOSE: To assess the relationship between heart valve history and susceptibility artifacts at magnetic resonance (MR) imaging of the brain in patients with Bjork-Shiley convexoconcave (BSCC) valves. MATERIALS AND METHODS: MR images of the brain were obtained in 58 patients with prosthetic heart

  15. Out of Hours Emergency Computed Tomography Brain Studies: Comparison of Standard 3 Megapixel Diagnostic Workstation Monitors With the iPad 2.

    Science.gov (United States)

    Salati, Umer; Leong, Sum; Donnellan, John; Kok, Hong Kuan; Buckley, Orla; Torreggiani, William

    2015-11-01

    The purpose was to compare performance of diagnostic workstation monitors and the Apple iPad 2 (Cupertino, CA) in interpretation of emergency computed tomography (CT) brain studies. Two experienced radiologists interpreted 100 random emergency CT brain studies on both on-site diagnostic workstation monitors and the iPad 2 via remote access. The radiologists were blinded to patient clinical details and to each other's interpretation and the study list was randomized between interpretations on different modalities. Interobserver agreement between radiologists and intraobserver agreement between modalities was determined and Cohen kappa coefficients calculated for each. Performance with regards to urgent and nonurgent abnormalities was assessed separately. There was substantial intraobserver agreement of both radiologists between the modalities with overall calculated kappa values of 0.959 and 0.940 in detecting acute abnormalities and perfect agreement with regards to hemorrhage. Intraobserver agreement kappa values were 0.939 and 0.860 for nonurgent abnormalities. Interobserver agreement between the 2 radiologists for both diagnostic monitors and the iPad 2 was also substantial ranging from 0.821-0.860. The iPad 2 is a reliable modality in the interpretation of CT brain studies in them emergency setting and for the detection of acute and chronic abnormalities, with comparable performance to standard diagnostic workstation monitors. Copyright © 2015 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  16. Emerging roles of epigenetic mechanisms in the enduring effects of neonatal stress and experience on learning and memory

    Science.gov (United States)

    McClelland, Shawn; Korosi, Aniko; Cope, Jessica; Ivy, Autumn; Baram, Tallie Z.

    2011-01-01

    Epigenetic mechanisms are involved in programming gene expression throughout development. In addition, they are key contributors to the processes by which early-life experience fine-tunes the expression levels of key neuronal genes, governing learning and memory throughout life. Here we describe the long-lasting, bi-directional effects of early-life experience on learning and memory. We discuss how enriched postnatal experience enduringly augments spatial learning, and how chronic early-life stress results in persistent and progressive deficits in the structure and function of hippocampal neurons. The existing and emerging roles of epigenetic mechanisms in these fundamental neuroplasticity phenomena are illustrated. PMID:21338703

  17. 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

  18. 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.

  19. Brief report: changes in brain function during acute cannabis intoxication: preliminary findings suggest a mechanism for cannabis-induced violence.

    Science.gov (United States)

    Howard, Richard C; Menkes, David B

    2007-01-01

    Recent evidence suggests that cannabis use may be associated with antisocial and violent behaviour, raising the question: What brain mechanisms mediate the disinhibiting effects of cannabis on behaviour? To examine whether an electrocortical measure of affective impulsivity, Go/No Go contingent negative variation, is affected by acute cannabis intoxication. Slow brain potentials were recorded in a Go/No Go noise avoidance task from five habitual cannabis users before, during and after they smoked a cannabis reefer containing 11 mg D-9-tetrahydrocannabinol. Slow brain potentials developed normally in both Go and No Go conditions before and during cannabis smoking but were severely disrupted 20-40 minutes later, coincident with peak intoxication. Cannabis effects on Go/No Go brain activity resembled those reported to occur in patients with lateral prefrontal cortex lesions. Our findings are preliminary, calling for larger-scale studies, to confirm the present findings and to investigate whether brain responses to cannabis intoxication differentiate those who are predisposed to suffer adverse consequences of cannabis use from those who are not.

  20. Injury mechanism of midfacial fractures in football causes in over 40% typical neurological symptoms of minor brain injuries.

    Science.gov (United States)

    Krutsch, Volker; Gesslein, Markus; Loose, Oliver; Weber, Johannes; Nerlich, Michael; Gaensslen, Axel; Bonkowsky, Viktor; Krutsch, Werner

    2017-02-08

    The injury mechanisms of midfacial fractures may be typical causes of concussion, but hardly any scientific data on midfacial injuries sustained in football are available. Head and brain trauma represent frequent injuries in athletes of different sports that require appropriate treatment by sports and trauma physicians. This study investigated the management of midfacial fractures in football and the association of such fractures with concomitant brain injury. In a prospective cohort study lasting 24 months (2012 to 2013), midfacial injuries of football players were analysed with regard to the injury mechanisms, first aid procedures on the field, treatment and return-to-play. To analyse concomitant and potentially overlooked minor brain injuries due to the trauma, we retrospectively investigated the neurological symptoms of the study population. The study included 132 football players (37 semi-professionals and 95 amateurs) with midfacial fractures. The main injury mechanisms were head-to-head and head-to-elbow trauma. The mean period of return-to-play after trauma was 33.5 days, which was significantly shortened if a protective face mask was worn (mean 10.4 days earlier, p = 0.0006). Semi-professional football players returned to play earlier (p = 0.009) and more often used protective face masks (p = 0.001). 55 players (41.6%) had neurological symptoms immediately after trauma as a possible sign of concomitant minor brain injury. 5 of 132 players with concussion had been hospitalised for 24 h, but no persistent neurological symptoms were detected. In football, midfacial fractures represent moderate-to-severe injuries with time away from sports of more than 4 weeks. Over 40% of athletes with a midfacial fracture showed concomitant neurological symptoms as a sign of minor brain injury. Therefore, sports physicians and other staff supervising athletes in daily practice should be aware of the presence of neurological symptoms. Level III.

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

    Science.gov (United States)

    Asaridou, Salomi S.; McQueen, James 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 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. PMID:23761776

  2. 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.

  3. 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

  4. Towards a Pathway Inventory of the Human Brain for Modeling Disease Mechanisms Underlying Neurodegeneration.

    Science.gov (United States)

    Iyappan, Anandhi; Gündel, Michaela; Shahid, Mohammad; Wang, Jiali; Li, Hui; Mevissen, Heinz-Theodor; Müller, Bernd; Fluck, Juliane; Jirsa, Viktor; Domide, Lia; Younesi, Erfan; Hofmann-Apitius, Martin

    2016-04-12

    Molecular signaling pathways have been long used to demonstrate interactions among upstream causal molecules and downstream biological effects. They show the signal flow between cell compartments, the majority of which are represented as cartoons. These are often drawn manually by scanning through the literature, which is time-consuming, static, and non-interoperable. Moreover, these pathways are often devoid of context (condition and tissue) and biased toward certain disease conditions. Mining the scientific literature creates new possibilities to retrieve pathway information at higher contextual resolution and specificity. To address this challenge, we have created a pathway terminology system by combining signaling pathways and biological events to ensure a broad coverage of the entire pathway knowledge domain. This terminology was applied to mining biomedical papers and patents about neurodegenerative diseases with focus on Alzheimer's disease. We demonstrate the power of our approach by mapping literature-derived signaling pathways onto their corresponding anatomical regions in the human brain under healthy and Alzheimer's disease states. We demonstrate how this knowledge resource can be used to identify a putative mechanism explaining the mode-of-action of the approved drug Rasagiline, and show how this resource can be used for fingerprinting patents to support the discovery of pathway knowledge for Alzheimer's disease. Finally, we propose that based on next-generation cause-and-effect pathway models, a dedicated inventory of computer-processable pathway models specific to neurodegenerative diseases can be established, which hopefully accelerates context-specific enrichment analysis of experimental data with higher resolution and richer annotations.

  5. 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

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

    DEFF Research Database (Denmark)

    Tanner, Anne Nygaard

    that are related to the core scientific principle of the FC. Hence, the findings only partly corroborate the thesis of technological relatedness as an underlying logic for regional branching in the case of an emerging industry, suggesting the need to look further into how agency and supportive organizations...

  7. [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

  8. Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

    Science.gov (United States)

    Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

    2016-11-01

    Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

  9. Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats

    National Research Council Canada - National Science Library

    Bambico, F R; Bregman, T; Diwan, M; Li, J; Darvish-Ghane, S; Li, Z; Laver, B; Amorim, B O; Covolan, L; Nobrega, J N; Hamani, C

    2015-01-01

    ...) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels...

  10. Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury(TBI)

    Science.gov (United States)

    2016-10-01

    NSS) previously reported, staining of rat brain sections for hemosiderin (microbleeding), IgG (BBB breakdown) and amyloid precursor protein (APP...results for hemosiderin staining are provided below.   7  We also looked for evidence of

  11. Epigenetic mechanisms and associated brain circuits in the regulation of positive emotions: A role for transposable elements.

    Science.gov (United States)

    Gaudi, Simona; Guffanti, Guia; Fallon, James; Macciardi, Fabio

    2016-10-15

    Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how genomic and epigenetic mechanisms can modify and potentially alter our emotional (limbic) brain and affect our social interactions. J. Comp. Neurol. 524:2944-2954, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available 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.

  13. Invasion and Evasion: Investigations on Early Glioblastoma Growth Reveal Two Novel Mechanisms of Brain Tumor Progression

    OpenAIRE

    Baker, Gregory Joseph

    2014-01-01

    As glioma cells infiltrate the brain they associate with various microanatomic structures such as blood vessels and myelinated white matter tracts. How distinct invasion patterns coordinate tumor growth and influence clinical outcomes remains poorly understood. We have investigated how perivascular invasion affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to common...

  14. 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

    and validate therapeutic targets and to discover drug candidates for rapidly and effectively generating new interventions for human diseases. The recent emergence of genomic technologies and their application on genetically tractable model organisms like Drosophila melanogaster,Caenorhabditis elegans...... 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...... and Saccharomyces cerevisiae have provided momentum to cell biological and biomedical research, particularly in the functional characterization of gene functions and the identification of novel drug targets. We therefore anticipate that chemical genomics and the vast development of genomic technologies will play...

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Monica S Vavilala

    Full Text Available 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.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.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.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 discharge outcomes for patients with

  17. [Non-invasive mechanical ventilation and epidural anesthesia for an emergency open cholecystectomy].

    Science.gov (United States)

    Yurtlu, Bülent Serhan; Köksal, Bengü; Hancı, Volkan; Turan, Işıl Özkoçak

    2016-01-01

    Non-invasive ventilation is an accepted treatment modality in both acute exacerbations of respiratory diseases and chronic obstructive lung disease. It is commonly utilized in the intensive care units, or for postoperative respiratory support in post-anesthesia care units. This report describes intraoperative support in non-invasive ventilation to neuroaxial anesthesia for an emergency upper abdominal surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Non-invasive mechanical ventilation and epidural anesthesia for an emergency open cholecystectomy.

    Science.gov (United States)

    Yurtlu, Bülent Serhan; Köksal, Bengü; Hancı, Volkan; Turan, Işıl Özkoçak

    2016-01-01

    Non-invasive ventilation is an accepted treatment modality in both acute exacerbations of respiratory diseases and chronic obstructive lung disease. It is commonly utilized in the intensive care units, or for postoperative respiratory support in post-anesthesia care units. This report describes intraoperative support in non-invasive ventilation to neuroaxial anesthesia for an emergency upper abdominal surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. 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.

  20. Extracellular Tau Paired Helical Filaments Differentially Affect Tau Pathogenic Mechanisms in Mitotic and Post-Mitotic Cells: Implications for Mechanisms of Tau Propagation in the Brain.

    Science.gov (United States)

    Varghese, Merina; Santa-Maria, Ismael; Ho, Lap; Ward, Libby; Yemul, Shrishailam; Dubner, Lauren; Księżak-Reding, Hanna; Pasinetti, Giulio Maria

    2016-09-06

    The release of paired helical filaments (PHFs) from neurons into the extracellular space may contribute to the propagation of tau pathology across brain regions in Alzheimer's disease (AD) and other tauopathies. The majority of available mechanistic studies exploring the pathologic role of extracellular PHFs are conducted in proliferating cell lines. Here, we compare how extracellular PHFs induce tauopathy in mitotic cells and in post-mitotic brain neurons. In a mitotic cell line (HEK 293T), extracellular exposure to AD PHFs leads to an intracellular "aggresomal" type deposition of tau, coincidental with redistribution of dynein, a retrograde motor protein. We also observed that PHFs impaired proteasome degradation, but not autophagy. Exposure of cells to proteasome inhibitors was sufficient to induce intracellular tau aggregate formation as well as reorganization of dynein and the intermediate filament protein, vimentin. Thus, in mitotic cells, extracellular PHFs promote cellular tau aggregation, in part, by interfering with cellular proteasome degradation processes. In contrast with our observations with proliferating cells, exposure of post-mitotic primary neuronal cultures to AD PHFs did not promote "aggresomal" tau deposition, but instead resulted in a widespread accumulation of phosphorylated tau-immunoreactive swellings in neuritic processes, characterized by disturbed cytoskeletal organization of dynein and vimentin. Collectively, our observations suggest that extracellular PHFs may contribute to the propagation of tau pathology by independent mechanisms in post-mitotic and mitotic brain cells. These outcomes indicate that in addition to post-mitotic brain neurons, mitotic brain cells should also be considered as targets for therapeutic interventions to attenuate propagation of tauopathy.

  1. Metabolic Reprogramming in Brain Tumors.

    Science.gov (United States)

    Venneti, Sriram; Thompson, Craig B

    2017-01-24

    Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism. Furthermore, metabolic alterations directly impact epigenetics well beyond classical mechanisms of tumor pathogenesis. Metabolic reprogramming in brain tumors is also influenced by the tumor microenvironment contributing to drug resistance and tumor recurrence. Altered cancer metabolism can be leveraged to noninvasively image brain tumors, which facilitates improved diagnosis and the evaluation of treatment effectiveness. Many of these aspects of altered metabolism provide novel therapeutic opportunities to effectively treat primary brain tumors.

  2. Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats

    Directory of Open Access Journals (Sweden)

    Natalia Andreevna Krivova

    2015-03-01

    Full Text Available The Morris water maze (MWM is a tool for assessment of age-related cognitive deficits. In our work, MWM was used for appraisal of cognitive deficits in 11-month-old rats and investigation of the effect exerted by training in the Morris water maze on the redox mechanisms in rat brain parts. Young adult (3-month-old and aged (11-month-old male rats were trained in the water maze. 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.Cognitive deficits were 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 cognitive deficits in aged rats can be reversed by MWM training. 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 responsible for age-related cognitive deficits. 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.

  3. 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

  4. 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.

  5. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors.

    Science.gov (United States)

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Hart, John J; Bartz, Elizabeth K; Didehbani, Nyaz; Keebler, Molly W; Gardner, Claire M; Strain, Jeremy F; DeFina, Laura F; Lu, Hanzhang

    2015-02-01

    Complex mental activity induces improvements in cognition, brain function, and structure in animals and young adults. It is not clear to what extent the aging brain is capable of such plasticity. This study expands previous evidence of generalized cognitive gains after mental training in healthy seniors. Using 3 MRI-based measurements, that is, arterial spin labeling MRI, functional connectivity, and diffusion tensor imaging, we examined brain changes across 3 time points pre, mid, and post training (12 weeks) in a randomized sample (n = 37) who received cognitive training versus a control group. We found significant training-related brain state changes at rest; specifically, 1) increases in global and regional cerebral blood flow (CBF), particularly in the default mode network and the central executive network, 2) greater connectivity in these same networks, and 3) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy. Improvements in cognition were identified along with significant CBF correlates of the cognitive gains. We propose that cognitive training enhances resting-state neural activity and connectivity, increasing the blood supply to these regions via neurovascular coupling. These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors. © The Author 2013. Published by Oxford University Press.

  6. Resistance of human brain microvascular endothelial cells in culture to methylmercury: cell-density-dependent defense mechanisms.

    Science.gov (United States)

    Hirooka, Takashi; Fujiwara, Yasuyuki; Shinkai, Yasuhiro; Yamamoto, Chika; Yasutake, Akira; Satoh, Masahiko; Eto, Komyo; Kaji, Toshiyuki

    2010-06-01

    Vascular toxicity is important for understanding the neurotoxicity of methylmercury, because microvessels strongly influence the construction of microenvironment around neurons. Previously, we found that low density-human brain microvascular pericytes are markedly susceptible to methylmercury cytotoxicity due to high expression levels of the L-type amino acid transporter 1 (LAT-1) that transports methylmercury into the cells. Although LAT-1 can be, in general, highly expressed in sparse cells that require amino acids for growth, we found that human brain microvascular endothelial cells, regardless of cell density, were resistant to methylmercury cytotoxicity. To investigate the mechanisms underlying this resistance, we exposed the endothelial cells at low and high cell densities to methylmercury and determined the extent of nonspecific cell damage, intracellular accumulation of methylmercury, expression of LAT-1 and LAT-2 mRNAs, and intracellular expression of reduced glutathione and metallothionein. These experiments indicate that sparse endothelial cells intracellularly accumulate more methylmercury via the highly expressed LAT-1, but are resistant to methylmercury cytotoxicity by higher expression of the protective sulfhydryl peptides, namely, reduced glutathione and metallothionein. It is suggested that both nonspecific and functional damage is caused in pericytes, whereas functional abnormalities rather than nonspecific damage may occur to a greater extent in the endothelial cells in the brain microvessels exposed to methylmercury. The previous and present data also suggest that methylmercury exhibits toxicity in endothelial cells in a manner different from that in pericytes in the brain microvessels.

  7. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles.

    Science.gov (United States)

    Balusu, Sriram; Van Wonterghem, Elien; De Rycke, Riet; Raemdonck, Koen; Stremersch, Stephan; Gevaert, Kris; Brkic, Marjana; Demeestere, Delphine; Vanhooren, Valerie; Hendrix, An; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-10-01

    Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  8. Assessment of the effect of continuous sedation with mechanical ventilation on adrenal insufficiency in patients with traumatic brain injury.

    Science.gov (United States)

    Li, Min; Zhang, Ying; Wu, Kang-Song; Hu, Ying-Hong

    2016-03-01

    The aim of this study was to assess the effect of continuous propofol sedation plus prolonged mechanical ventilation on adrenal insufficiency (AI) in patients with traumatic brain injury (TBI). Eighty-five adult patients diagnosed with moderate TBI (Glasgow Coma Scale (GCS) score 9-13) from October 2011 to October 2012 were included in this prospective study. The patients comprised three groups: no mechanical ventilation and sedation (n=27), mechanical ventilation alone (n=24) and mechanical ventilation plus sedation (n=34). The low-dose short Synacthen test was performed at 8:00 on the first, third, and fifth days after TBI. Logistic regression analysis was performed to identify factors affecting the use of mechanical ventilation and sedation, and the incidence of AI. On the fifth day after injury, the mean baseline cortisol and simulated cortisol levels were significantly lower in the mechanical ventilation plus sedation group compared with the other two groups. Multivariate regression analysis showed that the Acute Physiology and Chronic Health Evaluation (APACHE) score was independently associated with treatment with mechanical ventilation and sedation compared to mechanical ventilation alone. Furthermore, hypoxemia on admission and shock were associated with the development of AI. The findings showed that sedation is associated with an increased incidence of AI. Patients with TBI who are treated with continuous sedation should be monitored for AI carefully. Copyright © 2016 American Federation for Medical Research.

  9. Neural Operant Conditioning as a Core Mechanism of Brain-Machine Interface Control

    Directory of Open Access Journals (Sweden)

    Yoshio Sakurai

    2016-08-01

    Full Text Available The process of changing the neuronal activity of the brain to acquire rewards in a broad sense is essential for utilizing brain-machine interfaces (BMIs, which is essentially operant conditioning of neuronal activity. Currently, this is also known as neural biofeedback, and it is often referred to as neurofeedback when human brain activity is targeted. In this review, we first illustrate biofeedback and operant conditioning, which are methodological background elements in neural operant conditioning. Then, we introduce research models of neural operant conditioning in animal experiments and demonstrate that it is possible to change the firing frequency and synchronous firing of local neuronal populations in a short time period. We also debate the possibility of the application of neural operant conditioning and its contribution to BMIs.

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzi, Tommaso [Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Chisholm, Rebecca H. [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia); Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Larsen, Annette K.; Escargueil, Alexandre [Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France); INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris (France)

    2016-06-08

    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.

  12. 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,

  13. Using Formal Game Design Methods to Embed Learning Outcomes into Game Mechanics and Avoid Emergent Behaviour

    Science.gov (United States)

    Grey, Simon; Grey, David; Gordon, Neil; Purdy, Jon

    2017-01-01

    This paper offers an approach to designing game-based learning experiences inspired by the Mechanics-Dynamics-Aesthetics (MDA) model (Hunicke et al., 2004) and the elemental tetrad model (Schell, 2008) for game design. A case for game based learning as an active and social learning experience is presented including arguments from both teachers and…

  14. Emerging Mechanisms of Innate Immunity and Their Translational Potential in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Daniele Corridoni

    2018-02-01

    Full Text Available Activation of the innate immune system through pattern-recognition receptor (PRR signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD. The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota. The purpose of this review is to evaluate the emerging functions of PRRs including their functional cross-talk, how they respond to mitochondrial damage, induce mitophagy or autophagy, and influence adaptive immune responses by interacting with the antigen presentation machinery. The review also summarizes some of the recent attempts to harness these pathways for therapeutic approaches in intestinal inflammation.

  15. Recurrent CME-like Eruptions in Emerging Flux Regions. I. On the Mechanism of Eruptions

    Science.gov (United States)

    Syntelis, P.; Archontis, V.; Tsinganos, K.

    2017-11-01

    We report on three-dimensional (3D) magnetohydrodynamic (MHD) simulations of recurrent eruptions in emerging flux regions. We find that reconnection of sheared field lines, along the polarity inversion line of an emerging bipolar region, leads to the formation of a new magnetic structure, which adopts the shape of a magnetic flux rope (FR) during its rising motion. Initially, the FR undergoes a slow-rise phase and, eventually, it experiences a fast-rise phase and ejective eruption toward the outer solar atmosphere. In total, four eruptions occur during the evolution of the system. For the first eruption, our analysis indicates that the torus instability initiates the eruption and that tether-cutting reconnection of the field lines, which envelop the FR, triggers the rapid acceleration of the eruptive field. For the following eruptions, we conjecture that it is the interplay between tether-cutting reconnection and torus instability that causes the onset of the various phases. We show the 3D shape of the erupting fields, focusing more on how magnetic field lines reconnect during the eruptions. We find that when the envelope field lines reconnect mainly with themselves, hot and dense plasma is transferred closer to the core of the erupting FR. The same area appears to be cooler and less dense when the envelope field lines reconnect with neighboring sheared field lines. The plasma density and temperature distribution, together with the rising speeds, energies, and size of the erupting fields, indicate that they may account for small-scale (mini) coronal mass ejections.

  16. Injury to the Preterm Brain and Cerebral Palsy: Clinical Aspects, Molecular Mechanisms, Unanswered Questions, and Future Research Directions

    Science.gov (United States)

    Babcock, Michael A.; Kostova, Felina V.; Ferriero, Donna M.; Johnston, Michael V.; Brunstrom, Jan E.; Hagberg, Henrik; Maria, Bernard L.

    2013-01-01

    Cerebral palsy will affect nearly 10% of the 60,000 very-low-birth-weight infants born in the United States in the next year, and an even greater percentage will display some form of permanent neurological impairment resulting from injury to the preterm brain. The 2008 Neurobiology of Disease in Children Symposium, held in conjunction with the 37th annual meeting of the Child Neurology Society, aimed to define current knowledge and to develop specific aims for future clinical, translational, and fundamental science. A complex interplay of both destructive and developmental forces is responsible for injury to the preterm brain. Advances in imaging and histology have implicated a variety of cell types, though pre-oligodendrocyte injury remains the focus. Research into different mechanisms of injury is facilitating new neuroprotective and rehabilitative interventions. A cooperative effort is necessary to translate basic research findings into clinically effective therapies and better care for these children. PMID:19745084

  17. Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

    Science.gov (United States)

    Jin, Byung-Ju; Smith, Alex J.

    2016-01-01

    A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. PMID:27836940

  18. Understanding Sequelae of Injury Mechanisms and Mild Traumatic Brain Injury Incurred during the Conflicts in Iraq and Afghanistan: Persistent Postconcussive Symptoms and Posttraumatic Stress Disorder

    National Research Council Canada - National Science Library

    Schneiderman, Aaron I; Braver, Elisa R; Kang, Han K

    2008-01-01

    A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI...

  19. 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…

  20. 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

    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

  1. Brain Mechanisms for Processing Direct and Averted Gaze in Individuals with Autism

    Science.gov (United States)

    Pitskel, Naomi B.; Bolling, Danielle Z.; Hudac, Caitlin M.; Lantz, Stephen D.; Minshew, Nancy J.; Vander Wyk, Brent C.; Pelphrey, Kevin A.

    2011-01-01

    Prior studies have indicated brain abnormalities underlying social processing in autism, but no fMRI study has specifically addressed the differential processing of direct and averted gaze, a critical social cue. Fifteen adolescents and adults with autism and 14 typically developing comparison participants viewed dynamic virtual-reality videos…

  2. Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy After Traumatic Brain Injury

    Science.gov (United States)

    2014-10-01

    impactor tip was pneumatically driven at a velocity of 4.0 m/s, depth of pentration 1.0 mm and duration of 100 msec to induce the traumatic brain... suspension is loaded in a glass pipette and pressure injected. The craniotomy is sealed with silicone elastomer and the skin reapposed with vetbond. The

  3. Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

    Science.gov (United States)

    Zebardast, Nazlee; Crowley, Michael J; Bloch, Michael H; Mayes, Linda C; Wyk, Brent Vander; Leckman, James F; Pelphrey, Kevin A; Swain, James E

    2013-10-30

    Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blocked-design fMRI paradigm. There were 33 participants: 17 with TS and 16 healthy individuals. As a measure of PPI-related brain activity, we looked for differential cerebral activation to prepulse-plus-pulse stimuli versus activation to pulse-alone stimuli. In healthy subjects, PPI was associated with increased activity in multiple brain regions, of which activation in the left middle frontal gyrus in the healthy controls showed a significant linear correlation with the degree of PPI measured outside of the magnet. Group comparisons identified nine regions where brain activity during PPI differed significantly between TS and healthy subjects. Among the TS subjects, activation in the left caudate was significantly correlated with current tic severity as measured by the total score on the Yale Global Tic Severity Scale. Differential activation of the caudate nucleus associated with current tic severity is consistent with neuropathological data and suggests that portions of cortical-striatal circuits may modulate the severity of tic symptoms in adulthood. © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Dynamic, regional mechanical properties of the porcine brain: indentation in the coronal plane.

    Science.gov (United States)

    Elkin, Benjamin S; Ilankova, Ashok; Morrison, Barclay

    2011-07-01

    Stress relaxation tests using a custom designed microindentation device were performed on ten anatomic regions of fresh porcine brain (postmortem time Prony series representation was used to describe the shear relaxation modulus for each anatomic region tested. Prony series parameters fit to load data from indentations performed to ∼10% strain differed significantly by anatomic region. The gray and white matter of the cerebellum along with corpus callosum and brainstem were the softest regions measured. The cortex and hippocampal CA1/CA3 were found to be the stiffest. To examine the large strain behavior of the tissue, multistep indentations were performed in the corona radiata to strains of 10%, 20%, and 30%. Reduced relaxation functions were not significantly different for each step, suggesting that quasi-linear viscoelastic theory may be appropriate for representing the nonlinear behavior of this anatomic region of porcine brain tissue. These data, for the first time, describe the dynamic and short time scale behavior of multiple anatomic regions of the porcine brain which will be useful for understanding porcine brain injury biomechanics at a finer spatial resolution than previously possible.

  5. The structure of brain glycogen phosphorylase-from allosteric regulation mechanisms to clinical perspectives.

    Science.gov (United States)

    Mathieu, Cécile; Dupret, Jean-Marie; Rodrigues Lima, Fernando

    2017-02-01

    Glycogen phosphorylase (GP) is the key enzyme that regulates glycogen mobilization in cells. GP is a complex allosteric enzyme that comprises a family of three isozymes: muscle GP (mGP), liver GP (lGP), and brain GP (bGP). Although the three isozymes display high similarity and catalyze the same reaction, they differ in their sensitivity to the allosteric activator adenosine monophosphate (AMP). Moreover, inactivating mutations in mGP and lGP have been known to be associated with glycogen storage diseases (McArdle and Hers disease, respectively). The determination, decades ago, of the structure of mGP and lGP have allowed to better understand the allosteric regulation of these two isoforms and the development of specific inhibitors. Despite its important role in brain glycogen metabolism, the structure of the brain GP had remained elusive. Here, we provide an overview of the human brain GP structure and its relationship with the two other members of this key family of the metabolic enzymes. We also summarize how this structure provides valuable information to understand the regulation of bGP and to design specific ligands of potential pharmacological interest. © 2016 Federation of European Biochemical Societies.

  6. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder

    NARCIS (Netherlands)

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, D.

    2015-01-01

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients

  7. The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Pathophysiological Mechanisms and Novel Treatments.

    Science.gov (United States)

    Kim, Yong-Ku; Shin, Cheolmin

    2017-09-15

    The human gut microbiome comprise a huge number of microorganisms with co-evolutionary associations with humans. It has been repeatedly revealed that bidirectional communication exists between the brain and the gut and involves neural, hormonal, and immunological pathways. Evidences from neuroscience researches over the past few years suggest that microbiota is essential for the development and maturation of brain systems that are associated to stress responses. This review provides that the summarization of the communication among microbiota, gut and brain and the results of preclinical and clinical studies on gut microbiota used in treatments for neuropsychiatric disorders. Recent studies have reported that diverse forms of neuropsychiatric disorders (such as autism, depression, anxiety, and schizophrenia) are associated with or modulated by variations in the microbiome, by microbial substrates, and by exogenous prebiotics, antibiotics, and probiotics. The microbiota-gut-brain axis might provide novel targets for prevention and treatment of neuropsychiatric disorders. However, further studies are required to substantiate the clinical use of probiotics, prebiotics and FMT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Brain dynamics of distractibility: interaction between top-down and bottom-up mechanisms of auditory attention.

    Science.gov (United States)

    Bidet-Caulet, Aurélie; Bottemanne, Laure; Fonteneau, Clara; Giard, Marie-Hélène; Bertrand, Olivier

    2015-05-01

    Attention improves the processing of specific information while other stimuli are disregarded. A good balance between bottom-up (attentional capture by unexpected salient stimuli) and top-down (selection of relevant information) mechanisms is crucial to be both task-efficient and aware of our environment. Only few studies have explored how an isolated unexpected task-irrelevant stimulus outside the attention focus can disturb the top-down attention mechanisms necessary to the good performance of the ongoing task, and how these top-down mechanisms can modulate the bottom-up mechanisms of attentional capture triggered by an unexpected event. We recorded scalp electroencephalography in 18 young adults performing a new paradigm measuring distractibility and assessing both bottom-up and top-down attention mechanisms, at the same time. Increasing task load in top-down attention was found to reduce early processing of the distracting sound, but not bottom-up attentional capture mechanisms nor the behavioral distraction cost in reaction time. Moreover, the impact of bottom-up attentional capture by distracting sounds on target processing was revealed as a delayed latency of the N100 sensory response to target sounds mirroring increased reaction times. These results provide crucial information into how bottom-up and top-down mechanisms dynamically interact and compete in the human brain, i.e. on the precarious balance between voluntary attention and distraction.

  9. Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism.

    Science.gov (United States)

    Collins, M A; Zou, J Y; Neafsey, E J

    1998-02-01

    Adult rats intubated with a single dose of ethanol (alcohol; approximately 5 g/kg) for 5 to 10 successive days incur neurodegeneration in the entorhinal cortex, dentate gyrus, and olfactory bulbs accompanied by cerebrocortical edema and electrolyte (Na+, K+) accumulation. The brain damage is not lessened by cotreatment with the NMDA receptor antagonist MK-801; also, as reported elsewhere, MK-801 as well as non-NMDA receptor and Ca2+ channel antagonists are not neuroprotective in a similar, but more compressed, intoxication protocol. However, cotreatment with the electrolyte transport inhibitor/diuretic furosemide reduces alcohol-dependent cerebrocortical damage by 75-85% while preventing brain hydration and electrolyte elevations; olfactory bulb neurodegeneration is not attenuated. In parallel in vitro studies, rat organotypic entorhinal/hippocampal slice cultures exposed to alcohol (50-200 mM) 15 h/day for 6 days, mirroring episodic intoxication in vivo, demonstrate concentration-related release of the cytotoxic indicator, lactate dehydrogenase. Analogous to the in vivo findings, furosemide blocks this alcohol-induced in vitro cytotoxicity. Our results showing neuroprotection by furosemide indicate that brain edema and swelling are essential events in the brain damage induced by episodic alcohol exposure. Furosemide and related agents might be useful as neuroprotective agents in alcohol abuse. We suggest that the neurodegeneration is elicited in part by edema-dependent oxidative stress, but the regional selectivity of the damage may be best explained by physical (mechanical) compression of the limbic cortex against the adjacent tympanic bulla and subsequent neuronal cytoskeletal collapse. A scheme for these apparently nonexcitotoxic metabolic and mechanical pathways initiated by repeated alcohol exposure is proposed.

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

    Science.gov (United States)

    Ueno, Masaki

    2017-03-28

    It is well-known that the blood-brain barrier (BBB) plays significant roles in transporting intravascular substances into the brain. The BBB in cerebral capillaries essentially impedes the influx of intravascular compounds from the blood to the brain, while nutritive substances, such as glucose, can be selectively transported through several types of influx transporters in endothelial cells. In the choroid plexus, intravascular substances can invade the parenchyma as fenestrations exist in endothelial cells of capillaries. However, the substances cannot invade the ventricles easily as there are tight junctions between epithelial cells in the choroid plexus. This restricted movement of the substances across the cytoplasm of the epithelial cells constitutes a blood-cerebrospinal fluid barrier (BCSFB). In the brain, there are circumventricular organs, in which the barrier function is imperfect in capillaries. Accordingly, it is reasonable to consider that intravascular substances can move in and around the parenchyma of the organs. Actually, it was reported in mice that intravascular substances moved in the corpus callosum, medial portions of the hippocampus, and periventricular areas via the subfornical organs or the choroid plexus. Regarding pathways of intracerebral interstitial and cerebrospinal fluids to the outside of the brain, two representative drainage pathways, or perivascular drainage and glymphatic pathways, are being established. The first is the pathway in a retrograde direction to the blood flow through the basement membrane in walls of cerebral capillaries, the tunica media of arteries, and the vessels walls of the internal carotid artery. The second is in an anterograde direction to blood flow through the para-arterial routes, aquaporin 4-dependent transport through the astroglial cytoplasm, and para-venous routes, and then the fluids drain into the subarachnoid CSF. These fluids are finally considered to drain into the cervical lymph nodes or veins

  11. Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Zeina Habli

    2017-02-01

    Full Text Available Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery.

  12. Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Mills

    2018-01-01

    Full Text Available Dimethyl fumarate (DMF is an effective treatment option for relapsing–remitting multiple sclerosis (MS, but its therapeutic mechanism of action has not been fully elucidated. A better understanding of its mechanism will allow for the development of assays to monitor its clinical efficacy and safety in patients, as well as guide the development of the next generation of therapies for MS. In order to build the foundation for determining its mechanism, we reviewed the manner in which DMF alters lymphocyte subsets in MS patients, its impact on clinical efficacy and safety, as well as its molecular effects in cellular and animal models. DMF decreases absolute lymphocyte counts, but does not affect all subsets uniformly. CD8+ T-cells are the most profoundly affected, but reduction also occurs in the CD4+ population, particularly within the pro-inflammatory T-helper Th1 and Th17 subsets, creating a bias toward more anti-inflammatory Th2 and regulatory subsets. Similarly, B-lymphocyte, myeloid, and natural killer populations are also shifted toward a more anti-inflammatory state. In vitro and animal models demonstrate a role for DMF within the central nervous system (CNS in promoting neuronal survival in an Nrf2 pathway-dependent manner. However, the impact of DMF directly within the CNS of MS patients remains largely unknown.

  13. Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Mills, Elizabeth A; Ogrodnik, Magdalena A; Plave, Andrew; Mao-Draayer, Yang

    2018-01-01

    Dimethyl fumarate (DMF) is an effective treatment option for relapsing-remitting multiple sclerosis (MS), but its therapeutic mechanism of action has not been fully elucidated. A better understanding of its mechanism will allow for the development of assays to monitor its clinical efficacy and safety in patients, as well as guide the development of the next generation of therapies for MS. In order to build the foundation for determining its mechanism, we reviewed the manner in which DMF alters lymphocyte subsets in MS patients, its impact on clinical efficacy and safety, as well as its molecular effects in cellular and animal models. DMF decreases absolute lymphocyte counts, but does not affect all subsets uniformly. CD8 + T-cells are the most profoundly affected, but reduction also occurs in the CD4 + population, particularly within the pro-inflammatory T-helper Th1 and Th17 subsets, creating a bias toward more anti-inflammatory Th2 and regulatory subsets. Similarly, B-lymphocyte, myeloid, and natural killer populations are also shifted toward a more anti-inflammatory state. In vitro and animal models demonstrate a role for DMF within the central nervous system (CNS) in promoting neuronal survival in an Nrf2 pathway-dependent manner. However, the impact of DMF directly within the CNS of MS patients remains largely unknown.

  14. Gut Microbiota and the Gut-Brain Axis : New Insights in the Pathophysiology of Metabolic Syndrome

    NARCIS (Netherlands)

    de Clercq, Nicolien C.; Frissen, Myrthe N.; Groen, Albert K.; Nieuwdorp, Max

    2017-01-01

    Objective: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut

  15. Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome

    NARCIS (Netherlands)

    de Clercq, Nicolien C.; Frissen, Myrthe N.; Groen, Albert K.; Nieuwdorp, Max

    2017-01-01

    Objective: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut

  16. 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

  17. 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.

  18. Mechanical Properties in Metal-Organic Frameworks: Emerging Opportunities and Challenges for Device Functionality and Technological Applications.

    Science.gov (United States)

    Burtch, Nicholas C; Heinen, Jurn; Bennett, Thomas D; Dubbeldam, David; Allendorf, Mark D

    2017-11-17

    Some of the most remarkable recent developments in metal-organic framework (MOF) performance properties can only be rationalized by the mechanical properties endowed by their hybrid inorganic-organic nanoporous structures. While these characteristics create intriguing application prospects, the same attributes also present challenges that will need to be overcome to enable the integration of MOFs with technologies where these promising traits can be exploited. In this review, emerging opportunities and challenges are identified for MOF-enabled device functionality and technological applications that arise from their fascinating mechanical properties. This is discussed not only in the context of their more well-studied gas storage and separation applications, but also for instances where MOFs serve as components of functional nanodevices. Recent advances in understanding MOF mechanical structure-property relationships due to attributes such as defects and interpenetration are highlighted, and open questions related to state-of-the-art computational approaches for quantifying their mechanical properties are critically discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Non-hemagglutinating flaviviruses: molecular mechanisms for the emergence of new strains via adaptation to European ticks.

    Directory of Open Access Journals (Sweden)

    Maxim A Khasnatinov

    2009-10-01

    Full Text Available Tick-borne encephalitis virus (TBEV causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards

  20. Identification of a novel mechanism of blood?brain communication during peripheral inflammation via choroid plexus?derived extracellular vesicles

    OpenAIRE

    Balusu, Sriram; Van Wonterghem, Elien; De Rycke, Riet; Raemdonck, Koen; Stremersch, Stephan; Gevaert, Kris; Brkic, Marjana; Demeestere, Delphine; Vanhooren, Valerie; Hendrix, An; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-01-01

    Abstract Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood?brain communication. Systemic inflammation induced an increase in EVs and associated pro?inflammatory miRNAs, including miR?146a and miR?155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS?stimulated primary CPE cells a...

  1. Mechanisms of psychopharmacological effects of alkaloid Z77 under conditions of brain ischemia.

    Science.gov (United States)

    Zyuz'kov, G N; Suslov, N I; Losev, E A; Zhdanov, V V; Udut, E V; Miroshnichenko, L A; Simanina, E V; Povet'eva, T N; Nesterova, Yu V; Udut, V V; Minakova, M Yu; Zamoshchina, T A; Dygai, A M

    2015-04-01

    We studied the psychopharmacological effects of atisine-type diterpene alkaloid Z77 in a rat model of brain ischemia in the morning and at night. The type of developing locomotor disorders in animals was shown to depend on circadian rhythms. Administration of Z77 substantially corrected manifestations of psychoneurological symptoms. The parameters of orientation and exploratory behavior and conditioned reflex activity were normalized. The key role of receptors of neural stem cells to fibroblast growth factor in the realization of their growth potential under the influence of the alkaloid was demonstrated. Under in vitro conditions, antibodies to fibroblast growth factor receptor abolished the increase in the number of neural CFU caused by Z77 in the culture of intact cells from the paraventricular region of the brain.

  2. Neural mechanisms of auditory categorization: from across brain areas to within local microcircuits

    Directory of Open Access Journals (Sweden)

    Joji eTsunada

    2014-06-01

    Full Text Available Categorization enables listeners to efficiently encode and respond to auditory stimuli. Behavioral evidence for auditory categorization has been well documented across a broad range of human and non-human animal species. Moreover, neural correlates of auditory categorization have been documented in a variety of different brain regions in the ventral auditory pathway, which is thought to underlie auditory-object processing and auditory perception. Here, we review and discuss how neural representations of auditory categories are transformed across different scales of neural organization in the ventral auditory pathway: from across different brain areas to within local microcircuits. We propose different neural transformations across different scales of neural organization in auditory categorization. Along the ascending auditory system in the ventral pathway, there is a progression in the encoding of categories from simple acoustic categories to categories for abstract information. On the other hand, in local microcircuits, different classes of neurons differentially compute categorical information.

  3. 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.

  4. 'Spreading depression of Leão' and its emerging relevance to acute brain injury in humans

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Strong, Anthony J

    2017-01-01

    A new research field in translational neuroscience has opened as a result of the recognition since 2002 that "spreading depression of Leão" can be detected in many patients with acute brain injury, whether vascular and spontaneous, or traumatic in origin, as well as in those many individuals...

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

    NARCIS (Netherlands)

    Namas, R.; Ghuma, A.; Hermus, L.; Zamora, R.; Okonkwo, D. O.; Billiar, T. R.; Vodovotz, Y.

    2009-01-01

    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

  6. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

    Directory of Open Access Journals (Sweden)

    Anne ePetzold

    2015-10-01

    Full Text Available 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. 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.

  7. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review

    OpenAIRE

    David O. Kennedy

    2016-01-01

    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 epid...

  8. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

    Science.gov (United States)

    Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

    2017-11-01

    The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Assessing signal-driven mechanism in neonates: brain responses to temporally and spectrally different sounds

    Directory of Open Access Journals (Sweden)

    Yasuyo eMinagawa-Kawai

    2011-06-01

    Full Text Available Past studies have found that in adults that acoustic properties of sound signals (such as fast vs. slow temporal features differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

  10. Molecular Mechanism Underlying Sialic Acid as an Essential Nutrient for Brain Development and Cognition123

    Science.gov (United States)

    Wang, Bing

    2012-01-01

    The early stages of neurodevelopment in infants are crucial for establishing neural structures and synaptic connections that influence brain biochemistry well into adulthood. This postnatal period of rapid neural growth is of critical importance for cell migration, neurite outgrowth, synaptic plasticity, and axon fasciculation. These processes thus place an unusually high demand on the intracellular pool of nutrients and biochemical precursors. Sialic acid (Sia), a family of 9-carbon sugar acids, occurs in large amounts in human milk oligosaccharides and is an essential component of brain gangliosides and sialylated glycoproteins, particularly as precursors for the synthesis of the polysialic acid (polySia) glycan that post-translationally modify the cell membrane-associated neural cell adhesion molecules (NCAM). Human milk is noteworthy in containing exceptionally high levels of Sia-glycoconjugates. The predominate form of Sia in human milk is N-acetylneuraminic acid (Neu5Ac). Infant formula, however, contains low levels of Sia consisting of both Neu5Ac and N-glycolyneuraminic acid (Neu5Gc). Current studies implicate Neu5Gc in several human inflammatory diseases. Polysialylated NCAM and neural gangliosides both play critical roles in mediating cell-to-cell interactions important for neuronal outgrowth, synaptic connectivity, and memory formation. A diet rich in Sia also increases the level of Sia in the brains of postnatal piglets, the expression level of 2 learning-related genes, and enhances learning and memory. PMID:22585926

  11. Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition.

    Science.gov (United States)

    Wang, Bing

    2012-05-01

    The early stages of neurodevelopment in infants are crucial for establishing neural structures and synaptic connections that influence brain biochemistry well into adulthood. This postnatal period of rapid neural growth is of critical importance for cell migration, neurite outgrowth, synaptic plasticity, and axon fasciculation. These processes thus place an unusually high demand on the intracellular pool of nutrients and biochemical precursors. Sialic acid (Sia), a family of 9-carbon sugar acids, occurs in large amounts in human milk oligosaccharides and is an essential component of brain gangliosides and sialylated glycoproteins, particularly as precursors for the synthesis of the polysialic acid (polySia) glycan that post-translationally modify the cell membrane-associated neural cell adhesion molecules (NCAM). Human milk is noteworthy in containing exceptionally high levels of Sia-glycoconjugates. The predominate form of Sia in human milk is N-acetylneuraminic acid (Neu5Ac). Infant formula, however, contains low levels of Sia consisting of both Neu5Ac and N-glycolyneuraminic acid (Neu5Gc). Current studies implicate Neu5Gc in several human inflammatory diseases. Polysialylated NCAM and neural gangliosides both play critical roles in mediating cell-to-cell interactions important for neuronal outgrowth, synaptic connectivity, and memory formation. A diet rich in Sia also increases the level of Sia in the brains of postnatal piglets, the expression level of 2 learning-related genes, and enhances learning and memory.

  12. Gene repressive mechanisms in the mouse brain involved in memory formation.

    Science.gov (United States)

    Yu, Nam-Kyung; Kaang, Bong-Kiun

    2016-04-01

    Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls. [BMB Reports 2016; 49(4): 199-200].

  13. Mechanism of Traumatic Brain Injury at Distant Locations After Exposure to Blast Waves: Preliminary Results from Animal and Phantom Experiments.

    Science.gov (United States)

    Nakagawa, Atsuhiro; Ohtani, Kiyonobu; Goda, Keisuke; Kudo, Daisuke; Arafune, Tatsuhiko; Washio, Toshikatsu; Tominaga, Teiji

    2016-01-01

    Purpose Primary blast-induced traumatic brain injury (bTBI) is the least understood of the four phases of blast injury. Distant injury induced by the blast wave, on the opposite side from the wave entry, is not well understood. This study investigated the mechanism of distant injury in bTBI. Materials and Methods Eight 8-week-old male Sprague-Dawley rats were divided into two groups: group 1 served as the control group and did not receive any shock wave (SW) exposure; group 2 was exposed to SWs (12.5 ± 2.5 MPa). Propagation of SWs within a brain phantom was evaluated by visualization, pressure measurement, and numerical simulation. Results Intracerebral hemorrhage near the ignition site and elongation of the distant nucleus were observed, despite no apparent damage between the two locations in the animal experiment. Visualization, pressure measurement, and numerical simulation indicated the presence of complex wave dynamics accompanying a sudden increase in pressure, followed by negative pressure in the phantom experiment. Conclusion A local increase in pressure above the threshold caused by interference of reflection and rarefaction waves in the vicinity of the brain-skull surface may cause distant injury in bTBI.

  14. Quantitative Study of Longitudinal Relaxation (T 1) Contrast Mechanisms in Brain MRI

    Science.gov (United States)

    Jiang, Xu

    Longitudinal relaxation (T1) contrast in MRI is important for studying brain morphology and is widely used in clinical applications. Although MRI only detects signals from water hydrogen ( 1H) protons (WPs), T1 contrast is known to be influenced by other species of 1H protons, including those in macromolecules (MPs), such as lipids and proteins, through magnetization transfer (MT) between WPs and MPs. This complicates the use and quantification of T1 contrast for studying the underlying tissue composition and the physiology of the brain. MT contributes to T1 contrast to an extent that is generally dependent on MT kinetics, as well as the concentration and NMR spectral properties of MPs. However, the MP spectral properties and MT kinetics are both difficult to measure directly, as the signal from MPs is generally invisible to MRI. Therefore, to investigate MT kinetics and further quantify T1 contrast, we first developed a reliable way to indirectly measure the MP fraction and their exchange rate with WPs, with minimal dependence on the spectral properties of MPs. For this purpose, we used brief, highpower radiofrequency (RF) NMR excitation pulses to almost completely saturate the magnetization of MPs. Based on this, both MT kinetics and the contribution of MPs to T1 contrast through MT were studied. The thus obtained knowledge allowed us to subsequently infer the spectral properties of MPs by applying low-power, frequencyselective off-resonance RF pulses and measuring the offset-frequency dependent effect of MPs on the WP MRI signal. A two-pool exchange model was used in both cases to account for direct effects of the RF pulse on WP magnetization. Consistent with earlier works using MRI at low-field and post-mortem analysis of brain tissue, our novel measurement approach found that MPs constitute an up to 27% fraction of the total 1H protons in human brain white matter, and their spectrum follows a super-Lorentzian line with a T2 of 9.6+/-0.6 mus and a resonance

  15. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers

  16. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC's efficacy and mechanism of action. ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. ARC treatment confers neuroprotection of brain tissue

  17. Manganese distribution across the blood-brain barrier III. The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake.

    Science.gov (United States)

    Crossgrove, Janelle S; Yokel, Robert A

    2004-03-01

    Manganese (Mn) is essential for and toxic to the brain. Brain Mn uptake utilizes both diffusion and transporter-mediated pathways. The divalent metal transporter-1 (DMT-1) has been suggested to mediate brain Mn uptake. The b/b Belgrade rat does not express significant amounts of functional DMT-1. In the present work, brain influx transfer coefficients of (54) Mn ion and (54) Mn transferrin (Mn Tf) were determined in b/b and +/b Belgrade and Wistar rats using the in situ brain perfusion technique. Brain Mn uptake was not significantly different among the three rat strains for either Mn species. We hypothesized that Mn may enter brain endothelial cells by a DMT-1-independent process but not be able to distribute across those cells into brain tissue due to the absence of DMT-1 activity. To test this hypothesis the brain capillary endothelial cells were isolated from b/b and +/b Belgrade rats and Wistar rats after in situ brain perfusion. Some animals received cerebrovascular washout after in situ brain perfusion to ascertain any affect of genotype on (54) Mn adsorption to the endothelial cell luminal surface. Less than 30% of the brain (54) Mn after (54) Mn ion or (54) Mn Tf perfusion remained associated with endothelial cells, suggesting the majority had distributed into brain extracellular fluid (ECF) and/or brain cells. Mn appears to distribute across the rat blood-brain barrier (BBB) into the brain by one or more carrier-mediated processes other than the DMT-1.

  18. 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.

  19. 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. PMID:26998365

  20. 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.

  1. Botryllus schlosseri, an emerging model for the study of aging, stem cells, and mechanisms of regeneration.

    Science.gov (United States)

    Voskoboynik, Ayelet; Weissman, Irving L

    2015-01-30

    The decline of tissue regenerative potential with the loss of stem cell function is a hallmark of mammalian aging. We study Botryllus schlosseri, a colonial chordate which exhibits robust stem cell-mediated regeneration capacities throughout life. Larvae, derived by sexual reproduction and chordate development, metamorphose to clonal founders that undergo weekly formation of new individuals by budding from stem cells. Individuals are transient structures which die through massive apoptosis, and successive buds mature to replicate an entire new body. As a result, their stem cells, which are the only self-renewing cells in a tissue, are the only cells which remain through the entire life of the genotype and retain the effects of time. During aging, a significant decrease in the colonies' regenerative potential is observed and both sexual and asexual reproductions will eventually halt. When a parent colony is experimentally separated into a number of clonal replicates, they frequently undergo senescence simultaneously, suggesting a heritable factor that determines lifespan in these colonies. The availability of the recently published B. schlosseri genome coupled with its unique life cycle features promotes the use of this model organism for the study of the evolution of aging, stem cells, and mechanisms of regeneration.

  2. Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms.

    Science.gov (United States)

    Murota, Hiroyuki; Matsui, Saki; Ono, Emi; Kijima, Akiko; Kikuta, Junichi; Ishii, Masaru; Katayama, Ichiro

    2015-01-01

    The various symptoms associated with excessive or insufficient perspiration can significantly reduce a patient's quality of life. If a versatile and minimally invasive method could be established for returning sweat activity to normalcy, there is no question that it could be used in the treatment of many diseases that are believed to involve perspiration. For this reason, based on an understanding of the sweat-gland control function and sweat activity, it was necessary to conduct a comprehensive search for the factors that control sweating, such as the central and peripheral nerves that control sweat-gland function, the microenvironment surrounding the sweat glands, and lifestyle. We focused on the mechanism by which atopic dermatitis leads to hypohidrosis and confirmed that histamine inhibits acetylcholinergic sweating. Acetylcholine promotes the phosphorylation of glycogen synthesis kinase 3β (GSK3β) in the sweat-gland secretory cells and leads to sensible perspiration. By suppressing the phosphorylation of GSK3β, histamine inhibits the movement of sweat from the sweat-gland secretory cells through the sweat ducts, which could presumably be demonstrated by dynamic observations of the sweat glands using two-photon microscopy. It is expected that the discovery of new factors that control sweat-gland function can contribute to the treatment of diseases associated with dyshidrosis. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Emergence of four dimensional quantum mechanics from a deterministic theory in 11 dimensions

    Science.gov (United States)

    Doyen, G.; Drakova, D.

    2015-07-01

    We develop a deterministic theory which accounts for the coupling of a high dimensional continuum of environmental excitations (called gravonons) to massive particle in a very localized and very weak fashion. For the model presented Schrödinger's equation can be solved practically exactly in 11 spacetime dimensions and the result demonstrates that as a function of time an incoming matter wave incident on a screen extinguishes, except at a single interaction center on the detection screen. This transition is reminiscent of the wave - particle duality arising from the ’’collapse” (also called ’’process one”) postulated in the Copenhagen-von Neumann interpretation. In our theory it is replaced by a sticking process of the particle from the vacuum to the surface of the detection screen. This situation was verified in experiments by using massive molecules. In our theory this ”wave-particle transition” is connected to the different dimensionalities of the space for particle motion and the gravonon dynamics, the latter propagating in the hidden dimensions of 11 dimensional spacetime. The fact that the particle is detected at apparently statistically determined points on the screen is traced back to the weakness and locality of the interaction with the gravonons which allows coupling on the energy shell alone. Although the theory exhibits a completely deterministic ”chooser” mechanism for single site sticking, an apparent statistical character results, as it is found in the experiments, due to small heterogeneities in the atomic and gravonon structures.

  4. Epigenetic mechanisms in neurogenesis

    Science.gov (United States)

    Yao, Bing; Christian, Kimberly M.; He, Chuan; Jin, Peng; Ming, Guo-li; Song, Hongjun

    2017-01-01

    In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms — including DNA and histone modifications, as well as regulation by non-coding RNAs — have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs. PMID:27334043

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

  6. BRAIN PLASTICITY: MUSICAL TRAINING INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    Verónika Diaz Abrahan

    2012-12-01

    Full Text Available The main research about the effect of musical training in adult and childhood brain was revised in this work. The music realizes unique demands to our ner-vous system. This call the attention of several researchers causing, in the past years, an enhancement of the exploration about this topic; this increment was benefit for the emergence of new neuroimaging techniques, the music positioned as an investigation tool of human cognition and superior brain mechanisms. The musical perception and production are specific functions of the human brain that depend of a wide cortical-subcortical neural net distributed across both hemi-spheres and cerebellum. The main findings in this area indicated structural and functional differences in the adult and child brain due to musical training, and this is more relevant that innate properties of the subject. There is brain plasticity due to adaptive processes product of the environmental stimulation.

  7. 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. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  8. Early Life Stress and the Anxious Brain: Evidence for A Neural Mechanism Linking Childhood Emotional Maltreatment to Anxiety in Adulthood

    Science.gov (United States)

    Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Simmons, Alan N.; Sullivan, Sarah G.; Allard, Carolyn B.; Paulus, Martin P.; Stein, Murray B.

    2016-01-01

    Background Childhood emotional maltreatment (CEM) increases likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. Methods One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. Results During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray matter volumes also partially mediated the CEM-anxiety relationship. Conclusions Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes. PMID:26670947

  9. Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis.

    Science.gov (United States)

    Brzozowski, Bartosz; Mazur-Bialy, Agnieszka; Pajdo, Robert; Kwiecien, Slawomir; Bilski, Jan; Zwolinska-Wcislo, Malgorzata; Mach, Tomasz; Brzozowski, Tomasz

    2016-01-01

    Stress of different origin is known to alter so called "braingut axis" and contributes to a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases. The stressful situations and various stressors including psychosocial events, heat, hypo- and hyperthermia may worsen the course of IBD via unknown mechanism. The aims of this paper were to provide an overview of experimental and clinical evidences that stress activates the brain-gut axis which results in a mucosal mast cells activation and an increase in the production of proinflammatory cytokines and other endocrine and humoral mediators. Research and online content related to effects of stress on lower bowel disorders are reviewed and most important mechanisms are delineated. Brain conveys the neural, endocrine and circulatory messages to the gut via brain-gut axis reflecting changes in corticotrophin releasing hormone, mast cells activity, neurotransmission at the autonomic nerves system and intestinal barrier function all affecting the pathogenesis of animal colitis and human IBD. Stress triggers the hypothalamus-pituitary axis and the activation of the autonomic nervous system, an increase in cortisol levels and proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-8, interleukin-1beta and interleukin-6. The acute or chronic stress enhances the intestinal permeability weakening of the tight junctions and increasing bacterial translocation into the intestinal wall. An increased microbial load in the colonic tissue, excessive cytokine release and a partially blunted immune reactivity in response to stress result in its negative impact on IBD.

  10. The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer

    Directory of Open Access Journals (Sweden)

    Hueng-Chuen Fan

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP, are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB. Taken together, its actions have been shown to have anti-proliferative, anti-chemoresistance, anti-invasion, anti-migration, and anti-dissemination effects against GBM. In addition, a local drug delivery system for the subcutaneous and intracranial implantation of BP wafers that significantly reduce tumor size in xenograft models, as well as orthotopic and spontaneous brain tumors in animal models, has been developed. Isochaihulactone (ICL, another kind of plant product, possesses a broad spectrum of pharmacological activities, including impacts on cancer cell apoptosis and cell cycle arrest, as well as anti-proliferative and anti-chemoresistance effects. Furthermore, these actions have been specifically shown to have cancer-fighting effects on GBM. In short, the results of various studies reviewed herein have provided substantial evidence indicating that BP and ICH are promising novel anticancer compounds with good potential for clinical applications.

  11. The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

    Science.gov (United States)

    Köhler, Cristiano A; Maes, Michael; Slyepchenko, Anastasiya; Berk, Michael; Solmi, Marco; Lanctôt, Krista L; Carvalho, André F

    2016-01-01

    Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

  12. 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.

  13. Similar brain mechanism of hypothesis-testing between children and adults.

    Science.gov (United States)

    Li, Fuhong; Cao, Bihua; Cai, Xueli; Li, Hong

    2011-01-01

    Fourteen children and 15 adults were sequentially presented with triplets of cookies and were asked to learn what kinds of cookies were eatable while event-related potentials (ERPs) were recorded. The results locked to the third cookies that served to strengthen or reject a preliminary hypothesis showed that (1) the parietal P220 and frontal HRP (Hypothesis Reject Potential) was larger in reject condition than in strengthen condition for both age groups; (2) the intensive process of hypothesis testing activated most of the left brain. These results suggest that the logical function of the frontal lobe has been formed during the critical period of development of thinking.

  14. 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...

  15. Incidence, Risk Factors and Consequences of Emergence Agitation in Adult Patients after Elective Craniotomy for Brain Tumor: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lu Chen

    Full Text Available Emergence agitation is a frequent complication that can have serious consequences during recovery from general anesthesia. However, agitation has been poorly investigated in patients after craniotomy. In this prospective cohort study, adult patients were enrolled after elective craniotomy for brain tumor. The sedation-agitation scale was evaluated during the first 12 hours after surgery. Agitation developed in 35 of 123 patients (29%. Of the agitated patients, 28 (80% were graded as very and dangerously agitated. By multivariate stepwise logistic regression analysis, independent predictors for agitation included male sex, history of long-term use of anti-depressant drugs or benzodiazepines, frontal approach of the operation, method and duration of anesthesia and presence of endotracheal intubation. Total intravenous anesthesia and balanced anesthesia with short duration were protective factors. Emergence agitation was associated with self-extubation (8.6% vs 0%, P = 0.005. Sedatives were administered more in agitated patients than non-agitated patients (85.7% vs 6.8%, P<0.001. In conclusion, emergence agitation was a frequent complication in patients after elective craniotomy for brain tumors. The clarification of risk factors could help to identify the high-risk patients, and then to facilitate the prevention and treatment of agitation. For patients undergoing craniotomy, greater attention should be paid to those receiving a frontal approach for craniotomy and those anesthetized under balanced anesthesia with long duration. More researches are warranted to elucidate whether total intravenous anesthesia could reduce the incidence of agitation after craniotomy.ClinicalTrials.gov NCT00590499.

  16. 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.

  17. 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.

  18. Mechanisms of Oxidative Stress Resistance in The Brain: Lessons Learned From Hypoxia Tolerant Extremophilic Vertebrates

    Science.gov (United States)

    Garbarino, Valentina R.; Orr, Miranda E.; Rodriguez, Karl A.; Buffenstein, Rochelle

    2016-01-01

    The Oxidative Stress Theory of Aging has had tremendous impact in research involving aging and age-associated diseases including those that affect the nervous system. With over half a century of accrued data showing both strong support for and against this theory, there is a need to critically evaluate the data acquired from common biomedical research models, and to also diversify the species used in studies involving this proximate theory. One approach is to follow Orgel’s second axiom that “evolution is smarter than we are” and judiciously choose species that may have evolved to live with chronic or seasonal oxidative stressors. Vertebrates that have naturally evolved to live under extreme conditions (e.g., anoxia or hypoxia), as well as those that undergo daily or seasonal torpor encounter both decreased oxygen availability and subsequent reoxygenation, with concomitant increased oxidative stress. Due to its high metabolic activity, the brain may be particularly vulnerable to oxidative stress. Here, we focus on oxidative stress responses in the brains of certain mouse models as well as extremophilic vertebrates. Exploring the naturally evolved biological tools utilized to cope with seasonal or environmentally variable oxygen availability may yield key information pertinent for how to deal with oxidative stress and thereby mitigate its propagation of age-associated diseases. PMID:25841340

  19. Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage by Mechanism Involving Nrf2.

    Science.gov (United States)

    Zhao, Xiurong; Sun, Guanghua; Zhang, Jie; Ting, Shun-Ming; Gonzales, Nicole; Aronowski, Jaroslaw

    2015-07-01

    Intracerebral hemorrhage (ICH) represents a devastating form of stroke for which there is no effective treatment. This preclinical study was designed to evaluate dimethyl fumarate (DMF), a substance recently approved for the treatment of multiple sclerosis, as therapy for ICH. We hypothesized that DMF through activating the master regulator of cellular self-defense responses, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), would act as effective treatment for ICH-mediated damage. Male rats and mice, including Nrf2 knockouts, were subjected to intracerebral injection of blood (to mimic ICH) and then treated with DMF. Neurological deficit, brain edema, gene induction profile and hematoma resolution were evaluated. Phagocytic functions of primary microglia in culture were used to study hematoma resolution. Treatment with DMF induced Nrf2-target genes, improved hematoma resolution, reduced brain edema, and ultimately enhanced neurological recovery in rats and wild-type, but not Nrf2 knockout, mice. Most importantly, the treatment of ICH with DMF showed a 24 h window of therapeutic opportunity. A clinically relevant dose of DMF demonstrates potent therapeutic efficacy and impressive 24 h therapeutic window of opportunity. This study merits further evaluation of this compound as potential treatment for ICH in humans. © 2015 American Heart Association, Inc.

  20. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review

    Science.gov (United States)

    Kennedy, David O.

    2016-01-01

    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. PMID:26828517